Search Results (346)

Metal–organic frameworks (MOFs) typically exist in the form of powders or dispersed crystals, which limits their direct application in practical engineering scenarios that require monolithic structures and processability. To address this issue, the present study successfully anchored MOF (zeolitic imidazolate framework-8, ZIF-8) nanocrystals within a porous silicon carbide (p-SiC) substrate via a facile in situ growth strategy, achieving both stable macroscopic loading and intimate microscopic interfacial bonding. The resulting ZIF-8/p-SiC composite exhibits a hierarchical porous structure, with a specific surface area approximately 183 times higher than that of the raw p-SiC, alongside a substantially enhanced CO₂ adsorption capacity. By utilizing a low-cost p-SiC support and mild ZIF-8 synthesis conditions, this work demonstrates excellent reproducibility and scalability, providing a facile and effective pathway for fabricating MOF/porous media composite systems that possess both superior mechanical properties and tailored pore structures. Additionally, the developed MOF/p-SiC composites can serve as controllable rock-analog porous media, offering new perspectives for investigating MOF-rock interfacial interactions and CO₂ geological sequestration mechanisms, thereby establishing an organic link between fundamental materials science and geological engineering applications. Full article

Background: Alcohol use disorder is a common condition with high morbidity and mortality and no highly effective treatments. Achieving and maintaining abstinence is necessary or desired for many persons with AUD, but is difficult due to the nature of the condition. Pharmacologic inhibition of the enzyme ALDH2, which increases levels of the substrate acetaldehyde when alcohol is imbibed, can serve as a powerful enforcer of efforts to remain abstinent. Disulfiram is an approved ALDH2 inhibitor via its active metabolite DETC-MeSO, but has many limitations, including numerous adverse effects, hepatotoxicity, oral administration, and unpredictable mechanistic activity. Methods: SOPH-110S, an analog of DETC-MeSO, was evaluated in a series of experiments to assess mechanism, pharmacokinetics in male beagle dogs, cardiovascular safety in telemeterized male beagle dogs, selectivity, off-target activity, CYP inhibition, and proof of mechanism in a rat model that included dosing and alcohol challenge followed by analysis of liver ALDH2 inhibition. Results: SOPH-110S showed high potency with a comparable IC₅₀ vs. positive controls and no physiologically relevant off-target binding in an 84-target panel. It did not inhibit or induce any major CYP enzymes or meaningfully inhibit the hERG channel. After 10 days’ dosing in rats, followed by administration of alcohol, SOPH-110S was a highly potent, dose-dependent inhibitor of ALDH2, comparable to DETC-MeSO. No cardiovascular safety concerns were found at multiples above expected clinical doses. Conclusions: The preclinical data support further clinical study of SOPH-110S as a potential ALDH2 inhibitor treatment for AUD. The FDA approved the IND to conduct a first-in-man phase 1 study in September 2025. Full article

The evolution of type I polyketide synthase (T1PKS) assembly lines remains poorly understood. Through systematic mining of polyene biosynthetic gene clusters, we identified a novel eurocidin biosynthetic pathway capable of producing identical compounds with divergent loading module architectures, thereby capturing an evolutionary transitional state. Biochemical analysis revealed unprecedented functional reprogramming of acyltransferase (AT) domains, shifting substrate specificity from extender units (malonyl-CoA) to starter units (acyl-CoA). This paradigm shift enables direct initiation of polyketide chain assembly via AT-mediated loading of starter units, thereby elucidating the origin of extant AT-initiated assembly lines and establishing AT functional plasticity as a novel mechanism for polyketide structural diversification. Parallel evolution of ketosynthase (KS) domains through KSS→KSQ mutations further diversified initiation strategies. Applying this evolutionary insight, we engineered the candicidin pathway by replacing its native aromatic-starting bimodule with a starter-selective monomodule from eurocidin, generating aliphatic-starting analogs. This demonstrates that evolution-inspired AT reprogramming provides a rational framework for modifying polyketide starter units, expanding structural diversity, and enhancing therapeutic potential. Full article

