Structural characterization of three acidic polysaccharides from Opuntia dillenii Haw.fruits and their protective effect against hydrogen peroxide-induced oxidative stress in Huh-7 cells

Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.

Therapeutic Characterization of ^(131)I-Labeled Humanized Anti-B7-H3 Antibodies for Radioimmunotherapy for Glioblastoma

B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.

Research on the Physiological and Psychological Ability Indexes of Coal Tunneling Workers

Studies have shown that accidents caused by human error account for 70-80% of the total number of accidents,and are the primary cause of casualties.In order to reduce the risk of safety accidents and reduce the human-caused accident rate,the evaluation index of safety occupational adaptability of coal excavation workers has been studied.Questionnaire survey method was used to conduct 13 physical and psychological abilities tests on 50 coal tunneling workers,and select the core ability indicators that reflect the mental load of the workers and the individual priority allocation of psychological resources.Secondly,using the Delphi method and the quartile method,the opinions of 20 experts in related fields were sought anonymously,and the main physical and mental ability indicators were screened and filtered through scoring methods.Finally,six indicators of"accuracy,attention,rapid response ability,proficiency,judgment,and foresight" were determined as the main physical and psychological indicators of coal tunneling workers.This study fills up the gap of safety occupational adaptability in the field of mining construction,and has important theoretical value and practical significance.

Ecdysone and Insulin Signaling Play Essential Roles in Readjusting the Altered Body Size Caused by the dGPAT4 Mutation in Drosophila

Body size is one of the features that distinguish one species from another in the biological world. Animals have developed mechanisms to control their body size during normal development. However, how animals cope with genetic alterations and/or environmental stresses to develop into normal-sized adults remain poorly understood. The ability of the animals to develop into a normal-sized adult after the challenges of genetic alterations and/or environmental stresses reveals a robustness of body size control. Here we show that the mutation of dGPAT4, a de novo synthase of lysophosphatidic acid, is a genetic alteration that triggers such a robust response of the animals to body size challenges in Drosophila. Loss of dGPAT4 leads to a severe delay of development, slow growth and resultant small-sized animals during the larval stages, but results in normal-sized adult flies. The robust body size adjustment of the dGPAT4 mutant is likely achieved by corresponding changes in ecdysone and insulin signaling, which is also manifested by compromised food intake. Thus, we propose that a strategy has been evolved by the animals to reach final body size when challenged by genetic alterations, which requires the coordinated ecdysone and insulin signaling.

Iron metabolism in non-alcoholic fatty liver disease: A promising therapeutic target

Non-alcoholic fatty liver disease(NAFLD)has become the most common cause of chronic liver disease worldwide,and is closely associated with the increased risk of the prevalence of obesity and diabetes.NAFLD begins with the presence of>5%excessive lipid accumulation in the liver,and potentially de-velops into non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.Therefore,insight into the pathogenesis of NAFLD is of key importance to its effective treatment.Iron is an essential element in the life of all mammalian organisms.However,the free iron deposition is positively associated with histological severity in NAFLD patients due to the production of reactive oxygen species via the Fenton reaction.Recently,several iron metabolism-targeted therapies,such as phlebotomy,iron chela-tors,nanotherapeutics.and ferroptosis,have shown their potential as a therapeutic option in the treatment of NAFLD and as a clinical strategy to intervene in the progression of NAFLD.Herein,we review the recent overall evidence on iron metabolism and provide the mechanism of hepatic iron overload-induced liver pathologies and the recent advances in iron metabolism-targeted therapeutics in the treatment of NAFLD.

