In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

We determined the effect of Omecamtiv Mecarbil, a novel allosteric effector of cardiac muscle myosin, on the kinetic and "in vitro" motility properties of the porcine ventricular heavy meromyosin (PV-HMM). Omecamtiv Mecarbil increases the equilibrium constant of the hydrolysis step (M-ATP ⇄ M-ADP-Pi) from 2.4 to 6 as determined by quench flow, but the maximal rates of both the hydrolysis step and tryptophan fluorescence increase are unchanged by the drug. OM also increases the amplitude of the fast phase of phosphate dissociation (AM-ADP-Pi → AM-ADP + Pi) that is associated with force production in muscle by 4-fold. These results suggest a mechanism in which hydrolysis of M-ATP to M-ADP-Pi occurs both before and after the recovery stroke, but rapid acceleration of phosphate dissociation by actin occurs only on post-recovery stroke A-M-ADP-Pi. One of the more dramatic effects of OM on PV-HMM is a 14-fold decrease in the unloaded shortening velocity measured by the in vitro motility assay. The increase in flux through phosphate dissociation and the unchanged rate of ADP dissociation (AM-ADP → AM + ADP) by the drug produce a higher duty ratio motor in which a larger fraction of myosin heads are strongly bound to actin filaments. The increased internal load produced by a larger fraction of strongly attached crossbridges explains the reduced rate of in vitro motility velocity in the presence of OM and predicts that the drug will produce slower and stronger contraction of cardiac muscle.

The BMP signaling pathway promotes muscle growth and inhibits muscle wasting via SMAD1/5-dependent signaling.

SummaryBackgroundAn adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends.MethodsWe estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development.FindingsBetween 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3·0%. The largest health spending growth rates were in upper-middle-income (5·9) and lower-middle-income groups (5·0), which both increased spending at more than 5% per year, and spent $914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4·6%, and health spending increased from $51 to $120 per capita. In 2014, 59·2% of all health spending was financed by the government, although in low-income and lower-middle-income countries, 29·1% and 58·0% of spending was OOP spending and 35·7% and 3·0% of spending was development assistance. Recent growth in development assistance for health has been tepid; between 2010 and 2016, it grew annually at 1·8%, and reached US$37·6 billion in 2016. Nonetheless, there is a great deal of variation revolving around these averages. 29 countries spend at least 50% more than expected per capita, based on their level of economic development alone, whereas 11 countries spend less than 50% their expected amount.InterpretationHealth spending remains disparate, with low-income and lower-middle-income countries increasing spending in absolute terms the least, and relying heavily on OOP spending and development assistance. Moreover, tremendous variation shows that neither time nor economic development guarantee adequate prepaid health resources, which are vital for the pursuit of universal health coverage.FundingThe Bill & Melinda Gates Foundation.

The electrocatalytic C–N coupling for one-step urea synthesis under ambient conditions serves as the promising alternative to the traditional urea synthetic protocol. However, the hydrogenation of intermediate species hinders the efficient urea synthesis. Herein, the oxygen vacancy-enriched CeO2 was demonstrated as the efficient electrocatalyst with the stabilization of the crucial intermediate of *NO via inserting into vacant sites, which is conducive to the subsequent C–N coupling process rather than protonation, whereas the poor selectivity of C–N coupling with protonation was observed on the vacancy-deficient catalyst. The oxygen vacancy-mediated selective C–N coupling was distinguished and validated by the in situ sum frequency generation spectroscopy. The introduction of oxygen vacancies tailors the common catalyst carrier into an efficient electrocatalyst with a high urea yield rate of 943.6 mg h–1 g–1, superior than that of partial noble-metal-based electrocatalysts. This work provides novel insights into the catalyst design and developments of coupling systems.

Pak4 is a member of the B group of p21-activated (Pak) kinases, originally identified as an effector protein for Cdc42. Although Pak4 is expressed at low levels in most adult tissues, it is highly overexpressed in tumor cell lines. Here, we show that Pak4 is also overexpressed in primary tumors, including colon, esophageal, and mammary tumors. Overexpression of Pak4 also leads to tumor formation in athymic mice, whereas deletion of Pak4 inhibits tumorigenesis. Although a constitutively active Pak4 mutant was previously shown to promote oncogenic transformation in cultured cells, our results are the first to show that Pak4 also promotes tumorigenesis in experimental animals. Furthermore, these results show for the first time that not only constitutively active Pak4, but also wild-type Pak4, is transforming, when experimental animals are used. These results are highly significant because wild-type Pak4, rather than activated Pak4, is overexpressed in tumor cells. Our results suggest that overexpression or activation of Pak4 is a key step in oncogenic transformation, due to its ability to promote cell survival and subsequent uncontrolled proliferation. The finding that Pak4 is up-regulated in so many types of cancers indicates that Pak4 may play a vital role in a wide range of different types of cancer. This makes it an attractive candidate for drug therapy for different types of cancer.

Micro/nanoscale multicolor barcodes with unique identifiability and a small footprint play significant roles in applications such as multiplexed labeling and tracking systems. Now, a strategy is reported to design multicolor photonic barcodes based on 1D Ln‐MOF multiblock heterostructures, where the domain‐controlled emissive colors and different block lengths constitute the fingerprint of a corresponding heterostructure. The excellent heteroepitaxial growth characteristics of MOFs enable the effective modulation of the coding structures, thereby remarkably increasing the encoding capacity. The as‐prepared multicolor barcodes enable an efficient authentication and exhibit great potential in fulfilling the functions of anti‐counterfeiting, information security, and so on. The results will pave an avenue to novel hybrid MOFs for optical data recording and security labels.

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