Browse Articles

A Modular Three‐Component Asymmetric Tsuji–Trost Reaction Enabled by Cooperative Palladium/Lewis Acid Catalysis

AbstractAsymmetric allylic substitution (AAS) reactions, named as the Tsuji–Trost reaction, stand as a landmark in modern organic synthesis. The merge of AAS reactions with the concept of multicomponent modular synthesis could allow flexible customization of molecular architectures from fundamental feedstocks, which remains underdeveloped. Herein, we disclose our recent observations on a novel three‐component asymmetric Tsuji–Trost reaction enabled by cooperative palladium/Lewis acid (LA) catalysis. This ‘1C + 2C + NuH’ approach starts from fundamental organic feedstocks, i.e., aldehyde, allylboronate, and a nucleophile with the in situ formation of a C═C double bond. Diverse nucleophiles have been demonstrated to be applicable in this three‐component AAS reaction, including malonates, acetylacetone, acetoacetate, phosphine oxides, sulfonyl hydrazides etc. The protocol successfully offers a novel platform to integrate two distinct bioactive molecular scaffolds to access diverse array of hybrids. Mechanistic studies suggest that the three‐component AAS approach proceeds via a reaction sequence of LA‐catalyzed allylation of aldehyde, olefin shift under palladium catalysis, and Pd/LA‐cocatalyzed asymmetric allylic substitution.

Replacing critical point drying with hexamethyldisilazane drying enhances the ultrastructural preservation of cell surface projections in the parasite Trichomonas vaginalis for scanning electron microscopy

The cell surface of Trichomonas vaginalis, causative agent of human trichomoniasis, plays a pivotal role in parasite adhesion, motility, and intercellular communication. Scanning electron microscopy (SEM) is widely used to explore the surface projections involved in these processes; however, standard sample preparation via critical point drying (CPD) often damages delicate membrane projections. Here, we optimized a hexamethyldisilazane (HMDS) drying protocol as a reliable alternative to CPD for ultrastructural analysis of T. vaginalis using SEM. Both drying methods were compared in terms of image quality and artifact formation. HMDS drying significantly improved the preservation of fragile projections, such as filopodia-, cytoneme-, and lamellipodia-like structures, compared to CPD. Our results show that susceptibility to CPD-induced artifacts may vary among highly adherent T. vaginalis strains, highlighting the need for caution in SEM interpretation. In a strain previously CPD-characterized by exhibiting a low number of cytonemes, quantitative analyses revealed a marked increase in the number of parasites with filopodia and cytonemes upon HMDS, accompanied by a reduction in drying-associated artifacts. In contrast, other strains exhibited similar quantitative results for both methods, though HMDS demonstrated a slight qualitative enhancement. HMDS drying also enabled the identification of novel ultrastructural features of T. vaginalis, including (a) long (>20 µm) cytonemes forming network-like connections between parasites and host cells, and (b) thin posterior and axostylar cytoneme-like structures that seems involved in host cell adhesion. Moreover, HMDS provided better morphological preservation of amoeboid forms and enhanced visualization of parasite–host interactions, revealing membranous networks not previously observed with CPD. Altogether, this study demonstrates the importance of the drying methods for sample preparation and expands the approaches for parasite imaging, revealing HMDS as a valuable option that could provide new ultrastructural insights into the surface morphology and intercellular communication mechanisms of T. vaginalis.

Local US officials’ views on the impacts and governance of AI: Evidence from 2022 and 2023 survey waves

This paper presents a survey of local US policymakers’ views on the future impact and regulation of AI. Our survey provides insight into US policymakers’ expectations regarding the effects of AI on local communities and the nation, as well as their attitudes towards specific regulatory policies. Conducted in two waves (2022 and 2023), the survey captures attitudinal changes within the six months following the public release of ChatGPT and the subsequent surge in public awareness of AI. Local policymakers express a mix of concern, optimism, and uncertainty about AI’s impacts, anticipating significant societal risks such as increased surveillance, misinformation, and political polarization, alongside potential benefits in innovation and infrastructure. Many also report feeling underprepared and inadequately informed to make AI-related decisions. On regulation, a majority of policymakers support government oversight and favor specific policies addressing issues such as data privacy, AI-related unemployment, and AI safety and fairness. Democrats show stronger and more consistent support for regulation than Republicans, but the latter experienced a notable shift towards majority support between 2022 and 2023. Our study contributes to understanding the perspectives of local policymakers—key players in shaping state and federal AI legislation—by capturing evolving attitudes, partisan dynamics, and their implications for policy formation. The findings highlight the need for capacity-building initiatives and bi-partisan coordination to mitigate policy fragmentation and build a cohesive framework for AI governance in the US.

