Search

Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA fluorescence in situ hybridization (FISH) and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein (RBP) commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumour suppressor and may be a novel biomarker and therapeutic target in CRC.

The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE2 was required for the proper control of inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) hyperactivation and hence the endoplasmic reticulum (ER) homeostasis in IgM-producing SLPCs. Disruption of the PGE2-EP4-AKT signaling pathway resulted in IRE1α-induced activation of JNK, leading to accelerated death of SLPCs. Consequently, Ptger4-deficient mice (C57BL/6) exhibited a markedly impaired IgM response to T-independent Ags and increased susceptibility to Streptococcus pneumoniae infection. This study reveals a highly selective impact of the PGE2-EP4 signal on the humoral immunity and provides a link between ER stress response and the life span of SLPCs.

Sup. Figure 4

Supplemental Method and Materials; Supplemental Figure Legends; Goes with the Longer version of the paper

High-risk neuroblastoma remains therapeutically challenging to treat, and the mechanisms promoting disease aggression are poorly understood. Here, we show that elevated expression of dihydrolipoamide S-succinyltransferase (DLST) predicts poor treatment outcome and aggressive disease in patients with neuroblastoma. DLST is an E2 component of the α-ketoglutarate (αKG) dehydrogenase complex, which governs the entry of glutamine into the tricarboxylic acid cycle (TCA) for oxidative decarboxylation. During this irreversible step, αKG is converted into succinyl-CoA, producing NADH for oxidative phosphorylation (OXPHOS). Utilizing a zebrafish model of MYCN-driven neuroblastoma, we demonstrate that even modest increases in DLST expression promote tumor aggression, while monoallelic dlst loss impedes disease initiation and progression. DLST depletion in human MYCN-amplified neuroblastoma cells minimally affected glutamine anaplerosis and did not alter TCA cycle metabolites other than αKG. However, DLST loss significantly suppressed NADH production and impaired OXPHOS, leading to growth arrest and apoptosis of neuroblastoma cells. In addition, multiple inhibitors targeting the electron transport chain, including the potent IACS-010759 that is currently in clinical testing for other cancers, efficiently reduced neuroblastoma proliferation in vitro. IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma. Together, these results demonstrate that DLST promotes neuroblastoma aggression and unveils OXPHOS as an essential contributor to high-risk neuroblastoma.Significance:These findings demonstrate a novel role for DLST in neuroblastoma aggression and identify the OXPHOS inhibitor IACS-010759 as a potential therapeutic strategy for this deadly disease.

Knowledge distance is used to measure the difference between granular spaces, which is an uncertainty measure with strong distinguishing ability in a rough set. However, the current knowledge distance failed to take the relative difference between granular spaces into account under the given perspective of uncertain concepts. To solve this problem, this paper studies the relative knowledge distance of intuitionistic fuzzy concept (IFC). Firstly, a micro-knowledge distance (md) based on information entropy is proposed to measure the difference between intuitionistic fuzzy information granules. Then, based on md, a macro-knowledge distance (MD) with strong distinguishing ability is further constructed, and it is revealed the rule that MD is monotonic with the granularity being finer in multi-granularity spaces. Furthermore, the relative MD is further proposed to analyze the relative differences between different granular spaces from multiple perspectives. Finally, the effectiveness of relative MD is verified by relevant experiments. According to these experiments, the relative MD has successfully measured the differences in granular space from multiple perspectives. Compared with other attribute reduction algorithms, the number of subsets after reduction by our algorithm is in the middle, and the mean-square error value is appropriate.

Solid tumors, especially those with aberrant MYCN activation, harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance1,2, yet the underlying mechanisms are elusive and effective strategies to tackle this challenge are lacking. Here we demonstrated the crucial role of T regulatory (Treg) cells in MYCN-mediated immune repression and tumor aggression using high-risk neuroblastoma (NB) as a model system. Human MYCN-activated NB attracts CD4+ Treg cells, which are also found enriched in MYCN-high primary patient samples. Zebrafish MYCN-overexpressing neural crests recruit Cd4+ cells before tumor formation and induce an immunosuppressive microenvironment, thereby promoting tumor onset and progression. Strikingly, disruption of Treg cells through depletion of forkhead box protein 3a restores anti-tumor immunity and impairs NB development. Together, our studies establish Treg cells as the key driver of MYCN-mediated immunosuppression and tumor aggressiveness, providing mechanistic insights and therapeutic implications.

