Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and ident...Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).展开更多
A simplified model for SO_(2) generation during spontaneous combustion of coal gangue was put forward and validated using the measured data.Using the proposed model,the effects of initial temperature inside the gangue...A simplified model for SO_(2) generation during spontaneous combustion of coal gangue was put forward and validated using the measured data.Using the proposed model,the effects of initial temperature inside the gangue and fresh air supply on SO_(2) generation were discussed.The results showed that,higher initial temperature inside the gangue could accelerate the oxidation rate of FeS_(2) and increase the maximum concentration of SO_(2).If initial temperature inside the gangue increased by about 37%,the total SO_(2) generation increased by 166%.Fresh air supply had less significant effect on the oxidation rate of FeS_(2).However,the higher the fresh air supply was,the more FeS_(2) could be oxidized,which ultimately produced more SO_(2).Although the computed results and the measured data concerning the inner locations inside the gangue had a certain degree of error,the proposed model can provide a relatively precise total release of SO_(2) within acceptable accuracy.Besides,this method provides a useful prototype to predict the generation of hazardous materials,such as CO,NO_(x),and chlorine during the spontaneous combustion of coal gangue.展开更多
We calculate the properties of static strange stars using a quark model with chiral mass scaling. The results are characterized by a large maximum mass （-1.6 M⊙） and radius （-10km）. Together with a broad collecti...We calculate the properties of static strange stars using a quark model with chiral mass scaling. The results are characterized by a large maximum mass （-1.6 M⊙） and radius （-10km）. Together with a broad collection of modern neutron star models, we discuss some recent astrophysical observational data that could shed new light on the possible presence of strange quark matter in compact stars. We conclude that none of the present astrophysical observations can prove or confute the existence of strange stars.展开更多
The indocyanine green(ICG)clearance test is an objective measurement of functional liver reserve(FLR)[1].The liver can preserve normal functions with a 70%−80%functional liver volume resection[2]and the remnant is cap...The indocyanine green(ICG)clearance test is an objective measurement of functional liver reserve(FLR)[1].The liver can preserve normal functions with a 70%−80%functional liver volume resection[2]and the remnant is capable of regeneration.However,liver regenerative properties are affected by hepatitis,fatty liver,cirrhosis and damage caused by chemotherapy[3].ICG combined with the Child-Pugh score are main criteria for evaluating FLR.A safe hepatectomy procedure requires the remnant liver to be 25%−30%of the normal volume.For patients with an indocyanine green retention rate at 15 min(ICG-R15)>20%,segment liver resection,limited hepatectomy or tumor enucleation is recommended,but there has been no clear clarification of the essential remnant liver volume[4].In China,the experts’consensus of preoperative evaluation of liver reserve function incorporates ICGR15 tests.展开更多
Previous studies have reported a relationship between exposure to metals and polycyclic aromatic hydrocarbons(PAHs)and blood glucose levels,but whether the mechanisms are mediated by amino acids remains to be elucidat...Previous studies have reported a relationship between exposure to metals and polycyclic aromatic hydrocarbons(PAHs)and blood glucose levels,but whether the mechanisms are mediated by amino acids remains to be elucidated.We conducted a three-wave repeated measurement study involving 201 elderly individuals(aged≥50 years)from five communities in Beijing,China.We simultaneously measured eightmetals in both blood and urine,six monohydroxy PAHs in urine,and 23 amino acids in blood.Linear mixed-effects and sparse partial least squares models were used to evaluate the individual effects,and Bayesian kernel machine regression was employed to mixture effects.Mediation analysis was further used to explore whether amino acids mediators mediate the association.We observed significant associations of selenium and strontium with increased blood glucose.Additionally,blood copper,urinary nickel,as well as urinary 1+9 hydroxyphenanthrene,were associated with irregular blood glucose regulation.Moreover,we found that amino acids such as leucine,proline,and alanine may mediate the associations.This study is the first to investigate the effect of metals and PAHs on blood glucose homeostasis,while also exploring the mediating role of amino acids,offering new insights into the impact of metals and PAHs on blood glucose regulation.展开更多
Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associate...Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associated with per-and polyfluoroalkyl substances(PFAS)exposure.However,there is limited evidence for this association in cardiovascular subpopulations,particularly in the ACS patients.Therefore,we performed this study to evaluate the association between plasma PFAS exposure and hepatobiliary system function biomarkers in patients with ACS.This study included 546 newly diagnosed ACS patients at the Second Hospital of Hebei Medical University,and data on 15 hepatobiliary system function biomarkers were obtained from medical records.Associations between single PFAS and hepatobiliary system function biomarkers were assessed using multiple linear regression models and restricted cubic spline model(RCS),and mixture effects were assessed using the Quantile g-computation model.The results showed that total bile acids(TBA)was negative associated with perfluorohexane sulfonic acid(PFHxS)(-7.69%,95%CI:-12.15%,-3.01%).According to the RCS model,linear associations were found between TBA and PFHxS(P for overall=0.003,P for non-linear=0.234).We also have observed the association between between PFAS congeners and liver enzyme such as aspartate aminotransferase(AST)and α-l-Fucosidase(AFU),but it was not statistically significant after correction.In addition,Our results also revealed an association between prealbumin(PA)and PFAS congeners as well as mixtures.Our findings have provided a piece of epidemiological evidence on associations between PFAS congeners or mixture,and serum hepatobiliary system function biomarkers in ACS patients,which could be a basis for subsequent mechanism studies.展开更多
BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose c...BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.展开更多
Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step...Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.展开更多
Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly di...Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.展开更多
AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly dist...AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.展开更多
Yangtze River Delta （YRD） area is one of the important economic zones in China. However, this area faces increasing environmental problems. In this study, we use ground-based multi-axis differential optical absorpti...Yangtze River Delta （YRD） area is one of the important economic zones in China. However, this area faces increasing environmental problems. In this study, we use ground-based multi-axis differential optical absorption spectroscopy （MAX-DOAS） network in Eastern China to retrieve variations of NO2, SO2, and formaldehyde （HCHO） in the YRD area. Three cities of YRD （Hefei, Nanjing, and Shanghai） were selected for long-term observations. This paper presents technical performance and characteristics of instruments, their distribution in YRD, and results of vertical column densities （VCDs） and profiles of NO2, SO2, and HCHO. Average diurnal variations of tropospheric NO2 and SO2 in different seasons over the three stations yielded minimum values at noon or in the early afternoon, whereas tropospheric HCHO reached the maximum during midday hours. Slight reduction of the pollutants in weekends occurred in all the three sites. In general trace gas concentrations gradually reduced from Shanghai to Hefei. Tropospheric VCDs of NO2, SO2, and HCHO were compared with those from Ozone Monitoring Instrument （OMI） satellite observations, resulting in R2 of 0.606, 0.5432, and 0.5566, respectively. According to analysis of regional transports of pollutants, pollution process happened in YRO under the north wind with the pollution dissipating in the southeast wind. The feature is significant in exploring transport of tropospheric trace gas pollution in YRD, and provides basis for satellite and model validation.展开更多
Microseismic(MS)event locations are vital aspect of MS monitoring technology used to delineate the damage zone inside the surrounding rock mass.However,complex geological conditions can impose significantly adverse ef...Microseismic(MS)event locations are vital aspect of MS monitoring technology used to delineate the damage zone inside the surrounding rock mass.However,complex geological conditions can impose significantly adverse effects on the final location results.To achieve a high-accuracy location in a complex cavern-containing structure,this study develops an MS location method using the fast marching method(FMM)with a second-order difference approach(FMM2).Based on the established velocity model with three-dimensional(3D)discrete grids,the realization of the MS location can be achieved by searching the minimum residual between the theoretical and actual first arrival times.Moreover,based on the calculation results of FMM2,the propagation paths from the MS sources to MS sensors can be obtained using the linear interpolation approach and the Runge–Kutta method.These methods were validated through a series of numerical experiments.In addition,our proposed method was applied to locate the recorded blasting and MS events that occurred during the excavation period of the underground caverns at the Houziyan hydropower station.The location results of the blasting activities show that our method can effectively reduce the location error compared with the results based on the uniform velocity model.Furthermore,the obtained MS location was verified through the occurrence of shotcrete fractures and spalling,and the monitoring results of the in-situ multipoint extensometer.Our proposed method can offer a more accurate rock fracture location and facilitate the delineation of damage zones inside the surrounding rock mass.展开更多
