Interplant communication increases aphid resistance and alters rhizospheric microbes in neighboring plants of aphid-infested cucumbers.

BACKGROUND: Aphis gossypii Glover is a prevalent phytophagous insect that inflicts significant damage on cucumber plants. Recent studies have provided insights into plant communication and signal transduction within conspecifics. However, understanding of the effect of these communication mechanisms on adjacent cucumbers and their resident aphids, especially in the context of an aphid infestation, is still in its early stages. RESULTS: Utilizing a partitioned root configuration, a tendency for aphids to gather on nearby cucumber leaves of non-infested plants was observed. Furthermore, neighboring plants near aphid-infested cucumber plants showed a reduction in aphid reproduction rates. Concurrently, these plants exhibited a significant increase in reactive oxygen species (ROS) levels, along with enhanced defensive and antioxidant enzymatic responses. Analysis of the microbial community in the rhizosphere showed significant differences in species composition among the samples. Among these, the bacterial families Microbacteriaceae and Rhizobiaceae, along with the fungal species Leucocoprinus ianthinus and Mortierella globalpina, exhibited increases in their relative abundance in cucumber seedlings located near aphid-infested plants. Significantly, this study unveiled robust correlations between dominant microbial phyla and physiological indicators, primarily associated with aphid resistance mechanisms in plants. CONCLUSION: The results show that aphid-infested cucumber plants trigger oxidative stress responses in adjacent seedlings through complex interplant communication mechanisms. In addition, these plants cause changes in the composition of the rhizospheric microbial community and the physiological activity of neighboring plants, consequently boosting their natural resistance to aphids. This study provides essential theoretical foundations to guide the development of sustainable strategies for managing cucumber aphids. © 2024 Society of Chemical Industry.

Powdery mildew-induced changes in phyllosphere microbial community dynamics of cucumber.

As an important habitat for microorganisms, the phyllosphere has a great impact on plant growth and health, and changes in phyllosphere microorganisms are closely related to the occurrence of leaf diseases. However, there remains a limited understanding regarding alterations to the microbial community in the phyllosphere resulting from pathogen infections. Here, we analyzed and compared the differences in phyllosphere microorganisms of powdery mildew cucumber from three disease severity levels (0% < L1 < 30%, 30% ≤ L2 < 50%, L3 ≥ 50%, the number represents the lesion coverage rate of powdery mildew on leaves). There were significant differences in α diversity and community structure of phyllosphere communities under different disease levels. Disease severity altered the community structure of phyllosphere microorganisms, Rosenbergiella, Rickettsia, and Cladosporium accounted for the largest proportion in the L1 disease grade, while Bacillus, Pantoea, Kocuria, and Podosphaera had the highest relative abundance in the L3 disease grade. The co-occurrence network analysis of the phyllosphere microbial community indicated that the phyllosphere bacterial community was most affected by the severity of disease. Our results suggested that with the development of cucumber powdery mildew, the symbiotic relationship between species was broken, and the entire bacterial community tended to compete.

Effectiveness of Immediate Video-Assisted Thoracoscopic Surgery for Empyema: A Multicentre, Retrospective Cohort Study.

BACKGROUND: Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. OBJECTIVE: This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. METHODS: This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. RESULTS: Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], -10.7 to 13.0%) and -0.08% (95% CI, -10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were -3.22 (95% CI, -6.19 to -0.25 days) and -5.04 days (95% CI, -8.19 to -1.90 days), respectively. CONCLUSIONS: Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted.

A Survey on the Integration of Blockchains and Databases.

The success of blockchain technology in cryptocurrencies reveals its potential in the data management field. Recently, there is a trend in the database community to integrate blockchains and traditional databases to obtain security, efficiency, and privacy from the two distinctive but related systems. In this survey, we discuss the use of blockchain technology in the data management field and focus on the fusion system of blockchains and databases. We first classify existing blockchain-related data management technologies by their locations on the blockchain-database spectrum. Based on the taxonomy, we discuss three types of fusion systems and analyze their design spaces and trade-offs. Then, by further investigating the typical systems and techniques of each type of fusion system and comparing the solutions, we provide insights of each fusion model. Finally, we outline the unsolved challenges and promising directions in this field and believe that fusion systems will take a more important role in data management tasks. We hope this survey can help both academia and industry to better understand the advantages and limitations of blockchain-related data management systems and develop fusion systems that meet various requirements in practice.

