OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine i...OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia,and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine.METHODS: In total,168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study,and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily,while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for12 weeks. Mini-mental state examinations(Chinese version) and Montreal Cognitive Assessments(Beijing version) were performed,and fasting plasma glucose,fasting insulin,hemoglobin A1 c,homeostasis model assessment of insulin resistance,plasma nitric oxide and endothelin-1 levels were measured before and after the treatment.RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treatment levels(P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group(P < 0.05).CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore,the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.展开更多
To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-ce...To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.展开更多
Domain of unknown function 1644 （DUF1644） is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regula...Domain of unknown function 1644 （DUF1644） is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of Os.SIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference （RNAi） were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid （ABA） treatment was not changed in OsStDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA- deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies （PBs） and stress granules （SGs） in rice protoplasts. Digital gene expression （DGE） profile analysis indicated that stress-related genes such as SNACl, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.展开更多
Heavy metals and ammonia are difficult to remove from wastewater,as they easily combine into refractory complexes.The struvite formation method（SFM） was applied for the complex decomposition and simultaneous removal...Heavy metals and ammonia are difficult to remove from wastewater,as they easily combine into refractory complexes.The struvite formation method（SFM） was applied for the complex decomposition and simultaneous removal of heavy metal and ammonia.The results indicated that ammonia deprivation by SFM was the key factor leading to the decomposition of the copper-ammonia complex ion.Ammonia was separated from solution as crystalline struvite,and the copper mainly co-precipitated as copper hydroxide together with struvite.Hydrogen bonding and electrostatic attraction were considered to be the main surface interactions between struvite and copper hydroxide.Hydrogen bonding was concluded to be the key factor leading to the co-precipitation.In addition,incorporation of copper ions into the struvite crystal also occurred during the treatment process.展开更多
To investigate the creep and instability properties of a cemented gangue backfill column under a highstress area,the uniaxial compression creep tests were conducted by single-step and multi-step loading of prismatic s...To investigate the creep and instability properties of a cemented gangue backfill column under a highstress area,the uniaxial compression creep tests were conducted by single-step and multi-step loading of prismatic samples made of cemented gangue backfill material(CGBM)under the high stressstrength ratio.The creep damage was monitored using an electrical resistivity device,ultrasonic testing device,and acoustic emission(AE)instrument.The results showed that the CGBM sample has a creep hardening property.The creep failure strength(CFS)is slightly larger than the uniaxial compressive strength(UCS),ranging in ratio from 108.9%to 116.5%.The instantaneous strain,creep strain,and creep rate increase with increasing stress-strength ratio in the single-step loading creep tests.The instantaneous strain and creep strain decrease first and then increase during the multi-step loading creep process.The axial creep strain of the CGBM column can be expressed by the viscoelastic-plastic creep model.Creep instability is caused by the accumulation of strain energy under multi-step loading and the continuous lateral expansion at the unconstrained middle position during the creep process.The creep stability of a CGBM column in a high-stress area can be monitored based on the variation of electrical resistivity,ultrasonic pulse velocity(UPV),and AE signals.展开更多
The effects of freeze-thaw cycles on sorption/desorption of dissolved organic carbon （DOC） in two wetland soils and one reclaimed wetland soil were investigated. DOC concentrations added were 0-600 mg/L. Laboratory ...The effects of freeze-thaw cycles on sorption/desorption of dissolved organic carbon （DOC） in two wetland soils and one reclaimed wetland soil were investigated. DOC concentrations added were 0-600 mg/L. Laboratory incubations of sorption/desorption of DOC had been carried out at -15℃ for 10 h, and then at ＋5℃ for 13 h. Soil samples were refrozen and thawed subsequently for 5 cycles. Initial Mass model was used to describe sorption behavior of DOC. The results indicate that freeze-thaw cycles can significantly increase the sorption capacity of DOC and reduce the desorption capacity of DOC in the three soils. The freeze-thaw effects on desorpfion of DOC in soils increase with the increasing freeze-thaw cycles. The conversion of natural wetlands to soybean farmland can decrease the sorption capacity and increase the desorption capacity of DOC in soils. Global warming and reclamation may increase DOC release, and subsequently increase the loss of carbon and the emission of greenhouse gas.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical pro...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.展开更多
