Distinct Modes Research Articles

Flexible Regulation of Optical Properties Based on Structure Size-Driven Intermolecular Interactions for Phototherapy.

The precise control of optical properties in molecular systems remains a challenge for phototherapy. Herein, the strategic combination of aggregation-caused quenching (ACQ) and aggregation-induced emission (AIE) molecule creates ACQ@AIE bimolecular systems with tunable optical properties, which are almost unattainable by single-component materials. Through systematic investigation of three ACQ@AIE bimolecular systems, it is established that molecule structure size differentials dictate their intermolecular interactions and consequent optical behaviors. Crucially, AIE molecule with a smaller structure size promotes ACQ molecule clustering to enhance the photothermal effect, while when the size becomes larger, particularly approaching that of ACQ molecule, facilitating π-π stacking and boosting the photodynamic effect. These distinct assembly modes revealed through combined experimental and theoretical analyses, enable precise regulation of photothermal versus photodynamic effects by simply regulating the structure size and ratio of ACQ and AIE molecules. Building on these mechanistic insights, the optimal molecule combination of ACQ@AIE bimolecular system is engineered into nanoparticles that exhibit mild photothermal effect, strong photodynamic effect, and excellent tumor accumulation and retention, achieving near-complete tumor eradication with minimal treatment cycles while maintaining good biosafety. This work not only elucidates the fundamental structure size-interaction-property relationships in ACQ@AIE bimolecular systems but also provides generalizable strategies for developing intelligent photo theranostic materials through controlled intermolecular interaction.

Investigation of the impact of magnetic field intensity on the multimode operational characteristics of kilowatt-class double-stage anode layer Hall thrusters utilizing krypton

To investigate the effect of magnetic field intensity on the discharge characteristics of three distinct operational modes (first-stage mode, second-stage mode, and double-stage mode), this study designs a kilowatt-class double-stage anode layer thruster employing krypton with a hybrid-produced magnetic field. Experiments and particle-in-cell simulations are conducted based on this design. The experimental background pressure ranges from 3.4 × 10−3 to 3.8 × 10−3 Pa. Results indicate that both the second-stage anode mode and double-stage mode achieve a maximum thrust of 42 mN, specific impulse of 2400 s, and anode efficiency of 42% at 30 SCCM. In contrast, the first-stage anode mode requires 35 SCCM (16.7% higher flow rate) to attain equivalent thrust, with peak performance reducing to 1900s specific impulse and 41% efficiency. Numerical simulations reveal electron number densities of 1.3–2.6 × 1018 m−3 during discharge. Both single-stage modes exhibit optimal magnetic field intensity ranges of 387–487 Gs. The second-stage anode mode demonstrates a narrowing optimal magnetic field range with increasing discharge voltage, while the first-stage mode maintains stable operational parameters. For the double-stage mode, magnetic flux density selection exhibits voltage dependence: Acceleration voltages exceeding 350 V threshold require stronger magnetic fields (437 Gs) to maintain performance compared to 387 Gs configurations. This threshold behavior emphasizes the necessity of high-voltage and high-magnetic-field-intensity synergy in double-stage optimization.

Antifungal Peptides SmAPα1-21 and SmAPγ27-44 Designed from Different Loops of DefSm2-D Have Distinct Modes of Action.

