AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated b...AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.展开更多
Dendritic molecules with dodecyl groups as the hyperbranchs were synthesized in methanol by Michael addition with dodecylamine and methyl acrylate as raw materials. This new-type dendritic molecules were called vivid...Dendritic molecules with dodecyl groups as the hyperbranchs were synthesized in methanol by Michael addition with dodecylamine and methyl acrylate as raw materials. This new-type dendritic molecules were called vividly ＂broom molecules＂ in this report. The surface tension of the aqueous solution of broom molecule terminated amino group was measured by using the dropvolume method. The demulsification performance of the broom molecules for the oil/water （O/W） simulated crude oil emulsion was examined. The experimental results revealed that, as a new-type of surfactants, the broom molecules terminated amino groups showed demulsification for the O/W simulated crude oil emulsion. 2007 Jun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.展开更多
BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary r...BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.展开更多
It is common that airlines encounter a disruption of a flight schedule,which is mainly caused by resource shortages.In case of a disruption,subject to scarce resources,most of airlines lose flexibility of performing a...It is common that airlines encounter a disruption of a flight schedule,which is mainly caused by resource shortages.In case of a disruption,subject to scarce resources,most of airlines lose flexibility of performing aircraft recovery on the basis of business interest priorities and need to delay,swap,and cancel flights.This paper proposes an air-rail inter-modal strategy to incorporate a High-Speed Rail(HSR)transport mode into an aviation network for aircraft recovery.The air-rail inter-modal strategy focuses on occasionally operational integration of existing airside and HSR infrastructure capacities.It is different from air-rail cooperation implemented in Europe which emphasizes a long-term strategy.In addition to modelling the air-rail inter-modal strategy,an inter-modal time-band network is presented.Modelling is applied to a pure aviation network and the inter-modal network.Comparison results show that the inter-modal air-rail strategy helps to reduce the number of cancelled flights and the total disruption cost.展开更多
Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there...Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical.Herein, a scorpion venom peptide(Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76(rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly,rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon(IFN)-b. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-b by activating interferon regulatory transcription factor 3(IRF3) phosphorylation, enhancing the type-Ⅰ IFN response and inhibiting viral infection.This mechanism is significantly different from traditional virucidal antimicrobial peptides(AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-Ⅰ IFN responses,demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.展开更多
This paper reports, for the first time, observation results of the Coherent Beacon System(CBS) onboard the China SeismoElectromagnetic Satellite-1(CSES-1). We describe the CBS, and the Computerized Ionospheric Tomogra...This paper reports, for the first time, observation results of the Coherent Beacon System(CBS) onboard the China SeismoElectromagnetic Satellite-1(CSES-1). We describe the CBS, and the Computerized Ionospheric Tomography(CIT) algorithm program is validated by numerical experiment. Two examples are shown, for daytime and nighttime respectively. The Equatorial Ionization Anomaly(EIA) can be seen, and the northern crest core is located at ～20°N in the reconstruction image at 07:28 UTC on 20 July 2018(daytime).Disturbances are shown in the reconstruction image at 18:40 UTC on 13 July 2018(nighttime). We find that beacon measurements are more consistent with ionosonde measurements than model results, by comparing Nm F2 at three sites at Lanzhou, Chongqing, and Kunming; consistency with ionosonde measurements validates beacon measurements. Finally, we have studied Vertical Total Electron Content(VTEC) variations from ground to ～500 km(the height of CSES-1 orbit) and ratios of VTEC between beacon measurements and CODE(Center for Orbit Determination in Europe) data. VTEC variation from ground to ～500 km has a range of 7.2–16.5 TECU for the daytime case and a range of 1.1–1.7 TECU for the nighttime case. The Beacon/CODE ratio of VTEC varies with latitude and time. The mean Beacon/CODE ratio is 0.69 for the daytime case and 0.26 for the nighttime case. The fact that the nighttime case yields lower ratios indicates the higher altitude of the ionosphere during nighttime when the ionosphere is assumed to be a thin layer.展开更多
BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC)....BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC).Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy.Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes.Protein arginine methylation is a common posttranslational modification.Protein arginine methyltransferase(PRMT)1 is deregulated in a wide variety of cancer types,whose biological role in tumor immunity is undefined.AIM To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo.METHODS PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity.A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy,toxic and side effects,and tumor growth in vivo.By flow cytometry,we determined the expression of key immune checkpoint proteins,detected the apoptosis in tumor tissues,and analyzed the immune cells.Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67,TUNEL assay,and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect.RESULTS Cultured Panc02 cells did not express PD-L1 in vitro,but tumor cells derived from Panc02 transplanted tumors expressed PD-L1.The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume(1054.00±61.37 mm3 vs 555.80±74.42 mm3,P<0.01)and tumor weight(0.83±0.06 g vs 0.38±0.02 g,P<0.05).PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells(32.74%±5.89%vs 17.95%±1.92%,P<0.05).The combination therapy upregulated tumorinfiltrating CD8+T lymphocytes(23.75%±3.20%vs 73.34%±4.35%,P<0.01)and decreased PD-1+leukocytes(35.77%±3.30%vs 6.48%±1.08%,P<0.001)in tumor tissue compared to the control.In addition,PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis.PRMT1 downregulation was correlated with PD-L1 downregulation.CONCLUSION PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.展开更多
BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing...BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing(EPSS)has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects.However,details regarding the efficacy of endoscopic pre-purse-string suture(P-EPSS)are unknown,especially that it offers several advantages over conventional EPSS(C-EPSS).AIM To elucidate the outcomes of EPSS-assisted closure in different clinical situations,and evaluate the efficacy of P-EPSS.METHODS This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS(n=63)or C-EPSS(n=117)between July 2014 and June 2020.The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size,location,and morphology,incidence of complete closure,intraoperative perforation,and delayed adverse events were evaluated.Data on the features and clinical course of cases with adverse events were collected for further analysis.RESULTS Patients with lesion size larger than 3 cm,lesions located at the fundus of stomach,or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure.The P-EPSS group showed a significantly higher proportion of intraoperative perforation(56%vs 17%)and a much shorter procedure time(9.06±6.14 min vs 14.84±7.25 min).Among adverse events,the incidence of delayed perforation(5%vs 4%;P=0.82)and delayed bleeding(3%vs 4%;P=0.96)did not differ significantly between the groups.Multivariate analysis revealed that lesions with incomplete closure[odds ratio(OR)=21.33;95%confidence interval(CI):5.45-83.45;P<0.01]or size greater than 3 cm(OR=3.14;95%CI:1.08-9.18;P=0.039)showed a statistical tendency to result in an increase in delayed adverse events.CONCLUSION The present study revealed that EPSS could achieve secure complete closure of mucosal defect.PEPSS could shorten the procedure and yield complete closure of mucosal defects.Rather than closure-type selection,incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.展开更多
In northern China’s agro-pastoral ecotone,there are conflicts between agricultural industry and ecological construction resource competition,and also problems urgently to be solved for economic growth and sustainable...In northern China’s agro-pastoral ecotone,there are conflicts between agricultural industry and ecological construction resource competition,and also problems urgently to be solved for economic growth and sustainable ecological improvement.Taking the development concept of"lucid waters and lush mountains being mountains of gold and silver"as the guiding principle of prioritizing ecological and green development,this paper studied the strategies for prioritizing ecological construction with consideration of economic development of agricultural industry from the perspective of opportunity cost.Through the