Search

Coenzyme Q0 (CoQ0), one of benzoquinone compounds, has been demonstrated to possess antineoplastic, anti-inflammatory and antioxidant activities. However, its antimicrobial effect has not been extensively reported. In this study, antimicrobial activity of CoQ0 against

Autophagy is a highly conserved intracellular degradation pathway in eukaryotic cells that responds to environmental changes. Genetic analyses have shown that more than 40 autophagy-related genes (ATG) are directly involved in this process in fungi. In addition to Atg proteins, most vesicle transport regulators are also essential for each step of autophagy. The present study showed that one Endoplasmic Reticulum protein in

Dendritic cells (DCs) can internalize and cross-present exogenous Ags to CD8+ T cells for pathogen or tumor cell elimination. Recently, growing evidences suggest the possible immunoregulatory role of flavonoids through modulating the Ag presentation of DCs. In this study, we report that naringenin, a grapefruit-derived flavonoid, possesses the ability to increase the Ag cross-presentation in both murine DC line DC2.4 as well as bone marrow–derived DCs, and naringenin-induced moderate intracellular oxidative stress that contributed to the disruption of lysosomal membrane enhanced Ag leakage to cytosol and cross-presentation. Moreover, in a murine colon adenocarcinoma model, naringenin induced more CD103+ DCs infiltration into tumor and facilitated the activation of CD8+ T cells and strengthened the performance of therapeutic E7 vaccine against TC-1 murine lung cancer. Our investigations may inspire novel thoughts for vaccine design and open a new field of potential applications of flavonoids as immunomodulators to improve host protection against infection and tumor.

Accumulated evidence has indicated that the gut microbiome affected the pharmacology of anti-diabetic agents, and their metabolic products induced by the agents transformed the structure of gastrointestinal microbiota in return. However, the studies around heredity, ethnicity, or living condition, referring to human microbiome were mostly represented by an occidental pattern partial and rare studies that focused on the effect of several first-line hypoglycemic agents on the gut flora in a single medical center. Therefore, we aimed to explore the interaction between gut microbiome and type 2 diabetes (T2D) or hypoglycemics in Chinese population. A total of 130 T2D patients with a specific hypoglycemic treatment and 50 healthy volunteers were enrolled in this study. Gut microbiome compositons were analyzed by 16S ribosomal RNA gene-based sequencing protocol. Hypoglycemic agents contributed to the alteration of specific species in gut bacteria rather than its total diversity. Metformin increased the abundance of Spirochaete, Turicibacter, and Fusobacterium. Insulin also increased Fusobacterium, and α-glucosidase inhibitors (α-GIs) contributed to the plentitude of Bifidobacterium and Lactobacillus. Both metformin and insulin improved taurine and hypotaurine metabolism, and α-GI promoted several amino acid pathways. Although the community of gut microbiota with metformin and insulin showed similarity, significant differences were available in each diabetic group with hypoglycemia. Gut microbiota is significantly associated with anti-diabetic agents. The gut microbiome and metabolism have shown respective characteristics in different T2D groups, which were also significantly different from the healthy group. This study provides some new insights for identification and exploration of the pathogenesis of T2D.

Background and Aims As ulcerative colitis [UC]-associated colorectal cancer [CRC] and sporadic CRC differ in presentation and molecular features, we sought to evaluate differences in the impact of DNA methylation on gene expression. Methods DNA methylation was assessed in 11 UC-CRCs and adjacent tissue and 11 sporadic CRCs and adjacent tissue, using Illumina arrays. RNA sequencing was performed on 10 UC-CRCs and adjacent tissue and eight sporadic CRCs and adjacent tissues. Differences in DNA methylation and transcript expression, as well as their correlation in the same tissues, were assessed. Immunohistochemistry was performed for three proteins, ANPEP, FAM92A1, and STK31, all of which exhibited an inverse correlation between DNA methylation and transcript expression in UC. Results Thirty three loci demonstrated differences in DNA methylation between UC-CRC and adjacent tissue. In contrast, there were 4204 differentially methylated loci between sporadic colon cancer and adjacent tissue. Eight hundred eighty six genes as well as 10 long non-coding RNAs [lncRNA] were differentially expressed between UC-CRC and adjacent tissues. Although there were no differentially methylated loci between UC and sporadic CRC, 997 genes and 38 lncRNAs were differentially expressed between UC-CRC and sporadic CRC. In UC, 18 genes demonstrated a negative correlation between DNA methylation and transcript expression. Evaluation of protein expression related to three genes, ANPEP, FAM92A1, and STK31, confirmed down-regulation of ANPEP and up-regulation of STK31 in UC-CRC. Conclusions Regulation of transcript expression by DNA methylation involves genes key to colon carcinogenesis and may account for differences in presentation and outcomes between inflammatory bowel disease and sporadic colon cancer.

Currently, periodic structures on lithium niobate crystal surface exhibit extensive application prospects in related fields of on-chip photonic-integrated platforms and nanophotonics. We fabricated periodic ripple structures on the surface of lithium niobate crystal by femtosecond laser pulses irradiation and observed the evolution of these structures irradiated by 50,100,500,1000 laser pulses respectively. The morphology of surface structure became more uniform with the increasing number of laser pulses. Especially fabricated by 1000 pulses, regular ripples were found over the ablation area. The direction of ripples is perpendicular to the laser polarization and the period is around 190 nm, which was calculated by 2D-Fast Fourier Transform. By Finite-Difference Time-Domain method, we simulated the effect of the initial periodic structure on subsequent energy distribution. Numerical simulation results show that energy is deposited in the grooves between the ripples. Therefore, the ablation of grooves is more efficient, and the ripples morphology resulting from subsequent laser pulses irradiation becomes more uniform. The simulation results are consistent with the experimental results. This research is considerably valuable for controlling precisely periodic micro- and nanostructures formation and providing innovative laser manufacturing technology for wide bandgap material.

