Search Results (397)

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

This study presents a cost-effective, carbon-negative construction material for affordable housing, developed entirely from locally available agricultural wastes: rice husk ash, wood ash, and rice straw—materials often problematic to dispose of in many African regions. Rice husk ash provides high amorphous silica, acting as a strong pozzolanic agent. Wood ash contributes calcium oxide and alkalis to serve as a reactive binder, while rice straw functions as a lightweight organic filler, enhancing thermal insulation and indoor climate comfort. These materials undergo natural pozzolanic reactions with water, eliminating the need for Portland cement—a major global source of anthropogenic CO₂ emissions (~900 kg CO₂/ton cement). This process is inherently carbon-negative, not only avoiding emissions from cement production but also capturing atmospheric CO₂ during lime carbonation in the hardening phase. Field trials in Kenya confirmed the composite’s sufficient structural strength for low-cost housing, with added benefits including termite resistance and suitability for unskilled laborers. In a collaboration between the University of Tartu and Kenyatta University, a semi-automatic mixing and casting system was developed, enabling fast, low-labor construction of full-scale houses. This innovation aligns with Kenya’s Big Four development agenda and supports sustainable rural development, post-disaster reconstruction, and climate mitigation through scalable, eco-friendly building solutions. Full article

Prussian blue and its analogs (PBAs), considered potential cathode materials for sodium-ion batteries (SIBs), still confront multiple challenges. For example, many defect vacancies and high crystal water content are generated during the fast crystallization of PBAs, impairing the rate performance. The stress accumulation during Na⁺ insertion/extraction destabilizes the lattice framework and then damages the electrochemical performance. Herein, iron-based Prussian blue with an open-pore skeleton structure (PB-3) is prepared using a facile template method which employs PVP and sodium citrate to control the crystallization rate and adjust the particle morphology. The prepared materials exhibit excellent kinetic properties and are conducive to mitigate the volume changes during ion insertion/extraction processes. PB-3 electrode not only exhibits a superior rate performance (92 mAh g⁻¹ reversible capacity at 2000 mA g⁻¹), but also presents superior cycling performance (capacity retention remained at 90.2% after 600 cycles at a current density of 500 mA g⁻¹). The highly reversible sodium ion insertion/extraction mechanism of PB-3 is investigated by ex situ XRD tests, which proves that the stabilized lattice structure can enhance the long cycling performance. In addition, the considerable capacitance contributes to the rate performance. This study provides valuable insights for the subsequent development of high-performance and stable cathodes for SIBs. Full article

The Mixed Ombrophyllous Forest (MOF), inserted in the Atlantic Forest biome, is of great ecological value, with deficient management strategies. In this context, sustainable management helps to promote the regeneration and growth of individual trees and control others, while maintaining the natural forest structure. This study therefore aimed to discuss opportunities and limitations of biochar, produced from two species from the MOF, which are currently only utilized to a limited extent in the study area in southern Brazil. A slow pyrolysis process at a lab scale was designed, biochar was produced, and key properties were analyzed from Hovenia dulcis Thunb. (chosen as an invasive species) and Mimosa scabrella Benth. (chosen as a native, fast-growing species), including branches and stems. The results showed that branches of Mimosa scabrella (BMS) had the highest biochar yield (30.32 ± 0.3%) and the highest electrical conductivity (415.08 ± 24.75 mS cm⁻¹). Stems of Mimosa scabrella (SMS) showed the highest higher heating value (HHV—31.76 ± 0.01 MJ kg⁻¹), lower heating value (LHV—31.03 ± 0.01 MJ kg⁻¹), and energy yield (49.1%), while the branches of Hovenia dulcis (BHD) showed the lowest values. For the elemental analysis, SMS showed the best results, with the highest amount of fixed carbon (78.62 ± 0.22%) and carbon content (85.87 ± 0.083%), and consequently the lowest amount of ash (3.52 ± 0.08%). BHD showed a better water-holding capacity (303.26 ± 15.21%) and higher pH value (7.65 ± 0.14). The investigations conducted on the biochar from both species indicate a strong suitability of these woods for producing high-quality biochar. Full article

