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"Pu Jing"
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Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine
The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.
Journal Article
esFont: A guided diffusion and multimodal distillation to enhance the efficiency and stability in font design
Font design is an area that presents a unique opportunity to blend artistic creativity and artificial intelligence. However, traditional methods are time-consuming, especially for complex fonts or large character sets. Font transfer streamlines this process by learning font transitions to generate multiple styles from a target font. Yet, existing Generative Adversarial Network (GAN) based approaches often suffer from instability. Current diffusion-based font generation methods typically depend on single-modal inputs, either visual or textual, limiting their capacity to capture detailed structural and semantic font features. Additionally, current diffusion models suffer from high computational complexity due to their deep and redundant architectures. To address these challenges, we propose esFont, a novel guided Diffusion framework. It incorporates a Contrastive Language–Image Pre-training (CLIP) based text encoder, and a Vision Transformer (ViT) based image encoder, enriching the font transfer process through multimodal guidance from text and images. Our model further integrates deep clipping and timestep optimization techniques, significantly reducing parameter complexity while maintaining superior performance. Experimental results demonstrate that esFont improves both efficiency and quality. Our model shows clear enhancements in structural accuracy (SSIM improved to 0.91), pixel-level fidelity (RMSE reduced to 2.68), perceptual quality aligned with human vision (LPIPS reduced to 0.07), and stylistic realism (FID decreased to 13.87). It reduces the model size to 100M parameters, cuts training time to just 1.3 hours, and lowers inference time to only 21 minutes. In summary, esFont achieves significant advancements in both scientific and engineering domains by the innovative combination of multimodal encoding, structural depth pruning, and timestep optimization.
Journal Article
Antibiotic Toxicity and Absorption in Zebrafish Using Liquid Chromatography-Tandem Mass Spectrometry
Evaluation of drug toxicity is necessary for drug safety, but in vivo drug absorption is varied; therefore, a rapid, sensitive and reliable method for measuring drugs is needed. Zebrafish are acceptable drug toxicity screening models; we used these animals with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify drug uptake in zebrafish to better estimate drug toxicity. Analytes were recovered from zebrafish homogenate by collecting supernatant. Measurements were confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with different polarities were tested to explore any correlation of drug polarity, absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed more drug than those at 6 h post-fertilization (hpf), and different developmental periods appeared to be differentially sensitive to the same compound. By observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf were adapted to measure acute drug toxicity in adult mammals. Thus, we can exploit zebrafish to study drug toxicity and can reliably quantify drug uptake with LC-MS/MS. This approach will be helpful for future studies of toxicology in zebrafish.
Journal Article
An Inactivated Enterovirus 71 Vaccine in Healthy Children
Enterovirus 71 (EV71), a cause of hand, foot, and mouth disease, may be associated with poliomyelitis-like paralysis. In this report from China, a vaccine was shown to significantly decrease EV71-associated illness in children.
Epidemics of hand, foot, and mouth disease in children have emerged recently in Asia and have been caused primarily by enterovirus 71 (EV71) and coxsackievirus A16,
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which typically show two peak epidemic incidences each year, in May and October.
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An important clinical concern regarding hand, foot, and mouth disease is central nervous system injury, which occurs during the disease course in some severe cases and may result in a poor outcome.
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Infection with the EV71 C4 genotype accounts for 40.1 to 55.4% of cases of hand, foot, and mouth disease, with considerable associated mortality, including thousands of deaths . . .
Journal Article
Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations
The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.