analysis of opportunity cost,externality,and Pareto optimal theory,and using the calculation method of the unit equivalent factor value of terrestrial ecological service function,this paper calculated the ecological service value of forest,grassland,and farmland.It found that the ecological value of forest and grassland per unit area was greater than the ecological value of agricultural industry.This indicates that the opportunity cost of farmland for ecological construction was less than that of agricultural industry.Based on the theoretical and quantitative analysis,it came up with recommendations for establishing a comprehensive system for prioritizing ecological construction with consideration of agricultural industry development and establishing and improving the incentive mechanism of ecological construction.展开更多
The modified Hofmann degradation of koumine(1) has proved abortive. The struture and stereochemistry of the main product(3) were deduced by spectral methods and confirmed by X-ray diffration analysis. From the roots o...The modified Hofmann degradation of koumine(1) has proved abortive. The struture and stereochemistry of the main product(3) were deduced by spectral methods and confirmed by X-ray diffration analysis. From the roots of Gelsemium elegans, dihydrokounine was first isolated as a natural product.展开更多
AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in v...AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.展开更多
0 INTRODUCTION Skarn deposits,one of the most important ore types in the Earth's crust,are mined for a range of metals,including Cu,Au,Fe,W,Sn,and Mo(Chang et al.,2019;Meinert et al.,2005).Precise dating of the mi...0 INTRODUCTION Skarn deposits,one of the most important ore types in the Earth's crust,are mined for a range of metals,including Cu,Au,Fe,W,Sn,and Mo(Chang et al.,2019;Meinert et al.,2005).Precise dating of the mineralization is critical for understanding skarn ore formation(Stein et al.,2001;Mao et al.,1999).展开更多
The ecological civilization education will be introduced into primary school courses in the future,aiming to enhance people’s environmental awareness.As the model school of Beijing green ecology and sustainable devel...The ecological civilization education will be introduced into primary school courses in the future,aiming to enhance people’s environmental awareness.As the model school of Beijing green ecology and sustainable development education,Beijing experimental primary school attached to Capital Normal University,focus on new energy and sustainable development education,has been practicing and exploring effectively on ecological education.Detailed works are as follows:Making sure the educating purpose of ecological technology educational development;Improving the normative development of ecological education;Training and taking good advantages of core teachers;Constructing ecological special course system;Combining the school clubs with social programs with wonderful works created by both teachers and students.展开更多
Electrochemical nitrate reduction reaction(NtrRR)has been emerging as an appealing route for both water treatment and NH_(3)synthesis.Herein,we report the structure analysis and electrocatalytic performance of a novel...Electrochemical nitrate reduction reaction(NtrRR)has been emerging as an appealing route for both water treatment and NH_(3)synthesis.Herein,we report the structure analysis and electrocatalytic performance of a novel homoleptic alkynyl-protected Ag_(20)Cu_(12)nanocluster(Ag_(20)Cu_(12)in short)with atomic precision,which has eight free electrons and displays characteristic absorbance feature.Single crystal X-ray diffraction(SC-XRD)discloses that,it adopts a Ag_(14)kernel capped by three Ag_(2)Cu_(4)(C≡CArF)_(8)metal–ligand binding motifs in the outer shell.Ag_(20)Cu_(12)exhibited excellent catalytic performance toward NtrRR,as manifested by the superior NH_(3)Faradaic efficiency(FE,84.6%)and yield rate(0.138 mmol·h^(−1)·mg−1)than the homoleptic alkynyl-protected Ag_(32)nanoclusters.Additionally,it demonstrates good catalytic recycling capability.Density functional theory(DFT)calculations revealed that,the de-ligated Ag_(20)Cu_(12)cluster can expose the available AgCu bimetallic sites as the efficient active sites for NH_(3)formation.In particular,the participation of Cu sites greatly facilitates the initial capture of NO_(3)−and simultaneously promotes the selectivity of the final product.This study discovers a novel homoleptic alkynyl-protected AgCu superatom,and offers a great example to elucidate the structure–performance relationship of bimetallic catalyst for NtrRR and other multiple protons/electrons coupled electrocatalytic reactions.展开更多
Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients.The complex architecture of the human kidney makes it very difficul...Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients.The complex architecture of the human kidney makes it very difficult to study the pathophysiology of renal diseases in vitro and to develop effective therapeutic options for patients.Even though cell lines and animal models have enriched our understanding,they fail to recapitulate key aspects of human kidney development and renal disease at cellular and functional levels.Organoids can be derived from either pluripotent stem cells or adult stem cells by strictly regulating key signalling pathways.Today,these self-differentiated organoids represent a promising technology to further understand the human kidney,one of the most complex organs,in an unprecedented way.The newly established protocols improved by organ-on-chip and coculture with immune cells will push kidney organoids towards the next generation.Herein,we focus on recent achievements in the application of kidney organoids in disease modelling,nephrotoxic testing,precision medicine,biobanking,and regenerative therapy,followed by discussions of novel strategies to improve their utility for biomedical research.The applications we discuss may help to provide new ideas in clinical fields.展开更多
Rapidly spreading coronavirus disease 2019(COVID-19)is currently affecting the world.Specifically,cytokine storms are a key feature in a substantial num ber of COVID-19 patients,1 and studies from our group and others...Rapidly spreading coronavirus disease 2019(COVID-19)is currently affecting the world.Specifically,cytokine storms are a key feature in a substantial num ber of COVID-19 patients,1 and studies from our group and others suggest that the IL-6/IL-6R cascade plays a dom inant role in symptom-correlated cytokine storms.展开更多
We report a superatomic homoleptic alkynyl-protected Ag_(32)L_(24)(L=3,5-bis(trifluoromethylbenzene)acetylide,Ag_(32) for short)nanocluster with atomic precision,which possesses eight free electrons.Ag_(32) is formed ...We report a superatomic homoleptic alkynyl-protected Ag_(32)L_(24)(L=3,5-bis(trifluoromethylbenzene)acetylide,Ag_(32) for short)nanocluster with atomic precision,which possesses eight free electrons.Ag_(32) is formed by an Ag17 core with C3 symmetry and the remaining 15 Ag atoms bond to each other and coordinate with the 24 surface ligands.When applied as electrocatalyst for CO_(2) reduction reaction(CO_(2)RR),Ag_(32) exhibited the highest Faradaic efficiency(FE)of CO up to 96.44%at−0.8 V with hydrogen evolution being significantly suppressed in a wide potential range,meanwhile it has a reaction rate constant of 0.242 min−1 at room temperature and an activation energy of 45.21 kJ·mol−1 in catalyzing the reduction of 4-nitrophenol,both markedly superior than the thiolate and phosphine ligand co-protected Ag_(32) nanocluster.Such strong ligand effect was further understood by density functional theory(DFT)calculations,as it revealed that,one single ligand stripping off from the intact cluster can create the undercoordinated Ag atom as the catalytically active site for both clusters,but alkynyl-protected Ag_(32) nanocluster possesses a smaller energy barrier for forming the key*COOH intermediate in CO_(2)RR,and favors the adsorption of 4-nitrophenol.This study not only discovers a new member of homoleptic alkynyl-protected Ag nanocluster,but also highlights the great potentials of employing alkynyl-protected Ag nanoclusters as bifunctional catalysts toward various reactions.展开更多
基金National Key Research and Development Plan‘Precision Medicine Research’,No.2017YFSF090203National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840+2 种基金State Key Development Program for Basic Research of China,No.2012CB517501100 Talents Program,No.XBR2011007hProgram of the Committee of Science and Technology,No.09140903500
文摘AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.
文摘Dendritic molecules with dodecyl groups as the hyperbranchs were synthesized in methanol by Michael addition with dodecylamine and methyl acrylate as raw materials. This new-type dendritic molecules were called vividly ＂broom molecules＂ in this report. The surface tension of the aqueous solution of broom molecule terminated amino group was measured by using the dropvolume method. The demulsification performance of the broom molecules for the oil/water （O/W） simulated crude oil emulsion was examined. The experimental results revealed that, as a new-type of surfactants, the broom molecules terminated amino groups showed demulsification for the O/W simulated crude oil emulsion. 2007 Jun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.
