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Abstract Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a “Trojan horse” to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.

Abstract In this study, we used the LC‐ESI‐MS/MS technique to elucidate the effects of stir‐frying on the lipidomics of oat flour before and after storage. We detected 1540 lipids in 54 subclasses; triglycerides were the most abundant, followed by diacylglycerol, ceramide (Cer), digalactosyldiacylglycerol, cardiolipin, and phosphatidylcholine. Principal component analysis and orthogonal least squares discriminant analysis analyses showed that oat flour lipids were significantly different before and after storage in stir‐fried oat flour and raw oat flour. After oat flour was stir‐fried, most of the lipid metabolites in it were significantly downregulated, and the changes in lipids during storage were reduced. Sphingolipid metabolism and ether lipid metabolism were the key metabolic pathways, and Cer, PC, and lyso‐phosphatidylcholine were the key lipid metabolites identified in the related metabolic pathways during oat flour storage. Frying inhibits lipid metabolic pathways during storage of oat flour, thereby improving lipid stability and quality during storage. This study laid the foundation for further investigating quality control and the mechanism of changes in lipids during the storage of oat flour.

In this study, foodborne microorganisms capable of fermenting and decomposing soy proteins were screened, and molecular weight analysis was performed for the peptides produced during decomposition. Subsequently, oligopeptides were obtained via isolation and purification, and their antioxidant activities were studied. The experiment results showed that a PZ1 strain was isolated from homemade kimchi and identified as Lactococcus lactis based on morphology and 16S rDNA sequence analysis. Whole genome analysis showed that the PZ1 strain contained a variety of peptidases and protease genes that had the potential to decompose proteins. Soybean proteins were then fermented by PZ1, and the polypeptides produced during fermentation were analyzed via gel permeation chromatography, revealing that 85% of polypeptides had a molecular weight below 1000 Da. The oligopeptides with molecular weight 300～1000 Da were obtained via ultrafiltration purification, and their antioxidant activity was studied. The oligopeptides demonstrated a good scavenging effect on DPPH, hydroxyl (·OH), and superoxide anion (O2−·) radicals, at an oligopeptide concentration of 2 mg/mL, the clearance rates were 79.31%, 78.27%, and 84.62%, respectively. Therefore, L. lactis PZ1 could degrade soybean protein efficiently and could be used as a probiotic for developing functional soybean products.

Abstract Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities for migration and organ colonization. Single-cell RNA sequencing of aneuploid primary teratomas and metastases identified a unique cell population with high stemness that was absent in diploid ESCs-derived teratomas. Further investigation revealed that aneuploid cells displayed decreased proteasome activity and overactivated endoplasmic reticulum (ER) stress during differentiation, thereby restricting the degradation of proteins produced from extra chromosomes in the ESC state and causing differentiation deficiencies. Noticeably, both proteasome activator Oleuropein and ER stress inhibitor 4-PBA can effectively inhibit aneuploid teratoma metastasis.

The presentation of high pressure processing (HPP) on corn starch has been reported, but the effect on protein in corn gluten meal (CGM) is rarely explored. The purposes of this study were to investigate the effect of HPP treatment on structural and functional properties of the protein in CGM. Protein was treated at 200–600 MPa for 5–15 min. Results showed that HPP treatment increased protein solubility, water and oil binding capacities, emulsion stability, foaming and foam stability. Protein which treated at 400 MPa for 15 min had the more enhanced functionality. Moreover, under this condition, the protein aggregates gradually dissociated, and the particle size decreased. These results indicated that the functional groups and structure of CGM protein were affected by the HPP treatment. We hope to convert an underutilized material into a valuable one through HPP in food industry.

Abstract Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Abstract Oat bran (OB) is a by‐product of oat, which is rich in β‐glucan. As a new food processing technology, ultrafine powder can improve the surface properties of samples. OB with different grinding times was prepared, and its functional components, physical properties, adsorption properties, and antioxidant properties were evaluated. Results showed that with increased grinding times, the average particle size of OB decreased significantly (p