In the last few years, Thin Film Transistors (TFTs) based on materials such as amorphous Indium–Gallium–Zinc Oxide (a-IGZO) have gained interest in large-area and low-cost electronics due to their high carrier mobility, high on/off current ratio, low off-state current, and steep subthreshold slope. These characteristics make IGZO TFTs suitable for radio-frequency identification (RFID) tags, analog-to-digital converters (ADCs), logic circuits, sensors, and analog components, including operational amplifiers (OPAMPs). This work presents the implementation and characterization of an OPAMP based on n-type a-IGZO TFTs fabricated on glass substrate. Two previously reported design strategies were integrated: a positive feedback network to increase the output impedance and a topology to enhance the transconductance of the driver transistors, both in the differential input stage. A gain of 26 dB, a bandwidth of 2.4 kHz, a gain–bandwidth product (GBWP) of 48 kHz, and a phase margin of 64° were obtained, which confirms the reliability of the design and the fabrication process. Full article

Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs—producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory–metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut–brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. Full article

Background and Objectives: Implant-associated complications, including foreign-body responses and infection risk, remain major concerns in reconstructive and aesthetic breast surgery. Antimicrobial polymer coatings have been proposed as potential preventive strategies, but early-stage development requires simple and ethically refined in vivo models. This pilot study aimed to (i) establish a practical workflow for applying PLGA–vancomycin coatings onto PTFE substrates used as experimental analogs for smooth silicone implants, and (ii) develop a small-animal implantation protocol for short-term evaluation of surgical feasibility and local tissue tolerability. Materials and Methods: PLGA microparticles and PLGA–vancomycin microparticles were prepared using a double-emulsion solvent-evaporation method and applied onto PTFE discs. Particle size and polydispersity were assessed based on dynamic light scattering (DLS), and surface charge was measured via zeta potential. A bilateral subcutaneous implantation model was used in four Wistar rats, each receiving a PTFE disc coated with PLGA-only on one side and a disc coated with PLGA–vancomycin on the other. Animals were monitored for postoperative recovery, wound appearance, and general condition. After four weeks, implants and surrounding tissues were harvested for macroscopic and preliminary histological evaluation. Results: Both PLGA-only and PLGA–vancomycin microparticles showed submicron mean hydrodynamic diameters and moderately polydisperse distributions typical for double-emulsion formulations. All animals recovered normally, maintained stable body weight, and exhibited no macroscopic signs of adverse reactions. Preliminary histology showed early fibrous capsule formation with mild inflammatory infiltrate around both types of coated implants, without qualitative differences observed in this pilot setting. Conclusions: This preliminary study demonstrates the feasibility of applying PLGA-only and PLGA–vancomycin coatings onto PTFE implant analogs and establishes a reproducible, minimal-use rat model for short-term evaluation of local tissue tolerability. The protocol provides a practical foundation for future work on coating stability, drug-release kinetics, antibacterial activity, and long-term tissue responses on medical-grade silicone substrates. Full article

