Phenylthiol-BODIPY-based supramolecular metallacycles for synergistic tumor chemo-photodynamic therapy.

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (1O2) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 µM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.

Substrate pH Influences the Nutrient Absorption and Rhizosphere Microbiome of Huanglongbing-Affected Grapefruit Plants.

The substrate pH directly affects nutrient availability in the rhizosphere and nutrient uptake by plants. Macronutrients such as nitrogen, potassium, calcium, magnesium, and sulfur are highly available at pH 6.0-6.5, while micronutrients become less available at higher, alkaline pH (pH > 7.0). Recent research has indicated that low pHs can enhance nutrient uptake and improve sweet orange (Citrus sinensis) tree health. We designed a study to understand the influence of a wide range of substrate pH values on plant size and biomass, nutrient availability, leaf gas exchange, and rhizosphere microbiome of grapefruit (Citrus paradisi) affected by Huanglongbing (HLB). Two-year-old "Ray Ruby" grapefruit plants grafted on sour orange (Citrus aurantium) rootstock were cultivated indoors in 10-cm wide × 40-cm tall pots with peat:perlite commercial substrate (80:20 v/v). We tested two disease statuses [HLB-free or healthy (negative, HLB-) and HLB-affected (positive, HLB+)] and six substrate pH values (4, 5, 6, 7, 8, 9) in a 2 × 6 factorial arranged on a complete randomized design with four replications. The canopy volume of HLB+ plants was 20% lower than healthy plants, with pHs 7 and 9 resulting in 44% less canopy volume. The root and shoot ratio of dry weight was 25.8% lower in HLB+ than in healthy plants. Poor root growth and a decrease in fibrous roots were found, especially in pH 5 and 6 treatments in HLB+ plants (p < 0.0001). The disease status and the substrate pHs influenced the leaf nutrient concentration (p < 0.05). High substrate pH affects nutrient availability for root uptake, influencing the nutrient balance throughout the plant system. pH values did not affect plant photosynthesis, indicating that pH does not recover HLB+ plants to the photosynthetic levels of healthy plants-even though high pH positively influenced internal CO2. There were collectively over 200 rhizobacterial identified by the 16S rRNA gene sequencing in individual phylogenetic trees. Most rhizobacteria reads were identified in pH 9. Our results indicated no effect of substrate pHs on the plant disease status induced by enhanced nutrient uptake.

CsiLAC4 modulates boron flow in Arabidopsis and Citrus via high-boron-dependent lignification of cell walls.

The mechanisms underlying plant tolerance to boron (B) excess are far from fully understood. Here we characterized the role of the miR397-CsiLAC4/CsiLAC17 (from Citrus sinensis) module in regulation of B flow. Live-cell imaging techniques were used in localization studies. A tobacco transient expression system tested modulations of CsiLAC4 and CsiLAC17 by miR397. Transgenic Arabidopsis were generated to analyze the biological functions of CsiLAC4 and CsiLAC17. CsiLAC4's role in xylem lignification was determined by mRNA hybridization and cytochemistry. In situ B distribution was analyzed by laser ablation inductively coupled plasma mass spectrometry. CsiLAC4 and CsiLAC17 are predominantly localized in the apoplast of tobacco epidermal cells. Overexpression of CsiLAC4 in Arabidopsis improves the plants' tolerance to boric acid excess by triggering high-B-dependent lignification of the vascular system's cell wall and reducing free B content in roots and shoots. In Citrus, CsiLAC4 is expressed explicitly in the xylem parenchyma and is modulated by B-responsive miR397. Upregulation of CsiLAC4 in Citrus results in lignification of the xylem cell walls, restricting B flow from xylem vessels to the phloem. CsiLAC4 contributes to plant tolerance to boric acid excess via high-B-dependent lignification of cell walls, which set up a 'physical barrier' preventing B flow.

Polymeric Systems Containing Supramolecular Coordination Complexes for Drug Delivery.