基金Supported by National Natural Science Foundation of China,No.82172737Shanghai Science and Technology Development Funds(Shanghai Sailing Program),No.22YF1427600。
文摘BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.
基金co-supported by the Tianjin Natural Science Foundation, China (No. 18JCQNJC04300)the National Natural Science Foundation of China (No. 71801215)the Foundation for University Key Teacher by the Ministry of Education of China (Nos. 3122018C033, 3122015L010)
文摘It is common that airlines encounter a disruption of a flight schedule,which is mainly caused by resource shortages.In case of a disruption,subject to scarce resources,most of airlines lose flexibility of performing aircraft recovery on the basis of business interest priorities and need to delay,swap,and cancel flights.This paper proposes an air-rail inter-modal strategy to incorporate a High-Speed Rail(HSR)transport mode into an aviation network for aircraft recovery.The air-rail inter-modal strategy focuses on occasionally operational integration of existing airside and HSR infrastructure capacities.It is different from air-rail cooperation implemented in Europe which emphasizes a long-term strategy.In addition to modelling the air-rail inter-modal strategy,an inter-modal time-band network is presented.Modelling is applied to a pure aviation network and the inter-modal network.Comparison results show that the inter-modal air-rail strategy helps to reduce the number of cancelled flights and the total disruption cost.
基金supported by grants from National Science Fund of China (Nos. 31572289, 31872239 and 81630091)International S&T Cooperation Program of China (No. S2016G3110)+3 种基金Hubei Science Fund (Nos. 2015CFA042 and 2016CFA018)China-Kazakhstan Cooperation Program (No. CK-07-09)Fundamental Research Funds for the Central Universities in China (Nos. 2042017kf0242 and 2042017kf0199)financial support from Higher Education Commission (HEC) of Pakistan
文摘Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical.Herein, a scorpion venom peptide(Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76(rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly,rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon(IFN)-b. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-b by activating interferon regulatory transcription factor 3(IRF3) phosphorylation, enhancing the type-Ⅰ IFN response and inhibiting viral infection.This mechanism is significantly different from traditional virucidal antimicrobial peptides(AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-Ⅰ IFN responses,demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.
基金supported by the “China Seismo-Electromagnetic Satellite (CSES)” projectthe 13th Five-Year Technology Program (Grant No. 315030409)
文摘This paper reports, for the first time, observation results of the Coherent Beacon System(CBS) onboard the China SeismoElectromagnetic Satellite-1(CSES-1). We describe the CBS, and the Computerized Ionospheric Tomography(CIT) algorithm program is validated by numerical experiment. Two examples are shown, for daytime and nighttime respectively. The Equatorial Ionization Anomaly(EIA) can be seen, and the northern crest core is located at ～20°N in the reconstruction image at 07:28 UTC on 20 July 2018(daytime).Disturbances are shown in the reconstruction image at 18:40 UTC on 13 July 2018(nighttime). We find that beacon measurements are more consistent with ionosonde measurements than model results, by comparing Nm F2 at three sites at Lanzhou, Chongqing, and Kunming; consistency with ionosonde measurements validates beacon measurements. Finally, we have studied Vertical Total Electron Content(VTEC) variations from ground to ～500 km(the height of CSES-1 orbit) and ratios of VTEC between beacon measurements and CODE(Center for Orbit Determination in Europe) data. VTEC variation from ground to ～500 km has a range of 7.2–16.5 TECU for the daytime case and a range of 1.1–1.7 TECU for the nighttime case. The Beacon/CODE ratio of VTEC varies with latitude and time. The mean Beacon/CODE ratio is 0.69 for the daytime case and 0.26 for the nighttime case. The fact that the nighttime case yields lower ratios indicates the higher altitude of the ionosphere during nighttime when the ionosphere is assumed to be a thin layer.
