The transcription factor OsWRKY10 inhibits phosphate uptake via suppressing OsPHT1;2 expression under phosphate-replete conditions in rice.

Plants have evolved delicate systems for stimulating or inhibiting inorganic phosphate (Pi) uptake in response to the fluctuating Pi availability in soil. However, the negative regulators inhibiting Pi uptake at the transcriptional level are largely unexplored. Here, we functionally characterized a transcription factor in rice (Oryza sativa), OsWRKY10. OsWRKY10 encodes a nucleus-localized protein and showed preferential tissue localization. Knockout of OsWRKY10 led to increased Pi uptake and accumulation under Pi-replete conditions. In accordance with this phenotype, OsWRKY10 was transcriptionally induced by Pi, and a subset of PHOSPHATE TRANSPORTER 1 (PHT1) genes were up-regulated upon its mutation, suggesting that OsWRKY10 is a transcriptional repressor of Pi uptake. Moreover, rice plants expressing the OsWRKY10-VP16 fusion protein (a dominant transcriptional activator) accumulated even more Pi than oswrky10. Several lines of biochemical evidence demonstrated that OsWRKY10 directly suppressed OsPHT1;2 expression. Genetic analysis showed that OsPHT1;2 was responsible for the increased Pi accumulation in oswrky10. Furthermore, during Pi starvation, OsWRKY10 protein was degraded through the 26S proteasome. Altogether, the OsWRKY10-OsPHT1;2 module represents a crucial loop in the Pi signaling network in rice, inhibiting Pi uptake when there is ample Pi in the environment.

Visible light-activated prodrug system with a novel heavy-atom-free photosensitizer.

The use of light to activate prodrugs offers a promising method for the precise control of drug release, reducing drug-related side effects, and enhancing therapeutic effectiveness. We have created a novel prodrug system that utilizes a unique, heavy-atom-free photosensitizer to produce singlet oxygen, which then triggers the conversion of the prodrug into its active form. This system has been successfully demonstrated through the creation of "photo-unclick" prodrugs of paclitaxel (PTX), combretastatin A-4 (CA-4), and 10-hydroxy-7-ethylcamptothecin (SN-38). These prodrugs show decreased toxicity in the absence of light, but exhibit increased toxicity when exposed to red light.

Hyper non-CG methylation of expanded plant disease resistance NLR genes.

KEY MESSAGE: We explored the phylogenomics and methylomics of NLR genes in 41 plant species and found that highly duplicated plant NLR genes are hyper methylated in non-CG context.

Pyrethroids exposure alters the community and function of the internal microbiota in Aedes albopictus.

Large amounts of insecticides bring selection pressure and then develop insecticide resistance in Aedes albopictus. This study demonstrated for the first time the effect of pyrethroid exposure on the internal microbiota in Ae. albopictus. 36, 48, 57 strains of virgin adult Ae. albopictus were exposed to the pyrethroids deltamethrin (Dme group), ß-cypermethrin (Bcy group), and cis-permethrin (Cper group), respectively, with n-hexane exposure (Hex group) as the controls (n = 36). The internal microbiota community and functions were analyzed based on the metagenomic analysis. The analysis of similarity (ANOSIM) results showed that the Hex/Bcy (p = 0.001), Hex/Cper (p = 0.006), Hex/Dme (p = 0.001) groups were well separated, and the internal microbes of Ae. albopictus vary in the composition and functions depending on the type of pyrethroid insecticide they are applied. Four short chain fatty acid-producing genera, Butyricimonas, Prevotellaceae, Anaerococcus, Pseudorhodobacter were specifically absent in the pyrethroid-exposed mosquitoes. Morganella and Streptomyces were significantly enriched in cis-permethrin-exposed mosquitoes. Wolbachia and Chryseobacterium showed significant enrichment in ß-cypermethrin-exposed mosquitoes. Pseudomonas was significantly abundant in deltamethrin-exposed mosquitoes. The significant proliferation of these bacteria may be closely related to insecticide metabolism. Our study recapitulated a specifically enhanced metabolic networks relevant to the exposure to cis-permethrin and ß-cypermethrin, respectively. Benzaldehyde dehydrogenase (EC 1.2.1.28), key enzyme in aromatic compounds metabolism, was detected enhanced in cis-permethrin and ß-cypermethrin exposed mosquitoes. The internal microbiota metabolism of aromatic compounds may be important influencing factors for pyrethroid resistance. Future work will be needed to elucidate the specific mechanisms by which mosquito microbiota influences host resistance and vector ability.

