Salt stress can significantly affect plant growth and agricultural productivity. Receptor-like kinases (RLKs) are believed to play essential roles in plant growth, development, and responses to ...abiotic stresses. Here, we identify a receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase 1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative stress tolerance. Our results show that STRK1 anchors and interacts with CatC at the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210 and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits higher catalase activity both in vitro and in planta, and salt stress enhances STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants, STRK1-overexpressing plants exhibited higher catalase activity and lower accumulation of H2O2 as well as higher tolerance to salt and oxidative stress. Our findings demonstrate that STRK1 improves salt and oxidative tolerance by phosphorylating and activating CatC and thereby regulating H2O2 homeostasis. Moreover, overexpression of STRK1 in rice not only improved growth at the seedling stage but also markedly limited the grain yield loss under salt stress conditions. Together, these results offer an opportunity to improve rice grain yield under salt stress.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Abstract
Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn ...delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.
Uranium is important in the nuclear fuel cycle both as an energy source and as radioactive waste. It is of vital importance to recover uranium from nuclear waste solutions for further treatment and ...disposal. Herein we present the first chalcogenide example, (Me2NH2)1.33(Me3NH)0.67Sn3S7·1.25H2O (FJSM-SnS), in which organic amine cations can be used for selective UO2 2+ ion-exchange. The UO2 2+-exchange kinetics perfectly conforms to pseudo-second-order reaction, which is observed for the first time in a chalcogenide ion-exchanger. This reveals the chemical adsorption process and its ion-exchange mechanism. FJSM-SnS has excellent pH stability in both strongly acidic and basic environments (pH = 2.1–11), with a maximum uranium-exchange capacity of 338.43 mg/g. It can efficiently capture UO2 2+ ions in the presence of high concentrations of Na+, Ca2+, or HCO3 – (the highest distribution coefficient K d value reached 4.28 × 104 mL/g). The material is also very effective in removing of trace levels of U in the presence of excess Na+ (the relative amounts of U removed are close to 100%). The UO2 2+···S2– interactions are the basis for the high selectivity. Importantly, the uranyl ion in the exchanged products could be easily eluted with an environmentally friendly method, by treating the UO2 2+-laden materials with a concentrated KCl solution. These advantages coupled with the very high loading capacity, low cost, environmentally friendly nature, and facile synthesis make FJSM-SnS a new promising remediation material for removal of radioactive U from nuclear waste solutions.
A promising anode material consisting of bimetallic thiophosphate ZnxCo1−xPS3 and CoS2 with 2D/3D heterostructure is designed and prepared by an effective chemical transformation. Density functional ...theory calculations illustrate that the Zn2+ can effectively modulate the electrical ordering of ZnxCo1−xPS3 on the nanoscale: the reduced charge distribution emerging around the Zn ions can enhance the local built‐in electric field, which will accelerate the ions migration rate by Coulomb forces and provide tempting opportunities for manipulating Li+ storage behavior. Moreover, the merits of the large planar size enable ZnxCo1–xPS3 to provide abundant anchoring sites for metallic CoS2 nanocubes, generating a 2D/3D heterostructure with a strong electric field. The resultant ZnxCo1−xPS3/CoS2 can offer the combined advantages of bimetallic alloying and heterostructure in lithium storage applications, leading to outstanding performance as an anode material for lithium‐ion batteries. Consequently, a high capacity of 794 mA h g−1 can be retained after 100 cycles at 0.2 A g−1. Even at 3.0 A g−1, a satisfactory capacity of 465 mA h g−1 can be delivered. The appealing alloying‐heterostructure and electrochemical performance of this bimetallic thiophosphate demonstrate its great promise for applications in practical rechargeable batteries.
A promising anode material consisting of bimetallic thiophosphate ZnxCo1−xPS3 and CoS2 with 2D/3D heterostructure is prepared. The hetero‐Zn alloying can produce an enhanced asymmetric E‐field to accelerate electron transfer and adjust the interlayer distance to create small volume changed MPS3 electrodes. Additionally, metallic CoS2 deposited on semiconductor ZnxCo1−xPS3 can form a strong E‐field, favoring the transportation of electrons.
The Haber–Bosch process for industrial-scale NH3 production suffers from high energy consumption and serious CO2 emission. Electrochemical N2 reduction is an attractive carbon-neutral alternative for ...NH3 synthesis but is severely restricted due to N2 activation needing efficient electrocatalysts for the N2 reduction reaction (NRR) under ambient conditions. Here, we report that Ti3C2Tx (T = F, OH) MXene nanosheets act as high-performance 2D NRR electrocatalysts for ambient N2-to-NH3 conversion with excellent selectivity. In 0.1 M HCl, such catalysts achieve a large NH3 yield of 20.4 µg h−1 mgcat.−1 and a high faradic efficiency of 9.3% at −0.4 V vs. reversible hydrogen electrode, with high electrochemical and structural stability. Density functional theory calculations reveal that N2 chemisorbed on Ti3C2Tx experiences elongation/weakness of the N≡N triple bond facilitating its catalytic conversion to NH3 and the distal NRR mechanism is more favorable with the final reaction of *NH2 to NH3 as the rate-limiting step.