基金Supported by the National Natural Science Foundation of China,No. 81472844
文摘BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC).Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy.Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes.Protein arginine methylation is a common posttranslational modification.Protein arginine methyltransferase(PRMT)1 is deregulated in a wide variety of cancer types,whose biological role in tumor immunity is undefined.AIM To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo.METHODS PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity.A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy,toxic and side effects,and tumor growth in vivo.By flow cytometry,we determined the expression of key immune checkpoint proteins,detected the apoptosis in tumor tissues,and analyzed the immune cells.Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67,TUNEL assay,and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect.RESULTS Cultured Panc02 cells did not express PD-L1 in vitro,but tumor cells derived from Panc02 transplanted tumors expressed PD-L1.The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume(1054.00±61.37 mm3 vs 555.80±74.42 mm3,P<0.01)and tumor weight(0.83±0.06 g vs 0.38±0.02 g,P<0.05).PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells(32.74%±5.89%vs 17.95%±1.92%,P<0.05).The combination therapy upregulated tumorinfiltrating CD8+T lymphocytes(23.75%±3.20%vs 73.34%±4.35%,P<0.01)and decreased PD-1+leukocytes(35.77%±3.30%vs 6.48%±1.08%,P<0.001)in tumor tissue compared to the control.In addition,PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis.PRMT1 downregulation was correlated with PD-L1 downregulation.CONCLUSION PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.
基金the National Natural Science Foundation of China,No.82172737 and 82003277Shanghai Municipal Education Commission,No.16411950403 and 19411951605。
文摘BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing(EPSS)has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects.However,details regarding the efficacy of endoscopic pre-purse-string suture(P-EPSS)are unknown,especially that it offers several advantages over conventional EPSS(C-EPSS).AIM To elucidate the outcomes of EPSS-assisted closure in different clinical situations,and evaluate the efficacy of P-EPSS.METHODS This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS(n=63)or C-EPSS(n=117)between July 2014 and June 2020.The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size,location,and morphology,incidence of complete closure,intraoperative perforation,and delayed adverse events were evaluated.Data on the features and clinical course of cases with adverse events were collected for further analysis.RESULTS Patients with lesion size larger than 3 cm,lesions located at the fundus of stomach,or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure.The P-EPSS group showed a significantly higher proportion of intraoperative perforation(56%vs 17%)and a much shorter procedure time(9.06±6.14 min vs 14.84±7.25 min).Among adverse events,the incidence of delayed perforation(5%vs 4%;P=0.82)and delayed bleeding(3%vs 4%;P=0.96)did not differ significantly between the groups.Multivariate analysis revealed that lesions with incomplete closure[odds ratio(OR)=21.33;95%confidence interval(CI):5.45-83.45;P<0.01]or size greater than 3 cm(OR=3.14;95%CI:1.08-9.18;P=0.039)showed a statistical tendency to result in an increase in delayed adverse events.CONCLUSION The present study revealed that EPSS could achieve secure complete closure of mucosal defect.PEPSS could shorten the procedure and yield complete closure of mucosal defects.Rather than closure-type selection,incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.
基金Supported by Project of National Social Science Foundation of China(19BSH077).
文摘In northern China’s agro-pastoral ecotone,there are conflicts between agricultural industry and ecological construction resource competition,and also problems urgently to be solved for economic growth and sustainable ecological improvement.Taking the development concept of"lucid waters and lush mountains being mountains of gold and silver"as the guiding principle of prioritizing ecological and green development,this paper studied the strategies for prioritizing ecological construction with consideration of economic development of agricultural industry from the perspective of opportunity cost.Through the analysis of opportunity cost,externality,and Pareto optimal theory,and using the calculation method of the unit equivalent factor value of terrestrial ecological service function,this paper calculated the ecological service value of forest,grassland,and farmland.It found that the ecological value of forest and grassland per unit area was greater than the ecological value of agricultural industry.This indicates that the opportunity cost of farmland for ecological construction was less than that of agricultural industry.Based on the theoretical and quantitative analysis,it came up with recommendations for establishing a comprehensive system for prioritizing ecological construction with consideration of agricultural industry development and establishing and improving the incentive mechanism of ecological construction.