In Situ Click Chemistry Screen Facilitated by an On‐Nanoparticle DNA‐Encoded Library Identifies Highly Selective and Potent Peptoid Ligands for a Phosphatase

AbstractCapture agents that selectively bind to biological targets are indispensable tools in diagnostics, therapeutics, and biomedical research. However, discovering such capture agents, particularly for structurally conserved or challenging targets, remains a challenge. Here, we describe a protein‐templated in situ click strategy enabled by a nanoparticle‐based DNA‐encoded library (nanoDEL) platform. The nanoDEL enables the construction and screening of vastly large, chemically diverse combinatorial libraries with high redundancy, far exceeding the scale and throughput of conventional approaches, such as one‐bead‐one‐compound and solution‐phase in situ click methods. Thus, this enables the rapid and efficient identification of high‐affinity, high‐selectivity ligands in a single selection round, eliminating the need for iterative screening. To demonstrate the utility of this strategy, we performed an in situ click screening of a 27‐million‐member nanoDEL of azido‐functionalized peptoids, in the presence of a weak and promiscuous alkyne‐bearing anchor ligand. This yielded bidentate inhibitors of protein tyrosine phosphatase 1B, a challenging target due to its highly conserved active site. These inhibitors exhibited nanomolar potency and exceptional selectivity over closely related phosphatases. This work represents a broadly applicable strategy for discovering high‐performance capture agents, particularly for selectively targeting closely related protein families or isoforms where achieving selectivity remains a critical challenge.

How to promote the quality of technical education? A fuzzy-set qualitative analysis of 16 technical colleges in China

This study focuses on how technical and vocational education and training (TVET) institutions can effectively enhance educational quality to cultivate a globally competitive industrial workforce, addressing the World Banks projection that over 1.1 billion jobs worldwide will undergo skill transformations in the next decade due to automation, digitalization, and the green economy transition. Employing the fuzzy-set qualitative comparative analysis (fsQCA) method, the research conducts an in-depth analysis of developmental data from 16 Chinese TVET institutions to identify key factors influencing their competitiveness. The findings reveal that social service constitutes the foundation of high-quality vocational education. The social service capacity of TVET institutions is primarily reflected in vocational skill training, aligning with the core philosophy of Singapore Polytechnic’s “SkillsFuture” initiative. Through data analysis, a “social service-driven” development mechanism is identified: under similar conditions, TVET institutions achieve high-quality development by participating in government-funded vocational training programs. Simultaneously, two types of developmental bottlenecks are uncovered: (1) the “student skill level-international exchange constraints” type, where limited student proficiency and international collaboration hinder institutional progress; and (2) the “social service-technological R&D constraints” type, where weak social service delivery and technology transfer capabilities act as critical barriers. The outcomes provide a robust reference for global TVET stakeholders and policymakers to optimize industrial talent cultivation strategies and deepen integration into global value chains. The methodological framework also holds transferability to other domains, enabling regions to pinpoint success pathways and avoid ineffective measures.

Retraction: Overexpressed PKCδ Downregulates the Expression of PKCα in B16F10 Melanoma: Induction of Apoptosis by PKCδ via Ceramide Generation

Public sanitation interventions and household clean energy adoption: Evidence from China’s renovating water supply and toilets

By 2021, approximately 2.3 billion people worldwide still relied on polluting fuels and technologies for cooking. Such harmful fuels pose serious risks to both health and the environment, contributing to health issues and constraining economic activities. Based on the China Health and Retirement Longitudinal Study data, this study investigates whether and how the renovation of tap water and sanitary toilets affects clean energy adoption among rural households in China by utilizing a Probit model. The results demonstrates that the probability of rural households using clean energy for cooking significantly increased by 8.0 percentage points after undergoing the renovation of tap water and sanitary toilets. These effects are particularly pronounced in households with male heads and low-income households. Mechanism analysis suggests that the renovation of tap water and sanitary toilets significantly elevates educational levels, strengthens cognitive abilities, and fosters the accumulation of human capital, while also raising environmental awareness, thereby driving the utilization of clean energy sources. These findings underscore the significance of sanitation improvements in driving energy transition in rural areas of China. For policymakers focusing on sanitation facilities and socioeconomic development in developing countries, such as China, investments in sanitation infrastructure can yield broad benefits beyond public health, fostering human capital accumulation, environmental awareness, and energy transition. These outcomes have significant implications for long-term sustainable development goals.