Photostable Small-Molecule NIR-II Fluorescent Scaffolds that Cross the Blood-Brain Barrier for Noninvasive Brain Imaging.

The second near-infrared (NIR-II, 1000-1700 nm) fluorescent probes have significant advantages over visible or NIR-I (600-900 nm) imaging for both depth of penetration and level of resolution. Since the blood-brain barrier (BBB) prevents most molecules from entering the central nervous system, NIR-II dyes with large molecular frameworks have limited applications for brain imaging. In this work, we developed a series of boron difluoride (BF2) formazanate NIR-II dyes, which had tunable photophysical properties, ultrahigh photostability, excellent biological stability, and strong brightness. Modulation of the aniline moiety of BF2 formazanate dyes significantly enhances their abilities to cross the BBB for noninvasive brain imaging. Furthermore, the intact mouse brain imaging and dynamic dye diffusion across the BBB were monitored using these BF2 formazanate dyes in the NIR-II region. In murine glioblastoma models, these dyes can differentiate tumors from normal brain tissues. We anticipate that this new type of small molecule will find potential applications in creating probes and drugs relevant to theranostic for brain pathologies.

Design Strategies of Photoacoustic Molecular Probes.

Photoacoustic (PA) probes have been developed very quickly and applied in broad areas in recent years. Most of them are constructed based on organic dyes with intrinsic near-infrared (NIR) absorption properties. To increase PA contrast and improve imaging resolution and the sensitivity of detection, various methods for the design of PA probes have been developed. This minireview mainly focuses on the development and design strategies of activatable small-molecule PA probes in four aspects: reaction-cleavage, metal ion chelation, photoswitch, and protonation-deprotonation. It highlights some key points of designing PA probes corresponding to their properties and applications. The challenges and perspectives for small-molecule PA probes are also discussed.

OsWRKY21 and OsWRKY108 function redundantly to promote phosphate accumulation through maintaining the constitutive expression of OsPHT1;1 under phosphate-replete conditions.

Plant Phosphate Transporter 1 (PHT1) proteins, probably the only influx transporters for phosphate (Pi) uptake, are partially degraded on sufficient Pi levels to prevent excessive Pi accumulation. Therefore, the basal/constitutive expression level of PHT1 genes is vital for maintaining Pi uptake under Pi-replete conditions. Rice (Oryza sativa) OsPHT1;1 is a unique gene as it is highly expressed and not responsive to Pi, however the mechanism for maintaining its basal/constitutive expression remains unknown. Using biochemical and genetic approaches, we identified and functionally characterised the transcription factors maintaining the basal/constitutive expression of OsPHT1;1. OsWRKY21 and OsWRKY108 interact within the nucleus and both bind to the W-box in the OsPHT1;1 promoter. Overexpression of OsWRKY21 or OsWRKY108 led to increased Pi accumulation, resulting from elevated expression of OsPHT1;1. By contrast, oswrky21 oswrky108 double mutants showed decreased Pi accumulation and OsPHT1;1 expression in a Pi-dependent manner. Moreover, similar to ospht1;1 mutants, plants expressing the OsWRKY21-SRDX fusion protein (a chimeric dominant suppressor) were impaired in Pi accumulation in Pi-replete roots, accompanied by downregulation of OsPHT1;1 expression. Our findings demonstrated that rice WRKY transcription factors function redundantly to promote Pi uptake by activating OsPHT1;1 expression under Pi-replete conditions, and represent a novel pathway independent of the central Pi signalling system.

