Experimental Evidence Research Articles

Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis.

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart-brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments.

Artificial Intelligence and U.S. Military Cadets’ Attitudes About Future War

What shapes warfighters’ trust in military technologies augmented with Artificial Intelligence (AI)? Research often assumes that junior military personnel, including cadets training to become officers, will trust AI during future wars, and at higher levels than senior officers. We test these claims by fielding a survey experiment among a representative sample of cadets assigned to the Reserve Officers’ Training Corps (ROTC) program in the United States. Our analysis reveals that cadets are more trusting of AI-enhanced military technologies than senior officers, but that their trust is shaped by a more conservative understanding of the appropriate use and oversight of AI. We also find that cadets’ trust is shaped by a complex set of instrumental, normative, and operational considerations, including ongoing cognitive development, education, and professional enculturation. These results provide the first experimental evidence of cadets’ trust in AI-enhanced military technologies and have implications for future research, policy, and military modernization.

Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments.

Sucrose provides both sweetness and energy by binding to both Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose and aspartame only bind to one specific domain (VFD2) of T1R2, resulting in high-intensity sweetness. In this study, we investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites: VFD2, VFD3, transmembrane domain 2 (TMD2), and TMD3 through binding experiments and computational docking studies. Our docking results reveal multiple binding sites for the tested ligands, including the radiolabeled ligands. Our experimental evidence demonstrates that the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to the high-affinity state for steviol glycosides. These findings provide a mechanistic understanding of the structure and function of this heterodimeric sweet taste receptor.

Optical Forces on Chiral Particles: Science and Applications.

Chiral particles have attracted considerable attention due to their distinctive interactions with light, which enable a variety of cutting-edge applications. This review presents a comprehensive analysis of the optical forces acting on chiral particles, categorizing them into gradient force, radiation pressure, optical lateral force, pulling force, and optical force on coupled chiral particles. We thoroughly overview the fundamental physical mechanisms underlying these forces, supported by theoretical models and experimental evidence. Additionally, we discuss the practical implications of these optical forces, highlighting their potential applications in optical manipulation, particle sorting, chiral sensing, and detection. This review aims to offer a thorough understanding of the intricate interplay between chiral particles and optical forces, laying the groundwork for future advancements in nanotechnology and photonics.

Can Environmental Protection Tax Promote Urban Green Transformation? Experimental Evidence from China

Can Environmental Protection Tax Promote Urban Green Transformation? Experimental Evidence from China

Calcium ATPase (PMCA) and GLUT-4 Upregulation in the Transverse Tubule Membrane of Skeletal Muscle from a Rat Model of Chronic Heart Failure.

Intolerance to exercise is a symptom associated with chronic heart failure (CHF) resulting in SM waste and weakness in humans. The effect of CHF on skeletal muscle (SM) arose from experimental evidence in rat models to explain the underlying mechanism. We investigated SM mechanical and metabolic properties in sham rats and with coronary ligation-induced CHF. After twelve weeks of CHF, rats were catheterized to measure right auricular pressure, SM mechanical properties, SERCA-ATPase activity and plasma membrane Ca2+-ATPase (PMCA) hydrolytic activity in isolated sarcoplasmic reticulum (SR) and transverse tubule (TT membrane), respectively, in the sham and CHF. The right auricular pressure and plasma nitrite concentration in CHF increased two-fold with respect to the sham. Pleural effusion and ascites were detected in CHF, confirming CHF. SERCA activity was conserved in CHF. In TT membranes from CHF, the glucose transporter GLUT4 increased seven-fold, and the PMCA hydrolytic activity increased five-fold, but in isolated muscle, the mechanical properties were unaffected. The absence of a deleterious effect of coronary ligation-induced CHF in the rat model on SM could be explained by the increased activity of PMCA and increased presence of GLUT-4 on the TT membrane, which may be involved in the mechanical outcome of the EDL.