Background: The use of antimicrobial peptides (AMPs) as biotechnological tools is an area of growing interest in the research that seeks to improve crop defense. SmAPα1-21 and SmAPγ27-44 were previously reported to inhibit Fusarium graminearum, permeabilize the plasma membrane and induce cytoplasmic disorganization. To exert its activity, SmAPα1-21 initially enters through the basal and apical cells of F. graminearum conidia and then displays a general but non-homogeneous distribution in the cytoplasm of all conidial cells, in contrast. Methods: We analyzed, focusing on membrane interaction, the mode of action of SmAPγ27-44, a peptide based on the γ-core of defensins DefSm2-D and DefSm3, and SmAPα1-21, based on the α-core of DefSm2-D. Additionally, we compared the behavior of SmAPα1-21 with that of SmAP3α1-21 based on DefSm3 but with no activity against F. graminearum. Results: In this study, we showed that SmAPγ27-44 enters the cells with discrete intracellular localization. Furthermore, both peptides disrupted the plasma membrane, but with different modes of action. When large unilamellar liposomes (LUVs) containing phosphatidic acid and ergosterol were used as a filamentous fungal plasma membrane model, SmAPγ27-44 strongly induced aggregation concomitantly with the solubilization of the liposomes and showed the maximal insertion of its tryptophan moiety into the membrane's hydrophobic interior. In comparison, SmAPα1-21 showed a high effect on the ζ potential of anionic vesicles, vesicle aggregation capacity after reaching a concentration threshold, and moderate transfer of tryptophan to the membrane. SmAP3α1-21, on the other hand, showed poor superficial adsorption to liposomes. Conclusions: In view of our results, a cell penetration peptide-like effect was pictured for the γ-core defensin-derived peptide and a classical AMP action was observed for the α-core defensin-derived one.

Photocontrol of bacterial membrane potential regulates antibiotic persistence in B. subtilis

Bacterial persistence and resistance to antibiotics pose critical challenges in healthcare and environmental contexts. Recent studies revealing that bacteria possess a dynamic electrical membrane potential open new avenues for influencing bacterial behaviour and drug susceptibility. In this work, we present a novel light-responsive strategy to modulate bacterial antibiotic persistence using Ziapin2, an azobenzene photoswitch previously shown to alter bacterial membrane potential. We selected two broad-spectrum antibiotics with distinct modes of action: Kanamycin, which requires cytosolic uptake to inhibit protein synthesis, and Ampicillin, which targets cell wall polymerization at the cell envelope, to probe the role of membrane potential in antibiotic efficacy. Our findings show that when Bacillus subtilis is exposed to Kanamycin and Ziapin2, photoactivation (470 nm) significantly impacts bacterial viability: under illumination, the previously lethal effects of Kanamycin are markedly reduced, suggesting that membrane potential changes drive altered antibiotic uptake or intracellular accumulation. In contrast, Ampicillin-treated samples remain largely unaffected by light-induced membrane modulation, consistent with its action at the external cell envelope. Taken together, these results indicate that membrane potential manipulation can selectively influence the activity of antibiotics whose intracellular uptake is critical to their function. This proof-of-concept study underscores the potential of non-genetic, light-based interventions to modulate bacterial susceptibility in real time. Future work will expand this approach by exploring additional antibiotic classes and novel azobenzene derivatives, ultimately advancing our understanding of bacterial bioelectric regulation and its applications in antimicrobial therapies.

4f-orbital covalency enables a single-crystal-to-single-crystal ring-opening isomerization in a CeIV-cyclopropenyl complex.

Metal-ligand bonding interactions for f-element compounds are typically highly polarized with only minor covalent character. Whereas the 5d/6d orbitals are known to be chemically accessible for dative bonding, recent quantum chemical and spectroscopic analyses have indicated appreciable 4f/5f-orbital involvement in certain metal-ligand bonds. However, 4f-orbital covalency has not been compellingly linked to distinctive modes of chemical reactivity via rigorous comparative study and mechanistic investigation. Here a series of MIV-cyclopropenyl complexes (M = Ti, Zr, Ce, Hf, Th) are described, wherein the cerium congener exhibits a 4f-covalent Ce=Cα interaction, causing a ring-opening isomerization reaction through a single-crystal-to-single-crystal transformation. The results provide evidence for 4f-orbital covalency by demonstrating its expression in the reactivity of an f-element complex within an isostructural series of tetravalent d- and f-block metal complexes. They also provide new directions for the study of orbital covalency effects of molecular compounds in solid-state chemical transformations.

Rational Computational Workflow for Structure-Guided Discovery of a Novel USP7 Inhibitor.