Background/Objectives: Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited therapeutic options restricted to benznidazole and nifurtimox, both associated with significant toxicity and reduced efficacy during chronic infection. Seeking novel, safe, and sustainable chemotherapeutic candidates, two new saturated cardanol-derived phospholipid analogs—LDT10 and LDT119—were rationally designed based on the molecular scaffold of miltefosine and biosourced from cashew nut shell liquid (CNSL). This study aimed to evaluate the pharmacokinetic properties of these compounds in silico and assess their antiparasitic activity, cytotoxicity, and morphological and ultrastructural effects on all developmental forms of T. cruzi in vitro. Materials and Methods: In silico ADMET predictions (SwissADME, pkCSM) were performed to determine bioavailability, pharmacokinetic behavior, CYP inhibition, mutagenicity, and hepatotoxicity. Antiproliferative activity was evaluated in epimastigotes, trypomastigotes, and intracellular amastigotes using dose–response assays and flow cytometry. Cytotoxicity was assessed in HEPG2 and HFF-1 cells using resazurin-based viability assays. Morphological and ultrastructural alterations were investigated through scanning (SEM) and transmission (TEM) electron microscopy. Reactive oxygen species (ROS) generation was quantified with H₂DCFDA after 4 h and 24 h of exposure. Results: In silico analyses indicated favorable drug-like profiles, high intestinal absorption (>89%), absence of mutagenicity or hepatotoxicity, and non-penetration of the blood–brain barrier. LDT10 was not a P-gp substrate, and LDT119 acted as a P-gp inhibitor, suggesting reduced efflux and higher intracellular retention. Both compounds inhibited epimastigote proliferation with low IC₅₀ values (LDT10: 0.81 µM; LDT119: 1.2 µM at 48 h) and reduced trypomastigote viability (LD₅₀ LDT10: 2.1 ± 2 µM; LDT119: 1.8 ± 0.8 µM). Intracellular amastigotes were highly susceptible (IC₅₀ LDT10: 0.48 µM; LDT119: 0.3 µM at 72 h), with >90% inhibition at higher concentrations. No cytotoxicity was observed in mammalian cells up to 20 µM. SEM revealed membrane wrinkling, pore-like depressions, rounded cell bodies, and multiple flagella, indicating cell division defects. TEM showed Golgi disorganization, autophagic vacuoles, mitochondrial vesiculation, and abnormal kinetoplast replication, while host cells remained structurally preserved. Both compounds induced significant ROS production in trypomastigotes after 24 h in a dose-dependent manner. Conclusions: LDT10 and LDT119 exhibited potent and selective in vitro activity against all developmental stages of T. cruzi, with low micromolar to submicromolar IC₅₀/LD₅₀ values, minimal mammalian cytotoxicity, and extensive morphological and ultrastructural damage consistent with disruption of phospholipid biosynthesis pathways. Combined with favorable in silico pharmacokinetic predictions, these CNSL-derived phospholipid analogs represent promising candidates for future Chagas disease chemotherapy and warrant further in vivo evaluation. Full article

Lipid peroxidation plays a crucial role in living organisms. On the one hand, it contributes to the biosynthesis of several hormones; on the other, it can damage cellular structures, induce cell death, and participate in the pathogenesis of numerous human diseases. Therefore, the development of methods for real-time monitoring of lipid peroxidation, particularly within living systems, represents a highly relevant scientific goal. We previously demonstrated that peroxides of polyunsaturated fatty acids (PUFAs) or PUFA-containing lipids serve as substrates for Chaetopterus luciferase. Further studies revealed that the luminescence of this enzyme results from the decomposition products of PUFA peroxides or related lipids. Moreover, analogous luminescence-inducing products are generated during both enzymatic and chemical peroxidation of PUFAs or PUFA-containing lipids. Collectively, these findings indicate that Chaetopterus luciferase is a promising tool for online detection of lipid peroxidation. Full article

In the current paper, we study breather propagation and arrest in chains with significantly nonlinear interactions of elements depending on the type of nonlinearity. We extend the consideration of the two-stage propagation of breathers in these chains on the relevant substrates to the general case of power-law nonlinear nearest-neighbor interaction. Our work concerns the effect of the nonlinearity on breather propagation and breather arrest. We exploit the simplified model to predict the main features of breather arrest for a wide range of nonlinearity types, including smooth-function analogs for vibro-impact contact. Full article

