Summary
Brassinosteroids (BRs) are essential hormones that play crucial roles in plant growth, reproduction and response to abiotic and biotic stress. In Arabidopsis, AtCYP85A2 works as a ...bifunctional cytochrome P450 monooxygenase to catalyse the conversion of castasterone to brassinolide, a final rate‐limiting step in the BR‐biosynthetic pathway. Here, we report the functional characterizations of PtCYP85A3, one of the three AtCYP85A2 homologous genes from Populus trichocarpa. PtCYP85A3 shares the highest similarity with AtCYP85A2 and can rescue the retarded‐growth phenotype of the Arabidopsis cyp85a2‐2 and tomato dx mutants. Constitutive expression of PtCYP85A3, driven by the cauliflower mosaic virus 35S promoter, increased the endogenous BR levels and significantly promoted the growth and biomass production in both transgenic tomato and poplar. Compared to the wild type, plant height, shoot fresh weight and fruit yield increased 50%, 56% and 43%, respectively, in transgenic tomato plants. Similarly, plant height and stem diameter increased 15% and 25%, respectively, in transgenic poplar plants. Further study revealed that overexpression of PtCYP85A3 enhanced xylem formation without affecting the composition of cellulose and lignin, as well as the cell wall thickness in transgenic poplar. Our finding suggests that PtCYP85A3 could be used as a potential candidate gene for engineering fast‐growing trees with improved wood production.
•Proposing a new perspective of CS use in dyes selective and effective removal.•Constructing water- and acid-stablility composite film with simple physical modification.•Elucidating the mechanism of ...adsorption performance by CNF/CS films.
To effectively and selectively remove toxic anionic dyes which are heavily discharged and to promote them recovery, a sustainable cellulose nanofiber/chitosan (CNF/CS) composite film was elaborately designed through a facile procedure. Based on the strong supporting effect of CNF and excellent compatibility between CNF and CS, the composite film presents low swelling and acid-proof properties, which can prevent the adsorption process from the disintegration of adsorbent. Moreover, the positive electrical property of CNF/CS film increases the discrepancy in adsorption capacities for anionic and cationic dyes. The maximum adsorption capacity of anionic methyl orange (MO) on CNF/CS film reaches 655.23 mg/g with a desirable recyclability. The adsorption behavior attributed to a physico-chemical and monolayer adsorption process. This work opens a new route for the development of eco-friendly and highly efficient adsorbents on selective removal and recycling of anionic dyes from wastewater.
The halophyte Suaeda salsa displayed strong resistance to salinity. Up to date, molecular mechanisms underlying tolerance of S. salsa to salinity have not been well understood. In the present study, ...S. salsa seedlings were treated with 30‰ salinity and then leaves and roots were subjected to Illumina sequencing. Compared with the control, 68,599 and 77,250 unigenes were significantly differentially expressed in leaves and roots in saline treatment, respectively. KEGG enrichment analyses indicated that photosynthesis process, carbohydrate, lipid and amino acid metabolisms were all downregulated in saline treatment, which should inhibit growth of S. salsa. Expression levels of Na+/H+ exchanger, V-H+ ATPase, choline monooxygenase, potassium and chloride channels were upregulated in saline treatment, which could relieve reduce over-accumulation of Na+ and Cl-. Fe-SOD, glutathione, L-ascorbate and flavonoids function as antioxidants in plants. Genes in relation to them were all upregulated, suggesting that S. salsa initiated various antioxidant mechanisms to tolerate high salinity. Besides, plant hormones, especially auxin, ethylene and jasmonic acid signaling transduction pathways were all upregulated in response to saline treatment, which were important to gene regulations of ion transportation and antioxidation. These changes might comprehensively contribute to tolerance of S. salsa to salinity. Overall, the present study provided new insights to understand the mechanisms underlying tolerance to salinity in halophytes.
We show herein the phosphatase‐like catalytic activity of coordination polymers obtained after adding Ag+‐ions to thiols bearing hydrophobic alkyl chains terminated with a 1,4,7‐triazacyclononane ...(TACN) group. The subsequent addition of Zn2+ ‐ions to the self‐assembled polymers resulted in the formation of multivalent metal coordination polymers capable of catalysing the transphosphorylation of an RNA‐model compound (2‐hydroxypropyl‐4‐nitrophenyl phosphate, HPNPP) with high reactivity. Analysis of a series of metal ions showed that the highest catalytic activity was obtained when Ag+‐ions were used as the first metal ions to construct the backbone of the coordination polymer through interaction with the ‐SH group followed by Zn2+‐ions as the second metal ions complexed by the TACN‐macrocycle. Furthermore, it was demonstrated that the catalytic activity could be modulated by changing the length of the hydrophobic alkyl chain.
A series of self‐assembled multivalent Ag‐SR coordination polymers with high phosphatase‐like activity have been developed. This work represents a new alternative for the future rational design of highly efficient catalysts for hydrolysis of phosphates and carboxylates.
Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial ...omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G
or G
trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.
