Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in understanding the causes, processes, and outcomes of the disorder. Cognitive impairments in schizophrenia encompass a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcome and quality of life. Therefore, identifying the biological basis of cognitive deficits in schizophrenia and developing effective treatments are imperative. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptor, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia.

This paper presents the common methods and corresponding drawbacks concerning nonlinear analysis of fluxgate excitation circuits and emphasizes the importance of nonlinear analysis for these circuits. With regard to the nonlinearity of the excitation circuit, this paper proposes the use of the core-measured hysteresis curve for mathematical analysis and the use of a nonlinear model that considers the coupling effect of the core and winding and influence of the historical magnetic field on the core for simulation analysis. The feasibility of mathematical calculations and simulation for the nonlinear study of fluxgate excitation circuit is verified via experiments. The results demonstrate that, in this regard, the simulation is better than a mathematical calculation. The simulation and experimental results of the excitation current and voltage waveforms under different excitation circuit parameters and structures are essentially consistent with each other, thereby verifying the effectiveness of the nonlinear excitation analysis method.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multi-step nature of the process offers multiple regulation points prone to be deregulated and cause different human disease, but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within tumor microenvironment, but also to increase invasiveness and resistance to anti-cancer drugs such as chemotherapy. This review collects all clinical evidences of autophagy deregulation during cholangiocarcinogenesis together with all pre-clinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggests an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Pre-clinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer

This study investigates the impact of narrow-band terahertz pulses on the ferroelectric order parameter in Ba0.8Sr0.2TiO3 films on various substrates. The 375 nm thick BST film on an MgO (001) substrate exhibits enhanced THz-induced second harmonic generation when excited by THz pulses with a central frequency of 1.6 THz, due to the resonant excitation of the soft phonon mode. Conversely, the BST film on a Si (001) substrate shows no enhancement, due to its polycrystalline state. The 800 nm thick BST film on an MgO (111) substrate demonstrates maximum of second harmonic generation signal when excited by THz pulses at 1.8 THz, that is also very close to it`s soft mode frequency (1.9 THz). Notably, the frequency spectrum of the BST/MgO (111) film reveals peaks at both the fundamental and doubled frequencies, highlighting the quadratic dependence of SHG intensity on the THz pulse's electric field strength.

There is a growing demand and use of herbal cosmetics for skin purposes due to their perceived safety when applied to the skin. Three Cassipourea species commonly known as “ummemezi” are used interchangeable by women in rural areas of Eastern Cape and KwaZulu-Natal provinces to treat hypermelanosis as well as sun protection. We conducted a phytochemical comparison of three Cassipourea species; C. flanaganii, C. gummiflua and C. malosana by LC-MS/MS analysis in negative mode. The results obtained from the LC-MS/MS yielded a total number of twenty-four compounds of different chemical classes, including fatty acids, steroids, di- and tri-terpenoids, flavonoids, phenolic acids were detected, and eighteen among them were tentatively identified. Despite the recent popularity of modern cosmetic products, it is clear that plants continue to play an important role in the local cosmetics industry in South Africa's Eastern Cape and KwaZulu-Natal community provinces. The findings of this study suggest that an alternative treatment for hyper-melanosis disorders should be developed further. The residual wild plant stocks are insufficient to meet commercial needs, thus, encouraging their sustainable use is a means of harnessing the conservation of these plants. Indigenous communities should be supported in the commercialization which could be linked to the rural economic development.

Aims: Adolescence is a critical period because the brain is involved in the process of maturation that entails cognitive functions. On the way of maturation, an individual’s inhibitory control undergoes many changes and becomes vulnerable to different thrill-seeking like smoking, drinking, and so on. Smoking is highly prevalent among teenagers that are trying to take control of their behaviors in order to join society. They experience antisocial behavior too which is a trait that can lead adolescents to addiction. This trait is an inevitable part of psychopathy. Inhibitory deficits and psychopathy have been widely reported in addiction studies. The current study tried to investigate the relationship between psychopathic traits and behavioral inhibition between male smokers and non-smoker teenage students.Materials & Methods: Statistical sample of this research is 62 teenage students aged 17 years that are divided into smoker and non-smoker groups. The participants have been chosen through random sampling from the population of 10 high schools. The data have been gathered in Kordkoy and Gorgan in Golestan province. Behavioral bias has been measured by Go/NoGo task and psychopathic traits through youth psychopathic traits inventory. Also, the short form of Wechsler Adult Intelligence Scale test has been executed and used as a control variable.Findings: A meaningful difference has been found between the performance of smoker and non-smoker groups in Go/No Go task and psychopathic traits that are smokers performed weaker in comparison with non-smokers and psychopathic traits of smokers were meaningfully higher than non-smokers. On the other hand, there was no significant difference between these two groups in their Wechsler Adult Intelligence Scale scores.Conclusion: The results have shown that smokers have higher psychopathic traits and lower behavioral inhibition when compared with their non-smoker peers. According to the results of current research, smoking can decline the cognitive functions.

This work describes a resonance Raman study performed in domes of monolayer MoS2 using 23 different laser excitation energies covering the visible and near-infrared (NIR) ranges. The multiple-excitation results allowed us to investigate the exciton-phonon interactions of different phonons (A1’, E’ and LA) with different electronic and excitonic optical transitions in biaxially strained monolayer MoS2. The analysis of the intensities of the two first-order peaks, A1’ and E’, and the double-resonance 2LA Raman band as a function of the laser excitation furnished the values of the energies of the indirect gap and the excitonic transitions in the strained MoS2 domes. It was noticed that the out-of-plane A1’ phonon mode is significantly enhanced only by the indirect gap I and the C exciton, whereas the in-plane E’ mode is only enhanced by the C exciton of MoS2 dome, revealing thus a weak interaction of these phonons with the A and B excitons in the strained MoS2 domes. On the other hand, the 2LA Raman band is significantly enhanced at the indirect gap I transition and by the A (or B) exciton, but not enhanced by the C exciton, showing thus that the LA edge-phonons that participate in the double resonance process in MoS2 have a weak interaction with the C exciton.

The phenomenon of coupling between light and surface plasmon polaritons requires specific momentum matching conditions. In the case of a single scattering object on a metallic surface, like a nanoparticle or a nanohole, the coupling between a broadband effect, i.e. scattering, and a discrete one such as surface plasmon excitation, leads to Fano-like resonance lineshapes. The necessary phase matching requirements can be used to engineer the light-plasmon coupling and to achieve a directional plasmonic excitation. Here we investigate this effect by using a chiral nanotip to excite surface plasmons with a strong spin-dependent azimuthal variation. This effect can be described by a Fano-like interference with a complex coupling factor that can be modified thanks to a symmetry breaking of a nanostructure.

Consciousness is a special type of interaction between subjects exchanging by lingua quanta (phonemes). A set of lingua quanta composes a thesaurus placed on the edge of chaos. Its library is a memory, modification of which is due to tuning of memristive neural elements scattered in the brain volume. The memristive neural model takes into consideration two types of neurons - excitatory and inhibitory and the current leakage, all at the body temperature, T = 309 K. At such temperatures only heavy ions like hydrogen ions - protons can pass robustly through the water medium of the brain. The robust ion transport is proton water wires supported by the Grotthuss mechanism. Final aims of the ions are the gap junctions (electric synapses) linking nearest neurons. Following these observations, a model of excitable nervous tissue is constructed. Namely, a difference mapping on the basis of sigmoid curves can reproduce chaotic modes of neural activity proved by positive values of the Lyapunov exponent. The edge of chaos is placed near the bifurcation boundary dividing the chaos and the periodic convulsive activity typical at the epileptic discharges. In this region the self-sustained spiral waves occur. An intermittent activity of the competing excitatory and inhibitory neurons is observed on the edge of chaos. The intermittent electrical activity of neural tissues is demonstrated by records both from different literature issues and records made by the author together with DR. A. Dudkin on slices of CA1 field of the hippocampus.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research indicates that they share both distinctive and common pathways. Moreover, they exhibit intriguing intersections with mechanotransduction, a process that involves cells sensing and responding to mechanical forces. This review article describes the intricate interplay between mechanical forces and CI, shedding light on how these forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs) emerge as sensitive players in both CI and the mechanotransduction process. This article presents methods for identifying these TAFs and profiling the associated changes in chromatin structure, offering valuable insights into CI and mechanotransduction regulation. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

Low-energy Coulomb excitation is capable of providing unique information on static electromagnetic moments of short-lived excited nuclear states, including non-yrast states. The process selectively populates low-lying collective states and is therefore ideally suited to study phenomena such as shape coexistence and development of exotic deformation (triaxial or octupole shapes). Historically, these experiments were restricted to stable isotopes. However, the advent of new facilities providing intense beams of short-lived radioactive species has opened the possibility to apply this powerful technique to a much wider range of nuclei. We discuss the observables that can be measured in a Coulomb-excitation experiment, their relation to nuclear structure parameters with an emphasis on the nuclear shape, and present some recent examples of Coulomb-excitation studies that provided outcomes relevant for the Shell Model.

The excessive vibration caused by crowds walking across footbridges has attracted great public concerns in the past few decades. This paper presents, from considering the dynamic characteristics of the bipedal crowd model, a new stability limit criterion based on the bipedal excitation model. The stability limit can be used to estimate the upper boundary of crowd size. In addition, the dynamic stable performances of a structure, under a certain walking crowd size, can be predicted by the stability criterion. This proposed mechanism provides an alternative comprehension how crowd excite the excessive sway motion with a large-span structure.

