Key PointsQuestionWhat is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?FindingIn this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.MeaningAmong patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.

21 Background: At present, PCR-based nucleic acid detection cannot meet the demands 22 for coronavirus infectious disease (COVID-19) diagnosis. Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid 27 protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, 28 and their diagnostic feasibility was evaluated.29 Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully 30 diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 31 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, 32 respectively. The positive rates of the rN-based and rS-based ELISAs for antibody 33 (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of 34 the rS-based ELISA for IgM detection was significantly higher than that of the 35 rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with 36 an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM 37 dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG 38 ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of 39 IgM and IgG was obviously increased after 10 d.p.o.40 Conclusions: ELISA has a high sensitivity, especially for the detection of serum 41 samples from patients after 10 d.p.o, it can be an important supplementary method for 42 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from COVID-19 diagnosis.43

21 Background: At present, PCR-based nucleic acid detection cannot meet the demands 22 for coronavirus infectious disease (COVID-19) diagnosis. Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid 27 protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, 28 and their diagnostic feasibility was evaluated. 29 Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully 30 diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 31 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, 32 respectively. The positive rates of the rN-based and rS-based ELISAs for antibody 33 (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of 34 the rS-based ELISA for IgM detection was significantly higher than that of the 35 rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with 36 an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM 37 dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG 38 ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of 39 IgM and IgG was obviously increased after 10 d.p.o.40Conclusions: ELISA has a high sensitivity, especially for the detection of serum

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b-catenin is a multifunctional protein identified to be pivotal in embryonic patterning, organogenesis and adult homeostasis. It plays a critical structural role in mediating cadherin junctions and is also an essential transcriptional co-activator in the canonical Wnt pathway. Evidence has been documented that both the canonical Wnt pathway and cadherin junctions are deregulated or impaired in a plethora of human malignancies. In the light of this, there has been a recent surge in elucidating the mechanisms underlying the etiology of cancer development from the perspective of b-catenin. Here, we focus on the emerging roles of b-catenin in the process of tumorigenesis by discussing novel functions of old players and new proteins, mechanisms identified to mediate or interact with b-catenin and the most recently unraveled clinical implications of b-catenin regulatory pathways toward tumor suppression.Since its identification as an essential and central component in the Wnt signaling cascade, and the subsequent finding of its pivotal role in cadherin-based cell-cell adhesion, b-catenin has been critically studied to elucidate the coordination of these two pathways. The significance of this coordination is substantiated in a plethora of metabolic processes, such as axis and mesoderm formation, stem cell differentiation and carcinogenesis. 1,2 Generally, the Wnt pathway is divided into four branches, namely the canonical Wnt/b-catenin pathway, and the noncanonical (or heretical) Wnt/Ca 2þ and planar cell polarity pathways. Amongst them, the canonical Wnt pathway is the best studied and is reported to be highly conserved through evolution but is frequently altered in many human malignancies such as colorectal cancers, hepatocellular carcinomas and gastric cancers. 3-6 Ca 2þ -dependent cellcell adhesion in the cadherin family of proteins is typified by an extracellular segment that consists of five distinct Ca 2þ -binding domains and a conserved cytoplasmic domain, which interacts with b-catenin and p120 catenin (herein p120); b-catenin then provides a binding site for a-catenin. Cadherin junctions, among other cell-cell adhesion complexes, are essential for cellular processes such as cell polarity and migration. 7,8 Since an indispensible morphological hallmark of malignant tumors is reduced cell-cell adhesiveness, it is predicted that the components of cadherin junctions in many human malignancies, such as breast cancer, colorectal cancer and prostate cancer, are genetically altered. 9-11 Besides cellcell adhesion, cadherin junctions function as a potent competitor of free cytosolic b-catenin. This is supported by studies of the co-crystal structures of b-catenin/cadherin and b-catenin/TCF revealing that the two b-catenin ligands shared overlapping binding regions along b-catenin. 12 The role of the cadherin junction in the subcellular distribution of b-catenin has recently been further extended as discussed below.In this review, a myriad of recently emerged mechanisms governing the signaling and adhesive activity of ...

Regulator of Cullins-1 (ROC1) or RING box protein-1 (RBX1) is an essential RING component of Cullin-RING ligase (CRL). Our previous studies showed that ROC1 is required for the growth of several cancer cell lines while ROC1 siRNA silencing inactivates CRL, leading to cell cycle arrest, cell senescence and/or apoptosis. However, it is completely unknown whether ROC1 knockdown triggers autophagic response by inactivating CRL. Moreover, the role of ROC1 in liver cancer remains elusive. In this study, we reported that ROC1 knockdown significantly inhibited the growth of liver cancer cells by sequentially and independently inducing autophagy and p21-dependent cell senescence. Mechanism analysis revealed that ROC1 silencing triggered autophagy by inhibition of mammalian target of rapamycin (mTOR) activity due to accumulation of mTOR-inhibitory protein Deptor, a substrate of CRL. Consistently, Deptor knockdown significantly blocked autophagy response upon ROC1 silencing. Biologically, autophagy response upon ROC1 silencing was a survival signal, and blockage of autophagy pathway sensitized cancer cells to apoptosis. Finally, we demonstrated that ROC1 was overexpressed in hepatocellular carcinomas, which is associated with poor prognosis of liver cancer patients. These findings suggest that ROC1 is an appealing drug target for liver cancer and provide a proof-of-concept evidence for a novel drug combination of ROC1 inhibitor and an autophagy inhibitor for effective treatment of liver cancer by enhancing apoptosis.

30Background The outbreak of the recently emerged novel corona virus disease 2019

This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18–59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15–28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.