Browse Articles
Discover research articles across all indexed journals
Predicting age of respiratory syncytial virus infection from birth timing
Abstract Respiratory syncytial virus (RSV) infects nearly all children by age 2 to 3 years, and early-life infection—defined using active and passive surveillance with quantitative polymerase chain reaction- and serology-identified infection—has been implicated as a causal factor in childhood asthma. As such, identifying infants that are likely to be infected with RSV during this critical susceptibility window has important implications for identifying individuals at risk for chronic respiratory sequelae. However, determining the age of RSV infection in large populations is challenging because many infections are asymptomatic, making accurate detection dependent on intensive and costly surveillance. To address this, we developed a probability model for age of first RSV infection. It uses an infant’s birthdate, demographic covariates, and publicly available RSV circulation data to determine the probability they were first infected at any age from birth to one year. Our model is interpretable, accounts for nearly 37% of the variance in age at first infection, and generalizes across four independent datasets collected from participants in the United States, where we use it to accurately predict age of first infection in two independent cohorts. Our work facilitates reliable estimation of the age of infant RSV infection during the first year of life without the need for active surveillance.
First detection of Usutu virus in wild birds in Denmark, 2024
USP25 inhibition ameliorates Parkinson’s disease by restoring mitophagy
Parkinson’s disease (PD) is a progressive neurodegenerative disease that casts a significant shadow over global health and the identification of therapeutic targets for PD will empower more effective clinical treatment. The gene encoding the deubiquitinating enzyme USP25 has been identified as a susceptible locus for PD, but the role of USP25 in PD remains unknown. In this study, we found that USP25 exacerbated dopaminergic neuronal loss and motor deficits in murine models of PD by sabotaging the mitophagy machinery. USP25 physically interacted with the autophagy receptor optineurin and disrupted its linkage with K63-specific polyubiquitin chains, leading to impaired mitophagy and the accumulation of damaged mitochondria. Genetic ablation or pharmacological inhibition of USP25 significantly restored mitophagy and thereby impeded the neurodegenerative progression in PD model mice. Collectively, our results unravel a pivotal role of USP25 in PD and identify USP25 as a pharmacological target for the development of PD drugs.
A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation
Abstract Cellular polarization plays a crucial role in regulating immunological processes and is often associated with reorientation of the centrosome. During immune synapse formation, centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells such as dendritic cells amplify centrioles during maturation and immune activation. How centriole amplification in antigen-presenting cells affects immune synapse formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that extra centrioles in dendritic cells form over-active microtubule organizing centers, which cluster during dendritic cell-T cell interactions and, unlike in T cells, localize close to the cell center. Perturbing either centrosome integrity or centriole numbers and configuration in dendritic cells results in impaired T cell activation. Collectively, our results highlight a crucial role for centriole amplification and optimal centrosome positioning in antigen-presenting cells for controlling T cell responses.
The triglyceride HDL cholesterol ratio predicts sarcopenia risk in an aging National cohort from China
Multimetallic synergies in tandem plasmonic photocatalysis
A comprehensive N-glycoproteome atlas reveals tissue-specific glycan remodeling but non-random structural microheterogeneities
Novel niclosamide-derived Schiff bases as a dual-targeted anticancer agents
Abstract Nicosamide (NIC), an approved anthelmintic medication, has demonstrated encouraging antitumor action. To enhance NIC’s pharmacokinetic and pharmacodynamic characteristics and make it a potential anticancer drug, thirteen NIC-Schiff bases were created by condensation reaction of NIC-amine 2 with various monocyclic/bicyclic/tricyclic aromatic aldehydes/acetophenone in absolute ethanol. Several spectroscopic methods, such as elemental analysis, IR, ¹H NMR, and MS, were used to determine the structures of these novel synthesized compounds. MTT assay was used to assess the target compounds’ activity against prostate cancer cell line (PC-3) and two breast cancer cell lines (MCF-7) and (MDA-MB-231). IC 50 was determined for the most promising compounds using doxorubicin and NIC as reference standards. Among the compounds examined, the noteworthy compound 11 exhibited IC 50 values of 2.85, 4.61, and 7.69 µM against MCF-7, MDA-MB-231, and PC-3, respectively, whereas, compound 8 displayed IC 50 values of 8.70 and 8.20 µM against MCF-7 and MDA-MB-231, respectively. Using NIC as a reference standard, a mechanistic analysis of the interesting compounds 8 and 11 revealed dual inhibitory effect on JAK1 and CDK7 enzymes. They elicited greater amounts of JAK1 inhibition in MCF-7 and MDA-MB-231 (81-85.5%, 53.6-69.18%) than NIC (75.6% and 36.6%, respectively). Surprisingly, compound 11 inhibits CDK7 more than NIC does on MCF-7 (80.7%) and PC-3 (83.4%) cells. Additionally, compound 11 produced cell cycle arrest at G2/M (35.03%) with overexpression of pre-G (20.68%) in contrast to the control (20.95%) and (0.31%), respectively. With respect to the control, compound 11 performed better than NIC in raising the levels of apoptosis mediators, caspases 1, 3, and 9, in MDA-MB-231 cells by 4.60, 3.03, and 2.69 times, respectively. Like NIC, it also activates caspase 1 in PC-3 cells 3.5 times more than control. According to flow cytometry results, 11 significantly increased apoptotic cell death from 1.34% to 10.92% and necrotic cell death from 1.05% to 3.47% in comparison to control MCF-7 cells. The docking results of NIC-Schiff bases 8 and 11 confirmed the combined in vitro inhibitory effects of the JAK1 and CDK7 enzymes. Compound 11 establishes a more stable, tightly bound complex with JAK1, as indicated by molecular dynamics.
