Despite the high specificity between antigen and antibody binding, similar epitopes can be recognized or cross-neutralized by paratopes of antibody with different binding affinities. How to accurately characterize this slight variation which may or may not change the antigen-antibody binding affinity is a key issue in this area. In this report, by combining cylinder model with shell structure model, a new fingerprint was introduced to describe both the structural and physical-chemical features of the antigen and antibody protein. Furthermore, beside the description of individual protein, the specific epitope-paratope interaction fingerprint (EPIF) was developed to reflect the bond and the environment of the antigen-antibody interface. Finally, Proteochemometric Modeling of the antigen-antibody interaction was established and evaluated on 429 antigen-antibody complexes. By using only protein descriptors, our model achieved the best performance ( R2=0.91, Q test 2 =0.68 ) among peers. Further, together with EPIF as a new cross-term, our model ( R2=0.92, Q test 2 =0.74 ) can significantly outperform peers with multiplication of ligand and protein descriptors as a cross-term ( R2≤0.81, Q test 2 ≤0.44 ). Results illustrated that: 1) our newly designed protein fingerprints and EPIF can better describe the antigen-antibody interaction; 2) EPIF is a better and specific cross-term in Proteochemometric Modeling for antigen-antibody interaction. The fingerprints designed in this study will provide assistance to the description of antigen-antibody binding, and in future, it may be valuable help for the high-throughput antibody screening. The algorithm is freely available on request.
ABSTRACT China is among the top nitrous oxide (N2O)-emitting countries, but existing national inventories do not provide full-scale emissions including both natural and anthropogenic sources. We conducted a four-decade (1980–2020) of comprehensive quantification of Chinese N2O inventory using empirical emission factor method for anthropogenic sources and two up-to-date process-based models for natural sources. Total N2O emissions peaked at 2287.4 (1774.8–2799.9) Gg N2O yr−1 in 2018, and agriculture-developed regions, like the East, Northeast, and Central, were the top N2O-emitting regions. Agricultural N2O emissions have started to decrease after 2016 due to the decline of nitrogen fertilization applications, while, industrial and energetic sources have been dramatically increasing after 2005. N2O emissions from agriculture, industry, energy, and waste represented 49.3%, 26.4%, 17.5%, and 6.7% of the anthropogenic emissions in 2020, respectively, which revealed that it is imperative to prioritize N2O emission mitigation in agriculture, industry, and energy. Natural N2O sources, dominated by forests, have been steadily growing from 317.3 (290.3–344.1) Gg N2O yr−1 in 1980 to 376.2 (335.5–407.2) Gg N2O yr−1 in 2020. Our study produces a Full-scale Annual N2O dataset in China (FAN2020), providing emergent counting to refine the current national N2O inventories.
Abstract Suicide is increasingly recognized as a major public health concern among migrant workers in China. Despite negative mental and negative coping styles being core themes found in suicide notes, there is scarce research addressing the theoretical framework of underlying mechanisms between these variables. The study was designed to examine the relationships of negative mental, negative coping styles, and suicide risk among migrant workers. It hypothesized that negative mental would exert a positive effect on suicide risk via increased negative coping. Using a cross-sectional design, the study was conducted using a sample of 3095 migrant workers from Shenzhen, China. Self-made Suicide Risk Scale (SRS), Short-form of the ULCA Loneliness Scale (USL-6), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7), Simplified Coping Style Questionnaire (SCSQ) were used to collect data. Structural equation modeling (SEM) was performed to quantitatively explore the path effects between negative mental, negative coping styles and suicide risk. Results showed that negative coping style had a positive association with suicide risk (β = 0.029, P < 0.001). Negative mental had both direct and indirect positive effects on suicide risk through negative coping styles (β = 0.109, β = 0.013, P < 0.001). Therefore, to prevent suicidal behaviors among migrant workers, targeted interventions focusing on improving their mental health and coping strategies are needed.
Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.
Abstract BIRC5 is an immune-related gene that inhibits apoptosis and promotes cell proliferation. It is highly expressed in most tumors and leads to poor prognosis in cancer patients. This study aimed to analyze the relationship between the expression level of BIRC5 in different tumors and patient prognosis, clinical parameters, and its role in tumor immunity. Genes co-expressed with BIRC5 were analyzed, and functional enrichment analysis was performed. The relationship between BIRC5 expression and the immune and stromal scores of tumors in pan-cancer patients and the infiltration level of 22 tumor-infiltrating lymphocytes (TILs) was analyzed. The correlation of BIRC5 with immune checkpoints was conducted. Functional enrichment analysis showed that genes co-expressed with BIRC5 were significantly associated with the mitotic cell cycle, APC/C-mediated degradation of cell cycle proteins, mitotic metaphase, and anaphase pathways. Besides, the high expression of BIRC5 was significantly correlated with the expression levels of various DNA methyltransferases, indicating that BIRC5 regulates DNA methylation. We also found that BIRC5 was significantly correlated with multiple immune cells infiltrates in a variety of tumors. This study lays the foundation for future research on how BIRC5 modulates tumor immune cells, which may lead to the development of more effective targeted tumor immunotherapies.
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