Aims and Objectives To determine the health‐related quality of life (HRQoL) of COVID‐19 patients after discharge and its predicting factors. Background COVID‐19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID‐19 patients are impaired, but the studies focus on physical and psychological conditions of COVID‐19 patients after discharge from hospital are rare. Design A multicentre follow‐up study. Methods This was a multicentre follow‐up study of COVID‐19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow‐up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. Results Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID‐19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm ( p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04–3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33–4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68–166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21–10.59) was a risk factor for poor mental component summary. Conclusions Health‐related quality of life of discharged COVID‐19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge. Relevance to clinical practice Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID‐19 patients. Long‐term follow‐up on COVID‐19 patients after discharge is needed to determine the long‐term impact of COVID‐19.

The segmentation motor activity of the gut that facilitates absorption of nutrients, was first described in the late 19th century but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by ICC associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in ICC.

This study pertains to whether and how employees' organizational citizenship behaviors toward customers (OCB-C) influence customers' citizenship behaviors (CCB) directed toward the firm, employees, and other customers. Drawing on a social exchange perspective, this study proposes that a dual identification mechanism-spanning customer-employee identification (C-EI) and customer-firm identification (C-FI)-mediates the social exchange relationship between OCB-C and CCB. Service climate as a key contextual factor moderates the mediating mechanisms of identification. With data collected from a field survey and an experiment, the findings confirm that the dual identification mechanism mediates the effect of OCB-C on customers' reciprocation with CCB. The results also reveal a moderating effect of service climate, such that the positive effect of OCB-C on C-EI and C-FI grows stronger when the service climate is at low and high levels, respectively. In addition, the empirical results demonstrate that the underlying motive attribution explains the moderating effect of service climate. This work paints a more nuanced picture of the missing link in the OCB-C-CCB interface, by identifying a mediating mechanism and boundary condition. To promote CCB, managers should leverage their employees' OCB-C, as well as their firms' service climate.

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Lactate dehydrogenase B (LDHB) is a glycolytic enzyme that catalyses the conversion of lactate and NAD + to pyruvate, NADH and H+. Protons (H+) generated by LDHB promote lysosomal acidification and autophagy in cancer, but how this role is regulated has not been defined. In this study, we identified an important post‐translational mechanism by which LDHB is regulated during autophagy in cancer cells. Mass spectrometry revealed that protein sirtuin 5 (SIRT5) is a binding partner of LDHB that deacetylated LDHB at lysine‐329, thereby promoting its enzymatic activity. Deacetylated LDHB increased autophagy and accelerated the growth of colorectal cancer (CRC) cells. Notably, SIRT5 knockout or inhibition by GW5074 increased LDHB acetylation at K329 and inhibited LDHB activity, which downregulated autophagy and CRC cell growth in vitro and in vivo. Clinically, the LDHB‐Ac‐K329 staining score in CRC tissues was lower than that in corresponding peritumour tissues. Low LDHB‐Ac‐K329 status was associated with malignant progression of human CRC and served as a potential prognostic indicator for patients with CRC. Altogether, we conclude that SIRT5‐induced deacetylation of LDHB triggers hyperactivation of autophagy, a key event in tumorigenesis. Thus, the SIRT5/LDHB pathway may represent a novel target for treating CRC.

ZnO nanostructures were electrochemically deposited on the surfaces of carbon nanotubes (CNTs) supported on a Zn foil cathode, leading to the facile formation of ZnO/CNT composites with uniform mixing, high dispersion and high-quality interfaces. The electrochemical deposition method circumvents the need for bridging molecules to bring together the two phases and has the key advantage of controllability. By increasing the deposition time, the individual CNTs were first fully covered with ZnO and then the morphology of the deposited ZnO nanostructures was gradually changed from spherical nanoparticles to lily-like nanoflowers. The lily-like structures of ZnO/CNT nanocomposites showed enhanced electrochemiluminescence (ECL). Significantly, the ECL intensity of the lily-like structure of ZnO/CNT nanocomposites was almost an order of magnitude larger than that of pure ZnO nanoflowers, and the ECL starting voltage shifts positively from À1.06 to À0.41 V. These have been attributed to the presence of CNTs which decrease the barriers of ZnO reduction during the ECL process and the special structure of ZnO on the surface of CNTs as well. This work has demonstrated a new strategy to directly coat CNTs with oxides, probably many other inorganic materials, with tunable coverage and nanostructure. Furthermore, the significantly enhanced ECL of ZnO by interfacing with the CNTs highlights the importance and potential utility of such nanostructuring in the development of optoelectronic and biomedical devices.

BACKGROUNDSevere combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency. METHODSWe treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up. RESULTSOverall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade. CONCLUSIONSTreatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.

Upon hypoxia, the human erythropoietin (EPO) gene is transactivated by the heterodimeric hypoxia-inducible factor 1 (HIF-1). Mammalian SWI/SNF is a chromatin-remodeling complex involved in the modulation of gene expression. We demonstrate that Brahma (Brm) and Brahma/SWI2-related gene 1 (Brg-1), alternative ATPase subunits of SWI/SNF, potentiate reporter gene activation mediated by HIF-1 in an ATPase-dependent manner. Brm was more potent than Brg-1 in the reporter gene assays. Simultaneous depletion of both Brm and Brg-1 by small interfering RNAs significantly compromised the transcription of the endogenous EPO gene triggered by hypoxia. Whereas knocking down Brm alone resulted in a moderate reduction in transcription of the EPO gene, depletion of Brg-1 resulted in an augmentation of transcription of both the EPO gene and the Brm gene, indicating that Brm can compensate for loss of Brg-1. Chromatin immunoprecipitation (ChIP) and sequential ChIP (re-ChIP) analysis showed that both Brm and Brg-1 associate with the enhancer region of the EPO gene in vivo in a hypoxia-dependent fashion and that each is present in a complex with HIF-1. Brm and Brg-1 were also recruited to the promoter of the vascular endothelial growth factor (VEGF) gene in a hypoxiadependent fashion, although hypoxic induction of VEGF transcription was not affected by depletions of either or both Brm and Brg-1. Together these studies reveal a novel role for SWI/SNF in the activation of transcription of the EPO gene, indicate an important communication and compensation between Brm and Brg-1, and suggest that the requirement for SWI/SNF during hypoxic induction is gene-specific.Tissue oxygen concentration is an important regulatory stimulus for many physiological and pathological processes (1). Adaptation to hypoxia depends in part on appropriate alterations in the expression of a number of physiologically relevant genes. Induction of the erythropoietin (EPO) 1 gene by hypoxia is central to the regulation of the oxygen-carrying capacity of the blood (2). Hypoxic induction of genes encoding angiogenic growth factors such as the vascular endothelial growth factor (VEGF) leads to new blood vessel formation during development, wound repair, and tumor growth (3-5). Most if not all mammalian cell types share a common mechanism of oxygen sensing and signal transduction (6), enabling hypoxia-induced activation of the transcription factor hypoxia-inducible factor 1 (HIF-1) composed of HIF-1␣ and Arnt (7). The HIF-1␣ subunit is regulated by hypoxia both at the level of transactivation and protein stability (8 -11).In general, gene expression is not determined by the simple additive influences of individual transcription factor binding sites. Adjacent sites interact with each other to produce effects that range from repressive to highly synergistic. Multiprotein complexes involving transcription factors, coactivator proteins, and other proteins are thought to integrate signals and create the specificity and control required for the precise regulation of gene tra...