Histone deacetylase 11 (HDAC11), the sole member of class IV HDACs, has gained prominence due to its unique enzymatic profile and pathological relevance in cancer, neurodegenerative, inflammatory diseases, and metabolic disorders. However, only a limited number of selective HDAC11 inhibitors have been identified, and many of these contain a potentially mutagenic hydroxamic acid as a zinc-chelating motif. Consequently, there is an imperative to identify potent and selective non-hydroxamate HDAC11 inhibitors with improved physicochemical properties. In this study, we conducted an extensive experimental high-throughput screening of 10,281 structurally diverse compounds to identify novel HDAC11 inhibitors. Two promising candidates, caffeic acid phenethyl ester (CAPE) and compound 9SPC045H03, both lacking a hydroxamic acid warhead, were discovered, showing micromolar inhibitory potency (IC₅₀ = 1.5 and 2.3 µM, respectively), fast and reversible binding, and remarkable isozyme selectivity. Molecular docking revealed distinct zinc-chelating mechanisms involving either carbonyl oxygen (CAPE) or pyridine nitrogen (9SPC045H03), in contrast to canonical hydroxamates. Both compounds are drug-like and exhibit favorable physicochemical and pharmacokinetic profiles, particularly beneficial water solubility and good adsorption, making them valuable starting points for further optimization. These findings open new avenues for the development of selective, non-hydroxamate HDAC11 inhibitors with potential therapeutic applications. Full article

The short-term scheduling of pumped-storage hydropower plants is characterised by high dimensionality and nonlinearity and is subject to multiple operational constraints. This study proposes an intelligent scheduling framework that integrates an Atomic Orbital Search (AOS)-optimised Long Short-Term Memory (LSTM) network with the Deep Deterministic Policy Gradient (DDPG) algorithm to minimise water consumption during the generation period while satisfying constraints such as system load and safety states. Firstly, the AOS-LSTM model simultaneously optimises the number of hidden neurons, batch size, and training epochs to achieve high-precision fitting of unit flow–efficiency characteristic curves, reducing the fitting error by more than 65.35% compared with traditional methods. Subsequently, the high-precision fitted curves are embedded into a Markov decision process to guide DDPG in performing constraint-aware load scheduling. Under a typical daily load scenario, the proposed scheduling framework achieves fast inference decisions within 1 s, reducing water consumption by 0.85%, 1.78%, and 2.36% compared to standard DDPG, Particle Swarm Optimisation, and Dynamic Programming methods, respectively. In addition, only two vibration-zone operations and two vibration-zone crossings are recorded, representing a reduction of more than 90% compared with the above two traditional optimisation methods, significantly improving scheduling safety and operational stability. The results validate the proposed method’s economic efficiency and reliability in high-dimensional, multi-constraint pumped-storage scheduling problems and provide strong technical support for intelligent scheduling systems. Full article

Toona sinensis (A. Juss.) Roem, classified under the Toona genus of the Meliaceae family, is a fast-growing, woody species endemic to China, valued as both a vegetable crop and medicinal plant. Its seeds achieve rapid germination through a cascade of interconnected physiological, metabolic, and hormonal adaptations. Initially, physiological hydration is driven and accelerated by only two distinct phases of water imbibition. This hydration surge triggers storage reserve mobilization, with soluble sugars, proteins, and lipids undergoing rapid degradation during imbibition, while starch catabolism proceeds gradually—a pattern mirrored by progressive increases in enzymatic activities (amylase, protease, and acid phosphodiesterase (ACP)) that correlate with reserve reallocation. Concurrently, a metabolic shift from glycolysis to the pentose phosphate pathway (PPP) optimizes energy utilization, supporting germination acceleration. These biochemical changes are orchestrated by hormonal coordination: elevated gibberellin A₃ (GA₃), zeatin riboside (ZR), and indole-3-acetic acid (IAA) levels, coupled with rising GA₃/ABA, IAA/ABA, and ZR/ABA ratios, temporally aligned with germination progression. Finally, structural evidence confirms successful germination completion, as cotyledon lipid droplet breakdown and starch granule synthesis directly correlate with embryonic elongation. Together, these mechanisms underscore T. sinensis’ adaptive strategy, integrating physiological plasticity, metabolic flexibility, and endocrine precision to ensure efficient germination. Full article