Hepatitis B virus(HBV)has posed a threat to public health,mainly resulting in liver damage.With long-term accumulation of extracellular matrix,patients with chronic hepatitis B are at high risk of developing into live...Hepatitis B virus(HBV)has posed a threat to public health,mainly resulting in liver damage.With long-term accumulation of extracellular matrix,patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma.The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality.With deeper understanding of the bidirectional interaction between the liver and the gut(gut-liver axis),there is a growing consensus that the human health closely relates to the gut microbiota.Supported by animal and human studies,the gut microbiota alters as the HBV-related liver fibrosis initials and progresses,characterized as the decrease of the ratio between“good”and“potentially pathogenic”microbes.When the primary disease is controlled via antiviral treatment,the gut microbiota dysfunction tends to be improved.Conversely,the recovery of gut microbiota can promote the regression of liver fibrosis.Therapeutic strategies targeted on gut microbiota(rifaximin,probiotics,engineered probiotics and fecal microbiota transplantation)have been applied to animal models and patients,obtaining satisfactory results.展开更多
Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful fo...Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful for treatment of retinal diseases.The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice,a slow photoreceptor-degenerative model of retinitis pigmentosa.Luteolin(100 mg/kg)intraperitoneally injected daily from postnatal day 14(P14)to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25.Moreover,it increased the survival of photoreceptors and improved retinal structure.Mechanistically,luteolin treatment attenuated increases in reactive oxygen species,photoreceptor apoptosis,and reactive gliosis;increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines;and lowered the ratio of phospho-JNK/JNK.Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin,suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway.Therefore,luteolin may be useful as a supplementary treatment for retinitis pigmentosa.This study was approved by the Qualified Ethics Committee of Jinan University,China(approval No.IACUC-20181217-02)on December 17,2018.展开更多
AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five gr...AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.展开更多
BACKGROUND Handling of the inferior mesenteric artery(IMA)and maintaining anastomotic perfusion are important in radical resection of left-sided colorectal cancer.However,the branching of this artery and the drainage ...BACKGROUND Handling of the inferior mesenteric artery(IMA)and maintaining anastomotic perfusion are important in radical resection of left-sided colorectal cancer.However,the branching of this artery and the drainage patterns of this vein vary among individuals,and the characteristics and perfusion region of this artery in elderly patients remain unclear.AIM To evaluate the characteristics and perfusion region of the IMA in elderly patients using angiography.METHODS We enrolled 154 patients(>65 years old)who underwent digital subtraction angiography of the IMA.The characteristics,bifurcation,and distribution of the IMA and termination of the anastomotic perfusion of the left colon and rectum were examined using digital subtraction angiography.Collateral arterial arches and the IMA hemoperfusion region were also recorded.Perfusion regions were cross-referenced with clinical and anatomical features by the univariate analysis.RESULTS Of 154 patients,25(16.2%)had IMA lesions.The left colic artery arose independently from the IMA in 44.2%of patients,shared a trunk with the sigmoid artery in 35.1%,shared an opening with the sigmoid and superior rectal arteries in 16.9%,and was absent in 5.1%.The IMA perfusion region stopped at the splenic flexure in 50(32.5%)patients.The collateral circulation existed in the colonic perfusion region,including the marginal artery(Drummond’s artery),the ascending branch of the left colonic artery to supply the transverse colon,and the arc of Riolan with a frequency of 100%,22.7%,and 1.9%,respectively.The IMA perfusion region was independently associated with the comorbidity of atherosclerosis,IMA atherosclerotic lesion,branching pattern,collateral circulation,and marginal artery integrity.CONCLUSION The IMA and its branches are prone to arteriosclerosis,and IMA perfusion may be interrupted at the splenic flexure in elderly patients.The applicability and precision of preoperative angiography for evaluating the IMA branching and perfusion patterns could facilitate geriatric laparoscopic left-sided colorectal cancer surgery with suspicion of poor IMA perfusion.展开更多