Study on the mechanical properties and microscopic evolution mechanisms of weathered granite soil

Studying the effects of weathering on the mechanical properties and microscopic evolution of weathered granite soil (WGS) is essential for connecting microstructure with macroscopic behavior. This study conducts systematic monotonic and cyclic triaxial tests, along with a series of microscopic tests on WGS samples, to explore the influence of weathering on WGS mechanical properties and the mechanism of granite weathering. Results indicate that both effective internal friction angle and effective cohesion decrease progressively with increased weathering. Completely weathered granite (CWG) exhibits greater dynamic strength compared to granite residual soil (GRS). Additionally, as weathering progresses, quartz fragments are lost, while feldspar and biotite weather to form secondary minerals such as kaolinite and illite, leading to an overall enrichment in aluminum and iron in the granite. Weathering causes structural deterioration of WGS. Finally, the mechanical parameters of WGS and their chemical weathering indices show a coefficient of determination ranging from 60 to 99%. This study helps elucidate the fundamental causes of performance changes in WGS, thereby optimizing engineering design and enhancing disaster prediction accuracy, while providing new research perspectives and experimental evidence for WGS.

Selective Glycan Presentation in Liquid‐Ordered or ‐Disordered Membrane Phases and its Effect on Lectin Binding

Glycan‐protein interactions play a key role in various biological processes from fertilization to infections. Many of these interactions take place at the glycocalyx – a heavily glycosylated layer at the cell surface. Despite its significance, studying the glycocalyx remains challenging due to its complex, dynamic, and heterogeneous nature. This study introduces a glycocalyx model allowing for the first time to control spatial organization and heterogeneity of the glycan moieties. Glycan‐mimetics with lipid‐moieties that partition into either liquid‐ordered (Lo, lipid rafts) or liquid‐disordered (Ld) phases of giant unilamellar vesicles (GUVs), which serve as simplified cell membrane models micking lipid rafts, are developed. This phase‐specific allocation allows controlled placement of glycan motifs in distinct membrane environments, creating heteromultivalent systems that replicate the natural glycocalyx's complexity. We show that phase localization of glycan mimetics significantly influences recruitment of protein receptors to the membrane. Glycan‐conjugates in the ordered phase demonstrate enhanced lectin binding, supporting the idea that raft‐like domains facilitate stronger receptor interactions. This study provides a platform for systematically investigating spatial and dynamic presentation of glycans in biological systems and presents the first experimental evidence that glycan accumulation in lipid rafts enhances receptor binding affinity, offering deeper insights into the glycocalyx's functional mechanisms.

Extracellular Vesicles Contribute to Oxidized LDL-Induced Stromal Cell Proliferation in Benign Prostatic Hyperplasia.

Clinical and experimental evidence has linked Benign Prostatic Hyperplasia (BPH) with dyslipidemic and hypercholesterolemic conditions, though the underlying cellular mechanisms remain unclear. This study investigates the impact of dyslipidemia, specifically oxidized LDL (OxLDL), on prostatic stromal cell proliferation and the release of extracellular vesicles (EVs). Mice were fed a high-fat diet, and human prostatic stromal cells (HPSCs) were treated with OxLDL. Proliferation assays and EV characterization were performed to assess the role of EVs in BPH progression. Pro-atherogenic conditions significantly increased cell proliferation in both murine prostatic cells and HPSCs. Treatment with metformin effectively inhibited OxLDL-induced proliferation. Additionally, OxLDL stimulated the production and release of pro-proliferative EVs by HPSCs, which further promoted cellular proliferation. The findings suggest that dyslipidemia drives prostatic stromal cell proliferation and EV secretion, contributing to BPH progression. Metformin demonstrates potential as a therapeutic agent to mitigate these effects, offering insight into novel strategies for BPH management. This study highlights the complex interaction between dyslipidemia, cell proliferation, and extracellular communication in the context of BPH pathogenesis.

Selective Glycan Presentation in Liquid-Ordered or -Disordered Membrane Phases and its Effect on Lectin Binding.

Glycan-protein interactions play a key role in various biological processes from fertilization to infections. Many of these interactions take place at the glycocalyx - a heavily glycosylated layer at the cell surface. Despite its significance, studying the glycocalyx remains challenging due to its complex, dynamic, and heterogeneous nature. This study introduces a glycocalyx model allowing for the first time to control spatial organization and heterogeneity of the glycan moieties. Glycan-mimetics with lipid-moieties that partition into either liquid-ordered (Lo, lipid rafts) or liquid-disordered (Ld) phases of giant unilamellar vesicles (GUVs), which serve as simplified cell membrane models micking lipid rafts, are developed. This phase-specific allocation allows controlled placement of glycan motifs in distinct membrane environments, creating heteromultivalent systems that replicate the natural glycocalyx's complexity. We show that phase localization of glycan mimetics significantly influences recruitment of protein receptors to the membrane. Glycan-conjugates in the ordered phase demonstrate enhanced lectin binding, supporting the idea that raft-like domains facilitate stronger receptor interactions. This study provides a platform for systematically investigating spatial and dynamic presentation of glycans in biological systems and presents the first experimental evidence that glycan accumulation in lipid rafts enhances receptor binding affinity, offering deeper insights into the glycocalyx's functional mechanisms.

