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Signal enhancement of magnetic resonance imaging (MRI) in the diseased region is dependent on the molecular structure of the MRI contrast agent. In this study, a macromolecular contrast agent, Branched-LAMA-DOTA-Cy5.5-Gd (BLDCGd), was prepared to target liver cancer. Due to the affinity of lactose to the Asialoglycoprotein receptor (ASGPR) over-expressed on the surface of liver cancer cells, lactose was selected as the targeting moiety in the contrast agent. A cathepsin B-sensitive tetrapeptide, GFLG, was used as a linkage moiety to construct a cross-linked macromolecular structure of the contrast agent, and the contrast agent could be degraded into fragments for clearance. A small-molecular-weight molecule, DOTA-Gd, and a fluorescent dye, Cy5.5, were conjugated to the macromolecular structure

The evaporation duct is an abnormal refractive phenomenon with wide distribution and frequency occurrence at the boundary between the atmosphere and the ocean, which directly affects electromagnetic wave propagation. In recent years, the use of meteorological and hydrological data to predict the evaporation duct height has become an emerging and promising approach. There are some evaporation duct models that have been proposed based on the Monin–Obukhov similarity theory. However, each model adopts different stability functions and roughness length parameterization methods, so the prediction accuracies are different under different environmental conditions. To improve the prediction accuracy of the evaporation duct under different environmental conditions, a model selection optimization method (MSOM) of the evaporation duct model is proposed based on sensitivity analysis. According to the sensitivity of each model to input parameters analyzed by the sensor observation accuracy, curve graph, and Sobol sensitivity, the model input parameters are divided into several intervals. Then the optimization model is selected in different intervals. The model was established using numerical simulation data from local areas in the South China Sea, and its accuracy was verified by the observational data from the offshore observation platform located in the South China Sea. The results show that the MSOM can effectively improve the prediction accuracy of the evaporation duct height. Under unstable conditions, the maximum relative error is reduced by 7.1%, and under stable conditions, the relative error is reduced by 10.7%. Significance Statement The evaporation duct height has a significant effect on marine radar or wireless apparatus applications. To obtain the evaporation duct height, there are some evaporation duct models that have been proposed. However, different evaporation duct models are applicable to different meteorological and hydrological environments. A single model cannot achieve accurate evaporation duct height predictions in all environments. We propose a model selection optimization method of the evaporation duct model based on sensitivity analysis. This method can dynamically select the optimal model according to different meteorological and hydrological environment, and improve the prediction accuracy of the evaporation duct height. Under unstable conditions, the maximum relative error is reduced by 7.1%, and under stable conditions, the relative error is reduced by 10.7%.

Interaction between carcinoma-associated fibroblasts (CAFs) and tumor cells leads to the invasion and metastasis of breast cancer. Herein, we prepared a redox-responsive chondroitin sulfate (CS)-based nanomedicine, in which hydrophobic cabazitaxel (CTX) was conjugated to the backbone of CS via glutathione (GSH)-sensitive dithiomaleimide (DTM) to form an amphipathic CS-DTM-CTX (CDC) conjugate, and dasatinib (DAS) co-assembled with the CDC conjugate to obtain DAS@CDC. After CD44 receptor-mediated internalization by CAFs, the nanomedicine could reverse CAFs to normal fibroblasts, blocking their crosstalk with tumor cells and reducing synthesis of major tumor extracellular matrix proteins, including collagen and fibronectin. Meanwhile, the nanomedicine internalized by tumor cells could effectively inhibit tumor proliferation and metastasis, leading to shrinkage of the tumor volume and inhibition of lung metastasis in a subcutaneous 4T1 tumor model with low side effects. Collectively, the nanomedicine showed a remarkably synergistic therapy effect against breast cancer by modulating tumor-stromal crosstalk.

Peach encodes 14 INDETERMINATE DOMAIN (IDD) transcription factors. PpIDD4, -12 and -13 mediated PpDELLA1 binding to the PpGA20ox1 promoter. Each of these three PpIDD-DELLA1 complexes activated transcription of PpGA20ox1. PpTPR1 and -4 interrupted the interaction of PpIDDs with PpDELLA1. The plant growth regulator gibberellin (GA) plays an important role in the rapid growth of annual shoots in peach. Our previous study showed that the peach cultivar 'FenHuaShouXingTao' (FHSXT), a gibberellic acid receptor (gid1) mutant, accumulates active GAs in annual shoot tips. This mutant enhances GA feedback regulation in peach. The results of this study suggested that the PpIDD-DELLA1 complex is the underlying mechanism of GA feedback regulation in peach. Fourteen IDD genes were identified in peach, and three PpIDDs (PpIDD4, -12 and -13, all from group IV) interacted with PpDELLA1, an important component in GA signaling pathway. Truncation, segmentation and site mutation of the promoter of PpGA20ox1 (a GA biosynthesis gene) showed that all three PpIDD proteins recognized the core motif TTGTC. PpIDD4 and -13 mainly bind to site 3, while PpIDD12 binds to site 5 of the PpGA20ox1 promoter. All three PpIDD-DELLA1 complexes activated the PpGA20ox1 promoter-LUC fusion. These data suggested that PpIDDs bridge PpDELLA1 and the promoter of PpGA20ox1, which then activated the transcription of PpGA20ox1. In addition, PpTPR1 and -4 disrupted the interaction of PpIDDs with PpDELLA1. Our research will be helpful for understanding and possibly modifying the regulation of annual shoot growth and GA biosynthesis.

