Proposed Mechanism Research Articles

Obliteration of the Processus Vaginalis After Testicular Descent.

The testis develops in the abdominal cavity and descends into the scrotum. Although numerous theories have been proposed, the mechanism of descent and the reason for its inhibition remain unknown. Furthermore, none of the explanations account for the other occurrences related to the descent, such as failed obliteration of the processus vaginalis, or the reasons for the decrease in fertility and increase in the risk of malignancy associated with an undescended testis. The gubernaculum is a primitive mesenchymal tissue that was first described in 1786. However, the role of the gubernaculum in the descent process remains obscure. The testis descends through the processus vaginalis. Although the processus vaginalis (PV) is usually defined as a simple peritoneal protrusion, it actively develops into the gubernaculum. The gubernaculum gives rise to the smooth muscles that surround the processus vaginalis. The striated cremaster muscle (CM) is also derived from the gubernaculum. Because the testis descends through the processus vaginalis, the muscles develop to propel the testis. After propelling the testis, the smooth muscle (SM) undergoes programmed cell death. The initiation of programmed cell death through the intrinsic pathway requires activation of phospholipase C. A transient shift in the autonomic balance via a decrease in the sympathetic tonus and an increase in the parasympathetic tonus is essential for initiating this programmed cell death. Programmed cell death in the SM is the physiological pathway for the obliteration of the processus vaginalis. Differences in the timing, intensity, or duration of this physiological pathway result in pathological conditions. A shift before testicular descent diminishes the SM content that is required to propel the testis, and thus inhibits descent. The early shift persists throughout childhood and results in the decrease in fertility and increase in the risk of malignancy because of the differences in signal transduction. Despite a successful descent, persistence of the shift alters the contractility of the CM by increasing the cytosolic calcium levels. Contracted CMs retracts or even ascends the testis. Inadequate intensity or duration of the shift of autonomic tonus causes failure of the programmed cell death. Persistence of the SM hinders the obliteration of PV and gives rise to hydroceles or inguinal hernias depending on the amount of residual smooth muscles. Similar findings from different countries support these explanations. Thus, our proposed mechanism satisfactorily explains the process of descent while considering all the factors related to the process of testicular descent.

Immune Checkpoint Inhibitor-Associated Myocarditis: A Literature Review.

Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use. Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically.There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies.

Role of Skewed X-Chromosome Inactivation in Common Variable Immunodeficiency.

The term common variable immunodeficiency (CVID) encompasses a clinically diverse group of disorders, mainly characterized by hypogammaglobulinemia, insufficient specific antibody production, and recurrent infections. The genetics of CVID is complex, and monogenic defects account for only a portion of cases, typically <30%. Other proposed mechanisms include digenic, oligogenic, or polygenic inheritance and epigenetic dysregulation. In this study, we aimed to assess the role of skewed X-chromosome inactivation (XCI) in CVID. Within our cohort of 131 genetically analyzed CVID patients, we selected female patients with rare variants in CVID-associated genes located on the X-chromosome. Four patients harboring heterozygous variants in BTK (n = 2), CD40LG (n = 1), and IKBKG (n = 1) were included in the study. We assessed XCI status using the HUMARA assay and an NGS-based method to quantify the expression of the 2 alleles in mRNA. Three of the 4 patients (75%) exhibited skewed XCI, and the mutated allele was predominantly expressed in all cases. Patient 1 harbored a hypomorphic variant in BTK (p.Tyr418His), patient 3 had a pathogenic variant in CD40LG (c.288+1G>A), and patient 4 had a hypomorphic variant in IKBKG (p.Glu57Lys) and a heterozygous splice variant in TNFRSF13B (TACI) (c.61+2T>A). Overall, the analysis of our cohort suggests that CVID in a small proportion of females (1.6% in our cohort) is caused by skewed XCI and highly penetrant gene variants on the X-chromosome. Additionally, skewed XCI may contribute to polygenic effects (3.3% in our cohort). These results indicate that skewed XCI may represent another piece in the complex puzzle of CVID genetics.