Powdery mildew, one of devastating diseases of wheat worldwide, is caused by Erysiphe graminis f. sp. tritici, a fungal species with constant population changes, which often poses challenges in disease management with host resistance. Transgenic approaches that utilize broad-spectrum resistance may limit changes of pathogen populations and contribute to effective control of the disease. The harpin protein Hpa1, produced by the rice bacterial blight pathogen, can induce resistance to bacterial blight and blast in rice. The fragment comprising residues 10 through 42 of Hpa1, Hpa1

An intrinsic flame-retardant epoxy resin was synthesized by introducing biphenyl structures and phosphorous into epoxy resin. The biphenyl structures could increase the glass transition temperature by more than 10 °C, as well thermal stability as indicated by the elevation in char yield. They could also enhance mechanical properties as reflected by the increments of 86.4% and 176.5% in tensile strength and breaking elongation, respectively, and offset the negative effects of phosphorus-containing structures. The introduction of elemental phosphorus could improve the flame-retardant properties of epoxy resin. The resulting epoxy resin presented a high limiting oxygen index of 32.4% and a V-0 rating in the UL-94 test. Moreover, it exhibited better flame-retardant parameters than pure epoxy resin in the cone calorimeter test. It could be decomposed to generate PO∙ and PO2∙ radicals to quench active free radicals, reduce toxic and smoke gas generation, and form a dense and stable char layer. It could simultaneously achieve gas and condensed phase flame retardancy. The presence of the biphenyl structure and phosphorus element in the epoxy resin system improved the thermal, mechanical, and flame-retardant properties of epoxy resin simultaneously. This work offered a facile method for preparing intrinsic phosphorus-containing flame-retardant epoxy resin without sacrificing thermal and mechanical properties.

Efficient oil–water separation plays a vital role in treating large amounts of industrial wastewater. However, current traditional separation methods are entwined with problems such as low efficiency and poor operability. Herein, we reported a nanofiber based on electrospinning and electrospray technology and spraying microspheres on the surface of a fiber mat for efficient oil–water separation. Owing to the electrostatic repulsion among the microspheres, the surface of the developed membrane had a honeycomb-like through-hole structure and super-high oil–water separation efficiency and oil flux. After 10 cycles, the membrane showed good separation efficiency and flux. This innovative work may provide a new idea and method for the design of biomimetic biopolymers, with broad application prospects in the field of oil–water separation.

In this work, the structural and electronic properties of two-dimensional (111) diamond nanofilms with a layer number of n = 3 ‒ 6 are investigated by first-principles calculation. Two kinds of Janus models (both-side boron-termination model, one-side hydrogenation and another-side boron termination model) are dynamically and thermally stable. The nanofilms have direct bandgap characteristic, and their bandgaps are tunable in a region of 2.0 ‒ 2.7 eV. The reduced bandgaps are mainly related to the surface termination of boron atoms. Interestingly, the electron mobilities (>1500 cm2•V − 1•s − 1) are higher than their hole mobilities (

Shikonin is a bioactive compound found in the roots of Lithospermum erythrorhizon and has demonstrated antibacterial activity. In the current study, we aimed to examine the antibiofilm activity of shikonin against Listeria monocytogenes, and to investigate its effects on key L. monocytogenes virulence factors associated with human infection. Present results showed that the minimum inhibitory concentration of shikonin against L. monocytogenes ranged from 25 to 100 μg/mL. Crystal violet staining confirmed that sub-inhibitory concentrations (SICs) of shikonin significantly reduced biofilm biomass in as little as 24 h. Decreased biofilm adhesion, altered biofilm morphology, and disruption of biofilm architecture following treatment with SICs of shikonin were also confirmed by light microscopy and field-emission scanning electron microscopy. Further, at SICs, shikonin effectively reduced the ability of L. monocytogenes to adhere to and invade HT-29 cells and prevented the secretion of listeriolysin O. Moreover, the transcription of biofilm-associated genes and key virulence genes that contribute to infection was also suppressed by shikonin at SICs. Therefore, present results suggest that shikonin could be used as an alternative antibacterial agent to combat L. monocytogenes biofilm formation and infection.

The static calculation of ecological service value is the main basis for determining the value of water ecological service function in a river basin. The reasonable ecological service value calculation is the premise to determine the limit value of ecological compensation standard. Based on the types and calculation methods of watershed water ecological service value, on the basis of comprehensive comparison of the applicable scope and reliability of calculation results of various calculation methods, combined with the landscape characteristics of the study area, the ecological value assessment method of watershed forest system was given. Taking the Shanxi reservoir area in the Feiyun River basin as an example, the ecological value of the four service functions of supply, regulation, culture and support services was calculated, and the total ecological service value of the reservoir area was determined to be 7.062 billion yuan/a. The ecological services value of the forest in Shanxi reservoir area in terms of water retention, environmental purification, and reduction of soil waste requires cost inputs from the people upstream of the reservoir area. In order to achieve the overall equitable, coordinated and sustainable development of the basin, the beneficiaries of the downstream ecological service value of the basin should compensate the upstream 1.498 billion yuan/a, which is about 21% of the ecological service value.

With application of high-speed power line carrier communication (HPLC), some problems are emerging such as network outliers, low success rate of power outage reporting and short single hop communication distance. Wireless communication (RF) can effectively solve these problems and thus become an effective complement to HPLC. For OFDM based wireless communication in HPLC&RF dual mode system, a channel estimation method is proposed. Compared with LTF-based and pilot-based channel estimation methods applicable to cases with few and multiple physical layer load symbols respectively, the proposed method can be applied in all cases. When the number of symbols is small, it outperforms pilot-based method by 2~3 dB and is still better than LTF-based method. When the number of symbols is large, it outperforms LTF-based method by 2~5 dB and still better than pilot-based method.

This study was designed to evaluate the efficacy of slightly acidic electrolyzed water (SAEW) to reduce natural microbiota on celery and cilantro at different available chlorine concentrations (ACC), different treatment time and temperatures. Additionally, SAEW treated celery and cilantro were stored at 4 and 20 °C for 6 days and population of total aerobic bacteria and yeast and mold were also determined at day 0, 2, 4 and 6, separately. Results showed that log reduction of total aerobic bacteria and yeast and mold significantly increased with increasing ACC and treatment time, respectively (p 0.05). The microbial population on celery and cilantro maintained at a low level during storage at 4 and 20 °C after SAEW treatment (total aerobic bacteria: 3.3–4.1 log CFU/g, yeast and mold: 2.2–3.5 log CFU/g). The microbial inactivation effect as well as the absence of any sensory alterations on treated celery and cilantro rendered SAEW a promising disinfectant, which can be applied in fresh produce wash to control natural microbiota.

