IMPORTANCE A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. OBJECTIVE To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. INTERVENTIONS In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). DESIGN, SETTING, AND PARTICIPANTS Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. MAIN OUTCOMES AND MEASURES The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. CONCLUSIONS AND RELEVANCE In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

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Streptomyces mobaraenesis transglutaminase has been widely used in food processing. We here significantly improved the catalytic properties of S2P-S23V-Y24N-S199A-K294L (TGm1), a highly stabilized variant of the transglutaminase. First, a virtual proline scan was performed based on folding free energy changes to obtain TGm1 variants with enhanced thermostability. Second, the residues within 15 Å of Cys64 in the enzyme–substrate complex of TGm1 were subjected to virtual saturation mutagenesis to generate the variants with reduced binding free energy and increased activity. After combining the favorable mutations, we obtained the variant FRAPD-TGm1-E28T-A265P-A287P (FRAPD-TGm2), exhibiting 66.9 min of half-life at 60 °C (t 1/2(60 °C)), 67.8 °C of melting temperature (T m), and 71.8 U/mg of specific activity, which are 2-fold, 2.6 °C, and 43.8% higher than those of FRAPD-TGm1, respectively. At last, to increase the surface negative net charge of FRAPD-TGm2, we introduced the mutations N96E-S144E-N163D-R183E-R208E-K325E, yielding FRAPD-TGm3. The latter’s t 1/2(60 °C), T m, and specific activity were 122.9 min, 68.6 °C, and 83.7 U/mg, which are 83.8%, 0.8 °C, and 16.6% higher than the former, respectively. FRAPD-TGm3 is thus a robust candidate for transglutaminase application.

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The interaction of two Bacillus thuringiensis cytolytic toxins, CytA and CytB, with a phospholipid bilayer and their structure in the membrane-bound state were investigated by proteolysis using phospholipid vesicles as a model system. A toxin conformational change upon membrane binding was detected by comparing the proteolytic profile of membrane-bound toxin and saline-solubilized toxin. When membrane-bound toxin was exposed to protease K or trypsin, novel cleavage sites were found between the alpha-helical N-terminal half and beta-strand C-terminal half of the structure at K154 and N155 in CytA and at I150 and G141 in CytB. N-terminal sequencing of membrane-protected fragments showed that the C-terminal half of the toxin structure comprising mainly beta-strands was inserted into the membrane, whereas the N-terminal half comprising mainly alpha-helices was exposed on the outside of the liposomes and could be removed when liposomes with bound toxin were washed extensively after proteolysis. The C-termini of the membrane-inserted proteolytic fragments were also located by a combination of N-terminal sequencing and measurement of the molecular masses of the fragments by electrospray MS. Using a liposome glucose-release assay, the membrane-inserted structure was seen to retain its function as a membrane pore even after removal of exposed N-terminal segments by proteolysis. These data strongly suggest that the pores for glucose release are assembled from the three major beta-strands (beta-5, beta-6 and beta-7) in the C-terminal half of the toxin.

Lead halide perovskites have attracted increasing attention in photovoltaic devices, light-emitting diodes, photodetectors, and other fields due to their excellent properties. Besides optoelectronic devices, growing numbers of studies have focused on the perovskite-based electrical devices in the past few years, such as transistors and resistive random access memories (RRAMs). Here, this article summarizes the recent progress the researchers have made of RRAM devices. Primarily, the working mechanism and the key parameters of RRAM are introduced. Generally, the working principles, including the conductive filament model (containing the types of the model of the metal cationsinduced filament and the model of the ions migration in bulk), the interface effect, and the electronic effect are the origins of the RRAM behaviors, and hence, various factors that affect the device performance are explored. Then, RRAMs based on organolead halide perovskite and all-inorganic perovskite are discussed in terms of different structures, different compositions, and different fabrication methods. Finally, a brief conclusion and a broad outlook are given on the progress and challenges in the field of perovskite-based RRAMs. K E Y W O R D S all-inorganic perovskites, conductive filament models, organolead halide perovskites, resistive random access memories, resistive switching Jiayu Di and Jianhui Du contributed equally to this work.

The charge transport layer is crucial to the performance and stability of the perovskite solar cells (PSCs). Compared with other conventional metal oxide electron transport materials, SnO2 has a deeper conduction band and higher electron mobility, and can efficiently serve as an electron transport layer to facilitate charge extraction and transfer. Herein, an optimized low‐temperature solution‐processed SnO2 electron transport layer is achieved by doping polyethylenimine polyelectrolyte into SnO2 for the first time in the PSCs. It is found that the performance of all aspects of the doped SnO2 film is improved over that of the pristine SnO2 film. The better energy level alignment, larger built‐in field, enhanced electron transfer/extraction, and reduced charge recombination all contribute to the improved device performance. Finally, a PSC with a power conversion efficiency of 20.61% is successfully prepared under low temperature below 150 °C. Moreover, the stability of the doped SnO2‐based device is also greatly improved.

The IPEC-1 newborn swine intestinal epithelial cell line was used to determine the effects of the uptake of various fatty acids on the secretion of apolipoprotein (apo) B and apo A-I, as well as triglyceride and phospholipid. Long-chain saturated fatty acids were taken up and stimulated triglyceride synthesis, and palmitic (16:0) and stearic (18:0) acids also stimulated phospholipid synthesis. However, these fatty acids did not enhance triglyceride, phospholipid, or apo B or apo A-I secretion. Oleic acid (18:1) was the most effective of all fatty acids tested in stimulating triglyceride synthesis and the secretion of triglyceride, phospholipid, and apo B. Linoleic (18:2) and linolenic (18:3) acids were no more effective than long-chain saturated fatty acids in stimulating these processes. With saturated fatty acids, apo A-I followed the same secretory pattern as apo B. However, among the unsaturated fatty acids, oleic acid was the least effective and linolenic acid was the most effective in stimulating apo A-I secretion. Basolateral secretion of lipid and apolipoproteins by differentiated IPEC-1 cells is differentially regulated by apical exposure to fatty acids.