An efficient asymmetric dearomative 3+2 cycloaddition reaction of 2‐nitroindoles and 2‐nitrobenzothiophenes with 3‐isothiocyanato oxindoles was developed by using a chiral Zn(OTf)2/bis(oxazoline) ...complex as a catalyst. With the developed protocol, a range of enantioenriched complex heterocyclic compounds containing three contiguous stereocenters, one of which is spirocyclic center, could be obtained in quantitative yields with excellent diastereo‐ and enantioselectivities. The potential utility of this method was showcased by the diverse transformations of the products.
Aims
To investigate the pharmacokinetics and pharmacodynamics of a dual‐acting glucokinase activator, dorzagliatin, and its safety, tolerability and effect on pancreatic β‐cell function in Chinese ...patients with type 2 diabetes (T2D).
Materials and methods
A total of 24 T2D patients were selected, utilizing a set of predefined clinical biomarkers, and were randomized to receive dorzagliatin 75 mg twice or once daily (BID, QD respectively) for 28 days. Changes in HbA1c and glycaemic parameters from baseline to Day 28 were assessed. In addition, changes in β‐cell function from baseline to Day 32 were evaluated.
Results
Significant reductions in HbA1c were observed in both regimens on Day 28 (−0.79%, 75 mg BID; −1.22%, 75 mg QD). Similar trends were found in the following parameters, including reductions from baseline in fasting plasma glucose by 1.20 mmol/L and 1.51 mmol/L, in 2‐hour postprandial glucose by 2.48 mmol/L and 5.03 mmol/L, and in glucose AUC0–24 by 18.59% and 20.98%, for the BID and QD groups, respectively. Both regimens resulted in improvement in β‐cell function as measured by steady state HOMA 2 parameter, %B, which increased by 36.31% and 40.59%, and by dynamic state parameter, ΔC30/ΔG30, which increased by 24.66% and 167.67%, for the BID and QD groups, respectively. Dorzagliatin was well tolerated in both regimens, with good pharmacokinetic profiles.
Conclusions
Dorzagliatin treatment for 28 days in Chinese T2D patients, selected according to predefined biomarkers, resulted in significant improvement in β‐cell function and glycaemic control. The safety and pharmacokinetic profile of dorzagliatin supports a subsequent Phase II trial design and continued clinical development.
Chemokines play a key role in orchestrating the recruitment and positioning of myeloid cells within the tumor microenvironment. However, the tropism regulation and functions of these cells in ...hepatocellular carcinoma (HCC) are not completely understood. Herein, by scrutinizing the expression of all chemokines in HCC cell lines and tissues, we found that CCL15 was the most abundantly expressed chemokine in human HCC. Further analyses showed that CCL15 expression was regulated by genetic, epigenetic, and microenvironmental factors, and negatively correlated with patient clinical outcome. In addition to promoting tumor invasion in an autocrine manner, CCL15 specifically recruited CCR1+ cells toward HCC invasive margin, approximately 80% of which were CD14+ monocytes. Clinically, a high density of marginal CCR1+CD14+ monocytes positively correlated with CCL15 expression and was an independent index for dismal survival. Functionally, these tumor‐educated monocytes directly accelerated tumor invasion and metastasis through bursting various pro‐tumor factors and activating signal transducer and activator of transcription 1/3, extracellular signal‐regulated kinase 1/2, and v‐akt murine thymoma viral oncogene homolog signaling in HCC cells. Meanwhile, tumor‐derived CCR1+CD14+ monocytes expressed significantly higher levels of programmed cell death‐ligand 1, B7‐H3, and T‐cell immunoglobulin domain and mucin domain‐3 that may lead to immune suppression. Transcriptome sequencing confirmed that tumor‐infiltrating CCR1+CD14+ monocytes were reprogrammed to upregulate immune checkpoints, immune tolerogenic metabolic enzymes (indoleamine and arginase), inflammatory/pro‐angiogenic cytokines, matrix remodeling proteases, and inflammatory chemokines. Orthotopic animal models confirmed that CCL15‐CCR1 axis forested an inflammatory microenvironment enriched with CCR1+ monocytes and led to increased metastatic potential of HCC cells. Conclusion: A complex tumor‐promoting inflammatory microenvironment was shaped by CCL15‐CCR1 axis in human HCC. Blockade of CCL15‐CCR1 axis in HCC could be an effective anticancer therapy.
Pursuing novel materials with efficient photothermal conversion under irradiation at the near-infrared region windows (NIR, 750-850 nm; NIR-I and NIR-II, 1000-1320 nm)) is of great importance due to ...their irreplaceable applications, especially in the biomedical field. Herein, on the basis of a coordination chemistry strategy, an iron-based metal-organic framework (MOF) of N(CH
)
Fe
(NDC)
·DMF·3H
O (
, 1,4-H
NDC = 1,4-naphthalenedicarboxylic acid, N(CH
)
= tetramethyl-ammonium, and DMF = N,N-dimethylformamide) was prepared and characterized. Due to the
-
transition effect introduced by coordination with the transition-metal ion of iron and the highly conjugated naphthalenic moiety in 1,4-H
NDC, guaranteeing an energy transfer between iron and the organic module,
shows a remarkable broad absorption, which could be extended into the NIR-II section. As a result,
could be irradiated by NIR laser (both 808 and 1064 nm) to achieve photothermal conversion. This work sets a good example to inspire the future designation of NIR light-irradiated photothermal materials based on the first-row transition metals.
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