Auxin is an important plant hormone that is essential for growth and development due to its effects on organogenesis, morphogenesis, tropisms, and apical dominance. The functional diversity of auxin highlights the imp...Auxin is an important plant hormone that is essential for growth and development due to its effects on organogenesis, morphogenesis, tropisms, and apical dominance. The functional diversity of auxin highlights the importance of its biosynthesis, transport, and associated responses. In this study, we show that a NAC transcription factor, ANAC092(also named At NAC2 and ORESARA1),known to positively regulate leaf senescence and contribute to abiotic stress responses, also affects primary root development. Plants overexpressing ANAC092 had altered root meristem lengths and shorter primary roots compared with the wild-type control. Additionally, expression of the pro ANAC092::GUS was strongly induced by indole-3-acetic acid. Quantitative real-time RT-PCR(q RT-PCR) analysis revealed that the YUCCA2, PIN, and ARF expression levels were downregulated in ANAC092-overexpressing plants. Moreover, yeast one-hybrid and chromatin immunoprecipitation assays confirmed that ANAC092 binds to the promoters of AUXIN RESPONSE FACTOR 8(ARF8) and PIN-FORMED 4(PIN4). Furthermore, a dual-luciferase assay indicated that ANAC092 decreases ARF8 and PIN4 promoter activities. We also applied a CRISPR/Cas9 system to mutate ANAC092. The roots of three of the analyzed mutants were longer than normal. Collectively, our findings indicate that ANAC092 negatively affects root development by controlling the auxin pathway.展开更多
Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was...Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of100mL of autologous blood into the striatum. Rats were divided into three groups (n = 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed. Results: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P 0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T2) in the rim at 4 days after ICH (P 0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P 0.05) and increased number of blood vessels (P 0.05). Conclusions: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement.展开更多
The CREB1 gene encodes an exceptionally pleiotropic transcription factor that frequently dysregulated in human cancers.CREB1 can regulate tumor cell status of proliferation and/or migration;however,the molecular basis...The CREB1 gene encodes an exceptionally pleiotropic transcription factor that frequently dysregulated in human cancers.CREB1 can regulate tumor cell status of proliferation and/or migration;however,the molecular basis for this switch involvement in cell plasticity has not fully been understood yet.Here,we first show that knocking out CREB1 triggers a remarkable effect of epithelial-mesenchymal transition(EMT)and leads to the occurrence of inhibited proliferation and enhanced motility in HCT116colorectal cancer cells.By monitoring 45 cellular signaling pathway activities,we find that multiple growth-related pathways decline significantly while inflammatory pathways including NF-κB are largely upregulated in comparing between the CREB1wild-type and knocked out cells.Mechanistically,cells with CREB1 knocked out show downregulation of MYC as a result of impaired CREB1-dependent transcription of the oncogenic lnc RNA CCAT1.Interestingly,the unbalanced competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-κB pathway in cells with CREB1 disrupted,which induces an obvious EMT phenotype of the cancer cells.Taken together,these studies identify previously unknown mechanisms of CREB1 in CRC cell plasticity via regulating lnc RNA CCAT1 and NF-κB pathways,providing a critical insight into a combined strategy for CREB1-targeted tumor therapies.展开更多
The basic-nitrogen aromatic compounds in feedstocks and liquid products from the micro-reactor and soluble components of coke obtained during fluid catalytic cracking （FCC） process were analyzed by the micro-electro...The basic-nitrogen aromatic compounds in feedstocks and liquid products from the micro-reactor and soluble components of coke obtained during fluid catalytic cracking （FCC） process were analyzed by the micro-electrospray ioniza- tion （ESI） 9.4T Fourier transform ion cyclotron resonance mass spectrometry （FT-ICR MS） with an average mass resolving power of 300 000 at a mass range of 100--1 200. The analytical results revealed that the coker gas oil （CGO） contained a higher abundance of basic-nitrogen aromatic compounds with the type of-SN to -9N compared with those in deasphalted oil （DAO） and mixed FCC feedstock. After catalytic cracking, the abundance of lowly condensed basic-nitrogen aromatic compounds was much less than those of highly condensed aromatics in the liquid products, with the carbon number mainly ranging from 6 to 25 and the average carbon number of the side-chains equating to 1--5. On the contrary, with respect to the soluble components of coke, the abundance of lowly condensed basic-nitrogen aromatic compounds was more than those of highly condensed aromatics, and the carbon number ranged from 12 to 30, which was much smaller than that of the mixed FCC feedstock but slightly larger than that of the cracked liquid products. These results have provided some fundamental information on FCC process.展开更多
Hepatocellular carcinoma (HCC) has already become a severe health risk and brings a lot of healthcare burden to the world. Apart from traditional HCC treatment strategies (surgery, liver transplantation, etc.), the em...Hepatocellular carcinoma (HCC) has already become a severe health risk and brings a lot of healthcare burden to the world. Apart from traditional HCC treatment strategies (surgery, liver transplantation, etc.), the emergence of immunotherapy targeting the immune microenvironment of HCC has brought new promise to patients with advanced HCC. However, adverse effects like drug resistance still exist. The liver is the main organ for storing copper ions, in copper overload can lead to liver function impairment and even the development of HCC. In recent years, a new mode of cell death has been identified, namely cuproptosis, a mode of programmed cell death that is dependent on copper ions and the tricarboxylic acid (TCA) cycle with mitochondria. Interestingly, a potential relationship between cuproptosis and the development of HCC has been found. Conclusively, this review provides an in-depth discussion of copper homeostasis in humans, the mechanism of cuproptosis, the potential impact of cuproptosis with HCC, and the therapeutic modalities of HCC that target cuproptosis, which provide new insights to promote the development of research targeting cuproptosis in HCC.展开更多