High-risk neuroblastoma remains therapeutically challenging to treat, and the mechanisms promoting disease aggression are poorly understood. Here, we show that elevated expression of dihydrolipoamide S-succinyltransferase (DLST) predicts poor treatment outcome and aggressive disease in patients with neuroblastoma. DLST is an E2 component of the α-ketoglutarate (αKG) dehydrogenase complex, which governs the entry of glutamine into the tricarboxylic acid cycle (TCA) for oxidative decarboxylation. During this irreversible step, αKG is converted into succinyl-CoA, producing NADH for oxidative phosphorylation (OXPHOS). Utilizing a zebrafish model of MYCN-driven neuroblastoma, we demonstrate that even modest increases in DLST expression promote tumor aggression, while monoallelic dlst loss impedes disease initiation and progression. DLST depletion in human MYCN-amplified neuroblastoma cells minimally affected glutamine anaplerosis and did not alter TCA cycle metabolites other than αKG. However, DLST loss significantly suppressed NADH production and impaired OXPHOS, leading to growth arrest and apoptosis of neuroblastoma cells. In addition, multiple inhibitors targeting the electron transport chain, including the potent IACS-010759 that is currently in clinical testing for other cancers, efficiently reduced neuroblastoma proliferation in vitro. IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma. Together, these results demonstrate that DLST promotes neuroblastoma aggression and unveils OXPHOS as an essential contributor to high-risk neuroblastoma. Significance: These findings demonstrate a novel role for DLST in neuroblastoma aggression and identify the OXPHOS inhibitor IACS-010759 as a potential therapeutic strategy for this deadly disease.

The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE

LED array microscopy is an emerging platform for computational imaging . Existing LED array systems often exploit transmission imaging geometries of standard brightfield microscopes that leave the rich backscattered field undetected. Here, we develop an LED array reflectance microscope capturing the sample’s backscattered signal. In particular, we demonstrate multimodal brightfield, darkfield, and differential phase contrast imaging on fixed and living biological specimens including Caenorhabditis elegans (C. elegans), zebrafish embryos, and live cell cultures. Video-rate multimodal imaging records real-time features of freely-moving C. elegans and the fast beating heart of zebrafish embryo. Our new reflectance mode is a valuable addition to the LED array microscopic toolbox.

Most reports on oblique plane microscopy (OPM) have a limited microscopic field of view (FOV), typically within 1x1 mm2. We implemented an optical design of mesoscopic scanning oblique plane microscopy (OPM) to allow using low numerical aperture (NA) objective lens. The angle of the intermediate image before the remote focusing system was increased by a demagnification under Scheimpflug condition such that the light collecting efficiency in the remote focusing system was significantly improved. We demonstrate a mesoscopic FOV up to ~6× 5×0.6 mm3 volumetric imaging, the largest reported FOV by OPM so far.