Objective To construct an expression vector of small interfering RNA （siRNA） against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast can...Objective To construct an expression vector of small interfering RNA （siRNA） against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast cancer cell line MCF-7. Methods Constructed an expression vector of siRNA against survivin and transfected it into PC-2 and MCF-7 cells using lipofectamine^TM 2000. The expression of survivin was detected by semi-quanfifive RT-PCR and immunohistochemistry, and its effects on proliferation of PC-2 and MCF-7 cells were detected by MTT assay. Results The introduction of sequence-specific siRNA could efficiently suppress survivin expression at both mRNA and protein levels in the two cancer cell lines. In PC-2 cells, the expression inhibition rates were 81.25% at mRNA level and 74.24% at protein level In MCF-7 cells, the expression inhibition rates were 64.91% at mRNA level and 79. 72% at protein level The proliferation of PC-2 and MCF-7 cells was also suppressed, and24 and 48 hours after the cells were reseeded, the proliferation inhibition rates of PC-2 cells were 28. 00% and 33. 38%, and that of MCF-7 cells were 31.58% and 33.02%, respectively. Conclusions The expression vector of siRNA against survivin can block survivin expression in PC-2 and MCF-7 cells efficiently and specifically. Down regulation of survivin expression can suppress proliferation of PC-2 and MCF-7 cells. Survivin RNAi may have potential value in gene therapy of human cancers.展开更多
Aquaporins(AQPs)are a family of integral membrane proteins that have been shown to be important for osmoregulation in many vertebrates.To identify potential stress resistance-related aqp genes in salinity adaptation o...Aquaporins(AQPs)are a family of integral membrane proteins that have been shown to be important for osmoregulation in many vertebrates.To identify potential stress resistance-related aqp genes in salinity adaptation of the roughskin sculpin Trachidermus fasciatus,we investigated the time-course expression dynamics of seven aquaporin genes(aqp1,4,7,8,10,11 and 12)in three osmoregulatory tissues(kidney,gill and intestine)and one metabolic tissue(liver).The fish were subjected to two different acute osmotic treatments(seawater-tofreshwater transfer respectively achieved in 1 h and 24 h,namely,E-acute and acute group).The expression profiling of the seven aqp genes were performed using quantitative real-time PCR(qRT-PCR).At the time of all sampling time points(0 h,12 h,24 h and 48 h),no expression of aqp4 was found in the gill,liver and intestine;no expression of aqp7 was found in the gill and liver.Significant differences of aqp expression were determined in the four target tissues,and the mRNA levels were largely variable among gene members and tissues.Similar patterns of the time-course expression were detected in most of the aqp genes in T.fasciatus between the two acute groups,except that only one gene(aqp12)in the kidney and three genes(aqp7,aqp8 and aqp10)in the intestine revealed different expression patterns.These results suggest that the expression response of aqp genes was similar under osmotic changes with different rates.展开更多
With the explosive development of artificial intelligence(AI),machine learning(ML),and high-performance comput-ing(HPC),the ever-growing data movement is asking for high density interconnects with higher bandwidth(BW)...With the explosive development of artificial intelligence(AI),machine learning(ML),and high-performance comput-ing(HPC),the ever-growing data movement is asking for high density interconnects with higher bandwidth(BW),lower power and lower latency[1−3].The optical I/O leverages silicon photonic(SiPh)technology to enable high-density large-scale integrated photonics.展开更多
D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the imp...D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.展开更多
基金supported by the National Natural Science Foundation of China,No.81330042,81620108018(both to SQF),and 81702147(to ZJW)
文摘Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).
基金the financial support provided by the Major Science and Technology Projects of Inner Mongolia Autonomous Region under Grant No.RZ190001148Fund of Education Department of Inner Mongolia Autonomous Region under Grant No.NJZY21480.
文摘A simplified model for SO_(2) generation during spontaneous combustion of coal gangue was put forward and validated using the measured data.Using the proposed model,the effects of initial temperature inside the gangue and fresh air supply on SO_(2) generation were discussed.The results showed that,higher initial temperature inside the gangue could accelerate the oxidation rate of FeS_(2) and increase the maximum concentration of SO_(2).If initial temperature inside the gangue increased by about 37%,the total SO_(2) generation increased by 166%.Fresh air supply had less significant effect on the oxidation rate of FeS_(2).However,the higher the fresh air supply was,the more FeS_(2) could be oxidized,which ultimately produced more SO_(2).Although the computed results and the measured data concerning the inner locations inside the gangue had a certain degree of error,the proposed model can provide a relatively precise total release of SO_(2) within acceptable accuracy.Besides,this method provides a useful prototype to predict the generation of hazardous materials,such as CO,NO_(x),and chlorine during the spontaneous combustion of coal gangue.