Complement receptor 3 (CD11b/CD18) is an important receptor that mediates adhesion, phagocytosis and chemotaxis in various immunocytes. The conidia of the medically-important pathogenic fungus, Aspergillus fumigatus can be internalized into alveolar epithelial cells to disseminate its infection in immunocompromised host; however, the role of CR3 in this process is poorly understood. In the present study, we investigated the potential role of CR3 on A. fumigatus internalization into type II alveolar epithelial cells and its effect on host intracellular PA content induced by A. fumigatus. We found that CR3 is expressed in alveolar epithelial cells and that human serum and bronchoalveolar lavage fluid (BALF) could improve A. fumigatus conidial internalization into A549 type II alveolar epithelial cell line and mouse primary alveolar epithelial cells, which were significantly inhibited by the complement C3 quencher and CD11b-blocking antibody. Serum-opsonization of swollen conidia, but not resting conidia led to the increase of cellular phosphatidic acid (PA) in A549 cells during infection. Moreover, both conidial internalization and induced PA production were interfered by CD11b-blocking antibody and dependent on FAK activity, but not Syk in alveolar epithelial cells. Overall, our results revealed that CR3 is a critical modulator of Aspergillus fumigatus internalization into alveolar epithelial cells.

This paper presents the network-based modeling, validation and analysis of the nonlinear liquid spring damper model under vertical landing conditions of reusable launch vehicle. The impedance function of damper model is derived first. Then, its mechanical and hydraulic networks are newly established based on the hydro-mechanical analogy and network-based analysis. By comparing the networks between the corresponding symmetric and asymmetric structures, the meaning of each branch in the network is elucidated. After that, the validity of the network-based model for the liquid spring damper is confirmed by comparison against the experimentally verified nonlinear model in both frequency and time domain. The force and energy absorption characteristics of the damper model are further decomposed, and, specifically, the influence of the orifice area and orifice length on the attenuation performance is studied. The results show that the network-based model provides predictions consistent with those generated by the nonlinear model. The main discrepancy is attributed to the inaccuracy caused by the equivalent fluid bulk modulus. The network-based analysis indicates that the orifice area mainly influences the damping force in the network, which further affects the loads and efficiency of the damper. The orifice length mainly influences the inertia force in the network, which should be limited to a small value. The proposed novel interpretation of the damper models and responses under impact conditions constitutes a framework suitable for systematic design of typically highly nonlinear landing systems in reusable launch vehicles.

Background In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM− 1 s− 1) is about three times that of 3-CP (0.17 mM− 1 s− 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs. Graphical abstract

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here, a Drosophila system performs efficient somatic repair of both DSBs and single-strand breaks (SSBs) using intact sequences from the homologous chromosome in a process we refer to as homologous chromosome-templated repair (HTR). Unexpectedly, HTR-mediated allelic conversion at the white locus was more efficient (40 to 65%) in response to SSBs induced by Cas9-derived nickases D10A or H840A than to DSBs induced by fully active Cas9 (20 to 30%). Repair phenotypes elicited by Nickase versus Cas9 differ in both developmental timing (late versus early stages, respectively) and the production of undesired mutagenic events (rare versus frequent). Nickase-mediated HTR represents an efficient and unanticipated mechanism for allelic correction, with far-reaching potential applications in the field of gene editing.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer., Highlights • A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared. • Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment. • Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites. • The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy., Graphical abstract Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites.Image 1

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity. Here we report a dendronized polymer-doxorubicin (DOX) hybrid (DPDH) with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate (LPDC). The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4. DPDH efficiently enters 4T1 cells and releases DOX to induce cytotoxicity and apoptosis. Owing to the dendronzied structure, DPDH has a significantly longer blood circulation time than LPDC. DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4T1 mammary cancer model than LPDC as well as free drug, evidenced from tumor growth inhibition, TUNEL assessment and histological analysis. Biosafety of DPDH is also confirmed from hemolysis, body weight shifts during treatment and pathological analysis. This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as "eat me" signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Multiple sclerosis (MS) is a neurological disorder characterized by loss of the myelin sheath. Since the myelin sheath could insulate nerve fibers from the surrounding environment, its loss would result in dysfunction of the affected neurons in transmitting electrical signals, thus leading to sensation and motor disabilities. The treatment of MS is accompanied by a low treatment efficacy due to the existence of the blood-brain barrier (BBB) and occurrence of side effects due to a poor targeting efficacy. To overcome these obstacles of traditional MS treatment methods, nanomedicines have recently been employed to deliver MS therapeutic agents to the lesions. With deep BBB penetration and specific targeting, these nano-based interventions have received positively encouraging results and become another potential MS treatment method with better therapeutic outcomes. This review will focus on recent advances in nanomedicines for the treatment of MS by critically analyzing their strengths and weaknesses. We will propose perspectives on the development of these MS therapeutic nanomaterials.

