Understanding the toxicity mechanism of gelsemine in zebrafish.

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.

Inhibitory Effect of Acetaminophen on Ocular Pigmentation and its Relationship with Thyroxine in Zebrafish Embryos.

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.

Spatiotemporal Visualization of Paraquat Distribution, Toxicokinetics, and Its Detoxification in Zebrafish Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging.

Paraquat is a highly toxic quaternary ammonium herbicide. It can damage the functions of multiple organs and cause irreversible pulmonary fibrosis in the human body. However, the toxicological mechanism of paraquat is not yet fully understood, and due to the lack of specific antidotes, the clinical treatment of paraquat intoxication is still a great medical challenge. In-depth research on its toxicity mechanism, toxicokinetics, and effective antidotes is urgently demanded. A new molecular imaging technique, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), can simultaneously achieve quantitative and spatial analysis and offer an alternative, distinct, and useful technique for paraquat intoxication and consequent detoxication. Here, we visualized the spatial-temporal distribution and conducted toxicokinetic research on paraquat in zebrafish by using stable isotope-labeled internal-standard-aided MALDI-MSI for the first time. The results indicated that paraquat had a fast absorption rate and was widely distributed in different organs, such as the brain, gills, kidneys, and liver in zebrafish. Its half-life was long, and the elimination rate was slow. Paraquat reached its peak at 30 min and was mainly distributed in kidneys and intestines and then showed a tendency of declining first but mildly rising later at 6 h, accompanied by a wide distribution in kidneys and intestines again. It suggested that entero-systemic recirculation might lead to the observed secondary peaks, and perhaps it extended the residence time of paraquat in the body. In addition, we validated the potential detoxification effect of sodium salicylate as a potential antidote for paraquat from both the dimensions of distribution and quantification. In conclusion, MALDI-MSI conveniently provided the distinct and quantitative spatial-temporal distribution information on paraquat in the whole body of zebrafish; it will promote the understanding of its toxicokinetic characteristics and provide more valuable information for clinical treatment.

Occurrence and Chemical Control Strategy of Wheat Brown Foot Rot Caused by Microdochium majus.

Wheat brown foot rot (WBFR), caused by a variety of phytopathogenic fungi, is an important soilborne and seedborne disease of wheat. WBFR causes wheat lodging and seedling dieback, which seriously affect the yield and quality of wheat. In this study, 64 isolates of WBFR were isolated from different wheat fields in Yancheng city, Jiangsu Province, China. The internal transcribed spacer, elongation factor 1α, and RNA polymerase II subunit were amplified and the sequencing results of the fragments were analyzed with BLAST in NCBI. Through morphological and molecular identification, all of the isolates were identified as Microdochium majus. Verification by Koch's postulates confirmed that M. majus was the pathogen causing WBFR. The antifungal activities of fludioxonil and prochloraz against 64 isolates of M. majus were determined based on mycelial growth inhibition method. The results showed that fludioxonil and prochloraz had good antifungal activity against M. majus. The mean 50% effective concentration values of fludioxonil and prochloraz against M. majus were 0.2956 ± 0.1285 µg/ml and 0.0422 ± 0.0157 µg/ml, respectively. Control efficacy for seed-coating treatments conducted in a greenhouse indicated that M. majus severely damaged the normal growth of wheat, while seed coating with fludioxonil or prochloraz significantly reduced the disease incidence and improved the seedling survival rates. At fludioxonil doses of 7.5 g per 100 kg and prochloraz doses of 15 g per 100 kg, the incidence was reduced by 22.26 and 25.33%, seedling survival rates increased by 25.37 and 22.66%, and control efficacy reached 70.02 and 72.30%, respectively. These findings provide vital information for the accurate diagnosis and effective management of WBFR.

Activated Carbon nanoparticles Loaded with Metformin for Effective Against Hepatocellular Cancer Stem Cells.

Introduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.

KSS-ICP: Point Cloud Registration based on Kendall Shape Space.

Point cloud registration is a popular topic that has been widely used in 3D model reconstruction, location, and retrieval. In this paper, we propose a new registration method, KSS-ICP, to address the rigid registration task in Kendall shape space (KSS) with Iterative Closest Point (ICP). The KSS is a quotient space that removes influences of translations, scales, and rotations for shape feature-based analysis. Such influences can be concluded as the similarity transformations that do not change the shape feature. The point cloud representation in KSS is invariant to similarity transformations. We utilize such property to design the KSS-ICP for point cloud registration. To tackle the difficulty to achieve the KSS representation in general, the proposed KSS-ICP formulates a practical solution that does not require complex feature analysis, data training, and optimization. With a simple implementation, KSS-ICP achieves more accurate registration from point clouds. It is robust to similarity transformation, non-uniform density, noise, and defective parts. Experiments show that KSS-ICP has better performance than the state-of-the-art. Code1 and executable files2 are made public.

Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe).

It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.

Intrinsic and Isotropic Resampling for 3D Point Clouds.

With rapid development of 3D scanning technology, 3D point cloud based research and applications are becoming more popular. However, major difficulties are still exist which affect the performance of point cloud utilization. Such difficulties include lack of local adjacency information, non-uniform point density, and control of point numbers. In this paper, we propose a two-step intrinsic and isotropic (I&I) resampling framework to address the challenge of these three major difficulties. The efficient intrinsic control provides geodesic measurement for a point cloud to improve local region detection and avoids redundant geodesic calculation. Then the geometrically-optimized resampling uses a geometric update process to optimize a point cloud into an isotropic or adaptively-isotropic one. The point cloud density can be adjusted to global uniform (isotropic) or local uniform with geometric feature keeping (being adaptively isotropic). The point cloud number can be controlled based on application requirement or user-specification. Experiments show that our point cloud resampling framework achieves outstanding performance in different applications: point cloud simplification, mesh reconstruction and shape registration. We provide the implementation codes of our resampling method at https://github.com/vvvwo/II-resampling.

Evolution of Benzimidazole Resistance Caused by Multiple Double Mutations of ß-Tubulin in Corynespora cassiicola.

Cucumber target leaf spot caused by Corynespora cassiicola has devastated greenhouse cucumber production. In our previous study, the resistance monitoring of C. cassiicola to carbendazim was carried out, and a large number of resistant populations carrying various mutations (M163I&E198A, F167Y&E198A, F200S&E198A, or E198A) in ß-tubulin were detected. However, the single-point mutations M163I, F167Y, and F200S have remained undetected. To investigate the evolutionary mechanism of double mutations in ß-tubulin of C. cassiicola resistance to benzimidazoles, site-directed mutagenesis was used to construct alleles with corresponding mutation genotypes in ß-tubulin. Through PEG-mediated protoplast transformation, all the mutants except for the M163I mutation were obtained and conferred resistance to benzimidazoles. It was found that the mutants conferring the E198A or double-point mutations showed high resistance to carbendazim and benomyl, but the mutants conferring the F167Y or F200S mutations showed moderate resistance. Except, the F200S mutants showed low resistance, the resistance level of the other mutants to thiabendazole seemed no difference. In addition, compared to the other mutants, the F167Y and F200S mutants suffered a more severe fitness penalty in mycelial growth, sporulation, and virulence. Thus, combined with the resistance level, fitness, and molecular docking results, we concluded that the field double mutations (F167Y&E198A and F200S&E198A) evolved from the single mutations F167Y and F200S, respectively.

Risk assessment and molecular mechanism of Fusarium incarnatum resistance to phenamacril.

BACKGROUND: Cucumber fruit rot (CFR) caused by Fusarium incarnatum is a devastating fungal disease in cucumber. In recent years, CFR has occurred frequently, resulting in serious yield and quality losses in China. Phenamacril exhibits a specific antifungal activity against Fusarium species. However, no data for phenamacril against F. incarnatum is available. RESULTS: The sensitivity of 80 F. incarnatum strains to phenamacril was determined. The half maximal effective concentration (EC50 ) values ranged from 0.1134 to 0.3261 µg mL-1 with a mean EC50 value of 0.2170 ± 0.0496 µg mL-1 . A total of seven resistant mutants were obtained from 450 mycelial plugs by phenamacril-taming on potato dextrose agar (PDA) plates with 10 µg mL-1 of phenamacril, and the resistant frequency was 1.56%. Phenamacril-resistant mutants showed decreased mycelial growth, conidiation and virulence as compared with the corresponding wild-type strains, indicating that phenamacril resistance suffered a fitness penalty in F. incarnatum. In addition, using sequence analysis, the point mutations of S217P or I424S were discovered in Fimyosin-5 (the target of phenamacril). The site-directed mutagenesis of the S217P, P217S, I424S and S424I substitutions were constructed to reveal the relationship between the point mutations and phenamacril resistance. The results strongly demonstrated that the mutations of S217P and I424S in Fimyosin-5 conferred phenamacril-resistance in F. incarnatum. CONCLUSION: Phenamacril-resistant mutants were easily induced and their resistance level was high. The S217P or I424S substitutions in Fimyosin-5 conferring phenamacril resistance were detected and futherly verified by transformation assay with site-directed mutagenesis. Thus, we proposed that the resistance development of F. incarnatum to phenamacril is high risk. © 2022 Society of Chemical Industry.

