Soil salinity is one of several major abiotic stresses that constrain maize productivity worldwide. An improved understanding of salt-tolerance mechanisms will thus enhance the breeding of ...salt-tolerant maize and boost productivity. Previous studies have indicated that the maintenance of leaf Na+ concentration is essential for maize salt tolerance, and the difference in leaf Na+ exclusion has previously been associated with variation in salt tolerance between maize varieties.
Here, we report the identification and functional characterization of a maize salt-tolerance quantitative trait locus (QTL), Zea mays Na
+
Content1 (ZmNC1), which encodes an HKT-type transporter (designated as ZmHKT1).
We show that a natural ZmHKT1 loss-of-function allele containing a retrotransposon insertion confers increased accumulation of Na+ in leaves, and salt hypersensitivity. We next show that ZmHKT1 encodes a plasma membrane-localized Na+-selective transporter, and is preferentially expressed in root stele (including the parenchyma cells surrounding the xylem vessels). We also show that loss of ZmHKT1 function increases xylem sap Na+ concentration and causes increased root-to-shoot Na+ delivery, indicating that ZmHKT1 promotes leaf Na+ exclusion and salt tolerance by withdrawing Na+ from the xylem sap.
We conclude that ZmHKT1 is a major salt-tolerance QTL and identifies an important new gene target in breeding for improved maize salt tolerance.
Malus’ law regulating the intensity of light when passed through a polarizer, forms the solid basis for image steganography based on orthogonal polarizations of light to convey hidden information ...without adverse perceptions, which underpins important practices in information encryptions, anti‐counterfeitings, and security labels. Unfortunately, the restriction to orthogonal states being taken for granted in the common perceptions fails to advance cryptoinformation to upgraded levels of security. By introducing a vectorial compound metapixel design, arbitrary nonorthogonal polarization multiplexing of independent grayscale images with high fidelity and strong concealment is demonstrated. The Jones matrix treatment of compound metapixels consisting of double atoms with tailored in‐plane orientation sum and difference allows point‐by‐point configuring of both the amplitude and polarization rotations of the output beam in an analytical and linear form. With this, both multiplexing two continuous grayscale images in arbitrary nonorthogonal polarization angles and concealing grayscale image on another in an arbitrary disclosure angle window are experimentally demonstrated in the visible TiO2 metasurface platform. The methods shed new light on multifarious metaoptics by harnessing the new degree of freedom and unlock the full potential of metasurface polarization optics.
A vectorial compound metapixel design enables independent and linear modulations of the output beam in both amplitude and polarization rotations across the Malus metasurface. With this, arbitrary‐angle steganography is demonstrated by both multiplexing two continuous grayscale images in arbitrary nonorthogonal polarization angles and concealing one grayscale image on another in an arbitrary disclosure angle window.
Poly(1,2‐dithiolane)s are a family of intrinsically recyclable polymers due to their dynamic covalent disulfide linkages. Despite the common use of thiolate‐initiated anionic ring‐opening ...polymerization (ROP) under basic condition, cationic ROP is still not exploited. Here we report that disulfide bond can act as a proton acceptor, being protonated by acids to form sulfonium cations, which can efficiently initiate the ROP of 1,2‐dithiolanes and result in high‐molecular‐weight (over 1000 kDa) poly(disulfide)s. The reaction can be triggered by adding catalytic amounts of acids and non‐coordinating anion salts, and completed in few minutes at room temperature. The acidic conditions allow the applicability for acidic monomers. Importantly, the reaction condition can be under open air without inert protection, enabling the nearly quantitative chemical recycling from bulk materials to original monomers.
Acid can catalyze the reversible polymerization of cyclic disulfides, enabling a robust methodology that produces long poly(disulfide)s within a few minutes under open‐air condition. High‐yield chemical recycling from materials to monomers is achieved at gram scale, showing the capability of intrinsic dynamic polymers toward sustainable materials.
Measures taken to control the disease (Covid-19) caused by the novel coronavirus dramatically reduced the number of vehicles on the road and diminished factory production. For this study, changes in ...the air quality index (AQI) and the concentrations of six air pollutants (PM2.5, PM10, CO, SO2, NO2, and O3) were evaluated during the Covid-19 control period in northern China. Overall, the air quality improved, most likely due to reduced emissions from the transportation and secondary industrial sectors. Specifically, the transportation sector was linked to the NO2 emission reductions, while lower emissions from secondary industries were the major cause for the reductions of PM2.5 and CO. The reduction in SO2 concentrations was only linked to the industrial sector. However, the reductions in emissions did not fully eliminate air pollution, and O3 actually increased, possibly because lower fine particle loadings led to less scavenging of HO2 and as a result greater O3 production. These results also highlight need to control emissions from the residential sector.
