Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

Albumin and magnetic resonance imaging-liver volume to identify hepatitis B-related cirrhosis and esophageal varices

AIM:To investigate whether liver lobe volume and albumin(ALB) could predict the presence and severity of liver cirrhosis,and esophageal varices.METHODS:Seventy-one cirrhotic patients with hepatitis B and 21 healthy individuals were enrolled in this study.All the participants underwent abdominal enhanced magnetic resonance imaging to measure each liver lobe volume,and biochemical workup for testing ALB and Child-Pugh class.All cirrhotic patients underwent upper gastrointestinal endoscopy to show the presence of cirrhotic esophageal varices.Right liver lobe volume(RV),left medial liver lobe volume(LMV),left lateral liver lobe volume(LLV),and caudate lobe volume(CV) were measured using enhanced magnetic resonance imaging.The ratios of RV to ALB(RV/ALB),LMV to ALB(LMV/ALB),LLV to ALB(LLV/ALB) and CV to ALB(CV/ALB) were calculated.Statistical analyses were performed to determine whether and how the combination of liver lobe volume measured using magnetic resonance imaging and albumin could predict the presence and severity of liver cirrhosis,and the presence of esophageal varices.RESULTS:RV,LMV,LLV and CV decreased(r =-0.51-0.373; all P < 0.05),while RV/ALB increased(r = 0.424; P < 0.05),with the progress of Child-Pugh classof liver cirrhosis.RV,LMV,CV,LLV/ALB and CV/ALB could identify presence of liver cirrhosis; LLV and LMV could distinguish Child-Pugh class A from B; RV,LMV,LLV,CV,RV/ALB and LLV/ALB could distinguish class A from C; RV and LLV/ALB could differentiate B from C; and RV,RV/ALB and CV/ALB could identify presence of esophageal varices(all P < 0.05).Among these parameters,CV/ALB could best identify the presence of liver cirrhosis,with an area under receiver operating characteristic curve(AUC) of 0.860,a sensitivity of 82.0% and a specificity of 83.0%.LLV could best distinguish class A from B,with an AUC of 0.761,a sensitivity of 74.4% and a specificity of 73.1%.RV could best distinguish class A from C,with an AUC of 0.900,a sensitivity of 90.3% and a specificity of 84.5%.LLV/ALB could best distinguish class B from C,with an AUC of 0.900,a sensitivity of 93.8% and a specificity of 81.5%.RV/ALB could best identify esophageal varices,with an AUC of 0.890,a sensitivity of 80.0% and a specificity of 83.5%.CONCLUSION:The combination of liver lobe volume and ALB has potential to identify presence and severity of cirrhosis,and presence of esophageal varices.

Global burden of inflammatory bowel disease 1990-2019:A systematic examination of the disease burden and twenty-year forecast

BACKGROUND Inflammatory bowel disease(IBD)is an idiopathic intestinal disease with various levels and trends in different countries and regions.Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment.We report the average annual percentage change(AAPC)and estimated annual percentage change(EAPC)in age-standardized rates(ASR)of IBD in different regions based on the Global Burden of Disease(GBD)study from 1990-2019,and the relationships between IBD and the human development index(HDI)and socio-demographic index(SDI).The prevalence trends of IBD were predicted by gender from 2019-2039.AIM To comprehensively investigate IBD data,providing further insights into the management of this chronic disease.METHODS We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions.The relationships between IBD,HDI,and SDI were analyzed.The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039,and the reliability of the results was validated.RESULTS North America consistently had the highest IBD ASR,while Oceania consistently had the lowest.East Asia had the fastest average annual growth in ASR(2.54%),whereas Central Europe had the fastest decline(1.38%).Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019.Additionally,IBD increased faster in countries with a low age-standardized death rates in 1990,whereas the opposite was true in 2019.Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR.Finally,the projections showed a declining trend in the incidence of IBD from 2019-2039,but a gradual increase in the number of cases.CONCLUSION As the global population increases and ages,early monitoring and prevention of IBD is important to reduce the disease burden,especially in countries with a high incidence of IBD.