Profilin 2 and Endothelial Exosomal Profilin 2 Promote Angiogenesis and Myocardial Infarction Repair in Mice.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, wherein myocardial infarction (MI) is the most dangerous one. Promoting angiogenesis is a prospective strategy to alleviate MI. Our previous study indicated that profilin 2 (PFN2) may be a novel target associated with angiogenesis. Further results showed higher levels of serum PFN2 and exosomal PFN2 in patients, mice, and pigs with MI. In this study, we explored whether PFN2 and endothelial cell (EC)-derived exosomal PFN2 could increase angiogenesis and be beneficial for the treatment of MI. Serum PFN2, exosomes, and exosomal PFN2 were elevated in rats with MI. PFN2 and exosomes from PFN2-overexpressing ECs (OE-exo) enhanced EC proliferation, migration, and tube formation ability. OE-exo also significantly increased the vessel number in zebrafish and protected the ECs from inflammatory injury. Moreover, OE-exo-treated mice with MI showed improvement in motor ability, ejection fraction, left ventricular shortening fraction, and left ventricular mass, as well as increased vessel numbers in the MI location, and decreased infarction volume. Mechanistically, PI3K might be the upstream regulator of PFN2, while ERK might be the downstream regulator in the PI3K-PFN2-ERK axis. Taken together, our findings demonstrate that PFN2 and exosomal PFN2 promote EC proliferation, migration, and tube formation through the PI3K-PFN2-ERK axis. Exosomal PFN2 may be a valuable target in the repair of MI injury via angiogenesis.

Developmental disorders caused by cefixime in the otic vesicles of zebrafish embryos or larvae.

To explore the developmental toxicity of cefixime (CE) in the developmental disorder and toxicity mechanism of CE on otic vesicles, zebrafish embryos were used as an animal model. The results showed that CE increased mortality in a dose-dependent manner and decreased the hatching rate of zebrafish larva at 96 hpf. Interestingly, CE significantly reduced the area of the saccule and utricle, as well as the area of otic vesicles in zebrafish larvae (p < 0.001). Fibroblast growth factor 8a (Fgf8a) inhibitors and bone morphogenetic protein (BMP) inhibitors caused similar morphological changes. CE decreased the lateral hair cells of zebrafish larvae in a dose-dependent manner. Furthermore, CE caused the downregulation of cartilage and bone-related genes and Na+/K+-ATPase-related genes of zebrafish larvae at 72 hpf and 120 hpf according to RT-qPCR. A comparison with the control group revealed that 100 µg/mL CE also caused a decrease in Na+/K+-ATPase activity (p < 0.01). In addition, antibody staining verified that CE inhibited the expression of Na+/K+-ATPase in the otic vesicles and the nephridium of zebrafish larvae. The data obtained in this study suggested that CE has significant ototoxicity during embryonic development of zebrafish, which is closely related to Na+/K+-ATPase and the regulation of the Fgf8a/BMP signaling pathways. The effects and toxicity of CE on ear development in other animal models need to be further explored.

Alkoxy cyanoacrylate-based nanoparticles with stealth and brain-targeting properties.

Nanoparticles (NPs) with 'stealth' properties have been designed to decrease the phagocytosis of such particles by mononuclear phagocytes and to protect them from enzymatic degradation, thus improving circulation time and bioavailability after intravenous administration. Brain-targeting modifications endow NPs with the capacity to cross the blood-brain barrier, facilitating chemotherapy for brain diseases such as glioma. In this study, newly designed alkoxy cyanoacrylate (CA)-based NPs with stealth and brain-targeting properties were synthesised and evaluated. The monomers for NP core polymerisation were chemically modified to hydrophilic short alkoxy structure for stealth purposes and coated with polysorbate-80 for brain targeting. Two monomers (2-methoxyethyl CA and 2-(2-methoxyethyl)ethyl CA) were used to create NP2 and NP3, respectively. Both NPs were successfully loaded with anti-sense oligonucleotide (ASON) of transforming growth factor beta 2. Compared to traditional n-butyl CA-based ASON-NP1, ASON-NP3 was found to decrease phagocytosis by mononuclear macrophages (RAW264.7) and to increase cellular uptake by cancer cells. ASON-NP3 showed definite brain targeting and anti-cancer effects. This work provides a potential new strategy for preparing stealth NPs core, providing a new NP vehicle for clinical drug delivery that may be targeted to the brain and circulates in the blood for an extended period of time.

