A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Large-scale population structure and genetic architecture of agronomic traits of garlic

Garlic,an asexually propagated crop,is the second important bulb crop after the onion and is used as a vegetable and medicinal plant.Abundant and diverse garlic resources have been formed over thousands of years of cultivation.However,genome variation,population structure and genetic architecture of garlic agronomic traits were still not well elucidated.Here,1100258 single nucleotide polymorphisms(SNPs)were identified using genotyping-by-sequencing in 606 garlic accessions collected from43 countries.Population structure,principal component and phylogenetic analysis showed that these accessions were divided into five subpopulations.Twenty agronomic traits,including above-ground growth traits,bulb-related and bolt-related traits in two consecutive years were implemented in a genome-wide association study.In total,542 SNPs were associated with these agronomic traits,among which 188 SNPs were repeatedly associated with more than two traits.One SNP(chr6:1896135972)was repeatedly associated with ten traits.These associated SNPs were located within or near 858 genes,56 of which were transcription factors.Interestingly,one non-synonymous SNP(Chr4:166524085)in ribosomal protein S5 was repeatedly associated with above-ground growth and bulb-related traits.Additionally,gene ontology enrichment analysis of candidate genes for genomic selection regions between complete-bolting and non-bolting accessions showed that these genes were significantly enriched in‘vegetative to reproductive phase transition of meristem’,‘shoot system development’,‘reproductive process’,etc.These results provide valuable information for the reliable and efficient selection of candidate genes to achieve garlic genetic improvement and superior varieties.

Maternal Vascular Dysfunction in Congenital Heart Defects

Background:Research on fetal congenital heart defect(CHD)mostly focuses on etiology and mechanisms.However,studies on maternal complications or pathophysiology are limited.Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects.Methods:We conducted a case-control study.27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected.Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities.The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared.Results:The proangiogenic factors include vascular endothelial growth factor(VEGF)and placental growth factor(PlGF).The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1(sFlt-1)and soluble endoglin(sEng).No differences were found in maternal plasma concentrations of PlGF,VEGF,and sFlt-1 between case-control groups when analyzed at 36 weeks≤gestational age(GA)<39 weeks and 39 weeks≤GA≤41 weeks.The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group:0.60(0.77)vs.0.32(0.26)ng/ml at 36 weeks≤GA<39 weeks,p=0.001 and 0.75(0.55)vs.0.28(0.27)ng/ml at 39 weeks≤GA≤41 weeks,p<0.001.Conclusion:Vascular dysfunction exists in pregnant women with fetal congenital heart defects,manifesting significantly elevated sEng concentration at delivery.

Genome resequencing reveals the evolutionary history of garlic reproduction traits

The propagation of cultivated garlic relies on vegetative cloves,thus flowers become non-essential for reproduction in this species,driving the evolution of reproductive feature-derived traits.To obtain insights into the evolutionary alteration of reproductive traits in the clonally propagated garlic,the evolutionary histories of two main reproduction-related traits,bolting and flower differentiation,were explored by genome analyses using 134 accessions displaying wide diversity in these two traits.Resequencing identified 272.8 million variations in the garlic genome,198.0million of which represent novel variants.Population analysis identified five garlic groups that have evolved into two clades.Gene expression,single-cell transcriptome sequencing,and genome-wide trait association analyses have identified numerous candidates that correlate with reproductive transition and flower development,some of which display distinct selection signatures.Selective forces acting on the B-box zinc finger protein-encoding Asa2G00291.1,the global transcription factor group E protein-encoding Asa5G01527.1,and VERNALIZATION INSENSITIVE 3-like Asa3G03399.1 appear to be representative of the evolution of garlic bolting.Plenty of novel genomic variations and trait-related candidates represent valuable resources for biological studies of garlic.Numerous selective signatures from genes associated with the two chosen reproductive traits provide important insights into the evolutionary history of reproduction in this clonally propagated crop.

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.