Prognostic Value of Computed Tomography in Empyema: A Multicenter Retrospective Cohort Study.

Rationale: Chest computed tomography is performed in patients with empyema for various reasons. However, its predictive ability for patient outcomes in empyema has not been evaluated. Objectives: To evaluate the predictive ability of computed tomography findings (pleural thickness, loculation, interlobar pleural effusion, lung abscess, and bronchopleural fistula) for 90-day mortality in empyema. Methods: This multicenter retrospective cohort study was conducted across six acute care hospitals in Japan. We included patients with confirmed empyema diagnoses who underwent chest computed tomography within 7 days of diagnosis. Imaging findings were defined as pleural thickness, loculation, interlobar pleural effusion, lung abscess, or bronchopleural fistula. One radiologist interpreted the computed tomography scans without patient information. The primary outcome was 90-day mortality. We calculated the differences in 90-day mortality between the presence and absence of each computed tomography finding using logistic regression with or without adjustment for early thoracic surgery. Results: A total of 711 patients were included in our study. Thoracic surgery was performed in 27% of patients, and the 90-day mortality rate was 10%. The differences (95% confidence intervals) in 90-day mortality without and with adjustment for early thoracic surgery were as follows: pleural thickness, 3.09% (-1.35% to 7.54%) and 2.70% (-1.80% to 7.20%); loculation, -4.01% (-8.61% to 0.60%) and -3.80% (-8.41% to 0.81%); interlobar pleural effusion, -9.15% (-14.58% to -3.72%) and -8.96% (-14.39% to -3.53%); lung abscess, 7.04% (-1.16% to 15.2%) and 6.86% (-1.34% to 15.05%); and bronchopleural fistula, 13.80% (7.66% to 19.94%) and 13.63% (7.50% to 19.77%), respectively. Conclusions: Although interlobar pleural effusion predicted lower 90-day mortality regardless of early thoracic surgery, the presence of bronchopleural fistula predicted higher 90-day mortality with empyema. Our results warrant further validation.

Identification of undescribed key impurities of homoharringtonine bulk drug.

The knowledge of impurities is an important issue and the base of quality control in modern drugs. To date, the quality control of the antitumor drug homoharringtonine (HHT) is still not sufficiently solved and needs to be improved. Six main impurities, drupacine, cephalotaxine, desmethylcephalotaxinone, harringtonine, 3-O-acetyl-cephalotaxine and 2'R,3'S-isoharringtonine were traced during HHT drug production by HPLC and LC-MS analyses. Additionally, we were able to isolate and identify three undescribed key trace impurities, neohomoharringtonines A-C. Their structures were established by 1D-, and 2D NMR experiments combined with mass spectrometry. An improved quality inspection ability of HHT was constructed.

Exogenously applied melatonin alleviates the damage in cucumber plants caused by Aphis goosypii through altering the insect behavior and inducing host plant resistance.

BACKGROUND: Aphis gossypii Glover is the main pest found in most cucumber-producing areas. Melatonin (MT) has been widely studied in protecting plants from environmental stresses and pathogens. However, little knowledge is available on the impact of MT on insect resistance. RESULTS: The fecundity of aphids on MT-treated cucumber leaves was inhibited. Interestingly, MT-treated plants were more attractive to aphids, which would prevent the large-scale transmission of viruses caused by the random movement of aphids. Meanwhile, MT caused varying degrees of change in enzyme activities related to methylesterified HG degradation, antioxidants, defense systems and membrane lipid peroxidation. Furthermore, transcriptomic analysis showed that MT induced 2360 differentially expressed genes (DEGs) compared with the control before aphid infection. These DEGs mainly were enriched in hormone signal transduction, MAPK signaling pathway, and plant-pathogen interaction, revealing that MT can help plants acquire inducible resistance and enhance plant immunity. Subsequently, 2397 DEGs were identified after aphid infection. Further analysis showed that MT-treated plants possessed stronger JA signal, reactive oxygen species stability, and the ability of flavonoid synthesis under aphid infection, while mediating plant growth and sucrose metabolism. CONCLUSION: In summary, MT as an environmentally friendly substance mitigated aphid damage to cucumbers by affecting the aphids themselves and enhancing plant resistance. This will facilitate exploring sustainable MT-based strategies for cucumber aphid control. © 2022 Society of Chemical Industry.