BACKGROUND: Conventional light sheet fluorescence microscopy (LSFM), or selective plane illumination microscopy (SPIM), enables high-resolution 3D imaging over a large volume by using two orthogonally aligned objective lenses to decouple excitation and emission. The recent development of oblique plane microscopy (OPM) simplifies LSFM design with only one single objective lens, by using off-axis excitation and remote focusing. However, most reports on OPM have a limited microscopic field of view (FOV), typically within 1×1 mm(2). Our goal is to overcome the limitation with a new variant of OPM to achieve a mesoscopic FOV. METHODS: We implemented an optical design of mesoscopic scanning OPM to allow the use of low numerical aperture (NA) objective lenses. The angle of the intermediate image before the remote focusing system was increased by a demagnification under Scheimpflug condition such that the light collecting efficiency in the remote focusing system was significantly improved. A telescope composed of cylindrical lenses was used to correct the distorted image caused by the demagnification design. We characterized the 3D resolutions and imaging volume by imaging fluorescent microspheres, and demonstrated the volumetric imaging on intact whole zebrafish larvae, mouse cortex, and multiple Caenorhabditis elegans (C. elegans). RESULTS: We demonstrate a mesoscopic FOV up to ~6×5×0.6 mm(3) volumetric imaging, the largest reported FOV by OPM so far. The angle of the intermediate image plane is independent of the magnification as long as the size of the pupil aperture of the objectives is the same. As a result, the system is highly versatile, allowing simple switching between different objective lenses with low (10×, NA 0.3) and median NA (20×, NA 0.5). Detailed microvasculature in zebrafish larvae, mouse cortex, and neurons in C. elegans are clearly visualized in 3D. CONCLUSIONS: The proposed mesoscopic scanning OPM allows using low NA objectives such that centimeter-level FOV volumetric imaging can be achieved. With the extended FOV, simple sample mounting protocol, and the versatility of changeable FOVs/resolutions, our system will be ready for the varieties of applications requiring in vivo volumetric imaging over large length scales.

In this paper, the finite element model of oil-immersed amorphous alloy transformer was established. The eddy current field of amorphous debris and its surrounding structures were analyzed theoretically. The oil-immersed amorphous alloy transformers and the oil-immersed amorphous alloy transformers containing amorphous alloy core debris were simulated and analyzed respectively, and the influence of amorphous debris on the eddy current field distribution of amorphous alloy transformers was obtained.

We implemented a novel optical design to allow using low numerical aperture objective lens in OPM and achieved centimeter-scale volumetric imaging. It has great potential in large specimen imaging such as whole-brain imaging of mice.

Conventional light sheet fluorescence microscopy (LSFM), or selective plane illumination microscopy (SPIM), enables high resolution 3D imaging over a large volume by using two orthogonally aligned objective lenses to decouple excitation and emission. The recent development of oblique plane microscopy (OPM) simplifies LSFM design with only one single objective lens, by using off-axis excitation and remote focusing. However, most reports on OPM has a limited microscopic field of view (FOV), typically within 1×1 mm2. Our goal is to overcome the limitation with a new variant of OPM to achieve mesoscopic FOV. We implemented an optical design of mesoscopic scanning OPM to allow using low numerical aperture (NA) objective lens. The angle of the intermediate image before the remote focusing system was increased by a demagnification under Scheimpflug condition such that the light collecting efficiency in the remote focusing system was significantly improved. We characterized the 3D resolutions and FOV by imaging fluorescence microspheres, and demonstrated the volumetric imaging on intact whole zebrafish larvae, mouse cortex, and multipleCaenorhabditis elegans (C.elegans). We demonstrate a mesoscopic FOV up to ~6× 5×0.6 mm3volumetric imaging, the largest reported FOV by OPM so far. The angle of the intermediate image plane is independent of the magnification. As a result, the system is highly versatile, allowing simple switching between different objective lenses with low (10x, NA 0.3) and median NA (20x, NA 0.5). Detailed microvasculature in zebrafish larvae, mouse cortex, and neurons inC. elegansare clearly visualized in 3D. The proposed mesoscopic scanning OPM allows using low NA objective such that centimeter-level FOV volumetric imaging can be achieved. With the extended FOV, simple sample mounting protocol, and the versatility of changeable FOVs/resolutions, our system will be ready for the varieties of applications requiringin vivovolumetric imaging over large length scales.

