Phytophthora sojae Effector PsAvh113 Targets Transcription Factors in Nicotiana benthamiana.

Phytophthora sojae is a type of pathogenic oomycete that causes Phytophthora root stem rot (PRSR), which can seriously affect the soybean yield and quality. To subvert immunity, P. sojae secretes a large quantity of effectors. However, the molecular mechanisms regulated by most P. sojae effectors, and their host targets remain unexplored. Previous studies have shown that the expression of PsAvh113, an effector secreted by Phytophthora sojae, enhances viral RNA accumulations and symptoms in Nicotiana benthamiana via VIVE assay. In this study, we analyzed RNA-sequencing data based on disease symptoms in N. benthamiana leaves that were either mocked or infiltrated with PVX carrying the empty vector (EV) and PsAvh113. We identified 1769 differentially expressed genes (DEGs) dependent on PsAvh113. Using stricter criteria screening and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis of DEGs, we found that 38 genes were closely enriched in response to PsAvh113 expression. We selected three genes of N. benthamiana (NbNAC86, NbMyb4, and NbERF114) and found their transcriptional levels significantly upregulated in N. benthamiana infected with PVX carrying PsAvh113. Furthermore, individual silencing of these three genes promoted P. capsici infection, while their overexpression increased resistance to P. capsici in N. benthamiana. Our results show that PsAvh113 interacts with transcription factors NbMyb4 and NbERF114 in vivo. Collectively, these data may help us understand the pathogenic mechanism of effectors and manage PRSR in soybeans.

A Nomogram Based on Conventional and Contrast-Enhanced Ultrasound for Pre-operative Prediction of Nipple-Areola Complex Involvement in Breast Cancer: A Prospective Study.

OBJECTIVE: Accurately predicting nipple-areola complex (NAC) involvement in breast cancer is essential for identifying eligible patients for a nipple-sparing mastectomy. This study was aimed at developing a pre-operative nomogram for NAC involvement in breast cancer using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). METHODS: All patients with primary breast cancer confirmed by pre-operative biopsy underwent US and CEUS examinations. Post-operative pathology was used as the gold standard in assessing NAC involvement. Lasso regression was used to select the predictors most associated with NAC involvement. A nomogram was constructed to calculate the diagnostic efficacy. The data were internally verified with 500 bootstrapped replications, and a calibration curve was generated to validate the predictive capability. RESULTS: Seventy-six patients with primary breast cancer were included in this study, which included 16 patients (21.1%) with NAC involvement and 60 patients (78.9%) without NAC involvement. Among the 23 features of US and CEUS, Lasso regression selected one US feature and two CEUS features, namely, ductal echo extending from the lesion, ductal enhancement extending to the nipple and focal nipple enhancement. A nomogram was constructed, and the results revealed that the area under the curve, sensitivity, specificity and accuracy were 0.891, 81.3%, 86.7% and 85.5%, respectively. The calibration curve exhibited good consistency between the predicted probability and the actual probability. CONCLUSION: The nomogram developed based on US and CEUS had good performance in predicting NAC involvement in breast cancer before surgery, which may facilitate the selection of suitable patients for NAC preservation with greater oncological safety.

Polybrominated diphenyl ethers (PBDEs) in household dust: A systematic review on spatio-temporal distribution, sources, and health risk assessment.

Much attention has been paid on polybrominated diphenyl ethers (PBDEs) in household dust due to their ubiquitous occurrences in the environment. Based on the data from 59 articles sampled from 2005 to 2020, we investigated the spatio-temporal distribution, sources, and health risk of 8 PBDE homologues in household dusts worldwide. BDE-209 is the predominant PBDE in household dusts, followed by BDE-99 and BDE-47. The total concentrations of PBDEs (∑8PBDEs) are found to be high in household dusts sampled from 2005 to 2008 and show a significant decline trend from 2009 to 2016 (p < 0.05) and a little upward tendency from 2017 to 2020. The concentrations of PBDEs in household dusts vary greatly in different countries of the world. The use of penta-BDE is the main source of three to five bromo-biphenyl ether monomers contributing 17.4% of ∑8PBDEs, while BDE-209 and BDE-183 are derived from the use of household appliances contributing 82.6% of ∑8PBDEs. Ingestion is the main exposure route for adults and toddlers, followed by dermal contact. The values of hazard index (HI) exposed to PBDEs in household dusts are all less than 1 for both adults and toddlers, indicating a low non-cancer risk. The incremental lifetime cancer risks (ILCRs) of BDE-209 are less than 10-6 for both adults and toddlers, suggesting a negligible risk. However, the total carcinogenic risk of toddlers is higher than that of adults, indicating that much attention should be paid to toddlers exposed to BDE-209 in household dust.