The Voltammetric and polarographic methods are proposed to determine the short time corro-sion rates of brass in 1N HCl solution. It should be noted that it is also possible to determine the corrosion rates of each species present in the solution, simultaneously like Cu (II) and Zn (II) in brass. Samples extracted from bark of Babul (ESBB) is used as corrosion inhibitors. The corrosion inhibition efficiency is 96% at 24h after the test started. These results are compared with the av-erage corrosion rates obtained by using gravimetric (PIT) and some electrochemical methods i.e. galvanostatic and potentiodynamic polarization measurements.

Pulsed electric fields of specific frequencies emitted by a glass plasma antenna tube have been shown to slow the growth of Acute Lymphoblastic Leukemia cells by as much as 43% when exposed to a series of frequencies between 156kHz and 162kHz. This narrow band of frequencies is termed a “Destructive Cancer Resonant Frequency Formant” (DCRFF).

We used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. We found no evidence of inhibition by N. mucosa (n=24). Positive controls Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

The amyloid fibril formation by $\alpha$-synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson's disease. Epigallocatechin gallate (EGCG) has been reported to be an efficient aggregation inhibitor of numerous proteins, among them $\alpha$-synuclein. Here we show that this applies only to a small region of relevant parameter space and that under some conditions, EGCG can even accelerate α-synuclein amyloid fibril formation through facilitating its heterogeneous primary nucleation. Furthermore, we show through quantitative seeding experiments that contrary to previous reports, EGCG is not able to re-model α-synuclein amyloid fibrils into seeding-incompetent structures. Taken together, our results paint a complex picture of EGCG as a compound that can under some conditions inhibit the amyloid fibril formation of α-synuclein, but the inhibitory action is not robust against various relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterise promising amyloid inhibitors.

External motivational stimuli have been shown to improve athletic performance. However, the neurophysiological mechanisms underlying this improvement remain poorly understood. This randomized crossover study investigated the effects of music and verbal encouragement on measures of muscle excitation and myoelectric manifestations of fatigue in the biceps brachii (BB) and brachioradialis (BR) muscles during an endurance task. Fifteen untrained (mean age 29.57 ± 2.77 years) and 13 trained individuals (mean age 32.92 ± 2.90 years) were included. The endurance task, performed to exhaustion, consisted of keeping the dominant arm flexed to 90 degrees while holding a dumbbell loaded to 80% of 1RM with a supine grip in three randomized conditions: standard, with self-selected music, and with verbal encouragement. The untrained subjects showed an increase in task duration of 15.26% (p < 0.003) with music and 15.85% (p < 0.002) with verbal encouragement compared to the condition without external stimuli. There were no significant differences in the myoelectric manifestations of fatigue between the dif-ferent conditions. Regarding the muscle excitation metrics, although the mean amplitude, peak value and area under the curve remained unchanged across conditions, a significant reduction in the trend coefficient, indicating motor unit recruitment over time, was observed with both music (BB: -10.39%, p < 0.001; BR: -9.40%, p < 0.001) and verbal encouragement (BB: -7.61%, p < 0.001; BR: -6.51%, p < 0.001) compared to the standard condition. For the trained participants, no significant differences were observed between conditions in terms of task duration and outcome measures related to muscle excitation and myoelectric manifestations of fatigue, suggesting the possible presence of a ceiling effect on motivation. These results highlight the significant role of external motivational stimuli, such as music and verbal encouragement, in improving task performance in untrained subjects, probably through more ef-fective and efficient recruitment of motor units.

Melanoma is a type of highly malignant and metastatic skin cancer. In situ molecular imaging of endogenous levels of the melanoma biomarker tyrosinase (TYR) may decrease the likelihood of mortality. In this study we proposed the weakly fluorescent probe 1-(4-(2-(4-(dicyanomethylene)-4H-chromen-2-yl)vinyl)phenyl)-3-(4-hydroxybenzyl)urea (DCM-HBU), which releases a strong red-shifted fluorescent signal after a TYR-mediated oxidation followed by hydrolysis of the urea linkage. The large Stokes shift of the dye is owed to the recovery of the intramolecular charge transfer (ICT) effect. The resulting probe derivate shows a highly ratiometric fluorescence output. Furthermore, the simultaneous excitation by two near-infrared (NIR) photons of the released DCM-NH2 fluorophore could avoid the usual drawbacks, such as cellular absorption, autofluorescence and light scattering, due to an usually short wavelength of the excitation light on biological systems, resulting in images with deeper tissue penetration. In addition, the probe is useful for the quantitative sensing of TYR activity in vivo, as demonstrated in zebrafish larvae. This new ratiometric two photon NIR fluorescent probe is expected to be useful for the accurate detection of TYR in complex biosystems at greater depths than other one-photon excited fluorescent probes.

In this paper, we have shown the electronic circuit equivalence of a mechanical system consists of two oscillators coupled with each other. The mechanical design has the effects of the magnetic, resistance forces and the spring constant of the system is periodically varying. We have shown that the system’s state variables, such as the displacements and the velocities, under the effects of different forces, lead to some nonlinear behaviors, like a transition from the fixed point attractor to the chaotic attractor through the periodic and quasi-periodic attractors. We have constructed the equivalent electronic circuit of this mechanical system and have verified the numerically obtained behaviors using the electronic circuit.

Magnesium monofluoride is a polar molecule amenable to laser cooling which has caused renewed interest in its spectroscopy. In this work we consider the case of three low-lying electronic excitations, namely $\rm X \, {}^{2}\Sigma \to A \, {}^{2}\Pi, \ \to B \, {}^{2}\Sigma, \ \to C \,{}^{2}\Sigma$, using well developed quantum chemistry approaches, i.e., without reference to the spin-orbit splitting of the $\rm A \, {}^{2}\Pi$ states. Accurate experimental data for these transitions have been available for over 50 years. Here we explore the linear response method at the level of CC2 theory, as well as equation of motion methods at the level of CCSD and CC3, using two families of basis sets. Excellent agreement is obtained for the first three transitions when using the correlation-consistent basis sets and extrapolation to the complete basis limit within EOM-CC3 (at a relative precision of $10^{-4}$), and qualitative agreement for the other two methods. The purpose of this paper is to serve as a guide in how to approach the accurate calculation of excitations in polar diatomic molecules.

In today's human society, diesel generators (DGs) are highly applied into the human energy and electricity supply system due to its technical, operational and economic advantages. This paper proposes an intelligent nonlinear $H_2/H_{\infty}$ robust controller based on the chaos particle swarm gravity search optimization algorithm (CPSOGSA), which controls the speed and excitation of a DG. In this method, firstly, establish the nonlinear mathematical model of the DG and then design the nonlinear $H_2/H_{\infty}$ robust controller based on this. The direct feedback linearization and the $H_2/H_{\infty}$ robust control theory are combined and applied. Based on the design of the integrated controller for DG speed and excitation, the system's performance requirements are transformed into a standard robust $H_2/H_{\infty}$ control problem. The parameters of the proposed solution controller are optimized by using the proposed CPSOGSA. The introduction of CPSOGSA completes the design of an intelligent nonlinear $H_2/H_{\infty}$ robust controller for DG. The simulation is implemented in MATLAB/Simulink, and the results are compared with the PID control method. The obtained results prove that the proposed method can effectively improve the dynamic accuracy of the system and the ability to suppress disturbances and improve the stability of the system.

Magneto-rheological dampers (MR-dampers) are increasingly used in construction applications to reduce the dynamic response of structures to seismic activities or severe wind loading. Sensors attached to the structure will signal the computer to supply the dampers with electric charge that transfers the MR fluid to a near-solid material with different physical and mechanical properties (viscoelastic behavior). Control algorithms govern the fluid to near-solid conversion, which controls the behavior of the damper, and the performance of the structure under the seismic or wind loading event. The successful optimization of control parameters minimize the overall structural response to dynamic forces. The main objective of this research is to change the output behavior of specific floors within a building subjected to seismic excitation by optimizing the MR-dampers control parameters to impact the behavior of a specific floor or number of floors within the building. The adjustment of control parameters to attain this objective was validated in multiple case studies throughout this research. The successful implementation of the research outcome will result in optimized MR-damper design to meet the performance-based criteria of building projects.

In Parkinson's disease, neuroinflammation is a complex defense mechanism. Activated microglia and Proteinase-activated receptor-2 (PAR2) are key points in the regulation of neuroinflammation. 1-Piperidin Propionic Acid (1-PPA) has been recently described as a novel inhibitor of PAR2. The aim of our study was to evaluate the effect of 1-PPA in neuroinflammation and microglial activation in Parkinson's disease. Protein aggregates and PAR2 expression were analyzed by thioflavin S assay and immunofluorescence in cultured human fibroblasts from Parkinson's patients, treated or not with 1-PPA. A significant decrease of amyloid aggregates and expression of PAR2 were observed after 1-PPA treatment in all patients. A parallel decrease of PAR2 expression, that was higher in sporadic Parkinson’s patients, was also observed both at transcriptional and protein level. In addition, in mouse LPS-activated microglia, the inflammatory profile was significantly downregulated after 1-PPA treatment, with a remarkable decrease of IL-1, IL-6 and TNF-togheter with PAR2 decreased expression.In conclusion, 1-PPA determines reduced neuroglia inflammation and amyloid aggregates formation, suggesting that pharmacological inhibition of PAR2 could be proposed as a novel strategy to control neuroinflammation.

Cryptococcus neoformans is a fungus that mainly affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, part of the first line of defense, important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse" taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal or capsule total did not present toxic effects for the DH82 macrophage cell line. However, it was possible to demonstrate that phagocytic activity was decreased after treatment with polysaccharides. In addition, yeasts recovered from macrophages treated with the polysaccharides, after phagocytosis, could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR- expression. Furthermore, our data suggests that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. Detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research of immunogenicity and duration of antibody response to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in hemagglutination inhibition assay. The dynamics of anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase, and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody level after vaccination directly correlated with titers before vaccination. Difference was found in response to NA antigen between split and subunit adjuvanted vaccines and in NA functional activity in the vaccine formulations.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

The system identification problem with multiple nonlinearities is relevant. Its decision depends on many factors. These include: feedbacks, the method of connecting nonlinear links, signal properties. They affect the identifiability of the system parameters. We introduced a condition for the excitation constancy for state variables, which considers the S-identifiability of the system. We propose system decomposition by measuring input to identify parameters. Each subsystem has an implicit identification representation. It guarantees obtaining estimates of subsystem parameters based on experimental data. The trajectories boundedness of adaptive system proved in parametric and coordinate spaces. Conditions guaranteeing exponential stability of the system obtained. Systems of self-oscillation generation and nonlinear correction of a nonlinear system consider. Conditions for the trajectories boundedness of the adaptive system obtained for these cases. The influence of nonlinearity and feedback on the system performance estimated.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging nanoprobes due to their excellent photostability. As one of the most commonly-used lanthanide activators, Tm3+ ions have perfect ladder-type electron configuration and can be directly excited by bio-friendly near-infrared-II (NIR-II) wavelengths. Here, the emission characteristics of Tm3+-doped nanoparticles under laser excitations of different near-infrared-II wavelengths were systematically investigated. The 1064 nm, 1150 nm and 1208 nm lasers are proposed to be three excitation strategies with different response spectra of Tm3+ ions. Particularly we found that 1150 nm laser excitation enables intense three-photon 475 nm emission, which is nearly 100 times stronger than that excited by 1064 nm excitation. We further optimized the luminescence brightness after investigating the luminescence quenching mechanism of bare NaYF4:Tm (1.75%) core. After growing inert shell, ten-fold increase of emission intensity was achieved. Combining the advantages of NIR-II wavelength and the higher-order nonlinear excitation, a promising facile excitation strategy was developed for the application of thulium-doped upconversion nanoparticles in single nanoparticle imaging and cancer cell microscopic imaging.

Stability considerations play a central role in structural dynamics to determine states that are robust against perturbations during the operation. Linear stability concepts, such as the complex eigenvalue analysis, constitute the core of analysis approaches in engineering reality. However, most stability concepts are limited to local perturbations, i.e. they can only measure a state’s stability against small perturbations. Recently, the concept of basin stability has been proposed as a global stability concept for multi-stable systems. As multi-stability is a well-known property of a range of nonlinear dynamical systems, this work studies the basin stability of bi-stable mechanical oscillators that are affected and self-excited by dry friction. The results indicate how the basin stability complements the classical binary stability concepts for quantifying how stable a state is given a set of permissible perturbations.

Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or in a few cases beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1-2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg-laying) or fertility (development of progeny to adulthood), but equivalent doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila, and that further extension of life is difficult in comparatively long-lived flies.

Pakistan flora is enriched with potent bioactive compounds that must be explored while Alzheimer's disease (AD) poses a global challenge driven by neurochemical imbalances. Acetylcholinesterase (AChE) inhibitors traditionally alleviate symptoms, but addressing the root cause remains elusive. This gap has led to the exploration of herbal sources for interventions. In this context, we analyzed fifty 50 medicinal plants for their phytochemical composition and antioxidant and acetylcholinesterase inhibition activities. AChE activity was measured using Ellman’s method. Santalum album exhibited significant AChE inhibition (86.2%), surpassing galantamine hydrobromide (81.8%). Promising inhibition was also seen in Bombax ceiba (77.8%), Acacia karoo (52.9%), and Phaseolus lunatus (50.1%). Detailed analysis revealed Santalum album's abundance in terpenoids, flavonoids, tannins, and phenolics, potentially correlating with its antioxidant and AChE inhibitory effects. Acacia karoo demonstrated elevated levels of total alkaloids, antioxidants, terpenoids, and tannins. Both Acacia karoo and Santalum album show promise for AD intervention due to their AChE inhibitory activities and unique phytochemical attributes, warranting further exploration, particularly for Acacia karoo's novel potential in AChE inhibition, to advance targeted AD therapeutics utilizing natural resources. This study contributes to the search for effective AD strategies from nature's pharmacological resources.

Flavonoids, a diverse group of polyphenolic compounds found abundantly in fruits, vegetables, and beverages like tea and wine, offer a plethora of health benefits. However, their potential interaction with drug metabolism, particularly through inhibition of the cytochrome P450 3A4 enzyme, the most versatile and abundant enzyme in the liver. CYP3A4 is responsible for metabolizing approximately 50% of clinically prescribed drugs across diverse therapeutic classes, so these interactions have raised concerns about potential adverse effects. This review delves into the scientific evidence surrounding flavonoid-mediated CYP3A4 inhibition, exploring the inhibitory potential of investigated flavonoids and future implications. Kusehnol I, chrysin, leachianone A and sophoraflavone G showed the largest inhibitory potentials and lowest IC50 values. While the clinical significance of flavonoid-mediated CYP3A4 inhibition in dietary contexts is generally considered low due to moderate intake and complex interactions, it poses a potential concern for individuals consuming high doses of flavonoid supplements or concurrently taking medications metabolized by CYP3A4. This can lead to increased drug exposure, potentially triggering adverse reactions or reduced efficacy.

Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas’ associated with poor prognosis. Resistance to ADT arises through various mechanisms, and most castration-resistant PCas’ still rely on the androgen axis, while others become truly androgen receptor (AR)-independent. Our research identified the human tousled-like kinase 1 (TLK1) as a crucial early mediator of PCa cell adaptation to ADT, promoting androgen-independent growth, inhibiting apoptosis, and facilitating cell motility and metastasis. Although explicit, the growing role of TLK1 biology in PCa has remained under-represented and elusive. In this review, we aim to highlight the diverse functions of TLK1 in PCa, shed light on the molecular mechanisms underlying the transition from androgen-sensitive (AS) to an androgen-insensitive (AI) disease mediated by TLK1, and explore potential strategies to counteract this process. Targeting TLK1 and its associated signaling could prevent PCa progression to the incurable metastatic castration-resistant PCa (mCRPC) stage and provide a promising approach to treating PCa.

“Minas Frescal” cheese is a high moisture product, subject to the proliferation of several microorganisms. Essential oils are natural antimicrobial alternatives that can increase the quality of dairy products. This study aimed to analyze the antimicrobial action of oregano (Origanum vulgare) and rosemary (Rosmarinus officinalis) essential oils against Escherichia coli and Staphylococcus aureus. An antimicrobial test by diffusion and microdilution was performed to calculate the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration). The behavior of E. coli in “Minas Frescal” cheese added with oregano oil was evaluated. The MIC of oregano oil was 0.25% against E. coli and 1% against S. aureus. For rosemary essential oil, the MIC was 8% of against E. coli. There was no activity of rosemary oil against S. aureus. The MBC observed for oregano essential oil was 1% and 0.25% respectively for S. aureus and E. coli. Bacterial analysis during cheese storage with E. coli indicated inhibition of microorganisms by oregano essential oil at a concentration of 0.25%. No alterations were observed regards to physical-chemical attributes. The use of essential oil as an antimicrobial agent has potential for industrial use, and type of microorganism, oil and sensory reflexes in the product must be observed.

Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.

The Paeonia suffruticosa, called as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely paeobenzofuranone A‒E (1‒5), have been characterized. Their structures were determined by spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines with IC50 values ranging from 6.7 to 25.1 μM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time.

There is little information on the use of pollen in molecular research, despite the increased interest to genome editing by pollen mediated transformation. PCR is useful tool as an express-method to evaluate editing results before pollination. A direct PCR protocol for pollen suspension has been adapted without the need for DNA pre-extraction. We showed that pollenkitt is a limiting factor for successful PCR on pollen. A simple pre-washing step of pollen suspension was able to eliminate the pollenkitt and enormously affect the PCR results. All currently existing methods of delivery of the editing system to pollen are carried out in a wet medium. Our pollenkitt study helped us develop a simple and effective pollination method using wetted onion pollen grains.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 minute-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with 2 control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed.Reduced BRS in FM at baseline increased by 41% during two, ≈8 minute-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps<0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (P<0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic pain modulation. These processes seem to be linked by classical and operant conditioning.