The vanadium species were contaminated on FCC catalysts by using the Mitchell method. After the hydrothermal deactivation of the FCC catalysts, the cracking reaction was performed on these catalyst samples. The test r...The vanadium species were contaminated on FCC catalysts by using the Mitchell method. After the hydrothermal deactivation of the FCC catalysts, the cracking reaction was performed on these catalyst samples. The test results revealed that the conversion of feedstock and the gasoline yield obtained over the FCC catalysts with vanadium trapping components were obviously higher than those without addition of vanadium trapping components. The results also showed that the dry gas and coke selectivity on the FCC catalysts containing vanadium trapping components was improved. The X-Ray diffraction results proved that the zeolite crystal structure was well protected by the vanadium trapping components during its hydrothermal deactivation step. The results of SEM-EDX mapping disclosed that the vanadium was enriched on the vanadium trapping components which verified the positive function of vanadium trapping components.展开更多
Background Chemoresistance is common among patients with esophageal squamous cell carcinoma （ESCC）.We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophage...Background Chemoresistance is common among patients with esophageal squamous cell carcinoma （ESCC）.We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.Methods The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay.The times T1,when the number of living cells reached a plateau and T2,when the number of living cells reached a new plateau after the addition of insulin were found.T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin （MDC）.Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively.Apoptotic ratio and fluorescent intensity were analysed by flow cytometry （FCM） quantitatively.Western blotting analysis was used to estimate the protein expression levels of AKT,mTOR,PI3K,PTEN,autophage related indicator LC3-Ⅱ and autophage related protein Beclin1 changes that occurred in the course of treatment.Results A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin.Insulin can increase the apoptosis induced by cisplatin.Apoptotic ratio of T1 plateau cells （（32.6±4.3）％） is significantly less than T2 plateau （（47.5±5.6）％）.MDC fluorescent intensity at T1 plateau （104.9±13.2） was significantly higher than intensity at T2 plateau （82.6±10.3）.After cotreatment with insulin,the expression level of LC3-Ⅱ,Beclin1 and PTEN in T2 plateau cells were significantly downregulated,but AKT,mTOR and PI3K expressions significantly upregulated compared with T1 plateau.Conclusions Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy.The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells,which may be attributed to the anticancer effects of cisplatin.展开更多
Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a pre...Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.展开更多
Objective:Pyruvate kinases M(PKM),including the PKM1 and PKM2 isoforms,are critical factors in glucose metabolism.PKM2promotes aerobic glycolysis,a phenomenon known as"the Warburg effect".The purpose of this...Objective:Pyruvate kinases M(PKM),including the PKM1 and PKM2 isoforms,are critical factors in glucose metabolism.PKM2promotes aerobic glycolysis,a phenomenon known as"the Warburg effect".The purpose of this study was to identify the roles of PKM2 in regulating cellular metabolism.Methods:The CRISPR/Cas9 system was used to generate the PKM-knockout cell model to evaluate the role of PKM in cellular metabolism.Lactate levels were measured by the Vitros LAC slide method on an autoanalyzer and glucose levels were measured by the autoanalyzer AU5800.The metabolism of ^(13)C_6-glucose or ^(13)C_5-glutamine was evaluated by liquid chromatography/mass spectrometry analyses.The effects of PKM on tumor growth were detected in vivo in a tumor-bearing mouse model.Results:We found that both PKM1 and PKM2 enabled aerobic glycolysis,but PKM2 converted glucose to lactate much more efficiently than PKM1.As a result,PKM2 reduced glucose levels reserved for intracellular utilization,particularly for the production of citrate,and thus increased theα-ketoglutarate/citrate ratio to promote the generation of glutamine-derived acetylcoenzyme A through the reductive pathway.Furthermore,reductive glutamine metabolism facilitated cell proliferation under hypoxia conditions,which supports in vivo tumor growth.In addition,PKM-deletion induced a reverse Warburg effect in tumorassociated stromal cells.Conclusions:PKM2 plays a critical role in promoting reductive glutamine metabolism and maintaining proton homeostasis.This study is helpful to increase the understanding of the physiological role of PKM2 in cancer cells.展开更多