Nutritional intervention is becoming more prevalent as adjuvant therapy for many cancers in view of the tumor dependence on external sources for some nutrients. However, little is known about the mechanisms that make cancer cells require certain nutrients from the microenvironment. Herein, we report the dependence of glioma cells on exogenous cysteine/cystine, despite this amino acid being nonessential. Using several 13C‐tracers and analysis of cystathionine synthase and cystathioninase levels, we revealed that glioma cells were not able to support glutathione synthesis through the transsulfuration pathway, which allows methionine to be converted to cysteine in cysteine/cystine‐deprived conditions. Therefore, we explored the nutritional deprivation in a mouse model of glioma. Animals subjected to a cysteine/cystine‐free diet survived longer, although this increase did not attain statistical significance, with concomitant reductions in plasma glutathione and cysteine levels. At the end point, however, tumors displayed the ability to synthesize glutathione, even though higher levels of oxidative stress were detected. We observed a compensation from the nutritional intervention revealed as the recovery of cysteine‐related metabolite levels in plasma. Our study highlights a time window where cysteine deprivation can be exploited for additional therapeutic strategies.

As a non-thermal processing technology, high hydrostatic pressure (HHP) can be used for starch modification without affecting the quality and flavour constituents. The effect of HHP on starch is closely related to the treatment time of HHP. In this paper, we investigated the impacts of HHP treatment time (0, 5, 10, 15, 20, 25, 30 min) on the microstructure, gelatinization and thermal properties as well as in vitro digestibility of oat starch by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, 13C NMR and differential scanning calorimeter. Results showed that 5-min HHP treatment led to deformation and decreases in short-range ordered and double-helix structures of oat starch granules, and further extending the treatment time to 15 min or above caused the formation of a gelatinous connection zone, increase of particle size, disintegration of short-range ordered and double-helix structures, and crystal structure change from A type to V type, indicating gelatinization occurred. Longer treatment time also resulted in the reduction in both the viscosity and the stability of oat starch. These indicated that HHP treatment time greatly influenced the microstructure of oat starch, and the oat starch experienced crystalline destruction (5 min), crystalline disintegration (15 min) and gelatinization (> 15 min) during HHP treatment. Results of in vitro digestibility showed that the rapidly digestible starch (RDS) content declined first after treatment for 5 to 10 min then rose with the time extending from 15 to 30 min, indicating that longer pressure treatment time was unfavourable to the health benefits of oat starch for humans with diabetes and cardiovascular disease. Therefore, the 500-MPa treatment time for oat starch is recommended not more than 15 min. This study provides theoretical guidance for the application of HHP technology in starch modification and development of health foods.

Owing to its potential role in improving intestinal health, oat bran has received a lot of attention. In vitro digestion and fermentation were performed on oat brans that had been pretreated with steaming, microwave, and hot-air drying. The results showed that the dietary fiber after in vitro digestion and β-glucan content of pretreated oat brans changed insignificantly (p > 0.05). The abundance of Firmicutes and Proteobacteria varied significantly between samples (p

Astrocytomas are the most common subtype of brain tumors and no curative treatment exist. Longitudinal assessment of patients, usually via Magnetic Resonance Imaging (MRI), is crucial since tumor progression may occur earlier than clinical progression. MRI usually provides a means for monitoring the disease, but it only informs about the structural changes of the tumor, while molecular changes can occur as a treatment response without any MRI-visible change. Radiotherapy (RT) is routinely performed following surgery as part of the standard of care in astrocytomas, that can also include chemotherapy involving temozolomide. Monitoring the response to RT is a key factor for the management of patients. Herein, we provide plasma and tissue metabolic biomarkers of treatment response in a mouse model of astrocytoma that was subjected to radiotherapy. Plasma metabolic profiles acquired over time by Liquid Chromatography Mass Spectrometry (LC/MS) were subjected to multivariate empirical Bayes time-series analysis (MEBA) and Receiver Operating Characteristic (ROC) assessment including Random Forest as the classification strategy. These analyses revealed a variation of the plasma metabolome in those mice that underwent radiotherapy compared to controls; specifically, fumarate was the best discriminatory feature. Additionally, Nuclear Magnetic Resonance (NMR)-based 13C-tracing experiments were performed at end-point utilizing [U-13C]-Glutamine to investigate its fate in the tumor and contralateral tissues. Irradiated mice displayed lower levels of glycolytic metabolites (e.g. phosphoenolpyruvate) in tumor tissue, and a higher flux of glutamine towards succinate was observed in the radiation cohort. The plasma biomarkers provided herein could be validated in the clinic, thereby improving the assessment of brain tumor patients throughout radiotherapy. Moreover, the metabolic rewiring associated to radiotherapy in tumor tissue could lead to potential metabolic imaging approaches for monitoring treatment using blood draws.

Background: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. Objective: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. Method: This was a single-center, prospective cohort study that included 304 preterm infants weighing 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). Conclusion: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.

Using oat-corn-konjac extruded mixed powder, oat bran micro powder, skim milk powder, Pueraria whole powder, and pumpkin powder as raw materials, a formula powder with high dietary fiber was prepared, and its effect on obesity in mice with a high-fat diet was investigated. After 7 days of adaptive feeding, the mice were divided into blank group, high-fat diet group, formula powder + high-fat diet group, and weight-loss drug + high-fat diet group. After 8 weeks of treatment, the body weight of mice were observed and measured to determine the composition of tract flora, liver leptin content, insulin content, and activities of AMP-activated protein kinase (AMPK), lipoprotein lipase (LPL), fatty acid synthetase (FAS), sterol-regulatory element-binding proteins (SREBPs), and acetyl CoA carboxylase 1 (ACC1). The results indicated that treatment with the formula powder could reduce the body weight of mice and increase the abundance of Bifidobacterium, Akkermansia, and Romboutsia compared to the group given a high-fat diet. Moreover, the leptin and insulin contents of the experimental group decreased from 5.67 μg/L to 0.12 μg/L and from 12.71 μg/L to 7.13 μg/L, respectively, compared to the control group, which was not significantly different from the blank group (P > 0.05). Also, the activities of AMPK and LPL increased, and the activities of FAS, SREBPs, and ACC1 were significantly decreased (P < 0.05). Some pathogenic bacteria were significantly positively correlated with leptin and FAS and significantly negatively correlated with LPL. Some beneficial bacteria were positively correlated with LPL. Therefore, the formula powder used in this study could reduce the body weight of mice, increase the abundance of some beneficial bacteria in the colonic intestinal microbiota, and improve the activities of enzymes related to lipid metabolism in the liver. This study provides a theoretical reference for the pathway by which high-fiber diet improves liver and intestinal metabolic abnormalities.

Oats (Avena sativa L.) with similar amylose content were used to investigate the effects of ultra-high pressure treatment (UHPT) on the eating quality of steamed oat and oat protein structure. Water absorption and texture of steamed oat were evaluated and taste analysis was conducted by electronic tongue after a series of UHPT (400–600 MPa; holding time 5–15 min). The oat protein was extracted from the oat and treated with the same UHPT as the steamed oat (400–600 MPa; holding time 5–15 min). The oat protein structure was scanned by scanning electron microscopy (SEM). The water absorption rate of oat rice was increased by UHPT. Hardness values of steamed oat were reduced while springiness and cohesiveness were increased by UHPT. The UHPT samples showed significant differences in electronic tongue profiles from that of the original samples. The SEM results indicated that the structure of the protein was greatly affected by UHPT. The impact on protein structure significantly increased with an increasing level of pressure and treatment time. In general, the UHPT has strong potential to improve the texture and flavor of oat and change the structure of oat protein during industrial production.

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.

Abstract Background Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1 mut ) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG). Methods We have employed a combination of 13C tracers including glutamine and glucose for investigating the metabolism of patient-derived IDH1 mut glioma cell lines through NMR and LC/MS. Additionally, genetic loss-of-function (in vitro and in vivo) approaches were performed to unravel the adaptability of these cell lines to the inhibition of glutaminase activity. Results We report the adaptability of IDH1 mut cells’ metabolism to the inhibition of glutamine/glutamate pathway. The glutaminase inhibitor CB839 generated a decrease in the production of the downstream metabolites of glutamate, including those involved in the TCA cycle and 2HG. However, this effect on metabolism was not extended to viability; rather, our patient-derived IDH1 mut cell lines display a metabolic plasticity that allows them to overcome glutaminase inhibition. Conclusions Major metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1 mut gliomas.

In order to isolate antioxidant peptides from oats globulin hydrolyzed alcalase, an antioxidant peptide was isolated and purified using ultra-filtration and ion-exchange chromatography. Hydroxyl and 1,1-diphenyl-2-pycrylhydrazyl (DPPH) radical scavenging capacity was analyzed to evaluate the antioxidant activity of peptide. Five fractions were obtained after ultra-filtration, fraction with molecular weight >10KDa showed the strongest hydroxyl and DPPH radical scavenging ability of 58.38 ± 0.87% and 24.53 ± 0.53% (p < 0.05). Fraction C which was purified via ion-exchange chromatography, exhibited the maximum antioxidant activity (IC50 of hydroxyl and DPPH radical scavenging ability was 1.83 ± 0.03 mg mL−1 and 4.11 ± 0.07 mg mL−1) among other fractions (p < 0.05). Subsequently, five antioxidant peptides were identified by electrospray ionization mass spectrometry (ESI-MS/MS), with the amino acid sequence of IRIPIL, FLKPMT, NSKNFPTL, LIGRPIIY, and FNDILRRGQLL, with a molecular weight of 723.50, 735.40, 919.48, 943.59, and 1343.76 Da, respectively.

Umami peptides were derived from enzymatic hydrolysis of sunflower seed protein, followed by isolation and identification. The flavourzyme-enzymatic hydrolysates exhibited the highest umami intensity value of 10.72 ± 0.05 and the lowest bitterness, when pH was adjusted to 7.0, the flavorzyme was added at enzyme-to-substrate (E/S) ratio of 1:25 (w/w), then incubated in a temperature-controlled water bath at 55°C, and the hydrolysis time was 480 min. Ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) were used to isolate the umami peptides of sunflower seed. Five fractions were obtained after ultra-filtration, fraction with molecular weight 1-3 kDa showed highest umami intensity value 13.93 ± 0.06. Fraction F1, which was purified via sephadex gel filtration chromatography, exhibited high umami value (12.21 ± 0.06), and low bitterness (4.57 ± 0.06). Seven sub-fractions were purified by RP-HPLC, and the umami taste value of F1-4 was the highest (14.16 ± 0.05), which was 1.32 times stronger than that of sunflower seed protein hydrolysates without any purification. Furthermore, the structure of fraction F1-4 was characterized by mass spectrometry, and three peptide fractions were identified, with amino acid sequences of DVNNPANQLD, NNENQLDEYQR, and EFEGGSIEH, respectively.

Innovation is increasingly becoming the most crucial and effective way to tackle climate change and environmental pollution. Recently, innovation quality has received continuous attention from scholars, entrepreneurs and policymakers. It is necessary to measure innovation quality from the perspective of green development. Based on the statistics data of 30 provincial-level innovation systems in China, this study comprehensively evaluates regional innovation quality and identifies the configuration of factors which could lead to high regional innovation quality. Firstly, this study establishes an indicator system of measuring regional innovation quality which includes seven indicators from three aspects of technological, economic and ecological benefit of innovative activities, and entropy weight method is used to comprehensively evaluate regional innovation quality. The result reveals there are big differences between different regions in China in innovation quality. In terms of three economic regions in China, innovation quality in the eastern region is the highest, followed by the central region and the lowest in the western region. Then, fuzzy-set qualitative comparative analysis method is applied, which uncovers three configurations of factors that could lead to high regional innovation quality. Finally, the conclusion of this study provides policy pathways for improving regional innovation quality.

Technological innovation is increasingly becoming an important way to develop a low-carbon economy. Recently, exploring the driving path of low-carbon development has become the hot topic, however, the role of energy consumption in the carbon-reduction effect of technological innovation has been ignored. Based on China's provincial-level panel data from 2005 to 2016, this paper investigates the effect of technological innovation on energy saving and carbon emissions reduction and the role of energy consumption in the influencing process by using linear regression model, mediating effect model and threshold regression model. The results show that technological innovation has effectively promoted energy saving and carbon emissions reduction in China, with different effect coefficients between the three areas of China. Moreover, energy consumption plays a significant partial mediating role in the effect of technological innovation on carbon emissions reduction. Finally, the effect of technological innovation on carbon emissions is limited by energy consumption. Low energy consumption significantly promotes a reduction in carbon emissions through technological innovation. Once energy consumption exceeds a critical level, the promoting effect of technological innovation on carbon emissions reduction will turn into the inhibiting effect. Based on these findings, some policy recommendations are put forward to accelerate the low-carbon transformation of the economy.

Four coordination polymers have been synthesized by using Zn(II)/Cd(II) salt and bis(imidazole) ligand in the presence of the different flexible phenylenediacetate isomers under hydrothermal conditions. The flexible trans-conformation pda and biyb ligands in complexes 1, 3, 4 afford the 2D (4,4)-connected layer, which are further stacked in an offset fashion with an ABAB sequence to propagate into a 3D supramolecular architecture through strong C–H···π and C–H⋯O interactions. Differently, the flexible cis-conformation pda and biyb ligands in 2 can be seen as “V” type building block, linking Zn(II) atoms to form a 3D helix network. The structural diversity of these complexes is mainly attributed to the different coordination modes and isomer conformations of the flexible phenylenediacetic acids and bis(imidazole) ligand. The fluorescence property application and mechanisms of four complexes for detecting antibiotic cefixime (CEF) have been researched. Compared with 1, 3, 4 complex 2 has higher quenching percentage, this may be because 2 is a 3D structure with a large hole (18.99 × 20.02 Å window). The detection limits of complexes 1–4 have been measured to be 0.23 μΜ, 0.34 μΜ, 0.37 μΜ, 0.38 μΜ, respectively. The theoretic calculation and UV–vis absorption experiments confirmed that the fluorescence quenching of complexes 1–4 toward cefixime (CEF) should be attributed to the electron transfer and the fluorescence inner filter effect between the fluorescent matter and the analyte.

Pretreatment improves the edible quality of oat bran and prolongs the shelf life, whereas the effect of pretreatments (i.e., steaming(S-OB), microwaving(M-OB), and hot-air drying(HA-OB)) on the flavor characteristics of oat bran is unknown. This study identified volatile composition using HS-SPME/GC–MS and an electronic nose of oat bran. The amino acid compositions were determined by a High-Speed automatic amino acid analyzer and the fatty acids were determined by gas chromatography. The results showed that steaming and microwaving pretreatments enhanced the nutty notes of oat bran. Sixty-four volatile compounds in four oat brans were identified. OB exhibited higher aroma-active compounds, followed by S-OB, and M-OB, and the HA-OB had the lowest aroma-active compounds. Hexanal, nonanal, (E)-2-octenal,1-octen-3-ol, 2-ethylhexan-1-ol, and 2-pentylfuran were the key volatile compositions in oat bran. The aldehyde content decreased and the esters and ketones increased in steamed oat bran. Microwaving and hot air drying increased the aldehyde content and decreased the ester and alcohol content. Steamed oat bran had the lowest levels of total amino acids (33.54 g/100 g) and bitter taste amino acids (5.66 g/100 g). However, steaming caused a significant reduction in saturated fatty acid content (18.56%) and an increase in unsaturated fatty acid content (79.60%) of oat bran (p < 0.05). Hot air drying did not result in an improvement in aroma. The results indicated that steaming was an effective drying method to improve the flavor quality of oat bran.

Glioblastoma (GBM) is an aggressive brain malignancy with a dismal prognosis. With emerging evidence to disprove brain-immune privilege, there has been much interest in examining immunotherapy strategies to treat central nervous system (CNS) cancers. Unfortunately, the limited success of clinical studies investigating immunotherapy regimens, has led to questions about the suitability of immunotherapy for these cancers. Inadequate inherent populations of tumor infiltrating lymphocytes (TILs) and limited trafficking of systemic, circulating T cells into the CNS likely contribute to the poor response to immunotherapy. This paucity of TILs is in concert with the finding of epigenetic silencing of genes that promote immune cell movement (chemotaxis) to the tumor. In this study we evaluated the ability of GSK126, a blood-brain barrier (BBB) permeable small molecule inhibitor of EZH2, to reverse GBM immune evasion by epigenetic suppression of T cell chemotaxis. We also evaluated the in vivo efficacy of this drug in combination with anti-PD-1 treatment on tumor growth, survival and T cell infiltration in syngeneic mouse models. GSK126 reversed H3K27me3 in murine and human GBM cell lines. When combined with anti-PD-1 treatment, a significant increase in activated T cell infiltration into the tumor was observed. This resulted in decreased tumor growth and enhanced survival both in sub-cutaneous and intracranial tumors of immunocompetent, syngeneic murine models of GBM. Additionally, a significant increase in CXCR3+ T cells was also seen in the draining lymph nodes, suggesting their readiness to migrate to the tumor. Closer examination of the mechanism of action of GSK126 revealed its ability to promote the expression of IFN-γ driven chemokines CXCL9 and CXCL10 from the tumor cells, that work to traffic T cells without directly affecting T maturation and/or proliferation. The loss of survival benefit either with single agent or combination in immunocompromised SCID mice, suggest that the therapeutic efficacy of GSK126 in GBM is primarily driven by lymphocytes. Taken together, our data suggests that in glioblastoma, epigenetic modulation using GSK126 could improve current immunotherapy strategies by reversing the epigenetic changes that enable immune cell evasion leading to enhanced immune cell trafficking to the tumor.

Abstract Background The Epstein-Barr virus (EBV) is closely associated with several types of malignancies. EBV is normally present in the latent state in the peripheral blood B cell compartment. The EBV latent-to-lytic switch is required for virus spread and virus-induced carinogenesis. Immunosuppression or DNA damage can induce the reactivation of EBV replication. EBV alone is rarely sufficient to cause cancer. In this study, we investigated the roles of host microRNAs and environmental factors, such as DNA-damage agents, in EBV reactivation and its association with lymphomagenesis. Methods We first analyzed the publicly available microRNA array data containing 45 diffuse large B-cell lymphoma patients and 10 control lymph nodes or B cells with or without EBV infection. In situ hybridization for miR-18a and immunohistochemitry were performed to evaluate the correlation between the expression of miR-18a and nuclear EBV protein EBNA1 in lymphoid neoplasm. The proliferative effects of miR-18a were investigated in EBV-positive or –negative lymphoid neoplasm cell lines. EBV viral load was measured by a quantitative real-time EBV PCR and FISH assay. The genomic instability was evaluated by CGH-array. Results In this study, we analyzed the publicly available microRNA array data and observed that the expression of the miR-17-92 cluster was associated with EBV status. In situ hybridization for miR-18a, which is a member of the miR-17-92 cluster, showed a significant upregulation in lymphoma samples. miR-18a, which shares the homolog sequence with EBV-encoded BART-5, promoted the proliferation of lymphoma cells in an EBV status-dependent manner. The DNA-damaging agent UV or hypoxia stress induced EBV activation, and miR-18a contributed to DNA damaging-induced EBV reactivation. In contrast to the promoting effect of ATM on the lytic EBV reactivation in normoxia, ATM inhibited lytic EBV gene expression and decreased the EBV viral load in the prescence of hypoxia-induced DNA damage. miR-18a reactivated EBV through inhibiting the ATM-mediated DNA damage response (DDR) and caused genomic instability. Conclusions Taken together, these results indicate that DNA-damaging agents and host microRNAs play roles in EBV reactivation. Our study supported the interplay between host cell DDR, environmental genotoxic stress and EBV.

Adult T-cell leukemia (ATL) is an aggressive T-cell lymphoproliferative malignancy of regulatory T lymphocytes (Tregs), caused by human T-cell lymphotropic virus 1 (HTLV-1). Interleukin 2 receptor alpha (IL-2Rα) is expressed in the leukemic cells of smoldering/chronic ATL patients, leading to constitutive activation of the JAK/STAT pathway and spontaneous proliferation. The PI3K/AKT/mTOR pathway also plays a critical role in ATL cell survival and proliferation. We previously performed a high-throughput screen that demonstrated additive/synergistic activity of Ruxolitinib, a JAK1/2 inhibitor, with AZD8055, an mTORC1/C2 inhibitor. However, effects of unintended JAK2 inhibition with Ruxolitinib limits it therapeutic potential for ATL patients, which lead us to evaluate a JAK1-specific inhibitor. Here, we demonstrated that Upadacitinib, a JAK-1 inhibitor, inhibited the proliferation of cytokine-dependent ATL cell lines and the expression of p-STAT5. Combinations of Upadacitinib with either AZD8055 or Sapanisertib, mTORC1/C2 inhibitors, showed anti-proliferative effects against cytokine-dependent ATL cell lines and synergistic effect with reducing tumor growth in NSG mice bearing IL-2 transgenic tumors. Importantly, the combination of these two agents inhibited ex vivo spontaneous proliferation of ATL cells from patients with smoldering/chronic ATL. Combined targeting of JAK/STAT and PI3K/AKT/mTOR pathways represents a promising therapeutic intervention for patients with smoldering/chronic ATL.

