We report the confirmation of a sub-Saturn-size exoplanet,TOI-1194 b,with a mass of about 0.456+0.055-0.051M_(J),and a very low mass companion star with a mass of about 96.5±1.5 MJ,TOI-1251 B.Exoplanet candidates...We report the confirmation of a sub-Saturn-size exoplanet,TOI-1194 b,with a mass of about 0.456+0.055-0.051M_(J),and a very low mass companion star with a mass of about 96.5±1.5 MJ,TOI-1251 B.Exoplanet candidates provided by the Transiting Exoplanet Survey Satellite(TESS)are suitable for further follow-up observations by ground-based telescopes with small and medium apertures.The analysis is performed based on data from several telescopes worldwide,including telescopes in the Sino-German multiband photometric campaign,which aimed at confirming TESS Objects of Interest(TOIs)using ground-based small-aperture and medium-aperture telescopes,especially for long-period targets.TOI-1194 b is confirmed based on the consistent periodic transit depths from the multiband photometric data.We measure an orbital period of 2.310644±0.000001 days,the radius is 0.767+0.045-0.041RJ and the amplitude of the RV curve is 69.4_(-7.3)^(+7.9)m s^(-1).TOI-1251 B is confirmed based on the multiband photometric and high-resolution spectroscopic data,whose orbital period is 5.963054+0.000002-0.000001days,radius is 0.947+0.035-0.033 R_(J) and amplitude of the RV curve is 9849_(-40)^(+42)ms^(-1).展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their produc...The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.展开更多
Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/th...Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/threonine kinase 11(STK11)mutant non-small cell lung cancer(NSCLC)through an axis inhibition protein 1(AXIN1)-dependent manner.However,the alterations of tumor metabolism and metabolites upon metformin administration remain unclear.Methods:We performed untargeted metabolomics using liquid chromatography(LC)-mass spectrometry(MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis.Results:According to the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database,most metabolites were annotated into metabolism,including nucleotide metabolism.Next,the differentially expressed metabolites in H460(refers to H460 cells),H460_met(refers to metformin-treated H460 cells),and H460_KO_met(refers to metformin-treated Axin1-/-H460 cells)were distributed into six clusters based on expression patterns.The clusters with a reversed expression pattern upon metformin treatment were selected for further analysis.We screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were upregulated.Furthermore,these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes(STING)pathway independently of AXIN1.Conclusion:Relying on AXIN1,metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC,indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC.展开更多
All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Pla...All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.展开更多
V0405 Dra is a W UMa-type binary star.Based on the TESS data,we have conducted an orbital period study and performed a light curve analysis for the system.The orbital period study reveals that the O-C curve for V0405 ...V0405 Dra is a W UMa-type binary star.Based on the TESS data,we have conducted an orbital period study and performed a light curve analysis for the system.The orbital period study reveals that the O-C curve for V0405 Dra exhibits secular decrease at an extremely high rate of d P/dt=-2.71×10^(-6)day year^(-1),along with periodic variations characterized by an amplitude of A_(3)=0.0032 day and a period of P_(3)=1.413 years.The orbital periodic change is possibly due to the light-travel time effect resulting from an additional third body in the system,for which we estimate a minimum mass of M_(3)=0.77M_(⊙).By employing the 2013 version of the Wilson-Devinney(W-D)method to synthesize a light curve,we derived photometric solutions indicating that V0405 Dra is a new deep(f=68.7%)and low-mass ratio(q=0.175)contact binary.The fast decrease in its orbital period is likely caused by mass transfer from the more massive primary star to the less massive secondary star,or due to angular momentum loss.With further mass transfer and loss of angular momentum,the binary will gradually evolve into a tighter contact configuration,eventually leading to a merger into a single star,following the evolutionary paths suggested for such deep and low mass ratio contact binaries.展开更多
BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression...BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered CAFs-associated gene signature,which can be employed to estimate BC patient outcomes conveniently and accurately.展开更多
Sodium borohydride(NaBH_(4)) is considered as the most potential hydrogen storage material for portable proton exchange membrane fuel cells(PEMFC)because of its high theoretical hydrogen capacity.However,the slow and ...Sodium borohydride(NaBH_(4)) is considered as the most potential hydrogen storage material for portable proton exchange membrane fuel cells(PEMFC)because of its high theoretical hydrogen capacity.However,the slow and poor kinetic stability of hydrogen generation from NaBH_(4) hydrolysis limits its application.There are two main factors influencing the kinetics stability of hydrogen generation from NaBH_(4).One factor is that the alkaline byproducts(NaBO_(2)) of the hydrolysis reaction can increase the pH of the solution,thus inhibiting the reaction process.It mainly happens in the NaBH_(4) solution hydrolysis system.Another factor is that the monotonous increase in reaction temperature leads to uncontrollable and unpredictable hydrolysis rates in the solid NaBH_(4) hydrolysis system.This is due to the excess heat generated from this exothermic reaction in the initial reaction of NaBH_(4) hydrolysis.In this perspective,we summarize the latest research progress in hydrogen generation from NaBH_(4) and emphasize the design principles of catalysts for hydrogen generation from NaBH_(4) solution and solid state NaBH_(4).The importance of carbon as catalyst support material for NaBH_(4) hydrolysis is also highlighted.展开更多
Ag nanoparticles (NPs) thin films with various thicknesses were prepared by thermal evaporation method. Atomic force microscopy (AFM) and UV-Vis spectrophotometer were used to study the surface morphology, growth natu...Ag nanoparticles (NPs) thin films with various thicknesses were prepared by thermal evaporation method. Atomic force microscopy (AFM) and UV-Vis spectrophotometer were used to study the surface morphology, growth nature and optical properties of the films. The results indicate that the growth rates of Ag particles in lateral and vertical direction are variable, and the dominant growth rate of Ag particles in lateral direction will convert into dominant growth rate in vertical direction as films grow thicker. The mean value and distribution of Ag NPs height related with the location and width of SPR (surface plasmonresonance) peak. Higher mean height shifts SPR peak to longer wavelengths, and smaller deviation results in narrower width of SPR peaks.展开更多
Background: Weanling pigs, with immature immune system and physiological function, usually experience postweaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth ...Background: Weanling pigs, with immature immune system and physiological function, usually experience postweaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth performance, diarrhea, and immunity of weaned pigs challenged with lipopolysaccharide(LPS).Methods: In Experiment(Exp.) 1,144 weaned piglets were weaned at 21 d and randomly assigned to six groups,with six replicates per group and four pigs per replicate, receiving a control diet(CON) or diet supplemented with antibiotics(AB) or C. butyricum(CB)(0.1%, 0.2%, 0.4%, or 0.8%), respectively. All diets in Exp. 1 were a highly digestible basal diet, with 3,000 mg/kg zinc oxide supplied in the first 2 wk only. In Exp. 2, 180 piglets were weaned at 21 d and randomly assigned to five groups, with six replicates per group and six pigs per replicate, receiving CON, AB, or CB(0.2%, 0.4%, or 0.6%) diets. The digestibility of diets was lower than those in Exp. 1, and did not include zinc oxide. At 36 d of Exp. 2, 12 piglets were selected from each of the CON and 0.4% CB groups, six piglets were intraperitoneally injected with LPS(50 μg/kg body weight) and the other six piglets with normal saline;animals were killed at 4 h after injection to collect blood, intestine, and digesta samples for biochemical analysis.Results: In Exp. 1, CB and AB diets had no effect on growth performance of piglets. In Exp. 2, 0.4% CB decreased feed-gain ratio(P < 0.1), diarrhea score(P < 0.05), and increased duodenal, jejunal, and ileal villus height and jejunal villus height/crypt depth(P < 0.05). The 0.4% CB decreased the plasma tumor necrosis factor(TNF) α(P < 0.05) but increased ileal mucosa IL-10 and TLR2 mRNA expression(P < 0.05). Furthermore, 0.4% CB altered the microbial profile, with Bacillus and Ruminococcaceae UGG-003 at genus level and Lactobacillus casei and Parasutterella secunda at species level were higher than CON in colonic content(P < 0.05).Conclusions: Dietary C. butyricum supplementation had positive effects on growth of weaned piglets with less digestible diets. There was a tendency to reduce the feed-gain ratio, which could reduce feed costs in pig production. Moreover, C. butyricum decreased post-weaning diarrhea by improving the intestinal morphology,intestinal microflora profile, and immune function.展开更多
Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upr...Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 (COX-2), 5-1ipoxygenase (5-LOX) and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.展开更多
Hydrogen has been widely considered as a clean energy carrier that bridges the energy producers and energy consumers in an efficient and safe way for a sustainable society.Hydrogen can be stored in a gas,liquid and so...Hydrogen has been widely considered as a clean energy carrier that bridges the energy producers and energy consumers in an efficient and safe way for a sustainable society.Hydrogen can be stored in a gas,liquid and solid states and each method has its unique advantage.Though compressed hydrogen and liquefied hydrogen are mature technologies for industrial applications,appropriate measures are necessary to deal with the issues at high pressure up to around 100 MPa and low temperature at around 20 K.Distinct from those technologies,storing hydrogen in solid-state hydrides can realize a more compact and much safer approach that does not require high hydrogen pressure and cryogenic temperature.In this review,we will provide an overview of the majormaterial groups that are capable of absorbing and desorbing hydrogen reversibly.The main features on hydrogen storage properties of each material group are summarized,together with the discussion of the key issues and the guidance of materials design,aiming at providing insights for new material development as well as industrial applications.展开更多
Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods...Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. Results Matrine (1×10^-4 mol/L -3.3×10^-3 mol/L) relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation (3.3× 10^- 3 mol/L) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K^+ channel blocker glibenclamide (10.5 mol/L), either by the non-selective K^+channel blocker tetraethylammonium (10^-3 mol/L), or by the β-antagonist propranolol (10^-5 mol/L). In either "normal" or "Ca^2+-free" bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3×10^-3 mol/L), indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca^2+ mobilization. Conclusion Matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with the release of intracellular Ca^2+ and the influx of extracellular Ca^2+.展开更多
Optical logic gates play important roles in all-optical logic circuits,which lie at the heart of the next-generation optical computing technology.However,the intrinsic contradiction between compactness and robustness ...Optical logic gates play important roles in all-optical logic circuits,which lie at the heart of the next-generation optical computing technology.However,the intrinsic contradiction between compactness and robustness hinders the development in this field.Here,we propose a simple design principle that can possess multiple-input-output states according to the incident circular polarization and direction based on the metasurface doublet,which enables controlled-NOT logic gates in infrared region.Therefore,the directional asymmetric electromagnetic transmission can be achieved.As a proof of concept,a spin-dependent Janus metasurface is designed and experimentally verified that four distinct images corresponding to four input states can be captured in the far-field.In addition,since the design method is derived from geometric optics,it can be easily applied to other spectra.We believe that the proposed metasurface doublet may empower many potential applications in chiral imaging,chiroptical spectroscopy and optical computing.展开更多
The microstructure,texture evolution and mechanical properties of AZ31 magnesium alloy were investigated during the cyclic expansion extrusion with the asymmetrical extrusion cavity(CEE-AEC)process.The results show th...The microstructure,texture evolution and mechanical properties of AZ31 magnesium alloy were investigated during the cyclic expansion extrusion with the asymmetrical extrusion cavity(CEE-AEC)process.The results show that continuous dynamic recrystallization(CDRX)and discontinuous dynamic recrystallization(DDRX)occur during the CEE-AEC process.After 3 passes,the microstructures of the deformed samples are refined,and the average grain size of the alloys in asymmetrical cavity region is 6.9μm.The maximum intensities of the basal textures increase with the increase in the number of passes,and the basal textures are deflected during the deformation process.The basal texture of the alloys in asymmetrical cavity region is tilted by approximately±45°from the normal direction(ND)to the extrusion direction(ED).Grain refinement strengthening and texture deflection significantly improve the comprehensive mechanical properties of the deformed alloys.After 3 passes,tensile yield strength(TYS),ultimate tensile strength(UTS)and elongation-to-failure of the alloy in the asymmetric cavity region are 146 MPa,230 MPa and 29.7%,respectively.展开更多
Hydrogenation of N-ethylcarbazole(NEC),the hydrogen lean form of a liquid organic hydrogen carrier,on TiO2 supported Ru-Ni bimetallic catalysts is investigated.Crystal structure of TiO2 plays a critical role on the hy...Hydrogenation of N-ethylcarbazole(NEC),the hydrogen lean form of a liquid organic hydrogen carrier,on TiO2 supported Ru-Ni bimetallic catalysts is investigated.Crystal structure of TiO2 plays a critical role on the hydrogenation activity and selectivity towards fully hydrogenated product.Ru/anatase catalyst exhibits higher selectivity but lower reactivity compared to Ru/rutile catalyst.Ni addition significantly promotes the performance of Ru/anatase catalyst while causes severe performance deterioration of Ru/rutile catalyst.Commercial P25,a mixture of anatase and rutile phases in approximate ratio A/R1/4,is found to be the best TiO2 support for NEC hydrogenation.Ru/P25 catalyst outperforms both Ru/rutile and Ru/anatase and its activity can be further slightly improved by Ni addition.The unexpected synergism between the two different TiO2 phases for Ru based NEC hydrogenation catalysts is related to metal-support interaction and Ru-Ni interaction.展开更多
基金supported by National Natural Science Foundation of China(NSFC,Grant Nos.U1831209 and U2031144)the research fund of Ankara University(BAP)through the project 18A0759001。
文摘We report the confirmation of a sub-Saturn-size exoplanet,TOI-1194 b,with a mass of about 0.456+0.055-0.051M_(J),and a very low mass companion star with a mass of about 96.5±1.5 MJ,TOI-1251 B.Exoplanet candidates provided by the Transiting Exoplanet Survey Satellite(TESS)are suitable for further follow-up observations by ground-based telescopes with small and medium apertures.The analysis is performed based on data from several telescopes worldwide,including telescopes in the Sino-German multiband photometric campaign,which aimed at confirming TESS Objects of Interest(TOIs)using ground-based small-aperture and medium-aperture telescopes,especially for long-period targets.TOI-1194 b is confirmed based on the consistent periodic transit depths from the multiband photometric data.We measure an orbital period of 2.310644±0.000001 days,the radius is 0.767+0.045-0.041RJ and the amplitude of the RV curve is 69.4_(-7.3)^(+7.9)m s^(-1).TOI-1251 B is confirmed based on the multiband photometric and high-resolution spectroscopic data,whose orbital period is 5.963054+0.000002-0.000001days,radius is 0.947+0.035-0.033 R_(J) and amplitude of the RV curve is 9849_(-40)^(+42)ms^(-1).
基金supported by the Key Research and Development Program of Guangxi(2021AB13014)Major Project of Guangxi Innovation Driven(AA18118016)+7 种基金National Key Research and Development Program of China(2017YFC0908000)Natural Key Research and Development Project(2020YFA0113200)National Natural Science Foundation of China(81770759,82060145,31970814)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2021JJA140912)Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Key Laboratory for Genomic and Personalized Medicine(19-050-22,19-185-33,20-065-33,22-35-17)Major Project of Scientific Research and Technology Development Plan of Nanning(20221023)Guangxi Natural Science Foundation(2022GXNSFAA035641)Self-funded Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-A20230620)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
基金People’s Hospital of Xuyong County-Southwest Medical University Science and Technology Strategic Cooperation Project(2023XYXNYD05)Guangdong Association of Clinical Trials(GACT)/Chinese Thoracic Oncology Group(CTONG)and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer(2017B030314120)Natural Science Foundation of Chongqing Municipality(CSTB2023NSCQ-MSX0554).
文摘Background:Metformin has pleiotropic effects beyond glucose reduction,including tumor inhibition and immune regulation.It enhanced the anti-tumor effects of programmed cell death protein 1(PD-1)inhibitors in serine/threonine kinase 11(STK11)mutant non-small cell lung cancer(NSCLC)through an axis inhibition protein 1(AXIN1)-dependent manner.However,the alterations of tumor metabolism and metabolites upon metformin administration remain unclear.Methods:We performed untargeted metabolomics using liquid chromatography(LC)-mass spectrometry(MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis.Results:According to the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database,most metabolites were annotated into metabolism,including nucleotide metabolism.Next,the differentially expressed metabolites in H460(refers to H460 cells),H460_met(refers to metformin-treated H460 cells),and H460_KO_met(refers to metformin-treated Axin1-/-H460 cells)were distributed into six clusters based on expression patterns.The clusters with a reversed expression pattern upon metformin treatment were selected for further analysis.We screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were upregulated.Furthermore,these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes(STING)pathway independently of AXIN1.Conclusion:Relying on AXIN1,metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC,indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC.
基金supported by the National Science Fund for Distinguished Young Scholars(No:81901099 and 81703427)the 64th batch of China Postdoctoral Science Foundation(No:2018M641731).
文摘All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.
基金supported by the Joint Research Fund in Astronomy(grant No.U1631108)under a cooperative agreement between the National Natural Science Foundation of China(NSFC)the Chinese Academy of Sciences(CAS)the Chinese National Natural Science Foundation of China(NSFC,grant No.12103030)。
文摘V0405 Dra is a W UMa-type binary star.Based on the TESS data,we have conducted an orbital period study and performed a light curve analysis for the system.The orbital period study reveals that the O-C curve for V0405 Dra exhibits secular decrease at an extremely high rate of d P/dt=-2.71×10^(-6)day year^(-1),along with periodic variations characterized by an amplitude of A_(3)=0.0032 day and a period of P_(3)=1.413 years.The orbital periodic change is possibly due to the light-travel time effect resulting from an additional third body in the system,for which we estimate a minimum mass of M_(3)=0.77M_(⊙).By employing the 2013 version of the Wilson-Devinney(W-D)method to synthesize a light curve,we derived photometric solutions indicating that V0405 Dra is a new deep(f=68.7%)and low-mass ratio(q=0.175)contact binary.The fast decrease in its orbital period is likely caused by mass transfer from the more massive primary star to the less massive secondary star,or due to angular momentum loss.With further mass transfer and loss of angular momentum,the binary will gradually evolve into a tighter contact configuration,eventually leading to a merger into a single star,following the evolutionary paths suggested for such deep and low mass ratio contact binaries.
文摘BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered CAFs-associated gene signature,which can be employed to estimate BC patient outcomes conveniently and accurately.
基金supported by MOST of China(No.2021YFB4000603)NSFC(No.22179002 and 51971004).
文摘Sodium borohydride(NaBH_(4)) is considered as the most potential hydrogen storage material for portable proton exchange membrane fuel cells(PEMFC)because of its high theoretical hydrogen capacity.However,the slow and poor kinetic stability of hydrogen generation from NaBH_(4) hydrolysis limits its application.There are two main factors influencing the kinetics stability of hydrogen generation from NaBH_(4).One factor is that the alkaline byproducts(NaBO_(2)) of the hydrolysis reaction can increase the pH of the solution,thus inhibiting the reaction process.It mainly happens in the NaBH_(4) solution hydrolysis system.Another factor is that the monotonous increase in reaction temperature leads to uncontrollable and unpredictable hydrolysis rates in the solid NaBH_(4) hydrolysis system.This is due to the excess heat generated from this exothermic reaction in the initial reaction of NaBH_(4) hydrolysis.In this perspective,we summarize the latest research progress in hydrogen generation from NaBH_(4) and emphasize the design principles of catalysts for hydrogen generation from NaBH_(4) solution and solid state NaBH_(4).The importance of carbon as catalyst support material for NaBH_(4) hydrolysis is also highlighted.
文摘Ag nanoparticles (NPs) thin films with various thicknesses were prepared by thermal evaporation method. Atomic force microscopy (AFM) and UV-Vis spectrophotometer were used to study the surface morphology, growth nature and optical properties of the films. The results indicate that the growth rates of Ag particles in lateral and vertical direction are variable, and the dominant growth rate of Ag particles in lateral direction will convert into dominant growth rate in vertical direction as films grow thicker. The mean value and distribution of Ag NPs height related with the location and width of SPR (surface plasmonresonance) peak. Higher mean height shifts SPR peak to longer wavelengths, and smaller deviation results in narrower width of SPR peaks.
基金supported by the Program for Changjiang Scholars,Sichuan Province "135" Breeding Tackle Project(Project No.2016NYZ0052)
文摘Background: Weanling pigs, with immature immune system and physiological function, usually experience postweaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth performance, diarrhea, and immunity of weaned pigs challenged with lipopolysaccharide(LPS).Methods: In Experiment(Exp.) 1,144 weaned piglets were weaned at 21 d and randomly assigned to six groups,with six replicates per group and four pigs per replicate, receiving a control diet(CON) or diet supplemented with antibiotics(AB) or C. butyricum(CB)(0.1%, 0.2%, 0.4%, or 0.8%), respectively. All diets in Exp. 1 were a highly digestible basal diet, with 3,000 mg/kg zinc oxide supplied in the first 2 wk only. In Exp. 2, 180 piglets were weaned at 21 d and randomly assigned to five groups, with six replicates per group and six pigs per replicate, receiving CON, AB, or CB(0.2%, 0.4%, or 0.6%) diets. The digestibility of diets was lower than those in Exp. 1, and did not include zinc oxide. At 36 d of Exp. 2, 12 piglets were selected from each of the CON and 0.4% CB groups, six piglets were intraperitoneally injected with LPS(50 μg/kg body weight) and the other six piglets with normal saline;animals were killed at 4 h after injection to collect blood, intestine, and digesta samples for biochemical analysis.Results: In Exp. 1, CB and AB diets had no effect on growth performance of piglets. In Exp. 2, 0.4% CB decreased feed-gain ratio(P < 0.1), diarrhea score(P < 0.05), and increased duodenal, jejunal, and ileal villus height and jejunal villus height/crypt depth(P < 0.05). The 0.4% CB decreased the plasma tumor necrosis factor(TNF) α(P < 0.05) but increased ileal mucosa IL-10 and TLR2 mRNA expression(P < 0.05). Furthermore, 0.4% CB altered the microbial profile, with Bacillus and Ruminococcaceae UGG-003 at genus level and Lactobacillus casei and Parasutterella secunda at species level were higher than CON in colonic content(P < 0.05).Conclusions: Dietary C. butyricum supplementation had positive effects on growth of weaned piglets with less digestible diets. There was a tendency to reduce the feed-gain ratio, which could reduce feed costs in pig production. Moreover, C. butyricum decreased post-weaning diarrhea by improving the intestinal morphology,intestinal microflora profile, and immune function.
文摘Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 (COX-2), 5-1ipoxygenase (5-LOX) and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.
基金support by the program of studying/visiting abroad(No.450404).
文摘Hydrogen has been widely considered as a clean energy carrier that bridges the energy producers and energy consumers in an efficient and safe way for a sustainable society.Hydrogen can be stored in a gas,liquid and solid states and each method has its unique advantage.Though compressed hydrogen and liquefied hydrogen are mature technologies for industrial applications,appropriate measures are necessary to deal with the issues at high pressure up to around 100 MPa and low temperature at around 20 K.Distinct from those technologies,storing hydrogen in solid-state hydrides can realize a more compact and much safer approach that does not require high hydrogen pressure and cryogenic temperature.In this review,we will provide an overview of the majormaterial groups that are capable of absorbing and desorbing hydrogen reversibly.The main features on hydrogen storage properties of each material group are summarized,together with the discussion of the key issues and the guidance of materials design,aiming at providing insights for new material development as well as industrial applications.
基金supported by the Program for New Century Excellent Talents in Universities of the Ministry of Education of China (NCET-06-0916)Ningxia Natural Science Foundation (NZ0782)Ningxia Academic Scientific Research Program (2005-2007)
文摘Objective To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. Results Matrine (1×10^-4 mol/L -3.3×10^-3 mol/L) relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation (3.3× 10^- 3 mol/L) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K^+ channel blocker glibenclamide (10.5 mol/L), either by the non-selective K^+channel blocker tetraethylammonium (10^-3 mol/L), or by the β-antagonist propranolol (10^-5 mol/L). In either "normal" or "Ca^2+-free" bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3×10^-3 mol/L), indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca^2+ mobilization. Conclusion Matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with the release of intracellular Ca^2+ and the influx of extracellular Ca^2+.
基金supported by the National Natural Science Foundation of China (12104326,12104329 and 62105228)Natural Science Foundation of Sichuan Province (2022NSFSC2000)+3 种基金the Opening Foundation of State Key Laboratory of Optical Technologies on Nano-Fabrication and MicroEngineeringfunding by Deutsche Forschungsgemeinschaft (DFG,German Research Foundation) under Germany’s Excellence Strategy–EXC 2089/1–390776260 (e-conversion)the context of the Bavarian Collaborative Research Project Solar Technologies Go Hybrid (SolTech)the support from the China Scholarship Council (CSC)
文摘Optical logic gates play important roles in all-optical logic circuits,which lie at the heart of the next-generation optical computing technology.However,the intrinsic contradiction between compactness and robustness hinders the development in this field.Here,we propose a simple design principle that can possess multiple-input-output states according to the incident circular polarization and direction based on the metasurface doublet,which enables controlled-NOT logic gates in infrared region.Therefore,the directional asymmetric electromagnetic transmission can be achieved.As a proof of concept,a spin-dependent Janus metasurface is designed and experimentally verified that four distinct images corresponding to four input states can be captured in the far-field.In addition,since the design method is derived from geometric optics,it can be easily applied to other spectra.We believe that the proposed metasurface doublet may empower many potential applications in chiral imaging,chiroptical spectroscopy and optical computing.
基金financial supports from International Science and Technology Cooperation Program of Shanxi Province,China(No.201603D421024)Shanxi Scholarship Council of China(No.2017-095)。
文摘The microstructure,texture evolution and mechanical properties of AZ31 magnesium alloy were investigated during the cyclic expansion extrusion with the asymmetrical extrusion cavity(CEE-AEC)process.The results show that continuous dynamic recrystallization(CDRX)and discontinuous dynamic recrystallization(DDRX)occur during the CEE-AEC process.After 3 passes,the microstructures of the deformed samples are refined,and the average grain size of the alloys in asymmetrical cavity region is 6.9μm.The maximum intensities of the basal textures increase with the increase in the number of passes,and the basal textures are deflected during the deformation process.The basal texture of the alloys in asymmetrical cavity region is tilted by approximately±45°from the normal direction(ND)to the extrusion direction(ED).Grain refinement strengthening and texture deflection significantly improve the comprehensive mechanical properties of the deformed alloys.After 3 passes,tensile yield strength(TYS),ultimate tensile strength(UTS)and elongation-to-failure of the alloy in the asymmetric cavity region are 146 MPa,230 MPa and 29.7%,respectively.
基金NSFC (Nos. 21771006, U1607126 and 51771002)MOST of China (No. 2017YFB0405902)Beijing Municipal Commission of Science and Technology (Z17110000091702)
文摘Hydrogenation of N-ethylcarbazole(NEC),the hydrogen lean form of a liquid organic hydrogen carrier,on TiO2 supported Ru-Ni bimetallic catalysts is investigated.Crystal structure of TiO2 plays a critical role on the hydrogenation activity and selectivity towards fully hydrogenated product.Ru/anatase catalyst exhibits higher selectivity but lower reactivity compared to Ru/rutile catalyst.Ni addition significantly promotes the performance of Ru/anatase catalyst while causes severe performance deterioration of Ru/rutile catalyst.Commercial P25,a mixture of anatase and rutile phases in approximate ratio A/R1/4,is found to be the best TiO2 support for NEC hydrogenation.Ru/P25 catalyst outperforms both Ru/rutile and Ru/anatase and its activity can be further slightly improved by Ni addition.The unexpected synergism between the two different TiO2 phases for Ru based NEC hydrogenation catalysts is related to metal-support interaction and Ru-Ni interaction.