Reward Learning as a Potential Mechanism for Improvement in Schizophrenia Spectrum Disorders Following Cognitive Remediation: Protocol for a Clinical, Nonrandomized, Pre-Post Pilot Study.

Cognitive impairment is common with schizophrenia spectrum disorders. Cognitive remediation (CR) is effective in improving global cognition, but not all individuals benefit from this type of intervention. A better understanding of the potential mechanism of action of CR is needed. One proposed mechanism is reward learning (RL), the cognitive processes responsible for adapting behavior following positive or negative feedback. It is proposed that the structure of CR enhances RL and motivation to engage in increasingly challenging tasks, and this is a potential mechanism by which CR improves cognitive functioning in schizophrenia. Our primary objective is to examine reward processing in individuals with schizophrenia before and after completing CR and to compare this with a group of matched clinical controls. We will assess whether RL mediates the relationship between CR and improved cognitive function and reduced negative symptoms. Potential differences in social RL and nonsocial RL in individuals with schizophrenia will also be investigated and compared with a healthy matched control group. We propose a clinical, nonrandomized, pre-post pilot study comparing the impact of CR on RL and neurocognitive outcomes. The study will use a combination of objective and subjective measures to assess neurocognitive, psychiatric symptoms, and neurophysiological domains. A total of 40 individuals with schizophrenia spectrum disorders (aged 18-35 years) will receive 12 weeks of CR therapy (n=20) or treatment as usual (n=20). Reward processing will be evaluated using a reinforcement learning task with 2 conditions (social reward vs nonsocial reward) at baseline and the 12-week follow-up. Functional magnetic resonance imaging responses will be measured during this task. To validate the reinforcement learning task, RL will also be assessed in 20 healthy controls, matched for age, sex, and premorbid functioning. Mixed-factorial ANOVAs will be conducted to evaluate treatment group differences. For the functional magnetic resonance imaging analysis, computational modeling will allow the estimation of learning parameters at each point in time, during each task condition, for each participant. We will use a variational Bayesian framework to measure how learning occurred during the experimental task and the subprocesses that underlie this learning. Second-level group analyses will examine how learning in patients differs from that observed in control participants and how CR alters learning efficiency and the underlying neural activity. As of September 2023, this study has enrolled 15 participants in the CR group, 1 participant in the treatment-as-usual group, and 11 participants in the healthy control group. Recruitment is expected to be completed by September 2024. Data analysis is expected to be completed and published in early 2025. The results of this study will contribute to the knowledge of CR and RL processes in severe mental illness and the understanding of the systems that impact negative symptoms and cognitive impairments within this population. DERR1-10.2196/52505.

Mechanism of electrochemical carbon dioxide reduction to formate on tin electrode

Carbon dioxide can be electrochemically reduced to formate on tin electrodes. Formate is one of the most economically viable products of CO2 reduction reaction (CO2RR). While CO2 is reduced to formate, hydrogen evolution reaction (HER) occurs concomitantly. The kinetics of CO2RR and HER on the tin electrode was investigated. Potentiodynamic polarization studies were conducted in CO2 saturated and N2 saturated 0.1 M KHCO3 solutions, in the potential range from −0.014 V to −1.59 V vs. RHE. A faradaic efficiency of 93.95 % towards formate production was obtained at −1.09 V vs. RHE. The mass transfer effects and bicarbonate dissociation equilibrium were used to estimate the concentration of the reactants at the electrode surface. Density functional theory calculations indicate that –OCHO intermediate species is thermodynamically favoured, and a four-step reaction with two intermediates is proposed. The proposed mechanism captures the major features of the polarization data. CO2 reduction occurs via two intermediate species, viz. adsorbed H and OCHO species, while HER occurs via Volmer-Heyrovsky steps. The model predicts that in N2 saturated solutions, the fractional surface coverage of adsorbed H reaches a maximum of ∼0.48 at a potential of −0.82 V vs. RHE while in CO2 saturated solutions, the corresponding value is ∼0.29. In addition, the maximum fractional surface coverage of adsorbed OCHO is predicted to be ∼0.12 in CO2 saturated solutions.