Developing nanoparticles capable of detecting, targeting, and destroying cancer cells is of great interest in the field of nanomedicine. In vivo animal models are required for bridging the nanotechnology to its biomedical application. The mouse represents the traditional animal model for preclinical testing; however, mice are relatively expensive and have long experimental cycles due to limited progeny from each mother. The zebrafish has emerged as a powerful model system for developmental and biomedical research, including cancer research. In particular, due to its optical transparency and rapid development, zebrafish embryos are well suited for real-time in vivo monitoring of the behavior of cancer cells and their interactions with their microenvironment. Here, we developed a method that sequentially introduces human cancer cells and functionalized nanoparticles in transparent Casper zebrafish embryos, and monitors in vivo recognition and targeting of these cancer cells by nanoparticles in real-time. Our optimized protocol shows that fluorescently labeled nanoparticles, which are functionalized with folate groups, can specifically recognize and target metastatic human cervical epithelial cancer cells that are labeled with a different fluorochrome. The recognition and targeting process can occur as early as 30 min post-injection of the nanoparticles tested. We also demonstrate that the whole experiment only requires the breeding of a few pairs of adult fish and takes less than four days to complete. Moreover, zebrafish embryos lack a functional adaptive immune system, allowing the engraftment of a wide range of human cancer cells. Hence, the utility of the protocol described here enables the testing of nanoparticles on various types of human cancer cells, facilitating the selection of optimal nanoparticles in each specific cancer context for future testing in mammals and the clinic.

Dual-modal fluorescence-magnetic resonance imaging (MRI) techniques have gained great interest in biomedical research and clinical practice, since they integrate the advantages of both imaging techniques and provide a useful approach to simultaneously investigate both molecular and anatomical information at the same biological structures. Herein, we report the construction of a dual-modal time-gated luminescence (TGL)/MRI nanoprobe, BHHBB-Eu3+@MnO2, for glutathione (GSH) by anchoring luminescent β-diketone-Eu3+ complexes on layered MnO2 nanosheets. The fabricated nanoprobe exhibited very week luminescence and MR signals since the luminescence of the Eu3+ complex was quenched by MnO2 nanosheets and Mn atoms were isolated from water. Upon exposure to GSH, the MnO2 nanosheets were rapidly and selectively reduced to Mn2+ ions, resulting in remarkable enhancements of TGL and MR signals simultaneously. The combination of TGL and MR detection modes enables the nanoprobe to be used for detecting GSH in a wide concentration range (1-1000 μM) and imaging GSH at different resolutions and depths ranging from the subcellular level to the whole body. Furthermore, the as-prepared nanoprobe exhibited a low cytotoxicity and good biocompatibility, rapid response rate, long-lived luminescence, and high sensitivity and selectivity for responding to GSH. These features allowed it to be successfully used for the TGL detection of GSH in human sera, TGL imaging of GSH in living cells and zebrafish, as well as dual-modal TGL/MR imaging of GSH in tumor-bearing mice. All of these results highlighted the applicability and advantages of the nanoprobe for detecting GSH in vitro and in vivo.

New ultrabright fluorescent silica nanoparticles capable of the fast targeting of epithelial tumors in vivo are presented. The as-synthesized folate-functionalized ultrabright particles of 30-40 nm are 230 times brighter than quantum dots (QD450) and 50% brighter than the polymer dots with similar spectra (excitation 365 nm and emission 486 nm). To decrease non-specific targeting, particles are coated with polyethylene glycol (PEG). We demonstrate the in vivo targeting of xenographic human cervical epithelial tumors (HeLa cells) using zebrafish as a model system. The particles target tumors (and probably even individual HeLa cells) as small as 10-20 microns within 20-30 minutes after blood injection. To demonstrate the advantages of ultrabrightness, we repeated the experiments with similar but 200× less bright particles. Compared to those, ultrabright particles showed ∼3× faster tumor detection and ∼2× higher relative fluorescent contrast of tumors/cancer cells.