The effect of cooling rate and supplying water condition on the freezing properties of silty clay in seasonal freezing zones

A unidirectional freezing experiment was performed on silty clay from the Changchun area using a custom freezing apparatus to examine temperature variations, frost deformation, and moisture migration within the soil samples. The study aimed to investigate the influence of cooling rate and water supply conditions on the soil’s frost heave properties. The results indicated that under different cooling rates and water supply conditions, the internal temperature evolution of the specimens could be categorized into four distinct stages: rapid cooling, rebound and stabilization, sustained cooling, and steady state.The final temperature of specimens under open water supply conditions was 2–3°C higher than that under closed conditions. The cryostructure exhibited a reticulated pattern, and its width increased from 3–4 cm to 6–7 cm with increasing cooling rate under the same water supply condition. The cooling rate significantly affected the frost heave ratio: under closed conditions, the ratio decreased, whereas under open water supply conditions, the vertical frost heave displacement increased with higher cooling rates.Moisture migration within the specimen was notably different under the two replenishment conditions. Under open water replenishment, the water content of the soil increased near the negative-temperature top plate and decreased in the surrounding areas.

Building health: Motivational factors to enhance systematic work environment management in the construction industry

Objective The aim of the study was to investigate whether and how the interventions have been beneficial in developing a well-functioning systematic OSH management. The aim was also to investigate whether and how the interventions have facilitated or impeded autonomous motivation to develop a well-functioning systematic OSH management. Method Data were collected through individual interviews with participants in the Health Construction intervention project and audio recordings from the concluding workshop for each batch. The data were analyzed using an inductive thematic analysis. Results The seven themes from the analysis yielded the following results. Participation in the project was highlighted as a key factor for development, as it offered opportunities to collaborate and share experiences and insights about the domain of the occupational environment with representatives from other companies. Establishing a development team within participating companies appears to have influenced the legitimacy of occupational safety and health, as well as the assigned safety priority. A process consultative approach by external consultants seems to have contributed to an enhanced ability to articulate thoughts, identify solutions, synthesize discussions, and work effectively within the development team. The results suggest that the assigned safety priority of the respective participating companies has increased. Additionally, there are indications that autonomous motivation to continue and deepen efforts to address safety and health issues in a structured way has increased within the participating companies. Conclusions The results of this study indicate that the interventions implemented in the project have been beneficial in fostering the development of a well-functioning systematic occupational safety and health management. This may have been achieved by enhancing the autonomous motivation to prioritize and develop a healthy and safe work environment within the participating companies.

Assessing and comparing early warning signal performance in spatially-structured systems

Critical transitions occur when a system undergoes a sudden shift from one state to another. Early warning signals (EWS) are indicators that can be used to potentially anticipate critical transitions in such systems, which may be temporal or spatio-temporal. Temporal systems are those whose state varies over time, whereas spatio-temporal systems also vary over a spatial domain. While temporal EWS can be applied to spatio-temporal systems by averaging over the spatial domain, spatially-informed EWS should, in principle, be able to outperform their temporal counterparts by making use of the additional spatial information. We seek to understand how EWS for spatial systems compare to those used for temporal systems. To facilitate comparison, we explore how EWS performance is measured. We use the strength of EWS trends, quantified using Kendall’s τ, as a proxy for performance. Other factors, such as robustness to choices of parameters used for detrending, statistical significance, and agreement with expected EWS behaviour, are considered. This assessment of EWS based on these factors enables an informed comparison and decision regarding which signals to apply to different systems for potential indications of critical transitions. We find that while spatially-informed EWS generally offer improved performance over temporal EWS for the example systems studied, we find the choice is system specific.