An effective way of increasing the effectiveness, energy use decline, and reducing emissions are the Combined Cooling, Heating, and Power (CCHP) system. In this paper, an optimization procedure bas...

RNA interference (RNAi), one of the strategies that organisms use to defend against invading viruses, is an important tool for functional genomic analysis. In insects, the efficacy of RNAi varies amongst taxa. Lepidopteran insects are, in large part, recalcitrant to RNAi. The overall goal of this study is to overcome such insensitivity in lepidopterans to RNAi. We hypothesize that over-expression of core RNAi machinery enzymes can improve RNAi efficacy in traditionally recalcitrant species. A transgenic Bombyx mori strain, Baculovirus Immediate-Early Gene, ie1, promoter driven expression of silkworm Dicer2 coding sequence (IE1-BmDicer2), which over-expresses BmDicer2, was generated by piggyBac transposon-mediated transgenesis. Two indexes, the ratio of animals that showed a silencing phenotype and the duration of silencing, were used to evaluate silencing efficiency. Significant knockdown of target gene expression was observed at 48 h postinjection at both the transcriptional and translational levels. Furthermore, we coexpressed B. mori Argonaute 2 BmAgo2）and BmDicer 2 and found that 22% of the animals (n = 18) showed an obvious silencing effect even at 72 h, suggesting that coexpression of these two RNAi core machinery enzymes further increased the susceptibility of B. mori to injected double-stranded RNAs. This study offers a new strategy for functional genomics research in RNAi-refractory insect taxa in general and for lepidopterans in particular.

Magnetic resonance (MR) contrast agents have been explored to improve the diagnosis of vascular diseases or tumors, yet clinically used small molecular agents have not been very successful owing to their poor contrast efficiency and short circulation time. Herein we reported a biodegradable HPMA polymeric micelle-based MR contrast agent containing gadolinium (Gd3+) for imaging murine vascular structures and tumors. This nano-sized polymeric agent has a high relaxivity, good biosafety and great biodegradability for MR applications. In vivo MR angiography (MRA) clearly reveals the abdominal, intracranial and tumor-surrounding blood vessels for a longer time after injection of the polymeric agent compared to DTPA-Gd. Furthermore, orthotopic and subcutaneous imaging of a murine breast cancer tumor model demonstrates that this polymeric agent has excellent contrast enhancement in tumors. The enhancement may be due to great accumulation of the polymeric agent in tumors and tumor associated macrophages (TAM) might help improve the accumulation of the polymeric agent in tumors. Thus, in comparison with DTPA-Gd, this polymeric micelle-based biodegradable and biocompatible contrast agent has been demonstrated to have a high MRI contrast efficacy for murine vasculatures and tumors.

In this paper, a solid acid(base) MoO3(MgO)/ZrO2 was prepared for the catalytic hydrolysis of difluorodichloromethane (CFC-12). The effects of the catalyst preparation method, calcination temperature, and hydrolysis temperature on the conversion rate of CFC-12 were studied. The catalysts were characterized by XRD, N2 isotherm adsorption desorption, NH3-TPD, and CO2-TPD. Meanwhile, the equivalence of the catalytic activity of MoO3(MgO)/ZrO2 for CFC-12 was studied. Research shows that the solid acid MoO3/ZrO2 and solid base MgO/ZrO2 catalyzed hydrolysis of CFC-12 is equivalent; the solid acid MoO3/ZrO2 is calcined at 600 °C for 3 h and the solid base MgO/ZrO2 is calcined at 600 °C for 6 h (co-precipitation) and 700 °C for 6 h (impregnated) at a catalytic hydrolysis temperature of 300–400 °C and CFC-12 concentration of 4%. The catalytic hydrolysis products obtained were CO, HCl, and HF, and the CFC-12 conversion rate almost reached 100%.