Journal Article
A Rapid Assessment Model for Liver Toxicity of Macrolides and an Integrative Evaluation for Azithromycin Impurities
Impurities in pharmaceuticals of potentially hazardous materials may cause drug safety problems. Macrolide antibiotic preparations include active pharmaceutical ingredients (APIs) and different types of impurities with similar structures, and the amount of these impurities is usually very low and difficult to be separated for toxicity evaluation. Our previous study indicated that hepatotoxicity induced by macrolides was correlated with c-fos overexpression. Here, we report an assessment of macrolide-related liver toxicity by ADMET prediction, molecular docking, structure–toxicity relationship, and experimental verification via detection of the c-fos gene expression in liver cells. The results showed that a rapid assessment model for the prediction of hepatotoxicity of macrolide antibiotics could be established by calculation of the -CDOCKER interaction energy score with the FosB/JunD bZIP domain and then confirmed by the detection of the c-fos gene expression in L02 cells. Telithromycin, a positive compound of liver toxicity, was used to verify the correctness of the model through comparative analysis of liver toxicity in zebrafish and cytotoxicity in L02 cells exposed to telithromycin and azithromycin. The prediction interval (48.1∼53.1) for quantitative hepatotoxicity in the model was calculated from the docking scores of seven macrolide antibiotics commonly used in clinics. We performed the prediction interval to virtual screening of azithromycin impurities with high hepatotoxicity and then experimentally confirmed by liver toxicity in zebrafish and c-fos gene expression. Simultaneously, we found the hepatotoxicity of azithromycin impurities may be related to the charge of nitrogen (N) atoms on the side chain group at the C5 position via structure–toxicity relationship of azithromycin impurities with different structures. This study provides a theoretical basis for improvement of the quality of macrolide antibiotics.
Journal Article
A retrospective descriptive study on the early identification of near-miss events in nursing
Objective
To analyze the status of near-miss nursing events reported in this tertiary hospital in 2024 and to explore early identification strategies for these events, with the aim of continuously optimizing patient safety management and providing data support for decision-making.
Methods
A retrospective analysis was conducted using data extracted from the hospital information system on near-miss nursing events reported in 2024. The analysis included both nurse-related and patient-related data associated with these risk events. Descriptive and statistical analyses were performed using SPSS version 25.0.
Results
A total of 120 near-miss nursing events were reported in 2024. Male patients accounted for 52.50% and female patients for 47.50%. The highest proportion of patients involved were aged over 60 years (51.67%), while those aged 0–2 years accounted for the lowest proportion (4.17%). Inpatients comprised the majority of cases (90.83%). Most events were reported during day shifts (76.67%), and 34.17% occurred during vulnerable time periods. The majority of incidents occurred in inpatient wards (67.50%), with fall/bed-drop risks (25.83%) and unplanned extubation risks (21.67%) being the most common types. The events involved 42 departments, with the Department of Respiratory and Critical Care Medicine reporting the highest proportion (8.33%). A total of 111 nurses were involved in the reported events, with 98.20% being female. Nurses aged 31–40 years accounted for the largest group (55.86%), and those with a bachelor’s degree made up 88.29% of the sample. In terms of professional title, nurse-in-charge represented the highest proportion (68.47%). Most events were reported by individual nurses (91.89%), while a small number reported two events (8.11%).
Conclusion
This study analyzed 120 near-miss nursing events reported in 2024. The results showed that most events occurred in inpatient wards (67.50%), with fall/bed-exit (25.83%) and unplanned extubation (21.67%) being the most common types. Temporally, events were concentrated during day shifts (76.67%) and patient-vulnerable periods (34.17%). Patients aged over 60 accounted for the majority of cases, and the Department of Respiratory and Critical Care Medicine reported the highest number of incidents. Based on these distribution patterns, it is recommended to enhance monitoring of key scenarios, time periods, and patient groups in nursing practice. Future efforts should focus on expanding multi-center data collection, adopting systematic monitoring tools, and conducting qualitative research to further optimize event reporting and safety management strategies.
Journal Article
EARP is a multisubunit tethering complex involved in endocytic recycling
Recycling of endocytic receptors to the cell surface involves passage through a series of membrane-bound compartments by mechanisms that are poorly understood. In particular, it is unknown if endocytic recycling requires the function of multisubunit tethering complexes, as is the case for other intracellular trafficking pathways. Herein we describe a tethering complex named endosome-associated recycling protein (EARP) that is structurally related to the previously described Golgi-associated retrograde protein (GARP) complex. The two complexes share the Ang2, Vps52 and Vps53 subunits, but EARP contains an uncharacterized protein, syndetin, in place of the Vps54 subunit of GARP. This change determines differential localization of EARP to recycling endosomes and GARP to the Golgi complex. EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs. Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. These findings implicate EARP in canonical membrane-fusion events in the process of endocytic recycling.
Bonifacino and colleagues identify a four-protein complex, called the endosome-associated recycling protein (EARP) complex, that associates with Rab4-positive endosomes and promotes recycling-endosome tethering and fusion.
Journal Article