e Porcine epidemic diarrhea coronavirus (PEDV) has significantly damaged America's pork industry. Here we investigate the receptor usage and cell entry of PEDV. PEDV recognizes protein receptor aminopeptidase N from pig and human and sugar coreceptor N-acetylneuraminic acid. Moreover, PEDV infects cells from pig, human, monkey, and bat. These results support the idea of bats as an evolutionary origin for PEDV, implicate PEDV as a potential threat to other species, and suggest antiviral strategies to control its spread. P orcine epidemic diarrhea coronavirus (PEDV) causes largescale outbreaks of diarrhea in pigs and an 80 to 100% fatality rate in suckling piglets (1-3). Since 2013, PEDV has swept throughout the United States, wiped out more than 10% of America's pig population in less than a year, and significantly damaged the U.S. pork industry (4-6). No vaccine or antiviral drug is currently available to keep the spread of PEDV in check. PEDV belongs to the ␣ genus of the coronavirus family (7,8), which also includes porcine transmissible gastroenteritis coronavirus (TGEV), bat coronavirus 512/2005 (BtCoV/512/2005), and human NL63 coronavirus (HCoV-NL63). Although both PEDV and TGEV infect pigs, PEDV is genetically more closely related to BtCoV/512/ 2005 than to TGEV, leading to the hypothesis that PEDV originated from bats (9).Receptor binding and cell entry are essential steps in viral infection cycles, critical determinants of viral host range and tropism, and important targets for antiviral interventions. An envelope-anchored spike protein mediates coronavirus entry into cells. The spike ectodomain consists of a receptor-binding subunit, S1, and a membrane fusion subunit, S2. S1 contains two domains, an N-terminal domain (S1-NTD) and a C-terminal domain (S1-CTD), both of which can potentially function as receptor-binding domains (RBDs) (Fig. 1A) (10, 11). The ability of coronavirus RBDs to recognize receptor orthologs from different species is one of the most important determinants of coronavirus host range and tropism (8,(12)(13)(14). HCoV-NL63 S1-CTD recognizes human angiotensin-converting enzyme 2 (ACE2), whereas TGEV S1-CTD recognizes porcine aminopeptidase N (APN), and its S1-NTD recognizes two sugar coreceptors, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) (15-18). Usage of sugar coreceptors is linked to the enteric tropism of coronaviruses (18,19). It has been shown that PEDV uses porcine APN as its receptor (20). However, it is not known whether PEDV recognizes APN from other species or whether it uses sugar coreceptors. Addressing these questions will be critical for understanding the host range, tropism, and evolutionary origin of PEDV, for evaluating its potential risk to other species, particularly humans, and for developing effective vaccines and antiviral drugs to curb the spread of PEDV in pigs and to other species.To characterize the receptor usage of PEDV, here we identified the two S1 domains of PEDV based on the sequence similarity between PEDV and TGEV S1 subun...

Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor model. Then, we observed that hUCMSC-derived extracellular vesicles (hUCMSC-EVs) contribute to the hUCMSC-promoted LUAD cell growth through a direct effect on LUAD cells. Furthermore, we showed that hUCMSC-EV-mediated LUAD growth is associated with increased proliferation and decreased apoptosis in LUAD cells, concomitant with reduced PTEN expression mediated by the hUCMSC-EV-transmitted miR-410. Our findings provide novel insights into the intercellular communications between cancer cells and MSCs through MSC-EV-miRNA and suggest that modification of hUCMSC-EVs might be an attractive therapeutic option for the clinical application of hUCMSC-EVs that would reduce unwanted side effects.

L-3-n-Butylphthalide (L-NBP) exerts neuroprotective effects in animal models of cerebral ischemia, but its potential benefits in repeated cerebral ischemia-reperfusion (RCIR) injury remain unknown. We investigated the effect of L-NBP on cognitive impairment induced by RCIR in mice. Male C57Bl/6 mice received sham surgery or bilateral common carotid artery occlusion (3 times, 20 min each) and were orally administered preoperative L-NBP (30 mg/kg/day, 7 days), postoperative L-NBP (30 or 60 mg/kg/day, 28 days) or postoperative vehicle (28 days). Learning and memory were assessed by the Morris water maze task and step-down passive avoidance test. Nissl staining was used to identify pathologic changes in the hippocampal CA1 region. The expressions of proteins associated with signaling, apoptosis and autophagy were assessed by quantitative PCR and western blot. RCIR induced deficits in learning and memory that were alleviated by preoperative or postoperative L-NBP administration. Pathologic lesions in the hippocampal CA1 region induced by RCIR were less severe in mice treated with L-NBP. Preoperative or postoperative L-NBP administration in mice receiving RCIR promoted hippocampal expression of phospho-Akt and phospho-mTOR (suggesting activation of Akt/mTOR signaling), increased the Bcl-2/Bax ratio (indicating suppression of apoptosis) and reduced the LC3-II/LC3-I ratio (implying inhibition of autophagy). Preoperative or postoperative L-NBP administration also depressed hippocampal levels of beclin-1 mRNA (indicating suppression of autophagy). These findings suggest that the effect of L-NBP to alleviate learning and memory deficits in mice following RCIR may involve activation of Akt/mTOR signaling and regulation of the expressions of proteins related to apoptosis and autophagy.

The efficient separation of the orbital angular momentum (OAM) is essential to both the classical and quantum applications with twisted photons. Here we devise and demonstrate experimentally an efficient method of mimicking the Faraday rotation to sort the OAM based on the OAM-to-polarization coupling effect induced by a modified Mach-Zehnder interferometer. Our device is capable of sorting the OAM of positive and negative numbers, as well as their mixtures. Furthermore, we report the first experimental demonstration to sort optical vortices of noninteger charges. The possibility of working at the photon-count level is also shown using an electron-multiplying CCD camera. Our scheme holds promise for quantum information applications with single-photon entanglement and for high-capacity communication systems with polarization and OAM multiplexing.