A novel system for enhancing the properties of P(N-isopropylacrylamide-co-poly(ethylene glycol)diacrylate) (P(NIPAM-co-PEGDA)) temperature-sensitive hybrid hydrogels by incorporating acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) was developed in this study. Inorganic/organic hybrid P(NIPAM-co-PEGDA) hydrogels based on MAPOSS were synthesized via free radical polymerization. Environmental scanning electron microscopy images showed that hydrogels with different feed ratios exhibited significant changes in the porous structure and average pore size. The heterogeneous and irregular network was caused mainly by MAPOSS aggregation. The rigid cage-like nanostructure of MAPOSS had dual opposite effects on polymer thermal properties; this effect was proven through differential scanning calorimetry and thermogravimetric analysis. The mechanical behaviors of the swollen hydrogels investigated through compression test showed that MAPOSS incorporation enhanced the yield strength. Swelling, deswelling and reswelling behaviors of hydrogels with different feed ratios were systematically examined and compared. The increase in MAPOSS provided the hydrogels with improved deswelling rate because of its cage-like nanostructure and hydrophobicity.

The objective of this study was to determine the efficacy of electrolyzed oxidizing (EO) water in reducing natural microbiota on radish seed and sprout during seed soaking and sprouting. EO water with different available chlorine concentrations (ACC, 15, 20, 28, 33 and 40 mg/L) and different pH (2.5, 3.5, 4.5, 5.5 and 6.5) were used to soak radish seeds for 12 h and the surviving population of total aerobic bacteria, yeast and mold, and germination rate were determined. On the other hand, EO water with ACC of 30 and 50 mg/L was applied to spray sprouts during seed sprouting and the antimicrobial efficacy of EO water, as well as length, gross weight and dry weight of sprout were evaluated. The results showed that the population of natural microbiota decreased with increasing ACC of EO water, while no significant difference was observed among EO waters with different pH levels that were applied while soaking the seeds. EO water with higher ACC and lower pH slightly reduced the germination percentage of radish seed during seed soaking. EO waters with ACC of 30 and 50 mg/L sprayed during seed sprouting resulted in 1.39 and 1.58 log reductions of total aerobic bacteria, yeast and mold, respectively, and improved the length, gross weight and dry weight of the sprouts. Therefore, EO water with low ACC and near neutral pH could be used to soak seeds and water sprouts throughout seed germination and sprouting to control the population of natural microbiota on seeds and sprouts.

A novel triple reasserted H1N2 virus A/swine/Shanghai/1/2007 (SH07) was isolated from nasal swabs of weaned pig showing clinical symptoms of coughing and sneezing. To explore the virus characteristics, mice, chickens and pigs were selected for pathogenicity study. Pigs inoculated intranasally with 10(6) TCID50 SH07 showed clinical symptoms with coughing and sneezing, but no death. The virus nuclear acid was detected in many tissues using real-time PCR, which was mainly distributed in respiratory system particularly in the lungs. The virus was low-pathogenic to chickens with 10(6) TCID50 dose inoculation either via intramuscular or intranasal routes. However virus nuclear acid detection and virus isolation confirmed that the virus can also be found in nasal and rectum. When virus was inoculated into mice by intramuscular or intranasal routes we observed 100% and 80% lethality respectively. The third generation of samples passaged on MDCK cell were SIV positive in indirect immunofluorescence assay (IFA) using antiserum against H1N2 SIV. Furthermore, the lungs of mice showed obvious lesion with interstitial pneumonia. Data in our study suggest that SH07 is preferentially pathogenic to mammals rather than birds although it is a reasserting virus with the fragments from swine, human and avian origin.

Background OSA is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first-line treatment for OSA, as well as for obesity hypoventilation syndrome (OHS), its most severe phenotype. However, the molecular and cellular mechanisms underlying OHS-induced morbidities and their response to PAP treatment remain unclear, and could be mediated, in part, by OSA-induced epigenetic changes. Methods Blood was collected before starting PAP treatment (PRE group), as well as 6 weeks after PAP treatment (POST group) in 15 adult patients with OHS. DNA methylation profiles were studied by methylated DNA immunoprecipitation coupled to microarrays (MeDIP-chip) in six representative patients and further verified in a cohort of 15 patients by MeDIP-quantitative PCR. Results We identified 1,847 regions showing significant differential DNA methylation ( P 4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPARs). Single-locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR-responsive elements (PPAREs) of eight genes in the post-treatment samples (PRE/POST fold changes: ABCA1 , 3.11; ABCG1 , 1.72; CD36 , 5.04; FABP4 , 2.49; HMOX , 2.74; NOS2 , 7.78; PEPCK , 9.27; and ADIPOQ , 1.73), suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPAR-γ complex and downstream gene expression. Conclusions Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in patients with OHS who are responsive to PAP treatment.

In this study, polyaniline (PANI) and different mass ratios of PANI/glass flake (PANI–GF, PGF) composites were prepared via in situ oxidative polymerization. The chemical structure of the composites was investigated via Fourier transform infrared spectroscopy and X-ray diffraction. PANI, GF, and PGF composites were added as fillers into epoxy coating and then applied on a steel substrate. The corrosion resistance of the coatings was evaluated through electrochemical impedance spectroscopy and salt spray test. The coatings added with PANI, GF, and PGF composites displayed improved corrosion resistance. The greatest improvement in corrosion resistance was exhibited by the coating loaded with PGF composites at a PANI/GF mass ratio of 2:1. This enhancement was attributed to the passivation ability of PANI and the penetration resistance of the GF in the coating. Moreover, PANI was coated uniformly on the GF surface, and the composites were uniformly dispersed in the epoxy resin.

A series of In and B co-doped TiO 2 samples are prepared by sol–gel method under different pH values. The detailed existing states of introduced In and B ions are investigated via XRD, FT-IR, XPS and HRTEM. It is found that the B ions are mainly doped into TiO 2 in interstitial mode and In ions exist as surface O-In-Cl x species when the pH values are in the range of 0.31∼0.65. With the increase of the pH values (0.82∼3.40), the introduced In and B ions would react with each other to form InBO 3 . The existing states of In and B ions in TiO 2 can be easily changed by adjusting the pH values to achieve a new type of TiO 2 based materials with controlled structures.

This study discussed the effects of different bacterial concentrations and centrifugations on the antimicrobial efficacy of electrolyzed oxidizing (EO) water on Bacillus subtilis and Escherichia coli O157:H7. Overnight grown bacterial cultures were centrifuged 1 to 3 times and bacterial concentrations were adjusted to approximately 9 (high), 7 (medium), or 5 (low) log10 CFU/mL. Antimicrobial efficacy of acidic EO water (AEW) and neutral pH EO water (NEW) containing 0.25–30 mg/L available chlorine was determined. In order to ascertain the effects of AEW and NEW on targeted pathogens, cellular properties at bio-molecular levels were also studied. The results showed that the susceptibility of both pathogens decreased significantly with increasing bacterial concentrations. AEW with 10, 0.25 and 0.25 mg/L and NEW with 30, 0.5 and 0.25 mg/L available chlorine were needed for high, medium and low bacterial concentrations, respectively to non-detectable levels by direct plating for E. coli O157:H7. B. subtilis was found more resistant to both EO water treatments and only 4.1 and 3.8 log reductions were achieved for AEW and NEW containing 30 mg/L available chlorine. On the other hand, it was observed that as centrifugation time increased, both bacteria became significantly more sensitive to EO water treatments. When centrifugation period increased from 1 to 3 times, additional 2.67 and 3.38 log E. coli O157:H7 reductions were observed for AEW and NEW treatments, respectively. A similar trend was observed for B. subtilis. DNA and protein leakage increased when pathogens were treated by AEW and NEW with increasing available chlorine concentration, but decreased DNA and protein leakage were observed with increased centrifugation times. These results indicate that initial bacterial concentration and the centrifugation time are two important factors and should be carefully considered in chlorine-based antimicrobial efficacy testing.

Spores of some Bacillus species are responsible for food spoilage and foodborne disease. These spores are highly resistant to various interventions and cooking processes. In this study, the sporicidal efficacy of acidic electrolyzed oxidizing (EO) water (AEW) and slightly acidic EO water (SAEW) with available chlorine concentration (ACC) of 40, 60, 80, 100, and 120 mg/L and treatment time for 1, 2, 3, 4, 5, and 6 min were tested on Bacillus subtilis and Bacillus cereus spores in suspension and on carrier with or without organics. The reduction of spore significantly increased with increasing ACC and treatment time (P 6 log reductions of B. subtilis spore. Both types of EO water with ACC of 60 mg/L and 6 min treatment achieved a reduction of B. subtilis and B. cereus spores to nondetectable level. EO water with ACC of 80 mg/L and treatment time of 3 min on carrier test without organics addition resulted in reductions of B. subtilis spore to nondetectable level. But, addition of 0.3% organics on carrier decreased the inactivation effect of EO water. This study indicated that EO water was highly effective in inactivation of B. subtilis and B. cereus spores in suspension or on carrier, and therefore, rendered it as a promising disinfectant to be applied in food industry.

In this work, 3D hierarchical flower-like MoS 2 spheres are successfully fabricated via a hydrothermal method followed by a heat treatment. The obtained product is composed of few-layered MoS 2 nanosheets with enlarged interlayer distance (ca. 0.66 nm) of the (002) plane. Meanwhile, the hydrogen storage properties of the as-prepared MoS 2 ball milled with LiBH 4 are systematically investigated. The results of temperature programmed desorption (TPD) and isothermal measurement suggest that the LiBH 4 –MoS 2 (as-prepared) mixture exhibits favorable dehydrogenation properties in both lowering the hydrogen release temperature and improving kinetics of hydrogen release rate. LiBH 4 –MoS 2 (as-prepared) sample (the preparation mass ratio is 1:1) starts to release hydrogen at 171 °C, and roughly 5.6 wt% hydrogen is released within 1 h when isothermally heated to 320 °C, which presents superior dehydrogenation performance compared to that of the bulk LiBH 4 . The excellent dehydrogenation performance of the LiBH 4 –MoS 2 (as-prepared) mixture may be attributed to the high active site density and enlarged interlayer distance of the MoS 2 nanosheets, 3D architectures and hierarchical structures.

To construct effective interfacial interactions between graphene-based flame retardants and epoxy resin (EP) matrixes, reactive cyclophosphazene was chemically synthesized with amino groups and grafted on graphene oxide (GO) to prepare a flame-retardant fGO nanosheets for EP nanocomposites. The obtained fGO presented good compatibility and endowed the composites with improved thermal stability and dynamic mechanical properties. With a low content of 1.0 wt.% fGO added, the EP nanocomposites exhibited distinctly lowered the peak of heat release rate, total heat release, and total smoke production by 49.0%, 21.1%, and 51.9%. Compact char residue layers and suppressed volatile products indicated the formation of protective char structures derived from fGO nanofillers. The flame-retardant mechanisms were investigated and ascribed to the effects in condensed and gas phases from phosphazene modified graphene components.

SUMMARY Dendritic cells (DCs) orchestrate the initiation, programming, and regulation of anti-tumor immune responses. Emerging evidence indicates that the tumor microenvironment (TME) induces immune dysfunctional tumor-infiltrating DCs (TIDCs), characterized with both increased intracellular lipid content and mitochondrial respiration. The underlying mechanism, however, remains largely unclear. Here, we report that fatty acid-carrying tumor-derived exosomes (TDEs) induce immune dysfunctional DCs to promote immune evasion. Mechanistically, peroxisome proliferator activated receptor (PPAR) α responds to the fatty acids delivered by TDEs, resulting in excess lipid droplet biogenesis and enhanced fatty acid oxidation (FAO), culminating in a metabolic shift toward mitochondrial oxidative phosphorylation, which drives DC immune dysfunction. Genetic depletion or pharmacologic inhibition of PPARα effectively attenuates TDE-induced DC-based immune dysfunction and enhances the efficacy of immunotherapy. This work uncovers a role for TDE-mediated immune modulation in DCs and reveals that PPARα lies at the center of metabolic-immune regulation of DCs, suggesting a potential immunotherapeutic target., Graphical Abstract, In Brief Yin et al. reveal that tumor-derived exosomes (TDEs), as fatty acid carriers, induce a metabolic shift toward oxidative phosphorylation, driving DC immune dysfunction. Transcriptomic analysis identifies PPARα as the fatty acid sensor mediating the immunosuppressive effects of TDEs on DCs. PPARα blockade effectively restores DC function and enhances the efficacy of immunotherapy.

Ethnopharmacological relevance Euonymus alatus (Thunb.) Siebold (E. alatus), a well-known medicinal plant, has been widely used thousands of years in China for the treatment of various diseases such as urticaria, dysmenorrhea, wound, dysentery, blood stasis, rheumatism and arthritis. Due to the extensive application of E. alatus in the fields of ethnopharmacological usage, the pharmaceutical researches of E. alatus keeps deepening. Aim of the study This paper reviewed and summarized the integrated research progress of this medicinal plant. A comprehensive summary and comparison of traditional usages, botany, phytochemistry, pharmacology, toxicology, separation and analysis technologies of the E. alatus highlight recent scientific advances, which provides new insights into the research and development of this medicinal plant and would be helpful to promote the research situation of underlying pharmacological mechanisms and further utilizations of E. alatus. Material and methods Literature survey was carried out via classic books of herbal medicine, PhD. and MSc. Dissertations. Online scientific databases including Pubmed, SciFinder, Science Direct, Scopus, the Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI) and others were searched up to February 2020 to identify eligible studies. All literatures of the research subject are analyzed and summarized in this review. Results The E. alatus has been widely used in traditional practice in China, Korea and other Asian Countries. In the study of phytochemistry, more than 230 chemical constituents have been isolated and identified from E. alatus, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, phenylpropanoids, lignans, steroids, alkaloids and other compounds. Among them, literature reports show that flavonoids and steroids are the most important bioactive substances found in this plant. A number of researches also have shown that extracts and compounds from E. alatus exert a wide spectrum of pharmacological effects, including antidiabetic effect, anti-tumor effects, anti-inflammatory effects, hepatoprotective effects, antioxidant effects, antibacterial effects, as well as other effects. However, most of the studies without clinical research. Research into plant's toxicological effects has also been limited. In addition, this review also summarizes and compares the separation and analysis technologies of E. alatus. Conclusions E. alatus has potential for the treatment of many diseases, especially tumors and diabetes. But many traditional uses of E. alatus have not been validated by current investigations. Additionally, modern studies haven't gone far enough into its pharmacological effects and the corresponding chemical constituents, more efforts should be made to illuminate the underlying mechanisms of E. alatus for treatment of tumors and diabetes. Moreover, the toxicological effects of this plant can be further studied. Currently, there are limited studies on its side effects and toxicological effects, which should provide further guidance for the safety of clinical use.

To explore the composition characteristics of atmospheric fine particulate matter (PM2.5) and bronchoalveolar lavage fluid (BALF), and their impact on the development of chronic obstructive pulmonary disease (COPD).The atmospheric PM2.5 samples and BALF samples from COPD patients were collected from June 2, 2017 to October 30, 2018, and allocated into a high-risk of PM2.5 inhalation group and a low-risk PM2.5 inhalation group according to the heating season in Harbin. Inorganic elements were detected by ICP-MS, and polycyclic aromatic hydrocarbons (PAHs) were detected by GC/MS.Twenty-six inorganic elements were found in 54 BALF specimens. There was a high correspondence in inorganic elements between BALF and atmospheric PM2.5. Trace elements Cr, Mn, V, and Co, and toxic trace elements Al, Pb, Cd, As, and Ag were above the upper limit of normal blood. There were significant higher K, Ti, Fe, Co, Cu, Se, Rb, Ag, and Sb in BALF of the high-risk PM2.5 inhalation group (p 0.05). Sixteen PAHs were detected in 32 BALF samples. The main components of BALF and atmospheric PM2.5 were the high molecular weight PAHs, and the species and concentration of PAHs in BALF and atmospheric PM2.5 are highly consistent.The types and concentrations of inorganic elements and PAHs in BALF of COPD patients are highly consistent with those of atmospheric PM2.5. The sustained high concentrations of Benzo(a)anthracene, Chrysene, Benzo(b)Fluoranthene, Benzo(k)Fluoranthene, Indeno(123-c,d)Pyrene, and Benzo(a)Pyrene in BALF of COPD patients may have long-term adverse effects on COPD patients.

Induced resistance after anticancer agent treatment is the main reason for cancer relapse and short median survival of patients. Here we employed in vivo and in vitro approaches to establish and optimize a drug-resistant platform based on patient-derived xenografts (PDXs). PDXs derived from lung cancer patients who acquired drug resistance reproduced the insensitivity to standard target therapies in mice. Alternatively, resistance was induced in established PDX by continuously exposing with dosage increasing, which demonstrated the induced response declining after the treatment of one second-line therapy drug (Irinotecan). These drug resistant models were additionally confirmed by the in vitro 3D cell based assay, which mimicked the precise histologic structure and cellular composition of the corresponding patient samples. These results from in vivo and in vitro studies displayed good correlation, suggesting that this platform of PDXs and 3D cell based assay can be applied to preclinical development, mechanism research and new drug screen to overcome treatment resistance and have the potential for application to personalized medicine programs. Citation Format: Xiaoying Zhuang, Nan Xie, Lei Jin, Wengang Zeng, Yuhui Zheng, Chunling Zhang, Liping Cai, Hanmei Sun, Jie Xu, Wenjie Gao, Qunsheng Ji. Establishment and optimization of a drug-resistant PDX-based platform using in vivo and in vitro approaches [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2814.

Enzyme modified non-oxidative LDL (ELDL) is effectively taken up by vascular smooth muscle cells (SMC) and mediates transition into foam cells and produces phenotypic changes in SMC function. Our data show that incubation of human coronary artery SMC (HCASMC) with low concentration of ELDL (10 μg/ml) results in significantly enhanced foam cell formation compared to oxidized LDL (200 μg/ml; p

The emergence of multidrug-resistant bacterial pathogens has severely threatened global health. A phage with the ability to efficiently and specifically lyse bacteria is considered an alternative for controlling multidrug-resistant bacterial pathogens. The discovery of novel agents for controlling the infections caused by K. pneumoniae is urgent due to the broad multidrug-resistance of K. pneumoniae. Only a few phage isolates have been reported to infect multidrug-resistant K. pneumoniae. In this study, by using the multidrug-resistant K. pneumoniae strain as an indicator, a novel phage called vB_KleS-HSE3, which maintains high antibacterial activity and high physical stability, was isolated from hospital sewage. This phage infected one of four tested multidrug-resistant K. pneumoniae strains. This phage belongs to the Siphoviridae family and a comparative genomic analysis showed that this phage is part of a novel phage lineage among the Siphoviridae family of phages that infect strains of Klebsiella. Based on its features, the vB_KleS-HSE3 phage has potential for controlling infections caused by multidrug-resistant K. pneumoniae.