Chloroperoxidase-catalyzed oxidative degradation of sulfur mustard.

As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of sulfur mustard (HD), a persistent chemical warfare agent that has been widely disposed since World War II and continuously leaks into aquatic environments. Herein, we report the first systematic investigation of CPO-catalyzed degradation of HD and the potential application of CPO in destroying chemical weapons under mild conditions. The related Michaelis-Menten parameters (Km=0.17 mM, Vmax=0.06 mM s-1 (R2 =0.935), and kcat= 2717 s-1) indicated nearly a prominent enzymatic efficiency. Under optimal conditions, 80% of HD was transformed to bis(2-chloroethyl) sulfoxide as identified by mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Other metabolites were also generated during the decontamination process. A plausible oxidation mechanism was proposed based on the degradation products, NMR titration experiments, and molecular dynamics simulations. CPO also promoted the degradation of other chemical weapon agents, namely, Lewisite (L) and venomous agent X (VX), thereby exhibiting a broad substrate scope. The high potential of the developed system for the decontamination of aquatic environments was demonstrated by the successful hatching of zebrafish embryos after HD degradation and the survival of zebrafish (Danio rerio, AB strain) larvae after the degradation of Agent Yellow (L+HD).

Approximate Intrinsic Voxel Structure for Point Cloud Simplification.

A point cloud as an information-intensive 3D representation usually requires a large amount of transmission, storage and computing resources, which seriously hinder its usage in many emerging fields. In this paper, we propose a novel point cloud simplification method, Approximate Intrinsic Voxel Structure (AIVS), to meet the diverse demands in real-world application scenarios. The method includes point cloud pre-processing (denoising and down-sampling), AIVS-based realization for isotropic simplification and flexible simplification with intrinsic control of point distance. To demonstrate the effectiveness of the proposed AIVS-based method, we conducted extensive experiments by comparing it with several relevant point cloud simplification methods on three public datasets, including Stanford, SHREC, and RGB-D scene models. The experimental results indicate that AIVS has great advantages over peers in terms of moving least squares (MLS) surface approximation quality, curvature-sensitive sampling, sharp-feature keeping and processing speed. The source code of the proposed method is publicly available. (https://github.com/vvvwo/AIVS-project).

Substance P containing peptide gene delivery vectors for specifically transfecting glioma cells mediated by a neurokinin-1 receptor.

Gene therapy provides a promising treatment for glioblastoma multiforme, which mainly depends on two key aspects, crossing the blood brain barrier (BBB) effectively and transfecting target cells selectively. In this work, we reported a series of peptide-based vectors for transfecting glioma cells specifically consisting of several functional segments including a cell-penetrating peptide, targeting segment substance P (SP), an endosomal escape segment, a PEG linker and a stearyl moiety. The conformations and DNA-loading capacities of peptide vectors and the self-assembly behaviors of peptide/pGL3 complexes were characterized. The in vitro gene transfection was evaluated in U87, 293T-NK1R, and normal 293T cell lines. The transfection efficiency ratio of P-02 (SP-PEG4-K(C18)-(LLHH)3-R9) to Lipo2000 in the U87 cell line was about 36% higher than that in the 293T cell line. The neurokinin-1 receptor (NK1R) in U87 cells mediated the transfection process via interactions with the ligand SP in peptide vectors. The mechanism of NK1R mediated transfection was demonstrated by the use of gene-modified 293T cells expressing NK1R, as well as the gene transfection in the presence of free SP. Besides, P-02 could promote the pGL3 plasmids to cross the BBB model in vitro and achieved the EGFP gene transfection in the brain of zebrafish successfully. The designed peptide vectors, owing to their specific transfection capacity in glioma cells, provide a potential approach for glioblastoma multiforme gene therapy.

Particle hydrodynamic simulation of thrombus formation using velocity decay factor.