Au···I coinage bonds: Boosting photoluminescence efficiency and solid‐state molecular motion

AbstractCoinage bonds, a type of noncovalent interaction, occur between group 11 elements (Au, Ag, and Cu) with electron donor groups. Despite theoretical validation, empirical evidence remains limited. In this study, an aggregation‐induced emission (AIE)‐active Au(I) complex, ITCPAu, which exhibits Au···I coinage bonds, was revealed based on the single‐crystal X‐ray diffraction and theoretical calculations. Further examination of the luminescence properties of the ITCPAu revealed multiswitchable behavior, including mechanochromism and thermochromism. Nearly pure white‐light emission was achieved with Commission Internationale de L'Eclairage (CIE) 1931 chromaticity coordinates of (0.30, 0.31) by grinding the green‐emissive ITCPAu monomer crystals. Moreover, visualization and manipulation of solid‐state molecular motion (SSMM) in the yellow‐emissive ITCPAu dimer crystals, driven by the robust Au···I coinage bonds, were revealed through a combination of crystal engineering and luminescent properties. Furthermore, to support the robust Au···I coinage bonds, a versatile carrier for small solvent molecules in crystal lattices was developed for uptake and release. Our findings provide experimental and theoretical evidence for Au···I coinage bonds, highlighting their ability to boost photoluminescence quantum yield (PLQY) and trigger SSMM, emphasizing their potential in developing smart materials with stimuli‐responsive properties.

Reduction in Floor Impact Noise Using Resilient Pads Composed of Machining Scraps.

Floor impact noise is a significant social concern to secure a quiescent living space for multi-story building residents in South Korea. The floating floor, consisting of a concrete structure on resilient pads, is a specifically designed system to minimize noise transmission. This floating structure employs polymeric pads as the resilient materials. In this study, we investigated the utilization of helically shaped machining scraps as a resilient material for an alternative approach to floor noise reduction. The dynamic elastic modulus and loss factor of the scrap pads were measured using the vibration test method. The scrap pads exhibited a low dynamic elastic modulus and a high loss factor compared to the polymeric pads. Heavyweight impact sound experiments in an actual building were conducted to evaluate the noise reduction performance. The proposed pads showed excellent performance on the reduction in the structure-borne vibration of the concrete slab and resulting sound generation. The analytical model was used to simulate the response of the floating floor structure, enabling a parametric study to examine the effects of the resilient layer viscoelastic properties. Both experimental and analytical evidence confirmed that the proposed scrap pads contribute to the development of sustainable solutions for the minimization of floor impact noise.

Controlling (E/Z)-Stereoselectivity of -NHC=O Chlorination: Mechanism Principles for Wide Scope Applications.

Organic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in the halo-ligand design. Straightforward (but expensive) catalyzed stereospecific halogenation has been reported. Historically, PCl5 served access to uncatalyzed stereoselective chlorination although the stereochemical outcomes were influenced by steric parameters. Nonetheless, stereochemical investigation of PCl5 reaction mechanism with carbamoyl (RCONHX) compounds has never been addressed. Herein, we provide the first comprehensive stereochemical mechanistic explanation outlining halogenation of carbamoyl compounds with PCl5; the key regioselectivity-limiting nitrilimine intermediate (8-Z.HCl); how substitution pattern influences regioselectivity; why oxadiazole byproduct (P1) is encountered; stereo-electronic factors influencing the hydrazonoyl chloride (P2) production; and discovery of two stereoselectivity-limiting parallel mechanisms (stepwise and concerted) of elimination of HCl and POCl3. DFT calculations, synthetic methodology optimization, X-ray evidence and experimental reaction kinetics study evidence all supported the suggested mechanism proposal (Scheme 2). Finally, we provide mechanism-inspired future recommendations for directing the reaction stereoselectivity toward elusive and stereochemically inaccessible (E)-bis-hydrazonoyl chlorides along with potentially pivotal applications of both (E/Z)-stereoisomers especially in medicinal chemistry and protein modification.