Nutrient mTORC1 signaling contributes to hepatic lipid metabolism in the pathogenesis of non-alcoholic fatty liver disease

Energy metabolism is maintained by the complex homeostatic system in multiple cells and organs involving“nutrient signaling”or“nutrient sensor”.Overnutrient-induced chronic metabolic diseases,as the hallmarks of the 21st century’s public health,are growing threat worldwide.In the past two decades,non-alcoholic fatty liver disease(NAFLD)has emerged as the most prevalent form of chronic liver dis-ease,affecting globally,and increases the risk of incident obesity,type 2 diabetes,and insulin resistance.NAFLD begins with the excessive triglyceride accumulation in hepatocytes,and develops to hepatocel-lular steatosis with inflammation(non-alcoholic steatohepatitis,NASH),fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The liver is the central mediator of lipid metabolism by regulation of fatty acid(FA)uptake,manufacture,store,export,and oxidation in response to physiological fluctuations of nutrient.Sterol regulatory element-binding protein c(SREBP-1c)-mediated de novo lipogenesis(DNL)is an important nutritional regulator in biosynthesis of FAs and triglyceride in the liver.Mechanistic target of rapamycin complex 1(mTORC1),as a central hub of nutrient signaling,controls cellular metabolism and growth mainly via increasing anabolic processes and inhibiting catabolic processes in response to physiological fluctuations of nutrient.mTORC1 activation contributes to regulation of DNL by increasing SREBP1 transcription,which contributes to NAFLD pathogenesis and accelerates NAFLD-related HCC development.In this review,we provide the comprehensive understanding of the molec-ular mechanism of SREBPs and autophagy to control hepatic lipid homeostasis under nutrient availability in physiological and pathophysiological states,and highlight how nutrient mTORC1 signaling coordi-nately to integrate the lipid metabolic regulation and therapeutic targets in NAFLD and HCC.

Interobserver Agreement and Reliability of Intrapartum Nonreassuring Cardiotocography and Prediction of Neonatal Acidemia

Objective:To evaluate the agreement and reliability of intrapartum nonreasurring cardiotocography(CTG)interpretation and prediction of neonatal acidemia by obstetricians working in different centers.Methods:A retrospective cohort study involving two tertiary hospitals(The First Affiliated Hospital of Sun Yat-sen University and Perking University Third Hospital)was conducted between 30th September 2018 and 1st April 2019.Six obstetricians from two hospitals with three levels of experience(junior,medium,and senior)reviewed 100 nonreassuring fetal heart rate(FHR)tracings from 1 hour before the onset of abnormalities until delivery.Each reviewer determined the FHR pattern,the baseline,variability,and presence of acceleration,deceleration,sinusoidal pattern,and predicted whether neonatal acidemia and abnormal umbilical arterial pH<7.1 would occur.Inter-observer agreement was assessed using the proportions of agreement(Pa)and the proportion of specific agreement(Pa for each category).Reliability was evaluated with the kappa statistic(k-Light’s kappa for n raters)and Gwet’s AC1 statistic.Results:Good inter-observer agreement was found in evaluation of most variables(Pa>0.5),with the exception of early deceleration(Pa=0.39,95%confidence interval(CI):0.36,0.43).Reliability was also good among most variables(AC1>0.40),except for acceleration,early deceleration,and prediction of neonatal acidemia(AC1=0.17,0.10,and 0.25,respectively).There were no statistically significant differences among the three groups,except in the identification of accelerations(Pa=0.89,95%CI:0.83,0.95;Pa=0.50,95%CI:0.41,0.60,and Pa=0.35,95%CI:0.25,0.43 in junior,medium and senior groups,respectively)and the prediction of neonatal acidemia(Pa=0.52,0.52,and 0.62 in junior,medium and senior groups,respectively),where agreement was highest and lowest in the junior-level group,respectively.The accuracy and sensitivity of the prediction for umbilical artery pH<7.1 were similar among the three groups,but the specificity was higher in the senior groups(93.68%vs.92.53%vs.98.85%in junior,medium and senior groups,P=0.015).Conclusion:Although we found a good inter-observer agreement in the evaluation of the most basic CTG features and FHR category statistically,it was insufficient to meet the clinical requirements for"no objection"interpretation for FHR tracings.Further specialized training is needed for standardized interpretation of intrapartum FHR tracings.