基金funded by the National Basic Research Program of China (Grant No. 2009CB824800)the National Natural Science Foundation of China (Grant No. 10905048)the Youth Innovation Foundation of FujianProvince (Grant No. 2009J05013)
文摘We calculate the properties of static strange stars using a quark model with chiral mass scaling. The results are characterized by a large maximum mass （-1.6 M⊙） and radius （-10km）. Together with a broad collection of modern neutron star models, we discuss some recent astrophysical observational data that could shed new light on the possible presence of strange quark matter in compact stars. We conclude that none of the present astrophysical observations can prove or confute the existence of strange stars.
基金This study was supported by a grant from the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201712).
文摘The indocyanine green(ICG)clearance test is an objective measurement of functional liver reserve(FLR)[1].The liver can preserve normal functions with a 70%−80%functional liver volume resection[2]and the remnant is capable of regeneration.However,liver regenerative properties are affected by hepatitis,fatty liver,cirrhosis and damage caused by chemotherapy[3].ICG combined with the Child-Pugh score are main criteria for evaluating FLR.A safe hepatectomy procedure requires the remnant liver to be 25%−30%of the normal volume.For patients with an indocyanine green retention rate at 15 min(ICG-R15)>20%,segment liver resection,limited hepatectomy or tumor enucleation is recommended,but there has been no clear clarification of the essential remnant liver volume[4].In China,the experts’consensus of preoperative evaluation of liver reserve function incorporates ICGR15 tests.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0513200)the National Natural Science Foundation of China(Nos.82404278 and 82404365)China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066).
文摘Previous studies have reported a relationship between exposure to metals and polycyclic aromatic hydrocarbons(PAHs)and blood glucose levels,but whether the mechanisms are mediated by amino acids remains to be elucidated.We conducted a three-wave repeated measurement study involving 201 elderly individuals(aged≥50 years)from five communities in Beijing,China.We simultaneously measured eightmetals in both blood and urine,six monohydroxy PAHs in urine,and 23 amino acids in blood.Linear mixed-effects and sparse partial least squares models were used to evaluate the individual effects,and Bayesian kernel machine regression was employed to mixture effects.Mediation analysis was further used to explore whether amino acids mediators mediate the association.We observed significant associations of selenium and strontium with increased blood glucose.Additionally,blood copper,urinary nickel,as well as urinary 1+9 hydroxyphenanthrene,were associated with irregular blood glucose regulation.Moreover,we found that amino acids such as leucine,proline,and alanine may mediate the associations.This study is the first to investigate the effect of metals and PAHs on blood glucose homeostasis,while also exploring the mediating role of amino acids,offering new insights into the impact of metals and PAHs on blood glucose regulation.
基金supported by the National Natural Science Foundation of China(No.21976050)the Science and Technology Program of Hebei Province(No.21377779D)+3 种基金the Natural Science Foundation of Hebei Province(No.B2020206008)China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301).
文摘Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associated with per-and polyfluoroalkyl substances(PFAS)exposure.However,there is limited evidence for this association in cardiovascular subpopulations,particularly in the ACS patients.Therefore,we performed this study to evaluate the association between plasma PFAS exposure and hepatobiliary system function biomarkers in patients with ACS.This study included 546 newly diagnosed ACS patients at the Second Hospital of Hebei Medical University,and data on 15 hepatobiliary system function biomarkers were obtained from medical records.Associations between single PFAS and hepatobiliary system function biomarkers were assessed using multiple linear regression models and restricted cubic spline model(RCS),and mixture effects were assessed using the Quantile g-computation model.The results showed that total bile acids(TBA)was negative associated with perfluorohexane sulfonic acid(PFHxS)(-7.69%,95%CI:-12.15%,-3.01%).According to the RCS model,linear associations were found between TBA and PFHxS(P for overall=0.003,P for non-linear=0.234).We also have observed the association between between PFAS congeners and liver enzyme such as aspartate aminotransferase(AST)and α-l-Fucosidase(AFU),but it was not statistically significant after correction.In addition,Our results also revealed an association between prealbumin(PA)and PFAS congeners as well as mixtures.Our findings have provided a piece of epidemiological evidence on associations between PFAS congeners or mixture,and serum hepatobiliary system function biomarkers in ACS patients,which could be a basis for subsequent mechanism studies.