Rationally applied, structurally guided computational methods hold the promise of identifying potent and distinct chemotypes while enabling the precise targeting of structural determinants. Here, we implemented a computational workflow combining insights from cocrystal poses and monitoring the dynamical structural determinants from our previous studies for the identification of potential candidates against USP7. We identified and tested several diverse chemical scaffolds, which underwent in vitro validation across six cancer cell lines. Among these hits, compound M15, belonging to the benzothiazole chemical class, exhibited remarkable anticancer activities, demonstrating dose-dependent reduction in cancer cell viability across all cell lines and indicating that it is a promising candidate to explore as a potent anticancer drug. Biophysical binding confirms binding of M15 on USP7. M15 also exhibited certain USP7 inhibitory activity, as observed in the enzymatic assay. A comparative cocrystal mining of reported USP7 inhibitors unveiled a distinct binding mode of M15, which nicely cross-corroborated with MD and binding-pose metadynamics simulations. Notably, M15 occupies both the determinants, i.e., BL1 and the allosteric checkpoint, which has not yet been underscored as a druggable site. In essence, our study presents a robust and multifaceted computational method for the discovery and characterization of a novel inhibitor scaffold, exemplified by the identification and mechanistic elucidation of M15 against USP7. This integrated approach not only advances our understanding of USP7 inhibition and underscores mechanistic determinants but also offers promising avenues for the discovery of target-specific therapeutic intervention.

Evidence for a push-pull interaction between superior colliculi in monocular dynamic vision mode

Visual perception can operate in two distinct vision modes—static and dynamic—that have been associated with different neural activity regimes in the superior colliculus (SC). However, the associated pathway-wide mechanisms remain poorly understood, especially in terms of corticotectal and tectotectal feedback upon encoding the continuity illusion during the dynamic vision mode. Here, we harness functional MRI combined with rat brain lesions to investigate whole-pathway neural interactions in the dynamic vision mode. We find a push-pull mechanism embodying contralateral suppression of SC activity opposing positive ipsilateral neural activation upon monocular visual stimulation. Cortical amplification is confirmed through cortical lesions, while further lesioning the ipsilateral SC leads to a boost in the contralateral SC negative signals, suggesting a tectal origin for the push-pull interaction. These results highlight hitherto unreported frequency-dependent modulations in the tectotectal pathway and further challenge the notion that intertectal connections solely serve as reciprocal inhibitory mechanisms for avoiding visual blur during saccades.

The structure of the Vibrio natriegens 70S ribosome in complex with the proline-rich antimicrobial peptide Bac5(1-17).

Proline-rich antimicrobial peptides (PrAMPs) are produced as part of the innate immune response of animals, insects, and plants. The well-characterized mammalian PrAMP bactenecin-5 (Bac5) has been shown to help fight bacterial infection by binding to the bacterial ribosome and inhibiting protein synthesis. In the absence of Bac5-ribosome structures, the binding mode of Bac5 and exact mechanism of action has remained unclear. Here, we present a cryo-electron microscopy structure of Bac5 in complex with the 70S ribosome from the Gram-negative marine bacterium Vibrio natriegens. The structure shows that, despite sequence similarity to Bac7 and other type I PrAMPs, Bac5 displays a completely distinct mode of interaction with the ribosomal exit tunnel. Bac5 overlaps with the binding site of both A- and P-site transfer RNAs bound at the peptidyltransferase center, suggesting that this type I PrAMP can interfere with late stages of translation initiation as well as early stages of elongation. Collectively, our study presents a ribosome structure from V. natriegens, a fast-growing bacterium that has interesting biotechnological and synthetic biology applications, as well as providing additional insights into the diverse binding modes that type I PrAMPs can utilize to inhibit protein synthesis.

Informal historical learning at home: on historical culture and everyday historical thinking of children

This article presents several insights from an ethnographic study that explores the private lives of 39 children aged between 7 and 12 in Austria. It examines the forms of historical culture present in their home environments, how these objects are engaged with by the children, and how such interactions influence their conceptualisations of the past and history. The data for this study were collected between 2017 and 2020. Unlike the laboratory-style tests frequently employed in empirical research conducted in schools, the methodology adopted here seeks to provide deeper insights into the cognitive habits and social practices related to engaging with the past and history by slowing down the research pace and meeting children in their home environments. The study particularly emphasises the everyday historical thinking, a distinct mode of thought that fundamentally differs from academic historical thinking.