Correlated topological flat bands in rhombohedral graphite

Flat bands and nontrivial topological physics are two important topics of condensed matter physics. With a unique stacking configuration analogous to the Su-Schrieffer-Heeger model, rhombohedral graphite (RG) is a potential candidate for realizing both flat bands and nontrivial topological physics. Here, we report experimental evidence of topological flat bands (TFBs) on the surface of bulk RG, which are topologically protected by bulk helical Dirac nodal lines via the bulk-boundary correspondence. Moreover, upon in situ electron doping, the surface TFBs show a splitting with exotic doping evolution, with an order-of-magnitude increase in the bandwidth of the lower split band, and pinning of the upper band near the Fermi level. These experimental observations together with Hartree-Fock calculations suggest that correlation effects are important in this system. Our results demonstrate RG as a platform for investigating the rich interplay between nontrivial band topology, correlation effects, and interaction-driven symmetry-broken states.

What Kind of Cognitive Technology Is the "Memory House"?

Ancient Roman "technical memory" is not (as much of the modern specialist literature would have it) a generative technology of association. Rather it is (as a literal reading of the texts would suggest) a specialized tool for precise serial recall. Modern experimental evidence both confirms the fitness for the purpose of the technique and shows why that purpose is not trivial, as some have suggested. While the mechanism(s) by which the technique operates are not fully understood, a review of the current literature suggests that it would have had the advantage over other mnemonic techniques by virtue of recruiting a variety of cognitive capacities. These likely include spatial/navigational mechanisms and possibly visual/imagery-based ones as well. Finally, small differences between the method as recorded in the ancient texts and similar methods that have been the subject of laboratory experiments are used to suggest possible directions for further experimentation.

The impact of socialisation services in the whole process of agricultural production on food security—quasi-natural experimental evidence from China

Food security (FS) is an important guarantee for world peace and development and the basis for building a community of human destiny, which has a bearing on the sustainable development and future destiny of humankind. This study empirically analysis the relationship between socialisation services in the whole process of agricultural production (ASS) and guaranteeing FS, as well as the path of their role, using provincial panel data from 2010 to 2022 in China as an example, using the double-difference method. The regression results show that ASS can have the ability to contribute to the level of FS, and the conclusion still holds after a series of robustness tests. The results of the heterogeneity analysis show that the role of ASS in guaranteeing FS receives the influence of the level of agricultural development in each region, while it plays a greater role in the main food-producing areas. The mechanism analysis analyses the mechanism of the role of ASS in the whole process of agricultural production in guaranteeing FS from the three links of pre-production, mid-production and post-production respectively, and finds that ASS in the whole process of agricultural production is able to guarantee FS by reducing the cost of purchasing means of production in the pre-production stage, fostering a new type of agricultural management main body in the mid-production stage, and increasing the income of farmers’ household management in the post-production stage. Based on the above findings, this study proposes corresponding policy recommendations. This study can provide insights for ensuring world FS and contribute to maintaining social stability and development. The conclusions of the study are universally applicable, and all countries in the world can benefit from and draw lessons from it.

Counting and hardness-of-finding fixed points in cellular automata on random graphs

Abstract We study the fixed points of outer-totalistic cellular automata on sparse random regular graphs. These can be seen as constraint satisfaction problems, where each variable must adhere to the same local constraint, which depends solely on its state and the total number of its neighbors in each possible state. Examples of this setting include classical problems such as independent sets or assortative/dissasortative partitions. We analyse the existence and number of fixed points in the large system limit using the cavity method, under both the replica symmetric (RS) and one-step replica symmetry breaking (1RSB) assumption. This method allows us to characterize the structure of the space of solutions, in particular, if the solutions are clustered and whether the clusters contain frozen variables. This last property is conjectured to be linked to the typical algorithmic hardness of the problem. We bring experimental evidence for this claim by studying the performance of the belief-propagation reinforcement algorithm, a message-passing-based solver for these constraint satisfaction problems.

Polydimethylsiloxanes - Based Fluorescent Probe for H2S Detection in Living Cells.