Peripheral blood leukocytes are able to migrate to the inflamed tissue, and to engulf and kill invading microbes. This requires rapid modifications of cell morphology and volume through fast movements of osmotic water into or out of the cell. In this process, membrane water channels, aquaporins (AQPs), are critical for cell shape changes as AQP-mediated water movement indirectly affects the cell cytoskeleton and, thereby, the signaling cascades. Recent studies have shown that the deletion or gating of two immune cell AQPs, AQP3 and AQP9, impairs inflammation and improves survival in microbial sepsis. Here, we assessed the expression and distribution of AQP3 and AQP9 in human leukocytes and investigated their involvement in the phagocytosis and killing of the Gram-negative pathogenic bacterium Klebsiella pneumoniae, and their role in lipopolysaccharide (LPS)-induced cell migration. By RT-qPCR, AQP3 mRNA was found in peripheral blood mononuclear cells (PBMCs) but it was undetectable in polymorphonuclear white blood cells (PMNs). AQP9 was found both in PBMCs and PMNs, particularly in neutrophil granulocytes. Immunofluorescence confirmed the AQP3 expression in monocytes and, to a lesser degree, in lymphocytes. AQP9 was expressed both in PBMCs and neutrophils. Specific inhibitors of AQP3 (DFP00173) and AQP9 (HTS13286 and RG100204) were used for bacterial phagocytosis and killing studies. No apparent involvement of individually blocked AQP3 or AQP9 was observed in the phagocytosis of K. pneumoniae by neutrophils or monocytes after 10, 30, or 60 min of bacterial infection. A significant impairment in the phagocytic capacity of monocytes but not neutrophils was observed only when both AQPs were inhibited simultaneously and when the infection lasted for 60 min. No impairment in bacterial clearance was found when AQP3 and AQP9 were individually or simultaneously blocked. PBMC migration was significantly impaired after exposure to the AQP9 blocker RG100204 in the presence or absence of LPS. The AQP3 inhibitor DFP00173 reduced PBMC migration only under LPS exposure. Neutrophil migration was considerably reduced in the presence of RG100204 regardless of whether there was an LPS challenge or not. Taken together, these results indicate critical but distinct involvements for AQP3 and AQP9 in leukocyte motility, while no roles are played in bacterial killing. Further studies are needed in order to understand the precise ways in which these two AQPs intervene during bacterial infections. Full article

The interaction of the Almone River with groundwater in the Caffarella area (Rome, Italy) was investigated using a multi-method approach based on hydrogeological and radon analyses. Eleven measurement stations were established along the river at distances of approximately 270 m from one another. Stream discharge, water physicochemical properties, and radon levels were measured from June 2024 to March 2025. The contribution of two tributaries of the Almone was evaluated, but it was found to be negligible in terms of radon contribution. Except for an average increase of 40 L/s between stations 1A and 2A, the Almone’s discharge (corrected for the streams input) was constant (around 150 L/s) in June and slightly increasing from 6A to 11A in March due to heavier rainfalls. The increased discharge between stations 1A and 2A was interpreted as groundwater overflow from the volcanic aquifer into the alluvial body and in turn into the river due to a change in geometry and volume of the volcanic aquifer. In that part of the river, radon concentration increased only in March, due to the fast transition of the groundwater from a high to a lower radon emanation unit. Radon decreased along the valley due to atmospheric evasion, as confirmed by pH growth due to CO₂ degassing. Full article