Abstract 6832: SYS6041, a next-generation Folate Receptor α-targeted antibody-drug conjugates for the treatment of FRα-expressing malignancies

Abstract Folate Receptor α(FRα)exhibits an increased expression on cell surfaces in multiple solid tumors, including ovarian, lung, endometrial cancer, with limited expression in normal tissues. Recently, an antibody drug conjugate (ADC) with a microtubule inhibitor (MTI) payload, was approved by FDA for FRα-expressing platinum-resistant ovarian cancer. However, it can cause severe ocular toxicities and show therapeutic efficacies only in patients with high expression. In order to address the unmet needs of additional patient populations, we sought to develop a next generation FRα-targeting ADC, SYS6041, actively targeting tumors with a broad range of FRα expression, especially moderate or low expression levels. SYS6041 was developed adopting a novel ADC platform with a camptothecin-based topoisomerase 1 inhibitor payload, Exatecan, tethered to a cleavable linker. The drug-to-antibody ratio standed 8.0. Upon binding to FRα, SYS6041 underwent receptor-mediated internalization. Subsequent proteolytic cleavage released the cytotoxic payload Exatecan, leading to DNA strand breaks and consequently disrupting DNA replication and transcription. SYS6041 demonstrated potent cytotoxicities against FRα expressing cancer cell-lines and effective bystander activities towards tumor cells without FRα expression. It demonstrated superior antitumor effects across ovarian endometrial and lung cancer CDX models compared to the MTI-ADC especially in models with low or moderate FRα expression, with a minimum effect dose(MED) at 0.75 mg/kg. In a FRα moderate ovarian PDX model with Olaparib resistance, SYS6041 significantly inhibited tumor growth at 3 mg/kg, whereas the MTI-ADC showed no inhibitory effect at 6 mg/kg. Furthermore, Exatecan demonstrated a significant enrichment in the tumors of mice bearing tumors, achieving a tumor-to-blood ratio of 182 following a dosage of 6 mg/kg of SYS6041.SYS6041 exhibited a stable PK profile with AUC of Exatecan less than 0.01% of that of total Exatecan in ADC. In a GLP toxicity study in cynomolgus monkey, SYS6041 demonstrated an encouraging tolerability with an HNSTD of 50 mg/kg, and favorable PK and DAR stability, and presented a good tolerability profile with therapeutic window (TW)>66 (HNSTD/MED). In conclusion, the distinct mode of action along with the proprietary drug-linker platform resulted in an excellent in-vivo antitumor potency and safety, which supports the potential of SYS6041 as a novel therapeutic agent that may help address unmet needs in patients with moderate and low FRα expressing malignancies. Citation Format: Jieru Liu, Huan Li, Mo Dan, Xiwu Hui, Bin Yao, Yang Zhang, Linlin Xiao, Bin Kang, Can Yuan, Bin Bao, Miaomiao Wei, Chunqing Qu, Yanling Li, Wei Yang. SYS6041, a next-generation Folate Receptor α-targeted antibody-drug conjugates for the treatment of FRα-expressing malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6832.

VocalMind: A Stereotactic EEG Dataset for Vocalized, Mimed, and Imagined Speech in Tonal Language

Speech BCIs based on implanted electrodes hold significant promise for enhancing spoken communication through high temporal resolution and invasive neural sensing. Despite the potential, acquiring such data is challenging due to its invasive nature, and publicly available datasets, particularly for tonal languages, are limited. In this study, we introduce VocalMind, a stereotactic electroencephalography (sEEG) dataset focused on Mandarin Chinese, a tonal language. This dataset includes sEEG-speech parallel recordings from three distinct speech modes, namely vocalized speech, mimed speech, and imagined speech, at both word and sentence levels, totaling over one hour of intracranial neural recordings related to speech production. This paper also presents a baseline model as the reference model for future studies, at the same time, ensuring the integrity of the dataset. The diversity of tasks and the substantial data volume provide a valuable resource for developing advanced algorithms for speech decoding, thereby advancing BCI research for spoken communication.