COVID-19 has amplified long-standing emotional distress for vulnerable families. While abundant research highlights the importance of resilience under adverse circumstances, little has been undertaken to understand its effectiveness in helping caregivers of individuals with eating disorders (ED) navigate pandemic-related challenges. This paper presents findings of a cross-sectional study investigating the effects of COVID-19-related life disruptions (COLD) and COVID-19-related psychological distress (CORPD) on caregivers’ depression, anxiety and stress, as well as the moderation role of individual resilience (IR) and family resilience (FR) during the post-pandemic period in China. A total of 201 caregivers of individuals experiencing ED participated in our online survey from May 2022 to June 2022. The association between pandemic-related stressors (i.e., COLD and CORPD) and mental health conditions were confirmed. FR moderated the relationship between CORPD and mental health outcomes, while IR independently contributed to low emotional distress. We call for intervention programs strengthening caregivers’ FR and IR, which might benefit both patients and caregivers’ well-being in the post-pandemic period.

Peach (Prunus persica) is one of the most important fruit crops globally, but its cultivation can be hindered by large tree size. 'Zhongyoutao 14' (CN14) is a temperature-sensitive semi-dwarf (TSSD) cultivar which might be useful as breeding stock. The genome of CN14 was sequenced and assembled de novo using single-molecule real-time sequencing and chromosome conformation capture assembly. A high-quality genome was assembled and annotated, with 228.82 Mb mapped to eight chromosomes. Eighty-six re-sequenced F

The growth of grapevine [Vitis vinifera L.] is commonly limited by drought stress. The mechanisms by which grapevine copes with drought stress have not yet been extensively clarified. In this study, the drought and abscisic acid (ABA)-induced gene VvWRKY18 was demonstrated to decreased drought tolerance of Arabidopsis thaliana overexpression (VvWRKY18-OE) lines. Compared to wild-type plants, VvWRKY18-OE lines showed increased levels of malonaldehyde (MDA) and the reactive oxygen species (ROS) H

Background Ubiquitin ligases (E3) are the enzymes in the ubiquitin/26S proteasome pathway responsible for targeting proteins to the degradation pathway and play major roles in multiple biological activities. However, the E3 family and their functions are yet to be identified in the fruit of peach. Results In this study, genome-wide identification, classification and characterization of the E3 ligase genes within the genome of peach (Prunus persica) was carried out. In total, 765 E3 (PpE3) ligase genes were identified in the peach genome. The PpE3 ligase genes were divided into eight subfamilies according to the presence of known functional domains. The RBX subfamily was not detected in peach. The PpE3 ligase genes were not randomly distributed among the 8 chromosomes, with a greater concentration on the longer chromosomes. The primary mode of gene duplication of the PpE3 ligase genes was dispersed gene duplication (DSD). Four subgroups of the BTB subfamily never characterized before were newly identified in peach, namely BTBAND, BTBBL, BTBP and BTBAN. The expression patterns of the identified E3 ligase genes in two peach varieties that display different types of fruit softening (melting flesh, MF, and stony hard, SH) were analyzed at 4 different stages of ripening using Illumina technology. Among the 765 PpE3 ligase genes, 515 (67.3%) were expressed (FPKM > 1) in the fruit of either MF or SH during fruit ripening. In same-stage comparisons, 231 differentially expressed genes (DEGs) were identified between the two peach cultivars. The number of DEGs in each subfamily varied. Most DEGs were members of the BTB, F-box, U-box and RING subfamilies. PpE3 ligase genes predicted to be involved in ethylene, auxin, or ABA synthesis or signaling and DNA methylation were differentially regulated. Eight PpE3 ligase genes with possible roles in peach flesh texture and fruit ripening were discussed. Conclusions The results of this study provide useful information for further understanding the functional roles of the ubiquitin ligase genes in peach. The findings also provide the first clues that E3 ligase genes may function in the regulation of peach ripening.

Background The glyoxalase system usually comprises two enzymes, glyoxalase I (GLYI) and glyoxalase II (GLYII). This system converts cytotoxic methylglyoxal (MG) into non-toxic D-lactate in the presence of reduced glutathione (GSH) in two enzymatic steps. Recently, a novel type of glyoxalase III (GLYIII) activity has observed in Escherichia coli that can detoxify MG into D-lactate directly, in one step, without a cofactor. Investigation of the glyoxalase enzymes of a number of plant species shows the importance of their roles in response both to abiotic and to biotic stresses. Until now, glyoxalase gene families have been identified in the genomes of four plants, Arabidopsis, Oryza sativa, Glycine max and Medicago truncatula but no similar study has been done with the grapevine Vitis vinifera L. Results In this study, four GLYI-like, two GLYII-like and three GLYIII-like genes are identified from the genome database of grape. All these genes were analysed in detail, including their chromosomal locations, phylogenetic relationships, exon-intron distributions, protein domain organisations and the presence of conserved binding sites. Using quantitative real-time PCR analysis (qRT-PCR), the expression profiles of these genes were analysed in different tissues of grape, and also when under infection stress from downy mildew (Plasmopara viticola). The study reveals that most VvGLY-like genes had higher expressions in stem, leaf, tendril and ovule but lower expressions in the flower. In addition, most of the VvGLY-like gene members were P. viticola responsive with high expressions 6-12 h and 96-120 h after inoculation. However, VvGLYI-like1 was highly expressed 48 h after inoculation, similar to VvPR1 and VvNPR1 which are involved in the defence response. Conclusions This study identified the GLYI-like, GLYII-like and GLYIII-like full gene families of the grapevine. Based on a phylogenetic analysis and the presence of conserved binding sites, we speculate that these glyoxalase-like genes in grape encode active glyoxalases. Moreover, our study provides a basis for discussing the roles of VvGLYI-like, VvGLYII-like and VvGLYIII-like genes in grape’s response to downy mildew infection. Our results shed light on the selection of candidate genes for downy mildew tolerance in grape and lay the foundation for further functional investigations of these glyoxalase genes. Electronic supplementary material The online version of this article (10.1186/s12864-019-5733-y) contains supplementary material, which is available to authorized users.