Two birds with one stone: Facile fabrication of a ternary ZnIn2S4/BiVO4/MWCNTs nanocomposite for photocatalytic detoxification of priority organic pollutants and hydrogen production with a proposed mechanism

A series of ternary nanocomposites with different weight percentages of zinc indium sulfide, bismuth vanadate, and multiwalled carbon nanotubes (ZnIn2S4/BiVO4/MWCNTs) were synthesized using a simple thermal impregnation method to obtain high charge separation and transfer efficiency, thus improving their photocatalytic performance. The 20 wt% ZnIn2S4/BiVO4/MWCNTs (20 wt% ZBM) nanocomposite exhibited enhanced photocatalytic activity compared to pure BiVO4 and ZnIn2S4 for the degradation of methylene blue, acetaminophen, and allopurinol in an aqueous solution when exposed to a visible light source and atmospheric oxygen. This nanocomposite demonstrated a particularly high degradation rate constant (k = 6.39 × 10−2 min−1) for the photocatalytic degradation of methylene blue. The introduction of MWCNTs boosted the photocatalytic performance of the 20 wt% ZBM nanocomposite, attaining a maximum H2 production of 1704 μmol g−1. Repeated photocatalytic H2 generation reached 1621 μmol g−1 after 5 h of irradiation with four consecutive cycles. Therefore, we propose a “two birds with one stone” strategy for greatly improved photocatalytic wastewater detoxification and H2 production by prolonging the lifetime of the photogenerated electron–hole pair separation.

A platoon-based eco-driving control mechanism for low-density traffic flow

Forming traffic into platoons on the road has the potential for mitigation of traffic congestion and improvement in fuel economy, and can be more readily achieved by leveraging emerging connected and automated vehicles. This paper proposes a platoon-based eco-driving control mechanism that forms small-sized platoons and guides them to move on low-density traffic corridors. To facilitate this investigation, a low-density traffic corridor is divided into an initial road segment plus a series of subsequent road segments. To ensure computational efficiency, an approximate model based on the predefined function is employed. Simulation shows that traffic flow of small-sized platoons can bring considerable benefits in fuel consumption compared to that of large-sized platoons. This proposed control mechanism is shown to be significant in fuel economy.

Magnetically separable Cu-Fe nanophotocatalyst with enhanced photocatalytic performance under visible-light irradiation: Optimizing the fuel type and heating approach in the synthesis process

This study aimed to examine the influence of fuel type and heating technique on the solution one-step solution combustion synthesis of CuFe2O4 spinel-type photocatalysts. The primary goal was to establish the best configuration of nanophotocatalysts with desirable characteristics, leading to improved photodegradation of dye pollutants when exposed to simulated solar radiation. Cu-spinel nanophotocatalysts were generated using a one-step combustion method involving three distinct fuels (urea, glycine, and citric acid) and two heating strategies (microwave and muffle furnace). The synthesized nanophotocatalysts were characterized through a range of tests, including XRD, FESEM, EDX, BET-BJH, FTIR, VSM, PL, DRS, and pHpzc analyses. During the simulated irradiation of sunlight, the efficacy of the Cu-spinel photocatalyst was evaluated using high-concentration Congo red, a widely used textile dye. Test results indicate that the Cu-spinel nanophotocatalyst formed utilizing glycine and microwave combustion displayed a desirable photocatalytic activity by degradation of 97 % of Congo red in 100 min. In addition, the photocatalytic efficiency of Congo red degradation was significantly enhanced compared to the other fuels and the conventional heating approach. Furthermore, CuFe(G-MW) demonstrated high stability throughout four cycles. Finally, a proposed mechanism for the degradation of Congo red using a CuFe(G-MW) nanophotocatalyst was presented.