A rare case of mitral valve dissection and aortic-left ventricular tunnel associated with possible autoimmune vasculitis

We report a very rare case of mitral valve dissection and aorticleft ventricular tunnel caused by possible autoimmune vasculitis.We suspected Behcet’s disease in this patient.There was no obvious clinical evidence of infective endocarditis.Echocardiography is the diagnostic tool of choice to recognize valvular dysfunction,related pathology and possible complications.The patient may require immunosuppressive therapy due to the high likelihood of recurrence perioperation period.

Effects of Stable Chlorine Dioxide on Sterilization and Preservation of Fresh-cut Narrow-leaf Cattail

At present, chlorine dioxide has been widely used as a bactericide that may become an alternative to chlorine. In this study, fresh-cut narrow-leaf cattail was soaked with 45, 70 and 95 mg/L chlorine dioxide solution, respectively. Fresh-cut narrow-leaf cattail samples were collected regularly to determine changes in surface microbe amount, cellulose content, Vc content, reduction sugar content and sensory quality of narrow-leaf cattail, thus analyzing the effects of chlorine diox- ide on sterilization and preservation of fresh-cut narrow-leaf cattail. The results showed that all three concentrations of chlorine dioxide solution could significantly reduce the amount of microbes on the surface of fresh-cut narrow-leaf cattail and improve the edible safety of products. The initial sterilization efficiency was im- proved gradually as the concentration of chlorine dioxide increased. In addition, chlorine dioxide treatment postponed the increase of cellulose content of fresh-cut narrow-leaf cattail. However, chlorine dioxide oxidized Vc and reducing sugar, and its bleaching effect also exerted a certain impact on the sensory quality of fresh- cut narrow-leaf cattail. Based on comprehensive comparisons, 45 - 70 mg/L chlorine dioxide solution exerted the best effects on sterilization and preservation of fresh-cut narrow-leaf cattail. This study laid the foundation for the production and application of chlorine dioxide solution and promotion of rapid development of nar- row-leaf cattail industry.

Genetic relationship between serum pregnancy-associated plasma protein-A gene polymorphism and ischemic cerebrovascular disease in a Northern Han Chinese population

The present study recruited 193 patients with ischemic cerebrovascular disease from Inpatient and Outpatient Departments at the Affiliated Hospital of Qingdao University Medical College, China from August 2008 to May 2010, as well as 120 healthy volunteers from the Medical Examination Center at the Affiliated Hospital of Qingdao University Medical College, China, who served as controls for this study. Patients and control subjects were from the Han population in northern China. Enzyme- linked immunosorbent assay analysis revealed increased levels of serum pregnancy-associated plasma protein-A （PAPP-A） in ischemic cerebrovascular disease patients compared with healthy controls. In addition, the patients exhibited greater frequency of genotype CC and C alleles in a missense A/C （Tyr/Ser） polymorphism （dbSNP： rs7020782） of exon 14 in the PAPP-A gene. Multiple-factor logistic regression analysis on correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and ischemic stroke family history showed that the risk for ischemic cerebrovascular disease in the population without the A allele at the A/C genetic locus in exon 14 of the PAPP-A was 2-folds greater than the population expressing the A allele. These experimental findings suggested that ischemic cerebrovascular disease correlated with the C allele in exon 14 of PAPP-A. In addition, the A allele is likely a protective gene; individuals carrying the A allele were less prone to ischemic cerebrovascular disease compared with individuals without the A allele.

A new look at cardiac pathophysiology difference in type 2 diabetic mice by comparative analysis

Objective To clarify the differences in cardiac structure,cardiac function,and myocardial metabolism in type 2 diabetes mellitus mice with obesity or non-obesity and to elucidate the key molecular mechanisms leading to this difference.Methods Db/db mice and low-dose STZ injection combined with HFD-induced diabetes mellitus mice were used in this study as the model of type 2 diabetes mellitus with obesity or non-obesity.