CRISPR-based active genetic elements, or gene-drives, copied via homology-directed repair (HDR) in the germline, are transmitted to progeny at super-Mendelian frequencies. Active genetic elements also can generate widespread somatic mutations, but the genetic basis for such phenotypes remains uncertain. It is generally assumed that such somatic mutations are generated by non-homologous end-joining (NHEJ), the predominant double stranded break repair pathway active in somatic cells. Here, we develop CopyCatcher systems in Drosophila to detect and quantify somatic gene conversion (SGC) events. CopyCatchers inserted into two independent genetic loci reveal unexpectedly high rates of SGC in the Drosophila eye and thoracic epidermis. Focused RNAi-based genetic screens identify several unanticipated loci altering SGC efficiency, one of which (c-MYC), when downregulated, promotes SGC mediated by both plasmid and homologous chromosome-templates in human HEK293T cells. Collectively, these studies suggest that CopyCatchers can serve as effective discovery platforms to inform potential gene therapy strategies.

Periodic post-embryonic changes in insects, including growth, development and metamorphosis, are strictly controlled by many compounds, including steroid hormones. The biosynthesis and clearance of 20-hydroxyecdysone (20E), the major active form of the insect steroid hormone ecdysone, result in titer fluctuations that help control insect development. The inactivation of 20E in the silkworm Bombyx mori is highly tissue-specific, with CYP18A1 and ecdysone oxidase controlling 20E inactivation specifically in the mid-silk gland and midgut, respectively. Here, we characterized silkworm 3-dehydroecdysone 3α reductase (Bm3DE3α) and 3-dehydroecdysone 3β reductase (Bm3DE3β), two enzymes involved predominantly in the C-3-mediated catalysis of 20E in fat bodies. The ubiquitous and silk gland-specific overexpression of Bm3DE3α decreased the 20E titer, resulting in larval lethality and larval-pupal transition failure, respectively. In contrast, the ubiquitous and mid-silk gland-specific overexpression of Bm3DE3β increased the 20E titer, resulting in larval growth delays and lethality at the mid-fifth larval stage, respectively. Thus, Bm3DE3α and Bm3DE3β mediate fat body-specific steroid hormone metabolism in B. mori, indicating that highly diversified 20E metabolism-related mechanisms exist in different insect species.

Peach (Prunus persica L. Batsch) trees grow vigorously and are subject to intense pruning during orchard cultivation. Reducing the levels of endogenous gibberellins (GAs) represents an effective method for controlling branch growth. Gibberellin 2-oxidases (GA2oxs) deactivate bioactive GAs, but little is known about the GA2ox gene family in peach. In this study, we identified seven PpGA2ox genes in the peach genome, which were clustered into three subgroups: C19-GA2ox-I, C19-GA2ox-II, and C20-GA2ox-I. Overexpressing representative genes from the three subgroups, PpGA2ox-1, PpGA2ox-5, and PpGA2ox-2, in tobacco resulted in dwarf plants with shorter stems and smaller leaves than the wild type. An analysis of the GA metabolic profiles of the transgenic plants showed that PpGA2ox-5 (a member of subgroup C19-GA2ox-II) is simultaneously active against both C19-GAs and C20-GAs,which implied that C19-GA2ox-II enzymes represent intermediates of C19-GA2oxs and C20-GA2oxs. Exogenous GA3 treatment of shoot tips activated the expression of all seven PpGA2ox genes, with different response times: the C19-GA2ox genes were transcriptionally activated more rapidly than the C20-GA2ox genes. GA metabolic profile analysis suggested that C20-GA2ox depletes GA levels more broadly than C19-GA2ox. These results suggest that the PpGA2ox gene family is responsible for fine-tuning endogenous GA levels in peach. Our findings provide a theoretical basis for appropriately controlling the vigorous growth of peach trees.