Cyclic Oxime Esters as Deconstructive Bifunctional Reagents for Cyanoalkyl Esterification of 1,6-Enynes.

A concise copper catalysis strategy for the addition-cyclization of cyclic oxime esters across 1,6-enynes with high stereoselectivity to generate 1-indanones bearing an all-carbon quaternary center is reported. In this process, single-electron reduction of cyclic oxime esters enables deconstructive carbon-carbon cleavage to provide a key cyanopropyl radical poised for the addition-cyclization. This reaction is redox-neutral, exhibits good functional group compatibility, and features 100% atomic utilization. This process driven by copper catalyst makes readily available cyclic oxime esters as bifunctional reagents to demonstrate convergent synthesis.

Syntheses, Structures and Luminescent Properties of Eu- and Tb-MOFs with 3,5-Pyridinedicarboxylate and 1,2-Benzenedicarboxylate.

Two lanthanide-based MOFs (Ln-MOFs) were synthesized by reaction of Eu(III) or Tb(III) perchlorates with mixed dicarboxylates of 3,5-pdc and 1,2-bdc (3,5-H2pdc = 3,5-pyridinedicarboxylic acid; 1,2-H2bdc = 1,2-benzenedicarboxylic acid) by hydrothermal method. The chemical formulas of the two complexes were [Eu2(3,5-pdc)(1,2-bdc)2(H2O)4]n (1) and {[Tb2(3,5-pdc)(1,2-bdc)2(H2O)4]·2H2O}n (2). IR spectra and element analyses were tested to characterize the two compounds. The crystal structures were determined by X-ray single crystal diffraction. MOF 1 was 3D porous network structure but MOF 2 was 2D layered structure. The two MOFs emitted the characteristic fluorescence of Eu(III) or Tb(III) ion with the excitations of UV-rays. Their lifetimes of excited states for Eu(III) (5D0) and Tb(III) (5D4) were 0.31 and 0.82 ms. The absolute quantum yields (Фa) of MOF1 and 2 were also tested and the Фa(1) (λex = 320 nm) and Фa(2) (λex = 296 nm) were 15% and 48%, respectively.

Single-Atom Switching as a General Approach to Designing Colorimetric and Fluorogenic Probes for Mercury Ions.

By performing a single-atom replacement within common fluorophores, we have developed a facile and general strategy to prepare a broad-spectrum class of colorimetric and fluorogenic probes for the selective detection of mercury ions in aqueous environments. Thionation of carbonyl groups from existing fluorophore cores results in a great reduction of fluorescence quantum yield and loss of fluorescence emission. The resulting thiocaged probes are efficiently desulfurized to their oxo derivatives in the presence of mercury ions, leading to pronounced changes in chromogenic and fluorogenic signals. Because these probes exhibit high selectivity, excellent sensitivity, good membrane-permeability, and rapid responses towards mercury ions, they are suitable for visualization of mercury in both aqueous and intracellular environments.

Transcriptional regulation of microRNA-126a by farnesoid X receptor in vitro and in vivo.

OBJECTIVES: Recent research has indicated the microRNA-126a (miR-126a) is an endothelial cell-specific and highly conserved endogenous small non-coding RNA molecule. It contributes to the vascular integrity and angiogenesis, but the molecular regulation mechanism of miR-126a remains unknown. RESULTS: Herein, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that Farnesoid X Receptor (FXR) activation promoted miR-126a expression in HepG2, LO2, and Hep1-6 cells. Furthermore, FXR was found to transcriptionally regulate the miR-126a by binding to its DR8 site. The binding site of FXR was confirmed on intron 6 or 7 of miR-126a host gene epidermal growth factor-like domain 7 (EGFL7) by luciferase reporter assays, electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays. CONCLUSIONS: All these data collectively suggest that FXR regulates transcripts of miR-126a by binding to DR8 in miR-126a gene promoter. This study may provide a molecular therapeutic target for angiogenic disorders, aging, and liver failure.

Polar Side Chain Effects on the Thermoelectric Properties of Benzo[1,2-b:4,5-b']Dithiophene-Based Conjugated Polymers.