BACKGROUND：Various molecular mechanisms of cell death following traumatic brain injury have been previously described.However,the time course of cell death remains unclear.TUNEL and Fluoro-Jade B labeling have been w...BACKGROUND：Various molecular mechanisms of cell death following traumatic brain injury have been previously described.However,the time course of cell death remains unclear.TUNEL and Fluoro-Jade B labeling have been widely used to label apoptotic cells and neuronal degeneration.Propidium iodide （PI） functions as a biomarker of cell death in vivo.OBJECTIVE：To explore the role of PI labeling compared to TUNEL and Fluoro-Jade B staining for detecting neural cell death,and to observe time course of traumatic brain injury-induced cell death in mice.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Laboratory of Aging and Nervous Diseases,Soochow University from September 2007 to December 2008.MATERIALS：PI （B1221） was purchased from Sigma,USA.TUNEL kit was purchased from Roche Molecular Biochemicals,USA.Fluoro-Jade B was purchased from Chemicon,USA.METHODS：A total of 70 healthy,male,Kunming mice were randomly assigned to sham-surgery （n = 5） and model （n = 65） groups.Traumatic brain injury was established using the controlled cortical impact method.PI was intraperitoneally injected at 1 hour prior to animal sacrifice.MAIN OUTCOME MEASURES：TUNEL,Fluoro-Jade B,and Pl-positive cells were quantified using a double-labeling method to determine the time course of traumatic brain injury-induced cell death.RESULTS：PI labeled cells in an earlier phase of cell death than TUNEL and Fluoro-Jade B labeling.Pl-positive cells were observed immediately following injury,and the numbers rapidly increased in injured brain areas at 1 hour,peaked at 24-48 hours,and subsequently decreased at 3-21 days post-injury.TUNEL-labeled cells were significantly increased at 12 hours,while Fluoro-Jade B-labeled cells were increased at 6 hours after injury,with cells still visible at 6-48 hours post-injury.Moreover,a greater number of Pl-positive cells were observed compared to TUNEL- and Fluoro-Jade B-labeled cells.CONCLUSION：PI labeling is more sensitive and reliable than TUNEL and F展开更多
Objective:To investigate the anti-tumor effect of macromolecular fractions of fresh gecko (M-AG) in vivo and their differentiation-inducing activity in Bel-7402 cells in vitro.Methods:An H22 hepatocarcinoma-bearing mo...Objective:To investigate the anti-tumor effect of macromolecular fractions of fresh gecko (M-AG) in vivo and their differentiation-inducing activity in Bel-7402 cells in vitro.Methods:An H22 hepatocarcinoma-bearing mouse model was used to evaluate the anti-tumor activity of M-AG samples.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to analyze cell viability.Cell morphology was observed by phase contrast microscopy.The quantity of the alpha-fetoprotein was detected by a radioimmunoassay.Chromatometry was used to assay the albumin quantity.Activities of alkaline phosphatase and γ-glutamyl trans-peptidase were measured by biochemical methods.Finally,western blotting was applied to assess proteins in the mitogen-activated protein kinase (MAPK) signaling pathway.Results:Macromolecular fractions of fresh gecko exerted a significant anti-tumor effect in mice.The inhibition rate of tumor growth was 63% in the moderate M-AG dose group.Cells treated with M-AG displayed a differentiated state.The treatment lowered alphafetoprotein secretion and significantly decreased the activities of γ-glutamyl trans-peptidase and alkaline phosphatase in Bel-7402 cells.In contrast,M-AG increased the amount of albumin in the cell culture medium.All biochemical indices demonstrated that M-AG induced Bel7402 cell differentiation.Western blotting showed no changes in the quantities of extracellular signal-regulated kinase (ERK) 1/2,p38MAPK,or c-Jun N-terminal protein kinase 1/2.However,M-AG significantly activated the phosphorylation of ERK1/2 in a dose-dependent manner.In addition,M-AG had no significant influence on the expression of nuclear factor-kappa B.Conclusion:Macromolecular fractions of fresh gecko has an anti-tumor activity in H22 hepatocarcinoma-bearing mice in vivo and inhibits Bel-7402 cell proliferation in vitro by inducing cell differentiation related to activation of ERK1/2.展开更多
Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized an...Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized and afforded excellent catalytic performance with 99.0%conversion and 97.7%selectivity to CPO in a near-neutral solution under 2.0 MPa H2 at 160℃ for 5 h,much higher than those on other molecular sieve supports including MCM-41,SBA-15,HY,and ZSM-5.A small amount of Al highly dispersed in MCM-41 plays an anchoring role and ensures the formation of highly dispersed CuNi bimetallic nanoparticles(NPs).The remarkably improved catalytic performance may be attributed to the bimetallic synergistic and charge transfer effects.In addition,the initial FA concentration and the aqueous system pH required precise control to minimize polymerization and achieve high selectivity of CPO.Fourier transform infrared spectroscopy and mass spectra results indicated that polymerization was sensitive to pH values.Under acidic conditions,FA and intermediate furfuryl alcohol polymerize,while the intermediate 4-hydroxy-2-cyclopentenone mainly polymerizes under alkaline conditions,blocking the cascade of multiple reactions.Therefore,near-neutral conditions are most suitable for minimizing the impact of polymerization.This study provides a useful solution for the current universal problems of polymerization side reactions and low carbon balance for biomass conversion.展开更多
Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) pa...Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.展开更多
基金Supported by Research Project for Practice Development of National Traditional Chinese Medicine Clinical Research Bases(No.JDZX2012128)
文摘OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia,and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine.METHODS: In total,168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study,and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily,while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for12 weeks. Mini-mental state examinations(Chinese version) and Montreal Cognitive Assessments(Beijing version) were performed,and fasting plasma glucose,fasting insulin,hemoglobin A1 c,homeostasis model assessment of insulin resistance,plasma nitric oxide and endothelin-1 levels were measured before and after the treatment.RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treatment levels(P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group(P < 0.05).CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore,the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.