Cancer has become a common disease that seriously endangers human health and life. Up to now, the essential treatment method has been drug therapy, and drug delivery plays an important role in cancer therapy. To improve the efficiency of drug therapy, researchers are committed to improving drug delivery methods to enhance drug pharmacokinetics and cancer accumulation. Supramolecular coordination complexes (SCCs) with well-defined shapes and sizes are formed through the coordination between diverse functional organic ligands and metal ions, and they have emerged as potential components in drug delivery and cancer therapy. In particular, micelles or vesicles with the required biocompatibility and stability are synthesized using SCC-containing polymeric systems to develop novel carriers for drug delivery that possess combined properties and extended system tunability. In this study, the research status of SCC-containing polymeric systems as drug carriers and adjuvants for cancer treatment is reviewed, and a special focus is given to their design and preparation.

Metagenomic Analysis Reveals the Mechanism for the Observed Increase in Antibacterial Activity of Penicillin against Uncultured Bacteria Candidatus Liberibacter asiaticus Relative to Oxytetracycline in Planta.

Citrus huanglongbing (HLB) is a devastating disease for the citrus industry. The previous studies demonstrated that oxytetracycline and penicillin are effective antibiotics against Candidatus Liberibacter asiaticus (CLas). However, since CLas is uncultured, the mechanisms of action of antibiotics against CLas are still unclear. It was recently reported that the endophytic microbial communities are associated with the progression of citrus HLB after oxytetracycline and penicillin treatment. Therefore, we hypothesize that penicillin has greater antibacterial activity against CLas than oxytetracycline, which may be associated with the alteration of the structure and function of endophytic microbial communities in HLB-affected citrus in response to these antibiotics. To test this hypothesis, the microbiome of HLB-affected citrus leaves treated with these two antibiotics was analyzed using a metagenomic method. Our results indicate that the microbial structure and function in HLB-affected citrus were altered by these two antibiotics. The relative abundance of beneficial bacterial species, including Streptomyces avermitilis and Bradyrhizobium, was higher in penicillin-treated plants compared to those treated with oxytetracycline, and the relative abundance of the bacterial species (such as Propionibacterium acnes and Synechocystis sp PCC 6803) associated with CLas survival was lower for penicillin-treated plants compared to oxytetracycline-treated plants. These results indicate that penicillin has greater antibacterial activity against CLas. Based on the metagenomic analysis, this study elucidated the mechanism for the observed increase in antibacterial activity of penicillin against CLas. The data presented here are not only invaluable for developing eco-friendly and effective biocontrol strategies to combat citrus HLB, but also provide a method for revealing mechanism of antimicrobial against uncultured bacteria in host.

Self-Healing Heterometallic Supramolecular Polymers Constructed by Hierarchical Assembly of Triply Orthogonal Interactions with Tunable Photophysical Properties.

Here, we present a method for the building of new bicyclic heterometallic cross-linked supramolecular polymers by hierarchical unification of three types of orthogonal noncovalent interactions, including platinum(II)-pyridine coordination-driven self-assembly, zinc-terpyridine complex, and host-guest interactions. The platinum-pyridine coordination provides the primary driving force to form discrete rhomboidal metallacycles. The assembly does not interfere with the zinc-terpyridine complexes, which link the discrete metallacycles into linear supramolecular polymers, and the conjugation length is extended upon the formation of the zinc-terpyridine complexes, which red-shifts the absorption and emission spectra. Finally, host-guest interactions via bis-ammonium salt binding to the benzo-21-crown-7 (B21C7) groups on the platinum acceptors afford the cross-linked supramolecular polymers. By continuous increase of the concentration of the supramolecular polymer to a relatively high level, supramolecular polymer gel is obtained, which exhibits self-healing properties and reversible gel-sol transitions stimulated by various external stimuli, including temperature, K+, and cyclen. Moreover, the photophysical properties of the supramolecular polymers could be effectively tuned by varying the substituents of the precursor ligands.

A series of novel BODIPY-fluorene copolymers: Synthesis, characterization, optical-electronic and nonlinear optical properties.

A series of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with different connection sites and conjugation length and fluorene alternating conjugated polymers have been synthesized via palladium-catalyzed Suzuki coupling reaction. The polymers were fully characterized by 1H NMR spectroscopy and gel permeation chromatography (GPC), and their properties were measured by thermogravimetric analysis (TGA), UV-vis absorption spectroscopy, cyclic voltammetry (CV), photoluminescence (PL) spectroscopy, the Z-scan technique, and theoretical calculation using density-functional theory (DFT) method. The results indicate that the connection sites and conjugation length of BODIPY have great effect on the optical-electronic and nonlinear optical properties of the conjugated BODIPY- fluorene copolymers although they don't affect the polymerization process. The absorption and emission peaks of P1 exhibit red shifts compared to those of P2 and P3. The polymers show good nonlinear optical properties that are closely related to the connection sites of the BODIPY pendants. P1 exhibits relatively richer nonlinear optical (NLO) properties than P2 and P3. The third order nonlinear optical coefficient (χ(3)) of P1 is 3.57 × 10-11 esu, which is ~4 times larger than those of P2 and P3.

