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Cobalt‐Catalyzed Asymmetric Hydrogenation of α‐Hydroxy Ketones Enabled by a Carboxylic Acid Additive Promotion Strategy
Abstract Highly enantioselective hydrogenation of α‐hydroxy ketones was achieved by applying the catalytic combination of cobalt acetate and chiral Ph‐BPE ligand, supplemented by a carboxylic acid additive promotion strategy. The carboxylic acid additive significantly increases both reactivity and enantioselectivity, allowing for the highly efficient generation of chiral 1,2‐diols with up to 99% ee. The application utility is proved through derivations and a total synthesis of ( R )‐(−)‐eliprodil. Mechanistic studies, including control experiments and DFT calculations, support the proposed catalytic mechanism and explain the origin of enantioselectivity.
How does the institutional environment improve the entrepreneurial quality of returnees? A configuration analysis based on a complex system view
Enhancing high-quality entrepreneurship among returnees stands as a pivotal mechanism in driving the robust economic development of emerging economies. The inquiry into crafting an enabling institutional framework to bolster the excellence of returnee entrepreneurship has garnered significant interest within academia and pertinent industries. Existing research primarily explores the impact of single institutional elements on returnee entrepreneurship, overlooking the diverse pathways to improve its quality under institutional complexity. Building on these insights, the current study explores the complex relationship between institutional configurations and the quality of returnee entrepreneurship in China. It also employs Necessary Condition Analysis (NCA) and dynamic Qualitative Comparative Analysis (QCA) methods based on a complex systems perspective. The research samples include 30 provinces in China. The findings reveal that while individual institutional factors do not, on their own, drive high-quality entrepreneurship among returnees in Periods 1 and 2, the importance of market environment and digital infrastructure becomes pronounced by Period 3. In the initial period, resource-driven entrepreneurship paired with emerging opportunities fosters high-quality outcomes. By Period 2, two additional configurations take shape: legitimacy-driven entrepreneurship under opportunity emergence and a dual-driver model that integrates both opportunities and resources. This dual-driver approach remains the dominant pathway for returnees in Period 3. Additionally, the market environment remains a critical factor across all periods. Digital infrastructure has become increasingly crucial for returnee entrepreneurship. Initially, the market environment focused primarily on financial services, but its connection with digital infrastructure intensified over time. In that regard, differences in economic resources and development across provinces have also led to region-specific pathways for improving the quality of returnee entrepreneurship. The findings contribute to a nuanced comprehension of the disparate progress of returnee entrepreneurial endeavors across regions within emerging economies. Most importantly, they offer theoretical insights to enhance the institutional framework in diverse regions, fostering the attainment of high-quality returnee entrepreneurship.
Influence of bond strength in treated mixed recycled aggregate concrete incorporating olivine sand
Development of Cu-ZnO ZrO2 based polyacrylonitrile polymer composites for removing pharmaceutical pollutants and heavy metals from wastewater
ADCY4 inhibits cAMP-induced growth of breast cancer by inactivating FAK/AKT and ERK signaling but is frequently silenced by DNA methylation
A NoSQL document based eCRF system for study of vaccines with variable adverse events case study on COVID19 vaccines
Predict the degree of secondary structures of the encoding sequences in DNA storage by deep learning model
Oxyresveratrol suppressed melanogenesis, dendrite formation, and melanosome transport in melanocytes via regulation of the MC1R/cAMP/MITF pathway
Abstract Oxyresveratrol, a natural derivative of resveratrol, has been shown to possess antimelanogenic properties. However, the underlying mechanism and its effect on melanin transfer remain poorly understood. In this study, the effects and mechanisms of oxyresveratrol on melanogenesis, dendrite formation, and melanosome transport were investigated. In vitro assays indicated that oxyresveratrol is a potent inhibitor of human tyrosinase, with an IC50 value of 2.27 µg/mL. Treatment of B16F10 melanoma cells with oxyresveratrol suppressed melanogenesis through the down-regulation of the MC1R/cAMP/MITF signaling pathway. In a co-culture model of B16F10 and HaCaT cells, oxyresveratrol inhibited both melanin transfer and dendrite formation by down-regulating the expression of small GTPases (CDC42, RAB17, RAB11B, RAC1) and the kinesin KIF5B. These findings suggested that oxyresveratrol may serve as a promising therapeutic agent for pigment-related disorders by inhibiting melanogenesis, dendrite formation, and melanosome transport.
Prenatally and postnatally sequential genetic etiology detection in corpus callosum abnormalities
The impact of pilot policy for innovative industrial clusters on green innovation efficiency
FDA approves first-in-class TRPM8 ion channel agonist for dry eye disease
FAK activity exacerbates disturbed flow-mediated atherosclerosis via VEGFR2-CBL-NF-κB signaling
Deep mutational scanning identifies Cas1 and Cas2 variants that enhance type II-A CRISPR-Cas spacer acquisition
Abstract A remarkable feature of CRISPR-Cas systems is their ability to acquire short sequences from invading viruses to create a molecular record of infection. These sequences, called spacers, are inserted into the CRISPR locus and mediate sequence-specific immunity in prokaryotes. In type II-A CRISPR systems, Cas1, Cas2 and Csn2 form a supercomplex with Cas9 to integrate viral sequences. While the structure of the integrase complex has been described, a detailed functional analysis of the spacer acquisition machinery is lacking. We developed a genetic system that combines deep mutational scanning (DMS) of Streptococcus pyogenes cas genes with a method to select bacteria that acquire new spacers. Here, we show that this procedure reveals key interactions at the Cas1-Cas2 interface critical for spacer integration, identifies Cas variants with enhanced spacer acquisition and immunity against phage infection, and provides insights into the molecular determinants of spacer acquisition, offering a platform to improve CRISPR-Cas-based applications.
