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Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches and validate epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induce antibody production, six of these are immunodominant epitopes in individuals, and 23 are conserved within SARS-CoV-2, SARS-CoV, and bat coronavirus RaTG13. We find that the immunodominant epitopes of individuals with domestic (China) SARS-CoV-2 are different from those of individuals with imported (Europe) SARS-CoV-2, which may be caused by mutations on the S (G614D) and N proteins. Importantly, we find several epitopes on the S protein that elicit neutralizing antibodies against D614 and G614 SARS-CoV-2, which can contribute to vaccine design against coronaviruses., Graphical Abstract, Highlights • B cell epitopes of SARS-CoV-2 are obtained using structure-based approaches • The predicted epitopes effectively induce robust antibody responses • D614 and G614 SARS-CoV-2 display different immunodominant epitopes • Epitopes on S protein elicit D614 and/or G614 SARS-CoV-2-neutralizing antibodies, Lu et al. predict and validate B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches. The immunodominant epitopes vary between D614 and G614 SARS-CoV-2. The epitopes on the S protein elicit neutralizing antibodies against D614 and G614 SARS-CoV-2.

Background Accurately diagnosing pleural effusion is a frequent and significant problem in clinical practice. Combining pleural biomarkers with patients’ age may be a valuable method for diagnosing TPE. We sought to evaluate the influence of age on diagnostic values of pleural adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) for tuberculous pleural effusion (TPE). Methods Two hundred seventy-four consecutive adult patients with pleural effusion were selected from Beijing and Wuhan between January 1, 2014 and June 30, 2015, and their pleural fluid concentrations of ADA, IFN-γ, and IL-27 were tested. Biomarker performance was analyzed by standard receiver operating characteristic (ROC) curves according to different ages. Results Data from the Beijing cohort showed that ADA, IFN-γ, and IL-27 could all accurately diagnose TPE in young patients (≤ 40 years of age). With a cutoff of 21.4 U/L, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ADA for diagnosing TPE were 1.000 (95% confidence interval: 0.884–1.000), 100.0, 100.0%, 100.0, and 100.0, respectively. In older patients (> 40 years of age), IL-27 and IFN-γ were excellent biomarkers for discriminating TPE versus non-TPE cases. With a cutoff of 591.4 ng/L, the AUC, sensitivity, specificity, PPV, and NPV of IL-27 for diagnosing TPE were 0.976 (95% confidence interval: 0.932–0.995), 96.3, 99.0%, 96.3, and 99.0, respectively. Similar diagnostic accuracy among the three pleural biomarkers was validated in the Wuhan cohort. Conclusions Among young patients, ADA is reliable for diagnosing TPE. Conversely, in older patients, IL-27 and IFN-γ are excellent biomarkers to differentiate TPE versus non-TPE cases.

Supplemental material, Reviewer_2_v.2 for Prognosis of combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis alone by Chun-guo Jiang, Qiang Fu and Chun-ming Zheng in Therapeutic Advances in Respiratory Disease

Supplemental material, Author_Response_1 for Prognosis of combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis alone by Chun-guo Jiang, Qiang Fu and Chun-ming Zheng in Therapeutic Advances in Respiratory Disease

Activation of cannabinoid receptor type 2 has been shown to have anti-fibrosis function in skin and heart. However, whether activating cannabinoid receptor type 2 inhibits pulmonary fibrosis remains elusive. Lung fibroblasts and TGF-β1 are key players in the pathogenesis of pulmonary fibrosis. In this research, we aimed to investigate the role of cannabinoid receptor type 2 in pulmonary fibrosis in vitro and in vivo. In lung fibroblasts stimulated by TGF-β1, preincubated by cannabinoid receptor type 2 agonist JWH133 not only reduced the elevated levels of collagen I and α-SMA, but also inhibited fibroblasts' proliferation and migration. The dosage of JWH133 had no clear cytotoxic activity, and all these JWH133 effects were partially abrogated by cannabinoid receptor type 2 antagonist SR144528. In bleomycin-induced mice pulmonary fibrosis model, CT images of the lung tissue revealed an extensive ground-glass opacity, reticular pattern and fibrosis stranding. Notably, JWH133 treatment controlled the ongoing fibrotic process (showed by decreased lung density and fibrosis score). Meanwhile, lung histological results revealed that JWH133 treatment suppressed both the inflammatory response and extracellular collagen deposition. SR144528 may increase the pulmonary fibrosis, but no statistically significant difference was proved. Importantly, JWH133 reduced serum profibrotic cytokines levels of TGF-β1 and inhibited TGF-β1/Smad2 pathway in vitro and in vivo. Our research indicated that activating cannabinoid receptor type 2 by a pharmacological method might be a potential strategy for pulmonary fibrosis.

In this study, a new series of bis-benzimidazole derivatives were designed and synthesized. Most of these new compounds showed significant anti-tumor activity in vitro compared to Hoechst 33258. Among them, the most potent compound 8 had the IC(50) values of 0.56μM for HL60 (Human promyelocytic leukemia cells) tumor cell line and 0.58μM for U937 (Human leukemic monocyte lymphoma cells) tumor cell line. Subsequent toxicity study on human peripheral blood mononuclear cells (PBMC) showed that compound 8 exhibited less toxicity than 5-FU. We also found that apoptosis and autophagy were simultaneously induced by compound 8 in HL60 cells, and inhibition of autophagy by 3-MA decreased compound 8-induced apoptosis, indicating that they acted in synergy to exert tumor cell death.

