Globally 113 702 confirmed (4125 new) 4012 deaths (203 new) China 80 924 confirmed (20 new) 3140 deaths (17 new) Outside of China 32 778 confirmed (4105 new) 872 deaths (186 new) 109 countries/territories/ areas (5 new) WHO RISK ASSESSMENT China Very High Regional Level Very High Global Level Very High HIGHLIGHTS • 5 new countries/territories/areas (Brunei Darussalam, Mongolia, Cyprus, Guernsey and Panama) have reported cases of COVID-19 in the past 24 hours. 1 https://www.iatatravelcentre.com/international-travel-document-news/1580226297.htm 2 https://pandemic.internationalsos.com/2019-ncov/ncov-travel-restrictions-flight-operations-and-screening 3 https://www.iata.org/en/pressroom/pr/2020-03-02-01/ 4 https://www.who.int/ith/2019-nCoV_advice_for_international_traffic-rev/en/

Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.

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Mechanical strain plays a crucial role in bone remodeling during growth and development and healing of bone besides systemic and local factors. One of the major factors involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues. To study how mechanical strain affects extracellular matrix degradation by MMP-13, a biaxial strain was applied to MC3T3-E1 osteoblastic cells plated onto a collagen-coated flexible elastic membrane. The MMP-13 protein and mRNA expression were determined by Western blotting and reverse transcriptase-PCR, respectively. The zymographic activities of MMP-13 increased dramatically at 30 min, reached a peak by 2-fold at 1 h, and maintained up to 4 h. Moreover, the MMP-13 and c-fos mRNA expressed at 5 min, increased to 2.8-and 3-fold at 1 h, respectively, and gradually declined thereafter. Cycloheximide and actinomycin D did not inhibit the MMP-13 and c-fos mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. To investigate which of the mitogen-activated protein kinase (MAPK) pathways involves in the expression of MMP-13, inhibitors such as PD98059, SB203580, and SP600125 were used. However, only PD98059 (an inhibitor of MEK1/2 activation) inhibited MMP-13 and c-fos gene expression; the result was further substantiated by transfecting with the dominant negative mutants of MEK1/2 (MEK K97R) and ERK2. Taken together, our results showed that mechanical strain induces the MMP-13 expression through MEK-ERK signaling pathway to regulate mechanical adaptation.Bone is constantly remodeled throughout life to meet the functional demands of its physiological and mechanical environment (1-4). Remodeling of bone is regulated by a wide variety of systemic and local factors such as 1␣,25-dihydeoxyvitamin D 3 , parathyroid hormone, calcitonin, sex hormones, prostaglandin, transforming growth factor-␤, bone morphogenetic protein, and insulin-like growth factors. It is also a well known fact during growth and in the adult skeleton, a moderate level of mechanical loading is considered essential for maintaining and adaptation to the physiological bone remodeling (4, 5). In particular, mechanical loading on osteoblasts in vitro has been demonstrated to increase prostaglandin release (6), stimulate cell division (7), alter collagen synthesis (8), and promote collagenase activity (9).The remodeling of the mineralized connective tissue involves coupling of the degradation of the extracellular matrix (ECM) 1 with the synthesis of new matrix components. Although osteoblasts have been implicated only in bone formation, in response to resorption stimulators, they may cease synthesis of collagen and start secreting neutral proteinases such as collagenase (10 -12). These collagenases may degrade the unmineralized osteoid layer covering bone surfaces, leading to the exposure of the mineralized matrix to osteoclasts. On the other hand, recent findi...