Choline kinase inhibitors are an important class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here we present the characterization and the structure activity relationship of a series of non-symmetrical choline kinase inhibitors characterized by a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and for their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the best inhibitory results were those connected to the linker by the N-atom (4a-h) and these results are supported by docking studies. The compounds with the best antiproliferative results were those connected to the linker by the O-atom (3a-h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is greater the shorter the length of the linker, while in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with a low toxicity in non-tumoral cells (e.g human peripheral lymphocytes) respect to cancer cells. These compounds were also able to induce to induce apoptosis in Jurkat leukemic cells without causing significative variations of cell cycle. It is worth to mention that these derivatives, beside their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

Arylsulfatase and β-glucuronidase are two important enzymes in human, which play important role on dynamic equilibrium of steroidal estrogens. This work probably for the first time reported that hydrogen peroxide (H2O2), hypochlorite and peracetic acid (PAA) could effectively inhibit the activities of arylsulfatase and/or β-glucuronidase. The 50 percent of inhibitions (IC50) of H2O2, and PAA on arylsulfatase were found to be 142.90±9.00, 91.83±10.01, and 43.46±2.92 μM, respectively. The corresponding respective IC50 of hypochlorite and PAA on β-glucuronidase were 704.90±41.40 and 23.26±0.82 μM, while H2O2 showed no inhibition on β-glucuronidase. It was further revealed that the inhibition of hypochlorite on both arylsulfatase and β-glucuronidase was irreversible. On the contrary, the inhibition by H2O2 and PAA was reversible. Moreover, it was found that the inhibitions of arylsulfatase and/or β-glucuronidase by these three chemicals were pH-dependent, among which the inhibition by H2O2 was competitive and non-competitive for PAA. In general, H2O2 and hypochlorite can be endogenously produced in human, which suggested that the two compounds are potential endocrine disruption compounds (EDCs) as they can cause endocrine disruption via inhibition of arylsulfatase and β-glucuronidase. This work further indicated that any agent that can induce production of H2O2 or hypochlorite in human is potential EDC, which explains why some EDCs with very weak or no estrogenic potency can cause endocrine disruption that confirmed in epidemiological studies.

The study compared antibacterial potential of hydrolysates of casein and alpha-lactalbumin from cow and goat milk on diarrhea-causing Escherichia coli and Staphylococcus aureus. Milk samples were aseptically obtained from lactating cows and goats. The samples were skimmed; casein was isolated using acetic acid and alpha-lactalbumin by filtrate thermoprecipitation at 75 °C. 50% of each isolate was reconstituted in a buffer and hydrolyzed with papain at 55 °C for 2 hours. The hydrolysates were heated to 75 °C to inactivate papain, cooled and their antibacterial activity determined by disc diffusion method. Results showed alpha-lactalbumins had higher degrees of hydrolysis and antibacterial activity than caseins; goat alpha-lactalbumin had the highest antibacterial activity with mean inhibition zones of 19.60 mm and 19.50 mm on E. coli and S. aureus. Cow alpha-lactalbumin inhibited E. coli more than S. aureus with inhibition zones of 16.80 mm and 12.50 mm. Cow and goat milk casein hydrolysates inhibited E. coli with mean inhibition zones of 8.00 mm and 10.90 mm and inhibited S. aureus with inhibition zones of 4.13 mm and 1.90 mm respectively. The research showed that the milk hydrolysates can be a source of antibiotics for diarrhea treatment. Research should be done to establish the peptide fractions associated with the observed bioactivity.

Acetic acid bacteria (AAB) form a bacterial film on the surface of alcoholic solutions and ferment ethanol to acetic acid while also producing bioactive compounds. To discover functional AAB for industrial use, we isolated and selected strains from farm-produced vinegars using a CaCO3-containing medium. The seven strains belonged to Acetobacter cerevisiae and A. pasteurianus. Physiological properties were determined, including ethanol tolerance at up to 12% (v/v). Acidification at a growth temperature of 40 ℃ was seen for GHA 7, GYA 23, JGB 21-17, and GHA 20 strains, which may be useful in vinegar production where thermotolerant AAB are required. The seven AAB isolates had strong antibacterial activity against Staphylococcus aureus. Antioxidant activity was 2- and 4-fold higher, respectively, for A cerevisiae and A. pasteurianus than for the control, 1% acetic acid. We also observed 91.3% inhibition of angiotensin-converting enzyme activity for the KSO 5 strain, higher than that for the positive control, 0.1% captopril (76.9%). All strains showed complete inhibition of α-glucosidase, except JGB 21-17 and GHA 7 with 98.3% inhibition. Our work suggests usefulness of the strains selected as seed strains for highly efficient production of functional vinegar and illustrates identification of useful functional characteristics on a scientific basis.

Low-energy cosmic rays (LECRs) play a crucial role in the formation of planetary systems, and detecting and reconstructing the properties of early LECRs is essential for understanding the mechanisms of planetary system formation. Given that LECRs interact with the surrounding medium to produce nuclear de-excitation line emissions with energy mainly within 0.1–10 MeV, which are unaffected by stellar wind modulation, these gamma-ray emissions can accurately reflect the properties of LECRs. This study introduces an innovative method for using gamma-ray emissions to infer LECR properties. We employed the Parker transport equation to simulate the propagation and spectral evolution of LECRs in a protoplanetary disk and calculated the characteristic gamma-ray emissions resulting from interactions between LECRs and disk material. These gamma-ray emissions encapsulate the spectral information of LECRs, providing a powerful tool to reconstruct the cosmic ray environment at that time. This method, supported by further theoretical developments and observations, will fundamentally enhance our understanding of the impact of CRs on the origin and evolution of planetary systems and address significant scientific questions regarding the cosmic ray environment at the origin of life.

The traffic light detection and recognition are crucial for enhancing the security of unmanned systems. This study proposes a YOLOv5-based traffic light detection algorithm to tackle the challenges posed by small targets and complex urban backgrounds. Initially, the mosaic-9 method is employed to enhance the training dataset, thereby boosting the network’s ability to generalize and adapt to real-world scenarios. Furthermore, the network incorporates the Squeezed-and-Excitation (SE) attention mechanism to improve. Moreover, the YOLOv5 algorithm’s loss function has been optimized by substituting it with EIoU_loss, which addresses issues like missed detection and false alarms. Experimental results demonstrate that the model , trained with this enhanced network, achieves a 99.4% mAP on a custom dataset, which is 6.3% higher than the original YOLOv5, while maintaining a detection speed of 74 f/s. Therefore, this algorithm offers higher detection accuracy and effectively meets real-time operational requirements.

The mechanisms of formation of induced intrinsic and impurity radiative states, which consist of intrinsic and impurity electron-hole trapping centers in irradiated Ca2P2O7-Mn and Ca2P2O7 phosphates, were investigated using thermoactivation and vacuum-ultraviolet spectroscopy methods. These centers are excited at photon energies of 4.0 eV and 4.5 eV, which are within the matrix's transparency region. New radiative induced states at 3.06 eV and 2.92 eV are demonstrated to be generated upon the excitation of anions by photons with energies of 5.0 and 5.64 eV. This process is due to charge transfer from the ion to the impurities, specifically Mn^2+ O^2- Mn^2+ and the neighboring ion O^2- (P2O7)^4-. Furthermore, upon the excitation of matrix anions with photon energies exceeding the band gap (8.0 - 8.25 eV), electron trapping by impurities such as Mn^2+ and (P2O7)^4- ions results.

This study utilises NaOH to treat composite cementitious materials containing aeolian sand and zeolite powders, which were used to replace 50% of the cement in aeolian-sand concrete (ASC). The mechanical properties of treated ASC considerably improved, especially when the NaOH dosage was 4% by mass. After curing this sample (denoted as AAZC-4) for 28 d, its compressive strength improved by 17.2% and its split tensile was increased by 16.3%. Potassium feldspar and montmorillonite in zeolite powder and SiO2 in the sand were decomposed by OH− and combined with other elements to generate various silicate gels and A-type potassium zeolite crystals inside the concrete. Microscopic examination showed that the gels and crystals intertwined to fill the pores, decreasing (increasing) the percentage of large (small) pores, thus optimising the pore structure. This substantially improved the mechanical properties of ASC. Freeze–thaw salt-intrusion tests showed that the extent of mass loss, degree of damage and loss of compressive strength of AAZC-4 were similar to those of ordinary concrete but were reduced by 36.8%, 19% and 52.1%, respectively, compared with those of ASC. Therefore, AAZC-4 has sustainable working performance in the chloride ion permeable environment in cold and arid areas.

. Interconnected control systems (ICS) widely apply to various technical systems. ICS has a complex description. Therefore, simplified models use, which the specifics of an object do not always reflect. So, the problem of synthesizing mathematical models is topical. The work purpose is to develop an approach to obtaining models in conditions of incomplete a priori information. We use an adaptive approach. As examples, two-channel systems (TCS) with cross-links and identical channels consider, and a method for mathematical model design. We consider the system with asymmetric cross-links and evaluate their impact on properties of an adaptive identification system. Approach proposed to assessing the TCS identifiability with cross-links. The excitation constancy influence on TСS parameter estimates is studied. A generalization of the proposed approach is given for an interconnected system.

We have investigated the canine of olive flounder in terms of the nonlinear optical signals of two-photon excitation autofluorescence (2PEF) and second harmonic generation (SHG), whereby two kinds of nonlinear microscope images of the canine were obtained using ~140 femtosecond pulses. For increasing excitation power of laser pulses, a photobleaching effect was found to be significant in the red and green ranges of autofluorescence, where a double-exponential decay of the intensity occurs within hundreds of second due to collagen fluorophores in the canine. In the blue range of autofluorescence, the photobleaching is suppressed due to an energy conversion of the incident laser pulse to SHG signal. As a result, the signal in blue range remains constant for long term exposure to laser. We have also found that the SHG intensity depends on the orienta-tion of linearly polarized excitation, and the optical anisotropy of SHG can be attributed to the collagen alignment of canines.