Conventional cancer cell lines and animal models have been mainstays of cancer research. More recently, human pluripotent stem cells (hPSCs) and hPSC-derived organoid technologies, together with genome engineering approaches, have provided a complementary platform to model cancer progression. Here, we review the application of these technologies in cancer modeling with respect to the cell-of-origin, cancer propagation, and metastasis. We further discuss the benefits and challenges accompanying the use of hPSC models for cancer research and discuss their broad applicability in drug discovery, biomarker identification, decoding molecular mechanisms, and the deconstruction of clonal and intra-tumoral heterogeneity. In summary, hPSC-derived organoids provide powerful models to recapitulate the pathogenic states in cancer and to perform drug discovery.

Glutelins derived from oats were purified and hydrolyzed sequentially using alcalase proteases for production of antioxidant peptides. The antioxidant activities of oat glutelin peptides were evaluated using reducing power methods including hydroxyl and 1,1-diphenyl-2-pycrylhydrazyl (DPPH) radical-scavenging assays. The results demonstrated that oats glutelin peptide D-1a exhibited the highest antioxidant activity compared to the other hydrolysates. D-1a was identified to be His–Tyr–Asn–Ala–Pro–Ala–Leu (784.38 Da) by electrospray ionization mass spectrometry (ESI-MS/MS).

In vitro hemolysis testing is commonly used to determine hemocompatibility of ExtraCorporeal Membrane Oxygenation (ECMO). However, poor reproducibility remains a challenging problem, due to several unidentified influencing factors. The present study investigated potential factors, such as flow rates, the use of anticoagulants, and gender of blood donors, which could play a role in hemolysis. Fresh human whole blood was anticoagulated with either citrate (n = 6) or heparin (n = 12; 6 female and 6 male blood donors). Blood was then circulated for 360 min at 4 L/min or 1.5 L/min. Regardless of flow rate conditions, hemolysis remained unchanged over time in citrated blood, but significantly increased after 240 min circulation in heparinized blood (p ≤ 0.01). The ratio of the normalized index of hemolysis (NIH) of heparinized blood to citrated blood was 11.7-fold higher at 4 L/min and 16.5–fold higher at 1.5 L/min. The difference in hemolysis between 1.5 L/min and 4 L/min concurred with findings of previous literature. In addition, the ratio of NIH of male heparinized blood to female was 1.7-fold higher at 4 L/min and 2.2-fold higher at 1.5 L/min. Our preliminary results suggested that the choice of anticoagulant and blood donor gender could be critical factors in hemolysis studies, and should be taken into account to improve testing reliability during ECMO.

Abstract Background Epstein Barr virus (EBV) plays a causal role in some diseases, including infectious mononucleosis, lymphoproliferative diseases and nasopharyngeal carcinoma. Detection of EBV infection has been shown to be a useful tool for diagnosing EBV-related diseases. In the present study, we compared the performance of molecular tests, including fluorescence in situ hybridization (FISH) and EBV real-time PCR, to those of serological assays for the detection of EBV infection. Methods Thirty-eight patients with infectious mononucleosis (IM) were enrolled, of whom 31 were diagnosed with a mild type, and seven were diagnosed with IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection. Twenty healthy controls were involved in the study. The atypical lymphocytes in peripheral blood were detected under a microscope and the percentage of positive cells was calculated. EBV DNA load in peripheral blood was detected using real-time PCR. The FISH assay was developed to detect the EBV genome from peripheral blood mononuclear cells (PBMC). Other diagnosis methods including the heterophil agglutination (HA) test and EBV-VCA-IgM test, to detect EBV were also compared. SPSS17.0 was used for statistical analysis. Results In all, 5–41% atypical lymphocytes were found among the PBMC in mild IM patients, whereas 8–51% atypical lymphocytes were found in IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. There was no significant difference in the ratios of atypical lymphoma between patients of the different types. We observed that 71.2% of mild IM patients and 85.7% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients were positive for EBV-VCA-IgM. EBV-VCA-IgM was negative in all healthy control subjects. In addition, 67.1% of mild IM patients tested heterophile antibody positive, whereas 71.4% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection tested positive. EBV DNA detected using real-time PCR was observed in 89.5% of these IM patients. The EBV genome was detected by the FISH assay in 97.4% of the IM patients. The EB viral loads detected by FISH and real-time PCR increased with the severity of IM. The EBV genome was detected in almost all the PBMC of IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. Conclusion Molecular tests, including FISH and EBV real-time PCR, are more sensitive than serological assays for the detection of EBV infection. The FISH assay detecting EBV copies in unfractionated whole blood is preferable and superior to plasma real-time PCR in its reflection of the absolute viral burden circulating in the patients.