Sacrifice-layer-free transfer of wafer-scale atomic-layer-deposited dielectrics and full-device stacks for two-dimensional electronics
Vulnerability in research ethics: A systematic review of policy guidelines and documents
Background The history of research involving human subjects has demonstrated the importance of offering everyone an equal opportunity to participate in research, while safeguarding those who require special attention. When it comes to vulnerable individuals, this consideration is relevant. However, disagreement still exists about the meaning of vulnerability, the identification and definition of vulnerable populations, and how these concepts should be operationalised in policy documents in order to implement appropriate, preventive and respectful measures for all those subsumed within this category. Objectives Following the PRISMA-Ethics guidance, we performed a systematic review of policy documents to provide a comprehensive overview of how vulnerability is conceptualised and operationalised in research ethics. The aim is to investigate the meaning and definition of vulnerability in research ethics, its normative justification, the comprehensive set of subjects it refers to, and consequent provisions. Methods Our search centred on three main sources: three overview lists that provide comprehensive coverage of research ethics policy documents and guidelines (the International Compilation of Human Research Standards, the Listing of Social-behavioral Research Standards and the Ethics Legislation, Regulation and Conventions); search databases (PubMed and Web of Science) and grey literature (Google Scholar), to ensure completeness of included policy documents. Search strings were developed by the last author (VS) in consultation with the co-first author (GB). The whole screening process was performed by the first (AG) and co-first author (GB), separately. The search was originally performed in April 2023, and then re-performed in May 2025 to exclude obsolescent results. English-language policy documents in the field of human research ethics and addressing the subject of vulnerability were included. Eligibility criteria covered both national and international application. For data analysis and synthesis, the authors followed the steps of the QUAGOL methodology: policy documents’ reading (AG), highlighting of relevant parts (AG), development of a summary of each document’s highlighted parts (AG), summary evaluation and verification against previous QUAGOL steps (AG, GB, VS), creation of a comprehensive scheme (AG, GB, VS), and description of results (AG, GB, VS). No automation tools were used at any stage of the review. Results and discussion Seventy-nine policy documents were included in the review. Research findings were organised in four different subsections, corresponding to four research questions. The analysis of such a significant number and variety of documents allowed us to identify several recurring patterns that characterise the way vulnerability is described and addressed by policy documents. Based on our roles as bioethicists, research ethicists, biotechnologies expert in clinical trials, and study coordinators, we identified some key themes, e.g., a tendency to identify and define vulnerable groups, rather than providing a general definition of vulnerability, and a tendency to define vulnerability in relation to informed consent. Conclusions Only a proper understanding of the meaning of vulnerability, its implications and its normative justifications will make it possible to ensure a fair and ethically legitimate participation in research for all involved subjects. As to the study limitation, only publications written in English, or officially translated in English, were included in the review.
Medium-sized protein language models perform well at transfer learning on realistic datasets
Abstract Protein language models (pLMs) can offer deep insights into evolutionary and structural properties of proteins. While larger models, such as the 15 billion parameter model ESM-2, promise to capture more complex patterns in sequence space, they also present practical challenges due to their high dimensionality and high computational cost. We systematically evaluated the performance of various ESM-style models across multiple biological datasets to assess the impact of model size on transfer learning via feature extraction. Surprisingly, we found that larger models do not necessarily outperform smaller ones, in particular when data is limited. Medium-sized models, such as ESM-2 650M and ESM C 600M, demonstrated consistently good performance, falling only slightly behind their larger counterparts—ESM-2 15B and ESM C 6B—despite being many times smaller. Additionally, we compared various methods of compressing embeddings prior to transfer learning, and we found that mean embeddings consistently outperformed other compression methods. In summary, ESM C 600M with mean embeddings offers an optimal balance between performance and efficiency, making it a practical and scalable choice for transfer learning in realistic biological applications.
Choroidal evaluation of FTLD-Tau and biomarker-determined Alzheimer’s disease
Longitudinal surveillance of Aedes aegypti (Diptera: Culicidae) in urban coastal Kenya: population dynamics, blood feeding frequency and dengue virus infection rates
Abstract The coastal region of Kenya has emerged as a focal point for urban dengue virus transmission driven by Aedes aegypti as the primary vector. To gain a deeper understanding of the epidemiological situation, we carried out a year-long longitudinal study (December 2021- November 2022) of the population dynamics of A. aegypti through weekly mosquito surveys using ovitrap and CO2-baited Biogents (BG) mosquito traps in Ukunda, an urban township in the coastal region. Aedes eggs laid in ovitraps were exclusively A. aegypti with 80.8% mean hatch rate. A total of 35,109 adult A. aegypti were captured, with twice as many females than males. The density of adult A. aegypti trap captures varied monthly, but there was no discernible delineation by season. Aedes aegypti fed more on humans (human blood index = 0.72). Two dengue-2 virus RNA was detected in two blood-fed specimens that had fed on humans. Multiple linear regression model indicated 59% variation in adult female abundance explained by weather variables including daily range in wind speed (82.9%) and temperature (17.1%). In contrast, random forest model revealed 83% variation in egg abundance attributed to weather variables, being positively influenced by mean daily temperature, wind speed, relative humidity and negatively by total precipitation. Our results confirm year-round vector presence and active circulation of dengue virus indicative of endemicity in urban Kenya. The findings highlight the importance of short-term climatic factors as predictors of A. aegypti dynamics of value in surveillance and control of arboviral diseases such as dengue.