Background: In order to solve the potential toxicity of metal-based Magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2, 2, 6, 6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal based contrast agents (such as Gd3+ chelate-based clinical CAs). However, nitroxides lower relaxivity and metabolizes rapidly in vivo are still challenge. Previous researches have proven that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through the macromolecularization of nitroxides (ie, large molecules carry nitroxides). Macromolecular effects not only improve the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results: Branched pDHPMA-mPEG-Ppa-PROXYL with high molecular weight (MW=160 kDa) and nitroxides content (0.059 mmol/g), it can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by the hydrophilic outer layer to obtain the strong reduction resistance in vivo. Compared with the small molecular 3-Carboxy-PROXYL (3-CP), Branched pDHPMA-mPEG-Ppa-PROXYL displays there prominent performance: 1) its longitudinal relaxivity (0.50 mM-1 s-1) is about three times that of the 3-CP (0.17 mM-1 s-1); 2) the blood retention time of nitroxides is increased significantly from a few minutes of 3-CP to 6 h; 3) it could provide long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions: As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in tumor, liver and kidney imaging, but also in cardiovascular system imaging, which expands the application scope of this kind of CAs.

In this study, an experimental hydrometeorological forecasting system was developed based on the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) model. The system downloads global real-time ocean, atmosphere, and wave forcing data, producing regional forecasts every day. A coastal area in South China, encompassing Hainan Island, Leizhou Peninsula, and surrounding sea areas, was chosen as the study domain. A series of 72-hour forecasting simulations were conducted in the area, lasting from July 27 to August 31, 2019. The forecasts throughout August were chosen for evaluation with station observations, along with two sets of reanalysis data, ERA5 and CLDAS. The evaluation results revealed that the COAWST model had high potential for routine forecasting operations. The 24 h forecasts, with a lead time of 24 hours, had high accuracy, while the 48 h and 72 h forecasts did not differ greatly in terms of performance. The distributions of bias between forecast and reanalysis data showed obvious differences between land and sea, with more forecasted precipitation and lower temperatures in land grids than in sea grids. In most cases, the forecasts were closer to ERA5 in terms of means and other statistical measures. The forecasts enlarged the land-sea differences of temperature when compared with ERA5 and strengthened summer monsoon with more moisture transported to land areas. Resulting from that, a forecasted bias of lower surface pressure, higher air humidity, stronger south wind, and so forth was also detected over the domain but at low values.

The catalytic hydrolysis of Difluorodichloromethane(CFC-12) by solid acid of MoO3/ZrO2-TiO2 calcined at different temperature had been studied. The effects of catalytic hydrolysis temperature and water vapor concentration on catalytic hydrolysis of CFC-12were also studied. The results showed that catalytic hydrolysis rate of CFC-12 reached to 98.65% at 400 ℃ when the MoO3/ZrO2-TiO2 catalyst was calcined at 500 ℃ with a concentration of water vapor of 83.18%, and the main hydrolysis products were CO, CO2, HF and HCl. After 30 hours’ continuous reaction, the hydrolysis rate of CFC-12 was 65.34%. The XRD result reveals that the main phase of solid MoO3/ZrO2-TiO2 catalyst is the tetragonal Zr (MoO4)2 with doped TiO2 of anatase.

To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG)-functionalized HP-based polymers conjugated with pyropheophorbide-a (Ppa): a non-GSH-responsive nanoagent (HP-Ppa-mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH-responsive nanoagent (HP-Ppa-SS-mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa-functionalized HP without PEGylation (HP-Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP-Ppa-SS-mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 % tumor growth inhibition rate, suggesting that tumor microenvironment-responsive PEGylated HP-based nanomedicines may act as efficient anticancer agents.

The catalytic behaviors of solid acid of MoO3/ZrO2-TiO2 calcined at different temperature for the catalytic hydrolysis of Dichlorodifluoromethane have been studided. The effects of catalytic hydrolysis temperature and water vapor concentration on catalytic hydrolysis of Dichloro difluoromethane were also studied. The Results show 98.65 % of Dichlorodifluoromethane is degraded over MoO3/ZrO2-TiO2 catalyst calcined at 500 ℃ with a concentration of water vapor of 83.18% when the hydrolysis temperature is 350 ℃ and the Dichlorodifluoromethane flux rate is 1 mL/min with main degradation products were CO, CO2, HF and HCl. A maintained degradation rate of 65.34% of Difluoromethylene Chloride has been observed through 30 hours’ continuous reaction over the catalyst of MoO3/ZrO2-TiO2. The XRD result reveals the main phase of solid MoO3/ZrO2-TiO2 catalyst is the tetragonal Zr (MoO4)2 that dopedTiO2 of anatase.

