Search Results (9,577)

As AI workloads move to edge devices, the von Neumann architecture is hindered by memory- and power-wall limitations We present an SRAM-based compute-in-memory binary convolution accelerator that stores and transports only 1-bit weights and activations, maps MACs to bitwise XNOR–popcount, and fuses BatchNorm, HardTanh, and binarization into a single affine-and-threshold uni. Residual paths are handled by in-accumulator summation to minimize data movement. FPGA validation shows 87.6% CIFAR 10 accuracy consistent with a bit-accurate software reference, a compute-only latency of 2.93 ms per 32 × 32 image at 50 MHz, sustained at only 1.52 W. These results demonstrate an efficient and practical path to deploying edge models under tight power and memory budgets. Full article

Background/Objectives: Signaling imbalances involving epidermal growth factor receptor (EGFR) and aldose reductase (ALR2) are frequently associated with the biology of several solid tumors, including non-small-cell lung cancer (NSCLC) and breast cancer. This work sought to prepare and investigate a small set of hydrazonylthiazole derivatives as potential modulators of both targets with relevance to cancer therapy. Methods: Thirteen compounds (1–13) were synthesized and examined for their effects on A549 (NSCLC), MCF-7 (breast cancer), and Jurkat leukemia cells, together with peripheral blood mononuclear cells (PBMCs) to determine selectivity. The most active molecules were further analyzed through apoptosis studies, EGFR and ALR2 inhibition assays, docking calculations, and 200 ns molecular dynamics (MD) simulations. SwissADME was used to estimate pharmacokinetic and drug-likeness features. Results: Among all derivatives, compound 13, prepared here for the first time, showed the strongest activity on A549 and MCF-7 cells (IC₅₀: 1.33 ± 0.41 µM; 1.74 ± 0.38 µM) and displayed a very high selectivity index (SI = 138.9). It also triggered apoptosis in A549 cells and reduced EGFR activity by 74% at 10 µM. In contrast, compound 5 acted as the most efficient ALR2 blocker (K_I = 0.08 ± 0.01 µM). MD simulations showed that both compounds maintained stable contact patterns with essential residues in the EGFR and ALR2 binding pockets. SwissADME analysis suggested suitable oral absorption and drug-likeness for both molecules. Conclusions: Compound 13 behaves as a selective EGFR-directed agent capable of inducing apoptotic cell death in NSCLC, while compound 5 shows strong affinity toward ALR2. These outcomes indicate that both structures may serve as useful starting points for further development of small molecules acting on EGFR- and ALR2-related pathways. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

Aflatoxin B₁ (AFB₁), a major metabolite of aflatoxin, is a highly toxic carcinogen. It frequently contaminates feed due to improper storage of feed ingredients such as corn and peanut meal, with the contamination risk further escalating alongside the increasing incorporation of plant-based proteins in feed formulations. Upon entering an organism, AFB₁ is metabolized into highly reactive derivatives, which trigger an oxidative stress-inflammation vicious cycle by binding to biological macromolecules, damaging cellular structures, activating apoptotic and inflammatory pathways, and inhibiting antioxidant systems. This cascade leads to stunted growth, impaired immunity, and multisystem dysfunction in animals. Long-term accumulation can also compromise reproductive function, induce carcinogenesis, and pose risks to human health through residues in the food chain. Tannins are natural polyphenolic compounds widely distributed in plants which exhibit significant antioxidant and anti-inflammatory activities and can effectively mitigate the toxicity of AFB₁. They can repair intestinal damage by increasing the activity of antioxidant enzymes and up-regulating the gene expression of intestinal tight junction proteins, regulate the balance of intestinal flora, and improve intestinal structure. Meanwhile, tannins can activate antioxidant signaling pathways, up-regulate the gene expression of antioxidant enzymes to enhance antioxidant capacity, exert anti-inflammatory effects by regulating inflammation-related signaling pathways, further reduce DNA damage, and decrease cell apoptosis and pyroptosis through such means as down-regulating the expression of pro-apoptotic genes. This review summarizes the main harm of AFB₁ to animals and the mitigating mechanisms of tannins, aiming to provide references for the resource development of tannins and healthy animal farming. Full article