Ultrasound monitoring of magnet-guided delivery of mesenchymal stem cells labeled with magnetic lipid-polymer hybrid nanobubbles.

Restenosis remains a pressing clinical problem that occurs in patients undergoing revascularization procedures, such as coronary artery bypass surgery and percutaneous transluminal angioplasty. Previous reports have proved that mesenchymal stem cells (MSCs) could effectively reduce the restenosis resulting from intimal hyperplasia following vascular injury. However, non-invasive delivery of MSCs and real-time monitoring of their retention at the site of vascular injury still remain a significant challenge. Therefore, we synthesized magnetic lipid-polymer hybrid nanobubbles (Mag-LPNs) as ultrasound contrast agents for cellular labeling of MSCs, endowing these MSCs with magnetic responsibility and real-time tracking capability by ultrasound. In order to enhance the internalization efficiency of MSCs, Mag-LPNs were modified with cationic polymers to generate positively charged Mag-LPNs (P-Mag-LPNs). Intriguingly, the internalization of P-Mag-LPNs did not exhibit obvious harmful effects on the labeled MSCs in terms of cell viability and differentiation capacity. Moreover, the magnet-guided delivery of labeled MSCs in a rat carotid artery injury model developed using a 2-French balloon catheter could be tracked by ultrasound in a real-time manner. About 5-fold more MSCs were attached at the site of the injured artery with the aid of an external magnet field, compared with the absence of a magnet field. Herein, our study provides an innovative tracking platform for magnet-guided delivery of stem cells treating cardiovascular diseases.

The use of aggregation-induced emission probe doped silica nanoparticles for the immunoassay of human epididymis protein 4.

A sensitive sandwich immunoassay for the sensing of human epididymis protein 4 (HE4) is developed based on aggregation-induced emission probe doped silica nanoparticles. Fluorescent silica nanoparticles (TSiO2) with excellent performance were prepared using a tetraphenylethylene based probe (TPE-C4-4) to produce a controlled aggregation effect, and HE4 was detected using antibody-functionalized fluorescent silica nanoparticles. The fluorescent silica nanoparticles possess good photophysical properties. The TSiO2 NPs were surface modified with carboxyl groups, and the antibody was covalently attached onto the surface of the nanoparticles. In addition, magnetic beads were modified with N-hydroxysulfosuccinimide sodium salt (NHS) on their surface, capable of forming stable peptide bonds with the antibody. TSiO2 NPs modified by an antibody and the magnetic beads modified by an antibody were used for the sandwich immunoassay for HE4 protein. The assay is quite sensitive and selective. The detection limit of HE4 is estimated to be 40 pM. The assay shows promising applications for the early diagnosis of ovarian cancer and the development of ovarian cancer-related drugs.

A label free Ag+ sensing method via in situ formation of metal coordination polymer.

Metal ions sensing play critical roles in environmental monitoring and in biology. In this assay, we report the development of a facile fluorometric method for the sensing of Ag+ ions via the in situ formation of metal coordination polymer, based on the selective interactions of GSH with Ag+. The formation of coordination polymer with net multiple negative charges in an aqueous buffer solution (Tris-HAc, pH 9.0) resulted in aggregation and fluorescence quenching of a cationic perylene probe. The difference in emission intensity spurred us to develop a new strategy for sensing Ag+ ions. The proposed Ag+ detection method is simple, convenient, selective and sensitive, and can be used for Ag+ detection in lake water samples.

[Determination of 16 polycyclic aromatic hydrocarbons in marine sediments by gas chromatography-tandem mass spectrometry with accelerated solvent extraction].

A method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) with accelerated solvent extraction (ASE) was developed for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in marine sediments. The sediment samples were extracted with hexane-acetone (1:1, v/v). The extracts were dehydrated with anhydrous sodium sulfate, and concentrated with a termovap sample concentrator. The concentrated solutions were further cleaned up with Si SPE columns. The purified solutions were then isolated by HP-5MS column (30 m×0.25 mm×0.25 µm). The analytes were detected using electron impact source under multiple reaction monitoring (MRM) mode. The results showed that the 16 PAHs had good linearities in the range of 0.01-1.00 mg/L with the correlation coefficients (R) greater than 0.997. The spiked recoveries of the 16 PAHs were in the range of 75.8%-97.8%, and the relative standard deviations (RSDs) were less than 10%. The method detection limits (MDLs) of the 16 PAHs ranged from 0.048-0.234 µg/kg with 20.0 g sampling weight. This method is suitable for the determination of trace PAHs in marine sediments.