Relationship between physical activity and bone mineral density loss after gastrectomy in gastric cancer patients.

PURPOSE: The prevention of osteoporosis is a particularly relevant issue for gastric cancer survivors. We investigated the relationship between postoperative physical activity and the change of bone mineral density (BMD) in patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer were enrolled in this single-center prospective cohort study. Physical activity was evaluated using the International Physical Activity Questionnaire Short Form at postoperative month (POM) 6 and patients were classified into high, middle, and low physical activity groups accordingly. The primary outcome was the change in BMD from baseline at POM 12, which was expressed as a percentage of the young adult mean (YAM). The YAM of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. RESULTS: One hundred ten patients were enrolled in this study. The physical activity level at POM 6 was classified as high (n = 50; 45%), middle (n = 25; 23%), and low (n = 35; 32%). The mean decrease of YAM% was 5.1% in the lumbar spine and 4.2% in the femoral neck at POM 12. A multivariable-adjusted logistic regression model revealed that low physical activity at POM 6 was a significant risk factor for BMD loss at POM 12 (odds ratio, 3.76; 95% confidence interval, 1.48-9.55; p = 0.005). CONCLUSION: Low physical activity after gastrectomy is an independent risk factor for decreased BMD at POM 12. The introduction of exercise may prevent osteoporosis after the surgical treatment of gastric cancer.

Fusobacterium Nucleatum Is a Risk Factor for Metastatic Colorectal Cancer.

OBJECTIVE: Increasing evidence has indicated that there is a correlation between Fusobacterium nucleatum (F. nucleatum) abundance and poor prognosis of colorectal cancer (CRC). Furthermore, tumor metastasis plays a decisive role in the prognosis of CRC patients. Therefore, it was hypothesized that the abundance of F. nucleatum in CRC tissues affects the tumor metastasis. METHODS: In the present study, F. nucleatum DNA obtained from 141 resected CRC samples was quantified by qPCR to determine whether there were differences in F. nucleatum abundance between groups with and without CRC metastasis. RESULTS: The results revealed that F. nucleatum was more abundant in CRC patients with metastasis, and CRC tissues enriched with F. nucleatum had a higher risk of lymph node metastasis and distant metastasis. The receiver operating characteristic curve indicated that F. nucleatum in CRC tissues could be used as an indicator for CRC metastasis, to some extent. Furthermore, the in vitro experiments (electron microscopy, and migration and invasion trials) revealed that F. nucleatum was a highly invasive bacterial strain, and could significantly enhance the invasion and migration capacity of SW480 and SW620 cells. In addition, a meta-analysis comprehensively indicated a slight correlation between F. nucleatum abundance and advanced CRC stage (RR=1.17, 95% CI: 1.00-1.37, P=0.04, random effect). CONCLUSION: There is a correlation between F. nucleatum abundance and CRC metastasis, and F. nucleatum may serve as a metastasis biomarker for CRC patients.

Identification and establishment of type IV interferon and the characterization of interferon-υ including its class II cytokine receptors IFN-υR1 and IL-10R2.

Interferons (IFNs) are critical soluble factors in the immune system and are composed of three types, (I, II and III) that utilize different receptor complexes IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively. Here we identify IFN-υ from the genomic sequences of vertebrates. The members of class II cytokine receptors, IFN-υR1 and IL-10R2, are identified as the receptor complex of IFN-υ, and are associated with IFN-υ stimulated gene expression and antiviral activity in zebrafish (Danio rerio) and African clawed frog (Xenopus laevis). IFN-υ and IFN-υR1 are separately located at unique and highly conserved loci, being distinct from all other three-type IFNs. IFN-υ and IFN-υR1 are phylogenetically clustered with class II cytokines and class II cytokine receptors, respectively. Therefore, the finding of this IFN ligand-receptor system may be considered as a type IV IFN, in addition to the currently recognized three types of IFNs in vertebrates.

A phase II study of bevacizumab in non-squamous, non-small-cell lung cancer patients with malignant pleural effusion.