BACKGROUND AND OBJECTIVE: Thrombus simulation plays an important role in many specialist areas in the field of medicine such as surgical education and training, clinical diagnosis and prediction, treatment planning, etc. Although a considerable number of methods have been developed to simulate various kinds of fluid flows, it remains a non-trivial task to effectively simulate thrombus because of its unique physiological properties in contrast to other types of fluids. To tackle this issue, this study introduces a novel method to model the formation mechanism of thrombus and its interaction with blood flow. METHODS: The proposed method for thrombus formation simulation mainly consists of three steps. First, we formulate the formation of thrombus as a particle-based model and obtain the fibrin concentration of the particles with a discretized form of the convection-diffusion-reaction equation; then, we calculate the velocity decay factor using the obtained fibrin concentration. Finally, the formation of thrombus can be simulated by applying the velocity decay factor on particles. RESULTS: We carried out extensive experiments under different settings to verify the efficacy of the proposed method. The experimental results demonstrate that our method can yield more realistic simulation of thrombus and is superior to peer method in terms of computational efficiency, maintaining the stability of the dynamic particle motion, and preventing particle penetration at the boundary. CONCLUSION: The proposed method can simulate the formation mechanism of thrombus and the interaction between blood flow and thrombus both efficiently and effectively.

BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair.

PARP inhibitors have been approved for the therapy of cancers with homologous recombination (HR) deficiency based on the concept of "synthetic lethality". However, glioblastoma (GBM) patients have gained little benefit from PARP inhibitors due to a lack of BRCA mutations. Herein, we demonstrated that concurrent treatment with the PARP inhibitor rucaparib and the PI3K inhibitor BKM120 showed synergetic anticancer effects on GBM U251 and U87MG cells. Mechanistically, BKM120 decreased expression of HR molecules, including RAD51 and BRCA1/2, and reduced HR repair efficiency in GBM cells, therefore increasing levels of apoptosis induced by rucaparib. Furthermore, we discovered that the two compounds complemented each other in DNA damage response and drug accumulation. Notably, in the zebrafish U87MG-RFP orthotopic xenograft model, nude mouse U87MG subcutaneous xenograft model and U87MG-Luc orthotopic xenograft model, combination showed obviously increased antitumor efficacy compared to each monotherapy. Immunohistochemical analysis of tumor tissues indicated that the combination obviously reduced expression of HR repair molecules and increased the DNA damage biomarker γ-H2AX, consistent with the in vitro results. Collectively, our findings provide new insight into combined blockade of PI3K and PARP, which might represent a promising therapeutic approach for GBM.

Diversity and community structure of ectomycorrhizal fungi in Pinus thunbergii coastal forests bordering the Yellow Sea of China.

Ectomycorrhizas play a fundamental role in the function of forest ecosystems, being essential for plant nutrition absorption and soil quality. Many afforestation and reforestation programmes have begun to recover and maintain coastal forests in China, using pine species including Pinus thunbergii. We investigated the ectomycorrhizal colonization status of P. thunbergii in coastal pine forests of the Yellow Sea of China. We identified a total of 53 ectomycorrhizal fungal species in 74 soil samples collected from three sites and found that Thelephoraceae (10 spp.) and Russulaceae (8 spp.) were the most species-rich ectomycorrhizal fungal lineages. Russula sp. 1 was the most abundant species, accounting for 15.3% of the total ectomycorrhizal tips identified. Most of the remaining species were rare. At this small scale, host identity had no significant effect on the ectomycorrhizal fungal community composition (A = 0.036, P = 0.258), but sampling sites did (A = 0.135, P = 0.041). In addition, Na+ and K+ content and soil pH had significant effects on the ectomycorrhizal fungal community. The ectomycorrhizal fungal community associated with different host plants will become an important new direction for research, as ectomycorrhiza may have the potential to improve host capacity to establish in salt-stressed environments. This will provide a theoretical basis and technical support for saline soil reforestation and rehabilitation using pine species with compatible, native ectomycorrhizal fungi in Yellow Sea coastal areas.

Ilomastat contributes to the survival of mouse after irradiation via promoting the recovery of hematopoietic system.

Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), has drawn attentions for its function in alleviating radiation damage. However, the detailed mechanisms of Ilomastat's protection from animal model remain not fully clear. In this study, the C57BL/6 mice were pre-administrated with Ilomastat or vihicle for 2 h, and then total body of mice were exposed to 6 Gy of γ-rays. The protective effect of Ilomastat on the hematopoietic system in the irradiated mice were investigated. We found that pretreatment with Ilomastat significantly reduced the level of TGF-ß1 and TNF-α, and elevated the number of bone marrow (BM) mononuclear cells in the irradiated mice. Ilomastat pretreatment also increased the fraction of BM hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) at day 30 after irradiation, and protected the spleen of mouse from irradiation. These results suggest that Ilomastat promotes the recovery of hematopoietic injury in the irradiated mice, and thus contributes to the survival of mouse after irradiation.