Epoxy resin (EP) composites with improved flame retardancy were fabricated. To solve the problem of the large addition of phosphazene flame retardants, we designed a system based on phosphorus–nitrogen–silicon synergistic flame-retardant Si(H) microcapsules with silica as the shell and hexaphenoxycyclotriphosphazene as the core. Si(H)/EP composites were manufactured with two coupling agents to promote interactions. In cone calorimetric tests, heat and gas releases of Si(H)/EP composites were reduced, and fire hazard was minimized. Residual analysis indicated the strong rigidity and mechanical robustness. The mechanism included phosphorus quenching effect and nitrogenous diluting effect of flame inhibition effect in gas phase, and phosphorus charring effect and silicic barrier and protective effect in solid phase. This research provides an effective flame-retardant method for EP composites with a low additive content.

Objective:To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma.Patients and methods:Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m2and oxaliplatin 85 mg/m2on day 1, and oral S-1 40 mg/m2twice daily on days 1–14, repeating the regimen every 21 days until one of the following occurred: disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021.Results:A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI): 2.83–5.88] and the median OS was 11.00 months (95% CI: 9.16–12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively. The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed.Conclusion:Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.

Functionalized graphene oxide sheets (FGO) with improved dispersive and smoke-suppressive properties were synthesized by covalently grafting octa (propyl glycidyl ether) polyhedral oligomeric silsesquioxane on graphene oxide sheets (GO) with γ-aminopropyl triethoxysilane as a chemical bridge. The good dispersion of FGO sheets in the epoxy resin (EP) matrix endowed EP composites with stable thermal resistance, enhanced tensile and smoke-suppressive properties. Cone calorimeter tests indicated that the addition of 0.7 wt% FGO sheets to EP composites reduced the peak of heat release rate, total heat release, and total smoke release by 49.7%, 34.3%, and 41.5%, respectively. Two important effects that originated from FGO promoted this improvement; that is, well-dispersed FGO sheets exhibited a tortuous effect by lengthening the heat path and inhibiting heat diffusion in the EP matrix, and the increase in char residue and the reduction in gas volatiles confirmed the barrier effect of FGO sheets by forming protective char structures on the surface of the matrix, which restrained smoke release. This method provided a feasible concept for effectively enhancing the flame retardancy of EP composites by combining the characteristics of graphene and polyhedral oligosilsesquioxane through the construction of effective interfacial interactions.

Using first-principles density functional theory calculations, we investigate the structural and electronic properties of layer number (n) dependent two-dimensional (2D) atomically thick (100) diamond nanofilms related to surface functionalization of hydrogen and fluorine. The nanofilms with functionalized surface are dynamically and thermally stable demonstrated by phonon dispersion curves and ab initio molecular dynamics simulations. The band gaps of semi-functionalized nanofilms are in the region of 2.41–2.65 eV almost unchanged related to n or surface functionalization, contributed by the electronic feature of the unfunctionalized side. For the cases of full-functionalization on both sides of the nanofilms, the band gaps are larger than that for the semi-functionalized 2D nanofilms. These band gaps decrease following a nonlinear inverse law of n, attributed to a quantum confinement effect. The fluorine-functionalized nanofilms present the larger band gaps with respect to the cases of hydrogen-functionalization. Moreover, the absorption spectra of these 2D nanofilms show an absorption edge at around 2.8 eV for semi-functionalized and upon 4.8 eV for full-functionalized nanofilms. Based on the theoretical results, the proposed nanofilms can inspire more efforts in practical applications and fabricating low-dimensional diamond-based optoelectronics devices.

Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet. A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol. We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p

Dendritic cells (DCs), a type of professional antigen-presenting cells, play a key role in orchestrating anti-tumor immune responses. In the tumor microenvironment, tumor infiltrating DCs (TIDCs) present tumor associated antigens to effector T cells and facilitate the induction of memory T cells to prevent tumor recurrence. However, emerging evidences indicate that TIDCs become immunosuppressive with a high intracellular lipid content phenotype. TIDCs with abnormal lipid accumulation are associated with endoplasmic reticulum (ER) stress responses or increased fatty acid oxidation which also contribute to immunosuppressive. However, the critical factor inducing lipid-laden immunosuppressive TIDCs remains to be determined. Here we report: (a) In vitro, tumor derived exosomes (TDEs), isolated from tumor culture medium can directly induce lipid accumulation in DCs rather than TDE-free tumor culture medium. In vivo, we generate GFP-CD9-tumor cells to trace the receiver cells of GFP-labeled TDEs in the tumor microenvironment. The results show that TIDCs capture GFP-labeled TDEs and become lipid abundant. By treating DCs with TDEs from different tumor cell lines and of different concentrations or time, we observe that TDE-induced lipid accumulation in DCs is tumor-origin independent but time and concentration dependent. Collectively, we can conclude that TDEs are responsible for the intracellular lipid accumulation in DCs. (b) Upon internalization of TDEs, increased expression of genes involved in lipid accumulation and higher mitochondrial respiration are observed in DCs, which results in lower ability to prime tumor-specific T cell responses. (c) Then, we demonstrate that the fatty acids contained in TDEs directly contribute to lipid laden DC, rather than proteins or nucleic acids. Moreover, we identify PPARα as the key player in orchestrating both lipid metabolism and immunological features of DCs. (d) PPARα initiates both de novo lipid synthesis and fatty acids β-oxidation in DCs by sensing the excess fatty acids, which leads to immunosuppression in DCs. Pharmacological inhibitor of PPARα can overcome TDE-induced lipid accumulation, fatty acids β-oxidation and immunosuppressive function in DCs. (e) Combination therapy of PPARα pharmacological inhibitor and immunotherapy (such as the check point blocker or the therapeutic cancer vaccine) shows superior anti-tumor efficacy over monotherapy. The present study unprecedentedly provides substantial evidences that TDEs can act as a major immunosuppressive component within tumor microenvironment to undermine the proper functions of TIDCs. More importantly, we demonstrate targeting PPARα could be a potential strategy to design novel immunotherapy combinations, in order to maximize the induction, expansion and cytotoxicity of tumor-specific CD8+ T cells by restoring TIDCs function. Citation Format: Xiaozhe Yin, Wenfeng Zeng, Bowen Wu, Zihao Wang, Hongjian Tian, Luyao Wang, Luoyang Wang, Xiuli Wei, Yan Qin, Fayun Zhang, Chunling Zhang, Lingtao Jin, Wei Liang. Tumor derived exosomal lipids-induced dendritic cell immunosuppression by PPARα [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C109. doi:10.1158/1535-7163.TARG-19-C109