Fzf1 is a Saccharomyces cerevisiae transcription factor that contains five zinc finger domains (ZF1-5) and induces the expression of at least five genes in response to various chemical stresses by recognizing the shared promoter consensus sequence CS2. The N-terminal ZF1-3 are required and sufficient for binding to CS2, while ZF4 negatively regulates the activity of Fzf1. However, the effect of ZF5 on the activity of Fzf1 is not well defined. In this study, substitutions of the two zinc-coordinating Cys residues (C248S and C253S) of ZF5, or deletion of the whole ZF5 domain, compromised the chemical stress-induced activation of Fzf1. Since the elevated Fzf1-regulated gene expression caused by fzf1-ZF4 could also be reversed by additional deletion of ZF5 or C248S/C253S substitutions, fzf1-ZF5 mutations are epistatic over fzf1-ZF4 mutations. Furthermore, fzf1-ZF5 mutations are recessive to FZF1, while ZF5 is dispensable for the CS2 binding. Finally, Fzf1-ZF5 is required and sufficient to serve as a transcription activation domain when fused to a Gal4 DNA-binding domain. These observations collectively support a working model in which Fzf1 bound to its target gene promoters remains inactive due to an inhibitory activity of ZF4. Upon chemical stress, ZF4 is no longer able to inhibit the ZF5 transactivation activity, leading to the induction of Fzf1-regulated gene expression and subsequent chemical detoxification. Full article

This study investigates the effectiveness of cold atmospheric plasma (CAP) treatment for improving the microbiological and physicochemical quality of wastewater generated in tourism-affected coastal regions. Experiments were performed on influent and effluent samples from the Ravda Wastewater Treatment Plant (WWTP) collected in April, August, and November 2024, representing different seasonal loading conditions. The plasma pre-treatment of influent aimed to minimize toxic micropollutants that inhibit activated sludge activity, reduce pathogenic and opportunistic microorganisms, and enhance oxidative potential before biological processing. The post-treatment of effluent focused on the elimination of residual pathogens, mainly Enterobacteriaceae, and the oxidative degradation of xenobiotics resistant to conventional treatment. Combined fluorescent (CTC/DAPI) and culture-based analyses were used to assess microbial viability and activity. Plasma exposure (1, 3 and 5 min) caused measurable changes in metabolic potential and bacterial abundance across all sampling periods. The results demonstrate that 1 min CAP treatment does not increase pathogen removal, but enhances oxidation capacity of the influent, while 3 min of CAP treatment ensures the disinfection of the effluent. Both can be combined to improve the effluent safety prior to Black Sea discharge. CAP is showing strong potential as a sustainable technology for wastewater management in tourism-intensive coastal zones. Full article

Background: Marine-derived secondary metabolites such as phlorotannins from the edible brown alga Ecklonia cava exhibit diverse bioactivities. However, their mechanisms in inflammation-associated cancer remain insufficiently understood. Methods: This study explored the anticancer potential of three major phlorotannins (dieckol, 7-phloroeckol, and 8,8′-bieckol) through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation in SKOV3 ovarian cancer cells and tumor-associated macrophages (TAMs). Results: Computational analyses revealed stable binding of phlorotannins to IL-17RA, with 7-phloroeckol and 8,8′-bieckol preferentially engaging loop-proximal regions of the receptor, while dieckol interacted with spatially distinct residues. In SKOV3 ovarian cancer cells, phlorotannins suppressed migration and invasion by approximately 40 to 60%, accompanied by reduced MMP expression linked to IL-17RA–Act1 signaling attenuation and by increased TIMP1 expression in association with transient ERK1/2 activation. In TAMs, phlorotannins attenuated pro-tumorigenic cytokine production and polarization marker expression, indicating suppression of tumor-supportive immune activity. Conclusions: Collectively, these findings demonstrate that E. cava-derived phlorotannins exert anti-metastatic effects through dual regulation of IL-17RA/Act1 and ERK1/2 signaling pathways, offering mechanistic insight into their therapeutic potential against inflammation-driven malignancies. Full article

Idiopathic nephrotic syndrome (INS) is the most prevalent glomerular illness in children. Even while immunologic processes are well-established, oxidative stress is becoming more widely acknowledged as a significant factor in the etiopathogenesis of illness. Assessing its activity and treatment response may be made easier with the use of trustworthy, non-invasive indicators to track redox balance. We report on the oxidative stress levels of a 10.7-year-old boy with INS with five clinical time points in one year. The FRAS5 analyzer was used to calculate the oxidative stress index (OSI), plasma antioxidant capacity (PAT) and derivatives of reactive oxygen metabolites (d-ROMs) as biomarkers. A 4-tier oxidative state classification scheme based on d-ROM and PAT thresholds was used to interpret the values. The patient had low antioxidant defense, moderate oxidative and increased OSI at relapses, a positive transition to reduced oxidative burden and enhanced defense during remission. The order of events showed a dynamic redox response associated with glucocorticoid (GC) medication and disease activity. The potential value of d-ROM, PAT, and OSI as dynamic biomarkers for tracking disease activity, response to treatment and residual oxidative burden in pediatric INS is supported by this case. To confirm their function in more comprehensive clinical decision-making, more research is required. Full article