基金Peking University First Hospital Institutional Review Board(No.2018104).
文摘BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.
基金supported by the National Natural Science Foundation of China(No.82404365)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0513200)+7 种基金China Medical Board(No.15-230)China Postdoctoral Science Foundation(Nos.2023M730317and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the National Key Research and Development Program of China(No.2022YFC3703000)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2022-JKCS-11)the CAMS Innovation Fund for Medical Sciences(No.2022-I2M-JB-003)the Programs of the National Natural Science Foundation of China(No.21976050).
文摘Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.
基金supported by the China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)+3 种基金the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the Programs of the National Natural Science Foundation of China(No.21976050)the Science and Technology Program of Hebei Province(No.21377779D)the Natural Science Foundation of Hebei Province,China(No.B2020206008).
文摘Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.
基金Supported by Beijing Municipal Science & Technology Commission Major Scitech Program,No.H020920050130
文摘AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.
基金supported by the National Natural Science Foundation of China (No: 41530644)the Monitoring and Assessment of Regional Air Quality in China using space Observations, Project Of Long-term sino-5 european co-Operation (MarcoPolo), FP7 (No: 606953)
文摘Yangtze River Delta （YRD） area is one of the important economic zones in China. However, this area faces increasing environmental problems. In this study, we use ground-based multi-axis differential optical absorption spectroscopy （MAX-DOAS） network in Eastern China to retrieve variations of NO2, SO2, and formaldehyde （HCHO） in the YRD area. Three cities of YRD （Hefei, Nanjing, and Shanghai） were selected for long-term observations. This paper presents technical performance and characteristics of instruments, their distribution in YRD, and results of vertical column densities （VCDs） and profiles of NO2, SO2, and HCHO. Average diurnal variations of tropospheric NO2 and SO2 in different seasons over the three stations yielded minimum values at noon or in the early afternoon, whereas tropospheric HCHO reached the maximum during midday hours. Slight reduction of the pollutants in weekends occurred in all the three sites. In general trace gas concentrations gradually reduced from Shanghai to Hefei. Tropospheric VCDs of NO2, SO2, and HCHO were compared with those from Ozone Monitoring Instrument （OMI） satellite observations, resulting in R2 of 0.606, 0.5432, and 0.5566, respectively. According to analysis of regional transports of pollutants, pollution process happened in YRO under the north wind with the pollution dissipating in the southeast wind. The feature is significant in exploring transport of tropospheric trace gas pollution in YRD, and provides basis for satellite and model validation.
基金the Key Program of National Natural Science Foundation of China(52039007)for providing financial support.
文摘Microseismic(MS)event locations are vital aspect of MS monitoring technology used to delineate the damage zone inside the surrounding rock mass.However,complex geological conditions can impose significantly adverse effects on the final location results.To achieve a high-accuracy location in a complex cavern-containing structure,this study develops an MS location method using the fast marching method(FMM)with a second-order difference approach(FMM2).Based on the established velocity model with three-dimensional(3D)discrete grids,the realization of the MS location can be achieved by searching the minimum residual between the theoretical and actual first arrival times.Moreover,based on the calculation results of FMM2,the propagation paths from the MS sources to MS sensors can be obtained using the linear interpolation approach and the Runge–Kutta method.These methods were validated through a series of numerical experiments.In addition,our proposed method was applied to locate the recorded blasting and MS events that occurred during the excavation period of the underground caverns at the Houziyan hydropower station.The location results of the blasting activities show that our method can effectively reduce the location error compared with the results based on the uniform velocity model.Furthermore,the obtained MS location was verified through the occurrence of shotcrete fractures and spalling,and the monitoring results of the in-situ multipoint extensometer.Our proposed method can offer a more accurate rock fracture location and facilitate the delineation of damage zones inside the surrounding rock mass.
基金National Key Research and Development Program of China,No.2018YFC2000500Research Project of Jinan Microecological Biomedicine Shandong Laboratory,No.JNL-2022001ANational Natural Science Foundation of China,No.U2004121,No.82070643 and No.U1904164
文摘Hepatitis B virus(HBV)has posed a threat to public health,mainly resulting in liver damage.With long-term accumulation of extracellular matrix,patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma.The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality.With deeper understanding of the bidirectional interaction between the liver and the gut(gut-liver axis),there is a growing consensus that the human health closely relates to the gut microbiota.Supported by animal and human studies,the gut microbiota alters as the HBV-related liver fibrosis initials and progresses,characterized as the decrease of the ratio between“good”and“potentially pathogenic”microbes.When the primary disease is controlled via antiviral treatment,the gut microbiota dysfunction tends to be improved.Conversely,the recovery of gut microbiota can promote the regression of liver fibrosis.Therapeutic strategies targeted on gut microbiota(rifaximin,probiotics,engineered probiotics and fecal microbiota transplantation)have been applied to animal models and patients,obtaining satisfactory results.
基金The work was supported by the National Natural Science Foundation of China,Nos.81470656(to YX),82071372(to AL),82074169(to XSM)Guangdong Grant Key Technologies for Treatment of Brain Disorders’,China,No.2018B030332001(to YX)+3 种基金Ningxia Key Research and Development Program Grant(Yinchuan,Ningxia Hui Autonomous Region,China)(to KFS)Program of Introducing Talents of Discipline to Universities,China,No.B14036(to YX,AL,KFS)Outstanding Scholar Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),No.2018GZR110102002(to KFS,AL)Science and Technology Program of Guangzhou,No.202007030012(to KFS and AL).
文摘Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful for treatment of retinal diseases.The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice,a slow photoreceptor-degenerative model of retinitis pigmentosa.Luteolin(100 mg/kg)intraperitoneally injected daily from postnatal day 14(P14)to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25.Moreover,it increased the survival of photoreceptors and improved retinal structure.Mechanistically,luteolin treatment attenuated increases in reactive oxygen species,photoreceptor apoptosis,and reactive gliosis;increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines;and lowered the ratio of phospho-JNK/JNK.Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin,suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway.Therefore,luteolin may be useful as a supplementary treatment for retinitis pigmentosa.This study was approved by the Qualified Ethics Committee of Jinan University,China(approval No.IACUC-20181217-02)on December 17,2018.
基金Supported by the National Natural Science Foundation of China,No.81672422,No.81600506,and No.81702757Open Project in State Key Laboratory for Diagnosis and Treatment of Infectious Disease,No.2015KF03+4 种基金National S&T Major Project of China,No.2018ZX10301201Natural Science Foundation of Zhejiang Province,No.LY15H160033China Postdoctoral Science Foundation,No.2017464Zhejiang Province Health Department Program,No.2014KYB081,and No.2017KY322Academician Jieshou Li Mucosal Barrier Fund,No.201208
文摘AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.
基金Supported by the National Natural Science Foundation of China,No.81800483.
文摘BACKGROUND Handling of the inferior mesenteric artery(IMA)and maintaining anastomotic perfusion are important in radical resection of left-sided colorectal cancer.However,the branching of this artery and the drainage patterns of this vein vary among individuals,and the characteristics and perfusion region of this artery in elderly patients remain unclear.AIM To evaluate the characteristics and perfusion region of the IMA in elderly patients using angiography.METHODS We enrolled 154 patients(>65 years old)who underwent digital subtraction angiography of the IMA.The characteristics,bifurcation,and distribution of the IMA and termination of the anastomotic perfusion of the left colon and rectum were examined using digital subtraction angiography.Collateral arterial arches and the IMA hemoperfusion region were also recorded.Perfusion regions were cross-referenced with clinical and anatomical features by the univariate analysis.RESULTS Of 154 patients,25(16.2%)had IMA lesions.The left colic artery arose independently from the IMA in 44.2%of patients,shared a trunk with the sigmoid artery in 35.1%,shared an opening with the sigmoid and superior rectal arteries in 16.9%,and was absent in 5.1%.The IMA perfusion region stopped at the splenic flexure in 50(32.5%)patients.The collateral circulation existed in the colonic perfusion region,including the marginal artery(Drummond’s artery),the ascending branch of the left colonic artery to supply the transverse colon,and the arc of Riolan with a frequency of 100%,22.7%,and 1.9%,respectively.The IMA perfusion region was independently associated with the comorbidity of atherosclerosis,IMA atherosclerotic lesion,branching pattern,collateral circulation,and marginal artery integrity.CONCLUSION The IMA and its branches are prone to arteriosclerosis,and IMA perfusion may be interrupted at the splenic flexure in elderly patients.The applicability and precision of preoperative angiography for evaluating the IMA branching and perfusion patterns could facilitate geriatric laparoscopic left-sided colorectal cancer surgery with suspicion of poor IMA perfusion.