The development of fluorescent probes for H2S detection especially in living cells is of great significance due to its fundamental role as signal molecule. A promising scaffold for the development of such probes is polydimethylsiloxanes (PDMS), which is cost-effectiveness, non-toxicity, flexibility, and biocompatibility and easy to post-functionalize. Surprisingly, fluorescent probes for H2S detection based on PDMS have not been investigated. Moreover, 4-nitro - 2,1,3-benzoxadiazole (NBD) derivates provides high fluorescence quantum yield, a large molar absorption coefficient, and sensitivity to environmental changes. Through reasonable design and adjustment of substituents on the NBD group, precise control of its fluorescence properties can be achieved. Herein, a novel H2S fluorescent probe, P-NBD, was designed and synthesized by a one-step aromatic ring nucleophilic substitution of Cl-NBD with a PDMS derivative. Due to the occurrence of the cleavage reaction strategy and the intramolecular charge transfer process, P-NBD can detect H2S via a colorimetric method. The limit of detection is down to 93 nM. P-NBD demonstrated considerable detection capability comparable to other reported types of H2S probes. Moreover, the probe can also be utilized for H2S imaging in HeLa cells. This work provides new insights into the design and synthesis of novel H2S probes while also offering experimental evidence for the application of PDMS in cellular imaging.

Optimizing fertilizer use by providing soil quality information: experimental evidence from Madagascar

BackgroundImproving food security in sub-Saharan Africa (SSA) requires increasing agricultural productivity. The increased and effective use of chemical fertilizers is widely recognized as one of the key strategies for achieving this goal. However, many smallholder farmers in SSA still grow crops without using fertilizer, and even when they do use fertilizer, the amount applied is often less than the recommended level. In addition to various constraints related to input markets and farmers’ socioeconomic characteristics, uncertainty about crop yield response is known to discourage fertilizer use. The purpose of this study was to investigate how site-specific information on soil characteristics can help farmers optimize their fertilizer application decisions by reducing uncertainty in yield response. Our unique approach uses simple binary information about the expected effectiveness of nitrogen fertilizer based on a single soil parameter.MethodologyThe simple binary information was generated for a focal rice plot of each 70 household. Based on the evaluation of oxalate-extractable phosphorus content in the soil composites collected from each of these plots, each plot was categorized into either high or low in terms of the expected effectiveness of nitrogen application. A randomized controlled trial was conducted to estimate the impact of providing this simple binary information primarily on nitrogen application rate and, consequently, on rice yield and income at plot-level and household-level.ResultsThe results showed that first, compared to those in the target plots of the control households, the nitrogen application rate was greater in the target plots of the treatment households who were informed of the high expected effectiveness. Second, information that the expected effectiveness was high increased the amount of nitrogen fertilizer in the target plot compared to that in other plots with no information about expected effectiveness within a household. Third, this change in fertilizer allocation led to higher rice yields and higher rice incomes at the household level.ConclusionsThese results highlight how the binary information about the expected effectiveness with a single soil parameter can improve fertilizer allocation among rice plots and its use efficiency to increase rice productivity and income.

SVPWM‐Based Algorithm for Reduced THD and Switching Losses Under Varying Fundamental Frequency and Load in a VSI

ABSTRACTThe present study explores the influence exerted by various pulse width modulation (PWM) techniques upon harmonic distortion and switching losses of a voltage source inverter. In the context of this inquiry, a generalized algorithm for variable frequency operations, inspired by continuous and discontinuous PWM is outlined in this article. The algorithm is explicitly formulated as a function of fundamental frequency and the load power factor angle with the objective of minimizing total harmonic distortion (THD) and switching losses within a specified frequency range. The algorithm is segmented into various regions of frequency, guided by the theory that each region corresponds to a distinct PWM technique that yields reduced harmonic distortion. In this article, a minimum switching loss algorithm is introduced and implemented using both BCPWM and ABCPWM techniques. The algorithm is specifically designed to minimize switching losses across the entire range of load power factor angles. The integration of switching loss algorithm with the selection of the optimal PWM technique across different frequency ranges results in reduced switching losses and harmonic distortion. This leads to a comprehensive PWM algorithm that efficiently reduces both THD and switching losses during dynamic frequency and load changes. Experimental and theoretical evidences demonstrate the efficacy of the proposed algorithm in attaining minimum harmonic distortion and reduced switching loss operation during variations in fundamental frequency and load.