LncRNAs play significant roles in various cell biological processes. In the present study, we demonstrated that PICART1 expression was down-regulated in non-small cell lung cancer (NSCLC) tissues. Lower expression level of PICART1 was associated with advanced stage. In addition, PICART1 expression was down-regulated in NSCLC cell lines. Overexpression of PICART1 inhibited NSCLC cell growth and induced cell cycle arrest at G2/M phase. Elevated expression of PICART1 suppressed NSCLC cell colony formation and cell invasion. Ectopic expression of PICART1 promoted the expression of epithelial marker E-cadherin while suppressed the mesenchymal marker expression such as N-cadherin and Snail and Vimentin. Furthermore, PICART1 overexpression suppressed AKT phosphorylation and c-Myc expression while inhibited the p21 expression in NSCLC cell. AKT phosphorylation was involved in PICART1 mediated suppression of cell growth and invasion. These results suggested that overexpression of PICART1 suppressed cell growth and invasion partly through regulating AKT signaling pathway in NSCLC.

To explore the porcine epidemic diarrhea virus(PEDV)epidemiology in domestic pigs, virus isolation and identification were carried out in pig herds in Shanghai and Jiangsu province. Based on sequences of PEDV strains in GenBank, a pair of primers targeting the M gene were designed for PEDV detection. Two clinical pig diarrhea samples were amplified and sequencing results confirmed that the fragments amplified were M gene. PEDV-positive samples were inoculated in Vero cells with different concentrations of trypsin. Our results showed that these two isolates could proliferate effectively in Vero cells with a specific concentration of trypsin. Twenty-second passages viruses were added to the feeding of newborn piglets, and animal regression test showed obvious clinical symptoms of diarrhea, confirming the the PEDV isolates, named as JSLS/PEDV/1/2014 and JS/PEDV/2/2014,were successfully obtained. Phylogenetic analysis of the M genes showed that JSLS/PEDV/1/2014 and JS/PEDV/2/2014 displayed the greatest similarity with the Chinese strains HLJ-2012 and BJ-2012-1,respectively.The S genes of the two isolates were classified in group I. There were 51 bases deletion in the ORF3 genes of these two isolates which were located in the same big branch with the DR13 strain rather than the CV777 strain.

With the raise of environmental protection awareness, applying models to control NPS (non-point source) pollution has become a key approach for environmental protection and pollution prevention and control in China. In this study, we implanted the semi-conceptual model SWAT (Soil and Water Assessment Tool) using information on rainfall runoff, land use, soil and slope. The model was used to quantify the spatial loading of NPS nutrient total nitrogen (TN) and total phosphorus (TP) to the Huntai River Watershed (HTRW) under two scenarios: without and with projected buffer zones of approximately 1 km within both banks of the Huntai, Taizi and Daliao river trunk streams and 5 km around the reservoirs. Current land-use types within the buffer zone were varied to indicate the natural ecology and environment. The Nash–Sutcliffe efficiency coefficient (ENS) and R2 for flow and predicted nutrient concentrations (TN and TP) in a typical hydrological station were both greater than 0.6, and the relative deviation (|Dv|) was less than 20 %. Under the status quo scenario (SQS), the simulated soil erosion in the HTRW per year was 811 kg/ha, and the output loadings of TN and TP were 19 and 7 kg/ha, respectively. The maximum loadings for TN and TP were 365 and 260 kg/ha, respectively. Under environmental protection scenarios (EPS), the TN and TP pollutant loadings per unit area were reduced by 26 % and 14 % annually, respectively. Loading analysis showed that land-use type is a key factor controlling NPS pollution. The NPS pollutant loading decreased under the simulated EPS, indicating that environmental protection measures may reduce the NPS pollutant loading in HTRW. The 22 % pollutant reduction under the EPS. We finally quantified the ratio of the land area lost to agricultural production compared with that lost to ecosystem services. We calculated the agricultural yield elasticity and concluded that the corresponding crop yield would be reduced by 2 % when the land area for ecosystem services in the basin increased by 1 % under the EPS.

The key to arthritis management is early diagnosis and treatment to prevent further joint destruction and maximize functional ability. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis that the primary care provider must differentiate, in terms of diagnosis and treatment. Effective and non-invasive strategies for early detection and disease identification are sorely needed. Growing evidence suggests that RA has a correlation with oral microbiome and may be affected by its dynamic variations. There is already a study comparing oral microbiome in patients with RA and OA, however, it did not screen for potential biomarkers for arthritis. In this study, we assessed the oral microbiome in saliva samples from 110 RA patients, 67 OA patients and 155 healthy subjects, using 16S rRNA gene amplicon sequencing. The structure and differences in oral microbiome between RA, OA and healthy subjects were analyzed. Eight oral bacterial biomarkers were identified to differentiate RA from OA. This report provides proof of oral microbiota as an informative source for discovering non-invasive biomarkers for arthritis screening.

N,N'-Bis(4-n-alkyloxybenzoyl)hydrazine (4D16) was demonstrated to show three different aggregates, i.e. a crystalline cubic phase and two kinds of lamellar structure with layer spacings of 34.20 A (termed the L1 structure) and 40.85 A (L2 structure) depending on the type of solvents. Lamellar (L1)-crystalline cubic transition during heating was confirmed for 4D16 showing the L1 structure. 4D16 organogels in cyclohexane and benzene exhibited either a mixture of the L1 structure and the crystalline cubic phase or only one of the two structures. 4D16 gels prepared at a higher concentration or a lower incubation temperature consisted of more lamellar L1 structures compared to those obtained at a lower concentration or a higher incubation temperature. Annealing of the as-prepared 4D16 gels at certain temperatures for different time periods caused gradual lamellar L1-cubic transition, and thus increased the content of the cubic phase in the gels, which showed lower Tgel compared to those of the as-prepared ones. The existence of the cubic phase in 4D16 gels in cyclohexane and benzene destabilized the gels.