Cancer recurrence and metastasis are worldwide challenges but current bimodular strategies such as combined radiotherapy and chemotherapy (CTX), and photothermal therapy (PTT) and immunotherapy have ...succeeded only in some limited cases. Thus in the present study, a multifunctional nanomedicine has been rationally designed via elegantly integrating three FDA-approved therapeutics, that is, indocyanine green (for PTT), doxorubicin (for CTX), and CpG (for immunotherapy) into the structure of layered double hydroxide (LDH) nanoparticles, aiming to completely prevent the recurrence and metastasis of invasive breast cancer. This multifunctional hybrid nanomedicine has been demonstrated to eliminate the primary tumor and efficiently prevent tumor recurrence and lung metastasis through combined PTT/CTX and induction of specific and strong immune responses mediated by the hybrid nanomedicine in a 4T1 breast cancer mouse model. Furthermore, the promoted in situ immunity has significantly inhibited the growth of reinoculated distant tumors. Altogether, our multifunctional LDH-based nanomedicine has showed an excellent efficacy in invasive cancer treatment using much lower doses of three FDA-approved therapeutics, providing a preclinical/clinical alternative to cost-effectively treat invasive breast cancer.
Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus ...lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.
We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.
At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.
The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.
ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Genetic markers have emerged as one of the most promising tools for species identification and geographic traceability in biodiversity conservation and international trade of biological products. ...However, traditional molecular markers rarely have sufficient resolution at lower taxonomic levels, especially for discriminating closely related forest tree species and their populations. In this study, we developed a panel of RNA‐Seq based single nucleotide polymorphism (SNP) markers for tracing the geographic origin of an endangered conifer, Cathaya argyrophylla, which is a paleoendemic restricted to four mountain regions in subtropical China. A total of 69 individuals from five populations (DLS, SHS, HP, BMS, and DYS) covering the entire range were used for transcriptome sequencing. Based on these transcriptomic data, we evaluated genetic variation and population structure of C. argyrophylla, and found extremely low nucleotide diversity but strong population differentiation. We also screened 113 population‐specific SNP loci, including 96 for BMS, eight for DYS, six for SHS, two for HP, and one for one of the three subpopulations from DLS. According to these geographically diagnostic SNPs, we designed four population‐specific molecular barcodes for PCR amplification. To test the utility and efficiency of the four markers in geographic discrimination, double‐blind experiment was performed using 157 individuals labelled without any locality information. We found that almost all tested individuals could be successfully assigned to their geographic localities. Our study not only sheds some new light on the genetic profile of C. argyrophylla, but also provides a practical and cost‐efficient solution for geographic traceability using transcriptome‐derived SNPs.
Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance. However, the conventional subcutaneous (SC) vaccination ...normally induces limited anti-tumor immune responses with low therapeutic efficacy. Herein, we devised clay-based nanovaccines and directly delivered them to the spleen via intravenous (IV) injection to induce the stronger anti-tumor immunity with higher efficacy for tumor prevention and treatment. The clay, i.e., layered double hydroxide (LDH) was prepared as nanoadjuvant with the average size from 77 to 285 nm and co-loaded with the model antigen ovalbumin (OVA) and bioadjuvant CpG to form CpG/OVA-LDH (CO-LDH) nanovaccines. We found that CO-LDH-215 (the size of LDH was 215 nm) promoted dendritic cells to present the most antigen, and moreover showed the highest spleen enrichment (~ 1.67% of CO-LDH-215 enriched in the spleen at 24 h post IV injection). The
in vivo
immunologic data showed that CO-LDH-215 induced the most potent anti-tumor immune responses and completely prevented the growth of E.G7-OVA tumor in the mouse model. Furthermore, IV injected CO-LDH-215 nanovaccine more effectively delayed tumor growth than that SC injected, largely due to the direct and quick delivery of more nanovaccines to the spleen. This study demonstrates that the therapeutic efficacy of nanovaccines can be greatly enhanced by targeted delivery of nanovaccines to the spleen via the proper vaccination route.
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•IV priming and SC boosting vaccination strategy most efficiently inhibits malignant tumor growth.•Delivering nanovaccines to spleen promotes rapid and strong Th1-biased anti-tumor ...immunity.•Nanovaccine depot formed after SC injection slowly induces potent and durable anti-tumor immunity.•Simultaneous IV/SC vaccination strategy significantly delays the progress of advanced tumors.
The advantage of rapid tumor growth over slow immune induction often limits the efficiency of cancer therapeutic vaccines. Many functionalized micro-/nano-vaccines are shown to enhance cancer immunotherapy, but few studies correlate the therapeutic efficacy of these micro-/nano-vaccines to the vaccination route such as intravenous (IV), subcutaneous (SC) injection or their combination. Herein, we employed classical “priming + boosting” vaccination strategy to investigate the influence of four vaccination combinations (IV + IV, IV + SC, SC + IV and SC + SC) of nanovaccines on the anti-tumor therapeutic efficacy in mice bearing E.G7-OVA-lymphoma and B16F10-melanoma. The nanovaccines were constructed by loading antigen and CpG onto layered double hydroxide (LDH) nanoparticles. Our experimental data indicate that “IV-priming + SC-boosting” vaccination combination most efficiently inhibits the growth of early stage tumors, with the tumor volume reduced by >75-90 % in comparison with the control group. Based on these findings, a novel vaccination strategy, i.e. simultaneous IV and SC injection was proposed, which significantly delayed the progression of both early stage and advanced B16F10 tumors. Our current research for the first time correlates the vaccination route of nanovaccines to the anti-tumor therapeutic efficacy, and the highest efficacy of optimal vaccination combination (IV + SC) is benefited from that fact that IV priming quickly induces strong anti-tumor responses that are well sustained by subsequent SC boosting. Moreover, the simultaneous IV/SC vaccination potentially provides a novel vaccination strategy for enhanced immunotherapy of early stage and advanced tumors.
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