Insights on the chlorine resistance of polyester composite nanofiltration membranes

The use of chlorine as a pretreatment of water treatment and desalination processes causes a loss in performance and lifespan of the membranes usually employed in these processes. Polyester (PE) membranes have been proposed as an alternative due to the absence of amidic hydrogen; however, fabricating PE composite membranes with equivalent performance and high tolerance towards chlorine has proven challenging. In this work, we evaluate the effects of monomer concentration and blends, proton scavenger, surfactant concentration, reaction time and temperature on interfacial polymerization (IP) of trimesoyl chloride and resorcinol. Reaction temperature was the most crucial factor to achieve a PE coating film with high crosslinking degree (XD), high divalent rejection and excellent chlorine tolerance. The resorcinol membrane showed a Na2SO4 rejection of >90 % before and after 6000 ppmh-Cl2 at pH 7. XPS analysis showed that chlorination of PE membranes resulted in loss of CC bonds and increase in C–C and C–O bonds. At high crosslinking degrees, the changes caused by chlorine were minimal. Based on the characterization and the performance of the chlorinated membranes, ring chlorination followed by ring hydrolysis is the proposed mechanism for degradation of lower XD membranes.

Contrasting Dynamics in Isoelectronic Anions Formed by Electron Attachment.

Cyanogen NCCN and cyanoacetylene HCCCN are isoelectronic molecules, and as such, they have many similar properties. We focus on the bond cleavage in these induced by the dissociative electron attachment. In both molecules, resonant electron attachment produces CN- with very similar energy dependence. We investigate the very different dissociation dynamics, in each of the two molecules, revealed by velocity map imaging of this common fragment. Different dynamics are manifested both in the excess energy partitioning and in the angular distributions of fragments. Based on the comparison with electron energy loss spectra, which provide information about possible parent states of the resonances (both optically allowed and forbidden excited states of the neutral target), we ascribe the observed effect to the distortion of the nuclear frame during the formation of core-excited resonance in cyanoacetylene. The proposed mechanism also explains a puzzling difference in the magnitude of the CN- cross section in the two molecules which has been so far unexplained.

QoS-Based Secure Data Communication for Software-Defined Autonomous Vehicles Using Blockchain

Data security in autonomous vehicles is of primary importance due to the possibility of cyberattacks on these interconnected and complex systems. As these vehicles are equipped with a number of sensors, software, and communication infrastructure, they are more vulnerable to different types of security issues. In this article. blockchain-supported QoS-based secure data communication (QoS-SDC) is proposed for high-speed, software-defined autonomous vehicles. This proposed mechanism will provide a promising solution for delivering protected data among autonomous vehicles. This model is evaluated by using the NS3 simulator, and the simulation results exhibit satisfactory secure data transactions.

Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.

Connexin 43 (Cx43) is a protein encoded by the GJA1 gene and is a component of cell membrane structures called gap junctions, which facilitate intercellular communication. Prior evidence indicates that elevated GJA1 expression in the HER2-positive (HER2+) subtype of breast cancer is associated with poor prognosis. Prior evidence also suggests that HER2+ breast cancers that have become refractory to HER2-targeted agents have a loss of Cx43 gap junction intercellular communication (GJIC). In this study, a Cx43-targeted agent called alpha-connexin carboxyl-terminal peptide (aCT1) is examined to determine whether GJIC can be rescued in refractory HER2+ breast cancer cells. A proposed mechanism of action for aCT1 is binding to the tight junction protein Zonal Occludens-1 (ZO-1). However, the true scope of activity for aCT1 has not been explored. In this study, mass spectrometry proteomic analysis is used to determine the breadth of aCT1-interacting proteins. The NanoString nCounter Breast Cancer 360 panel is also used to examine the effect of aCT1 on cancer signaling in HER2+ breast cancer cells. Findings from this study show a dynamic range of binding partners for aCT1, many of which regulate gene expression and RNA biology. nCounter analysis shows that a number of pathways are significantly impacted by aCT1, including upregulation of apoptotic factors, leading to the prediction and demonstration that aCT1 can boost the cell death effects of cisplatin and lapatinib in HER2+ breast cancer cells that have become resistant to HER2-targeted agents.