Aim: To investigate the efficacy, safety and optimal dosage of bevacizumab in non-squamous, non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE). Methods: 20 patients were enrolled and received intrapleural injection of bevacizumab (group A: 2.5 mg/kg d1, d8; group B: 5 mg/kg d1, d8; group C: 7.5 mg/kg d1, d8). Results: The objective response rate (ORR) of MPE was 50%. The median progression-free survival (PFS) of MPE was 7.0 months (95% CI 4.9-9.2). The ORR and PFS of MPE from group B were better than those of group A and group C. The most common adverse events (AEs) were hypertension (15%) and anemia (15%). Conclusion: Bevacizumab has certain efficacy in non-squamous NSCLC patients with MPE. Clinical Trial Registration: NCT02942043 (ClinicalTrials.gov).

[Clinical effect of cortical incision with rapid maxillary expansion to assist orthodontic-orthognathic treatment of skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the clinical effect of rapid maxillary expansion with cortical osteotomy combined with orthodontic- orthognathic treatment for skeletal Class Ⅲ malocclusion. METHODS: A total of 84 patients with skeletal Class Ⅲ malocclusion admitted to Jining Dental Hospital from March 2018 to May 2020 were randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with orthodontic-orthognathic treatment, while the experimental group was treated with orthodontic-orthognathic treatment with rapid maxillary arch expansion by cortical incision. The time of closing gap, alignment time, maxillary first molar and maxillary central incisor tooth movement distance in the sagittal direction were compared between the two groups. Before treatment and 4 weeks after treatment, the vertical distance from the end of the upper central incisor edge to the horizontal plane(U1I-HP), the distance from the apex of the upper central incisor to the coronal plane(U1I-CP), the vertical distance from the edge of the upper pressure groove to the coronal plane(Sd-CP), the vertical distance from the upper alveolar seat point to the horizontal plane(A-HP), the vertical distance from the point of the upper lip to the coronal plane(Ls-CP), and the vertical distance from the inferior point of nose to coronal plane(Sn-CP) were measured, and the relevant changes were calculated. During the treatment period, the complications of the two groups were compared. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: There was no significant difference in alignment time, A-HP change, Sn-CP change, maxillary first molar movement distance and maxillary central incisor movement distance between the two groups (P＞0.05). The closing interval in the experimental group was significantly shorter than that of the control group (P＜0.05). The changes of U1I-HP, U1I-CP, Sd-CP, and Ls-CP in the experimental group were significantly higher than those in the control group (P＜0.05). There was no significant difference in the incidence of complications between the two groups during treatment (P＞0.05). CONCLUSIONS: Rapid maxillary expansion of cortical incision assisted orthodontic-orthognathic treatment of skeletal Class Ⅲ malocclusion patients can shorten the closing gap time and improve the treatment effect, which has no obvious influence on the sagittal direction of the teeth.

Roles of exosomes in diagnosis and treatment of colorectal cancer.

Exosomes are extracellular vesicles that mediate intercellular communication. They contain different molecules, such as DNA, RNA, lipid, and protein, playing essential roles in the pathogenesis of colorectal cancer (CRC). Exosomes derived from CRC are implicated in tumorigenesis, chemotherapy resistance, and metastasis. Besides, they can enhance CRC progression by increasing tumor cell proliferation, reducing apoptosis mechanistically through altering particular essential regulatory genes, or controlling several signaling pathways. Therefore, exosomes derived from CRC are essential biomarkers and can be used in the diagnosis. Indeed, it is crucial to understand the role of exosomes in CRC, which is necessary to develop diagnostic and therapeutic strategies for early detection and treatment. In the present review, we discuss the roles of exosomes in the diagnosis and treatment of CRC.

A High Precision Modeling Technology of Material Surface Microtopography and Its Influence on Interface Mechanical Properties.

In order to accurately and effectively obtain the contact performance of the mating surface under the material surface topography characteristics, a numerical simulation method of rough surface based on the real topography characteristics and a multi-scale hierarchical algorithm of contact performance is studied in this paper. Firstly, the surface topography information of materials processed by different methods was obtained and characterized by a measuring equipment; Secondly, a non-Gaussian model considering kurtosis and skewness was established by Johnson transform based on Gaussian theory, and a rough surface digital simulation method based on real surface topography was formed; Thirdly, a multi-scale hierarchical algorithm is given to calculate the contact performance of different mating surfaces; Finally, taking the aeroengine rotor as the object, the non-Gaussian simulation method was used to simulate the mating surfaces with different topographies, and the multi-scale hierarchical algorithm was used to calculate the contact performance of different mating surfaces. Analysis results showed that the normal contact stiffness and elastic-plastic contact area between the mating surfaces of assembly 1 and assembly 2 are quite different, which further verifies the feasibility of the method. The contents of this paper allow to perform the fast and effective calculation of the mechanical properties of the mating surface, and provide a certain analysis basis for improving the surface microtopography characteristics of materials and the product performance.

