Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12-18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students' awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19.

Tumor development is characterized by an initial phase of rapid expansion, followed by a period of slowed growth as the proliferating malignant cells outstrip the local supply of oxygen and nutrients. In the absence of a dedicated blood supply, early-stage tumors attain steady-state volumes of only a few cubic millimeters, at which time the rate of cell death, due to oxygen and nutrient depletion, equals the rate of cell division (19). To resume growth, these microtumors must adapt to hypoxic stress through alterations in cellular metabolism and the stimulation of neovascularization, which provides the additional blood needed to sustain cellular proliferation. Accordingly, cellular adaptation to growth during hypoxic stress contributes to malignant progression and is correlated with a poor clinical outcome in several types of cancer (3, 4, 18). Two hallmark features of hypoxic adaptation are increased rates of anaerobic glycolysis and the secretion of proangiogenic factors, such as vascular endothelial growth factors (VEGFs) (28, 39). The molecular mechanisms that underlie cellular responses to hypoxic stress are therefore of considerable relevance to cancer biology and therapy.A key regulator of the cellular response to oxygen deprivation is the transcription factor, hypoxia-inducible factor 1 (HIF-1). Originally identified as an oxygen-responsive activator of erythropoietin gene transcription, HIF-1 is now known to play a central role in the maintenance of oxygen homeostasis in virtually all bodily tissues (42, 43). The predominant form of HIF-1 is a heterodimer consisting of HIF-1␣ and HIF-1␤ subunits, both of which are members of the basic helix-loop-helix family of transcription factors. Although HIF-1␤ is a constitutively expressed nuclear protein, the expression of the HIF-1␣ subunit is tightly coupled to the ambient oxygen tension. Under normoxic conditions, the HIF-1␣ gene is continuously transcribed and translated; however, the HIF-1␣ protein is expressed at very low levels due to rapid destruction via the ubiquitin-proteasome pathway. In addition to its DNA-binding and transactivating motifs, HIF-1␣ contains a stretch of ca. 200 amino acids, termed the oxygen-dependent degradation (ODD) domain. As its name implies, the ODD domain mediates the interaction between HIF-1␣ and the E3 ubiquitin ligase complex that mediates continuous poly ubiquitination of HIF-1␣ in normoxic cells.The oxygen-dependent turnover of HIF-1␣ is governed by a novel family of prolyl 4-hydroxylases (PHDs) that specifically modify HIF-1␣ at two conserved proline residues (Pro-402 and Pro-564), both located in the ODD domain (5,15,27,41). Prolyl hydroxylation triggers the recognition of HIF-1␣ by the product of the VHL tumor suppressor gene, which serves as the targeting subunit of an E3 ubiquitin ligase complex (20). Although the exact mechanism remains unclear, a decrease in ambient oxygen tension leads to a correlative decrease in HIF-1␣ prolyl hydroxylation, which in turn leads to decreased rates of HIF-1␣ polyubiquitination and...

Background 24The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public 25 health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to 26 correlate with recovery and protection of this disease. However, the characteristics of 27 these antibodies have not been well studied in association with the clinical 28 manifestations in patients. 30 Methods 31Plasma collected from 175 COVID-19 recovered patients with mild symptoms were 32 screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization 33 assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, 34 and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-35 specific NAbs and the spike-binding antibodies were monitored at the same time. 36 37 Findings 38 SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-39 2-specific NAbs were detected in patients from day 10-15 after the onset of the disease 40 and remained thereafter. The titers of NAb among these patients correlated with the 41 spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were 42 variable in different patients. Elderly and middle-age patients had significantly higher 43 plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young 44 patients. Notably, among these patients, there were ten patients whose NAb titers were 45 under the detectable level of our assay (ID50: < 40); while in contrast, two patients, 46 showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb 47 titers were positive correlated with plasma CRP levels but negative correlated with the 48 lymphocyte counts of patients at the time of admission, indicating an association 49 between humoral response and cellular immune response.50 51 Interpretation 52The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may 53 raise the concern about the role of NAbs on disease progression. The correlation of 54 NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the 55 interplay between virus and host immune response in coronavirus infections should be 56 further explored for the development of effective vaccine against SARS-CoV-2 virus. 57 Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for 58 prevention or treatment. Sciences 64 65 66 67 All rights reserved. No reuse allowed without permission.

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website.

To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment. MethodsWe conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC[n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinicalpathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. ConclusionRCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.

The outbreak of 2019 novel coronavirus (COVID-19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found

BackgroundHPV is important in a subset of HNSCC. Our meta-analysis determined the clinical characteristics of HPV-related HNSCC.MethodPubmed search terms "HPV" and "HNSCC" were used to identify 34 studies since 1980. We obtained pooled adjusted odds ratio (OR) or hazard ratio (HR) using random or fixed-effects model and compared OS depicted in forest plot.ResultsA total of 5681 patients were included. The prevalence of HPV+ tumors was 22%, with 86.7% of HPV16+ genotype. The OR for HNSCC in HPV16+ patients was 4.44 (95% CI = 2.87-6.02). HPV status was associated with p16 expression (adj OR = 3.00; 0.90-9.70), and HPV+ tumors were less likely to harbor p53 mutations (adj OR = 0.21; 0.04-0.38). The HR for death in HPV+ patients was 0.42 (0.27-0.57). HPV+ HNSCC also had a better response to therapy.ConclusionHPV+ HNSCC are established as a separate biologic entity. Prospective trials are needed to establish the optimal therapy for HPV+ HNSCC.