In this paper, the mechanism of interlayer bonding under a low-temperature environment is systematically revealed in terms of the temperature control difficulties in the continuous multilayer construction of an asphalt concrete core wall in winter. A field simulation paving test was conducted using a temperature-controllable simulated paving system, and the key laws of the temperature transfer and mechanical property evolution were discovered by precisely regulating the surface temperature of the bonded surface (the test range covered from −5 °C to 70 °C). This study shows that a bonding surface temperature of 40 °C is a critical point of engineering importance, at which the material exhibited a unique performance compensation effect. Under this temperature condition, although the mechanical index was reduced compared with the parent material, the flexural strength was reduced by 11.39%, the maximum bending strain was reduced by 9.65%, the tensile strength was reduced by 7.89%, the critical tensile strain was reduced by 16.11%, and the crack curvature coefficient was reduced by 10.06%. However, thanks to the unique structural reorganization characteristics of asphalt materials, these performance losses were effectively compensated, thus ensuring the stability of engineering applications. In particular, a fast rise–stable–slow decline evolution law of the interlayer temperature transfer was found, proving the existence of a temperature-adaptive interval of the bond surface. The research results not only enrich the theory of asphalt concrete interlayer bonding but also provide innovative technical solutions for the construction of water conservancy projects in cold regions. In particular, the fast rise–stable–slow drop evolution law of the interlayer temperature transfer was found, which proves the existence of a temperature-adaptive interval of the bond surface. The research results not only enrich the theory of asphalt concrete interlayer bonding but also provide innovative technical solutions for the construction of water conservancy projects in cold regions. Full article

Hydrogen-bonded cross-linked main chain azobenzene (azo) photoactive polymers have broad application prospects in flexible actuators, optical actuators, and other fields. Most of the research on this kind of photoresponsive material is mainly focused on air, and exploration in solvents remains underexplored. In this paper, azobenzene polyamide ester semicrystalline polymer (PEA-6T) with hydrogen-bond cross-linking was synthesized by Michael addition polymerization. The uniaxially oriented polymer film with high orientation (48.85%) and fast response (5 s under UV light and 55 s under visible light) was obtained by a simple solution casting/mechanical stretching method. Compared with PEA-2T and PEA-4T, PEA-6T exhibits enhanced mechanical properties (elastic modulus increased by 17.4%; yield strength increased by 34.1%; breaking strength increased by 75.4%; elongation at break increased by 33.8%; toughness increased by 101.3%; photoinduced stress increased by 43.5%) and reduced light response time (decreased by 58.3% in ultraviolet light and 50% in visible light) due to the elongation of the compliant chain length. The thin PEA-6T film exhibited light-induced deformation not only in air but also in polar solvents such as water, methanol, ethanol, butanol, and saline solutions (e.g., normal saline, 0.9 wt% NaCl, and simulated seawater, 3.5 wt% NaCl). In addition, polarizing optical microscope (POM) observations showed that the brightness and texture direction of the films remained stable (Δ_Brightness < 5%), the light response time was consistent (6 s under UV light, 65 s under visible light), the light-induced stress retention rate was 95%, and the films exhibited good solvent resistance. This study bridges the research gap in azobenzene photoresponsive materials in solvent environments, and the material shows potential for applications in marine equipment coatings or biomedical actuators. Full article

This study focuses on enhancing the photoelectrocatalytic (PEC) performance of LaFeO₃ photocathodes by incorporating Ag nanocrystals. LaFeO₃, a perovskite-type metal oxide semiconductor, has potential in PEC water splitting but suffers from fast charge carrier recombination. Ag nanoparticles are introduced due to their surface plasmon resonance (SPR) property and ability to form Schottky junctions with LaFeO₃. A series of Ag/LaFeO₃ materials are prepared using the molten salt method for LaFeO₃ synthesis and the direct reduction method for Ag loading. The results show that Ag nanoparticles are uniformly dispersed on LaFeO₃. The 3 mol% Ag/LaFeO₃ photocathode demonstrates a remarkable ninefold increase in photocurrent density (15 mA·cm⁻² at −0.2 V vs. RHE) compared to pure LaFeO₃ (1.7 mA·cm⁻²). The band gap of LaFeO₃ is reduced from 2.07 eV to 1.92 eV with 3 mol% Ag loading, and the charge transfer impedance is reduced by 77%, while the carrier concentration increases by 2.3 times. The novelty of this work lies in the comprehensive investigation of the interaction mechanisms between Ag nanoparticles and LaFeO₃, which lead to enhanced light absorption, improved charge separation, and increased electrochemical activity. The optimized Ag loading not only improves the photocatalytic efficiency but also enhances the stability of the photocathode. This work provides valuable insights into the interaction between Ag and LaFeO₃, and offers experimental and theoretical support for developing efficient photocatalytic materials for PEC water splitting. Full article