Inside Front Cover: A Photoresponsive Hybrid of Viruses and Supramolecular Peptide Fibers for Multidimensional Control of Patterning and Infection (Angew. Chem. Int. Ed. 41/2025)

Do the interpersonal effects of gamified online destination websites better stimulate tourists’ travel intentions?

With the growing prevalence of user-generated content in disseminating travel information, the current design of online destination websites should emphasize interactive engagement and fulfill users’ increasing social needs, thereby aligning with the behavioral characteristics and development trends of the digital age. This study conducts two empirical studies to examine the feasibility of integrating gamification into destination platforms and its influence on interpersonal value within users’ decision-making processes. Through scenario-based simulations comparing feedback from 931 participants on gamified versus non-gamified websites, the study applies structural equation modeling to test path coefficients and confirm the effectiveness and advantages of gamification, as well as the role of interpersonal value in shaping decision-making pathways. This study found that: (1) Gamification effectively brings personal hedonic and utilitarian value, is suitable for destination websites, and positively influences user decisions. (2) There is no significant difference between gamified and non-gamified experiences in terms of utilitarian and hedonic value experiences, nor in the influence of utilitarian value on decision-making. (3) The personal value experience brought by gamification will positively influence users’ interpersonal value. (4) Interpersonal value—experience sharing, identity recognition, and social support—under gamified experiences will positively influence user decisions. These findings reveal that gamified design can not only effectively enhance the practical attributes of online destination websites but also significantly strengthen individuals’ information dissemination about the destination and activate the website’s interpersonal effects. This makes gamification a new model for optimizing the information display of existing online destination websites, and it highlights the crucial role of interpersonal value in studying consumer decision-making paths.

Health assessment of non-native red-eared sliders (Trachemys scripta elegans) and their impact potential on native species

Red-eared sliders (RES; Trachemys scripta elegans) are a globally invasive species that can impact native chelonian populations through resource competition and disease introduction. In Cook County, Illinois, invasive RES co-occur with, and greatly outnumber, a species of conservation priority in the Great Lakes region: the Blanding’s turtle (Emydoidea blandingii). This study sampled free-ranging RES in Cook County during spring, summer, and fall in four unique locations to characterize the possible effect of this non-native species on the health of regional, sympatric, aquatic chelonians. RES (n = 242) were captured and sampled for qPCR pathogen detection, clinical pathology, and necropsy from 2018 to 2022. Multiple pathogens were detected, including Mycoplasma spp., multiple adenoviruses, Trachemys herpesvirus 1 (TrHV-1), frog virus 3, human-pathogenic Leptospira spp., Emydomyces testavorans, and Salmonella typhimurium. Mycoplasma spp. prevalence was significantly higher (p < 0.05) at one isolated site with a suspected greater density of turtles. Detection of TrHV-1 was significantly associated with season (p < 0.001), with detections occurring only in spring and fall. For the 28 hematology, plasma biochemistry, and protein electrophoresis analytes assayed, significant and variable associations occurred based on sample year, season, pathogen detection, age, and sex. Population-based reference intervals were created for hematologic, plasma biochemistry, and plasma protein electrophoresis analytes. Common necropsy findings included mild endoparasitism and related vascular lesions such as endarteritis. Notably, qPCR detection of above pathogens was not associated with any gross or histologic lesions indicative of clinically relevant disease. This study indicates that invasive RES in Cook County may be infected with pathogens of concern for co-occurring turtle species, and absence of associated lesions in the RES suggests they likely serve as carrier species for these pathogens. Continued health monitoring of this species is important as interactions with chelonians of conservation priority increase.

Saudi secondary school science textbooks’ ability to inculcate a PISA-Informed Scientific Identity

Saudi Arabia’s low performance in the 2018 Programme for International Student Assessment (PISA) science tests (M = 386 compared to M = 489 overall) prompted a content analysis of Saudi secondary school science textbooks (N = 9, three books for each of Grade, 7, 8, and 9) (86% intracoder reliability). Using a definition of scientific identity formed using PISA’s conceptual framework, we recommend future textbook revisions that ensure more balanced coverage to offset the current uneven weighing of scientific knowledge (55%), scientific competencies (28%), and science context (17%). Right now, students receive substantial coverage of major facts, concepts, and theories (knowledge) but less so for competencies (e.g., proficiency in scientific explanations, design, evaluation, and interpretation) or for how to understand and use science in different contexts at different levels (i.e., personal, local, and global). We assumed that secondary students’ appreciation that “science is for me” (i.e., positive scientific identity) will happen, if they are evenly exposed to all PISA dimensions. Because grade level profiles were very similar (both what was present and missing), rebalancing must occur in all three grades. Revised science textbooks that augment current weak spots should positively influence Saudi secondary student’s scientific identity and improve PISA performance.