Differences in expression of retinal proteins between diabetic and normal rats

AIM： To compare and identify the differences in expression of retinal proteins between normal and diabetic rats, and to analyze the molecular pathogenetic mechanisms of retinal diseases caused by diabetes.METHODS： Changes in protein expression of retinal tissues from diabetic and normal rats were observed using 2-dimensional polyacrylamide gel electrophoresis （2-DE）. Some protein spots exhibiting statistically significant variations （P 〈 0.05） were selected randomly and identified by tandem mass spectrometry and analyzed by bioinformatics.RESULTS： 2-DE showed that the expression was upregulated in 5 retinal proteins, down-regulated in 23retinal proteins, and disappeared in 8 retinal proteins.Eight spots were identified from the 36 spots by tandem mass spectrometry （MS/MS） and analyzed by bioinformatics. Guanylate kinase 1, triosephosphate isomerase 1, ATP synthase subunit d, albumin and dimethylarginine dimethylaminohydrolase 2 played an important role in signal transduction. Triosephosphate isomerase 1, crystallin alpha B, ATP synthase subunit d and peroxiredoxin 6 were involved in energy metabolism of retinal tissues. Guanylate kinase 1 played an important role in photoexcitation of retinal rod photoreceptor cells.Whether crystallin beta A1 plays a role in diabetic retinas is unknown so far.CONCLUSION： There are differences in expression of retinal proteins between diabetic and normal rats.These proteins may be involved in the mechanisms and prognosis of retinal diseases caused by diabetes.

Involvement of α5 integrin in survivin-mediated osteosarcoma metastasis

Objective: To investigate the role of survivin in osteosarcoma metastasis. Methods: Small interfering RNA(si RNA) was used to knockdown the expression of survivin and α5 integrin in the human osteosarcoma cell line MG63. Western blotting and immunostaining methods was used to assessed the effect of survivin knockdown on the expression of α5 integrin through flow cytometry and fluorescence microscopy detection. Meanwhile, the invasion and migration of transfected cells in Transwell and wound healing assays were probed, and the growth situation of these cells transplanted into nude mice was monitored. Results: Knockdown of survivin expression could inhibit the invasion and migration of osteosarcoma MG64 cells in vitro and the expression of α5 integrin on osteosarcoma MG64 cell surface, suggesting that survivin can inhibit the invasion and migration of osteosarcoma cells through downregulation of α5 integrin. Anti-α5 integrin antibody could also markedly decrease the capability of invasion and migration of osteosarcoma MG64 cells. Additionally, knockdown of survivin expression could slow the growth of osteosarcoma MG63 cells transplanted into nude mice. Conclusions: Survivin-directed anti-tumor strategies might be an effective method in the treatment of osteosarcoma.

Inherently Chiral and Symmetrical Heteroatom-Doped Zigzag-Type Hydrocarbon Belts

hydrocarbon belts due to their potential applications in carbon nanotechnology.By contrast,heteroatomembedded zigzag hydrocarbon belts as advanced design strategies with fascinating structures and desirable,unique properties have remained largely unexplored,and inherently chiral ones are unknown.Herein,we report the synthesis of a diversity of symmetric and highly enantiopure inherently chiral O-and N-doped zigzag-type hydrocarbon belts starting from strainless macrocycles based on fjord-stitching strategy.The readily available pertriflated resorcin[6]arene underwent partial hydrolyses and intramolecular S_(N)Ar reactions to form a calix[3](9H-xanthene)derivative and a prochiral half-belt selectively.Straightforward transformations of calix[3](9H-xanthene)into C_(3v)-symmetric molecular belts were achieved by closing the rest of the fjords with triple intramolecular S_(N)Ar reactions and Yamamoto homo coupling reactions,as well as palladiumcatalyzed intermolecular acridination reactions with primary amines.The prochiral half-belt underwent enantioselective desymmetrizative mono-acridination to afford an inherently chiral N,O_(4)-bridged pseudo-belt with an enantiomeric excess(ee)value of>99%under the catalysis of Pd(OAc)_(2)and(R)-Antphos.Ring closure reactions of the pseudo-belt produced diverse heteroatom-inlayed zigzag-type hydrocarbon belts of inherent chirality.Further,we showed the unique cavity structures of the belts and demonstrated interesting chiroptic properties of the inherently enantiopure chiral belts.This research opens the door for the exploration of novel and sophisticated symmetric and inherently chiral molecular nanobelt structures with outstanding physical and chemical properties,as well as potential applications.