The conducted vascular response as a mediator of hypercapnic cerebrovascular reactivity: A modelling study

It is well established that the cerebral blood flow (CBF) shows exquisite sensitivity to changes in the arterial blood partial pressure of CO2 (Pa,CO2), which is reflected by an index termed cerebrovascular reactivity. In response to elevations in Pa,CO2 (hypercapnia), the vessels of the cerebral microvasculature dilate, thereby decreasing the vascular resistance and increasing CBF. Due to the challenges of access, scale and complexity encountered when studying the microvasculature, however, the mechanisms behind cerebrovascular reactivity are not fully understood. Experiments have previously established that the cholinergic release of the Acetylcholine (ACh) neurotransmitter in the cortex is a prerequisite for the hypercapnic response. It is also known that ACh functions as an endothelial-dependent agonist, in which the local administration of ACh elicits local hyperpolarization in the vascular wall; this hyperpolarization signal is then propagated upstream the vascular network through the endothelial layer and is coupled to a vasodilatory response in the vascular smooth muscle (VSM) layer in what is known as the conducted vascular response (CVR). Finally, experimental data indicate that the hypercapnic response is more strongly correlated with the CO2 levels in the tissue than in the arterioles. Accordingly, we hypothesize that the CVR, evoked by increases in local tissue CO2 levels and a subsequent local release of ACh, is responsible for the CBF increase observed in response to elevations in Pa,CO2. By constructing physiologically grounded dynamic models of CBF and control in the cerebral vasculature, ones that integrate the available knowledge and experimental data, we build a new model of the series of signalling events and pathways underpinning the hypercapnic response, and use the model to provide compelling evidence that corroborates the aforementioned hypothesis. If the CVR indeed acts as a mediator of the hypercapnic response, the proposed mechanism would provide an important addition to our understanding of the repertoire of metabolic feedback mechanisms possessed by the brain and would motivate further in-vivo investigation. We also model the interaction of the hypercapnic response with dynamic cerebral autoregulation (dCA), the collection of mechanisms that the brain possesses to maintain near constant CBF despite perturbations in pressure, and show how the dCA mechanisms, which otherwise tend to be overlooked when analysing experimental results of cerebrovascular reactivity, could play a significant role in shaping the CBF response to elevations in Pa,CO2. Such in-silico models can be used in tandem with in-vivo experiments to expand our understanding of cerebrovascular diseases, which continue to be among the leading causes of morbidity and mortality in humans.

Microglia contribute to mammary tumor-induced neuroinflammation in a female mouse model.

Following diagnosis but before treatment, up to 30% of breast cancer patients report behavioral side effects (e.g., anxiety, depression, memory impairment). Our rodent mammary tumor model recapitulates aspects of these behavioral sequelae, as well as elevated circulating and brain inflammatory mediators. Neuroinflammation is a proposed mechanism underlying the etiology of mood disorders and cognitive deficits, and therefore may be contributing to tumor-associated behavioral side effects. The cellular mechanisms by which tumor-induced neuroinflammation occurs remain unknown, making targeted treatment approaches inaccessible. Here, we tested the hypotheses that microglia are the primary cells driving tumor-induced neuroinflammation and behavioral side effects. Young adult female BALB/c mice were induced with a 67NR mammary tumor; tumor-free controls underwent a sham surgery. Mammary tumors increased IBA1+ and GFAP+ staining in the amygdala and hippocampus relative to tumor-free controls. However, tumors did not alter gene expression of Percoll-enriched microglia isolated from the whole brain. While cognitive, social, and anhedonia-like behaviors were not altered in tumor-bearing mice, tumors increased central tendency in the open-field test; microglia depletion did not reverse this effect. Brain region RT-qPCR data indicated that microglia depletion attenuated tumor-induced elevations of neuroinflammatory gene expression in a region- and mediator-specific manner. These results indicate a causal role of microglia in tumor-induced neuroinflammation. This research advances our understanding of the cellular mechanisms underlying tumor-induced neuroinflammation in order to understand how brain responses (e.g., behavior) may be altered with subsequent cancer-related immune challenges.