Consent in the practice of molecular HIV epidemiology: A qualitative study of the perspectives of diverse communities of interest

Background The practice of using molecular HIV epidemiology (MHE) to enhance surveillance activities has generated much discussion, partly because it typically involves sequencing viral samples from persons living with HIV without their knowledge or consent. Methods Using individual, semi-structured in-depth interviews, we asked 41 individuals from a range of groups affected and/or involved in MHE and related health services in North Carolina their views about consent and MHE. Findings Although there was no unanimity of opinion, our interview participants were largely (82.5%) supportive using MHE for public health surveillance without obtaining consent, including those living with HIV, though there was also broad support across groups for raising public awareness about MHE. The reasons against consent for MHE included: consent is not traditionally solicited or required in other medical or public health surveillance activities; consent for MHE could deter people from getting tested or entering care; refusals could diminish the accuracy and utility of MHE data due to the resulting evidence gaps; and consent is impractical when there is an urgent need for data during disease outbreaks. Reasons in favor of consent included: a sample is something personal for which it is appropriate to ask permission for its use; failure to ask for consent is an unjustified curtailment of personal rights; people should be able to choose what information related to themselves that they share or do not share with others. There were also mixed responses, where the appropriateness of asking for consent depended on certain conditions. Conclusion These study findings reveal some support among communities of interest for the current approach to consent along with a need for greater community awareness of MHE, and contribute to the ongoing policy conversation about whether the current practice of not obtaining consent for MHE and HIV surveillance purposes should be revisited.

Tunable acoustic scattering in composite duct structures with elastic membrane discontinuities

This study investigates acoustic wave scattering in a composite duct structure incorporating a rigid annular shell connected to a flexible cylindrical shell via an embedded elastic membrane disc. The presence of the membrane introduces a vibratory discontinuity that significantly influences acoustic propagation and scattering characteristics. We develop a semi-analytical framework combining the Mode Matching (MM) technique for rigid-fluid interfaces with a Galerkin-based approach to model the elastic membrane vibrations. The formulation enforces continuity of pressure and axial velocity at the fluid-structure interfaces through truncated modal expansions, with convergence rigorously verified. By varying membrane edge constraints (spring-like, clamped, free) and geometric parameters, we identify distinct scattering regimes and demonstrate how structural and boundary variations can enhance or suppress acoustic reflection. Under spring-like conditions, a transmission loss of 13.5 dB is achieved, with subsequent variations governed by changes in scattering powers due to different parametric settings and edge conditions. The findings provide insights for the design of advanced tunable acoustic devices, including silencers and metamaterial waveguides, where controlling wave scattering is critical.

General Synthesis of 2D Mesoporous Multimetal Spinel Supracrystals for High‐Efficiency Electrochemical Applications

AbstractTwo‐dimensional (2D) mesoporous metal oxide crystals that integrate atomic‐level single crystallinity with ordered mesoporosity represent a promising but rarely realized class of materials, particularly in multicomponent systems. Here, we report a universal strategy for synthesizing freestanding 2D mesoporous spinel supracrystals with tunable compositions, spanning from unary to multinary spinel oxide systems. This approach decouples crystalline framework formation from mesopore generation, combining emulsion‐mediated, on‐surface crystallization of 2D nanocrystal superlattices with thermally‐induced collective nanocrystal reorientation and facet‐selective epitaxial fusion. Concurrent surface reconstruction exposes {110} facets along nanocrystal edges, which define the internal surfaces of vertically aligned mesopores. As a proof of concept, 2D mesoporous FeMnCoO supracrystals are employed as functional interlayers in lithium–sulfur (Li–S) batteries. These interlayers demonstrate strong polysulfide adsorption, accelerated redox kinetics, and enhanced Li+ ion transport, enabled by their multimetal‐induced electronic modulation, facet‐specific catalytic activity, and 2D mesoporous architecture. As a result, Li–S cells equipped with FeMnCoO‐modified separators deliver exceptional electrochemical performance, even under high sulfur loading and lean electrolyte conditions. This work addresses a longstanding challenge in reconciling ordered mesoporosity with crystallographic coherence in mesoporous materials, establishing a molecularly modular approach for synthesizing 2D mesoporous spinel crystals with programmable compositions and facet‐engineered functionality.