In this paper, a solid acid(base) MoO

Summary Seedlessness in grapes is one of the features most appreciated by consumers. However, the mechanisms underlying seedlessness in grapes remain obscure. Here, we observe small globular embryos and globular embryos in Pinot Noir and Thompson Seedless from 20 to 30 days after flowering (DAF). From 40 to 50 DAF, we observe torpedo embryos and cotyledon embryos in Pinot Noir but aborted embryos and endosperm in Thompson Seedless. Thus, RNA‐Seq analyses of seeds at these stages from Thompson Seedless and Pinot Noir were performed. A total of 6442 differentially expressed genes were identified. Among these, genes involved in SA biosynthesis, VvEDS1 and VvSARD1, were more highly expressed in Thompson Seedless than in Pinot Noir. Moreover, the content of endogenous SA is at least five times higher in Thompson Seedless than in Pinot Noir. Increased trimethylation of H3K27 of VvEDS1 and VvSARD1 may be correlated with lower SA content in Pinot Noir. We also demonstrate that VvHDZ28 positively regulates the expression of VvEDS1. Moreover, over‐expression of VvHDZ28 results in seedless fruit and increased SA contents in Solanum lycopersicum. Our results reveal the potential role of SA and feedback regulation of VvHDZ28 in seedless grapes.

Objective: Application of diffusion tensor imaging (DTI) to explore the changes of FA value in patients with Parkinson's disease (PD) with mild cognitive impairment. Methods: 27 patients with PD were divided into PD with mild cognitive impairment (PD-MCI) group (n = 7) and PD group (n = 20). The original images were processed using voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Results: The average age of pd-mci group was longer than that of PD group, and the course of disease was longer than that of PD group. Compared with PD group, the voxel based analysis-fractional anisotropy (VBA-FA) values of PD-MCI group decreased in the following areas: bilateral frontal lobe, bilateral temporal lobe, bilateral parietal lobe, bilateral subthalamic nucleus, corpus callosum, and gyrus cingula. Tract-based spatial statistics-fractional anisotropy (TBSS-FA) values in PD-MCI group decreased in bilateral corticospinal tract, anterior cingulum, posterior cingulum, fornix tract, bilateral superior thalamic radiation, corpus callosum(genu, body and splenium), bilateral uncinate fasciculus, bilateral inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, bilateral superior fronto-occipital fasciculus, bilateral inferior fronto-occipital fasciculus, and bilateral parietal-occipital tracts. The mean age of onset in the PD-MCI group was greater than that in the PD group, and the disease course was longer than that in the PD group. Conclusion: DTI-based VBA and TBSS post-processing methods can detect abnormalities in multiple brain areas and white matter fiber tracts in PD-MCI patients. Impairment of multiple cerebral cortex and white matter fiber pathways may be an important causes of cognitive dysfunction in PD-MCI.

To enhance the drug delivery efficiency of hyaluronic acid (HA), we designed and prepared glycodendron and pyropheophorbide-a (Ppa)-functionalized HA (HA-Ppa-Dendron) as a nanosystem for cancer photodynamic therapy. Linear Ppa-modified HA (HA-Ppa) was also prepared as a control. Cellular uptake of both polymers by MDA-MB-231 cells led to mitochondrial dysfunction and generation of reactive oxygen species under the irradiation of a laser. Compared to the linear polymer, HA-Ppa-Dendron had higher molecular weight, a more compact nanoscale particle size, and a dendritic structure, resulting in a much longer blood circulation time and higher tumor accumulation. HA-Ppa-Dendron outperformed HA-Ppa in inhibiting cell growth, with 60 % of tumors was eradicated under laser irradiation. Tumor growth inhibition (TGI) up to 99.2 % was achieved from HA-Ppa-Dendron, which was much higher than that of HA-Ppa (50.6 %). Therefore, glycodendron-functionalized HAs by integration of HA and dendritic polymers may act as efficient anti-cancer nanomedicine.

Invasive pulmonary aspergillosis induced by the pathogenic fungus Aspergillus fumigatus is one of the common fatal complications in immunocompromised patients. Lung epithelial cells play an important role in host immune defense against A. fumigatus. However, the interaction between lung epithelial cells and A. fumigatus conidia is not fully understood. In this study, we used the swollen conidia of A. fumigatus to stimulate the type II lung epithelial A549 cells. Results showed that swollen conidia could significantly increase RNA transcription and protein expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1), but not TNF-α in A549 cells in a time-dependent manner. Moreover, serum opsonization was able to improve the release of inflammatory factors induced by swollen conidia. Blocking of the dectin-1 or CR3 receptors, or both simultaneously, in the A549 cells could decrease the release of IL-8 and MCP-1. Additionally, blocking dectin-1 or CR3 could inhibit the transcription of nuclear factor NF-κB that was activated by swollen conidia. Here we reported for the first time that dectin-1 and CR3 receptors in A549 cells mediate the release of pro-inflammatory factors IL-8 and MCP-1 induced by A. fumigatus.

