Inositol Alleviates Pulmonary Fibrosis by Promoting Autophagy via Inhibiting the HIF-1α-SLUG Axis in Acute Respiratory Distress Syndrome.

The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

[Expression of a SARS-CoV-2 neutralizing nanobody in Trichoderma reesei].

Nanobodies derived from camelid single-chain antibodies have the advantages of being small, simple, highly soluble and stable. Nanobodies can be administered by inhalation and therefore is potentially valuable for the prevention and control of respiratory viruses. Trichoderma reesei is a food-grade protein expression host with a cellulase production capacity of up to 80 g/L, which can be employed for low-cost production of therapeutic proteins. In this study, a codon-optimized SARS-CoV-2 neutralizing nanobody Nb20 was expressed in T. reesei under a strong constitutive promoter Pcdna1. Nb20 protein was fused downstream of the N-terminal fragment of cellobiohydrolase Ⅰ, and the fusion protein can be intracellularly cleaved by the KEX2 protease to release Nb20. In a shake-flask fermentation using glucose medium, 47.4 mg/L Nb20 was detected in the culture after 48 h of cultivation. The expressed Nb20 showed the ability to interact with the receptor-binding domain of SARS-CoV-2 spike protein, suggesting that it can be used for the neutralization of SARS-CoV-2. The results indicate that T. reesei has the potential for recombinant production of nanobodies.

Navigating Through Uncertainty in the Era of COVID-19: Experiences of International Graduate Students in the United States

With the spread of COVID-19 around the world, the lives of international students became affected by a sudden shift to online learning, sheltering in place, and travel restrictions. Drawing upon the stress and coping framework, this study explores the experiences and coping of international graduate students at a large Western research university in the United States. We employed a phenomenological inquiry of in-depth interviews with 20 participants. Findings reveal increased levels of stress and anxiety among participants as they faced academic challenges, personal challenges, and immigration-related uncertainties. Over time, students developed emotion-focused and problem-focused coping strategies to minimize the impact of the pandemic on their lives. Participants' concerns about the host country's treatment of international students raise important questions about the future of international student mobility. Finally, this study demonstrates the need for host institutions to develop emergency responding mechanisms.

Vaccine design based on 16 epitopes of SARS-CoV-2 spike protein.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently requires an effective vaccine for prevention. In this study, 66 epitopes containing pentapeptides of SARS-CoV-2 spike protein in the IEDB database were compared with the amino acid sequence of SARS-CoV-2 spike protein, and 66 potentially immune-related peptides of SARS-CoV-2 spike protein were obtained. Based on the single-nucleotide polymorphisms analysis of spike protein of 1218 SARS-CoV-2 isolates, 52 easily mutated sites were identified and used for vaccine epitope screening. The best vaccine candidate epitopes in the 66 peptides of SARS-CoV-2 spike protein were screened out through mutation and immunoinformatics analysis. The best candidate epitopes were connected by different linkers in silico to obtain vaccine candidate sequences. The results showed that 16 epitopes were relatively conservative, immunological, nontoxic, and nonallergenic, could induce the secretion of cytokines, and were more likely to be exposed on the surface of the spike protein. They were both B- and T-cell epitopes, and could recognize a certain number of HLA molecules and had high coverage rates in different populations. Moreover, epitopes 897-913 were predicted to have possible cross-immunoprotection for SARS-CoV and SARS-CoV-2. The results of vaccine candidate sequences screening suggested that sequences (without linker, with linker GGGSGGG, EAAAK, GPGPG, and KK, respectively) were the best. The proteins translated by these sequences were relatively stable, with a high antigenic index and good biological activity. Our study provided vaccine candidate epitopes and sequences for the research of the SARS-CoV-2 vaccine.