Cloning and functional characterization of IRAK1 from rainbow trout (Oncorhynchus mykiss).

As a key molecule in innate immune signalling pathway, interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) mediates downstream signalling cascades in immune response. In the present study, an IRAK1 orthologue was characterized from rainbow trout (Oncorhynchus mykiss), with a 2115 bp open reading frame (ORF), encoding a protein of 704 amino acids (aa). Multiple alignments showed that IRAK1 contains highly conserved features among different species, with a conservative N-terminal death domain (DD) and a C-terminal conserved serine/threonine protein kinase (STKc) domain. Expression analysis indicated that IRAK1 was widely expressed in examined organs/tissues, with the highest level observed in muscle and lowest in stomach. In RTG-2 cell line, the induced expression of IRAK1 was observed following the stimulation by the fish bacterial pathogen Flavobacterium columnare. Luciferase activity assays revealed that IRAK1 induced significantly the activity of NF-κB in Human embryonic kidney 293T (HEK293T) cell line; but after co-transfected with rainbow trout IL-1 receptor-associated kinase 4 (IRAK4), the induction was significantly down-regulated when compared with the expression of IRAK1 alone. Co-immunoprecipitation (Co-IP) assays indicated that IRAK1 was associated with rainbow trout myeloid differentiation factor 88 (MyD88), IRAK4 and TNF receptor associated factor 6 (TRAF6) in transfected HEK293T cells, and may form a complex with MyD88, IRAK4 and TRAF6 during the signalling pathway.

In Primitive Zebrafish, MHC Class II Expression Is Regulated by IFN-γ, IRF1, and Two Forms of CIITA.

Mammalian CIITA isoforms are tightly regulated by independent promoters. These promotors are induced by IFN-γ through JAK-STAT signaling pathway. The induction of CIITA controls the expression of MHC class II (MHCII) and Ag presentation to the adaptive immune system. In the current study, to our knowledge, we first identified two independent promoters, p1 and p2, in the zebrafish (Danio rerio) that control the expression of the two variants of CIITA, CIITA variant 1 (CIITAv1), and CIITA variant 2 (CIITAv2), respectively. Moreover, although IRF1 in an IFN-γ signaling pathway induced CIITAv2, which has two ISRE motifs in its promoter, CIITAv1 expression was not induced by this signal. Further, the transcription of MHCII DAB was controlled by IRF1 via two distinct mechanisms: 1) the transcription of MHCII DAB was controlled by IRF1 indirectly through the two ISREs in p2; and 2) directly via the ISRE in MHCII DAB promoter. We also found that IRF1 associated with CIITAv1 and CIITAv2 via protein-protein interactions to synergistically drive the transcription of MHCII DAB. The IFN-γ-IRF1-CIITA-MHCII signaling cascade was functional in early life stages of CIITA-/- and IRF1-/- zebrafish. Our findings imply that the immune system develops early in fishes and that the IFN-γ signaling cascade-induced CIITA and MHCII DAB is conserved in teleost fishes and mammals.

Unique Composition of Intronless and Intron-Containing Type I IFNs in the Tibetan Frog Nanorana parkeri Provides New Evidence To Support Independent Retroposition Hypothesis for Type I IFN Genes in Amphibians.

In vertebrates, intron-containing and intronless type I IFN genes have recently been reported in amphibian model species Xenopus tropicalis and X. laevis. However, whether intronless type I IFNs in amphibians are the ancestral genes of type I IFNs in amniotes or just represent the independent divergence in amphibians is unknown or even uninvestigated. In this study, both intron-containing and intronless type I IFN genes, as well as their receptor genes, were identified in the Tibetan frog Nanorana parkeri The evidence obtained from homology, synteny, phylogeny, and divergence time showed that intronless type I IFN genes in N. parkeri and in Xenopus might have arisen from two independent retroposition events occurred in these two lineages, and the retrotransposition causing the generation of intronless type I IFN genes in amniotes is another independent event beyond the two in amphibians. It can then be proposed that intronless type I IFNs in N. parkeri and Xenopus may not be the ancestral genes of intronless type I IFNs in amniotes but may just represent two independent bifurcations in the amphibian lineage. Furthermore, both intronless and intron-containing type I IFNs in N. parkeri showed strong ability in inducing the expression of IFN-stimulated genes and the strong antiviral activity against frog virus 3. The present study thus provides the evolutionary evidence to support the independent retroposition hypothesis for the occurrence of intronless type I IFN genes in amphibians and contributes to a functional understanding of type I IFNs in this group of vertebrates.