Background Heat shock factors (HSFs) play important roles during normal plant growth and development and when plants respond to diverse stressors. Although most studies have focused on the involvement of HSFs in the response to abiotic stresses, especially in model plants, there is little research on their participation in plant growth and development or on the HSF (PpHSF) gene family in peach (Prunus persica). Methods DBD (PF00447), the HSF characteristic domain, was used to search the peach genome and identify PpHSFs. Phylogenetic, multiple alignment and motif analyses were conducted using MEGA 6.0, ClustalW and MEME, respectively. The function of PpHSF5 was confirmed by overexpression of PpHSF5 into Arabidopsis. Results Eighteen PpHSF genes were identified within the peach genome. The PpHSF genes were nonuniformly distributed on the peach chromosomes. Seventeen of the PpHSFs (94.4%) contained one or two introns, except PpHSF18, which contained three introns. The in silico-translated PpHSFs were classified into three classes (PpHSFA, PpHSFB and PpHSFC) based on multiple alignment, motif analysis and phylogenetic comparison with HSFs from Arabidopsis thaliana and Oryza sativa. Dispersed gene duplication (DSD at 67%) mainly contributed to HSF gene family expansion in peach. Promoter analysis showed that the most common cis-elements were the MYB (abiotic stress response), ABRE (ABA-responsive) and MYC (dehydration-responsive) elements. Transcript profiling of 18 PpHSFs showed that the expression trend of PpHSF5 was consistent with shoot length changes in the cultivar ‘Zhongyoutao 14’. Further analysis of the PpHSF5 was conducted in 5-year-old peach trees, Nicotiana benthamiana and Arabidopsis thaliana, respectively. Tissue-specific expression analysis showed that PpHSF5 was expressed predominantly in young vegetative organs (leaf and apex). Subcellular localization revealed that PpHSF5 was located in the nucleus in N. benthamiana cells. Two transgenic Arabidopsis lines were obtained that overexpressed PpHSF5. The root length and the number of lateral roots in the transgenic seedlings were significantly less than in WT seedlings and after cultivation for three weeks. The transgenic rosettes were smaller than those of the WT at 2–3 weeks. The two transgenic lines exhibited a dwarf phenotype three weeks after transplanting, although there was no significant difference in the number of internodes. Moreover, the PpHSF5-OE lines exhibited enhanced thermotolerance. These results indicated that PpHSF5 might be act as a suppresser of growth and development of root and aerial organs.

The catalytic behaviors of solid acid of MoO3/ZrO2-TiO2 calcined at different temperature for the catalytic hydrolysis of Dichlorodifluoromethane have been studided. The effects of catalytic hydrolysis temperature and water vapor concentration on catalytic hydrolysis of Dichlorodifluoromethane were also studied. The Results show 98.65 % of Dichlorodifluoromethane is degraded over MoO3/ZrO2-TiO2 catalyst calcined at 500 ℃ with a concentration of water vapor of 83.18% when the hydrolysis temperature is 400。C and the Dichlorodifluoromethane flux rate is 1mL/min with main degradation products were CO, CO2, HF and HCl. A maintained degradation rate of 65.34 % of Difluoromethylene Chloride has been observed through 30 hours’ continuous reaction over the catalyst of MoO3/ZrO2-TiO2. The XRD result reveals the main phase of solid MoO3/ZrO2-TiO2 catalyst is the tetragonal Zr(MoO4)2 that doped TiO2 of anatase.

Production of seedless V. vinifera L. cultivars is one of the major goals of table grape breeding. Traditional methods result in only a low percentage of seedless progeny. Modern techniques, such as embryo rescue, are used to improve production efficiency of seedless cultivars. In this study, the effects of various putrescine concentrations (0, 1, 2, 3, 4, and 5 mmol L−1) and different stages of embryo development (globular-, heart-, torpedo-, and cotyledon-shaped embryo) on the success rate of embryo rescue were assessed in three lines of the F1 Vitis vinifera L., cross ‘Delight’ × ‘Ruby Seedless,’ ‘DR2,’ ‘DR3,’ and ‘DR6’ (with small seed traces). The plant development rates of ‘DR2,’ ‘DR3,’ and ‘DR6’, which contain small seed traces, as female parents, were significantly higher than those of seedless varieties. The rates of embryo development on woody plant medium (WPM) of ‘DR2’ × ‘Thompson Seedless,’ ‘DR3’ × ‘Thompson Seedless,’ and ‘DR6’ × ‘Monukka’ were highest with 2, 2, and 4 mmol L−1 putrescine, respectively. The germination rates of torpedo- and cotyledon-shaped embryos were significantly higher than those of globular- and heart-shaped embryos. Characteristics of the embryo germination progress of ‘DR2’ × ‘Thompson Seedless’ at different developmental stages were recorded. The Grape Seedless gene Probe 1 (GSLP1) marker was used to help identify the seedless descendants; 14 plantlets showed a corresponding electrophoresis band at 569 bp and were preliminarily defined as seedless.