The structural identification (SI) problem of control objects has not been solved. The formalization and interpretation complexity of the structure concept is the main problem. In identification systems, the form of the model (its structure) choice is intuitive and bases on the experience and knowledge of the researcher in most cases. The task of parametric identification is often interpreted as SI. It introduces certain confusion in understanding of the task and decision-making. This is two different areas of research. The structural identification problem is multifaceted and includes many subtasks, and their solution gives the final result. Some tasks have been solved. The purpose of this work is to review existing approaches and methods to the structural identification problem of control objects from a system perspective. It is necessary to give the SI problem statement at the multiple-informational level to reflect the difficulties of formalizing SI. New directions to analyse that were not SI areas until now.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth and proliferation by down-regulating PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury and immune response. Therefore, recently PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Here we provide an overview of studies that highlight the role of oxidative inhibition of PTEN in physiological processes.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

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

Hydatid cyst fluid is a complex biological substance consisting primarily of water, proteins, lipids, carbohydrates, salts, enzymes, hormones, growth factors, immune modulators, and other bioactive molecules. Antigens, including antigen B (AgB) and antigen 5 family members (Ag5), have been identified in hydatid cyst fluid and have been shown to have the ability to inhibit cancer progression. The exact mechanisms by which these components exert inhibitory effects on cancer progression are not fully understood, but it is believed that they may influence multiple signaling pathways involved in cell proliferation, survival, angiogenesis, and metastasis. In vitro studies have demonstrated that treatment with hydatid cyst fluid or specific antigens can inhibit cell growth, induce apoptosis, and suppress the migration of cancer cells. Animal model studies have also demonstrated significant inhibition of tumor growth, reduction in angiogenesis, and suppression of metastasis. Limited clinical studies have shown promising outcomes, including improved overall survival and reduced recurrence rates among breast cancer patients receiving AgB immunotherapy alongside standard treatment.

Multiresistant pathogens pose a serious threat to human health. The genus candida is one class of human pathogenic yeasts responsible for infections affecting healthy and immunocompromised patients. In this context, plant essential oils emerged as a future natural alternative to control the diseases caused by these pathogens. Here, it highlighted antimicrobial activity and the mechanisms of action of the essential oil extracted from Croton pluriglandulosus Carn.-Torres & Riina (CpEO) leaves on human pathogenic microorganisms in planktonic and biofilm lifestyles. In addition, for the first time, the oil composition was revealed by GC-MS analysis and the toxicity to human red blood cells (HRBC). Twenty-six chemical compounds were identified in EOCp, Elemicin, Bicyclogermacrene, caryophyllene, brevifolin and 2,4,6-trimethoxy-styrene. Through hemolytic assay, it was shown that CpEO has no toxicity to human RBCs. At the concentration of 50 μg mL-1, CpEO did not show great antibacterial potential. However, promising data were found for C. krusei and C. parapsilosis inhibiting by 89.3% and 80.7% of planktonic cell growth and 83.5% and 77.9% the biofilm formation, respectively. Furthermore, the mechanisms of action CpEO were elucidated by fluorescence. Scanning electron microscopy revealed damage to the cell membrane and pore formation, ROS overproduction, and Induction of apoptosis in candida cells. Our results reinforce the potential of CpEO as an effective alternative molecule of pharmaceutical interest.

7α- and 7β-hydroxysteroid dehydrogenases (HSDH) are a pair of enzymes that can catalyze the isomerization of hydroxyl group at site 7 of bile acids. In previous study, we found that the activities of 7α- and 7β-HSDH can be inhibited by bilirubin. In order to clarify the impact, the effects of bilirubin on enzymes were studied by kinetics, spectrum and docking analysis. Relative activity of 7α-HSDH remained less than 40 % under 1 mM bilirubin, for 7β-HSDH, only 18 % activity left at the same condition. Using taurochenodeoxycholic acid (TCDCA) as substrate, the Km of 7α-HSDH was up to 0.63 mM from 0.24 mM after binding with bilirubin, the Km of 7β-HSDH rose from 1.14 mM to 1.87 mM for the catalysis of tauroursodeoxycholic acid (TUDCA). The affinity of 7α- and 7β-HSDH to substrate decreased with the effect of bilirubin. The binding of bilirubin with 7α- or 7β-HSDH were analyzed by UV–Vis spectra, Fluorescence spectra and Circular dichroism (CD) spectra. The results reflected that bilirubin caused a slight change in the secondary structure of 7α- or 7β-HSDH, and the changes were correlated with the ratio of bilirubin to enzyme. 10 candidate molecular docking results were presented to reflect the binding of bilirubin with 7α- or 7β-HSDH and to explore the inhibition mechanism. This research not only provides the more in-depth understanding of 7α- and 7β-HSDH, but also reminds us to avoid the inhibition of bilirubin on hydroxysteroid dehydrogenases.

Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.

Application of chemical pesticides to protect agricultural crops from pests and diseases is discouraged due to their harmful effects on human and environment. Therefore, alternative approaches for crop pro-tection through microbial or microbe originated pesticides have been gaining momentum. Wheat blast is a destructive fungal disease caused by Magnaporthe oryzae Triticum (MoT) pathotype, which poses a seri-ous threat to global food security. Screening of secondary metabolites against MoT revealed that antimy-cin A isolated from a marine Streptomyces sp. had significant inhibitory effect on mycelial growth in vitro. This study aimed to investigate the inhibitory effects of antimycin A on some critical life stages of MoT and evaluate the efficacy of wheat blast disease control by this natural product. Bioassay indicated that antimycin A suppressed mycelial growth, conidiogenesis, germination of conidia and formation of ap-pressoria in germinated conidia of MoT in a dose-dependent manner with minimum inhibitory concen-tration 0.005 μg/disk. If germinated, antimycin A induced abnormal germ tubes (4.8%) and suppressed the formation of appressoria. Interestingly, application of antimycin A significantly suppressed wheat blast disease in both seedling and heading stages of wheat supporting the results from invitro study. This is the first report on inhibition of mycelial growth, conidiogenesis, conidia germination, detrimental morphological alterations in germinated conidia, and suppression of wheat blast disease caused by a Triticum pathotype of M. Oryzae. Further study is required to unravel the precise mode of action of this promising natural compound for considering it as a biopesticide to combat wheat blast.

Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP [N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium)] inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while acting through different mechanisms. Charged phospholipids were found to have antiviral effects and can may be used to inhibit EHV-1 infection.

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

New approaches to deal with drug-resistant pathogenic bacteria are urgent. We studied the antibacterial effect of chitosans against an E. coli quorum sensing biosensor reporter strain, and selected a non-toxic chitosan to evaluate its QS inhibition activity and its effect on bacterial aggregation. To this end, chitosans of varying DA (12 to 69%) and M_w (29 to 288 KDa) were studied. Only chitosans of low DA (~12%) inhibited the bacterial growth, regardless of the M_w. Chitosan MDP DA30 (DA 42% and M_w 115 kDa) was selected for further QS inhibition and SEM imaging studies. MDP DA30 chitosan exhibited QS inhibition activity in an inverse dose-dependent manner (≤12.5 µg/mL). SEM images revealed that this chitosan, when added at low concentration (≤30.6 µg/mL), induced substantial bacterial aggregation, whereas at high concentration (234.3 µg/mL), it did not. Aggregation explains the QS inhibition activity as the consequence of retardation of the diffusion of AHL.

1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-4-phenyl-1H-1,2,3-triazole (Ph4) and1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-5-phenyl-1H-1,2,3-triazole (Ph5) are new isomers of the triazole derivative family, were synthesized and tested on the corrosion of mild steel in molar hydrochloric acid molar media using weight loss, electrochemical polarization and impedance spectroscopy. Then the experimental results were confirmed by quantum chemical calculations using DFT at B3LYP /6-31G (d,p). The compound Ph4 is the best inhibitor and its inhibitory efficiency increased with increasing concentration and reaching 95% at 10⁻³ M. Polarization curves studies show that both compounds tested are mixed-type inhibitors. Nyquist curves presented a single capacitive loop, their diameter increases progressively with both inhibitors concentration. The change of the substitution phenyl from position 5 to position 4 in the triazole ring increases the inhibitory effect of the triazole compounds. The effect of temperature on the corrosion behavior of iron indicates that the inhibitory efficiency of the two inhibitors decreases with increasing temperature in the range of 308 to 338K. DFT study is in good correlationwith the experimental results.

The optimal regime of three-photon resonant excitation of a helium atom by a femtosecond ul-traviolet (UV) pulse was discovered and numerically studied, at which the maximum power of the third harmonic of the UV field is achieved in the spectrum of dipole acceleration (the second time derivative of the induced dipole moment) of the atom. It is shown that the optimal frequency of the UV field nearly coincides with the frequency of the three-photon transition 1s2 – 1s2p, taking into account its shift as a result of the dynamic Stark effect, and the intensity of the UV field is dictated by the condition of maximizing the product of the populations of the 1s2 and 1s2p states, averaged over the time interval during which the UV field is non-zero. For the considered UV field durations, from 10 to 100 cycles of the carrier frequency (from units to tens of femtoseconds), the optimal intensity lies in the range from 10^14 W/cm^2 to several units of 10^14 W/cm^2. It is shown that with an optimal choice of the frequency and intensity of the UV field, the dynamics of excitation of bound and continuum states, as well as the shape of the time envelope of the dipole acceleration of the atom, weakly depend on the duration of the UV field envelope; only their time scale changes significantly. In addition, under the optimal conditions the average power of the third harmonic signal in the dipole acceleration spectrum is practically independent of the duration of the UV field envelope.