LED array microscopy is an emerging platform for computational imaging with significant utility for biological imaging. Existing LED array systems often exploit transmission imaging geometries of standard brightfield microscopes that leave the rich backscattered field undetected. This backscattered signal contains high-resolution sample information with superb sensitivity to subtle structural features that make it ideal for biological sensing and detection. Here, we develop an LED array reflectance microscope capturing the sample’s backscattered signal. In particular, we demonstrate multimodal brightfield, darkfield, and differential phase contrast imaging on fixed and living biological specimens including Caenorhabditis elegans (C. elegans), zebrafish embryos, and live cell cultures. Video-rate multimodal imaging at 20 Hz records real time features of freely moving C. elegans and the fast beating heart of zebrafish embryos. Our new reflectance mode is a valuable addition to the LED array microscopic toolbox.

B7-H3 (CD276) is broadly overexpressed by multiple human cancers. It plays a vital role in tumor progression and has been accepted as one of the inhibitory B7 family checkpoint molecules. To identify the functions and underlying mechanisms of B7-H3 in multiple myeloma, we analyzed B7-H3 expression in myeloma patients and used siRNAs and overexpression plasmid of B7-H3 to investigate its roles and downstream signaling molecules in myeloma cell lines. The results showed that surface expression of B7-H3 was upregulated in myeloma samples and cell lines. Lower expression of B7-H3 in myeloma cells was associated with better progression-free survival. Myeloma cell survival, drug resistance, and tumor growth could be promoted by B7-H3. The molecular basis for these functional roles of B7-H3 involved the activation of JAK2/STAT3 via redox-mediated oxidation and activation of Src. We further identified a STAT3-promoting signaling pathway by which oxidant-mediated Src phosphorylation led to secondary activation of the E3 ubiquitin ligase c-Cbl. Activated c-Cbl subsequently caused specific proteasomal degradation of SOCS3, a negative regulator of JAK2/STAT3. These data indicate B7-H3's important role in the activation of ROS/Src/c-Cbl pathway in multiple myeloma which integrates redox regulation and sustained STAT3 activation at the level of degradation of STAT3 suppressor.

Bimodal fluorescence–magnetic resonance imaging (MRI) technique has shown great utilities in bioassays because it combines the advantages of both optical imaging and MRI to provide more sufficient information over any modality alone. In this work, on the basis of a MnO2 nanosheet–Ru(II) complex nanoarchitecture, a bimodal phosphorescence–MRI nanoprobe for glutathione (GSH) has been constructed. The nanoprobe, Ru(BPY)3@MnO2, was constructed by integrating MnO2 nanosheets with a phosphorescent Ru(II) complex [Ru(BPY)3](PF6)2 (BPY = 2,2′-bipyridine), which resulted in complete phosphorescence quenching of the Ru(II) complex, accompanied by very low longitudinal and transverse relaxivity. Upon exposure to GSH, the reduction of MnO2 nanosheets by GSH triggers a recovery of phosphorescence and simultaneously produces a number of Mn2+ ions, a perfect MRI contrast agent. The as-prepared nanoprobe showed good water dispersion and biocompatibility and a rapid, selective, and sensitive response toward GSH in the pho...

Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of α5β1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-β1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis.

Since the concept of sustainable development and energy-saving emission reduction enjoying popular support, energy-saving amorphous alloy transformer is widely promoted, and the problem of oil-immersed amorphous debris is further highlighted. This paper simulated the magnetic field of the oil-immersed amorphous alloy transformer containing amorphous debris to determine the effect of the amorphous debris on the performance of magnetic field. This paper draws the conclusions that the magnetic field intensity internal the amorphous debris is almost zero but not equal to zero, the magnetic induction intensity inside the amorphous alloy core debris being much larger than that inside the dielectric oil and the maximum value can be increased by 7 times.

In order to improve the efficiency of the power system, in recent years, China has been actively promoting the use of energy-saving amorphous alloy transformer. As the oil- immersed amorphous alloy distribution transformer is the fully sealed and maintenance-free transformer, iron core debris of amorphous alloy once produced will accumulate and this will result in great harm on the insulation and stability of the amorphous alloy transformer. This article uses the finite element analysis for the study of distribution characteristics of amorphous alloy iron core debris and the impact of electromagnetic performance of the oil-immersed amorphous alloy transformer. The electric field internal the amorphous alloy core debris is zero, and the electric field around it becomes three times larger. Amorphous debris cause uneven distribution of electric field in the oil, which will easily lead to insulating oil breakdown.