Readily available drugs and other interventions to potentially improve the efficacy of immune checkpoint blockade in cancer.

To improve the efficacy of immune checkpoint inhibitors (ICIs) for cancer treatment, various strategies, including combination therapies with repurposed drugs, are being explored. Several readily available interventions with potential to enhance programmed death 1 (PD-1) blockade have been identified. However, these interventions often remain overlooked due to the lack of financial incentives for their development, making them financial orphans. This review summarizes current knowledge regarding off-label drugs, supplements, and other readily available interventions that could improve the efficacy of PD-1 blockade. The summary of each intervention includes the proposed mechanism of action for combination with checkpoint inhibitors and data from animal and human studies. Additionally, we include summaries of common interventions to be avoided by patients on PD-1 blockade. Finally, we present approaches for conducting further studies in patients, with the aim of expediting the clinical development of these interventions. We strive to increase awareness of readily available combination therapies that may advance cancer immunotherapy and help patients today.

An Evolutionary Algorithm for Task Clustering and Scheduling in IoT Edge Computing

The Internet of Things (IoT) edge is an emerging technology of sensors and devices that communicate real-time data to a network. IoT edge computing was introduced to handle the latency concerns related to cloud computing data management, as the data are processed closer to their point of origin. Clustering and scheduling tasks on IoT edge computing are considered a challenging problem due to the diverse nature of task and resource characteristics. Metaheuristics and optimization methods are widely used in IoT edge task clustering and scheduling. This paper introduced a new task clustering and scheduling mechanism using differential evolution optimization on IoT edge computing. The proposed mechanism aims to optimize task clustering and scheduling to find optimal execution times for submitted tasks. The proposed mechanism for task clustering is based on the degree of similarity of task characteristics. The proposed mechanisms use an evolutionary mechanism to distribute system tasks across suitable IoT edge resources. The clustering tasks process categorizes tasks with similar requirements and then maps them to appropriate resources. To evaluate the proposed differential evolution mechanism for IoT edge task clustering and scheduling, this study conducted several simulation experiments against two established mechanisms: the Firefly Algorithm (FA) and Particle Swarm Optimization (PSO). The simulation configuration was carefully created to mimic real-world IoT edge computing settings to ensure the proposed mechanism’s applicability and the simulation results’ relevance. In the heavyweight workload scenario, the proposed DE mechanism started with an execution time of 916.61 milliseconds, compared to FA’s 1092 milliseconds and PSO’s 1026.09 milliseconds. By the 50th iteration, the proposed DE mechanism had reduced its execution time significantly to around 821.27 milliseconds, whereas FA and PSO showed lesser improvements, with FA at approximately 1053.06 milliseconds and PSO stabilizing at 956.12 milliseconds. The simulation results revealed that the proposed differential evolution mechanism for edge task clustering and scheduling outperforms FA and PSO regarding system efficiency and stability, significantly reducing execution time and having minimal variation across simulation iterations.

Why do metals become superhydrophilic during nanosecond laser processing? Design of superhydrophilic, anisotropic and biphilic surfaces

This research investigates the impact of the surrounding environment on the characteristics of copper, nickel and tin during nanosecond laser processing. By comparing the results of processes conducted in vacuum and air, we conclude that changes in wetting properties cannot be solely attributed to development of surface microstructure. To elucidate this phenomenon, we conducted model experiments using a tin target. Laser processing parameters for the tin target were established, involving deep cavity melting without ablation, resulting in highly evolved material morphology. Under these conditions, laser processing in air did not lead to metal hydrophilization. Therefore, our study demonstrates that the primary cause of changes in material wetting properties during nanosecond laser processing is the re-deposition of ablation products onto the material surface. These products form a nanoporous layer that enhances wicking capabilities and subsequently serves as a sorbent for various impurities, gradually leading to the hydrophobization of most commonly used materials. The proposed mechanism opens the possibility for the development of new methods to create materials with biphilic and anisotropic wetting properties. The key insight lies in the control of the thickness of the nanoporous layer, as it emerges as a pivotal factor dictating wettability properties and wicking capability.