Silicon light funnels are three-dimensional subwavelength structures in the shape of inverted cones with respect to the incoming illumination. Light funnel arrays can serve as an efficient absorbing layers on account of their light trapping capabilities associated with the presence of high density complex Mie modes. Specifically, light funnel arrays exhibit broadband absorption enhancement of the of the solar spectrum. In the current study, we numerically explore the optical coupling between surface light funnel arrays and underlying substrates. We show that the absorption in LF array-substrate complex is higher than the absorption in LF arrays of the same height (~10% increase). This, we suggest, imply that a LF array serves as an efficient surface element that imparts additional momentum components to the impinging illumination, and hence optically excites the substrate by near-field light concentration, excitation of traveling guided modes in the substrate and mode hybridization.

The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

The impacts of spice (sumac, cumin, black pepper, and red pepper) extract on Gram-positive (S. aureus and E. faecalis) and Gram-negative (K. pneumonia, P. aureginosa, C. jejuni, A. hydrophila, S. Paratyphi A, and Y. enterocolitica) food-borne pathogen bacterial strains (FBP) for their antibacterial activity and accumulation of ammonia (AMN), trimethylamine (TMA), and biogenic amines (BAs) in tyrosine decarboxylase broth (TDB) were investigated. Sumac extract exhibited the highest an-tibacterial potential against all FBP followed by cumin and peppers. Ammonia (AMN) production (844.24-543 mg/L) was strongly inhibited by sumac extract (55.10 mg/L), whilst suppression of trimethylamine (TMA) production (53.66-3.21 mg/L) was observed by sumac (1.28 mg/L), followed by red pepper (0.91 mg/L) extract. Cumin extracts stimulated the production of cadaverine, spermidine, tryptamine, and 2-phenylethylamine. Furthermore, sumac extracts inhibited hista-mine and tyramine production in the majority of FBP. This research suggests the application of sumac extracts as natural preservatives for inhibiting the growth of FBP and inhibiting the pro-duction of AMN, TMA, and BAs.

Therapeutic phages are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this study, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we show that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in presence of active complement. Our results indicate that interactions with complement may affect in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

The primary goal of this research is to examine the α-amylase inhibitory effect of phytoconstituents found in the roots of the Cyclea peltata plant. The extract will also be used to investigate the effect of root extract on α-amylase inhibition assay. The roots were gathered, processed, and extracted in petroleum ether before being kept at 4ºC. The extract was exposed to a preliminary phytochemical examination. The extract was employed in the α-amylase inhibition experiment at concentrations of 50, 100, 200, 400, 600, 800, and 1000 µg/ml with acarbose as a control. Molecular docking analysis was performed on the phytoconstituents cycleapeltine, cycleadrine, cycleacurine, cycleanorine, cycleahomine chloride, and acarbose on human pancreatic alpha-amylase 1B2Y. A preliminary phytochemical study revealed the presence of alkaloids, saponins, and terpenoids. The tests came back negative for flavonoids, steroids, and tannin. The root extract inhibited α-amylase at 69.42 ± 0.74 % at 1000 µg/ml and acarbose at 94.63 ± 0.57 %. The IC50 value was calculated and found to be 484.08 µg/ml for the extract and 42.47 µg/ml. The docking studies, revealed that cycleacurine (-4.751 Kcal/mol) has a comparable anti-diabetic effect to Acarbose (-6.713 Kcal/mol). Furthermore, the function groups –OH and –NH found in phytoconstituents interacted with the active site of 1B2Y similarly to acarbose. This provides evidence that the function groups –OH and –NH present in the phytoconstituents might inhibit alpha amylase.

Antibiotic-sparing treatments are required to prevent the further emergence of anti-microbial resistance in Neisseria gonorrhoeae. Commensal Neisseria species have previously been found to inhibit the growth of pathogenic Neisseria species. For example, a previous study found that 3 out of 5 historical isolates of Neisseria mucosa could inhibit the growth of N. gonorrhoeae. In this study, we used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. Although pitting around each colony of N. mucosa created an optical illusion of decreased growth of N. gonorrhoeae, we found no evidence of inhibition (n=24). In contrast, positive controls of Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.

Obesity is a condition associated with the accumulation of excess fat in the body, energy imbalance, lipogenesis etc. which increases adipose tissue mass through adipogenesis and probes a health risk. Its prevalence has become a large burden on the world at large. One of the solutions to tackling obesity is with the use of bioactive compounds. We critically examined the effectiveness of hibiscus sabdariffa (HS) on various parameters associated with development of obesity such as; effect of HSE on body weight and energy expenditure, effect of HSE on fat accumulation, effect of HSE on lipase inhibition, effect of HSE on adipocyte differentiation/adipogenesis. This review has gathered reports on the various anti-obesity effects of HS bioactives in cell and animal models, as well as in humans. Reports have shown that hibiscus sabdariffa derived bioactives are potent in the treatment of obesity with evident reduction in body weight, inhibition of lipid accumulation and suppression of adipogenesis through PPARγ pathway and other transcriptional factors.

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

TaABCC13 is member of wheat ABCC subclass of transporters. The RNAi mediated silencing of this transporter in wheat results in lowering of seed phytic acid level and other developmental defects. In addition to that, wheat ABCC13 was involved in cadmium detoxification as evident by the complementation assays in yeast. The appearance of early lateral roots in these transgenic seedlings speculated the possibility for studying the role of localized auxin-mediated effects. In the current study, firstly, the expression of auxin related genes was studied in the transgenic roots. Enhanced expression of genes pertaining to either auxin biosynthesis or its transport was observed in transgenic wheat seedling roots suggesting the direct effect of the hormone. Further, the early emergence of lateral roots in transgenic wheat seedlings was affected due to the presence of auxin-transport inhibitor suggesting the direct effect of hormones in root development. In conclusion, herein we provide the novel evidence for the auxin mediated regulation of lateral root emergence in TaABCC13:RNAi seedlings.

Climate-induced changes contribute to the thawing of ice-rich permafrost in the Arctic, which leads to the release of large volumes of organic carbon into the atmosphere in the form of greenhouse gases, mainly carbon dioxide and methane. Ground ice constitutes a considerable volume of the cryogenically sequestered labile dissolved organic carbon (DOC) subjected to fast mineralization upon thawing. In this work we collected an unique geochemical database of the ground and glacier ice comprising the samples from various geographic locations characterized by a variety of key parameters, including ion composition, carbon-bearing gases (methane and carbon dioxide) bulk biogeochemical indicators and fluorescent dissolved organic matter (DOM) fractions. Our results show that interaction with solid material—such as sediments, detritus, and vegetation—is likely the overriding process in enrichment of the ground ice in all the dissolved compounds. Terrigenous humic-like dissolved organic matter was predominant in all the analyzed ice samples except for glacier ice and pure tabular ground ice from Mare Sale (Western Yamal). The labile protein-like DOM, indicating an autochthonous source, showed no correlation to humic components and probably associated with microbial abundance in the ground ice. The sum of the fluorescent DOM components satisfactory correlates to DOC, indicating the adequacy of the estimation. The pure tabular ground ice samples exhibit the highest biogeochemical quality which may be responsible for the amplification of permafrost organic matter decomposition upon thawing. Yamal impure tabular ground ice and ice wedges are extremely enriched in methane compared to the samples from other locations which should cause a portion of direct methane emission upon the putative thawing.

Object recognition is an essential element of machine intelligence tasks. However, one model cannot practically be trained to identify all the possible objects it encounters. An ensemble of models may be needed to cater to a broader range of objects. Building a mathematical understanding of the relationship between various objects that share comparable outlined features is envisaged as an effective method of improving the model ensemble through a pre-processing stage, where these objects' features are grouped under a broader classification umbrella. This paper proposes a mechanism to train an ensemble of recognition models coupled with a model selection scheme to scale-up object recognition in a multi-model system. An algorithmic relationship between the learnt parameters of a trained classification model and the features of input images is presented in the paper for the system to learn the model selection scheme. The multiple models are built with a CNN structure, whereas the image features are extracted using a CNN/VGG16 architecture. Based on the models' excitation weights, a neural network model selection algorithm, which links a new object with the models and decides how close the features of the object are to the trained models for selecting a particular model for object recognition is developed and tested on a five-model neural network platform. The experiment results show the proposed model selection scheme is highly effective and accurate in selecting an appropriate model for a network of multiple models.

Blood perfusion quantification is important vital parameters in different diagnostic procedure, using infrared thermography imaging; it is reliable to use this technique as non-contact, non-invasive blood flow measurement method. Therefore, we developed a measurement protocol for blood flow over the arm's anterior surface. By using the superficial brachial and radial veins to be monitored under the impact of cold-excitation of (2 °C to 5 °C), the blood perfusion signal was detected using thermal imager of long-wave infrared spectral range (LWIR, 7μm - 14 μm). The simulation of Penne's bioheat transfer equation was performed to be compared with results obtained from the infrared thermography. Furthermore, the proposed blood flow monitoring using external adjusting of the excitation temperature, by using (cold-compress, or cold air-stream) applied to the region under testing. The signal detected resembles to the hemodynamic pulse of the superficial veins, in the definition of systolic and diastolic phases of the cardiac cycle. Moreover, statistical analysis applied to the BFIRT signals from 24 subjects to estimate the skin's mean temperature after recovery from the thermal excitation.