文摘To clarify the modulation of dragon's blood on the tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root ganglion (DRG) neurons and explore its corresponding material basis for the efficacy, using whole-cell patch clamp technique, the effects of dragon's blood and the combined effects of three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from dragon's blood on the TTX-R sodium currents in acute-isolated DRG neurons of rats were observed. According to the operational definition of material basis for the efficacy of TCM established, the material basis of the modulation on the TTX-R sodium currents in DRG neurons of dragon's blood was judged from the experimental results. The drug interaction equation of Greco et al. was used to assess the interaction of the three components extracted from dragon's blood. This investigation demonstrated that dragon's blood suppressed the peak TTX-R sodium currents in a dose-dependent way and affected the activations of TTX-R sodium currents. The effects of the combination of cochinchinenin A, cochinchinenin B, and loureirin B were in good agreement with those of dragon's blood. Although the three components used alone could modulate TTX-R sodium currents, the concentrations of the three components used alone were respectively higher than those used in combination when the inhibition rates on the TTX-R sodium currents of them used alone and in combination were the same. The combined effects of the three components were synergistic. These results suggested that the interference with pain messages caused by the modulation of dragon's blood on TTX-R sodium currents in DRG neurons may explain some of the analgesic effect of dragon's blood and the corresponding material basis for the efficacy is the combination of cochinchinenin A, cochinchinenin B, and loureirin B.
基金supported by Prophase Project of National Key Basic Research Program of China(2012CB126312)Science and Technology Foundation of Guizhou Province of China([2012]2277)
文摘Domain of unknown function 1644 （DUF1644） is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of Os.SIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference （RNAi） were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid （ABA） treatment was not changed in OsStDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA- deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies （PBs） and stress granules （SGs） in rice protoplasts. Digital gene expression （DGE） profile analysis indicated that stress-related genes such as SNACl, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.
基金supported by the National Natural Science Foundation of China(No.51204213)the Key Project of Science and Technology of Hunan Province(No.2013WK2007)the Innovation Stimulating Program of Central South University(No.2015CX001)
文摘Heavy metals and ammonia are difficult to remove from wastewater,as they easily combine into refractory complexes.The struvite formation method（SFM） was applied for the complex decomposition and simultaneous removal of heavy metal and ammonia.The results indicated that ammonia deprivation by SFM was the key factor leading to the decomposition of the copper-ammonia complex ion.Ammonia was separated from solution as crystalline struvite,and the copper mainly co-precipitated as copper hydroxide together with struvite.Hydrogen bonding and electrostatic attraction were considered to be the main surface interactions between struvite and copper hydroxide.Hydrogen bonding was concluded to be the key factor leading to the co-precipitation.In addition,incorporation of copper ions into the struvite crystal also occurred during the treatment process.
基金supported by the National Natural Science Foundation of China(No.51974192)Shanxi Province Postgraduate Education Innovation Project(No.2020SY567)+2 种基金the Applied Basic Research Project of Shanxi Province(No.201801D121092)Distinguished Youth Funds of National Natural Science Foundation of China(No.51925402)Shanxi Science and Technology Major Project(No.20201102004)。
文摘To investigate the creep and instability properties of a cemented gangue backfill column under a highstress area,the uniaxial compression creep tests were conducted by single-step and multi-step loading of prismatic samples made of cemented gangue backfill material(CGBM)under the high stressstrength ratio.The creep damage was monitored using an electrical resistivity device,ultrasonic testing device,and acoustic emission(AE)instrument.The results showed that the CGBM sample has a creep hardening property.The creep failure strength(CFS)is slightly larger than the uniaxial compressive strength(UCS),ranging in ratio from 108.9%to 116.5%.The instantaneous strain,creep strain,and creep rate increase with increasing stress-strength ratio in the single-step loading creep tests.The instantaneous strain and creep strain decrease first and then increase during the multi-step loading creep process.The axial creep strain of the CGBM column can be expressed by the viscoelastic-plastic creep model.Creep instability is caused by the accumulation of strain energy under multi-step loading and the continuous lateral expansion at the unconstrained middle position during the creep process.The creep stability of a CGBM column in a high-stress area can be monitored based on the variation of electrical resistivity,ultrasonic pulse velocity(UPV),and AE signals.
基金Under the auspices of Knowledge Innovation Programs of Chinese Academy of Sciences (No. KZCX2-YW-309)National Natural Science Foundation of China (No. 40871089, 40830535)
文摘The effects of freeze-thaw cycles on sorption/desorption of dissolved organic carbon （DOC） in two wetland soils and one reclaimed wetland soil were investigated. DOC concentrations added were 0-600 mg/L. Laboratory incubations of sorption/desorption of DOC had been carried out at -15℃ for 10 h, and then at ＋5℃ for 13 h. Soil samples were refrozen and thawed subsequently for 5 cycles. Initial Mass model was used to describe sorption behavior of DOC. The results indicate that freeze-thaw cycles can significantly increase the sorption capacity of DOC and reduce the desorption capacity of DOC in the three soils. The freeze-thaw effects on desorpfion of DOC in soils increase with the increasing freeze-thaw cycles. The conversion of natural wetlands to soybean farmland can decrease the sorption capacity and increase the desorption capacity of DOC in soils. Global warming and reclamation may increase DOC release, and subsequently increase the loss of carbon and the emission of greenhouse gas.
基金National Key R&D Program of China(2017YFB0202600 and 2020YFC0841400)National Natural Science Foundation of China(91742109,8152204,31770978,81773674,and 21877134)+8 种基金National Health&Medical Research of Australia(1080321,1143976 and 1150425)Science Foundation of Guangzhou City(201904020023,China)Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme(2016 and 2019,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(China)National Health&Medical Research of Australia(1080321,1143976,and 1150425)Taikang Insurance Group Co.,Ltd.Beijing Taikang Yicai Foundation(Beijing,China)
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.
