Mutation in the Agrobacterium his I gene enhances transient expression in pepper

Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.

利拉鲁肽和有氧运动对肥胖大鼠下丘脑弓状核神经元凋亡的影响（英文）

目的:探讨利拉鲁肽和有氧运动对肥胖大鼠下丘脑弓状核(ARC)神经元形态学及细胞凋亡的影响。方法:高脂饮食建立肥胖大鼠模型,并随机分为高脂饮食+生理盐水组(HS组)、高脂饮食+利拉鲁肽组(HL组)、高脂饮食+有氧运动组(HE组);基础饲料喂养作为对照组(NC组)。HL组予皮下注射利拉鲁肽200μg/(kg·d),NC组和HS组均予皮下注射等量生理盐水,HE组进行无负重游泳训练,60 min/d。干预6周后,采用尼式染色观察下丘脑ARC神经元形态结构,免疫荧光染色法检测Bax、Bcl-2表达水平,TUNEL法检测神经细胞凋亡率。结果:尼式染色结果显示,NC组下丘脑弓状核区神经元结构完整,排列紧密;HS组下丘脑ARC神经元显著减少,排列紊乱,可见核固缩等明显改变;HL组和HE组神经细胞均有改善。与NC组相比,HS组细胞凋亡率和Bax表达显著增高,Bcl-2表达显著降低(均P<0.01)。利拉鲁肽或有氧运动可降低TUNEL阳性细胞数和Bax表达,同时上调Bcl-2表达(均P<0.01),且HL组改善效果更明显。结论:利拉鲁肽可明显改善下丘脑ARC神经元形态结构,抑制肥胖大鼠神经元凋亡,且效果优于有氧运动。

^(18)F-FDG PET/CT在结外NK/T细胞淋巴瘤中的预后价值

结外NK/T细胞淋巴瘤(extranodal natural killer/T-cell lymphoma,ENKTL)是一种与EB病毒(epstein-barr virus,EBV)相关的侵袭性非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL),好发于亚洲和南美洲,其病程进展较快、病死率较高、预后不佳。目前应用的预后模型主要包括国际预后指数(international prognostic index,IPI)、韩国预后指数(Korean prognostic index,KPI)、NK细胞淋巴瘤预后指数(prognostic index of natural killer cell lymphoma,PINK)及包含EBV DNA的NK细胞淋巴瘤预后指数(prognostic index of natural killer cell lymphoma with epstein-barr virus DNA,PINK-E),尚存在一定的局限性。正电子发射断层显像融合计算机断层扫描(positron emission tomography/computed tomography,PET/CT)是一种将解剖结构成像和代谢功能成像相结合的影像技术,具有高敏感性、高特异性的优势,在多种恶性淋巴瘤的诊断、分期、疗效评价和预后评估等方面发挥重要的作用,但其对于ENKTL的预后价值仍存争议。因此,本文针对治疗前、治疗中期和治疗结束后PET/CT对于ENKTL的预后价值进行综述。

发酵莲花花瓣美白功效提升及作用机制研究

随着现代生物工程技术快速发展,利用发酵技术提高草药提取物在食品和化妆品添加剂领域的生物活性已成为新趋势。在本研究中,以蘑菇酪氨酸酶活性和黑色素形成为评价指标,对5种益生菌的莲花提取物(LPE)发酵产物进行活性筛选。结果显示植物乳杆菌CGMCC 1.124发酵产物(FLPE)具有酪氨酸酶抑制活力;在A-MSH诱导的小鼠黑色素瘤细胞(B16F10)美白模型中,经50μg/mL FLPE处理的B16F10黑色素含量为模型对照组的86%±4.6%。为进一步阐明FLPE主要活性成分,利用HPLC,NMR和LC-MS对莲花提取物发酵前后产物中的主要黄酮类化合物进行定性定量分析。结构分析和生物活性评价结果表明,山奈酚-3-O-β-D-葡萄糖苷(49.8%,94.22 mg/g)和槲皮素-3-O-β-D-葡萄糖醛酸(13.6%)生物转化为两个生物活性苷元-槲皮素(14.4%,26.43 mg/g)和山奈酚(60.9%,70.76 mg/g)。在这些单体中,槲皮素通过调节酪氨酸酶活性、黑素发生相关酶(TYR,TRP-1和TRP-2)和小眼畸形相关转录调控因子(MITF)的表达抑制黑素形成。总体而言,利用植物乳杆菌CGMCC 1.124发酵提高了莲花提取物美白功效,转化生成的槲皮素是植物乳杆菌发酵产物抑制黑色素合成的物质基础之一。