Reactivity of thyroid papillary carcinoma cells to thyroid stimulating hormone-dominated endocrine therapy.

This study investigated the effect of thyroid stimulating hormone (TSH) on the proliferation of papillary thyroid carcinoma (PTC) cells and the therapeutic effect of levothyroxine sodium (TH). PTC cells (TPC-1) were cultured using 0.1, 1.0 and 10 U/l TSH and 10-2, 10-4 and 10-6 mol/l TH. After the appropriate concentration was screened, TPC-1 cells were further divided into control group, TSH group, TH group and TSH+TH group. The cell proliferation was detected via methyl thiazolyl tetrazolium (MTT) method, TPC-1 cell cycle was detected via flow cytometer, and the mRNA and protein expression of cyclin D1 were detected via real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Compared with control group, TSH significantly promoted the proliferation of TPC-1 cells (P<0.05 or P<0.01), obviously promoted the transition of TPC-1 cells from G1 phase to S phase (P<0.01) and remarkably increased the mRNA and protein expression of cyclin D1 (P<0.01); but TH had a significant inhibitory effect on these results of TSH (P<0.05 or P<0.01). TSH can promote the proliferation of PTC cells, and the appropriate complement of TH can inhibit its proliferation.

Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD.

Major depressive disorder (MDD) is a common neuropsychiatric disorder characterized by diverse symptoms. Although several antidepressants can influence dopamine system in the medial prefrontal cortex (mPFC), but the role of D1R or D2R subtypes of dopamine receptor during anti-depression process is still vague in PFC region. To address this question, we investigate the antidepressant effect of levo-stepholidine (l-SPD), an antipsychotic medication with unique pharmacological profile of D1R agonism and D2R antagonism, and clarified its molecular mechanisms in the mPFC. Our results showed that l-SPD exerted antidepressant-like effects on the Sprague-Dawley rat CMS model of depression. Mechanism studies revealed that l-SPD worked as a specific D1R agonist, rather than D2 antagonist, to activate downstream signaling of PKA/mTOR pathway, which resulted in increasing synaptogenesis-related proteins, such as PSD 95 and synapsin I. In addition, l-SPD triggered long-term synaptic potentiation (LTP) in the mPFC, which was blocked by the inhibition of D1R, PKA, and mTOR, supporting that selective activation of D1R enhanced excitatory synaptic transduction in PFC. Our findings suggest a critical role of D1R/PKA/mTOR signaling cascade in the mPFC during the l-SPD mediated antidepressant process, which may also provide new insights into the role of mesocortical dopaminergic system in antidepressant effects.

Nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs with enhanced drug uptake and the activity of overcoming drug resistance.

Here, a nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs [biodegradable polymer-di-cisPt(IV)] for overcoming cisplatin drug resistance is reported. From the MTT assays, lower IC50 values of polymer-di-cisPt(IV) on A2780DDP cells than A2780 were observed with the lowest resistance factor of 0.7. Inductively coupled plasma mass spectroscopy results showed that more drugs were delivered into cancer cells and greater number of Pt-DNA adducts were formed with the use of the polymer-di-cisPt(IV) conjugate nanoparticles. By a mechanistic study with endocytosis inhibitors to treat A2780 cells, we proved that polymer-di-cisPt(IV) conjugate nanoparticles were internalized by the cancer cells through endocytosis rather than through passive diffusion or copper transporter 1-mediated active transportation. This well illustrates the way how the polymer-di-cisPt(IV) micelles overcome cisplatin resistance.

Bis{2-[(2-benzoyl-hydrazin-1-yl-idene)meth-yl]-6-meth-oxy-phenolato}iron(III) chloride monohydrate.

In the title mononuclear iron(III) complex, [Fe(C(15)H(13)N(2)O(3))(2)]Cl·H(2)O, the Fe(III) atom has a distorted octa-hedral geometry and is six-coordinated by four O atoms and two N atoms from two ligands. In the crystal structure, the complex cations, Cl(-) anions and water mol-ecules are connected into a chain along [100] through N-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonds. Two adjacent chains are linked by O-H⋯O hydrogen bonds.