The spectra currently emerging from modern ground- and space-based astronomical instruments are of exceptionally high quality and resolution. To meaningfully analyse these spectra researchers utilise complex modelling codes to replicate the observations. The main inputs to these codes are atomic data such as excitation and photoionisation cross sections as well as radiative transition probabilities, energy levels and line strengths. In this publication the current capabilities of the numerical methods and computer packages used in the generation of these data are discussed. Particular emphasis is given to Fe-peak species and the heavy systems of tungsten and molybdenum. Some of the results presented to highlight certain issues and/or advances have already been published in the literature, while other sections present, for the first time, new recently evaluated atomic data.

This study used Dutch potatoes at the end of dormancy as the material to explore the impact of menthol (0.2 and 0.5 g/kg based on potato mass) treatment on sprouting inhibition and potato quality. The findings revealed that a menthol concentration of 0.5 g/kg effectively inhibited potato tuber sprouting and significantly reduced glucoside alkaloids production. After a storage period of 15 days, the sprouting percentage and glucoside alkaloids content of potatoes treated with 0.5 g/kg menthol were observed to be significantly lower at 4.17% and 68.63 mg/kg, respectively, compared to the control group which exhibited values of 100% and 282.01 mg/kg, respectively (P < 0.05). Throughout the storage period, 0.5 g/kg of menthol promoted respiration, reduced malondialdehyde production in potatoes, inhibited polyphenol oxidase activity, and slowed down tissue browning. Additionally, it mitigated the decline in starch and soluble protein content, inhibiting the accumulation of reducing sugars.

Core chlorophytes possess glycerol-3-phosphate dehydrogenases (GPDs) with an unusual bidomain structure, consisting of a glycerol-3-phosphate phosphatase (GPP) domain fused to canonical GPD domains. These plastid-localized enzymes have been implicated in stress responses, being required for the synthesis of glycerol under high salinity and triacylglycerols under nutrient deprivation. However, their regulation under varying environmental conditions is poorly understood. C. reinhardtii transgenic strains expressing constitutively bidomain GPD2 did not accumulate glycerol or triacylglycerols in the absence of any environmental stress. Although, the glycerol contents of both wild type and transgenic strains increased significantly upon exposure to high salinity. Cycloheximide, an inhibitor of cytoplasmic protein synthesis, abolished this response in the wild type. In contrast, GPD2 transgenic strains were still capable of glycerol accumulation when cultured in medium containing cycloheximide and NaCl. Thus, pre-existing GPD2 protein appears to become activated for glycerol synthesis upon salt stress. Interestingly, staurosporine, a non-specific inhibitor of protein kinases, prevented this post-translational GPD2 protein activation. Structural modeling analyses suggested that substantial conformational rearrangements, possibly triggered by high salinity, may characterize an active GPD2 GPP domain. Understanding this mechanism(s) may provide insights into the rapid acclimation responses of microalgae to osmotic/salinity stress.

World population is in a demographic transition, with an increase in number of older adults and prevalence of diseases related to aging. This study evaluated in vitro the potential of an ultrasound-assisted extract from Durvillaea incurvata to inhibit key enzymes associated with development of age-related diseases. Results show that an ultrasound-assisted extract as well as conventional extract from Durvillaea incurvata presented anti-diabetes potential by exhibiting inhibitory activity against α-glucosidase enzymes (91.8 ± 1.0 % and 93.8 ± 0.3 % respectively, at 500 µg/mL) and α-amylase (42.2 ± 1.4 % and 61.9 ± 0.9 % respectively, at 1500 µg/mL), related to starch digestion and postprandial glycemic response. Also, extracts presented inhibitory activity on the enzyme acetylcholinesterase (51.5% and 50.8% respectively, at 500 µg/mL) and butyrylcholinesterase (32.8% and 34.4% respectively, at 0.5 mg /mL), biomarkers associated with Alzheimer's disease, and showed inhibitory activity against angiotensin-I converting enzyme (98.7 ± 7.4% and 93.0 ± 3.4% respectively, at 2.0 mg /mL), key in the regulation of vascular tone and blood pressure, which helps to prevent the development of hypertension. In conclusion, the ultrasound-assisted extract of Durvillaea incurvata has the potential to prevent the development of age-related pathologies, such as diabetes, Alzheimer's disease, and hypertension.

Marine yeasts have versatile applications in industrial, medical and environmental fields, but have received little attention compared to terrestrial yeasts and filamentous fungi. In this study, a phylogenetic analysis of 11 marine-derived yeasts was conducted using internal transcribed spacers and nuclear large subunit rDNA, and their bioactivities, such as antioxidant, antibacterial, and tyrosinase inhibition activities, were investigated. The 11 marine-derived yeasts were identified to belong to seven species including Geotrichum candidum, Metschnikowia bicuspidata, Papiliotrema fonsecae, Rhodotorula mucilaginosa, Vishniacozyma carnescens, Yamadazyma olivae, and Yarrowia lipolytica, and three strains of these were candidates for new species of the genera Aureobasidium, Rhodotorula, and Vishniacozyma. Most extracts showed antioxidant activity, whereas seven strains exhibited antibacterial activities against Bacillus subtilis. Only Aureobasidium sp. US-Sd3 among the 11 isolates showed tyrosinase inhibition. Metschnikowia bicuspidata BP-Up1 and Yamadazyma olivae K2-6 showed notable radical-scavenging activity, which has not been reported previously. Among the isolates, Aureobasidium sp. US-Sd3 exhibited the highest antibacterial and tyrosinase inhibitory activities. Overall, our results demonstrate the potential of marine-derived yeasts as a source of bioactive compounds for improving industrial applications.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

High production cost is one of the major factors that limit the market growth of polyhydroxyalkanoates (PHAs) as a biopolymer. Improving PHA synthesis performance and utilizing low grade feedstock are two logical strategies for reducing the cost. As an oleaginous yeast, Y. lipolytica has a high carbon flux through acetyl-CoA (main PHB precursor) which makes it a desired cell factory for PHB biosynthesis. Two different metabolic pathways introduced into Y. lipolytica PO1f in this study for enhancing PHB biosynthesis, along with glucose and acetate as co-substrates. Results showed that NBC pathway led to more than 11% PHB accumulation, while there was non-detectable PHB accumulations using ABC pathway. Further modifications were done using peroxisomal compartmentalization and gene-dose overexpression. Final strain showed up to 41% PHB of CDW with a growth rate of 0.227 h-1. Low growth rate was observed using acetate or glucose as sole carbon and energy source. The co-substrate strategy showed compensatory effect on overcoming inhibitory and toxic effects of both substrates at high concentrations. Cultivating the engineered strain in optimal co-substrate condition predicted by RSM led to 83.4 g/L biomass concentration and 31.7 g/L PHB.

This article presents a low-cost and flexible solution for acoustic startle response (ASR) tests that can be used in any laboratory with CED Power1401 or a similar Spike2-based interface. ASR is a reflexive response to an unexpected, loud acoustic stimulus, and prepulse inhibition (PPI) is a phenomenon in which the startle response is reduced when preceded by a weak prestimulus of the same modality. Measuring PPI is important because changes in PPI have been observed in patients with various psychiatric and neurological disorders. Commercial ASR testing systems are expensive, and their closed source code affects their transparency and result reproducibility. The proposed setup is easy to install and use, and simultaneous recording of ASR and brain activity (electrocorticogram or intracerebral local field potential) is possible. The Spike2 script is customizable and supports a wide range of PPI protocols. The article presents data obtained in female rats, both wild-type (WT) and dopamine transporter knockout (DAT-KO), showing the same tendency as the data obtained in males, with ASR on single pulse higher than ASR on prepulse+pulse, and PPI reduced in DAT-KO rats compared to WT.

Human induced pluripotent stem cells (hiPSCs) have two characteristic abilities 1) self-renewal and 2) differentiation into all cell types in the human body. It is this ability of iPSCs to differentiate into any desired cell type that makes them amenable to disease modeling. iPSCs can further be engineered to carry a disease-specific mutation or be derived from patients to phenocopy the disease. To model neurodegenerative/neurodevelopmental disorders iPSCs are differentiated into neurons. This chapter describes protocols for two different approaches to generate neurons from iPSCs, first using dual SMAD inhibition to generate neural progenitor cells which are then differentiated into neurons, and second using single transcription factor (NGN2) over-expression to drive differentiation of iPSCs directly into neurons.

Background: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β -Lapachone, a novel synthetic compound. Methods: The antibacterial activity of the β -Lapachone compound was examined against laboratory strains by agar well diffusion method, minimal inhibitory concentration (MICs), and minimal bactericidal concentration (MBCs). Growth kinetics inhibition in presence of β -Lapachone on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (ATCC 27853) was assessed by MABA. Crystal violet blue assay was used for biofilm inhibition assays, biofilm eradication assay and for molecular modeling PyMOL was used. Results: β -Lapachone exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Molecular modeling predicted the binding of β -Lap at active site and heme binding site of catalase, KatA. The activity of some commercial antibiotics was enhanced in association with β -Lap. In addition, β -Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains.

Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.