文摘The modified Hofmann degradation of koumine(1) has proved abortive. The struture and stereochemistry of the main product(3) were deduced by spectral methods and confirmed by X-ray diffration analysis. From the roots of Gelsemium elegans, dihydrokounine was first isolated as a natural product.
基金Supported by National Natural Science Foundation of China,No.81472844
文摘AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.
基金financially supported by the National Key Research and Development Program of China(No.2023YFF0804200)the MOST Special Fund(No.GKZ22Y607)from the GPMR,China University of Geosciences(Wuhan)。
文摘0 INTRODUCTION Skarn deposits,one of the most important ore types in the Earth's crust,are mined for a range of metals,including Cu,Au,Fe,W,Sn,and Mo(Chang et al.,2019;Meinert et al.,2005).Precise dating of the mineralization is critical for understanding skarn ore formation(Stein et al.,2001;Mao et al.,1999).
文摘The ecological civilization education will be introduced into primary school courses in the future,aiming to enhance people’s environmental awareness.As the model school of Beijing green ecology and sustainable development education,Beijing experimental primary school attached to Capital Normal University,focus on new energy and sustainable development education,has been practicing and exploring effectively on ecological education.Detailed works are as follows:Making sure the educating purpose of ecological technology educational development;Improving the normative development of ecological education;Training and taking good advantages of core teachers;Constructing ecological special course system;Combining the school clubs with social programs with wonderful works created by both teachers and students.
基金Z.H.T.acknowledges the financial support from the Guangdong Natural Science Funds(No.2022A1515011840)Q.T.thanks the grants from the National Natural Science Foundation of China(No.21903008)the Chongqing Science and Technology Commission(No.cstc2020jcyj-msxmX0382).
文摘Electrochemical nitrate reduction reaction(NtrRR)has been emerging as an appealing route for both water treatment and NH_(3)synthesis.Herein,we report the structure analysis and electrocatalytic performance of a novel homoleptic alkynyl-protected Ag_(20)Cu_(12)nanocluster(Ag_(20)Cu_(12)in short)with atomic precision,which has eight free electrons and displays characteristic absorbance feature.Single crystal X-ray diffraction(SC-XRD)discloses that,it adopts a Ag_(14)kernel capped by three Ag_(2)Cu_(4)(C≡CArF)_(8)metal–ligand binding motifs in the outer shell.Ag_(20)Cu_(12)exhibited excellent catalytic performance toward NtrRR,as manifested by the superior NH_(3)Faradaic efficiency(FE,84.6%)and yield rate(0.138 mmol·h^(−1)·mg−1)than the homoleptic alkynyl-protected Ag_(32)nanoclusters.Additionally,it demonstrates good catalytic recycling capability.Density functional theory(DFT)calculations revealed that,the de-ligated Ag_(20)Cu_(12)cluster can expose the available AgCu bimetallic sites as the efficient active sites for NH_(3)formation.In particular,the participation of Cu sites greatly facilitates the initial capture of NO_(3)−and simultaneously promotes the selectivity of the final product.This study discovers a novel homoleptic alkynyl-protected AgCu superatom,and offers a great example to elucidate the structure–performance relationship of bimetallic catalyst for NtrRR and other multiple protons/electrons coupled electrocatalytic reactions.