The molecular structure of polymers has a great influence on their thermoelectric properties; however, the relationship between the molecular structure of a polymer and its thermoelectric properties remains unclear. In this work, two benzo[1,2-b:4,5-b']dithiophene (BDT)-based conjugated polymers are designed and synthesized, which contain alkyl side chains or polar side chains. The effects of the polymer side chain on the physicochemical properties are systematically investigated, especially the thermoelectric performance of the polymers after doping with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane. It is found that the BDT-based conjugated polymer with polar side chains exhibits good miscibility with the dopants, leading to higher thermoelectric properties than those of the polymer with alkyl side chains. This work can serve as a reference for the future design of high-performance organic thermoelectric polymers.

Light-harvesting metal-organic framework nanoprobes for ratiometric fluorescence energy transfer-based determination of pH values and temperature.

Light-harvesting nanoprobes were developed by self-assembly of nanoscale metal-organic frameworks (NMOFs) and stimuli-responsive polymers for fluorometric sensing of pH values and temperature. Two kinds of fluorescent NMOFs (acting as the energy donor) and stimuli-responsive polymers conjugated to fluorophores (acting as energy acceptors) were prepared and characterized. The NMOFs include zirconium(IV) and π-conjugated dicarboxylate ligands. The fluorophores inclued cyaine dyes and a Bodipy dye. The energy donor and energy acceptor form a Förster resonance energy transfer (FRET) nanosystem. In the light-harvesting system, the chain lengths of the stimuli-responsive polymers vary when the local pH value or temperature change. Ratiometric sensing of pH and temperature was accomplished by monitoring fluorescence. pH values were can be sensed between 3.0 and 8.0 under 420 nm excitation and by ratioing the emission peaks at 645 and 530 nm. Temperature can be sensed in the range from 25 to 50 °C under 550 nm excitation and by ratioing the emission peaks at 810 and 695 nm. The nanoprobes display excellent water dispersibility and cell membrane permeability. They were applied to image pH values and temperature in HeLa cells. Graphical abstract Schematic presentation of an effective strategy to fabricate light-harvesting nanoprobes by self-assembly of MOFs and stimuli-responsive polymers for ratiometric pH and temperature sensing. The distance as the polymer length between energy donor and acceptor is crucial for energy transfer efficiency.

Activatable Small-Molecule Photoacoustic Probes that Cross the Blood-Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease.

Copper enrichment in the brain is highly related to Alzheimer's disease (AD) pathogenesis, but in vivo tracing of Cu2+ in the brain by imaging techniques is still a great challenge. In this work, we developed a series of activatable photoacoustic (PA) probes with low molecular weights (less than 438 Da), RPS1-RPS4, which can specifically chelate with Cu2+ to form radicals with turn-on PA signals in the near-infrared (NIR) region. Introducing the electron-donating group N,N-dimethylaniline into the probe was found to significantly enhance the radical stability and PA intensity. The best probe in the series, RPS1, showed a fast response (within seconds) to Cu2+ with high selectivity and a low PA detection limit of 90.9 nm. Owing to the low molecular weight and amphiphilic structure, RPS1 could effectively cross the blood-brain barrier (BBB) and thus allowed us, for the first time, to visualize Cu2+ in vivo via PA imaging in the brains of AD mice.

Elucidating the Structure-Reactivity Correlations of Phenothiazine-Based Fluorescent Probes toward ClO.