基金supported by the Ministry of Agriculture of the People’s Republic of China (No. 2016ZX08009-001008)The National Natural Science Foundation of China (No. 31471152)
文摘Auxin is an important plant hormone that is essential for growth and development due to its effects on organogenesis, morphogenesis, tropisms, and apical dominance. The functional diversity of auxin highlights the importance of its biosynthesis, transport, and associated responses. In this study, we show that a NAC transcription factor, ANAC092(also named At NAC2 and ORESARA1),known to positively regulate leaf senescence and contribute to abiotic stress responses, also affects primary root development. Plants overexpressing ANAC092 had altered root meristem lengths and shorter primary roots compared with the wild-type control. Additionally, expression of the pro ANAC092::GUS was strongly induced by indole-3-acetic acid. Quantitative real-time RT-PCR(q RT-PCR) analysis revealed that the YUCCA2, PIN, and ARF expression levels were downregulated in ANAC092-overexpressing plants. Moreover, yeast one-hybrid and chromatin immunoprecipitation assays confirmed that ANAC092 binds to the promoters of AUXIN RESPONSE FACTOR 8(ARF8) and PIN-FORMED 4(PIN4). Furthermore, a dual-luciferase assay indicated that ANAC092 decreases ARF8 and PIN4 promoter activities. We also applied a CRISPR/Cas9 system to mutate ANAC092. The roots of three of the analyzed mutants were longer than normal. Collectively, our findings indicate that ANAC092 negatively affects root development by controlling the auxin pathway.
文摘Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of100mL of autologous blood into the striatum. Rats were divided into three groups (n = 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed. Results: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P 0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T2) in the rim at 4 days after ICH (P 0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P 0.05) and increased number of blood vessels (P 0.05). Conclusions: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement.
基金supported by the National Natural Science Foundation of China(31970604,31900903,31770879)the Major Research Plan of the National Natural Science Foundation of China(91940000)+3 种基金the National Key Research and Development Program of China(2017YFA0504400)in part by the Guangdong Province Key Laboratory of Computational Science(13lgjc05)the Guangdong Province Computational Science Innovative Research Team(14lgjc18)the Fundamental Research Funds for the Central Universities(20lgpy112,2021qntd26)。
文摘The CREB1 gene encodes an exceptionally pleiotropic transcription factor that frequently dysregulated in human cancers.CREB1 can regulate tumor cell status of proliferation and/or migration;however,the molecular basis for this switch involvement in cell plasticity has not fully been understood yet.Here,we first show that knocking out CREB1 triggers a remarkable effect of epithelial-mesenchymal transition(EMT)and leads to the occurrence of inhibited proliferation and enhanced motility in HCT116colorectal cancer cells.By monitoring 45 cellular signaling pathway activities,we find that multiple growth-related pathways decline significantly while inflammatory pathways including NF-κB are largely upregulated in comparing between the CREB1wild-type and knocked out cells.Mechanistically,cells with CREB1 knocked out show downregulation of MYC as a result of impaired CREB1-dependent transcription of the oncogenic lnc RNA CCAT1.Interestingly,the unbalanced competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-κB pathway in cells with CREB1 disrupted,which induces an obvious EMT phenotype of the cancer cells.Taken together,these studies identify previously unknown mechanisms of CREB1 in CRC cell plasticity via regulating lnc RNA CCAT1 and NF-κB pathways,providing a critical insight into a combined strategy for CREB1-targeted tumor therapies.
基金supported by the National Basic Research Program of China (2010CB226901)
文摘The basic-nitrogen aromatic compounds in feedstocks and liquid products from the micro-reactor and soluble components of coke obtained during fluid catalytic cracking （FCC） process were analyzed by the micro-electrospray ioniza- tion （ESI） 9.4T Fourier transform ion cyclotron resonance mass spectrometry （FT-ICR MS） with an average mass resolving power of 300 000 at a mass range of 100--1 200. The analytical results revealed that the coker gas oil （CGO） contained a higher abundance of basic-nitrogen aromatic compounds with the type of-SN to -9N compared with those in deasphalted oil （DAO） and mixed FCC feedstock. After catalytic cracking, the abundance of lowly condensed basic-nitrogen aromatic compounds was much less than those of highly condensed aromatics in the liquid products, with the carbon number mainly ranging from 6 to 25 and the average carbon number of the side-chains equating to 1--5. On the contrary, with respect to the soluble components of coke, the abundance of lowly condensed basic-nitrogen aromatic compounds was more than those of highly condensed aromatics, and the carbon number ranged from 12 to 30, which was much smaller than that of the mixed FCC feedstock but slightly larger than that of the cracked liquid products. These results have provided some fundamental information on FCC process.
文摘Hepatocellular carcinoma (HCC) has already become a severe health risk and brings a lot of healthcare burden to the world. Apart from traditional HCC treatment strategies (surgery, liver transplantation, etc.), the emergence of immunotherapy targeting the immune microenvironment of HCC has brought new promise to patients with advanced HCC. However, adverse effects like drug resistance still exist. The liver is the main organ for storing copper ions, in copper overload can lead to liver function impairment and even the development of HCC. In recent years, a new mode of cell death has been identified, namely cuproptosis, a mode of programmed cell death that is dependent on copper ions and the tricarboxylic acid (TCA) cycle with mitochondria. Interestingly, a potential relationship between cuproptosis and the development of HCC has been found. Conclusively, this review provides an in-depth discussion of copper homeostasis in humans, the mechanism of cuproptosis, the potential impact of cuproptosis with HCC, and the therapeutic modalities of HCC that target cuproptosis, which provide new insights to promote the development of research targeting cuproptosis in HCC.
基金supported by the National Basic Research Development Program "973" Project of China(2010CB732301)the SINOPEC Research and Development Program(No.112034)
文摘The vanadium species were contaminated on FCC catalysts by using the Mitchell method. After the hydrothermal deactivation of the FCC catalysts, the cracking reaction was performed on these catalyst samples. The test results revealed that the conversion of feedstock and the gasoline yield obtained over the FCC catalysts with vanadium trapping components were obviously higher than those without addition of vanadium trapping components. The results also showed that the dry gas and coke selectivity on the FCC catalysts containing vanadium trapping components was improved. The X-Ray diffraction results proved that the zeolite crystal structure was well protected by the vanadium trapping components during its hydrothermal deactivation step. The results of SEM-EDX mapping disclosed that the vanadium was enriched on the vanadium trapping components which verified the positive function of vanadium trapping components.
文摘Background Chemoresistance is common among patients with esophageal squamous cell carcinoma （ESCC）.We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.Methods The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay.The times T1,when the number of living cells reached a plateau and T2,when the number of living cells reached a new plateau after the addition of insulin were found.T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin （MDC）.Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively.Apoptotic ratio and fluorescent intensity were analysed by flow cytometry （FCM） quantitatively.Western blotting analysis was used to estimate the protein expression levels of AKT,mTOR,PI3K,PTEN,autophage related indicator LC3-Ⅱ and autophage related protein Beclin1 changes that occurred in the course of treatment.Results A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin.Insulin can increase the apoptosis induced by cisplatin.Apoptotic ratio of T1 plateau cells （（32.6±4.3）％） is significantly less than T2 plateau （（47.5±5.6）％）.MDC fluorescent intensity at T1 plateau （104.9±13.2） was significantly higher than intensity at T2 plateau （82.6±10.3）.After cotreatment with insulin,the expression level of LC3-Ⅱ,Beclin1 and PTEN in T2 plateau cells were significantly downregulated,but AKT,mTOR and PI3K expressions significantly upregulated compared with T1 plateau.Conclusions Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy.The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells,which may be attributed to the anticancer effects of cisplatin.
基金supported by the National Natural Science Foundation of China(No.82060042)Guangxi Natural ScienceFoundation(China)(No.2020GXNSFBA297082)+1 种基金Guangxi Science and Technology Program Project(China)(No.AD19245005)The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi(China)(No.2020KY12017).
文摘Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.
基金supported by the funds from National Natural Science Foundation of China(Grant No.81672762,81622037 and 81602446)
文摘Objective:Pyruvate kinases M(PKM),including the PKM1 and PKM2 isoforms,are critical factors in glucose metabolism.PKM2promotes aerobic glycolysis,a phenomenon known as"the Warburg effect".The purpose of this study was to identify the roles of PKM2 in regulating cellular metabolism.Methods:The CRISPR/Cas9 system was used to generate the PKM-knockout cell model to evaluate the role of PKM in cellular metabolism.Lactate levels were measured by the Vitros LAC slide method on an autoanalyzer and glucose levels were measured by the autoanalyzer AU5800.The metabolism of ^(13)C_6-glucose or ^(13)C_5-glutamine was evaluated by liquid chromatography/mass spectrometry analyses.The effects of PKM on tumor growth were detected in vivo in a tumor-bearing mouse model.Results:We found that both PKM1 and PKM2 enabled aerobic glycolysis,but PKM2 converted glucose to lactate much more efficiently than PKM1.As a result,PKM2 reduced glucose levels reserved for intracellular utilization,particularly for the production of citrate,and thus increased theα-ketoglutarate/citrate ratio to promote the generation of glutamine-derived acetylcoenzyme A through the reductive pathway.Furthermore,reductive glutamine metabolism facilitated cell proliferation under hypoxia conditions,which supports in vivo tumor growth.In addition,PKM-deletion induced a reverse Warburg effect in tumorassociated stromal cells.Conclusions:PKM2 plays a critical role in promoting reductive glutamine metabolism and maintaining proton homeostasis.This study is helpful to increase the understanding of the physiological role of PKM2 in cancer cells.
