A B S T R A C T PurposeThe trial objectives were to identify the maximum-tolerated dose (MTD) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data. Additional objectives were to evaluate positron emission tomography (PET) scan response, secreted protein acidic and rich in cysteine (SPARC), and CA19-9 levels in relation to efficacy. Subsequent preclinical studies investigated the changes involving the pancreatic stroma and drug uptake. Patients and MethodsPatients with previously untreated advanced pancreatic cancer were treated with 100, 125, or 150 mg/m 2 nab-paclitaxel followed by gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 every 28 days. In the preclinical study, mice were implanted with human pancreatic cancers and treated with study agents. ResultsA total of 20, 44, and three patients received nab-paclitaxel at 100, 125, and 150 mg/m 2 , respectively. The MTD was 1,000 mg/m 2 of gemcitabine plus 125 mg/m 2 of nab-paclitaxel once a week for 3 weeks, every 28 days. Dose-limiting toxicities were sepsis and neutropenia. At the MTD, the response rate was 48%, with 12.2 median months of overall survival (OS) and 48% 1-year survival. Improved OS was observed in patients who had a complete metabolic response on [ 18 F]fluorodeoxyglucose PET. Decreases in CA19-9 levels were correlated with increased response rate, progression-free survival, and OS. SPARC in the stroma, but not in the tumor, was correlated with improved survival. In mice with human pancreatic cancer xenografts, nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma. The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone. ConclusionThe regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity, warranting phase III evaluation.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in fecal material has raised the possibility of viral transmission via a fecal–oral route. This study investigated whether SARS-CoV-2 transmission via fecal aerosols in the drainage pipe system may have been the cause of COVID-19 infection in a cluster of 3 families living in a high-rise building in China.

Plant pathogenic fungi deploy secreted effectors to suppress plant immunity responses. These effectors operate either in the apoplast or within host cells, so they are putatively glycosylated, but the posttranslational regulation of their activities has not been explored. In this study, the ASPARAGINE-LINKED GLYCOSYLATION3 (ALG3)-mediated N-glycosylation of the effector, Secreted LysM Protein1 (Slp1), was found to be essential for its activity in the rice blast fungus Magnaporthe oryzae. ALG3 encodes an a-1,3-mannosyltransferase for protein N-glycosylation. Deletion of ALG3 resulted in the arrest of secondary infection hyphae and a significant reduction in virulence. We observed that Dalg3 mutants induced massive production of reactive oxygen species in host cells, in a similar manner to Dslp1 mutants, which is a key factor responsible for arresting infection hyphae of the mutants. Slp1 sequesters chitin oligosaccharides to avoid their recognition by the rice (Oryza sativa) chitin elicitor binding protein CEBiP and the induction of innate immune responses, including reactive oxygen species production. We demonstrate that Slp1 has three N-glycosylation sites and that simultaneous Alg3-mediated N-glycosylation of each site is required to maintain protein stability and the chitin binding activity of Slp1, which are essential for its effector function. These results indicate that Alg3-mediated N-glycosylation of Slp1 is required to evade host innate immunity.

The synaptic weight modification depends not only on interval of the pre-/ postspike pairs according to spike-timing dependent plasticity (classical pair-STDP), but also on the timing of the preceding spike (triplet-STDP). Triplet-STDP reflects the unavoidable interaction of spike pairs in natural spike trains through the short-term suppression effect of preceding spikes. Second-order memristors with one state variable possessing short-term dynamics work in a way similar to the biological system. In this work, the suppression triplet-STDP learning rule is faithfully demonstrated by experiments and simulations using second-order memristors. Furthermore, a leaky-integrate-and-fire (LIF) neuron is simulated using a circuit constructed with second-order memristors. Taking the advantage of the LIF neuron, various neuromimetic dynamic processes, including local graded potential leaking out, postsynaptic impulse generation and backpropagation, and synaptic weight modification according to the suppression triplet-STDP rule, are realized. The realized weight-dependent pairand triplet-STDP rules are clearly in line with findings in biology. The physically realized triplet-STDP rule is powerful in developing direction and speed selectivity for complex pattern recognition and tracking tasks. These scalable artificial synapses and neurons realized in second-order memristors can intrinsically capture the neuromimetic dynamic processes; they are the promising building blocks for constructing brain-inspired computation systems.

Memory cells have always been an important element of information technology. With emerging technologies like big data and cloud computing, the scale and complexity of data storage has reached an unprecedented peak with a much higher requirement for memory technology. As is well known, better data storage is mostly achieved by miniaturization. However, as the size of the memory device is reduced, a series of problems, such as drain gate‐induced leakage, greatly hinder the performance of memory units. To meet the increasing demands of information technology, novel and high‐performance memory is urgently needed. Fortunately, emerging memory technologies are expected to improve memory performance and drive the information revolution. This review will focus on the progress of several emerging memory technologies, including two‐dimensional material‐based memories, resistance random access memory (RRAM), magnetic random access memory (MRAM), and phase‐change random access memory (PCRAM). Advantages, mechanisms, and applications of these diverse memory technologies will be discussed in this review.

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Receptor-like protein kinases (RLKs) are a large group of transmembrane proteins playing critical roles in cell-cell and cell-environment communications. Based on extracellular domain structures, RLKs were classified into more than 21 subfamilies, among which leucine-rich repeat RLKs (LRR-RLKs) belong to the largest subfamily in plants such as Arabidopsis and rice. In Arabidopsis, there are approximately 223 LRR-RLKs, but only about 60 of which have been functionally described to date. To systematically investigate the roles of LRR-RLKs in regulating plant growth, development, and stress adaptations, we generated promoter::GUS transgenic plants for all 223 LRR-RLK genes in Arabidopsis and analyzed their detailed expression patterns at various developmental stages. The results provide valuable resources for functionally elucidating this large and essential signaling protein subfamily.

This study provides evidence for one independent WGD in the ancestry of Actinidia (Ad-alpha), a WGD shared by Actinidia and Camellia (Ad-beta), and the well-established At-gamma WGD that occurred prior to the divergence of all taxa examined. More ESTs in other taxa are needed to elucidate which groups in Ericales share the Ad-beta or Ad-alpha duplications and their impact on diversification.