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Background Traditional risk factors are insufficient to explain all cases of coronary artery disease (CAD) in patients with diabetes mellitus (DM). Advanced glycation end-products (AGEs) and their receptors may play important roles in the development and progression of CAD. Body Hyperglycemia is the hallmark feature of DM. An increase in the incidence of both micro-and macrovascular complications of diabetes has been observed with increased duration of hyperglycemia. This association persists even after glycemic control has been achieved, suggesting an innate mechanism of “metabolic memory.” AGEs are glycated proteins that may serve as mediators of metabolic memory due to their increased production in the setting of hyperglycemia and generally slow turnover. Elevated AGE levels can lead to abnormal cross linking of extracellular and intracellular proteins disrupting their normal structure and function. Furthermore, activation of AGE receptors can induce complex signaling pathways leading to increased inflammation, oxidative stress, enhanced calcium deposition, and increased vascular smooth muscle apoptosis, contributing to the development of atherosclerosis. Through these mechanisms, AGEs may be important mediators of the development of CAD. However, clinical studies regarding the role of AGEs and their receptors in advancing CAD are limited, with contradictory results. Conclusion AGEs and their receptors may be useful biomarkers for the presence and severity of CAD. Further studies are needed to evaluate the utility of circulating and tissue AGE levels in identifying asymptomatic patients at risk for CAD or to identify patients who may benefit from invasive intervention.

We consider a micromaser model of a quantum battery, where the battery is a single mode of the electromagnetic field in a cavity, charged via repeated interactions with a stream of qubits, all prepared in the same non-equilibrium state, either incoherent or coherent, with the matter–field interaction modeled by the Jaynes–Cummings model. We show that the coherent protocol is superior to the incoherent one, in that an effective pure steady state is achieved for generic values of the model parameters. Finally, we supplement the above collision model with cavity losses, described by a Lindblad master equation. We show that battery performances, in terms of stored energy, charging power, and steady-state purity, are slightly degraded up to moderated dissipation rate. Our results show that micromasers are robust and reliable quantum batteries, thus making them a promising model for experimental implementations.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects. In this manuscript, we present a computational protocol to extricate the underlying mechanism of action of basil compounds in neuroprotective effects. Molecular docking-based investigation of the chemical interactions between selected bioactive compounds from basil and key neuroprotective targets, including AChE, GSK3β, γ-secretase, and sirtuin2. Our results demonstrate that basil compound myricerone caffeoyl ester possesses a high affinity of −10.01 and −8.85 kcal/mol against GSK3β and γ-secretase, respectively, indicating their potential in modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed to explore the protein–ligand complexes’ stability and to analyze the bound basil compounds’ dynamic behavior. This comprehensive computational investigation enlightens the putative mechanistic basis for the neuroprotective effects of basil compounds, providing a rationale for their therapeutic use in neurodegenerative disorders after further experimental validation.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

Alzheimer’s disease (AD) is the prime cause of 65–80% of dementia cases and is caused by plaque and tangle deposition in the brain neurons leading to brain cell degeneration. β-secretase (BACE-1) is a key enzyme responsible for depositing extracellular plaques made of β-amyloid protein. Therefore, efforts are being applied to develop novel BACE-1 enzyme inhibitors to halt plaque build-up. In our study, we analyzed some Elenbecestat analogues (a BACE-1 inhibitor currently in clinical trials) using a structure-based drug design and scaffold morphing approach to achieve a superior therapeutic profile, followed by in silico studies, including molecular docking and pharmacokinetics methodologies. Among all the designed compounds, SB306 and SB12 showed good interactions with the catalytic dyad motifs (Asp228 and Asp32) of the BACE-1 enzyme with drug-likeliness properties and a high degree of thermodynamic stability confirmed by the molecular dynamic and stability of the simulated system indicating the inhibitory nature of the SB306 and SB12 on BACE 1.

Prolonged exposure to stress alters brain pathophysiology by increasing inflammation leading to cellular and molecular dysfunction and initiation of neurobehavioral changes like anxiety, depression and cognitive impairment. Various signaling pathways and downstream cascades modulate the inflammatory responses within the Central Nervous System (CNS), notably cGAS-STING pathway and Nuclear factor kappa B (NF-κB) signaling are majorly affected. The present research aims to assess the consequence of modulation of cGAS with suramin in chronic unpredictable stress (CUS), and examining the impact on neurobehavioral alterations. For evaluating the impact of CUS and pharmacological interventions on neurobehavioral changes, Swiss albino mice of either sex were exposed to various stressors for 8 weeks. The behavioral traits for anxiety, depression and memory impairment were assessed by Elevated Plus Maze (EPM), Forced Swim Test (FST), Sucrose Preference Test (SPT), Tail Suspension Test (TST), Morris Water Maze (MWM) and Passive Avoidance Test (PAT). The level of corticosterone and neurotransmitters (dopamine and serotonin); various parameters of oxidative stress and neuroinflammation; acetylcholinesterase (AChE) activity and histological changes in hippocampus and cortex were also assessed. The results highlighted that administration of suramin (5, 10 and 20 mg/kg, i.p. ) dose dependently improves neurobehavioral parameters, decreases corticosterone; elevates the level of neurotransmitters, and reduces the deleterious effects of CUS on oxidative stress and neuroinflammation; along with the histological improvement by inhibiting the cGAS-STING pathway and modulating NF-κB signaling as observed from decrease NF-κB levels in our study This study provides insights into suramin as a new treatment approach for mitigating the effects of chronic stress on restoring neurobehavioral changes.

