30Qing Mao (Phone +86 135 9418 0020;Abstract: An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 5 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these 10 highly pathogenic coronaviruses. Short Title: SARS-CoV N over-activates complement by MASP-2One Sentence Summary: The lectin pathway of complement activation is a promising target for 15 the treatment of highly pathogenic coronavirus induced pneumonia.All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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ABSTRACT

aazaisowurtzitane (HNIW) and benzotrifuroxan (BTF) has been prepared. The structure of this cocrystal was characterized by single crystal X-ray diffraction (SXRD). Properties of the cocrystal including thermal decomposition and detonation performance were studied. Further, the cocrystal explosive is predicted to display superior detonation power compared to BTF.

Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin.

Energy and safety are the two most important concerns of energetic materials (EMs), while they usually contradict each other: the high energy typically goes together with low safety. Low sensitivity and highly energetic materials (LSHEMs) balance well the energy and safety and thus are highly desired for extensive applications. Nevertheless, on the whole, the energy–safety contradiction, the energy and component limits, and insufficient knowledge about the relationships among components, structures, and properties and performances of EMs have made the development of LSHEMs, or even the entire group of EMs, evolve slowly. This Perspective focuses upon the current progress in the clarifications of the energy–safety contradiction and the crystal packing–impact sensitivity relationship of EMs. Also, we propose strategies for creating new LSHEMs or desensitized EMs through crystal engineering, covering traditional EMs composed of neutral single-component molecules, energetic cocrystals, and energetic ionic salts. Two levels of intrinsic structures, molecule and crystal, are accounted for in constructing LSHEMs: at the molecular level, it is proposed to store much chemical energy in bonds while avoiding any bond formation in an energetic molecule that is too weak to intrinsically balance the energy and safety; at the level of crystal, it is suggested that intermolecular interactions be enhanced to increase packing compactness and energy density and to strengthen the anisotropy of the intermolecular interactions to facilitate ready shear slide and low mechanical sensitivity; and overall, a big π-bonded energetic molecule with an oxygen balance close to zero and a hydrogen bond-aided face-to-face π–π molecular stacking is preferred as a LSHEM. Hopefully, this Perspective will set a root for establishing a systematic theory for creating LSHEMs.

The molecular mechanisms that promote progression of localized prostate cancer to hormone-refractory and disseminated disease are poorly understood. Prolactin (Prl) is a local growth factor produced in high-grade prostate cancer, and exogenously added Prl in tissue or explant cultures of normal and malignant prostate is a strong mitogen and survival factor for prostate epithelium.

Purpose: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in human prostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade human prostate cancers. Here, we investigated whether activation of Stat5 in prostate cancer was linked to clinical outcome with disease recurrence as end point. Experimental Design: Immunohistochemistry was used to detect active, nuclear Stat5 in 357 paraffin-embedded prostate cancer specimens on a tissue microarray with clinical follow-up data. Stat5 activation status in prostate cancer specimens was analyzed by univariate and multivariate survival analysis to determine whether activation of Stat5 predicts earlier prostate cancer recurrence. Separate sets of statistical analysis were done for all patients regardless of Gleason grade and for patients with prostate cancer of intermediate Gleason grades (3 and 4). Results and Conclusions: Stat5 activation in prostate cancer was associated with early disease recurrence (P = 0.0399). Importantly, active Stat5 also predicted shorter progression-free survival in intermediate Gleason grade prostate cancers (P = 0.0409). Stat5 activation remained an independent prognostic marker after adjusting for Gleason grade, pTstage, perineural invasion, or seminal vesicle infiltration in all patients (P = 0.0565) and in Gleason grade 3 or 4 patients (P = 0.0582). The results of this work also confirmed our previous finding of association of Stat5 activation with a high histologic grade of prostate cancer (R = 0.11, P = 0.033). In summary, our study shows that active Stat5 distinguished prostate cancer patients whose disease is likely to progress earlier; therefore, active Stat5 may be a useful marker for selection of more individualized treatment. The results of this study need to be validated in a large prospective cohort.