The absence of a unifying pathogenetic mechanism in metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has significantly hindered therapeutic progress. Appreciation that the delivery of excessive amounts of calories to the liver via the portal circulation might be a key parallel between MASLD and the twin steatotic liver disease, alcohol-related liver disease (ALD), establishes a consolidated framework that could guide rational drug design and precise therapeutic approaches. This review contends that, in both ALD and MASLD, the unique dual blood supply to the liver, from both portal vein and hepatic artery as well as the distinctive blood flow control physiology, prevents hepatic arterial oxygen delivery from adequately compensating for the increased metabolic demands induced by excess caloric intake—alcohol in ALD and food in MASLD—resulting in hepatocellular injury. Over four decades ago, Lautt postulated that this ‘oxygen-nutrient mismatch’ could play a role in ALD. We have extended this paradigm to MASLD, theorizing that analogous mechanisms may be involved in both conditions. Evidence that comorbidities, which are associated with recurrent episodes of hypoxemia, such as obstructive sleep apnea (OSA), exacerbate MASLD progression, supports this. ALD is less strongly linked to metabolic syndrome than MASLD. This may be due to inherent differences in hepatic substrate processing. Carbohydrates, lipids, and proteins undergo diverse and flexible cytosolic metabolic pathways, especially under metabolic stress. In contrast, hepatic ethanol metabolism is predominantly linear and obligately oxidative, providing limited metabolic adaptability. Future perspectives could focus on rectifying the imbalance between hepatic oxygen delivery and nutrient availability. This might be accomplished by attenuating hepatic caloric excess using emerging pharmacotherapies for weight reduction, augmenting hepatic oxygenation through hyperbaric oxygen therapy, or increasing hepatic arterial blood flow with agents such as obeticholic acid. Furthermore, enhancement of hepatic basal metabolic activity with thyroid hormone receptor-β agonists, like resmiritom may confer similar therapeutic effects. Full article

This paper describes an ultra-high-speed monolithic global shutter CMOS image sensor capable of continuous motion capture at 326,000 fps with a resolution of 640 × 480 pixels. The performance is enabled by a novel combination of pixel technology and circuit techniques. The highly sensitive BSI pixel with a 52 μm pitch employs a fully depleted substrate to facilitate rapid photocarrier transport. In-pixel voltage mode storage enables pipelined readout, while in-pixel analog CDS provides low noise with minimal impact on readout speed. The sensor achieves an equivalent row time of 6.4 ns through separate top and bottom readout together with multiple parallel ADCs per column. Independent row drivers on both the left and right sides ensure the global shutter accuracy needed for the minimum exposure time of 59 ns. The dynamic range is enhanced by on-chip reduction in FPN and by PTC-based data compression. The sensor delivers a throughput of 100 Gpix/sec, transferred off chip via 128 CML channels operating at 6.6 Gbps each. The device is fabricated using a 130 nm monolithic CIS process with BSI postprocessing and is in series production. Full article

This study presents a novel strategy for controlling the orientation of MoS₂ films on thick metallic substrates through precise regulation of the sulfur flux alone. In contrast to previous approaches that rely on substrate modifications or complex parameter tuning, orientation control is achieved here solely by adjusting the sulfur concentration during the sulfurization of 400 nm RF-sputtered Mo films. The metallic Mo substrate also allows potential film transfer via selective etching—analogous to the graphene/Cu system—providing a viable route for device integration on arbitrary substrates. Analyses (XRD, Raman, and TEM) reveal that low sulfur flux (30–50 sccm) favors horizontal growth, whereas high flux (>300 sccm) induces vertical orientation. To rationalize this behavior, a reaction-diffusion model based on the Thiele modulus was developed, quantitatively linking sulfur flux to film orientation and identifying critical thresholds (~50 and ~300 sccm) governing the horizontal-to-vertical transition. This unified approach enables the realization of distinct MoS₂ orientations using identical materials and processes, analogous to the orientation control in graphene growth on copper. The ability to grow orientation-controlled MoS₂ on non-noble metal substrates opens new opportunities for integrating electronic (horizontal) and catalytic (vertical) functionalities, thereby advancing scalable manufacturing of TMDC-based technologies. Full article