Understanding the metabolic reprogramming of aggressive brain tumors has potential applications for therapeutics as well as imaging biomarkers. However, little is known about the nutrient requirements of isocitrate dehydrogenase 1 (IDH1) mutant gliomas. The IDH1 mutation involves the acquisition of a neomorphic enzymatic activity which generates D-2-hydroxyglutarate from α-ketoglutarate. In order to gain insight into the metabolism of these malignant brain tumors, we conducted metabolic profiling of the orthotopic tumor and the contralateral regions for the mouse model of IDH1 mutant glioma; as well as to examine the utilization of glucose and glutamine in supplying major metabolic pathways such as glycolysis and tricarboxylic acid (TCA). We also revealed that the main substrate of 2-hydroxyglutarate is glutamine in this model, and how this re-routing impairs its utilization in the TCA. Our 13C tracing analysis, along with hyperpolarized magnetic resonance experiments, revealed an active glycolytic pathway similar in both regions (tumor and contralateral) of the brain. Therefore, we describe the reprogramming of the central carbon metabolism associated with the IDH1 mutation in a genetically engineered mouse model which reflects the tumor biology encountered in glioma patients.

For the degree of orderly arrangement of the molecular chains at the interface of nanocomposites, the static and sheared polyethylene (PE)/carbon nanotube (CNT) models and the sheared pure PE model were constructed, and molecular simulation experiments were carried out in comparison. The micro-mechanism of molecular chains orientation, synergistically induced by the carbon nanotube and shear flow in injection molding, was discussed by analyzing the radius of gyration, molecular chain motion, conformation evolution of molecular chains, bond orientation parameter, interface binding energy and atom distribution. The results show that, for the static composite system, the conformation adjustment of PE molecular chains induced by CNT is limited due to the hindrance from the surrounding chains. Thus, the orientation and radius of gyration of molecular chains increase slightly. For the sheared pure PE system, the orientation induced by shear flow is unstable. After the cessation of shear, the molecular chains undergo intense thermal movement and relax quickly. The disorientation is obvious, and the radius of gyration decreases considerably. It is worth noting that for the sheared composite system, shear flow and the CNT have a synergistic effect on the orientation of the molecular chains, which is due to the adsorption effect of the CNT on shear-induced oriented chains and the inhibition effect of CNT on the relaxation of shear-induced oriented chains. Thus, the orientation stability of PE chains is greatly improved, and interface crystallization is promoted. Moreover, because of the more regular arrangement of molecular chains in the sheared composite system, more H atoms and C atoms are close to the surface of the CNT, which increases the van der Waals force, and correspondingly increases the interface binding energy.

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Aimed at the molding of polymer nanostructure parts, the interface model between long- and short-chain polycarbonates (PC) and nickel mold inserts was established by the molecular dynamics method. The molecular mechanism of the replication capability of polymer nanostructure part molding was discussed by analyzing the migration and diffusion of the molecular chain, concentration profile, filling morphology evolution, interface binding energy, and filling rate of conventional injection molding (CIM) and rapid heat cycle molding (RHCM). The results show that nanostructures are filled mainly during the packing stage. A short-chain PC system has a low glass transition temperature (Tg) and viscosity, good fluidity, and a high filling rate, so the replication capability of its nanostructures is good. A long-chain PC system has a fast cooling rate in CIM, its molecular chain motion is blocked, the filling rate is low, and the interface binding energy is small, and so its nanostructures have poor replication capability. However, the high temperature at the nanostructures can be maintained for a long time in RHCM, which promotes Brownian motion in the molecular chains. Under the action of packing pressure, molecular chains can overcome entanglement barriers and viscous resistance. Thus, the polymer concentration profile and filling rate increase with increasing packing pressure, which can produce more van der Waals energy. Furthermore, the evolution process of polymer filling morphology is realized by the Brownian motion of chain segments under packing pressure; that is, the diffusion motion of the molecular chain along the direction of a tube composed of other chains around it. With the increase of temperature or pressure, the migration and diffusion of the molecular chain can be promoted; thus, the replication capability of nanostructure parts for mold cavities can be enhanced.