基金This study was supported by grants from Undergraduate Inno-vation and Entrepreneurship Project(No.202321007)Hunan Innovative Provincial Construction Project(No.20195K2211)+7 种基金Changsha Science,Technology Plan Project(No.kq2001044)the National Natural Science Foundation of China(No.81970248)National Key Research and Development Program of China(No.2018YFA0108700,2017YFA0105602)NSFC Pro-jects of Intemational Cooperation and Exchanges(No.81720108004)National Natural Science Foundation of China(No.81974019)The Research Team Project of Natural Science Foundation of Guangdong Province of China(No.2017A030312007)The Key Program of Guangzhou Science Research Plan(No.201904020047)The Special Project of Dengfeng Program of Guangdong Provincial People's Hospital(No.DFJH201812,KJ012019119,KJ012019423).
文摘Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients.The complex architecture of the human kidney makes it very difficult to study the pathophysiology of renal diseases in vitro and to develop effective therapeutic options for patients.Even though cell lines and animal models have enriched our understanding,they fail to recapitulate key aspects of human kidney development and renal disease at cellular and functional levels.Organoids can be derived from either pluripotent stem cells or adult stem cells by strictly regulating key signalling pathways.Today,these self-differentiated organoids represent a promising technology to further understand the human kidney,one of the most complex organs,in an unprecedented way.The newly established protocols improved by organ-on-chip and coculture with immune cells will push kidney organoids towards the next generation.Herein,we focus on recent achievements in the application of kidney organoids in disease modelling,nephrotoxic testing,precision medicine,biobanking,and regenerative therapy,followed by discussions of novel strategies to improve their utility for biomedical research.The applications we discuss may help to provide new ideas in clinical fields.
基金supported by CAMS Research Units of Adaptive Evolution and Control of Emerging Viruses(2018RU009)Beijing New-star Plan of Science and Technology(Z181100006218080)+3 种基金supported by the Excellent Young Scientist Program of the National Natural Science Foundation of China(81822040)the National Youth Talent Support Programfunded by the National Natural Science Foundation of China(31900466)funded by the China Postdoctoral Science Foundation(2020T130080ZX).
文摘Rapidly spreading coronavirus disease 2019(COVID-19)is currently affecting the world.Specifically,cytokine storms are a key feature in a substantial num ber of COVID-19 patients,1 and studies from our group and others suggest that the IL-6/IL-6R cascade plays a dom inant role in symptom-correlated cytokine storms.
基金supported by the Open Fund of Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications(No.2021A07)support from Guangdong Natural Science Funds(No.2022A1515011840)+2 种基金the National Natural Science Foundation of China(No.21805170)the National Natural Science Foundation of China(No.21903008)the Chongqing Science and Technology Commission(No.cstc2020jcyj-msxmX0382).
文摘We report a superatomic homoleptic alkynyl-protected Ag_(32)L_(24)(L=3,5-bis(trifluoromethylbenzene)acetylide,Ag_(32) for short)nanocluster with atomic precision,which possesses eight free electrons.Ag_(32) is formed by an Ag17 core with C3 symmetry and the remaining 15 Ag atoms bond to each other and coordinate with the 24 surface ligands.When applied as electrocatalyst for CO_(2) reduction reaction(CO_(2)RR),Ag_(32) exhibited the highest Faradaic efficiency(FE)of CO up to 96.44%at−0.8 V with hydrogen evolution being significantly suppressed in a wide potential range,meanwhile it has a reaction rate constant of 0.242 min−1 at room temperature and an activation energy of 45.21 kJ·mol−1 in catalyzing the reduction of 4-nitrophenol,both markedly superior than the thiolate and phosphine ligand co-protected Ag_(32) nanocluster.Such strong ligand effect was further understood by density functional theory(DFT)calculations,as it revealed that,one single ligand stripping off from the intact cluster can create the undercoordinated Ag atom as the catalytically active site for both clusters,but alkynyl-protected Ag_(32) nanocluster possesses a smaller energy barrier for forming the key*COOH intermediate in CO_(2)RR,and favors the adsorption of 4-nitrophenol.This study not only discovers a new member of homoleptic alkynyl-protected Ag nanocluster,but also highlights the great potentials of employing alkynyl-protected Ag nanoclusters as bifunctional catalysts toward various reactions.