High-Frequency Oscillation Suppression Strategy for Renewable Energy Integration via Modular Multilevel Converter—High-Voltage Direct Current Transmission System Under Weak Grid Conditions

To address the high-frequency resonance issues in renewable energy systems integrated via MMC-HVDC transmission under weak grid conditions, this paper establishes a wide-frequency sequence impedance model for renewable energy grid-side converters and MMC-HVDC sending-end converters. The impedance characteristics of the MMC-HVDC transmission system under two distinct control modes are compared, and the constant power control mode is selected for detailed analysis to better evaluate the effectiveness of suppression strategies. Based on this framework, the superposition theorem is employed to analyze the interaction mechanism between the impedance characteristics of the MMC-HVDC sending-end converter and the renewable energy grid-connected system. Since the aim of this study is to propose suppression strategies for the MMC-HVDC transmission system, a sensitivity analysis of its control parameters is conducted. The results identify the current loop and voltage feedforward control as the dominant factors influencing high-frequency oscillations. Accordingly, a coordinated control strategy combining current loop regulation and voltage feedforward compensation is proposed. An electromagnetic transient simulation model is developed in MATLAB/Simulink. The simulations demonstrate that the proposed strategy effectively suppresses oscillations in the MMC-HVDC system across high-frequency ranges. Furthermore, it avoids negative damping characteristics within a broad frequency band, significantly enhancing the steady-state performance of renewable energy systems integrated via MMC-HVDC transmission.

Statistical Context Learning in Visual Search: Distinct Electrophysiological Signatures of Contextual Guidance and Context Suppression.

Facilitation of visual search by repeated distractor contexts is typically studied employing distractor configurations that are 100% predictive of the target location. Yet, real-world contexts vary in predictivity. We used electroencephalography (EEG) in human participants of either sex to explore how visual search facilitation arises from two distinct processing modes-contextual guidance and context suppression-that depend on the predictivity of distractor contexts, comparing repeated distractor arrangements that were either predictive or nonpredictive of target location against a baseline of nonrepeated arrangements. In Experiment 1, we manipulated context predictivity by shifting repeated contexts from predictive to nonpredictive and vice versa, while in Experiment 2, we restricted repeated contexts to one side of the display to assess lateralized effects of the two processing modes. Both types of contexts behaviorally facilitated visual search, but facilitation was larger with predictive contexts. Making predictive contexts nonpredictive reduced the facilitation while rendering nonpredictive contexts predictive failed to produce gains. Half-display predictive contexts facilitated target detection on both sides, while nonpredictive contexts facilitated same-side target detection only. EEG analyses revealed that predictive contexts triggered an early N1pc (guidance signal), followed by an enhanced N2pc (attentional selection) and an increased contralateral delay activity (CDA, indexing working memory processing of the target) in occipitoparietal regions, indicative of contextual guidance boosting the entire processing chain. In contrast, nonpredictive contexts produced only an increased N2pc accompanied by reduced CDA, consistent with context suppression. These differential patterns demonstrate contextual guidance and context suppression to operate as electrophysiologically distinct processing modes.

Receptor kinase pathway signal tuning through a nontranscriptional incoherent feedforward loop

Cellular signaling processes can elicit powerful responses and may need to be amplified to be efficient or dampened to prevent overstimulation. Therefore, they often involve autoregulatory feedbacks. Receptor kinase signaling pathways are abundant in plants, where they convey the presence of both exogenous and endogenous ligands. Among them, endogenous CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide signaling acts in an inherently quantitative manner to determine the size of stem cell pools and direct tissue formation. The plant-specific MEMBRANE-ASSOCIATED KINASE REGULATOR (MAKR) family proteins act downstream of receptor kinases. Among the seven family members in Arabidopsis (Arabidopsis thaliana), MAKR5 conveys CLE45 signaling downstream of the receptor kinase BARELY ANY MERISTEM 3 (BAM3). Here, we show that the distinct MAKR5 mode of action can only be fully mimicked by MAKR3, suggesting functional diversification of MAKR proteins. Moreover, we find that CLE45-stimulated and BAM3-dependent MAKR5 recruitment to the plasma membrane can be triggered independent of receptor-like cytoplasmic kinases that act downstream of BAM3 and depends on membrane charge. The CLE45-BAM3-triggered enhancement of MAKR5 production and plasma membrane association is mediated by autoregulatory feedback on MAKR5 mRNA translation, for which the 5' UTR is required. At the same time, this signal amplification is dampened through CLE45-stimulated MAKR5 phosphorylation, which inactivates MAKR5, enhances its turnover, and impinges on MAKR5 mRNA levels. In summary, our results reveal a nontranscriptional incoherent feedforward loop in which receptor kinase signaling is amplified via ligand-triggered translation of a signal enhancer's mRNA yet also balanced via ligand-triggered inactivation of the signal enhancer protein.