基金the National Natural Science Foundation of China,No. 30571909,30872666,30870808the Foundation of Shanghai Forensic Key Laboratory,No. KF0904
文摘BACKGROUND：Various molecular mechanisms of cell death following traumatic brain injury have been previously described.However,the time course of cell death remains unclear.TUNEL and Fluoro-Jade B labeling have been widely used to label apoptotic cells and neuronal degeneration.Propidium iodide （PI） functions as a biomarker of cell death in vivo.OBJECTIVE：To explore the role of PI labeling compared to TUNEL and Fluoro-Jade B staining for detecting neural cell death,and to observe time course of traumatic brain injury-induced cell death in mice.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Laboratory of Aging and Nervous Diseases,Soochow University from September 2007 to December 2008.MATERIALS：PI （B1221） was purchased from Sigma,USA.TUNEL kit was purchased from Roche Molecular Biochemicals,USA.Fluoro-Jade B was purchased from Chemicon,USA.METHODS：A total of 70 healthy,male,Kunming mice were randomly assigned to sham-surgery （n = 5） and model （n = 65） groups.Traumatic brain injury was established using the controlled cortical impact method.PI was intraperitoneally injected at 1 hour prior to animal sacrifice.MAIN OUTCOME MEASURES：TUNEL,Fluoro-Jade B,and Pl-positive cells were quantified using a double-labeling method to determine the time course of traumatic brain injury-induced cell death.RESULTS：PI labeled cells in an earlier phase of cell death than TUNEL and Fluoro-Jade B labeling.Pl-positive cells were observed immediately following injury,and the numbers rapidly increased in injured brain areas at 1 hour,peaked at 24-48 hours,and subsequently decreased at 3-21 days post-injury.TUNEL-labeled cells were significantly increased at 12 hours,while Fluoro-Jade B-labeled cells were increased at 6 hours after injury,with cells still visible at 6-48 hours post-injury.Moreover,a greater number of Pl-positive cells were observed compared to TUNEL- and Fluoro-Jade B-labeled cells.CONCLUSION：PI labeling is more sensitive and reliable than TUNEL and F
文摘Objective:To investigate the anti-tumor effect of macromolecular fractions of fresh gecko (M-AG) in vivo and their differentiation-inducing activity in Bel-7402 cells in vitro.Methods:An H22 hepatocarcinoma-bearing mouse model was used to evaluate the anti-tumor activity of M-AG samples.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to analyze cell viability.Cell morphology was observed by phase contrast microscopy.The quantity of the alpha-fetoprotein was detected by a radioimmunoassay.Chromatometry was used to assay the albumin quantity.Activities of alkaline phosphatase and γ-glutamyl trans-peptidase were measured by biochemical methods.Finally,western blotting was applied to assess proteins in the mitogen-activated protein kinase (MAPK) signaling pathway.Results:Macromolecular fractions of fresh gecko exerted a significant anti-tumor effect in mice.The inhibition rate of tumor growth was 63% in the moderate M-AG dose group.Cells treated with M-AG displayed a differentiated state.The treatment lowered alphafetoprotein secretion and significantly decreased the activities of γ-glutamyl trans-peptidase and alkaline phosphatase in Bel-7402 cells.In contrast,M-AG increased the amount of albumin in the cell culture medium.All biochemical indices demonstrated that M-AG induced Bel7402 cell differentiation.Western blotting showed no changes in the quantities of extracellular signal-regulated kinase (ERK) 1/2,p38MAPK,or c-Jun N-terminal protein kinase 1/2.However,M-AG significantly activated the phosphorylation of ERK1/2 in a dose-dependent manner.In addition,M-AG had no significant influence on the expression of nuclear factor-kappa B.Conclusion:Macromolecular fractions of fresh gecko has an anti-tumor activity in H22 hepatocarcinoma-bearing mice in vivo and inhibits Bel-7402 cell proliferation in vitro by inducing cell differentiation related to activation of ERK1/2.
文摘Tandem catalysis for the hydrogenation rearrangement of furfural(FA)provides an attractive solution for manufacturing cyclopentanone(CPO)from renewable biomass resources.The Cu-Ni/Al-MCM-41 catalyst was synthesized and afforded excellent catalytic performance with 99.0%conversion and 97.7%selectivity to CPO in a near-neutral solution under 2.0 MPa H2 at 160℃ for 5 h,much higher than those on other molecular sieve supports including MCM-41,SBA-15,HY,and ZSM-5.A small amount of Al highly dispersed in MCM-41 plays an anchoring role and ensures the formation of highly dispersed CuNi bimetallic nanoparticles(NPs).The remarkably improved catalytic performance may be attributed to the bimetallic synergistic and charge transfer effects.In addition,the initial FA concentration and the aqueous system pH required precise control to minimize polymerization and achieve high selectivity of CPO.Fourier transform infrared spectroscopy and mass spectra results indicated that polymerization was sensitive to pH values.Under acidic conditions,FA and intermediate furfuryl alcohol polymerize,while the intermediate 4-hydroxy-2-cyclopentenone mainly polymerizes under alkaline conditions,blocking the cascade of multiple reactions.Therefore,near-neutral conditions are most suitable for minimizing the impact of polymerization.This study provides a useful solution for the current universal problems of polymerization side reactions and low carbon balance for biomass conversion.
基金supported by the National Precision Medicine Project(2016YFC0905200)the National Natural Science Foundation of China(81790643,82121003,81570882,81770935,81670853,81271005)+1 种基金the grant from Chinese Academy of Medical Sciences(2019-I2M-5-032)the grant from the Department of Science and Technology of Sichuan Province(2021YFS0404,2021FS0369,2020YJ0445,2019JDJQ0031,2022JDTD0024)。
文摘Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.