基金Supported by the Key Science and Technology Research Project ofShaanxi Province [2003K10-G35,2004K13-G11(1)].
文摘Objective To construct an expression vector of small interfering RNA （siRNA） against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast cancer cell line MCF-7. Methods Constructed an expression vector of siRNA against survivin and transfected it into PC-2 and MCF-7 cells using lipofectamine^TM 2000. The expression of survivin was detected by semi-quanfifive RT-PCR and immunohistochemistry, and its effects on proliferation of PC-2 and MCF-7 cells were detected by MTT assay. Results The introduction of sequence-specific siRNA could efficiently suppress survivin expression at both mRNA and protein levels in the two cancer cell lines. In PC-2 cells, the expression inhibition rates were 81.25% at mRNA level and 74.24% at protein level In MCF-7 cells, the expression inhibition rates were 64.91% at mRNA level and 79. 72% at protein level The proliferation of PC-2 and MCF-7 cells was also suppressed, and24 and 48 hours after the cells were reseeded, the proliferation inhibition rates of PC-2 cells were 28. 00% and 33. 38%, and that of MCF-7 cells were 31.58% and 33.02%, respectively. Conclusions The expression vector of siRNA against survivin can block survivin expression in PC-2 and MCF-7 cells efficiently and specifically. Down regulation of survivin expression can suppress proliferation of PC-2 and MCF-7 cells. Survivin RNAi may have potential value in gene therapy of human cancers.
基金The Qingdao Applied Basic Research Project under contract No.14-2-4-15-jchthe National Natural Science Foundation of China under contract No.31772828。
文摘Aquaporins(AQPs)are a family of integral membrane proteins that have been shown to be important for osmoregulation in many vertebrates.To identify potential stress resistance-related aqp genes in salinity adaptation of the roughskin sculpin Trachidermus fasciatus,we investigated the time-course expression dynamics of seven aquaporin genes(aqp1,4,7,8,10,11 and 12)in three osmoregulatory tissues(kidney,gill and intestine)and one metabolic tissue(liver).The fish were subjected to two different acute osmotic treatments(seawater-tofreshwater transfer respectively achieved in 1 h and 24 h,namely,E-acute and acute group).The expression profiling of the seven aqp genes were performed using quantitative real-time PCR(qRT-PCR).At the time of all sampling time points(0 h,12 h,24 h and 48 h),no expression of aqp4 was found in the gill,liver and intestine;no expression of aqp7 was found in the gill and liver.Significant differences of aqp expression were determined in the four target tissues,and the mRNA levels were largely variable among gene members and tissues.Similar patterns of the time-course expression were detected in most of the aqp genes in T.fasciatus between the two acute groups,except that only one gene(aqp12)in the kidney and three genes(aqp7,aqp8 and aqp10)in the intestine revealed different expression patterns.These results suggest that the expression response of aqp genes was similar under osmotic changes with different rates.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.61925505,92373209 and 62235017).
文摘With the explosive development of artificial intelligence(AI),machine learning(ML),and high-performance comput-ing(HPC),the ever-growing data movement is asking for high density interconnects with higher bandwidth(BW),lower power and lower latency[1−3].The optical I/O leverages silicon photonic(SiPh)technology to enable high-density large-scale integrated photonics.
基金funded by the National Natural Science Foundation of China(No.32030083)。
文摘D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.
