Background In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. MethodsIn this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed.Findings Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29-34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of followup wasFeb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth.Interpretation The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature.

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T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtorf/f-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses.DOI: http://dx.doi.org/10.7554/eLife.17936.001

The coronavirus disease 2019 (COVID-19) pandemic remains threatening to women and children, but clinical evidence regarding women during pregnancy, puerperium and lactation is limited. We assessed clinical and immunologic features of and breastfeeding advice provided to mother–infant pairs. This observational analysis was conducted in a tertiary-care centre in Wuhan, China. Pregnant patients with laboratory-confirmed COVID-19 who delivered during hospitalization were enrolled. Clinical characteristics and serial specimens of the mother–infant pairs were examined, supplemented with follow-ups regarding recovery and breastfeeding. Fourteen pregnant patients had live births and recovered well; four patients continued breastfeeding while taking precautions. No neonatal infections were observed. No infants developed COVID-19 during breastfeeding. Common maternal symptoms were fever (11/14, 78.1%) and cough (6/14, 42.9%). A pregnancy-specific symptom was abnormal foetal movement, which was noticed by three patients (21.4%). The mean virus shedding time was 9 days (standard deviation, 6 days; range, 1–22 days). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome was not detected in breast milk or maternal vaginal secretions. Immunologic assay revealed seroconversion of IgM on day 8 after onset and IgG on day 28. Both IgM and IgG antibodies to SARS-CoV-2 were detected in breast milk, cord blood and neonatal serum. The study results suggest that passive acquisition of antibodies against SARS-CoV-2 is available by ingesting breast milk. Breastfeeding has a low risk of transmitting SARS-CoV-2 or escalating maternal disease, so continuing breastfeeding with prudent precautions is encouraged.

The electrochemistry of (tetraphenylporphinato)cobalt(II), (TPP)Co, and chloro(tetraphenylporphinato)cobalt(III), (TPP)Co"'Cl, is reported in methylene chloride solutions containing various concentrations of tetrabutylammonium chloride. The two-electron reduction of (TPP)Co"'CI or the one-electron reduction of (TPP)Co generates [ (TPP)Co']-, but these reversible electroreductions are followed by a rapid irreversible chemical reaction with the CH2C12 solvent to produce a a-bonded cobalt(II1) complex. Electrwxidation of (TPP)Co in the presence of C1-generates either (TPP)Co"'Cl or [(TPP)CO~~'CI~]-after abstraction of one electron and [(TPP)Co1"Cl]+ or (TPP)Co"'C12 after abstraction of a second electron. The [(TPP)CO~~CI]-/[(TPP)CO~~'CI~]-and [(TPP)CO~~'CI~]-/(TPP)CO~I~CI~ reactions occur at E, = 0.57 V (cyclic voltammetry, scan rate = 0.1 V/s) and E l j 2 = 0.63 V, respectively. (TPP)Co"'Cl is reversibly oxidized to [(TPP)Co"'Cl]+ at 0.90 V and to [(TPP)CO~"CI]~+ at 1.15 V in the absence of excess C1-. ESR, UV-visible, and thin-layer spectroelectrochemical methods were utilized to characterize the reactants and products of each electrode reaction. and a mechanism for the chloride-binding reactions and electrochemistry of (TPP)Co and (TPP)Co"'CI is presented. (17) Kobayashi, H.; Hara, T.; Kaizu, Y. Bull. Chem. SOC. Jpn. 1972, 45, 2148.-Clarke, D. A.; Dolphin, D.; Grigg, R.; Johnson, A. W.; Pinnock, H. A. Chem. Commun. 1967, 305. Ogoshi, H.; Watanabe, E.; Koketsu, N.; Yoshida, Z . Bull. Chem. Soc. Jpn. 1976, 49, 2529. Momenteau, M.; Fournier, M.; Rougee, M. J. Chim. Phys. 1970,67, 926. Yamamoto, K.; Uzawa, J.; Chizimatsu, T. Chem. Lett. 1979, 89. Ohya-Nishiguchi, H.; Khono, M.; Yamomoto, K. Bull. Chem. Soc. Jpn. 1981,54, 1923. Ichimori, K.; Ohya-Nishiguchi, H.; Hirota, N.; Yamomoto, K. Bull. Chem. SOC. Jpn. 1985,58, 623. Sakurai, T.; Yamamoto, K.; Naito, H.; Nakamoto, N. Bull. Chem. Soc. Jpn. 1976, 49, 3042. Yamamoto, K.; Konno, M.; Ohya-Nishiguchi, H. Chem. Lett. 1981, 255. Yamamoto, K.; Hoshino, M.; Kohno, M.; Ohya-Nishiguchi, H. Bull. Chem. SOC. Jpn. 1986, 59, 351.

Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes. We detected four modules related to one or more clinical features significantly shared across all modeling datasets, and identified one stage-associated module and one grade-associated module. Our analysis showed that MMP2, COL3A1, COL1A2, FBN1, COL5A1, COL5A2, and AEBP1 are top hub genes related to stage, while CDK1, BUB1, BUB1B, BIRC5, AURKB, CENPA, and CDC20 are top hub genes related to grade. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggest that extracellular matrix interactions and mitotic signaling pathways are crucial determinants of tumor stage and grade. The relationships between gene expression modules and tumor stage or grade were validated in five independent datasets. These results could potentially be developed into a more objective scoring system to improve prediction of SOC outcomes.

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Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing γδT (γδT17) cell differentiation and TCRVγ/δ recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated γδT17 differentiation and rearranging of fetal specific TCRVγ/δ in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy.