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Irreversible electroporation (IRE) is a promising non-thermal ablation technique for the treatment of patients with hepatocellular carcinoma. Early differentiation of the IRE zone from surrounding reversibly electroporated (RE) penumbra is vital for the evaluation of treatment response. In this study, an advanced statistical learning framework was developed by evaluating standard MRI data to differentiate IRE ablation zones, and to correlate with histological tumor biomarkers.Fourteen rabbits with VX2 liver tumors were scanned following IRE ablation and forty-six features were extracted from T1w and T2w MRI. Following identification of key imaging variables through two-step feature analysis, multivariable classification and regression models were generated for differentiation of IRE ablation zones, and correlation with histological markers reflecting viable tumor cells, microvessel density, and apoptosis rate. The performance of the multivariable models was assessed by measuring accuracy, receiver operating characteristics curve analysis, and Spearman correlation coefficients.The classifiers integrating four radiomics features of T1w, T2w, and T1w+T2w MRI data distinguished IRE from RE zones with an accuracy of 97%, 80%, and 97%, respectively. Also, pixelwise classification models of T1w, T2w, and T1w+T2w MRI labeled each voxel with an accuracy of 82.8%, 66.5%, and 82.9%, respectively. Regression models obtained a strong correlation with behavior of viable tumor cells (0.62 ≤ rMRI radiomics features provide descriptive power for early differentiation of IRE and RE zones while observing strong correlations among multivariable MRI regression models and histological tumor biomarkers.

Medulloblastoma is a highly malignant pediatric brain tumor associated with poor outcome. Developing treatments that target the cancer stem cell (CSC) population in medulloblastoma are important to prevent tumor relapse and induce long-lasting clinical responses. We utilized medulloblastoma neurospheres that display CSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. Of all class IA PI3Ks, only the PI3Kα isoform was required for sphere formation by medulloblastoma cells. Knockdown of p110α, but not p110β or p110δ, significantly disrupted cancer stem cell frequencies as determined by extreme limiting dilution analysis (ELDA), indicating an essential role for the PI3Kα catalytic isoform in medulloblastoma CSCs. Importantly, pharmacologic inhibition of the MAPK-interacting kinase (MNK) enhanced the antineoplastic effects of targeted PI3Kα inhibition in medulloblastoma. This indicates that MNK signaling promotes survival in medulloblastoma, suggesting dual PI3Kα and MNK inhibition may provide a novel approach to target and eliminate medulloblastoma CSCs. We also observed a significant reduction in tumor formation in subcutaneous and intracranial mouse xenograft models, which further suggests that this combinatorial approach may represent an efficient therapeutic strategy for medulloblastoma.Implications:These findings raise the possibility of a unique therapeutic approach for medulloblastoma, involving MNK targeting to sensitize medulloblastoma CSCs to PI3Kα inhibition.

Pairwise tests for differences in stem cell frequencies.

Body weight of mice from flank tumor xenograft experiment

Supplementary Figure S3

Supplementary Table S2

Purpose:Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG.Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts.Results:GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy.Conclusions:Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.

In this study, novel SnNb2O6–ZrO2 nanosheet composites were successfully synthesized by hydrothermal method and evaluated for the conversion of cellulose. As a result, the composite samples demonstrate excellent catalytic performance toward cellulose conversion to 5-hydroxymethylfurfural (H6MF), a crucial green platform chemical and excellent intermediate, in a bi-phase system of THF/H2O with the addition of NaCl. The SnNb2O–ZrO2 catalysts with different ZrO2 amounts were characterized by XRD, SEM, TEM, XPS, pyridine-FTIR and Raman to investigate the properties of the samples. The Lewis acid sites and Bronsted acid sites of the samples and the interaction between SnNb2O6 and ZrO2 were also discussed in this work. Since the reaction temperature, reaction time, NaCl amounts and the volume ratio of THF/H2O were altered, the highest conversion of cellulose achieved 85% over SnNb2O6–5% ZrO2 catalyst, with good selectivity (41.8%) and yield (35.5%) of HMF in THF/H2O (volume ratio of 3:1) within 6 h at 180 °C.

Direct conversion of cellulose into ethylene glycol is a promising route for transforming sustainable biomass resources into high-value chemicals. Although numerous attempts have been made to explo...

Oxidative coupling of methane (OCM) using CO2 as the oxidant is a potential advancement for methane conversion and greenhouse gases reduction. However, the reaction is usually limited by both high energy consumption and strict reaction condition. Here, we report, for the first time, photoinduced efficient ethylene (C2H4) and CO production by OCM over TiO2-supported Ag nanoparticles at mild conditions. The success relies on a synergy coupling visible-light-induced strong surface plasma resonance (SPR) effect localized on Ag(0), ultraviolet-light-induced photoelectric effect on TiO2, and the separated adsorption of CO2 and CH4 on TiO2 and Ag. The yields of CO and C2H4 reach 1149 and 686 μmol·g–1·h–1, respectively, under simulated solar irradiation. The origination of carbon-based gas products from CO2 and CH4 is also certified by a 13C isotope-labeled experiment. This work presents a new and ideal route of photocatalytic OCM reaction for C2H4 and CO production by coupling both SPR and photoelectric effects.

It is unknown whether the route of administration impacts dendritic cell (DC)-based immunotherapy for pancreatic ductal adenocarcinoma (PDAC). We compared the effect of intraperitoneal (i.p.), subcutaneous (s.c.), and intratumoral (i.t.) administration of DC vaccine on induction of antitumor responses in a KPC mouse model of PDAC. Histological analysis and flow cytometry were used to evaluate tumor progression and antitumor immunity after different routes of DC vaccination. Using a flank mouse model of PDAC, we found that the i.t. route of DC vaccination had no significant effect on tumor growth rates compared with i.p. and s.c. routes (i.p. 6.66 ± 2.58% vs s.c. 6.79 ± 1.36% vs i.t. 8.57 ± 2.36%; P = 0.33). However, in an orthotopic PDAC model, i.p. injection of DC vaccine effectively suppressed tumor growth, inhibited tumor progression, and increased antitumor immunity compared with s.c. vaccination (tumor weight: i.p. 71.60 ± 15.55 mg vs control 200.40 ± 53.04 mg; P = 0.048; s.c. 151.40 ± 41.64 mg vs control 200.40 ± 53.04 mg; P = 0.49). Our study suggests that immunization via an i.p. route results in superior antitumor immune response and tumor suppression when compared with other routes.

Epilepsy is a long-term neurological disease characterized by convulsions that can be recurrent. It is mainly caused by an imbalance between excitation and inhibition in the central nervous system. Currently, the pathogenesis is still unclear, although it may be related to changes in ion channels, neurotransmitters and glial cells. In recent years, increasing attention has been paid to the role of autophagy in the development of epilepsy. This chapter focuses on the role of the mTOR pathway in epileptogenesis and the relationship between autophagy, glycogen metabolism and Lafora disease and discusses the potential role of autophagy as a target for the treatment of epilepsy.

Neurodevelopmental diseases are a class of neurodevelopmental disorders characterized by cognitive impairment and behavioral abnormalities and are mainly manifested as developmental disorders of the brain and nervous system. The pathological mechanism is not fully understood and may be related to hereditary or environmental factors. The elevation of autophagy during neural development suggests that autophagy may be involved in the process of neurodevelopment. This chapter focuses on the important functions of autophagy in all aspects of neurodevelopment and the role and mechanism of autophagy in neurodevelopmental disorders, especially in autism spectrum disorder.

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with limited available drugs for treatment. Enhancing autophagy attenuates AD pathology in various AD model mice. Thus, development of potential drugs enhancing autophagy may bring beneficial effects in AD therapy. Methods: In the present study, we showed clemastine, a first-generation histamine H1R antagonist and being originally marketed for the treatment of allergic rhinitis, ameliorates AD pathogenesis in APP/PS1 transgenic mice. Chronic treatment with clemastine orally reduced amyloid-β (Aβ) load, neuroinflammation and cognitive deficits of APP/PS1 transgenic mice as shown by immunohistochemistry and behavioral analysis. We further analyzed the mechanisms underlying the beneficial effects of clemastine with using the combination of both in vivo and in vitro experiments. We observed that clemastine decreased Aβ generation via reducing the levels of BACE1, CTFs of APP. Clemastine enhanced autophagy concomitant with a suppression of mTOR signaling. Conclusion: Therefore, we propose that clemastine attenuates AD pathology via enhancing mTOR-mediated autophagy.

The LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18–5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm3)/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = −0.825, P = .043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.

This work studied a facile and template-free hydrothermal route for controlled synthesis of tungsten trioxide in the form of hexagonal nanorod (h-WO3) and monoclinic nanosheet (m-WO3). The surface morphology, crystal plane, surface bound water, and surface acid sites of the two kinds of WO3 nanocrystals were investigated systematically. They were further evaluated as catalysts for selective cellulose hydrolysis. While both of them exhibited good catalytic performance, h-WO3 was found to be more preferential for ethylene glycol (EG) generation. This catalytic performance relied on both the unique active crystal surface (1 0 0) and surface binding water (WO3-H2O) formed by h-WO3 crystals, which provided more Lewis acid sites for degrading cellulose into EG. Results showed that the highest EG yield reaches 77.5% by a combination of loading 1 wt% Ru on the h-WO3 catalyst.

A series of Ni/CeO2 catalysts were synthesized via a simple one-pot hydrothermal method and characterized by XRD, SEM, TEM, EDX, EDX mapping, Raman, H2-TPR, BET, XPS, TGA and ICP-MS. Their catalytic performances were systematically evaluated in hydroliquefaction of rice straw. The impact of reaction temperature, reaction time, H2 pressure and Ni/Ce molar ratios on product yields and distribution was also investigated. The conversion (89.08%) of rice straw and bio-oil yield (66.7%) obtained over Ni/CeO2 catalyst with a Ni/Ce molar ratio of 2/10 are superior to those over no catalyst (conversion of 73.65%, bio-oil yield of 47.96%) and pure CeO2 catalyst (conversion of 77.79%, bio-oil yield of 56.67%) under the optimum condition (290 °C, 1.0 h, and 2.0 MPa H2 pressure). GC–MS results show that the main components of bio-oil are phenols, which are high-value-added, important and useful chemicals in transportation and chemical industries. It is worth noting that the highly dispersed Ni nanoparticles and their stronger interaction between Ni and CeO2 with more oxygen vacancies facilitate high conversion of rice straw and bio-oil yield. In addition, a possible catalytic mechanism of Ni/CeO2 catalyst for hydrogenation of rice straw is accordingly proposed. This work thus offers an effective approach to improve the conversion of rice straw and bio-oil yield over Ni/CeO2 catalysts.

Aiming at the bottleneck of thermodynamics, kinetics and reaction systems in photothermal catalytic CO2 reduction conversion, a three-field coupling method based on the efficient utilization of solar energy and the application of a photo-thermal-magnetic three-field was proposed to achieve efficient and highly selective CO2 conversion. The composite monolithic catalyst with three field response functions and multiple active reaction interfaces was prepared by using photoactive copper supported by nickel foam. The effect of an external alternating magnetic field on photocatalytic CO2 reduction was studied using a range between 0.005 and 0.1 wt% Cu/Cu2O/Ni(OH)2/NF as catalysts. The results showed that 0.01 wt% Cu/Cu2O/Ni(OH)2/NF exhibited the best catalytic activity and CH4 selectivity under alternating magnetic field enhanced photocatalysis. The main products were CO (6.76 μmol g−1) and CH4 (167 μmol g−1). The selectivity of CH4 was 96.1%. The yields of CH4 using this method were 11 and 6 times higher than the yields obtained with photocatalysis (14.58 μmol g−1) and magnetic-thermal catalysis (26.75 μmol g−1), respectively. According to the analysis of temperature measurements and electrochemical measurements, the surface temperature of the three-field coupled catalyst reaches about 230 °C. Applying an alternating magnetic field can effectively reduce the recombination of photogenerated electron holes. Alternating magnetic field enhanced photocatalytic CO2 reduction conversion provides a new and promising method for the efficient conversion and utilization of solar energy.

This paper describes catalytic hydrogenation liquefaction of rice straw over metal (Ni, Co, and Cu)-modified CeO2 catalysts for bio-oil production. The results show that the highest rice straw conversion (89.08%) and bio-oil yield (66.7%) were obtained over Ni/CeO2 catalyst. The bio-oil contains mainly phenols, high-value-added, and widely used chemicals. Furthermore, metal-modified CeO2 catalysts can significantly influence the components of bio-oil with the highest percentage of C7-C10 compounds. This work thus demonstrates that metal/CeO2 catalysts can be effective in improving the bio-oil yield and selectivity in hydro-liquefaction of rice straw into bio-oil.

A series of Ce-doped TiO2 nanoparticles were prepared by a sol–gel process and characterized by XRD, SEM, TEM, EDX mapping, UV–vis DRS, Raman spectroscopy, N2 adsorption–desorption, PL spectra, CO2-TPD, and XPS. It is found that Ce ions can enter the lattice matrix of TiO2 and occupy of Ti sites. This atom replacement leads to the formation of impurity energy levels in the band gap of TiO2, extending light absorption into the visible light region. Because Ce has a more flexible valence state, both Ce3+ and Ce4+ could be formed in the composites. The preference facilitates the photoinduced charge separation inside of the crystals. Moreover, Pd nanoparticles were then loaded as a co-catalyst on the surface of doped composites. As the trapping center of electrons, it can efficiently adsorb and activate CO2 molecules, promoting their transformation into CH4. These composites were then evaluated as photocatalysts for CO2 hydrogenation. While all of them could efficiently catalyze the reaction, 1.0% Pd/0.5% Ce-...

Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7. Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS. Collectively, our study reveals a cytoplasmic function for a member of the COMPASS family, which could be harnessed for therapeutic regulation of signaling in human diseases, including cancer.

Purpose: Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG. Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts. Results: GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy. Conclusions: Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.

Purpose Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with high recurrence after surgery due to a paucity of effective post-surgical adjuvant treatments. DC vaccines can activate multiple anti-tumor immune responses but have not been explored for post-surgery PDAC recurrence. Intraperitoneal (IP) delivery may allow increased DC vaccine dosage and migration to lymph nodes. Here, we investigated the role of prophylactic DC vaccination controlling PDAC tumor growth with IP delivery as an administration route for DC vaccination. Methods DC vaccines were generated using ex vivo differentiation and maturation of bone marrow–derived precursors. Twenty mice were divided into four groups (n = 5) and treated with DC vaccines, unpulsed mature DCs, Panc02 lysates or no treatment. After tumor induction, mice underwent three magnetic resonance imaging scans to track tumor growth. Apparent diffusion coefficient (ADC), a quantitative magnetic resonance imaging measurement of tumor microstructure, was calculated. Survival was tracked. Tumor tissue was collected after death and stained with hematoxylin and eosin, Masson's trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling and anti-CD8 stains for histology. Results DC-vaccinated mice demonstrated stronger anti-tumor cytotoxicity compared with control groups on lactate dehydrogenase assay. DC vaccine mice also demonstrated decreased tumor volume, prolonged survival and increased ΔADC compared with control groups. On histology, the DC vaccine group had increased apoptosis, increased CD8+ T cells and decreased collagen. ΔADC negatively correlated with % collagen in tumor tissues. Discussion Prophylactic DC vaccination may inhibit PDAC tumor growth during recurrence and prolong survival. ΔADC may be a potential imaging biomarker that correlates with tumor histological features.

Medulloblastoma is a highly malignant pediatric brain tumor associated with poor outcome. Developing treatments that target the cancer stem cell (CSC) population in medulloblastoma are important to prevent tumor relapse and induce long-lasting clinical responses. We utilized medulloblastoma neurospheres that display CSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. Of all class IA PI3Ks, only the PI3Kα isoform was required for sphere formation by medulloblastoma cells. Knockdown of p110α, but not p110β or p110δ, significantly disrupted cancer stem cell frequencies as determined by extreme limiting dilution analysis (ELDA), indicating an essential role for the PI3Kα catalytic isoform in medulloblastoma CSCs. Importantly, pharmacologic inhibition of the MAPK-interacting kinase (MNK) enhanced the antineoplastic effects of targeted PI3Kα inhibition in medulloblastoma. This indicates that MNK signaling promotes survival in medulloblastoma, suggesting dual PI3Kα and MNK inhibition may provide a novel approach to target and eliminate medulloblastoma CSCs. We also observed a significant reduction in tumor formation in subcutaneous and intracranial mouse xenograft models, which further suggests that this combinatorial approach may represent an efficient therapeutic strategy for medulloblastoma. Implications: These findings raise the possibility of a unique therapeutic approach for medulloblastoma, involving MNK targeting to sensitize medulloblastoma CSCs to PI3Kα inhibition.

Lignocellulose, having great potential to become substitute for fossil fuels, can sustainably produce fuels and chemical resources. So far, the main techniques used to generate fuels and high value-added chemicals from lignocellulose have been catalytic hydrolysis and hydrogenation. In this study, MoS2 and CoS2/MoS2 catalysts were used in the hydrogenation of rice straw. In the obtained bio-oil it was detected that the main components were esters and phenols, which was the important part of transportation fuels and chemicals. The results of our study demonstrated that the MoS2 and CoS2/MoS2 samples could be used as effective catalysts for degrading lignocellulose to obtain important chemicals.

Pancreatic ductal adenocarcinoma (PDAC) carries the worst prognosis and caused one of the highest cancer-related mortalities. Dendritic cell (DC) vaccination is a promising cancer immunotherapy; however, the clinical outcomes are often poor. The administration route of DC vaccine can significantly alter the anti-tumor immune response. Here we report on the cytotoxic T lymphocyte (CTL) responses induced by DC vaccination administered via intraperitoneal (IP) for murine PDAC, and the longitudinal assessment of tumor growth and therapeutic responses using magnetic resonance imaging (MRI). In this study, we established murine orthotopic Panc02 models of PDAC and delivered apoptotic Panc02 cell-pulsed DCs via IP injection. The migration of Panc02-pulsed DCs into spleens significantly increased from 6 h to 12 h after initiation of treatment (

The LSL-Kras

Background: Previous studies have shown the poor prognosis of metastatic breast cancer including bone metastasis. The early prediction and intervention of invasive breast carcinoma with bone metastasis are crucial to the outcomes of patients. The purpose of our study is to test the hypothesis that the collagen deposition of primary breast cancer can be used as a quantitative biomarker for the early prediction of bone metastasis. Methods: A total of sixty breast cancer patients were included in our study, and the surgical specimens of these patients were divided into three groups: patients with no metastasis (group 1), lymph node metastasis (group 2), and bone metastasis (group 3). Masson’s trichrome staining and hematoxylin and eosin staining were applied to all primary breast cancers. Collagen area percentage and tumor cell measurement of each sample were measured by HistoQuest software. Results: Measurement results of collagen area percentage (%) in primary breast tumors were 32.39 ± 13.30, 25.37 ± 11.10, and 22.71 ± 8.91 for groups 1, 2, and 3, respectively. The corresponding P values were 0.0779 (group 1 vs. group 2), 0.4086 (group 2 vs. group 3), and 0.0102 (group 1 vs. group 3). The correlation between collagen area percentage and tumor cell measurement were group 1 (P = 0.5927, r = -0.1273), group 2 (P = 0.5711, r = -0.1348), and group 3 (P = 0.0003, r = -0.7253). Conclusions: The collagen deposition of primary breast cancer can be used as a quantitative biomarker for the early prediction of bone metastasis.

A novel heterojunction of a MoS2/SrZrO3 photocatalyst was successfully synthesized via a simple hydrothermal process and applied to photocatalytic H2 evolution under UV light irradiation. The samples were characterized by X-ray diffraction, UV-vis absorption spectroscopy, scanning and transmission electron microscopy, X-ray photoemission spectroscopy, energy dispersive X-ray spectroscopy and EDX mapping. The heterostructure with an optimal content of 0.05 wt% MoS2 exhibits the highest H2 evolution rate of 5.31 mmol h−1. This is due to the junction between SrZrO3 and MoS2, which suppresses the recombination of photogenerated electrons and holes. Our work indicated that the prepared MoS2/SrZrO3 heterostructured photocatalyst can be used as an effective material for water splitting.

PURPOSE: To test the hypothesis that biomarkers of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUV(max)) was calculated 3 days after IRE. The maximum lesion diameter change (ΔD(max)) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUV(max) and ΔD(max) were compared. The apoptosis index was calculated by using caspase-3–stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUV(max) at 3 days and ΔD(max) (or apoptosis index) at 14 days after IRE treatment. RESULTS: ΔSUV(max,) ΔD(max), and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUV(max) 3 days after IRE and ΔD(max) 14 days after IRE (R = 0.66, P = .01) and between ΔSUV(max) 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). CONCLUSION: (18)F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. (©) RSNA, 2017

Dendritic cells (DCs) are the most potent antigen-presenting cells, and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes (CTLs) in lymphatic tissues. DC vaccination is a newly emerging and potent form of cancer immunotherapy and has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC-vaccines is strongly influenced by various techniques for the priming antigen loading onto DCs and their ability to migrate to the draining lymph nodes (LNs). Therefore, it is critical to improve DC-vaccines homing to draining LNs after administration in order to optimize DC-based therapy for individual patients. This review underlines 1) appropriate strategy to load tumor antigens onto DCs and 2) to optimize vaccine administration methods to ensure loaded DCs can migrate to LNs, in particular, Intraperitoneal (IP) injection. IP injection of DC-based vaccine may be a potential regimen for gastrointestinal tumors including hepatocellular carcinoma (HCC) and pancreatic adenocarcinoma (PDAC) since huge populations of LNs are present throughout the gastrointestinal track. Which might improve the subsequent migration to LNs.

The catalytic conversion of alkali lignin to chemicals has been the subject of intense research efforts during the past few decades. In this study, VS2 catalysts, with different morphologies of sheets and nanoflowers, were prepared through hydrothermal methods and applied to the hydrogenation of alkali lignin. The conversion of alkali lignin and yield of bio-oil are 77.02 and 58.75%, respectively, at 250 °C under 2 MPa H2 for 1.5 h with a VS2 sheets catalyst, which is higher than that of a flower-like VS2 catalyst. It was found that mainly the components of bio-oil were phenols, important and useful chemicals in transportation fuels and chemical industries. Our results indicated that the prepared VS2 catalyst can be used as an effective material for degrading biomass to obtain valuable chemicals.

Hexadecyl trimethylammonium bromide (HDTMAB)-modified palygorskite with ultrasonic treatment was synthesized, characterized, and examined as a potential adsorbent for removal of bisphenol A (BPA) from aqueous solution. Batch studies were carried out to evaluate various influencing factors. The adsorption mechanism in the BPA/modified-palygorskite system was best described by pseudo-second-order kinetics with a significant contribution of film diffusion. Equilibrium data was fitted perfectly with Langmuir isotherm model, and the maximum monolayer adsorption capacity was 219.30 mg g−1 at 303 K. The adsorption process was exothermic, entropy decreased, and spontaneous in nature, and was driven by the collaboration of hydrophobic interaction, dipole-bonding, and hydrogen-bond interaction.

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor characterized by rapid and uniform patient demise. A heterozygous point mutation of histone H3 occurs in more than 80% of these tumors and results in a lysine-to-methionine substitution (H3K27M). Expression of this histone mutant is accompanied by a reduction in the levels of polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), and this is hypothesized to be a driving event of DIPG oncogenesis. Despite a major loss of H3K27me3, PRC2 activity is still detected in DIPG cells positive for H3K27M. To investigate the functional roles of H3K27M and PRC2 in DIPG pathogenesis, we profiled the epigenome of H3K27M-mutant DIPG cells and found that H3K27M associates with increased H3K27 acetylation (H3K27ac). In accordance with previous biochemical data, the majority of the heterotypic H3K27M-K27ac nucleosomes colocalize with bromodomain proteins at the loci of actively transcribed genes, whereas PRC2 is excluded from these regions; this suggests that H3K27M does not sequester PRC2 on chromatin. Residual PRC2 activity is required to maintain DIPG proliferative potential, by repressing neuronal differentiation and function. Finally, to examine the therapeutic potential of blocking the recruitment of bromodomain proteins by heterotypic H3K27M-K27ac nucleosomes in DIPG cells, we performed treatments in vivo with BET bromodomain inhibitors and demonstrate that they efficiently inhibit tumor progression, thus identifying this class of compounds as potential therapeutics in DIPG.

The phase behaviors of special hot microemulsion were studied and used to realize the controllable production of drug-loaded nanostructured lipid carriers (NLCs). The home-made detection instrument of phase diagram which includes a very important thermostatic unit was applied to monitor the phase change of polyoxyethylene(40)stearate (S40)/polyoxyethylene-b-polyoxypropylene (F68)/glycerol monostearate (GMS) + oleic acid (OA)/water microemulsion system. The several main phase regions, such as oil-in-water (O/W) microemulsion, water-in-oil (W/O) microemulsion, and liquid crystal region, were all founded in the phase diagram of the above-mentioned system. The O/W microemulsion region was the most important region for the preparation of lipid nanoparticles. The drug-free GMS/OA-NLCs and retinoid acid (RA)-loaded RA-GMS/OA-NLCs were produced by direct cooling of hot microemulsions which were obtained according to the component ratio in the corresponding O/W microemulsion region in their phase diagrams. The two obtainable NLC suspensions were all transparent and clear due to the very smaller average diameter of 10.2 ± 0.2 nm of both NLCs by means of photon correlation spectroscopy (PCS) measurements. TEM images showed that both SLNs were all irregular spherical particles with the diameter of about 10 nm. Zeta potential of both NLCs were in the range of −40.7 ± 0.8 mV, showing the good stability of both NLCs. Such NLCs could be used as not only drug carriers, but also other healthy-related products such as nanoscale carriers of nutrients and cosmetics additives.

In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and histopathologic features of the human disease. When GL261 cells are implanted intracranially in syngeneic C57BL/6 mice, the model has the added advantage of maintaining an intact immune microenvironment. Stable expression of luciferase in GL261 cells allows non-invasive cost effective bioluminescence monitoring of intracranial tumor growth. We have recently demonstrated that luciferase expression in GL261 cells does not affect the tumor growth properties, tumor cell immunomodulatory cytokine expression, infiltration of immune cells into the tumor, or overall survival of animals bearing the intracranial tumor. Therefore, it appears that the GL261 luciferase glioma model can be useful in the study of novel chemotherapeutic and immunotherapeutic modalities. Here we report the technique for generating stable luciferase expression in GL261 cells and how to study the in vitro and in vivo growth of the tumor cells by bioluminescence imaging.

Lignocellulose, having great potential to become substitute for fossil fuels, can sustainably produce fuels and chemical resources. So far, the main techniques used to generate fuels and high value-added chemicals from lignocellulose have been catalytic hydrolysis and hydrogenation. In this study, MoS2 and CoS2/MoS2 catalysts were used in the hydrogenation of rice straw. In the obtained bio-oil it was detected that the main components were esters and phenols, which was the important part of transportation fuels and chemicals. The results of our study demonstrated that the MoS2 and CoS2/MoS2 samples could be used as effective catalysts for degrading lignocellulose to obtain important chemicals.

During spermatogenesis, more than half of the differentiating spermatogenic cells undergo apoptosis before they mature into spermatozoa. Ultrastructure studies showed that the formation of lipid droplets in Sertoli cells was associated with phagocytosis of residual bodies and apoptotic germ cells by Sertoli cells. Here, a relationship between the phagocytosis of apoptotic spermatogenic cells and lipid droplet formation in Sertoli cells was studiedin vitroby Oil Red O (ORO) staining. The results confirmed that the formation of lipid droplets was a result of phagocytosis of apoptotic spermatogenic cells in Sertoli cells. By comparing phagocytosis of apoptotic spermatogenic cells and thymocytes by Sertoli cells to that by macrophages, we demonstrated that the lipid droplets accumulation in phagocytes depended on phagocytosed apoptotic cell type, but not phagocyte type. However, the size of lipid droplets was related to the type of phagocytes. By this approach, we found that Sertoli cells at different postnatal stages of development had a similar phagocytic ability. These results suggested that the detection of lipid droplets by ORO staining was a practical method to evaluate the phagocytic functions of Sertoli cellsin vitro. This approach could also be considered as anin vitromodel to study the lipid formation, metabolism, and function in Sertoli cells.

Dishevelled (Dsh in Drosophila or DVL in mice) is a member of the highly conserved Wg/Wnt signaling pathway, which regulates important processes such as cell proliferation, polarity, and specification of cell fate. Three orthologous genes of Dishevelled (Dvl-1, Dvl-2, and Dvl-3) have been found in both humans and mice. They play pivotal roles in regulating cell morphology and a variety of changes in cell behaviors. In the present study, we show that the expression of Dvl-1 is stage-dependent during mouse spermatogenesis, although Dvl-2 and Dvl-3 show relative consistent expression. The expression of Dvl-1 mRNA first appears in pachytene spermatocytes, increases in round and elongating spermatids, and then turns to an undetectable level in mature sperm cells. Analyses of immunohistochemistry and immunofluorescence staining show that DVL-1 is present diffusely in the cytoplasm of pachytene spermatocytes and exhibits mainly a vesicular pattern and perinuclear distribution and a weak diffusely cytoplasmic signal in round and elongating spermatids. The vesicular pattern of DVL-1 has been observed by previous studies in somatic cells, and suggested to play roles in signal transduction. Immunoprecipitation experiments show that DVL-1 coimmunprecipitates with spermatogenic cells beta-actin rather than alpha-tubulin. These results indicate that DVL-1 may be involved in spermatid morphological changes during mouse spermiogenesis through mediating signal transduction and/or regulating actin cytoskeleton organization.