Background: The antidiabetic drug gliclazide is often taken with antacids due to its gastrointestinal side effects. However, patients rarely report antacid use, making drug–drug interactions a potential cause of therapy failure. Therefore, this study aimed to investigate the in vitro effects of various antacids on gliclazide permeability and to explore the underlying mechanisms. Methods: The permeability of gliclazide alone and in the presence of antacids (sodium bicarbonate, calcium carbonate, aluminum hydroxide, hydrotalcite and calcium carbonate/magnesium carbonate) was investigated using the parallel artificial membrane permeability assay (PAMPA) in four media (buffers pH 1.2, pH 4.5, pH 6.8 and water). The permeability coefficients were calculated, and the effect of pH on gliclazide permeability was also evaluated. Results: At simulated fasting gastric conditions (pH 1.2), groups with calcium carbonate, hydrotalcite and the combination of calcium carbonate/magnesium carbonate showed significantly higher permeability of gliclazide than the control group. At fed-state gastric conditions (pH 4.5), only hydrotalcite did not significantly change the permeability of gliclazide. Sodium bicarbonate, aluminum hydroxide and hydrotalcite significantly reduced the gliclazide permeability in comparison to the control group at pH 6.8 as a representative of fasted-state intestinal fluid. Conclusions: Antacids significantly impact the permeability of gliclazide at different pH values, potentially influencing its bioavailability. Gliclazide permeability is mainly influenced by pH-dependent ionization, though complex or salt formation may also play a role. Since both gliclazide and antacids are taken with food, and gliclazide is primarily absorbed in the small intestine, calcium- and magnesium-based antacids can be considered the most suitable choice. Full article

Most parts of the earth are covered with water, but only 0.3% of it is available to living beings. Industrial growth, fast urbanization, and poor water management have badly affected the water quality. In recent years, a transition has been seen from the traditional (physical, chemical) wastewater treatment methods towards a greener, sustainable, and scalable membrane technology. Even though membrane technology offers a green pathway to address the wastewater treatment issue on a larger scale, the fabrication of polymeric membranes from toxic solvents is an obstacle in making it a fully green method. The concept of green chemistry has encouraged scientists to engage in research for new biodegradable and non-protic solvents to replace with already existing toxic ones. This review outlines the use of non-toxic solvents for the preparation of PVDF membranes and their application in membrane distillation and membrane crystallization. Full article

Saline lakes are rare and fragile habitats with a high conservation and scientific interest. We have studied the presence of microplastics (MPs) in the water of four inland saline lakes located in the Central Ebro Basin (CEB), NE Spain. Quantification and characterization of MPs were performed by optical microscopy and micro-Fourier Transform Infrared Spectroscopy (micro-FTIR). MPs analyzed covered the 5–5000 μm range. Most of the MPs collected were contained in the 250–500 and 500–1000 μm ranges. The concentration of MPs varied from 850 ± 271 to 1556 ± 59 MPs/L, fibers being the most dominant typology. Seven different colors were observed, the most abundant being black, and seven types of plastic were identified, polyester, polyethylene terephthalate, and nylon the most abundant. The smallest lakes presented a more homogeneous MP size distribution and a wider variety in color and polymer composition. This work shows that the MP concentration in these lakes is at least one order of magnitude higher than previous values reported in similar environments, and it is expected to multiply fast. This highlights the importance of the hydrological characteristics of these lakes, the evapotranspiration being the only water outflow, the atmospheric deposition of MPs, and other anthropogenic causes. Full article