Schizophrenia and bipolar disorder are complex psychiatric diseases with risks contributed by multiple genes. Dysregulation of gene expression has been implicated in these disorders, but little is known about such dysregulation in the human brain. We analyzed three transcriptome datasets from 394 postmortem brain tissue samples from patients with schizophrenia or bipolar disorder or from healthy control individuals without a known history of psychiatric disease. We built genome-wide coexpression networks that included microRNAs (miRNAs). We identified a coexpression network module that was differentially expressed in the brain tissue from patients compared to healthy control individuals. This module contained genes that were principally involved in glial and neural cell genesis and glial cell differentiation, and included schizophrenia risk genes carrying rare variants. This module included five miRNAs and 545 mRNAs, with six transcription factors serving as hub genes in this module. We found that the most connected transcription factor gene POU3F2, also identified on a genome-wide association study for bipolar disorder, could regulate the miRNA hsa-miR-320e and other putative target mRNAs. These regulatory relationships were replicated using PsychENCODE/BrainGVEX datasets and validated by knockdown and overexpression experiments in SH-SY5Y cells and human neural progenitor cells in vitro. Thus, we identified a brain gene expression module that was enriched for rare coding variants in genes associated with schizophrenia and that contained the putative bipolar disorder risk gene POU3F2 The transcription factor POU3F2 may be a key regulator of gene expression in this disease-associated gene coexpression module.

Radiation-induced lung injury (RILI) is the main complication of radiotherapy for thoracic malignancies. Since naringenin, a potent immune-modulator, has been found to relieve bleomycin-induced lung fibrosis by restoring the balance of disordered cytokines, we sought to determine whether naringenin would mitigate RILI and to investigate the underlying mechanism. Animals received fractionated irradiation in the thoracic area to induce RILI. Enzyme-linked immunosorbent assay and MILLIPLEX assays were used for serum and bronchoalveolar lavage fluid for cytokine analyses, hematoxylin and eosin staining for pathologic changes, and Masson trichrome staining for determination of lung fibrosis. Interleukin (IL)-1

We quantitatively demonstrate transient establishment of wavefronts for negative, zero, and positive refraction through a wedge-shaped metamaterial consisting of periodically arranged split-ring resonators and metallic wires. The wavefronts for the three types of refractions propagate through the second interface of the wedge along positive refraction angles at first, then reorganize, and finally propagate along the effective refraction angles after a period of establishment time respectively. The establishment time of the wavefronts prevents violating causality or superluminal propagation for negative and zero refraction. The establishment time for negative or zero refraction is longer than that for positive refraction. For all three refraction processes, transient establishment processes precede the establishment of steady propagation. Moreover, some detailed characters are proven in our research, including infinite wavelength, uniform phase inside the zero-index material, and the phase velocity being antiparallel to the group velocity in the negative-index material.

Poly(N-isopropylacrylamide) (PNIPAM) is a widely-studied polymers due to its excellent temperature sensitivity. PNIPAM-MAPOSS hybrid hydrogel, based on the introduction of acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) into the PNIPAM matrix in the presence of polyethylene glycol, was prepared via radical polymerization. The modified hydrogels exhibited a thick, heterogeneous porous structure. PEG was used as a pore-forming agent to adjust the pore size. MAPOSS reduced the swelling ratios of gels, and decreased the LCST, causing the hydrogels to shrink at lower temperatures. However, its hydrophobicity helped to improve the temperature response rate. The incorporation of rigid MAPOSS into the polymer network greatly increased the compressive modulus of the hydrogel. It is worth noting that, by adjusting the amount of MAPOSS and PEG, the hydrogel could have both ideal mechanical properties and swelling behavior. In addition, hydrogel containing 8.33 wt % MAPOSS could achieve stable and sustained drug release. Thus, the prepared PNIPAM-MAPOSS hybrid hydrogel can serve as drug carrier for 5-fluorouracil and may have potential application in other biomedical fields.

Purpose. To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods. Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS). After resistance to osimertinib treatment, tumor tissue was collected by core needle biopsy. DNA was extracted from 15 × 5 um sliced section of formalin-fixed paraffin-embedded (FFPE) material and NGS was done. The genetic changes were analyzed. Results. A total of 9 Chinese patients were studied, 5 females and 4 males, age 51–89 years. After progression with osimertinib treatment, core needle biopsy was performed and next-generation sequencing was performed. Nine patients had harboring 62 point mutations, 2 altered gene copies, 2 amplifications, and 1 EML4-ALK gene fusion. No MET or HER2 amplification was found in this cohort study. Nine patients still maintained initial EGFR 19 del or L858R activating mutations, while 7 of them kept EGFR T790M mutations. Among the 7 patients, 5 had secondary EGFR C797S and/or C797G mutations, which all happened in the same allele with T790M mutation. All patients were treated with targets therapies, chemotherapy, or best supportive care (BSC) in accordance with NGS genetic results and patients’ performance status; 7 of them are still alive and 2 of them died of disease progression at last follow-up. Conclusions. EGFR C797S/G mutation and the same one presented on the same allele with EGFR T790M mutation were the most common mutation feature and played a key role in resistance to osimertinib in Chinese patients with NSCLC. Tumor cells losing T790M mutation and maintaining EGFR activating mutation might benefit from first-generation EGFR-TKI treatment.

In this study, the mechanism of ferrite grain refinement during warm compression deformation in the (γ + α) region of Cu–P–Cr–Ni–Mo weathering steel was analyzed by optical microscopy and electron backscatter diffraction. Results showed that fine equiaxed ferrite grains surrounded by high-angle boundaries (HABs) formed along the initial boundaries as the strain is increased. As the deformation temperature decreased, some low-angle boundaries shifted to HABs in intragranular ferrite, and ferrite grain refinement was promoted by continuous dynamic recrystallization. Microstructural observations also indicated that the fine ferrite grains of approximately 1.4–3 µm in size can be obtained by deformation at 750 °C with a strain over 0.69 because of ferrite dynamic recrystallization. Moreover, both strain and deformation temperature influenced the ferrite grain size and volume fraction. Thus, the predominant mechanism for ferrite grain refinement in the (γ + α) region was continuous dynamic recrystallization.