A homogeneous time-resolved fluoroimmunoassay method for rapid and sensitive detection of microcystin-LR (MC-LR) in water samples was developed based on the interaction between water-soluble WS

Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells. The activation of FAK/Syk/Akt/mTOR and STAT3 pathways contributes to Reelin-induced cancer cell growth and metabolic reprogramming. Our findings further reveal that activated Akt and STAT3 pathways induce the upregulation of HIF1α and its downstream targets (LDHA and PDK1), leading to increased glycolysis in myeloma cells. Together, our results demonstrate the critical contributions of Reelin to myeloma growth and metabolism. It presents an opportunity for myeloma therapeutic intervention by inhibiting Reelin and its signaling pathways.

Neuroblastoma is one of the most common pediatric solid tumors that derives from sympathetic nerve ganglia. Children with MYCN-amplified tumors have a very poor prognosis. MYCN amplification is associated with impaired inflammatory profiles and reduced numbers of tumor-infiltrating cytotoxic T-lymphocytes (CTL). However, it remains elusive how MYCN blocks the trafficking of T-cells to tumors and protects tumor cells escaping from CTL-mediated cytotoxicity. Elucidation of the mechanism by which MYCN suppresses immune surveillance in the neuroblastoma microenvironment could lead to improved treatment outcomes through immunotherapy. We generated a zebrafish model, in which lymphocytes and tumor cells were differentially labeled with red and green fluorochromes. We monitored these fish for trafficking of mCherry-labeled lymphocytes to EGFP-positive MYCN-overexpressing premalignant neural crests on 5, 14, and 21 days post fertilization (dpf). We found that MYCN-overexpressing premalignant neural crests could attract lymphocytes in living fish. To observe lymphocyte infiltration in different stages of tumor development, we will perform cryosection and quantify lymphocyte infiltration in each stage of tumor development. While this zebrafish model is useful in studying the behaviors of immune cells at different stages of tumor development, it can be further exploited to understand how MYCN regulates immune escape and how immune cell infiltration can be enhanced in MYCN-amplified neuroblastoma to suppress tumor onset and progression. This knowledge is critical for development of more efficient immunotherapies in treating children with neuroblastoma. Citation Format: Xiaodan Qin, Andrew Lam, Hui Feng. Exploit the zebrafish to study lymphocyte infiltration in MYCN-amplified neuroblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A213.

The Oligocene to Lower Miocene of Site 1148, Ocean Drilling Program (ODP) Leg 184 was investigated palynologically to explore environmental change within the newly formed rifted South China Sea. The basin first developed 32.8 Ma ago during an initial rifting phase, and before sea floor spreading. Palynomorph Assemblage A contains abundant coastal and neritic dinoflagellate cysts (for example, Lingulodinium and Spiniferites) and a small number of oceanic Impagidinium species, together with abundant pollen, spores, and terrigenous phytoplankton. Offshore transportation induced by basement subsidence played an important role in the makeup of this assemblage. Paleoenvironments during the earliest Oligocene include shallow shelf, shelf/slope boundary, and mid slope regimes. The latter is indicated by the intermittent and rare occurrences of Impagidinium. Later, in the Early Oligocene to earliest Late Oligocene, there was a deepening of the basin with increasing influence of lower slope environments, i...