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•The overall air quality was improved during the control of Covid-19.•The improvement was caused by reduced emissions from transportation and industry.•It is necessary to strengthen emissions from the residential sector.
Nowadays, cell membrane‐targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane‐targeted self‐delivery theranostic chimeric ...peptide CMP‐PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real‐time therapeutic feedback. Self‐assembled CMP‐PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP‐PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)‐carboxyfluorescein (FAM) and 4‐(dimethylaminoazo)‐benzene‐4‐carboxylic acid (Dabcyl). More importantly, CMP‐PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP‐PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp‐Glu‐Val‐Asp (DEVD) is subsequently cleaved by activated caspase‐3 and activated caspase‐7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase‐3 in vitro and in vivo to feedback real‐time PDT therapeutic efficacy. In general, a novel cell membrane‐targeted self‐delivery theranostic chimeric peptide offers new promise for effective imaging‐guided PDT.
In this work, a theranostic chimeric peptide CMP‐PpIX with self‐delivery properties is developed for cell membrane‐targeting photodynamic therapy (PDT) and exhibits greatly improved therapy efficacy in vitro and in vivo. Moreover, in situ therapeutic feedback can be realized by the caspase sensitive probe segment in CMP‐PpIX. This study offers a new promise for imaging‐guided high efficient PDT.
Atomically thin 2D crystals have gained tremendous attention owing to their potential impact on future electronics technologies, as well as the exotic phenomena emerging in these materials. ...Monolayers of α‐phase Sb (α‐antimonene), which shares the same puckered structure as black phosphorous, are predicted to be stable with precious properties. However, the experimental realization still remains challenging. Here, high‐quality monolayerα‐antimonene is successfully grown, with the thickness finely controlled. The α‐antimonene exhibits great stability upon exposure to air. Combining scanning tunneling microscopy, density functional theory calculations, and transport measurements, it is found that the electron band crossing the Fermi level exhibits a linear dispersion with a fairly small effective mass, and thus a good electrical conductivity. All of these properties make the α‐antimonene promising for future electronic applications.
Monolayer α‐phase antimonene, a structural analog to black phosphorous, is fabricated on a WTe2 substrate. The α‐antimonene exhibits great stability upon exposure to air. Its electron band crossing the Fermi level exhibits a linear dispersion with a fairly small effective mass, and thus a good electrical conductivity. All of these properties make α‐antimonene promising in future electronic applications.
Background and Aims
Heparin‐binding epidermal growth factor (HB‐EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and ...regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB‐EGF to promote angiogenesis and HCC progression.
Approach and Results
A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB‐EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia‐inducible factor 1 α signaling pathway. In addition, HB‐EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3‐kinase/Akt signaling pathway. The level of HB‐EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence‐free survival, which suggests that HB‐EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB‐EGF inhibitor cross‐reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression.
Conclusions
HB‐EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB‐EGF inhibitor cross‐reacting material 197 with sorafenib might be used for individualized treatment of HCC.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health
. Bats have been recognized as one of the most important reservoirs for emerging ...viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)
. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
Background and Aims
Although NASH can lead to severe clinical consequences, including cirrhosis and hepatocellular carcinoma, no effective treatment is currently available for this disease. ...Increasing evidence indicates that LSECs play a critical role in NASH pathogenesis; however, the mechanisms involved in LSEC‐mediated NASH remain to be fully elucidated.
Approach and Results
In the current study, we found that LSEC homeostasis was disrupted and LSEC‐specific gene profiles were altered in methionine–choline‐deficient (MCD) diet‐induced NASH mouse models. Importantly, Notch signaling was found to be activated in LSECs of NASH mice. To then investigate the role of endothelial Notch in NASH progression, we generated mouse lines with endothelial‐specific Notch intracellular domain (NICD) overexpression or RBP‐J knockout to respectively activate or inhibit Notch signaling in endothelial cells. Notably, endothelial‐specific overexpression of the NICD accelerated LSEC maladaptation and aggravated NASH, whereas endothelial cell–specific inhibition of Notch signaling restored LSEC homeostasis and improved NASH phenotypes. Furthermore, we demonstrated that endothelial‐specific Notch activation exacerbated NASH by inhibiting endothelial nitric oxide synthase (eNOS) transcription, whereas administration of the pharmacological eNOS activator YC‐1 alleviated hepatic steatosis and lipid accumulation resulting from Notch activation. Finally, to explore the therapeutic potential of using Notch inhibitors in NASH treatment, we applied two gamma‐secretase inhibitors—DAPT and LY3039478—in an MCD diet‐induced mouse model of NASH, and found that both inhibitors effectively ameliorated hepatic steatosis, inflammation, and liver fibrosis.
Conclusions
Endothelial‐specific Notch activation triggered LSEC maladaptation and exacerbated NASH phenotypes in an eNOS‐dependent manner. Genetic and pharmacological inhibition of Notch signaling effectively restored LSEC homeostasis and ameliorated NASH progression.
Background & Aims Neutrophils can either promote or inhibit tumor progression, depending on the tumor microenvironment, via release of cytokines. Neither the factors produced by tumor-associated ...neutrophils (TANs) nor their effects on tumor progression have been characterized. We investigated the roles of TANs in progression of hepatocellular carcinoma (HCC) using cell lines and immune cells isolated from patients. Methods We performed studies with HepG2, PLC/PRF/5, MHCC97H, and HCCLM3 human and Hepa1-6 and H22 mouse HCC cell lines; expression of chemokines and cytokines were knocked down with small hairpin RNAs. Cells were analyzed in chemotaxis assays and as growth as tumors in mice. HCC tissues and peripheral blood were collected from 20 patients undergoing curative resection or 20 healthy individuals (controls) in 2012 at Zhongshan Hospital in China. TANs and peripheral blood neutrophils (PBNs) were isolated and exposed to conditioned media from HCC cell lines; reverse-transcription polymerase chain reaction was used to quantify the expression of cytokines and chemokines. We collected neutrophils from another 60 patients undergoing curative resection for HCC in 2012 to measure the production of CCL2 and CCL17. Patients were followed up until March 15, 2014. For immunohistochemical analyses, we collected HCC tissues and paired, adjacent, nontumor cirrhotic liver tissues from 832 HCC patients undergoing curative resection from 2006 through 2008. All patients were followed up until March 15, 2013. To study the effects of sorafenib, we collected clinical and pathology data from 46 patients who underwent curative resection in 2010. Results CCL2 and CCL17 were the cytokines most highly expressed by TANs and HCC cell-activated PBNs. Levels of CCL2 and CCL17 messenger RNAs and proteins were significantly higher in TANs than in PBNs, and increased in patients with HCC recurrence. CCL2 and CCL17 messenger RNA and proteins also increased when PBNs were exposed to conditioned media from HCC cell lines. Immunohistochemical analysis of a tissue microarray showed that CCL2+ and CCL17+ cells, which also expressed the neutrophil marker CD66b, were distributed throughout the HCC stroma, but not in tumor cells or the adjacent nontumor liver cells. The number of CCL2+ or CCL17+ TANs correlated with tumor size, microvascular invasion, tumor encapsulation, tumor differentiation, and stage. Patients whose tumors had lower levels of CCL2+ or CCL17+ cells had longer survival times than those with higher numbers of these cells. TAN-conditioned media, as well as recombinant CCL2 and CCL17, increased the migratory activity of the macrophages and T-regulatory (Treg) cells from patients or mice with HCC to a greater extent that PBN-conditioned media. Neutralizing antibodies against CCL2 and CCL17, or their receptors C-C chemokine receptor 2 and C-C chemokine receptor 4, reduced the migratory activities of macrophage and Treg cells. HCC cell lines injected into mice formed larger tumors when they were co-injected with TANs and formed more pulmonary metastases; these tumors were infiltrated by Ly6G+ cells, F4/80+ macrophages, and Foxp3+ Treg cells. In a phosphokinase array of human PBNs, levels of phosphorylated AKT and P38 increased after exposure to conditioned media from all 4 HCC cell types. Pharmacologic inhibitors of AKT and P38 inhibited secretion of CCL2 and CCL17 by these PBNs. In tumor-bearing mice, sorafenib increased the numbers of TANs and levels of CCL2 and CCL17 in tumors. HCC tissues from patients who received sorafenib before surgery contained more TANs than tissues from patients who did not receive sorafenib. In knockdown cells, HCC cell–derived CXCL5 was the strongest effector of neutrophil migration under hypoxic conditions. In mice, the combination of sorafenib and TAN depletion inhibited tumor growth and neovascularization to a greater extent than sorafenib alone. Conclusions TANs recruit macrophages and Treg cells to HCCs to promote their growth, progression, and resistance to sorafenib.
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