A New Robust Adaptive Neural Network Backstepping Control for Single Machine Infinite Power System With TCSC

For a single machine infinite power system with thyristor controlled series compensation(TCSC) device, which is affected by system model uncertainties, nonlinear time-delays and external unknown disturbances, we present a robust adaptive backstepping control scheme based on the radial basis function neural network(RBFNN). The RBFNN is introduced to approximate the complex nonlinear function involving uncertainties and external unknown disturbances, and meanwhile a new robust term is constructed to further estimate the system residual error,which removes the requirement of knowing the upper bound of the disturbances and uncertainty terms. The stability analysis of the power system is presented based on the Lyapunov function,which can guarantee the uniform ultimate boundedness(UUB) of all parameters and states of the whole closed-loop system. A comparison is made between the RBFNN-based robust adaptive control and the general backstepping control in the simulation part to verify the effectiveness of the proposed control scheme.

Identification of potential immune-related prognostic biomarkers of lung cancer using gene co-expression network analysis

Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.

Neurotrophin 3 hinders the growth and metastasis of hepatocellular carcinoma cells

Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms.Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data.Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3.Cell growth and proliferation were analyzed using a Cell Counting Kit-8(CCK-8)assay.Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays.Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction(qPCR).Cell apoptosis was evaluated with flow cytometry.Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues.Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features.NTF3 overexpression reduced the proliferation,migration,and invasion abilities of HCC cell lines.Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients,likely due to its action in promoting HCC cell proliferation,migration,and invasion.Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression,suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.

Research Progress of Anaerobic Digestion Pretreatment of Antibiotic Waste

Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.

A Range-Threshold Based Medical Image Classification Algorithm for Crowdsourcing

Medical images are important for medical research and clinical diagnosis.The research of medical images includes image acquisition,processing,analysis and other related research fields.Crowdsourcing is attracting growing interests in recent years as an effective tool.It can harness human intelligence to solve problems that computers cannot perform well,such as sentiment analysis and image recognition.Crowdsourcing can achieve higher accuracies in medical image classification,but it cannot be widely used for its low efficiency and the monetary cost.We adopt a hybrid approach which combines computer’s algorithm and crowdsourcing system for image classification.Medical image classification algorithms have a high error rate near the threshold.And it is not significant by improving these classification algorithms to achieve a higher accuracy.To address the problem,we propose a hybrid framework,which can achieve a higher accuracy significantly than only use classification algorithms.At the same time,it only processes the images that classification algorithms perform not well,so it has a lower monetary cost.In the framework,we device an effective algorithm to generate a range-threshold that assign images to crowdsourcing or classification algorithm.Experimental results show that our method can improve the accuracy of medical images classification and reduce the crowdsourcing monetary cost.

Research on the evolutionary game of the supervision of civil aviation dangerous goods transportation training

This study is carried out to promote the precise supervision of dangerous goods transportation training,improve the efficiency of civil aviation supervision and further ensure the safety of air transportation.First,from the perspective of behaviour interaction and interest demands,evolutionary game theory is used to construct a tripartite evolutionary game model of dangerous goods transportation training institutions,the Civil Aviation Administration of China(CAAC)and the public.Then,the evolutionary game equilibrium of the system is further analysed under the joint action of the three parties.Finally,the influences of important parameters of the model on the behavioural strategy selection of the three parties are investigated via MATLAB numerical simulation.The conclusions reveal that the system has three evolutionarily stable strategies under different parameters,namely(non-compliant training,supervision,non-participation in supervision),(non-compliant training,supervision,participation in supervision)and(compliant training,supervision,non-participation in supervision).Moreover,the CAAC supervision cost,the fine amount,the supervision cost of public participation,the supervision success rate and the reporting reward amount are the main parameters that affect the behavioural strategy selection of the tripartite game players.The conclusions and suggestions of this study provide a decision-making basis and guidance for the supervision and management of civil aviation dangerous goods transportation training.