MicroRNA Sequencing Revealed Citrus Adaptation to Long-Term Boron Toxicity through Modulation of Root Development by miR319 and miR171.

Boron (B) toxicity in Citrus is a common physiological disorder leading to reductions in both productivity and quality. Studies on how Citrus roots evade B toxicity may provide new insight into plant tolerance to B toxicity. Here, using Illumina sequencing, differentially expressed microRNAs (miRNAs) were identified in B toxicity-treated Citrus sinensis (tolerant) and C. grandis (intolerant) roots. The results showed that 37 miRNAs in C. grandis and 11 miRNAs in C. sinensis were differentially expressed when exposed to B toxicity. Among them, miR319, miR171, and miR396g-5p were confirmed via 5'-RACE and qRT-PCR to target a myeloblastosis (MYB) transcription factor gene, a SCARECROW-like protein gene, and a cation transporting ATPase gene, respectively. Maintenance of SCARECROW expression in B treated Citrus roots might fulfill stem cell maintenance, quiescent center, and endodermis specification, thus allowing regular root elongation under B-toxic stress. Down-regulation of MYB due to up-regulation of miR319 in B toxicity-treated C. grandis roots might decrease the number of root tips, thereby dramatically changing root system architecture. Our findings suggested that miR319 and miR171 play a pivotal role in Citrus adaptation to long-term B toxicity by targeting MYB and SCARECROW, respectively, both of which are responsible for root growth and development.

Functional analysis of an alpha-1,2-mannosidase from Magnaporthe oryzae.

Identification of enzymes that are expressed during host colonization and characterization of their biochemical properties are prerequisite to understanding their role in the pathogen-host interaction. Nine alpha-1,2-mannosidase homologs were identified in the analysis of the Magnaporthe oryzae genome. Endoplasmic reticulum localized alpha-1,2-mannosidases play an important role in protein glycosylation. However, several members of the alpha-1,2-mannosidase gene family are predicted to be secreted. The biological role of such extracellular enzymes in host colonization has not been defined. Here, we characterized a secreted alpha-1,2-mannosidase of M. oryzae, MGG_00994.6, and found that the mature polypeptide is a glycoprotein capable of hydrolyzing alpha-1,2 linked mannobiose. The gene is expressed during growth in vitro and during colonization on rice plants, however, deletion of the gene did not affect pathogenicity. Five other members of the alpha-1,2-mannosidase of M. oryzae were expressed with a pattern similar to MGG_00994.6, suggesting the potential for functional redundancy. These results form the basis for additional studies on the role of this gene family in the rice blast fungus and its interaction with rice.

Biochemical and molecular characterization of a putative endoglucanase in Magnaporthe grisea.

Microbial pathogens secrete an array of cell wall-degrading enzymes to break down the structure of the host cell wall to facilitate colonization of the host tissue. To better understand their role in the pathogenesis, a putative endoglucanase from Magnaporthe grisea was characterized in this paper. SignalP-3.0 analysis indicates that the protein encoded by gene MGG_02532.5 in M. grisea (named MgEGL1 for M. grisea endoglucanase 1) contains a secretory signal peptide. Multiple alignment shows that MgEGL1 has high level of homology to endoglucanases (EC 3.1.1.4) from Aspergillus nidulans and Trichoderma reesei. The three proteins share a conserved catalytic domain, but only the one from T. reesei contains a cellulose binding module. MgEGL1 was constitutively expressed with the highest level in mycelia and the lowest in conidia. Interestingly, the MgEGL1 RNA could be alternatively processed when cultured in vitro and after infection of rice. Expression analysis confirmed that the MgEGL1 is a secreted protein. Its endoglucanase activity was assayed by Congo red plates, and further confirmed by the dinitrosalicylic acid method. The finding in this paper will provide the basis for further determination of the biochemical properties of the endoglucanase protein and its relevant function in fungal pathogenesis.