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The brittle adhesive layer in carbon fiber-reinforced polymer (CFRP) laminates was strengthened by using short aramid fibers in this study. To ensure the feasibility and effectiveness of short aramid fiber interfacial toughening at the interface between the carbon-fiber face sheets, the self-prepared short aramid fibre tissue and the wettability treatment technology with resin pre-coating were applied to enable short aramid fibres to be well embedded in the uneven regions in the CFRP fabrics with fibres oriented at 0° and 90° to form a strong pulling resistance. The ultimate load and the mode I interlaminar fracture toughness have been improved by 75% and 103.9% from the double cantilever beam mode I crack propagation tests, respectively. The reinforcing mechanisms within the “composite adhesive layer” as a result of short aramid fibres are discussed together with detailed scanning electron microscopy observations and comparison test results.

This paper aims to report the conceptualization of a web-based Automated Speech Recognition Scoring System, project MELVA-S (Measuring the English Language Vocabulary Acquisition of Latinx Bilingual Students), to measure the science vocabulary of second- and third-grade Latinx students. ELVA (English Learner Vocabulary Acquisition First Iteration) and ELVA-2 (English Learner Vocabulary Acquisition Second Iteration) focused on student’s learning and comprehension on science vocabularies. Both of the iterations are the foundation to build MELVA-S, which intends to measure and evaluate student’s answers with greater accuracy with Machine Learning. As a web-based agent, this system increases satisfaction for both teachers’ and students’ User Experience (UX) from content, design, and engineering perspectives. The project utilized a design-thinking approach and prototyped both the algorithm and the automated system interfaces. Future iterations of ELVA-2 and MELVA-S could consider adopting a Human-Centered Machine Learning approach, implemented with incremental improvements that include evaluation and testing with users, to keep enhancing both usability and functionality of the system for better UX.

The interaction of the solo H3K79 methyltransferase DOT1-like (DOT1L) and its regulatory factor ALL1-fused gene from chromosome 10 protein (AF10) is crucial for the transcription of developmental genes such as HOXA in acute leukemia. The octapeptide motif and leucine zipper region of AF10 is responsible for binding DOT1L and catalyzing H3K79 monomethylation to demethylation. However, the characteristics of the mechanism between DOT1L and AF10 are not clear. Here, we present the crystal structures of coiled-coil regions of DOT1L-AF10 and AF10-inhibitory peptide, demonstrating the inhibitory peptide could form a compact complex with AF10 via a different recognition pattern. Furthermore, an inhibitory peptide with structure-based optimization is identified and decreases the HOXA gene expression in a human cell line. Our studies provide an innovative pharmacologic basis for therapeutic intervention in leukemia.

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14+ monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14+ monocytes ex vivo triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19., Graphical abstract, Immunology; Virology

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigen’s allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification.One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.

Dysregulated immune cell responses have been linked to the severity of Coronavirus Disease 2019 (COVID-19). However, the specific viral factor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributing to the immune-dysregulation is currently unclear. Herein, we identified the ectodomain of Ig-like fold viral proteinSARS-CoV-2 Orf7a interacted with CD14+ monocytes at the highest efficiency in human peripheral blood mononuclear cells, but not for the relative highly pathogenic protein SARS-CoV Orf7a. The 2.2 A resolutioncrystal structure of SARS-CoV-2 Orf7a reveals three remarkable changes in the amphipathic side of the four-strand β-sheet, implying the potential functional interface of the viral protein. Structure-based superimposition of SARS-CoV-2 Orf7a with SARS-CoV Orf7a - LFA1 working model suggests that SARS-CoV-2 Orf7a utilizes different binding patterns to recognize the specific immune cells. Importantly, SARS-CoV-2 Orf7a co-incubation with CD14+ monocytes ex vivo triggers a decrease of HLA-DR/DP/DQ and significant pro-inflammatory cytokines expressions, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 Orf7a is an immunomodulating factor for immune cells binding and trigging aberrant inflammatory responses, providing promising therapeutic drug targets in the pandemic disease COVID-19. Funding: This work is supported by the National Key RD the Special Fund for Scientific and Technological Innovation Strategy of Guangdong Province of China (2018B030306029), COVID-19 Emerging Prevention Products, Research Special Fund of Zhuhai City (ZH22036302200016PWC) granted to S.C.; the Fundamental Research Funds for the Central Universities (19ykzd36) granted to J.C; and the Science and Technology Program of Guangzhou (202002030069) granted to J.C. Conflict of Interest: The authors declare no conflict of interest. Ethical Approval: The human peripheral blood samples for the experiments were collected through The Health Management Center, The Fifth Affiliated Hospital, Sun Yat-sen University. This study was approved by The Medical Ethics Committee of The Fifth Affiliated Hospital, Sun Yat-sen University (2020-K195-1).

The natural phytoalexin resveratrol (RES) has exhibited excellent anti-tumor effects on a variety of tumors including malignant melanoma. However, its specific mechanism of anti-melanoma needs to be further explored. It has been reported, that the expression of tumor suppressor gene RUNX3 was lost or substantially decreased in melanoma. Whether RES exerts its anti-tumor effect by regulating the expression of RUNX3 gene in melanoma is worthy of study. In the present study, we found the RUNX3 promoter is hypermethylated and the expression of RUNX3 mRNA and protein are absent in melanoma cells B16F10. After intervention with RES, promoter hypermethylation of RUNX3 in B16F10 cells could be significantly decreased and mRNA and protein expression of it was upregulated in a dose-dependent manner. We further investigated the effects of RES on B16F10 xenograft models. The intervention of RES and treatment of melanoma positive drug dacarbazine (DTIC) both could significantly inhibit tumor growth in xenograft mice, but only RES could upregulate the expression of RUNX3 mRNA and protein in peripheral blood and tumor tissues. Therefore, the upregulation of mRNA and protein expression of RUNX3 resulting from promoter demethylation might be one of the mechanisms of RES inhibiting melanoma. This research has revealed a novel mechanism for RES against melanoma from the epigenetic perspective, which is helpful to improve the understanding of the anti-tumor mechanism of RES and provide new insights for the treatment of melanoma.