Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
The isothermal hot compression tests were carried out on Gleeble-3500 thermo mechanical simulator in the temperature range of 1323–1473K and strain rates of 0.01s−1, 0.1s−1, 1s−1 and 10s−1. Based on ...the experimental results, a modified Johnson Cook model is proposed to describe the flow behavior of T24 steel. The modified model considers not only the yield and strain hardening portion of the original model but also the coupled effects of strain and temperature, and of strain rate and temperature on the flow behaviors. The high temperature deformation behavior of T24 steel was characterized based on the analysis of the stress-strain curves. The results showed that the flow stress predicted by the proposed model agrees well with the experimental stress, which validates the efficiency of the modified model in describing the deformation behavior of the steel. The true stress–true strain curves exhibit a peak stress at a very small strain, after which the flow stresses decrease until high strains, showing a typical dynamic recrystallization (DRX) behavior of the steel under the deformation conditions of lower strain rates.
Millimeter-Wave (mmWave) communication is conceived as a viable approach for 5G vehicular communication systems, where vehicles are equipped with more sensors that generate Gbps data for future ...autonomous driving. However, such directional mmWave communication relies on accurate beam alignment and is sensitive to blockage. Dense deployment of mmWave base stations (mmBSs) and high mobility of vehicles also lead to frequent handovers and complex beam alignment calculation. 5G mmWave vehicular communication calls for a smart and stable solution. To this end, we propose an online learning scheme to address the problem of beam selection with blockage-free guarantee in 5G mmWave vehicular networks. We first model this problem as a contextual combinatorial multi-armed bandit (MAB) problem with QoS constraints and delayed feedback. Next, we propose an online learning algorithm, BPG, to predict beam directions, with provable sub-linear regret and blockage-free bounds. BPG exploits the context space and learns the expected weight of each beam from arrived vehicles’ contexts and the delayed feedback. To validate the efficiency of BPG, we also conduct trace-driven simulations based on real-world traffic patterns. Simulation results show that BPG achieves close-to-optimal throughput with low violation and outperforms other benchmark algorithms.
Doping has been established as a powerful approach for endowing lead halide perovskite nanocrystals (NCs) with novel properties. However, our fundamental understanding of the local structure of ...dopants, doping efficiency and luminescence properties of these NCs is still very sparse. Here, we provide the first experimental evidence regarding the local structure of rare earth ions in CsPbCl3 NCs, based on the analysis of extended X-ray absorption fine structure spectroscopy. Our result suggests that Yb3+ occupies the Pb2+ crystallographic sites in CsPbCl3 NCs. We further demonstrate a strategy to examine the determinant of the doping efficiency in lanthanide-doped lead halide perovskite NCs, which enables us to uncover the important role of structural defects in affecting the doping efficiency. A broad range of experimental characterization techniques including steady-state and time-resolved luminescence spectra, X-ray absorption spectra, and positron annihilation lifetime spectra, coupled with first-principles calculations, help us identify that the doping efficiency is associated with structural defects in NCs and that the formation of a higher-concentration of defects favors incorporation of a higher-concentration of dopants into the lattice. Importantly, we demonstrate that the concept of defect-assisted doping is not limited to the model system of Yb3+-doped CsPbCl3 NCs, but can be used as a guideline to rationally tune the doping efficiency of lanthanide-doped halide perovskite NCs. We also show that lanthanide-doped CsPbCl3 NCs demonstrate anomalous decay of the band-edge emission, which we propose is due to the existence of shallow trapping states near the conduction band. Our results greatly deepen the understanding of the structural and photophysical properties of lanthanide-doped lead halide perovskite NCs, and highlight the possibility to use the chemistry of defects to tailor the doping efficiency of halide perovskite NCs.
USP28, a member of the deubiquitinating enzymes family, plays a vital role in the physiological process of cell proliferation, differentiation and apoptosis, DNA repair, immune response, and stress ...response. USP28 has been reported to be overexpressed in bladder cancer, colon cancer, breast carcinomas, and so on. Nevertheless, the role of USP28 in gastric cancer has not yet been investigated. In our study, we examined the USP28 expression in 87 paired samples of gastric cancer and normal gastric tissues. We found that USP28 was overexpressed in gastric cancer compared with normal gastric tissues (P < 0.01), and its overexpression was related to the degree of differentiation and metastases. Inhibiting USP28 expression in vitro suppressed the proliferation and invasion of gastric cancer cells by downregulating lysine specific demethylase 1. On the basis of our data, it can be concluded that USP28 may be a novel therapeutic target for gastric cancer.
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USP28 was found to be overexpressed in gastric cancer compared with normal gastric tissues.
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Overexpression of USP28 was related to the degree of differentiation and metastases.
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Inhibiting USP28 expression in vitro suppressed the proliferation and invasion of gastric cancer cells by downregulating lysine specific demethylase 1 (LSD1).
The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor ...T-cell (CAR-T) therapy in patients with MRD is currently unclear.
We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.
A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8%
51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group 77.8% (95% CI, 64.8-90.7%)
68.7% (95% CI, 47.7-89.6%), P = 0.575 and had a significantly higher 3-year LFS than those in the intensified chemotherapy group 77.8% (95% CI, 64.8-90.7%)
28.6% (95% CI, 4.9-52.3%), P = 0.001. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.
Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
AMPAR-lacking silent synapses are prevailed and essential for synaptic refinement and synaptic plasticity in developing brains. In mature brain, they are sparse but could be induced under several ...pathological conditions. How they are regulated molecularly is far from clear. miR-34a is a highly conserved and brain-enriched microRNA with age-dependent upregulated expression profile. Its neuronal function in mature brain remains to be revealed. Here by analyzing synaptic properties of the heterozygous miR-34a knock out mice (34a_ht), we have discovered that mature but not juvenile 34a_ht mice have more silent synapses in the hippocampus accompanied with enhanced synaptic NMDAR but not AMPAR function and increased spine density. As a result, 34a_ht mice display enhanced long-term potentiation (LTP) in the Schaffer collateral synapses and better spatial learning and memory. We further found that Creb1 is a direct target of miR-34a, whose upregulation and activation may mediate the silent synapse increment in 34a_ht mice. Hence, we reveal a novel physiological role of miR-34a in mature brains and provide a molecular mechanism underlying silent synapse regulation.
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•Reducing miR-34a selectively enhanced NMDAR-mediated synaptic transmission in mature adult but not juvenile hippocampus.•Adult 34a_ht mice have more silent synapses in CA1 of the hippocampus.•miR-34a directly targets Creb1.•34a_ht mice have elevated CREB1 expression and activation that correlates with more silent synapses.•34a_ht mice express stronger LTP in the Schaffer collateral synapses and display better spatial learning and memory.
Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara , ...Oryza glaberrima , Oryza barthii , Oryza glumaepatula , and Oryza meridionalis . Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.
Significance Asian rice ( Oryza sativa ) is among the world’s most important crops. The genus Oryza has become a model for the study of plant genome structure, function, and evolution. We have undertaken de novo, full-genome sequence analysis of five diploid AA-genome species that are closely related to O. sativa . These species are native to quite different environments, representing four continents, thus exhibiting very different adaptations. Our studies identify specific genetic changes, in both gene copy number and the degree of diversifying natural selection, that indicate specific genes responsible for these adaptations, particularly in genes related to defense against pathogens and reproductive diversification. This genome discovery and comparative analysis provide a powerful tool for future Oryza study and rice improvement.
By introducing the unprecedented and flexible isomeric bis(pyridyl-tetrazole) ligands into a polyoxometalates (POMs) system, three POM-based compounds, {Ag2(4-bptzb)2(H2O)2H2PMo12O402}·4-bptzb·5H2O ...(1), Ag4(3-bptzb)2(PMoVMoVI 11O40)·2H2O (2), and Ag3(3-bptzb)2.5(H2O)2H3P2W18O62 (3) 4-bptzb = 1,4-bis(5-(4-pyridyl)tetrazolyl)butane and 3-bptzb =1,4-bis(5-(3-pyridyl)tetrazolyl)butane, were synthesized under hydrothermal conditions and structurally characterized by single-crystal X-ray diffraction analyses. Compound 1 exhibits a dimeric structure constructed from two Keggin PMo12O403– anions and a binuclear Ag2(trans-4-bptzb)22+ subunit in which the trans-4-bptzb acts as a bidentate bridging ligand with one tetrazolyl group. In 2, the 3-bptzb acts as a tetradentate bridging ligand with the tetrazolyl and pyridyl groups linking AgI ions to generate a 3D metal–organic framework (MOF), which contains charming meso-helix chains. The Keggin anions acting as bidentate inorganic ligands reside in the distorted tetragonal channels of the MOF. In compound 3, the 3-bptzb adopts versatile coordination modes linking AgI ions to first construct loop connecting loop 1D chains, which are linked by {AgP2W18O62} n zigzag chains to form a scarce hamburger-style 2D sheet. These adjacent sheets are further fused by 3-bptzb ligands to construct a 3D framework. The influences of isomeric bptzb ligands and POMs on the construction of Ag-bptzb subunits and the whole structures of the title compounds are discussed. The electrochemical behaviors and electrocatalytic activities of compounds 2 and 3 and their corresponding parent POMs as well as the fluorescent properties of the title compounds have been studied in detail. In addition, the photocatalytic activities of compounds 2 and 3 and their corresponding parent POMs for decomposition of methylene blue, rhodamine B, and methyl orange under UV irradiation have also been investigated.
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