Genome-wide identification and characterization of long non-coding RNAs in Tribolium castaneum

Long non-coding RNAs(lncRNAs)are poorly understood in insects.In this study,we performed genome-wide analysis of lncRNAs in Tribolium castaneum by RNA-seq.In total,4516 lncRNA transcripts corresponding to 3917 genes were identified from late embryos,early larvae,late larvae,early pupae,late pupae and early adults of T.castaneum,including 3152 novel lncRNAs and 1364 known lncRNAs.These lncRNAs have few exons and transcripts,and are short in length.During development,they exhibited nine different expression patterns.Functionally,they can act either by targeting messenger RNAs(1813 lncRNAs)and lncRNAs(45 lncRNAs)or as micro RNA(miRNA)precursors(46 lncRNAs).LncRNAs were observed to target the metabolic enzymes of glycolysis,TCA cycle and amino acids,demonstrating that lncRNAs control metabolism by regulating metabolic enzymes.Moreover,lncRNAs were shown to participate in cell differentiation and development via their targets.As miRNA precursors,lncRNAs could participate in the ecdysone signaling pathway.This study provides comprehensive information for lncRNAs of T.castaneum,and will promote functional analysis and target identification of lncRNAs in the insect.

Functional analysis of the circadian clock gene timeless in Tribolium castaneum

Circadian rhythms are endogenous oscillations with a period of about 24 h driven by a circadian clock. So far, variable oscillators have been found in insects. To explore the circadian clock of Tribolium castaneum, we cloned the clock gene timeless （Tctimeless）. Its open reading frame is 3240 bp in length and consists of 10 exons. Tctimeless＇ is highly expressed in the late pupal stage. Tissue-specific expression analysis in late adult stages revealed high expression of Tctimeless in the head, epidermis, fat body and accessory glands. Silencing of Tctimeless by RNA interference （RNAi） at the late larval stages caused a failure to initiate eclosion. Tctimeless knockdown in late pupal stages led to a gender-independent decline in egg production and progeny survival. As a core clock gene, Tctimeless exhibited one expression peak in the middle of the circadian day. Knockdown of Tctimeless disrupted daily expression patterns of Tccycle, Tcclock, Tcperiod and itself, while Tctimeless and Tcperiod expression patterns over the circadian day were also perturbed when Tccycle or Tcclock is suppressed by RNAi. This study identified a complex transcriptional relationship among circadian clock genes in T. castaneum.

A Large Chinese Text Dataset in the Wild

In this paper,we introduce a very large Chinese text dataset,in the wild.While optical character recognition(OCR)in document images is well studied and many commercial tools are available,the detection and recognition of text in natural images is still a challenging problem,especially for some more complicated character sets such as Chinese text.Lack of training data has always been a problem,especially for deep learning methods which require massive training data.In this paper,we provide details of a newly created dataset of Chinese text with about 1 million Chinese characters from 3850 unique ones annotated by experts in over 30 000 street view images.This is a challenging dataset with good diversity containing planar text,raised text,text under poor illumination,distant text,partially occluded text,etc.For each character,the annotation includes its underlying character,bounding box,and six attributes.The attributes indicate the charactcr's background complexity,appearance,style,etc.Besides the dataset,we give baseline results using state-of-the-art methods for tliree tasks:character recognition(top-1 accuracy of 80.5%),character detection(AP of 70.9%),and text line detection(AED of 22.1).The dataset,source code,and trained models are publicly available.