Massive Multiple-Input Multiple-Output (MIMO) systems with hundreds or thousands of antenna elements are fundamental to next-generation wireless networks, promising unprecedented spectral efficiency through spatial multiplexing and beamforming. However, the computational burden of channel state information (CSI) acquisition and processing scales dramatically with array size, creating a critical bottleneck for practical deployments. While previous works demonstrated that Fast Fourier Transform (FFT)-based beamspace processing can exploit the inherent angular sparsity of wireless channels to compress CSI feedback, the digital implementation requires intensive computations that become prohibitive for ultra-large arrays. This paper presents an analog alternative using Butler matrices—passive beamforming networks that realize the Discrete Fourier Transform in hardware—combined with RF switching circuits to select only dominant angular components. We provide a comprehensive analysis of Butler matrix architectures for arrays up to 32 × 32 elements, characterizing insertion losses across different technologies (microstrip, substrate-integrated waveguide, and waveguide) and operating frequencies (10–30 GHz). The proposed system incorporates parallel power sensing with Winner-Take-All circuits for sub-microsecond beam selection, drastically reducing the number of active RF chains. Full-wave simulations and capacity evaluations at 12 and 30 GHz demonstrate that the Butler-based approach achieves comparable performance to FFT methods while offering significant advantages in power consumption and processing latency. For a 256 × 256 array, FFT computation requires 0.36 ms compared to near-instantaneous analog processing, making Butler matrices particularly attractive for real-time massive MIMO systems. These findings establish Butler matrix front-ends as a practical pathway toward scalable, energy-efficient beamspace processing in 6G networks. Full article

The search for novel low-molecular regulators using molecular docking continues to be crucial for addressing challenges in modern biomedical science. However, the current literature lacks examples of modeling covalent interactions between the ligands being docked and those already present within the proteins, such as enzyme cofactors. This study aims to improve the existing algorithms for modeling such interactions, exemplified by those in thiamine diphosphate (ThDP)-dependent enzymes. Structures containing adducts of ThDP with enzyme substrates or inhibitors are used as protein templates; the putative ligand models are prepared as (R)- or (S)-hydroxy derivatives. The Gnina framework with AD4 or Vinardo favors ligand conformations resembling those found in the protein templates and consistent with their relative inhibitory potentials in experiments in vitro. For example, local hydrophobic regions within pyruvate and branched-chain 2-oxo acid dehydrogenase structures favor the binding of esterified substrate analogs compared to their de-esterified counterparts. The preferred binding of esterified vs. de-esterified ligands is absent or even reversed for 2-oxoglutarate dehydrogenase. As a result, covalent docking of 2-oxo acid analogs to enzyme structures containing ThDP coenzyme offers a predictive capability for protein–ligand complex formation and should be used when inhibitors mimic transition states in enzymatic reactions, as observed with ThDP-dependent catalysis. Full article

This review presents the novel synthesis of nature-inspired drilling strategies specifically tailored for extraterrestrial environments, where conventional technologies fail under the environmental conditions and power and mass constraints. Biomimetic drilling, inspired by insects, mollusks, reptiles, and other organisms, offers novel solutions for extraterrestrial subsurface exploration. Numerous organisms efficiently penetrate materials with low energy, using little force, and adapt to flexible substrates, which are essential capabilities for use off this planet. Traditional rotary and percussive drills do not function well under microgravity, at the end of the temperature spectrum, or in low energy and mass environments, such as landers which are typically under 300 kg and 200 W of power available. Nature-inspired approaches such as the reciprocating carpenter bee style have been shown to reduce overhead forces by as much as 50%; clam-like fluidization reduces drag by 90%; and sandfish-inspired methods improve mobility in granular media by 40%. These also improve the in situ resource utilization (ISRU) approaches for efficient sampling, water ice extraction, and planetary surface operations. This paper focuses on bio-drilling with other biological models, their engineering analogs, and exploration models for off-Earth use. Based on this synthesis, the paper recommends prioritizing dual-reciprocating and oscillatory mechanisms for near-term missions, while pursuing hybrid, AI-driven, and wear-resistant designs for long-term exploration. These approaches will help to improve penetration efficiency, reduce power demands, and extend the drilling system’s lifespan in challenging extraterrestrial environments. Full article