Hydride Generation-Based Purification Method for High-Precision Antimony Isotopic Analysis in Low-Concentration and Complex-Matrix Samples.

Antimony (Sb) isotopes have emerged as a powerful tool for tracing Sb sources and understanding their geochemical behavior in different systems. However, accurate and precise determination of Sb isotopic compositions (δ123Sb) in natural samples remains a challenge, especially in low-concentration samples with complex matrices. In this study, we introduce a novel two-step purification method for high-precision Sb isotope analysis. In the first step, hydride generation (HG) is employed to effectively isolate Sb from major elements, followed by further purification with a thiol silica column. After optimization, two distinct HG purification modes were established: a flow mode for water samples and a no-flow mode for solid geological samples. Our method achieved complete Sb purification recovery with effective removal of matrix elements and the procedure blank was under the detection limits (<0.1 ng). Moreover, the HG purification process is rapid, requiring only 1 h for a 1 L water sample and 1.5 h for a 1 g geological sample. Application of this method to Sb standard solutions and geochemical reference samples yielded δ123Sb values in excellent agreement with the reference data, confirming that no isotopic fractionation occurred during the HG purification. Finally, we successfully applied this technique to a range of low-Sb environmental samples, including river, seawater, and sediments, demonstrating its effectiveness in accurate and precise Sb isotopic analysis. Overall, this novel method offers a rapid and efficient purification strategy for high-precision Sb isotopic analysis, thereby enhancing our ability to investigate Sb isotopic reservoirs associated with biogeochemical cycles.

Comparative Evaluation of Transient Stability in MMCs: Grid-Forming vs. Grid-Following Strategies

This paper explores how different control strategies—grid-forming and grid-following—impact the transient stability of modular multilevel converters (MMCs) interfacing with AC power grids. By employing electromagnetic transient simulation tools (PSCAD/EMTDC) on an adapted IEEE three-machine, nine-bus system, various scenarios are analyzed, including faults of differing types and locations. In the simulation, traditional synchronous generators (SGs) are replaced by MMCs configured under distinct control modes. Results indicate that grid-forming (GFM) control enhances the receiving-end grid’s transient stability by providing superior phase support and extended fault-clearing times compared to grid-following (GFL) control, with hybrid approaches yielding intermediate performance. These findings underline the importance of converter control selection in achieving robust dynamic operation in modern power systems with a high penetration of renewable energy.

Wake transition and aerodynamics of a dragonfly-inspired airfoil

We investigate the dynamics and the stability of the incompressible flow past a corrugated dragonfly-inspired airfoil in the two-dimensional (2-D) $\alpha {-}Re$ parameter space, where $\alpha$ is the angle of attack and $Re$ is the Reynolds number. The angle of attack is varied in the range of $-5^{\circ } \leqslant \alpha \leqslant 10^{\circ }$ , and $Re$ (based on the free stream velocity and the airfoil chord) is increased up to $Re=6000$ . The study relies on linear stability analyses and three-dimensional (3-D) nonlinear direct numerical simulations. For all $\alpha$ , the primary instability consists of a Hopf bifurcation towards a periodic regime. The linear stability analysis reveals that two distinct modes drive the flow bifurcation for positive and negative $\alpha$ , being characterised by a different frequency and a distinct triggering mechanism. The critical $Re$ decreases as $|\alpha |$ increases, and scales as a power law for large positive/negative $\alpha$ . At intermediate $Re$ , different limit cycles arise depending on $\alpha$ , each one characterised by a distinctive vortex interaction, leading thus to secondary instabilities of different nature. For intermediate positive/negative $\alpha$ , vortices are shed from both the top/bottom leading- and trailing-edge shear layers, and the two phenomena are frequency locked. By means of Floquet stability analysis, we show that the secondary instability consists of a 2-D subharmonic bifurcation for large negative $\alpha$ , of a 2-D Neimark–Sacker bifurcation for small negative $\alpha$ , of a 3-D pitchfork bifurcation for small positive $\alpha$ and of a 3-D subharmonic bifurcation for large positive $\alpha$ . The aerodynamic performance of the dragonfly-inspired airfoil is discussed in relation to the different flow regimes emerging in the $\alpha {-}Re$ space of parameters.

Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies.

Sirtuin 3 (SIRT3), a pivotal mitochondrial deacetylase, plays a critical role in restoring mitochondrial function, particularly through the activation of autophagy. Despite its promise as a cardioprotective target, developing SIRT3 activators and their therapeutic applications remains challenging. Here, we report the identification of SKLB-11A, a SIRT3 activator with submicromolar affinity and high efficacy. Structural and mutagenesis analyses revealed a unique allosteric site for SKLB-11A in SIRT3, where a conformational change in Leu298 drives its potent activation. Subsequent studies demonstrated that SKLB-11A drives autophagy/mitophagy signaling pathways, effectively preventing mitochondrial dysfunction, and improving cardiac dysfunction in both doxorubicin (Dox)-induced cardiotoxicity and myocardial ischemia/reperfusion (I/R) models. Collectively, our data highlight the potential of pharmacological SIRT3 activation as an effective therapeutic strategy for cardioprotection. SKLB-11A, as a first-in-class SIRT3 allosteric activator with a distinct binding mode, not only offers a valuable tool for exploring the physiological and pathological roles of SIRT3 deacetylation but also holds promise for the development of targeted cardioprotective therapies.

Experimental investigation on mechanical behavior of sandwich structures using Digital Image Correlation (DIC)

The aim of this work is to investigate the mechanical behavior of sandwich structures when subjected to edgewise and flatwise compression loadings, using 2D Digital Image Correlation (DIC). These structures are made of Glass Fiber Reinforced Polymer (GFRP) skins with polyurethane foam (PU) core. Initially, the mechanical characterization of each component within the sandwich structure is exanimated. Subsequently, flatwise and edgewise compression tests are conducted on the sandwich panels, in accordance with ASTM C365 and ASTM C364 standards, respectively. Different geometries are studied by testing various lengths of sandwich structures exposed to edgewise compression loads. The DIC technique is applied to analyze and comprehend the deformation and failure mechanisms of GFRP skins and sandwich structures. The results of the present study indicate that the flatwise compression test revealed condensation and densification of PU foam, accompanied by microcracks in GFRP skin. On the other hand, the edgewise compression test on sandwich structures with an equal length-to-width ratio identified several distinct failure modes, including skin-core debonding, shear sliding damage of the skin, and localized buckling. This localized buckling was initially observed in the mid-section of the specimens, followed by skin cracking on both sides, which then propagated across the width of the samples. For other geometric configurations of the sandwich structures, the Euler general buckling mode was observed. The results show that the length of samples has a significant effect on the collapse modes of sandwich structures under edgewise compression.

Reciprocal actuation core and modular robotic limbs for flying, swimming and running

Investigations into animal locomotion across diverse environments have highlighted the universal applicability of adjustable reciprocal motion, offering insights into simplifying actuation systems for multi-modal robots. However, achieving unified and efficient reciprocal motion with environmental adaptability in miniature robotic systems is challenging due to constraints of size, weight, and the need for controlled degree of freedom. Here, we present the UniCore, a miniature unified actuation platform capable of flying, swimming, and running with modular appendages. This platform features bio-inspired motor-spring resonance actuation systems, with a central controller that generates four adjustable reciprocal control signals based on a central pattern generator model. Performance validation demonstrates UniCore’s proficiency in achieving three distinct modes of locomotion, underscoring the effectiveness of reciprocal motion for the locomotion of both animals and machines. All in all, this work demonstrates the potential of a unified reciprocal actuation platform to eliminate morphological and actuation redundancies commonly found in existing multi-modal robots, paving the way for more efficient and versatile miniature robotic systems.