Effect of GnRH analogs in advanced male breast cancer:10-year experience from the Henan Breast Cancer Center and literature review

To the Editor:Male breast cancer is relatively rare,accounting for just 1%of all breast cancer cases.[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies and speculation based on female breast cancer.This study presents a comprehensive account of a decade-long observation of male metastatic breast cancer(mMBC)in our institution.The Affiliated Cancer Hospital of Zhengzhou University database had records of 2853 advanced breast cancer cases that were treated from January 1,2010 to December 31,2019.Out of the total number,18 cases were identified as mMBC.The analysis encompassed data about the treatment administered,the treatment’s effectiveness,and the patient’s survival outcomes.The present investigation entails a retrospective examination of our institution’s 10-year experience with patients diagnosed with mMBC and a comprehensive evaluation of relevant literature.

A Pilot Study of the Therapeutic Efficacy and Mechanism of Artesunate in the MRL/lpr Murine Model of Systemic Lupus Erythematosus

Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model.MRL/lpr mice were divided into control,cyclophosphamide(CTX)and artesunate treatment groups.Blood was collected to measure serum levels of creatinine,antinuclear antibody(ANA)and anti-double-stranded DNA(anti-dsDNA)antibody.Twenty-four-hour urine was collected to measure levels of proteinuria.The concentration of monocyte chemotactic protein-1(MCP-1)in serum and urine was measured.The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay,respectively.The expression of B cell activating factor(BAFF)in spleen was determined by real time-PCR and immunoblotting.We found that artesunate significantly increased the survival rate,body weight and blood leukocyte counts,and reduced the serum levels of ANA and anti-dsDNA antibody titer,24 h urinary protein,and serum creatinine.Our results indicated that artesunate could decrease MCP-1,major pro-inflammation cytokine,in serum,urine and kidney.We also found that the level of BAFF,the major B cell activation factor,was decreased in artesunate treated MRL/lpr mice.Its efficacy was comparable with that of CTX in this study.Taken together,we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.

Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs

The rigidity of nanoparticles was newly reported to influence their oral delivery.Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells.However,it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs.This study was for the first time to validate the semi-elastic coreshell poly(lactic-co-glycolic acid)(PLGA)-lipid nanoparticles(LNPs)as the carrier of the oral peptide drug.The antihypertensive peptide Val-Leu-Pro-Val-Pro(VP5)loaded LNPs(VP5-LNPs)were prepared by a modified thin-film ultrasonic dispersion method.Uptake experiment was performed in Caco-2 and HT-29 cells and monito red by high content screening(HCS)and flow cyto metric(FCM).Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley(SD)rats and analyzed by DAS 2.0.The optimal VP5-LNPs had an average particle size of 247.3±3.8 nm,zeta potential of-6.57±0.45 mV and excellent entrapment efficiency(EE)of 89.88%±1.23%.Transmission electron microscope(TEM)and Differential scanning calorimeter(DSC)further confirmed the core-shell structure.VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h,indicating a great promotion of the o ral bioavailability.The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.

Diagnostic diversity and heterogeneity of tumors: a real-world study of metastasis re-biopsy in advanced breast cancer

Background::Re-biopsy of metastasis in advanced breast cancer(ABC)has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity.This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2)expression levels between primary and metastatic lesions.Methods::We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018.The pathological diagnosis of biopsies,distribution of biopsy sites,and severe puncture complications at each site were collected.In addition,the inconsistency rates and related factors of ER,PR,and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’demographic profiles and disease characteristics.Results::In total,1670 cases of breast cancer(BC)patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment,producing 2019 histopathological specimens which were analyzed in the study.Pathological diagnosis showed that eight patients had benign pathological diagnoses,11 patients had second primary malignant tumors but without recurrences of breast cancer,and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer.In 1173 patients who presented ER,PR,and HER2 expressions in primary and metastatic lesions,the inconsistency rates of ER,PR,and HER2 were 17.5%(205/1173),31.3%(367/1173),and 13.9%(163/1173),respectively.The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level.Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax,no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions::The pathological diagnosis of metastasis re-biopsy of ABC was diverse,and the ER,PR,and HER2 expression levels were inconsistent between primary and metastatic lesions.Therefore,more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

Core-shell lipid-polymeric nanoparticles for enhanced oral bioavailability and antihypertensive efficacy of KY5 peptide

Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides.