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.
Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an ...urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.
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.
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.
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 three-stage isothermal solidification process of TLP bonded Mar-M247 nickel-based superalloy was studied. The transient liquid phase bonding of Mar-M247 superalloys was conducted at 1150°C for 1, ...60, 120 and 240min. Dendritic formation and solute partitioning governed the microstructure development. Ni-rich solid solution, Ni-rich boride W-rich boride and other carboborides were formed in the joint area. The maximum tensile strength of 443MPa was obtained when TLP bonding at 1150°C for 240min. It had completed isothermal solidification. After isothermal solidification, the distribution of microhardness across the joints was more homogeneous. Enrichment of refractory elements in the Ni-Cr-Co-W-Ta-B interlayer was detrimental to the process of isothermal solidification. The presence of hard and brittle borides reduced the hardness and tensile strength of the bonded area. Post-bonding heat treatments are suggested to improve mechanical properties in future studies.
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.
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