NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

cGAS regulates the DNA damage response to maintain proliferative signaling in gastric cancer cells

The activation of some oncogenes promote cancer cell proliferation and growth,facilitate cancer progression and metastasis by induce DNA replication stress,even genome instability.Activation of the cyclic GMP-AMP synthase(cGAS)mediates classical DNA sensing,is involved in genome instability,and is linked to various tumor development or therapy.However,the function of cGAS in gastric cancer remains elusive.In this study,the TCGA database and retrospective immunohistochemical analyses revealed substantially high cGAS expression in gastric cancer tissues and cell lines.By employing cGAS high-expression gastric cancer cell lines,including AGS and MKN45,ectopic silencing of cGAS caused a significant reduction in the proliferation of the cells,tumor growth,and mass in xenograft mice.Mechanistically,database analysis predicted a possible involvement of cGAS in the DNA damage response(DDR),further data through cells revealed protein interactions of the cGAS and MRE11-RAD50-NBN(MRN)complex,which activated cell cycle checkpoints,even increased genome instability in gastric cancer cells,thereby contributing to gastric cancer progression and sensitivity to treatment with DNA damaging agents.Furthermore,the upregulation of cGAS significantly exacerbated the prognosis of gastric cancer patients while improving radiotherapeutic outcomes.Therefore,we concluded that cGAS is involved in gastric cancer progression by fueling genome instability,implying that intervening in the cGAS pathway could be a practicable therapeutic approach for gastric cancer.

A Survey of Chinese Secondary Student Perceptions of Affective Edu­cation

This article made an analysis of student opinions on affective education in secondary school in China.The purpose is to point out the obvious and potential problems as to affective education and contribute to improvement.The principal instrument was a questionnaire developed by the author.Semi-structured questionnaire was carried out in Zibo city--110 students in two secondary schools have participated in this small-scale research.In this research,a lot of cases have shown that the school and teachers still paid much attention to the academic development and affective education is basically‘blind area’.The suggestions for improvement were discussed.

Should Pastoral Care and PSE be Mainly Concerned with the Support of Achievement?

Pastoral care is being given more attention than in the past from schools and education authorities.Pastoral care can be seen as an aspect of affective education that aims to promote the personal and social development of students.This article will explore the relationship between pastoral care,PSE and students’achievement,and how achievement is promoted by pastoral care and PSE.In order to achieve the best,possible suggestions will be given in this article.

Research on a Pulse Interference Filter Used for the Fiber Bragg Grating Interrogation System

In this paper, a novel pulse interference filter for fiber Bragg grating （FBG） interrogation based on the tunable Fabry-Perot （F-P） filtering principle is proposed and experimentally demonstrated. The self-developed FBG interrogation system is devised for the aircraft health management of key structures. Nevertheless, the pulse interference is detected in the reflection spectrum of FBG causing interrogation system unstable. To address the problem, the first-order lag pulse broadening filter is proposed in this paper. The first-order lag filter is applied to preprocess and smooth the original signal, meanwhile enhancing the signal-to-noise ratio （SNR）. Afterwards, peaks of reflection spectrum are distinguished with pulse interference by pulse broadening. Experimental results indicate that 634 peaks are detected before adopting the first-order lag pulse broadening filter. Comparatively, the number of peaks decreases to 203 after filtering the interference pulse, and the correct rate of peak detection is higher than 98.5%. Through the comparison with the finite impulse response （FIR） filter, the advantage of first-order lag filter is proved. The vibration monitoring experiment demonstrates that this system has high dynamic precision with a dynamic interrogation range of 0Hz-400Hz, and the maximum repetition rate of 800Hz.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin(IL)-17A,a pro-inflammatory cytokine,is a fundamental function in the onset and advancement of multiple immune diseases.To uncover the primary compounds with IL-17A inhibitory activity,a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions.Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus,Myrothecium gramineum,showed remarkable IL-17A inhibitory activity.Nine new aureane-type sesquiterpene tetraketides,myrogramins A-I(1,4-11),and two known ones(2 and 3)were isolated and identified from the strain.Compounds 1,3,4,10,and 11 exhibited significant IL-17A inhibitory activity.Among them,compound 3,with a high fermentation yield dosedependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions.Strikingly,compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension.Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity,and hold great promise applications in treating IL-17A-mediated immune diseases.

Bombyx mori nucleopolyhedrovirus induces BmFABP1 downregulation to promote viral proliferation

Fatty acid binding proteins (FABPs) play an important role as endogenous cytoprotectants. However, studies on FABPs in invertebrates are scarce. Previously, we discovered Bombyx mori fatty acid binding protein 1 (BmFABP1) through co-immunoprecipitation. Here, we cloned and identified BmFABP1 from BmN cells. The results of immunofluorescence indicated that BmFABP1 was localized in the cytoplasm. The tissue expression profile of silkworms showed that BmFABP1 was expressed in all tissues except hemocytes. The expression level of BmFABP1 gradually decreases in BmN cells and B. mori larvae after infection with B. mori nucleopolyhedrovirus (BmNPV). Upregulation of BmFABP1 expression through overexpression or WY14643 treatment significantly inhibited the replication of BmNPV, while downregulation of BmFABP1 expression by RNA interference promoted the replication of BmNPV. The same results were obtained in experiments on silkworm larvae. These results suggest that BmNPV induces BmFABP1 downregulation to promote its proliferation and that BmFABP1 has a potential anti-BmNPV role. This is the first report on the antiviral effect of BmFABP1 in silkworms and provides new insights into the study of the FABP protein family. Also, it is important to study BmNPV resistance in silkworms to breed transgenic silkworms with BmNPV resistance.

Crystal structures of D-psicose 3-epimerase from Clostridium cellulolyticum H10 and its complex with ketohexose sugars

D-Psicose 3-epimerase(DPEase)is demonstrated to be useful in the bioproduction of D-psicose,a rare hexose sugar,from D-fructose,found plenty in nature.Clostridium cellulolyticum H10 has recently been identified as a DPEase that can epimerize D-fructose to yield D-psicose with a much higher conversion rate when compared with the conventionally used DTEase.In this study,the crystal structure of the C.cellulolyticum DPEase was determined.The enzyme assembles into a tetramer and each subunit shows a(β/α)8 TIM barrel fold with a Mn2+metal ion in the active site.Additional crystal structures of the enzyme in complex with substrates/products(D-psicose,D-fructose,D-tagatose and D-sorbose)were also determined.From the complex structures of C.cellulolyticum DPEase with D-psicose and D-fructose,the enzyme has much more interactions with D-psicose than D-fructose by forming more hydrogen bonds between the substrate and the active site residues.Accordingly,based on these ketohexosebound complex structures,a C3-O3 proton-exchange mechanism for the conversion between D-psicose and D-fructose is proposed here.These results provide a clear idea for the deprotonation/protonation roles of E150 and E244 in catalysis.

Effect of Unit Cell Shape on Switchable Infrared Metamaterial VO_(2)Absorbers/Emitters

Metamaterial absorber/emitter is an important aspect of infrared radiation manipulation.In this paper,we proposed four simple switchable infrared metamaterial absorbers/emitters with Ag/VO_(2)disks on the Ag plane employing triangle,square,hexagon,and circle unit cells.The spectral absorption peaks whose intensities are above 0.99 occur at~4μm after structure optimization when VO_(2)is in insulating state and disappear when VO_(2)becomes metallic state.The simulated electromagnetic field reveals that the spectral absorption peaks are attributed to the excitation of magnetic polariton within the insulating VO_(2)spacer layer,whose values exceed 1.59 orders of magnitude higher than the incident magnetic field.Longer resonant wavelength would be excited in square arrays because its configuration is a better carrier of charges at the same spans.For absorption stability,the absorbers/emitters with square and circular structures do not have any change with the polarization angles changing from 0°to 90°,due to the high rotational symmetric structure.And four absorbers/emitters reveal similar shifts and attenuations under different incident angles.We believed that the switchable absorber/emitter demonstrates promising applications in the sensing technology and adaptive infrared system.