In this work, with the aim of developing effective molecular probes and investigating the structure-reactivity correlation, a short series of phenothiazine-based fluorescent probes are designed for the detection of ClO- with differing electron push-pull groups. Sensing experiment results and single-crystal X-ray analysis with the aid of time-dependent DFT (TD-DFT) calculations reveal that substituting groups with increasing electron-withdrawing ability can increase the dihedral angle of the phenothiazine moiety and reduce the gap energy of the probes, leading to enhanced reactivity toward ClO- . Both PT1 and PT2 show two-color switching upon detection of ClO- . PT1, with the strong electron-donating group thiophene, shows a fluorescence color switch from salmon to blue. PT2, with a medium electron-donating/accepting group benzothiazole, shows a fluorescence color switch from red to green. However, both PT1 and PT2 show almost no response to ONOO- . Through the introduction of strong electron-withdrawing ketone combined with a cyano group, PT3 shows a cyan emission upon detection of ClO- and weak red emission upon detection of ONOO- . HRMS and 1 H NMR results confirm that PT1 and PT2 have the same sensing mode, in which the divalent sulfur of phenothiazine can be oxidized to sulfoxide by ClO- . Upon reaction with ClO- , PT3 experiences two-step reactions. It is first oxidized into the sulfone structure by ClO- , and then transformed into sulfoxide phenothiazine aldehyde. Upon encountering ONOO- , PT3 changes into an aldehyde structure and some nonfluorescent byproducts. Owing to their special selectivity and high sensitivity, PT1 and PT2 are applied to image the endogenous ClO- in macrophage cells and zebrafish larvae. This study is expected to provide useful guidelines for probe design for various applications.

Calcification: A Disregarded or Ignored Issue in the Gynecologic Tumor Microenvironments.

Although calcification in the gynecologic tumor microenvironments is a common phenomenon, doctors and researchers still disregard or ignore the issue. In fact, this change in the gynecologic tumor microenvironments is clinically significant and a number of studies have reported an association between calcification and gynecological tumor progression. In ovarian cancer, calcification is predominantly psammomatous and largely occurs in serous papillary ovarian tumors. In addition, calcification in ovarian cancer correlated with lower histologic grade and may indicate a poorer survival rate. In uterine fibroids, calcification occurs as a degenerative change and is predictive of a good prognosis. As for endometrial cancer and cervical cancer, calcification rarely occurs in these cancers. The mechanism of calcification in the gynecologic tumor microenvironments is not currently clear. One theory is that calcification occurs due to degeneration of the tumor cells; another theory is that calcification occurs in response to secretions from cells in the tumor microenvironment. Although previous studies have revealed a direct association between calcifications and gynecological tumors, this association has not been fully clarified. To better clarify the significance of calcification in terms of diagnosing and treating gynecological tumors, the associations between calcification and the different histologic stages and prognosis in gynecological tumors should be further studied. In particular, more attention should be paid to the morphological characteristics, chemical nature, and mechanism of calcifications in the gynecological tumor microenvironments.

[IL-8 Induces Epithelial-to-mesenchymal Transition of Ovarian Carcinoma Cells: a Preliminary Study].

OBJECTIVE: To explore the effect of IL-8 on the epithelial-to-mesenchymal transition (EMT) in ovarian cancer,which will provide experimental basis for revealing related molecular mechanism in malignant metastasis of ovarian cancer. METHODS: The migration of ovarian cancer cell line SKOV3 cells was explored with Real time label free cell analysis (RTCA) after treatment with recombinant human IL-8.SKOV3 cells were co-cultured with IL-8 for 48 h,proteins involved in EMT were investigated via Western blot to explore the effect of IL-8 on the activation of the EMT. Invasion of SKOV3 cells after treatment with IL-8 were evaluated by transwell assay. RESULTS: According to the results of RTCA,after treatment with IL-8 for 48 h,the migration of SKOV3 cells was in platform phase. The treatment of IL-8 unregulated vimentin and snail and downregulated E-cadherin,which suggested that IL-8 induced EMT in ovarian cancer. The results of transwell test showed that invasive ability of IL-8 pretreated SKOV3 cells was enhanced (P<0.05). CONCLUSION: IL-8 can induce the EMT of ovarian cancer and enhance the invasion and migration of ovarian cancer.

[The preliminary study on biomechanical properties of four synthetic implants for reconstructive surgery of pelvic floor dysfunction].