Targeting Alzheimer's Disease: Evaluating the Efficacy of C-1 Functionalized N-Aryl-Tetrahydroisoquinolines as Cholinergic Enzyme Inhibitors and Promising Therapeutic Candidates.

We have synthesized 22 C-1 functionalized-N-aryl-1,2,3,4-tetrahydroisoquinoline derivatives showing biological activities towards cholinergic enzymes. Synthesis was performed using visible-light-promoted photo-redox chemistry, starting from a common intermediate, and the application of this synthetic methodology drastically simplified synthetic routes and purification of desired compounds. All synthesized derivates were divided into four groups based on the substituents in the C-1 position, and their inhibition potencies towards two cholinergic enzymes, acetyl- and butyrylcholinesterase were evaluated. Most potent derivatives were selected, and kinetic analysis was further carried out to obtain insights into the mechanisms of inhibition of these two enzymes. Further validation of the mode of inhibition of cholinergic enzymes by the two most potent THIQ compounds, 3c and 3i, was performed using fluorescence-quenching titration studies. Molecular docking studies further confirmed the proposed mechanism of enzymes' inhibition. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the selected most potent derivatives were performed using Swiss ADME tool. This was followed by UPLC-assisted log P determination and in vitro BBB permeability studies performed in order to assess the potential of the synthesized compounds to pass the BBB.

Facile (3+2) Cycloaddition between an N‐Heterocyclic Olefin and Nitrous Oxide at Ambient Conditions

AbstractWe report that a gem‐dimethylated N‐heterocyclic olefin (NHO) reacts with N2O at ambient pressure and room temperature to give an imidazolone and an azine formed from intermediately generated 2‐diazopropane. The in situ formation of transient diazopropane was indirectly proven by its engagement in a facile cycloaddition with norbornene. According to our studies, the reaction sequence consists of a rate‐determining (3+2) cycloaddition between the NHO and N2O, followed by a cycloreversion that releases the diazoalkane. This mechanistic proposal is supported by DFT calculations. Eyring analysis using temperature‐variable 1H NMR spectroscopy allowed us to determine the activation parameters of the initial (3+2) cycloaddition (Δ≠H=11.2(4) kcal/mol, Δ≠S=−39.8(13) e.u., 293–308 K). Frontier molecular orbital analysis shows that the polarization of the π‐bond of the NHO decisively facilitates the cycloaddition.

Relative Age and Positive Youth Development in Youth Sport: Do Developmental Assets Play a Role in Creating Advantage Reversals in Female Soccer?

Relative age effects (RAEs) are commonly associated with advantages for older athletes. However, a variety of benefits attributed to 'advantage reversals' have been observed among relatively younger professional athletes. Considering psychosocial development as a proposed mechanism, the purpose of this study was twofold: (1) To explore an association between developmental assets (i.e., facilitators of positive youth development [PYD]) and RAEs; (2) To assess whether overall developmental asset levels are protective against sport dropout. The Developmental Assets Profile© was distributed to members of a one-year cohort of post-adolescent, female soccer players from Ontario, Canada. The presence of differences between groups of relatively older (H1; n = 64) and younger (H2; n = 57) participants and developmental asset scales were assessed using discriminant analysis. A binary logistic regression was conducted to assess whether overall developmental asset levels are protective against sport dropout, with consideration of relevant factors. Findings suggest that relatively younger, female players score higher in two internal categories: commitment to learning and positive values. The overall developmental asset scores were not found to be protective against dropout. This study provides preliminary, albeit cautious, support that 'advantage reversals' may be in part associated with enhanced PYD resulting from developmental sport experiences.