SUMMARY
Recent studies have shown that global metabolic reprogramming is a common event in plant innate immunity; however, the relevant molecular mechanisms remain largely unknown. Here, we ...identified a pathogen‐induced glycosyltransferase, UGT73C7, that plays a critical role in Arabidopsis disease resistance through mediating redirection of the phenylpropanoid pathway. Loss of UGT73C7 function resulted in significantly decreased resistance to Pseudomonas syringae pv. tomato DC3000, whereas constitutive overexpression of UGT73C7 led to an enhanced defense response. UGT73C7‐activated immunity was demonstrated to be dependent on the upregulated expression of SNC1, a Toll/interleukin 1 receptor‐type NLR gene. Furthermore, in vitro and in vivo assays indicated that UGT73C7 could glycosylate p‐coumaric acid and ferulic acid, the upstream metabolites in the phenylpropanoid pathway. Mutations that lead to the loss of UGT73C7 enzyme activities resulted in the failure to induce SNC1 expression. Moreover, glycosylation activity of UGT73C7 resulted in the redirection of phenylpropanoid metabolic flux to biosynthesis of hydroxycinnamic acids and coumarins. The disruption of the phenylpropanoid pathway suppressed UGT73C7‐promoted SNC1 expression and the immune response. This study not only identified UGT73C7 as an important regulator that adjusts phenylpropanoid metabolism upon pathogen challenge, but also provided a link between phenylpropanoid metabolism and an NLR gene.
Significance Statement
Global metabolic reprogramming is a common event in plant innate immunity; however, the relevant molecular mechanisms remain largely unknown. Here, we identified that the pathogen‐induced glycosyltransferase UGT73C7 is an important regulator that adjusts phenylpropanoid metabolism upon pathogen challenge and promotes SNC1‐dependent Arabidopsis immunity, thus providing a link between phenylpropanoid metabolism and an NLR gene.
The chemokine C-C motif ligand 11, also known as eotaxin-1, has been identified as a novel mediator of inflammatory bone resorption. However, little is known regarding a potential role for ...CCL11/Eotaxin-1 in postmenopausal osteoporosis.
The scope of this study was to explore the relationship between serum CCL11/Eotaxin-1 concentrations and disease progression of postmenopausal females with osteoporosis.
A total of 83 postmenopausal women diagnosed with osteoporosis were enrolled. Meanwhile, 82 postmenopausal women with normal bone mineral density (BMD) and 85 healthy controls inner child-bearing age were enrolled as control. The Dual-energy X-ray absorptiometry was used to examine the BMDs at the femoral neck, lumbar spine 1-4 and total hip of all participants. Serum CCL11/Eotaxin-1 levels were examined by enzyme-linked immunosorbent assay. We also included inflammation marker interleukin-6 (IL-6) as well as a serum marker of bone resorption C-telopeptide cross-linked collagen type 1 (CTX-1). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were recorded to evaluate the clinical severity in POMP females.
Serum CCL11/Eotaxin-1 levels were significantly elevated in postmenopausal osteoporotic patients PMOP patients compared with PMNOP and healthy controls. We observed a significant negative correlation of serum CCL11/Eotaxin-1 levels with lumbar spine, femoral neck and total hip BMD. Furthermore, serum CCL11/ Eotaxin-1 concentrations were also positively related to the VAS and ODI scores. Last, serum CCL11/ Eotaxin-1 concentrations were positively associated with IL-6 and CTX-1 levels. These correlations remain significant after adjusting for age and BMI. Multivariate linear regression analysis demonstrated that CCL11/Eotaxin-1 could serve as an independent marker.
Serum CCL 11/Eotaxin-1 may serve as a candidate biomarker for postmenopausal osteoporosis. Therapeutics targeting CCL11/Eotaxin-1 and its related signalling way to prevent and slow progression of PMOP deserve further study.
Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very ...urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3′-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3′-monoximes 5a–5z and 5aa–5ad displayed good potency against
S. aureus
ATCC25923 (MIC = 0.4–25.6 μg mL
−1
). Among them, we found that the 5-F, 5-Cl and 7-CF
3
substituted indirubin-3′-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for
S. aureus
(MICs up to 0.4 μg mL
−1
) than the prototype natural product indirubin (MIC = 32 μg mL
−1
). More importantly, indirubin-3′-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant
S. aureus
(fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating
S. aureus
with indirubin-3′-monoxime 5aa, and the results revealed that indirubin-3′-monoximes could increase the cell membrane permeability of
S. aureus
. Although indirubin-3′-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 μg mL
−1
had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.