This study aimed to investigate biomechanical properties of synthetic implants for reconstructive surgery of pelvic floor dysfunction. In this dissertation, we chose four synthetic implants, i.e. total pelvic floor repair system (PROLIFT), gynecone TVT obtutator system (TVT-O), intra-vaginal sling placement device (IVS) and acellular dermal matrix (Renov), for tensile test respectively. The biomechanical properties of four synthetic implants were measured and analyzed using a material testing machine (Instron 4302 versatile material testing machine). The biomechanical parameters included ultimate stress strength, modulus of elasticity, maximum load and maximum elongation. The results showed that the maximum load of the four symthetic implants was TVT-O > IVS > PROLIFT > Renov, and the maximum load of TVT-O was significantly higher than PROLIFT and Renov ( P < 0.05). The ultimate stress strength was TVT-O > IVS > PROLIFT > Renov, with no significant differences among them ( P > 0.05). The maximum elongation of the four implants was TVT-O > PROLIFT > IVS > Renov, and the maximum elongation of TVT-O and PROLIFT were both significantly higher than Renov ( P < 0.05). The modulus of elasticity was IVS > Renov > TVT-O > PROLIFT, with no significant differences among them ( P > 0.05). Taken together, the present study demonstrates that the modulus of elasticity of IVS was the highest in the four synthetic implants; TVT-O had the highest mechanical strength; The maximum load, ultimate stress strength and maximum elongation of Renov were all the lowest; The mechanical properties of PROLIFT was the most stable, and its modulus of elasticity was the lowest in the four synthetic implants, which had good extensibility and elasticity. Therefore, it is necessary to pay attention to the biomechanical properties of new pelvic reconstructive materials for the clinical pelvic reconstructive surgery.

Maintenance of phosphate homeostasis and root development are coordinately regulated by MYB1, an R2R3-type MYB transcription factor in rice.

The adaptive responses of plants to phosphate (Pi) starvation stress are fine-tuned by an elaborate regulatory network. In this study, we identified and characterized a novel Pi starvation-responsive gene, MYB1, encoding an R2R3-type transcription factor in rice. MYB1 was transcriptionally induced in leaf sheaths and old leaf blades. It was localized to the nucleus and expressed mainly in vascular tissues. Mutation of MYB1 led to an increase in Pi uptake and accumulation, accompanied by altered expression of a subset of Pi transporters and several genes involved in Pi starvation signaling. Furthermore, MYB1 affected the elongation of the primary root in a Pi-dependent manner and lateral roots in a Pi-independent manner. Moreover, gibberellic acid (GA)-triggered lateral root elongation was largely suppressed in wild-type plants under Pi starvation conditions, whereas this suppression was partially rescued in myb1 mutant lines, correlating with the up-regulation of a GA biosynthetic gene upon MYB1 mutation. Taken together, the findings of this study highlight the role of MYB1 as a regulator involved in both Pi starvation signaling and GA biosynthesis. Such a co-regulator might have broad implications for the study of cross-talk between nutrient stress and other signaling pathways.

High Thermal Stability of La2O3- and CeO2-Stabilized Tetragonal ZrO2.

Catalyst support materials of tetragonal ZrO2, stabilized by either La2O3 (La2O3-ZrO2) or CeO2 (CeO2-ZrO2), were synthesized under hydrothermal conditions at 200 °C with NH4OH or tetramethylammonium hydroxide as the mineralizer. From in situ synchrotron powder X-ray diffraction and small-angle X-ray scattering measurements, the calcined La2O3-ZrO2 and CeO2-ZrO2 supports were nonporous nanocrystallites that exhibited rectangular shapes with a thermal stability of up to 1000 °C in air. These supports had an average size of ∼ 10 nm and a surface area of 59-97 m(2)/g. The catalysts Pt/La2O3-ZrO2 and Pt/CeO2-ZrO2 were prepared by using atomic layer deposition with varying Pt loadings from 6.3 to 12.4 wt %. Monodispersed Pt nanoparticles of ∼ 3 nm were obtained for these catalysts. The incorporation of La2O3 and CeO2 into the t-ZrO2 structure did not affect the nature of the active sites for the Pt/ZrO2 catalysts for the water-gas shift reaction.