Gender stereotypes across nations relate to the social position of women and men: Evidence from cross-cultural public opinion polls
Gender stereotypes, defined as widely shared beliefs about the typical attributes of women and men, have far-reaching consequences for both stereotyped groups. This preregistered research examined cross-cultural variation in gender stereotypes based on public opinion poll data from 1995 (22 nations with 22,000 respondents) and 2023 (40 nations with 4,800 respondents). Results revealed that men were perceived as more agentic than women and women as more communal than men in all studied nations at both time points. Yet, substantial cross-cultural variation existed in the strength of these stereotypes whereby the communion stereotype in particular related to the distribution of women and men into social roles. The female advantage in communion was stronger the larger women’s share in the labor force and the greater the occupational sex segregation, both reflecting women’s employment primarily in communal domains. The male advantage in agency likely reflects that women’s considerable inroads into leader roles put them in versions of the role entailing lesser status and power and therefore conveying lesser agency. For competence, most respondents believed that women and men are equally competent in 17 of the 23 nations surveyed in 1995 and in all 40 nations surveyed in 2023. These beliefs in competence equality were stronger in nations with greater female educational attainment and labor force participation (in 2023 but not in 1995). By identifying cross-cultural patterns and socioeconomic indicators associated with variation in gender stereotyping, this research advances understanding of how the locations of women and men in nations’ social structures inform gender stereotypes.
Synthetic rewriting technologies in mammalian cells
Blind recognition of channel codes based on dual-branch feature fusion convolutional neural networks
Abstract Facing heterogeneous signals increasing in dynamic spectrum, cognitive radio urgently needs blind channel coding identification. This technology addresses the core challenge of unknown coding schemes in non-cooperative communications. Existing methods are typically restricted to specific coding types and suffer from poor identification accuracy and robustness. To mitigate this constraint, we propose a Dual-Branch Feature Fusion Convolutional Neural Network (DBFCNN) framework for fine-grained identification among seven common channel-coding schemes. The network adopts a two-branch architecture. One branch employs multi-scale dilated convolutions to extract long-range dependencies in the received bit sequence, the other is a statistical branch that extract descriptors such as run length, entropy values, coding depth and so on to expose code-specific algebraic characteristics. The fused representation is fed to a fully connected classifier to jointly identify the seven code types. Extensive simulations demonstrate that DBFCNN improves identification accuracy by about 5% (absolute) over a strong prior baseline under comparable settings, proving the feasibility and effectiveness of the method.
Reframing the axon initial segment: Giant ankyrin-G as a modulator of excitability and plasticity in neurodevelopment
Metallic tellurium for p-type contacts of two-dimensional MoTe2 field-effect transistors
Collaborative harm reduction efforts lead to the first detection of 5-cyano isotodesnitazene in illicit street drugs
Abstract In the ongoing opioid crisis, regulatory restrictions on fentanyl and its derivatives have led to the emergence of nitazenes, a class of highly potent synthetic opioids synthesised during the 1950s but never approved for medical use. Structurally distinct from traditional opioids, nitazenes have gained increasing presence in illicit drug markets since 2019, contributing to a growing number of drug-related deaths across Europe, North America, and Australia. The rapid proliferation of novel nitazene analogues presents a significant challenge to law enforcement and public health systems. Drug-checking services (DCS) are currently one of the most effective tool for early detection and response, enabling real-time surveillance and consequently reducing the impact of overdoses due to Novel Synthetic Opioids. As a complement, universities can provide the scientific expertise and infrastructure necessary to confirm molecules detected by DCS. This study is the first report identifying and confirming 5-cyano isotodesnitazene in a street-sold drug, through an international collaboration involving two DCSs and three academic institutions. The structural elucidation was achieved through complementary analytical techniques comprising gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The present work highlights the essential role that cross-sector cooperation and analytical innovation play in tackling the rapidly evolving threat of novel synthetic opioids.
Optimizing mRNA delivery with targeted elastin-like polypeptide–based LENN formulations: Insights into the endocytosis mechanism
Gene delivery has emerged as a groundbreaking technique for altering gene expression, offering new possibilities in treating a vast array of diseases. We report a layer-by-layer elastin-like polypeptide nucleic acid nanoparticle (LENN) system for mRNA delivery as an attractive alternative to viral vectors and lipid nanoparticle (LNP) systems. This study focuses on determining the physical characteristics of LENN bearing mRNA cargo and assessing their biological performance in T24 bladder tumor cells. Our data show that mRNA encoding luciferase forms stable 30 to 130 nm LENN particles via batch mixing to efficiently encapsulate the mRNA strands, are resistant to heparin challenge, and are capable of storage at −20 °C for 3 d as lyophilized powders while retaining full biological activity after rehydration. We also demonstrate that LENN targeted to the epidermal growth factor receptor (EGFR) can efficiently deliver the mRNA cargo to the cytosol of EGFR+ T24 human bladder cancer cells via clathrin-mediated endocytosis where it is translationally active. Lipid profiling analyses show the significant role that upregulated phospholipid biosynthesis plays in nanoparticle internalization and endosomal escape compared to untargeted LENN, indicating the importance of the clathrin pathway in contributing to the delivery efficiency of LENN. Endocytosis inhibition experiments further support the involvement of the clathrin pathway. These findings highlight the compelling features of LENN with respect to their size, in vitro and in vivo targetability, mRNA encapsulation efficiency, complex stability, gene expression, and “green” manufacturability, offering an attractive alternative to existing methods for gene delivery.