Design of the Rotation Angle Measurement System for the Atmospheric Dispersion Corrector (ADC)

In order to measure the rotation angle error of the worm and gear mechanisms in the atmospheric dispersion corrector( ADC),a novel measurement system based on the autocollimator is designed in this paper.Based on the position relations between the shaft and spot converged by rays of autocollimator,the rotation angle can be calculated quickly and conveniently using a brief algorithm. An optical wedge is introduced to the measurement system for suppressing the awful measuring error caused by the axial wobbly error. The measurement system can measure the shaft rotation angle at any rotation position,which is the novel usage of the two-dimensional autocollimator. Its optical layout is very simple. Only an optical wedge and two plane mirrors are needed besides the autocollimator. The measurement accuracy of the proposed method is less than±0.5 arcmin. In the measurement of two worms and gears mechanisms in ADC,the rotation angle error are±0.05° and ±0.07° respectively,which all satisfies the design demand( ±0.1°). The proposed measurement system can be also suits for some engineering fields.

WGCNA and LASSO algorithm constructed an immune infiltration-related 5-gene signature and nomogram to improve prognosis prediction of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a common immunogenic malignant tumor.Although the new strategies of immunotherapy and targeted therapy have made considerable progress in the treatment of HCC,the 5-year survival rate of patients is still very low.The identification of new prognostic signatures and the exploration of the immune microenvironment are crucial to the optimization and improvement of molecular therapy strategies.We studied the potential clinical benefits of the inflammation regulator miR-93-3p and mined its target genes.Weighted gene coexpression network analysis(WGCNA),univariate and multivariate COX regression and the LASSO COX algorithm are employed to identify prognostic-related genes and construct multi-gene signature-based risk model and nomogram for survival prediction.Support vector machine(SVM)based Cibersort’s deconvolution algorithm and gene set enrichment analysis(GSEA)is used to evaluate the changes in tumor immune microenvironment and pathway differences.The study found the favorable prognostic performance of miR-93-3p and identified 389 prognostic-related target genes.The risk model based on a novel 5-gene signature(cct5,cdk4,cenpa,dtnbp1 and flvcr1)was developed and has prominent prognostic significance in the training cohort(P<0.0001)and validation cohort(P=0.0016).The nomogram constructed by combining the gene signature and the AJCC stage further improves the survival prediction ability of the gene signature.The infiltration level of multiple immune cells(especially T cells,B cells and macrophages)were positively correlated with the expression of prognostic signature.In addition,we found that gene markers of T cells and B cells is monitored and regulated by prognostic signature.Meanwhile,several GSEA pathways related to the immune system are enriched in the high-risk group.In general,we integrated the WGCNA,LASSO COX and SVM algorithms to develop and verify 5-gene signatures and nomograms related to immune infiltration to improve the survival prediction of patients.

Investigation and Analysis on Agricultural Biological Resources of Wuchuan Gelao and Miao Autonomous County,Guizhou Province

Wuchuan Gelao and Miao Autonomous County is located in the northeast of Guizhou Province,and in the border of Guizhou and Chongqing,having a subtropical humid monsoon climate. There is no severe heat in summer,and no severe cold in winter. It has distinct national characteristics,and there are many biological resources with national characteristics. A systematic investigation of biological resources in the county for nearly a month was carried out by organizing a professional investigation team. The investigation covered 5 townships and we visited 12 village committees and 26 villagers' groups,involving three ethnic groups: Gelao,Tujia and Miao. The biological resources closely related to the agricultural production and life of local ethnic groups were investigated,collected and sorted out. A total of 230 samples of all kinds of resources were collected,including 47 food crops,75 vegetables and annual crops,37 fruit trees and perennial crops,and 71 medicinal plants. Of these,a total of 73 were unique,superior and special resources. Based on general investigation and professional investigation,this paper analyzes the present situation,growth and decline of local agricultural biological resources,and puts forward some suggestions for the protection,development and utilization of agricultural biological resources.

Effect of Storage Temperature on the Quality of Fresh-cut Cattail

Fresh-cut cattail was extremely not resistant to store at room temperature.In the first day,it began to etiolate and rot,the fiber content increased,but the vitamin C content and reducing sugar content decreased.The aerobic bacterial count increased,the weight loss rate sharply increased,and the sensory quality and food value were gradually lost.Low temperature storage could decrease the loss of vitamin C and reducing sugar of fresh-cut cattail,reduce the weight loss rate and delay the increase of fiber content,maintain the water and nutrient of fresh-cut cattail,and the storage effect of 0 ℃ was better than 4 ℃.