Efficient extraction of subsurface resources relies heavily on the performance of drilling fluids, which necessitates constant innovation in their formulation. This study introduces a novel Polylactic Acid/Henna composite for significant enhancement of drilling fluid properties. The composites was characterized via Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDS), and Fourier-Transform Infrared Spectroscopy (FTIR), confirming the uniform Henna particles dispersion in PLA matrix. The composite was added to water-based drilling fluids at concentrations of 0.5 wt%, 1 wt%, 2 wt%, 4 wt%, and 10 wt%, followed by rigorous evaluation of rheological and filtration performance. Experimental results demonstrated that fluids containing 2 wt% PLA/Henna composite exhibited the best performance, with a 32% increase in yield point and a 21% improvement in plastic viscosity compared to the base fluid. Furthermore, filtration volume decreased by 42%, while spurt loss was reduced by 35% due to improved filter cake formation. These quantitative improvements optimize fluid efficiency and minimize permeability, enhancing the ability to control fluid loss under simulated drilling conditions. Such enhancements promote better wellbore stability and operational reliability.

We study the optimal performance of Feynman’s ratchet and pawl, a paradigmatic model in nonequilibrium physics, using ecological criterion as the objective function. The analysis is performed by two different methods: (i) a two-parameter optimization over internal energy scales; and (ii) a one-parameter optimization of the estimate for the objective function, after averaging over the prior probability distribution (Jeffreys’ prior) for one of the uncertain internal energy scales. We study the model for both engine and refrigerator modes. We derive expressions for the efficiency/coefficient of performance (COP) at maximum ecological function. These expressions from the two methods are found to agree closely with equilibrium situations. Furthermore, the expressions obtained by the second method (with estimation) agree with the expressions obtained in finite-time thermodynamic models.

Alzheimer’s disease (AD) is responsible for more than 80% of cases of dementia in senior individuals globally. In the current study, the role of modulation of the FGF1/PI3K/Akt pathway in the protective effect of tozasertib was evaluated. Experimental dementia was induced in mice by injecting streptozotocin (STZ) intracerebroventricularly. Various biochemical parameters for oxidative stress & lipid peroxidation (SOD, GSH, catalase, TBARS), neuroinflammation (MPO, IL-6, IL-1 β, TNF-α, NFκB), apoptotic markers (Bax, Bcl-2, Caspase-3), and memory parameters (AChE activity, β1–40 levels) were assessed. The behavioral parameters evaluated included the Morris Water Maze test and the step-down passive avoidance test. Histological changes were assessed using H&E staining. ICV STZ-induced AD resulted in increased oxidative stress, lipid peroxidation, neuroinflammation, apoptosis, and decreased learning and memory. The results showed that administration of tozasertib improved memory, decreased levels of oxidative stress, inflammatory parameters, and apoptotic markers, and improved histological parameters in a dose-dependent manner. Pre-administration of LY294002, a PI3K/Akt pathway inhibitor, partially reversed the protective effects of Tozasertib, suggesting possible involvement of this pathway. However, as the mechanism was inferred primarily through pharmacological antagonism, further studies including direct molecular assessments (e.g. p-Akt/t-Akt) are warranted to confirm the role of FGF1/PI3K/Akt signaling in Tozasertib’s action.

Annually, an estimated 2.3 million infants die within their first month of life, primarily in sub-Saharan Africa and South Asia. Infections, including sepsis are among the major contributors to these deaths. Effective interventions added to standard antimicrobial therapy can reduce sepsis mortality. A recent meta-analysis suggests that adjunct zinc treatment of young infants with sepsis could reduce case fatality risk. This study evaluated the efficacy of zinc as an adjunct to antibiotics in young infants with suspected sepsis, defined as clinical severe infection (CSI). We conducted a randomized, double-blind, placebo-controlled trial across seven hospitals in India and Nepal from February 28, 2017, to February 22, 2022. Infants aged 3-59 days hospitalized with suspected sepsis, defined as CSI, adapted from the WHO Integrated Management of Childhood Illness (IMCI) criteria, were randomly assigned to receive 10 mg of elemental zinc daily or placebo orally for 14 days, in addition to standard of care. The primary outcomes were death during hospitalization and death within 12 weeks after enrollment. Among 3,153 enrolled infants (1,203 [38%] females), the median age at enrollment was 25 days (interquartile range 13-41 days), and the mean weight was 2.9 kg (standard deviation 0.8). During the hospital stay, 64 (4.1%) of 1,576 infants died in the zinc arm compared to 77 (4.9%) of 1,577 in the placebo arm (relative risk [RR] 0.83 (95% CI [0.60, 1.15]; p = 0.267)). Among those who completed 12 weeks of follow-up, 140 of 1,554 infants (9.0%) died in the zinc arm, and 133 of 1,550 (8.6%) in the placebo arm (RR 1.05 (95% CI [0.84, 1.32]; p = 0.674)). Adverse events were similar across trial arms, except for a slight increase in vomiting in the zinc arm; no events were attributed to the intervention. The main limitation of the study is that it was underpowered due to lower-than-anticipated event rates and a shortfall in the achieved sample size. In this setting, we found little evidence for an effect of adjunct zinc therapy on young infants with CSI on the risk of dying during hospitalization or for the subsequent 3 months. Our findings contrast previous studies that used more specific case definitions. This underscores the need for further RCTs to evaluate the effect of zinc in young infant sepsis before it can be recommended in treatment guidelines. Clinical Trials Registry-India (CTRI/2017/02/007966) on February 27, 2017, and Universal Trial Number is U1111-1187-6479.