DDIAS promotes endometrial cancer progression via β-catenin signaling

Background DDIAS has been recognized as an oncogene in various cancers, but its role in endometrial cancer remains unexplored. Methods The expression of DDIAS in normal endometrium and endometrial cancer samples was analysed via the The Cancer Genome Atlas (TCGA) database, and prognostic analysis was performed. The differential expression of DDIAS between endometrial cancer and normal endometrium tissues was analyzed using quantitative polymerase chain reaction (qPCR). To study the expression of DDIAS in endometrial cancer, immunohistochemistry was performed on endometrial cancer, atypical endometrial hyperplasia and normal endometrial tissue. The association between DDIAS expression and clinicopathology was analysed. The expression of DDIAS in endometrial cancer cell lines was studied via Western blot (WB) analysis. DDIAS was knocked down in endometrial cancer cell lines via small interfering RNA (siRNA), and the effects of DDIAS knockdown on endometrial cancer cell biology and its related regulatory mechanisms were investigated via Cell Counting Kit-8(CCK8), Colony formation assay, scratch test, Transwell, and WB assays. Finally, the relevant regulatory mechanisms were verified using rescue experiments. Results According to the public database analysis, High DDIAS expression correlates with endometrial cancer and predicts unfavorable prognosis..The qPCR confirmed higher expression of DDIAS in tumor samples.We found that DDIAS was highly expressed in endometrial cancer and atypical endometrial hyperplasia, and that the upregulation of DDIAS expression predicted poor prognosis. In endometrial cancer, higher DDIAS expression was associated with increased tumor grade and advanced FIGO stage. In terms of cellular function, knocking down DDIAS suppressed the proliferation, migration and invasion capabilities of endometrial cancer cells. In the mechanistic pathway, reducing DDIAS expression led to the inhibition of β-catenin and its downstream targets, including c-Myc, cyclin D1, and survivin, while also suppressing epithelial-mesenchymal transition (EMT).However, these changes were rescued by the upregulation of β-catenin. Conclusion DDIAS regulated EMT in endometrial cancer cell migration and invasion through the β-catenin pathway, demonstrating that DDIAS is a potential target for the treatment of endometrial cancer.

Inside Back Cover: Modeling Midbrain and Brainstem Neuromelanins to Characterize Metal Binding and Associated MRI Contrast in Parkinson's and Alzheimer's Diseases (Angew. Chem. Int. Ed. 41/2025)

Corral[<i>n</i>]Bicarbazoles: Redox‐Active Chiral Macrocycles for Air‐Stable Radical Cations Formation and Guest Capture/Release

AbstractMacrocyclic compounds are pivotal in both supramolecular chemistry and materials science, as their preorganized cavities enable selective molecular recognition, while their cyclic frameworks facilitate electronic and spatial coupling of monomeric units to yield advanced optoelectronic and magnetic properties. However, macrocycles that combine exceptional host–guest recognition with these properties remain rare and challenging to design. Herein, we report the synthesis of three pairs of enantiopure, redox‐active, conjugated macrocycles, termed corral[n]bicarbazole, employing axially chiral 4,4′‐bicarbazole units. These macrocycles display strong blue emission (quantum yields up to 78% in THF) and pronounced circularly polarized luminescence (|glum| up to 10−3). Notably, controlled oxidation of corral[n]bicarbazoles generates their mono‐ and polyradical cations with exceptional air stability (half‐lives up to five days) and intriguing magnetic properties. The electron‐rich deep‐cavity of corral[4]bicarbazole confers strong hosting ability (Ka = 104–105 M−1) toward cationic guests, facilitating redox‐responsive guest capture/release. By integrating a chiroptical, redox‐active backbone with a switchable recognition cavity, corral[n]bicarbazoles offer a versatile platform for advancing interdisciplinary innovation, with potential applications in optoelectronics, spintronics, and smart supramolecular materials.