Investigation and Analysis of Nutrition Components of Wild Chives Collected from Hezhang County of Guizhou Province

Guizhou Province is an important distribution area of wild onion resources,and a large area of wild( Chinese) chives are distributed in Hezhang County. In order to understand and study the distribution of wild chives,the geographical distribution,habitats and climate of wild chives in Hezhang County were investigated,and the main nutrition components of wild chives were analyzed. The results indicated that there were mainly three kinds of wild chives distributed in Hezhang County, including Allium wallichii Kunth., Allium ovalifolium Hand.-Mazz.( tentatively named),and Allium hookeri Thwaites( tentatively named). Among the 17 kinds of amino acids,except for proline,the content of other amino acids in wild chives was higher than that of the cultivated chives( Allaum tuberosum Rottler ex Spreng.). The sugar content of wild chives was significantly lower than the cultivated chives. Among nine trace elements,the manganese,zinc and iron content of A. ovalifolium Hand.-Mazz. were significantly higher than that of the cultivated chives and other wild chives. Among the four kinds of heavy metals,cadmium content in the three kinds of wild chives exceeded the limitation of the national standard,and cadmium content in A. ovalifolium Hand.-Mazz. was significantly higher than that of the others. Arsenic,mercury and lead content in A. ovalifolium Hand.-Mazz. also exceeded the limitation of the national standard. Vitamin C content in leaves and stalk of A. wallichii Kunth. in the original habits was higher than that of the cultivated chives. The biological characteristics and nutrition components of the wild chives from Hezhang County were significantly different from that of the cultivated chives. The collection and preservation of these resources are of great significance to the enriching of diversity of Chinese chive resources and has great development and utilization value to the improvement of nutritional quality of Chinese chives.

A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

内镜逆行胰胆管造影术后急性胆管炎的危险因素研究及其列线图的构建

目的探讨内镜逆行胰胆管造影术(endoscopic retrograde cholangiopancreatography,ERCP)后急性胆管炎的危险因素及其列线图的构建。方法回顾性分析2014年1月—2019年12月在兰州大学第一医院因胆总管结石接受ERCP的患者临床资料,纳入术后发生急性胆管炎的患者95例(胆管炎组),以1∶3比例通过软件随机抽样选择术后未发生急性胆管炎的患者285例(无胆管炎组)。采用Logistic回归模型分析影响ERCP术后急性胆管炎的独立危险因素,根据多因素分析结果,建立预测ERCP术后急性胆管炎发生率的列线图模型。结果单因素比较发现ERCP术后发生胆管炎患者和未发生胆管炎患者在年龄、合并糖尿病、丙氨酸转氨酶、碱性磷酸酶、葡萄糖、胆囊壁粗糙、胆管直径、胆管下端狭窄、行经内镜胆道内支架放置术比例、行经内镜鼻胆管引流术比例方面差异均有统计学意义(P<0.05)。Logistic多因素回归分析显示,高龄(OR=1.108,95%CI:1.079~1.138,P<0.001)、合并糖尿病(OR=4.524,95%CI:1.299~15.758,P=0.018)、胆囊壁粗糙(OR=2.495,95%CI:1.106~5.630,P=0.028)、胆管直径增加(OR=1.303,95%CI:1.181~1.437,P<0.001)、胆管下端狭窄(OR=4.192,95%CI:2.508~7.005,P<0.001)为ERCP术后急性胆管炎的独立危险因素。根据多因素分析结果建立的列线图,受试者工作特征曲线的曲线下面积为0.887。结论高龄、糖尿病病史、胆囊壁粗糙、胆管直径增加和胆管下端狭窄为ERCP术后急性胆管炎的独立危险因素,临床医师可依据上述危险因素建立的列线图进行临床干预,改善患者预后。