In flowering plants, sperm cells are delivered to the embryo sac by a pollen tube guided by female signals. Both the gametic and synergid cells contribute to pollen tube attraction. Synergids secrete ...peptide signals that lure the tube, while the role of the gametic cells is unknown. Previously, we showed that CENTRAL CELL GUIDANCE (CCG) is essential for pollen tube attraction in Arabidopsis thaliana, but the molecular mechanism is unclear. Here, we identified CCG BINDING PROTEIN1 (CBP1) and demonstrated that it interacts with CCG, Mediator subunits, RNA polymerase II (Pol II), and central cell-specific AGAMOUS-like transcription factors. In addition, CCG interacts with TATA-box Binding Protein 1 and Pol II as a TFIIB-like transcription factor. CBP1- knockdown ovules are defective in pollen tube attraction. Expression profiling revealed that cysteine-rich peptide (CRP) transcripts were downregulated in ccg ovules. CCG and CBP1 coregulate a subset of CRPs in the central cell and the synergids, including the attractant LURE1. CBP1 is extensively expressed in multiple vegetative tissues and specifically in the central cell in reproductive growth. We propose that CBP1, via interaction with CCG and the Mediator complex, connects transcription factors and the Pol II machinery to regulate pollen tube attraction.
Modification of natural polysaccharides such as chitosan (CS), β‑cyclodextrin (β-CD), and alginic acid offers a promising strategy for the preparation of smart drug carriers, and latest innovations ...on such carriers are focused on stimuli-responsive biomaterials. In this study, highly hydrophilic three-demensional (3D) porous CS-grafted β-CD (CS-g-β-CD) was prepared through the Williamson ether synthesis reaction with epichlorohydrin (ECH) as the crosslinker and the consequent nucleophilic reaction between the epoxide ring of ECH and the primary amine of CS, which was then characterized by 1H nuclear (1H NMR), Fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD) analysis, scanning electron microscope (SEM), thermogravimetry (TG), and N2 adsorption/desorption isotherms. When etoposide (VP16), an anti-cancer drug, was encapsulated in the CS-g-β-CD, the encapsulation ratio was up to 73.6%. Finally, the resultant CS-g-β-CD was successfully used as the responsive drug carrier for pH- and thermo-sensitive release of VP16. This work opens a new avenue for the preparation of stimuli-responsive drug carriers with modified natural polysaccharides.
•CS-g-β-CD is synthesized via Williamson ether synthesis and nucleophilic reaction.•Epichlorohydrin functions as a crosslinker in the synthesis of CS-g-β-CD.•The CS-g-β-CD is highly hydrophilic and exhibits a 3D porous network structure.•The release of etoposide (VP16) from the CS-g-β-CD is pH- and thermo-sensitive.•The sustained release of VP16 from the CS-g-β-CD is due to its 3D porous structure.
Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. ...Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU μL–1 (18 fM spike protein), with a linear range of 250–10,000 TU μL–1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.
This paper extends the second-order three-wave flow of Fordy and Kulish to propose a generalized second-order flow of the three-wave hierarchy. Then the Lax pair of the generalized second-order ...three-wave flow is constructed by the standard prolongation technique, and the infinite conservation laws for this flow are derived. Finally, the Riemann-Hilbert approach is applied to the initial value problem of this flow, and the N-soliton solutions to the second-order three-wave flow are derived explicitly. Collision behaviors of the two and three solitons are demonstrated graphically, which shows that our results have potential applications to the resonant three-wave interactions in nonlinear media.
To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their ...translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.
Summary of main observation and conclusion
The N‐glycans attached to some chloroviruses comprise a hyperbranched core structure without precedent. We are interested in the chemical synthesis of the ...hexasaccharide attached to ATCV‐1 (Acanthocystis turfacea Chlorella virus 1) for its distinct structure. After exploring four routes, the target hexasaccharide 2 was successfully synthesized for the first time in overall 10% yield over 8 steps from thioglycoside building blocks. This synthetic protocol is characterized by the three‐component one‐pot glycosylation and the regioselective glycosylation reactions. The disclosed synthetic approach to this new type of N‐glycans will facilitate the in‐depth understanding of their biological functions.
A highly branched hexasaccharide was successfully synthesized by the three‐component preactivation‐based one‐pot glycosylation and the regioselective glycosylation reactions for the first time.
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