Executive functions comprise top-down cognitive processes that exert control over information processing, from acquiring information to issuing a behavioural response. These cognitive processes of inhibition, working memory and shifting underpin complex cognitive skills, such as episodic memory and planning, which have been repeatedly investigated in several bird species in recent decades. Until recently, avian executive functions were studied in relatively few bird species, but have gained traction in comparative cognitive research following MacLean and colleagues’ large-scale study (2014). Therefore, in this review paper, relevant previous findings are collected and organized to facilitate further investigations of these core cognitive processes in birds. This review can assist in integrating findings from avian and mammalian cognitive research and further current understanding of executive functions’ significance and evolution.

Mayaro virus (MAYV) hijacks the host´s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPKs inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126 or Losmapimod were quantified using plaque assay. Also, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

The effects of mixing orders of tannic acid (TA), starch and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Besides, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol may have an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

The current research investigated the environmental risk of the polycyclic musk compounds, Galaxolide® (HHCB) and Tonalide® (AHTN), in the marine environments. These substances are lipophilic, bioaccumulated and potentially biomagnified in aquatic organisms. To understand the toxicity of HHCB and AHTN, we performed acute toxicity tests by exposing marine microalgae (Phaeodactylum tricornutum, Tretraselmis chuii and Isochrysis galbana), crustaceans (Artemia franciscana), echinoderms (Paracentrotus lividus), bivalves (Mytilus galloprovincialis), fish (Sparus aurata) and a candidate freshwater microalga (Raphidocelis subcapitata) to environmentally relevant concentrations (0.005 - 5 µg/L) following standardized protocols. The effects of both substances on microalgae growth were incipient and only I. galbana was sensitive to HHCB and AHTN, with IC10 values of 5.22 µg/L and 0.328 µg/L, respectively. Significant (p < 0.01) concentration dependent responses were measured in P. lividus and M. galloprovincialis larvae developments as well as S. aurata mortality tested with HHCB. The effect of HHCB on P. lividus larvae development was the most sensitive endpoint recorded, producing an EC50 value of 4.07 µg/L. Our results show that HHCB represents a high risk to P. lividus larvae development for early life stages in marine environments.

Recent studies suggest that the developmental curves in adolescence, related to the development of executive functions, could be fitted to a non-linear trajectory of development with progressions and retrogressions. Therefore, the present study proposes to analyze the pattern of development in Perceptual Inhibition (PI), considering all stages of adolescence (early, middle, and late) in intervals of one year. To this aim, we worked with a sample of 275 participants between 10 and 25 years, who performed a joint visual and search task (to measure PI). We have fitted exGaussian functions to the probability distributions of the mean response time across the sample and performed a covariance analysis (ANCOVA). The results showed that the 10- to 13-year-old groups performed similarly in the task and differ from the 14- to 19-year-old participants. We found significant differences between the older group and all the rest of the groups. We discuss the important changes that can be observed in relation to the nonlinear trajectory of development that would show the PI during adolescence.

There is an urgent need to identify effective therapies for COVID-19. The SARS-CoV-2 host factor protease TMPRSS2 is required for viral entry and thus an attractive target for therapeutic intervention. In mouse, knockout of tmprss2 led to protection against SARS-CoV-1 with no deleterious phenotypes, and in human populations genetic loss of TMPRSS2 does not appear to be selected against. Here, we mined publicly available gene expression data to identify several compounds that down-regulate TMPRSS2. Recognizing the need for immediately available treatment options, we focused on FDA-approved drugs. We found 20 independent studies that implicate estrogenic and androgenic compounds as transcriptional modulators of TMPRSS2, suggesting these classes of drugs may be promising therapeutic candidates for clinical testing and observational studies of COVID-19. We also note that expression of TMPRSS2 is highly variable and skewed in humans, with a minority of individuals having extremely high expression. Combined with literature showing that inhibition of TMPRSS2 protease activity reduces SARS-CoV-2 viral entry in human cells, our results raise the hypothesis that modulation of TMPRSS2 expression is a promising therapeutic avenue for COVID-19.

The anodic polarization response of magnesium alloy AZ31 was characterized during exposure to aerated 0.1M NaCl solutions with millimolar additions of NaVO₃, Na₃PO₄, Na₂HPO₄, NaF and various pairings to assess their ability to inhibit corrosion kinetics and retard localized corrosion. Each of the candidate inhibitors reduced the corrosion rate of the alloy to some degree. A Na₃PO₄ - NaVO₃ pair produced a powerful inhibiting response decreasing the corrosion rate to about 10^-7 A/cm², which was two orders of magnitude lower than the uninhibited control case. A Bliss Independence assessment indicated that this inhibitor pair acted synergistically. A Na₂HPO₄ - NaVO₃ pair reduced the corrosion rate to 10^-6 A/cm² but was not assessed to be acting synergistically. The NaVO₃ - NaF pair did not reduce the corrosion rate significantly compared to the control case and was an antagonistic pairing. SEM imaging showed film formation due to exposure, which appears to be the origins of the observed inhibition. The resistance to localized corrosion was assessed as the difference in the breakdown potential and the corrosion potential with larger values indicating a lower probability of localized corrosion during free corrosion exposures. Effects of the inhibitors on this characteristic were mixed, but each of the inhibitor pairs yielded potential differences in excess of 100mV. A conceptual conversion coating process based on a mixture of vanadate and phosphate compounds were demonstrated. A fluoride-bearing formulation produced coatings whose total impedance was increased by a factor or 2 compared to an uncoated control. A fluoride-free formulation produced coatings whose corrosion resistance was increased by more than a factor of 3.

Structural perturbations in the Mn4CaO5 cluster site, an oxygen-evolving complex of photosystem II, such as those induced by Ca2+/Sr2+ exchanges or Ca/Mn-removal have been known to induce long-range positive shifts (+30 mV to +150 mV) in the redox potential of the primary quinone electron acceptor plastoquinone A (QA) located 40 Å distant from the OEC. Here, we reanalyzed the crystal structure of Sr-PSII solved at 2.1 Å and compare it with the native Ca-PSII of 1.9 Å with focus on the acceptor site and report on the possible long-range interactions between the donor, Mn4Ca(Sr)O5 cluster, and acceptor sites.

The complexity of objects and control systems increases the requirements for mathematical models. The structural identifiability (SI) assessment of nonlinear systems is one of the identification problems. Until now, this problem solves by parametric methods using various approximation methods. This approach is not always effective under uncertainty. We apply an approach to SI estimation based on the analysis of virtual structures. The requirements form for the system input based on the expansion of the excitation constancy property and S-synchronizability. The approach generalization to structural identifiability used in the analysis of systems with symmetric nonlinearity is given. homothety and identifiability conditions for systems with non-symmetric nonlinearities (SNN) obtained. The detectability and recoverability proofed for virtual frameworks (VF) guaranteed the SI estimation under uncertainty. The conditions under which the non-symmetric nonlinearity is hypothetical symmetric nonlinearity obtained. SI estimation examples considered for closed nonlinear systems under uncertainty.

Swimming pools are examples of water-intensive facilities, where solutions for reducing economic and environmental costs are increasingly frequently searched. One of the solutions is the recovery of water from wastewater, including from washings obtained through the process of rinsing filter bed. The study objective was the qualitative and quantitative assessment of post-coagulation sludges, the main pollutant found in the washings. During the analyses, assessment of the sedimentation capabilities of the sludges was performed (gravitationally), particle size distribution was assessed (particle size distribution analyzer) and assessment of phytotoxicity with the use of plant indicators in short-term tests was performed (Lemna minor, Lepidium sativum, Sinapis alba, Raphanus sativus). The samples were collected from two independent circulations, which differed in terms of capacity and type of coagulant used. The tested post-coagulation sludges were characterized by high content of total suspended solids: in samples from Circulation 1 from 251 to 128 mg/l, in Circulation 2 from 489 to 228 mg/l. However, the sedimentation processes enabled significant separation of sludges. The hydrolyzed coagulant contributed to the improvement of sedimentation capabilities of sludges. Despite the fact that in many samples low sludge concentrations favored stimulation of plant growth, the post-coagulation sludges can constitute a hazard to plant growth, particularly in the long-term perspective.

The present study investigates the role of a simple inerter in supplemental devices for possible implementation in the matured seismic base isolation technique. Firstly, the response of the base-isolated structure with an optimally tuned mass damper-inerter (TMDI) is investigated to see the tuning effects. The time required to tune the TMDI was found to be significantly longer than the duration of a strong-motion earthquake. There was still a reduction in the response of the isolated structure, which is primarily due to the added damping and stiffness (ADAS) of TMDI and not because of the tuning effects. Hence, it is proposed that the corresponding ADAS of the TMDI be directly added to the isolation device. Secondly, the response of the base-isolated structures with the fluid inerter damper (FID) is studied. It was observed that the inerter of the FID does not influence the displacement variance of an isolated structure under broadband earthquake excitation. It implies that the response of the isolated structure with FID is primarily controlled by its counterpart fluid damper (FD). The performance of optimal TMDI, ADAS, FID, and FD to mitigate the seismic response of the flexible multi-story base-isolated structure under real earthquake excitations is also investigated. In terms of suppressing the displacement and acceleration responses of the isolated structure, it has been found that TMDI and ADAS perform similarly. Comparing the response of the isolated structure with FID and FD demonstrated that the inerter in the FID has detrimental effects on the isolated structures, in which the top floor's acceleration and base shear are substantially increased.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).