A homogeneous time-resolved fluoroimmunoassay method for rapid and sensitive detection of microcystin-LR (MC-LR) in water samples was developed based on the interaction between water-soluble WS2 nanosheets and the conjugate of MC-LR with a luminescent Eu3+ complex BHHBCB-Eu3+ (BHHBCB: 1,2-bis[4'-(1″,1″,1″,2″,2″,3″,3″-heptafluoro-4″,6″-hexanedion-6″-yl)- benzyl]-4-chlorosulfobenzene). The large lateral dimensions and high surface areas of two-dimensional layered WS2 nanosheets enable easy adsorption of the MC-LR-BHHBCB-Eu3+ conjugate, that lead to efficient quenching of the luminescence of Eu3+ complex via energy transfer or electron transfer process. However, the addition of monoclonal anti-MC-LR antibody can induce the formation of MC-LR-BHHBCB-Eu3+/antibody immune complex, which prevents the interaction between WS2 nanosheets and MC-LR-BHHBCB-Eu3+ to result in the restoration of Eu3+ luminescence. This signal transduction mechanism made it possible for analysis of the target MC-LR in a homogeneous system. The present method has advantages of rapidity and simplicity since the B/F (bound reagent/free reagent) separation steps, the solid-phase carrier and antibody labeling or modification process are not necessary. The proposed immunosensing system displayed a wide linear range, good precision and accuracy, and comparable sensitivity with a detection limit of 0.3 μg l-1, which satisfied the World Health Organization (WHO) provisional guideline limit of 1.0 μg l-1 for MC-LR in drinking water.

HeLa cells were exposed to formaldehyde and its metabolic derivatives, methanol, formic acid, and acetaldehyde, to investigate that the toxicity of formaldehyde is not caused by the chemical group. After 1 h of treatment with formaldehyde, mitochondrial assays showed that low concentrations (e.g. 10 μmol/L) of formaldehyde promoted growth of the HeLa cells, while higher concentrations (e.g. ≥62.5 μmol/L) inhibited cell growth; while all four chemicals at a concentration of 125 μmol/L affected cell growth, formaldehyde affected the largest. Reactive oxygen species concentration increased with the concentration of the exposure chemical. The endogenous formaldehyde content increased the most in the formaldehyde group, but in other three groups, it did not increase as the exposure concentration increased. Expression of dehydrogenase (formaldehyde dehydrogenase (FDH)) in the formaldehyde (10.40) and methanol (10.60) groups increased significantly compared with the control (1), while it was similar to the control in formic acid (0.90) and acetaldehyde (1.10) groups. Our results suggest that formaldehyde could affect cell activity and even enter cells. Exposure to formaldehyde changes the endogenous formaldehyde concentration in cells within 24 h, and this induces expression of FDH for formaldehyde degradation to maintain the formaldehyde balance. The toxicity of formaldehyde is not caused by the carbon atoms in the aldehyde, hydroxyl, or carboxyl groups. Formaldehyde is hypothesized to be an important signaling molecule in the regulation of cell growth and maintenance of the endogenous formaldehyde level.

In this study, normal saline, formaldehyde, acetaldehyde, methanol and formic acid with the same concentration(20 mg/kg) was gavaged in mice in order to detect these substances toxicity. After the contamination phase, we detected formaldehyde content of all mice's blood in different contamination groups by AHMT method. The results showed that the formaldehyde content in formaldehyde group and normal saline group was barely changeful, then the methanol group and formic acid group had a little changes compared with formaldehyde group. So it indicated that formaldehyde from outside can not change the level of formaldehyde in mice blood. Then, there might be some enzyme such as formaldehyde dehydrogenase conversing them through metabolic pathway. The detection of DPC ratio in liver organ after 6-day contamination showed that four toxic groups had similar values, which almost remain in the range of 15 %-18 %. The control's DPC ratio is 6%.

In order to explore the influence of CYP450 in the liver of mice after inhalation of formaldehyde, using SPF level purely Kunming male mice for the study, set 4 concentrations of gaseous formaldehyde dynamics: 0, 0.5, 1.0 and 3.0 mg/m3 in mice exposed to continuous 72 hours, then measured changes of total contents of CYP450 in the liver microsomes, and detected the varieties of CYP1B1 by RT-PCR technology, which plays an important part in activating carcinogens. The results showed: At the concentration range of formaldehyde set in this study, there is a visible difference in the contents of total CYP450 and CYP1B1 between exposure group and control group. This study suggests that FA can make change of CYP450 in the liver of mice, whose gene polymorphism are related to cancer.