To study the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for bleomycin-induced pulmonary fibrosis in mice.UC-MSCs were isolated from the umbilical cord after parental consent. One hundred C57BL/6 mice were randomly divided into 4 groups (12 of these for preliminary experiment). Mice in the control group (n = 20) were instilled with PBS via trachea and NS was injected via the tail vein after 3 days. Mice in the stem cell group (n = 20) were instilled with PBS via trachea and were injected with MSC via the tail vein after 3 days. Mice in the bleomycin group (n = 24) were instilled with bleomycin via trachea and NS was injected via the tail vein after 3 days. Mice in the bleomycin plus stem cell group (n = 24) were instilled with bleomycin via trachea and were injected with MSCs via the tail vein after 3 days. All of the mice were sacrificed at the 21(th) day, and the lungs were immediately fixed with 4% paraformaldehyde for 48 h, embedded in paraffin and sectioned at 5 µmol/L thickness. The sections were stained with hematoxylin and eosin (HE) and Masson-trichrome. Histopathological scoring of pulmonary fibrosis was performed according to Ashcroft's method. The concentrations of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-1were determined using immunohistochemistry.Compared with the bleomycin group, MSC transplantation significantly reduced pulmonary inflammation, fibrosis and deposition of collagen in the bleomycin plus stem cell group [(1.55 ± 0.51) vs (2.16 ± 0.77), and (1.45 ± 0.60) vs (2.32 ± 0.82), respectively, P0.05]. There was no difference between the control group and the stem cell group [(0.35 ± 0.49) vs (0.37 ± 0.50), P0.05]. The expression of MMP-2 in the bleomycin plus stem cell group was lower than the bleomycin group [(1.59 ± 0.59) vs (2.37 ± 0.68), P0.05], but there was no difference between the control group and the stem cell group [(0.80 ± 0.69) vs (0.84 ± 0.77), P0.05]. The expression of TIMP-1 in the bleomycin plus stem cell group was higher than the bleomycin group [(1.95 ± 0.58) vs (0.79 ± 0.71), P0.05], but there was no difference between the control group and the stem cell group [(1.10 ± 0.72) vs (1.32 ± 0.58), P0.05].UC-MSC transplantation could relieve bleomycin-induced fibrosing alveolitis in mice. The mechanism might be related to the expression of MMP-2 and TIMP-1. UC-MSC had no effect on normal lungs.

To describe the characteristic of Th17 cells in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis, and to investigate the effect of glucocorticoid therapy on the expression of RORγt mRNA, and therefore to explore the role of Th17 cells in the immunopathogenesis of pulmonary sarcoidosis.Ten patients with active pulmonary sarcoidosis who were prescribed with prednisone according to the guidelines were defined as the study group. All of them had positive pathological results and had definite response to corticosteroids. Ten healthy controls were recruited from volunteers with similar sex distribution and age. The proportion of CD(4)(+)IL-17A(+)T cells in peripheral blood mononuclear cells (PBMC) and BALF were calculated by flow cytometry. The mRNA expression of RORc in PBMC was measured by Real-time PCR.The mean age was (52 ± 8) years in both the study group and the controls, and there were 9 females and 1 male in both groups. The proportion of CD(4)(+)IL-17A(+)T cells was higher in the PB of sarcoidosis patients compared to that of the controls [(1.61 ± 1.09)% vs (0.51 ± 0.43)%, t = 3.02, P = 0.014]. For the same patients, the proportion of CD(4)(+)IL-17A(+)T cells was higher in the BALF compared to that in the PB [(3.05 ± 1.87)% vs (1.61 ± 1.09)%, t = 2.94, P = 0.001]. After 4 to 6 week therapy with glucocorticoids, all the 10 patients showed definite response. The level of RORc mRNA in the PB did not decrease significantly after treatment [(0.952 ± 0.367) vs (0.168 ± 0.272), t = 1.76, P = 0.057], although a trend was noted.Th17 cells was probably involved in the immunopathogenesis of sarcoidosis, and glucocorticoids might modulate the disturbance of Th17 cells in pulmonary sarcoidosis.

Background Pulmonary involvement is a common feature of MPA. Although alveolar hemorrhage is the most common pulmonary manifestation of MPA, a few recent studies have described instances of MPA patients with pulmonary fibrosis. Pulmonary fibrosis was seen to predate, be concomitant with, or occur after the diagnosis of MPA. The goal of this study was to describe the clinical features and prognosis of microscopic polyangiitis (MPA) patients whose initial respiratory presentation was pulmonary fibrosis. Methods We conducted a retrospective analysis of 19 MPA patients who presented with pulmonary fibrosis at Peking Union Medical College Hospital between 1990 and 2012. Results Of 67 total MPA cases, 19 patients presented with pulmonary fibrosis. There were 8 males and 11 females, with a median age of 63.6 years. Common clinical manifestations included fever (89.5%), cough (84.2%), dyspnea (78.9%) and velcro rales (84.2%). Eleven patients experienced weight loss, several had kidney involvement, and most had an increased erythrocyte sedimentation rate and C-reactive protein. All were positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA), with 6 patients being positive at the time of their initial diagnosis of pulmonary fibrosis. Every patient had typical features of usual interstitial pneumonia on High-resolution CT. All were treated with corticosteroids and cyclophosphamide, which lead to an improvement in twelve cases. One of the remaining patients progressed slowly, whereas six died. Conclusions Patients with MPA, who also presented with pulmonary fibrosis in our cohort, were more likely to be older, female, and have extrapulmonic involvement. Most patients had a delayed positive ANCA. Corticosteroids plus cyclophosphamide was the remission-induction treatment scheme for all cases. The current prognosis for MPA patients with pulmonary fibrosis appears to be poor, suggesting that they may be candidates for new therapies.