Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 . In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10 9 /L vs. 0.76 × 10 9 /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

No abstract

Background A pandemic is a very stressful event, especially for highly vulnerable people (e.g., older adults). The purpose of the current study was to investigate the main and interactive relationships of social support and resilience on individual mental health during the COVID-19 pandemic across three age groups: emerging adults, adults, and older adults. Methods A survey was conducted with 23,192 participants aged 18–85. Respondents completed a questionnaire, including items on the COVID-19-related support they perceived from different sources, the abbreviated version of the Connor-Davidson Resilience Scale, and the Mental Health Inventory. Results Latent profile analysis identified five profiles of social support, and the patterns of potential profiles were similar in all groups. However, category distribution in the five profiles was significantly different among the age groups. Furthermore, analysis using the BCH command showed significant differences in mental health among these profiles. Lastly, interactive analyses indicated resilience had a positive relationship with mental health, and social support served as a buffer against the negative impact of low resilience on mental health. Conclusions This study provides quantitative evidence for socioemotional selectivity theory (SST) and enables several practical implications for helping different age groups protecting mental health during pandemic.

No abstract

SUMMARY To identify therapeutic targets for Glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 "knockout" (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers). In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit Cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, likely as a result of oncogenic signaling, causing GBM-specific lethality.

Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease . In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65×10 9 /L vs. 0.76×10 9 /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials. Significance StatementCOVID-19is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explored the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was welltolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 days. Radiological examination All rights reserved. No reuse allowed without permission.

To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These screens identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, as compared with untransformed neural stem cells (NSCs) and fibroblasts. Given PHF5A's known involvement in facilitating interactions between the U2 snRNP complex and ATP-dependent helicases, we examined cancerspecific roles in RNA splicing. We found that in GSCs, but not untransformed controls, PHF5A facilitates recognition of exons with unusual C-rich 39 splice sites in thousands of essential genes. PHF5A knockdown in GSCs, but not untransformed NSCs, astrocytes, or fibroblasts, inhibited splicing of these genes, leading to cell cycle arrest and loss of viability. Notably, pharmacologic inhibition of U2 snRNP activity phenocopied PHF5A knockdown in GSCs and also in NSCs or fibroblasts overexpressing MYC. Furthermore, PHF5A inhibition compromised GSC tumor formation in vivo and inhibited growth of established GBM patient-derived xenograft tumors. Our results demonstrate a novel viability requirement for PHF5A to maintain proper exon recognition in brain tumor-initiating cells and may provide new inroads for novel anti-GBM therapeutic strategies.

Targeted protein degradation is a promising area in the discovery and development of innovative therapeutics. Molecular glues mediate proximity-induced protein degradation and have intrinsic advantages over heterobifunctional proteolysis-targeting chimeras, including unprecedented mechanisms, distinct biological activities, and favorable physicochemical properties. Classical molecular glue degraders have been identified serendipitously, but rational discovery and design strategies are emerging rapidly. In this review, we aim to highlight the recent advances in molecular glues for targeted protein degradation and discuss the challenges in developing molecular glues into therapeutic agents. In particular, discovery strategies, action mechanisms, and representative case studies will be addressed.