Improved sulfide mitigation in sewers through on-line control of ferrous salt dosing.

Water utilities worldwide spend annually billions of dollars to control sulfide-induced corrosion in sewers. Iron salts chemically oxidize and/or precipitate dissolved sulfide in sewage and are especially used in medium- and large-size sewers. Iron salt dosing rates are defined ad hoc, ignoring variation in sewage flows and sulfide levels. This often results in iron overdosing or poor sulfide control. Online dosing control can adjust the chemical dosing rates to current (and future) state of the sewer system, allowing high-precision, stable and cost-effective sulfide control. In this paper, we report a novel and robust online control strategy for the dosing of ferrous salt in sewers. The control considers the fluctuation of sewage flow, pH, sulfide levels and also the perturbation from rainfall. Sulfide production in the pipe is predicted using auto-regressive models (AR) based on current flow measurements, which in turn can be used to determine the dose of ferrous salt required for cost-effective sulfide control. Following comprehensive model-based assesment, the control was successfully validated and its effectiveness demonstrated in a 3-week field trial. The online control algorithm controlled sulfide below the target level (0.5 mg S/L) while reducing chemical dosing up to 30%.

Protective effects of folic acid on PM2.5-induced cardiac developmental toxicity in zebrafish embryos by targeting AhR and Wnt/ß-catenin signal pathways.

Our previous observations indicated that extractable organic matter (EOM) from PM2.5 induced malformations in the heart of zebrafish embryos by activating AhR and inhibiting canonical Wnt/ß-catenin signal pathway. As a nutritional factor, folic acid (FA) is reported to prevent cardiac defects during embryo development. Hence, we hypothesize that FA may prevent PM2.5-induced heart defects by interfering with AhR and Wnt/ß-catenin signaling pathways. Our results showed that FA supplementation alleviated the EOM-induced heart defects in zebrafish embryos, and both AhR inhibitor CH223191 and Wnt activator CHIR99021 enhanced the protective efficiency of FA. Furthermore, FA supplementation attenuated the EOM-induced upregulation of AhR and its target genes including Cyp1a1, Cyp1b1, Ahrra, and Ahrrb. EROD assay confirmed that the EOM agonized Cyp1a1 activity was diminished by FA. The EOM-induced downregulation of ß-catenin and its target genes including Nkx2.5, Axin2, Sox9b, and Cox2b were recovered or even overexpressed in embryos exposed to EOM plus FA. In conclusion, our study suggested that FA supplementation protected against PM2.5 cardiac development toxicity by targeting AhR and Wnt/ß-catenin signal pathways.

Autophagy associated cytotoxicity and cellular uptake mechanisms of bismuth nanoparticles in human kidney cells.

Bismuth compounds have been used for treatment of bacterial infection, and recently bismuth nanoparticles (BiNP) were synthesized for imaging and diagnostic purpose, while safety concern of bismuth cannot be ignored. Here, we prepared ultrasmall BiNP and showed an enhanced tumor imaging, but BiNP revealed a differentiated cytotoxicity in human embryonic kidney 293 cells (HEK293) compared to other cell types. For the first time, we found that BiNP can induce autophagy, shown as the increase of monodansylcadaverine fluorescence staining and the amount of LC3II that can be inhibited by 3-MA. BiNP were capable of entering cells in a dose and time dependent manner by fluorescence and element detection methods BiNP were found to be localized in the cytoplasm observed by transmission electron microscopy and intracellular bismuth element confirmed by energy dispersive X-ray analysis. Using endocytic inhibitors, BiNP were found to require ATP and endosomal trafficking pathways for their cellular uptake. Internalized BiNP did not co-localize with EEA1, but co-localized with Lysotracker/LAMP1/LAMP2 at late time points, indicating BiNP may be retained in the non-early endosomal vacuoles and late endosomes. With our novel finding of bismuth induced autophagy and endocytic mechanisms, potential approaches may be applied to reduce the toxicity by bismuth.