Metalloproteinases (MPs) are zinc-dependent endopeptidases, including matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs), implicated in various diseases such as cancer, neurodegenerative disorders, and cardiovascular conditions. Among MPs, ADAM-17, also known as tumor necrosis factor-α (TNF-α)-converting enzyme (TACE), plays a crucial role in extracellular matrix remodeling and cytokine release. Dysregulation of ADAM-17 contributes to inflammatory diseases, cancer progression, and immune modulation. While small-molecule inhibitors have been limited by off-target effects and instability, antibody-based approaches offer a more selective strategy. Monoclonal antibodies show promise in blocking ADAM-17 activity, but there are concerns about toxicity due to the lack of selectivity. Enhancing the binding affinity and selectivity of single-chain antibodies requires unraveling the structural details that drive MP targeting. This study uses yeast surface display (YSD) and fluorescence-activated cell sorting (FACS) to engineer single-chain variable fragment (scFv) antibodies with optimized complementarity-determining region 3 of the heavy chain (CDR-H3) conformations. Next-generation sequencing (NGS) was used to identify key residues contributing to high-affinity ADAM-17 binding. These findings offer a framework for designing monoclonal antibodies against ADAM-17 and other MPs, paving the way for novel antibody-based designer scaffolds with applications in developing therapeutics. Full article

This study examines the influence of physical biomass pretreatment on the pyrolysis behavior of woody pruning residues of Carya illinoinensis (pecan tree) processed in a stainless-steel batch reactor heated by concentrated radiative energy. Experiments were conducted with 25.5 g of biomass using a solar simulator equipped with a mirror concentrator, operating at three constant thermal power levels (234, 482, and 725 W). As a pretreatment strategy, the woody residues were deliberately processed without drying, while mechanical size reduction and sieving were applied to obtain a controlled particle size range of 1–4 mm. This approach enabled the isolated assessment of the effects of physical pretreatment, particularly particle size and bulk density, on heat transfer, thermal response, and pyrolysis behavior. The pyrolysis performance of the pretreated woody biomass was systematically compared with that of walnut shell biomass and inert volcanic stones subjected to the same particle size control. Two consecutive experimental cases were implemented: Case A (CA), comprising heating, pyrolysis of fresh biomass, and cooling; and Case B (CB), involving reheating of the resulting biochar under identical operating conditions. An improved analytical methodology integrating temperature–time profiles, their derivatives, and gas composition analysis was employed. The results demonstrated the apparently inert thermal behavior of biochar during reheating and enabled clear temporal identification of the main biomass conversion stages, including drying, active pyrolysis of hemicellulose and cellulose, and passive lignin degradation. However, relative to walnut shell biomass of equivalent volume, the woody pruning residues exhibited attenuated thermal and reaction signals, primarily attributed to their lower bulk density resulting from the selected pretreatment conditions. This reduced bulk density led to less distinct pyrolysis stages and a 4.66% underestimation of the maximum reaction temperature compared with thermogravimetric analysis, highlighting the critical role of physical pretreatment in governing heat transfer efficiency and temperature measurement accuracy during biomass pyrolysis. Full article

The Bayer process is used to extract alumina from bauxite, resulting in the formation of a highly alkaline solid residue known as bauxite residue (BR). However, such residue contains insufficient iron (<35% Fe) and complex impurity composition for use in blast furnace ironmaking. This study investigates the potential for enhancing the extraction of aluminium (Al) and increasing the concentration of Fe in residue by electrolytical reduction in suspension of BR in a spent Bayer process solution. A maximal current efficiency of 43.7% was obtained during the electroreduction of the coarse fraction of BR. The magnetite-containing residue obtained was further used as an aid in the high-pressure Bayer process leaching of gibbsitic bauxite. Adding the reduced BR increased the Al extraction rate by up to 7.2%. The kinetics of bauxite leaching at 120–160 °C and time interval 0–40 min in the presence of reduced BR were investigated using a shrinking core model (SCM). The results showed that the leaching kinetics of Al correlate well with the intraparticle SCM equation, indicating that the reaction velocity is regulated by the diffusion of the OH⁻ or Al(OH)₄⁻ through the product layer. The apparent activation energy of the process at 140–160 °C was found to be 32.2 kJ/mol. Al in the solid residue is closely associated with Fe, i.e., it is enclosed in a solid matrix of iron minerals. Full article

The inhibitory effects of natural cellulose (NC), microcrystalline cellulose (MC), and soluble fiber dextrin (SC) on amylase activity have been established; however, the underlying mechanisms remain poorly understood. This study employed fluorescence spectroscopy and fluorescence thermodynamics to investigate the quenching parameters, thermodynamic properties, and quenching mechanisms of cellulose interactions with α-amylase and amyloglucosidase. Structural alterations in both enzymes were examined using synchronous fluorescence and UV–visible absorption spectroscopy. The results indicated that NC, MC, and SC primarily induced static quenching of fluorophores in α-amylase and amyloglucosidase. When addition of SC reached 3%, SC reduced the fluorescence intensity of tyrosine and tryptophan residues in α-amylase by 70.9% and 86.8%, and in amyloglucosidase by 43.7% and 46.5%, respectively. Increasing SC levels also decreased hydrophobicity around tyrosine and tryptophan in α-amylase. These findings provide insights into designing cellulose-based amylase inhibitors through structural modulation for developing low-glycemic index (GI) foods. Full article

Irritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by recurrent abdominal pain associated with a change in the frequency and/or form of stools. Approximately one in three patients with quiescent inflammatory bowel disease (IBD), defined as the absence of endoscopic evidence of active inflammation, experience IBS-type symptoms. These symptoms are associated with reduced quality of life and increased psychological burden, and can complicate clinical assessment by mimicking conditions such as small intestinal bacterial overgrowth, bile acid malabsorption, or post-inflammatory complications. This up-to-date narrative review examines the mechanisms, diagnostic challenges, and management of IBS-type symptoms in quiescent IBD. Evidence suggests that these symptoms arise from a complex “matrimony” of functional and organic processes, including low-grade residual inflammation, altered intestinal permeability, microbiota dysbiosis, visceral hypersensitivity, and psychosocial impairment. Diagnosing IBS-type symptoms in IBD requires a “positive”, symptom-focused approach while carefully excluding active inflammation. Management should adopt a biopsychosocial approach, integrating dietary strategies (e.g., low-FODMAP diet), brain–gut behavioral therapy, biofeedback therapy, and/or pharmacological treatments such as antispasmodics, antidiarrheals, laxatives, and neuromodulators to address both physiological and psychological factors. Future research should integrate sensitive biomarkers and longitudinal follow-up to enhance diagnostic precision and guide personalized therapy. Understanding and addressing the overlap between IBS and IBD is essential to reduce the multidimensional burden on physical health, psychological well-being, and daily functioning. Full article

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase that catalyzes template-independent nucleotide addition at the 3′-end of DNA, playing a critical role in generating immune receptor diversity. While the structural importance of Loop1 in blocking template strand binding and enabling this activity is established, the precise molecular contribution of hydrophobic interactions within Loop1 to the catalytic mechanism of human TdT remains unclear. In the present study, we aim to elucidate the roles of hydrophobic Loop1 residues (L397, F400, F404) in the structural organization and catalytic function of TdT. We engineered alanine and tryptophan substitutions at these positions and systematically analyzed the resulting mutant forms using molecular dynamics simulations and pre-steady-state kinetic measurements. Our results show that substitutions L397A and F400A increase Loop1 flexibility and significantly reduce catalytic activity, particularly for purine nucleotide incorporation, while F404A completely abolishes enzymatic function. The F404W mutant largely preserves activity. All mutant forms retain the ability to bind single-stranded DNA and dNTP, but in some cases, their affinity and thermal stability were reduced. These findings demonstrate that hydrophobic interactions in Loop1 are essential for maintaining the catalytically competent conformation of TdT, ensuring precise substrate positioning and active site stability. Full article

The objective of this study was to establish the kinetic of gasification reactions involved in chemical looping gasification (CLG) using pelletized biomass as solid fuel. However, significant limitations have been found in obtaining such kinetics using a traditional methodology from a large number of tests in a thermogravimetric analyzer (TGA) for pelleted biomass. A novel methodology is presented in this article, namely: (i) the determination of the intrinsic gasification rate for several biomasses; (ii) the determination of the gasification rate of pelletized biomass under selected operating conditions; (iii) the development and validation of a reaction model for pelletized biomass considering the determined intrinsic kinetics and gas diffusion in the biomass particles; and (iv) obtaining an apparent kinetics from data calculated with the developed model, which will be easy to implement in the modeling of gasifiers. To evaluate the applicability of this methodology, it was demonstrated with three different types of biomasses: pine forest residue (PFR), industrial wood pellets (IWP), and wheat straw pellets (WSP). The intrinsic kinetics was derived from tests with powdered char under several operating conditions: reacting temperature (1073–1223 K), concentration of gasifying agent (10–40 vol.% H₂O or CO₂), and concentration of gasification product (0–40 vol.% H₂ or CO). The evolution of the char conversion with the reacting time was predicted using a model involving three different regimes: (I) deactivation at the beginning; (II) uniform progress in the main middle part following a n-order model; and (III) catalytic activation as complete conversion is approached. The second regime was included for all biomasses, being 1, 0.4, and zero-order for WSP, IWP, and PFR, respectively. However, the third regime was observed for PFR and IWP, and the first regime only for IWP. The intrinsic kinetics was successfully used in a theoretical model to properly predict the gasification rate of pelletized biomass, and, eventually, to determine an apparent gasification kinetics as simple as possible in order to be easily implemented in future gasifier modeling works. Full article