Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

经直肠超声结合剪切波弹性成像在直肠癌诊断及TNM分期中的应用

目的分析经直肠超声(TRUS)结合剪切波弹性成像(SWE)在直肠癌诊断及TNM分期中的应用。方法回顾性分析2019年12月—2021年2月中国医科大学附属第四医院收治的86例直肠肿瘤患者临床资料。所有患者术前接受TRUS和SWE检查。记录TRUS与SWE及两者联合诊断直肠癌及其TNM分期的敏感性、特异性及准确率。比较直肠癌与直肠腺瘤患者肿瘤病灶处、周围脂肪和正常直肠壁3个位置E_(max)值和E_(mean)值;绘制ROC曲线分析TRUS、SWE及联合诊断直肠癌的价值。结果联合诊断直肠癌的敏感性为97.18%(95%CI:0.80,0.99),特异性为86.67%(95%CI:0.71,0.98),准确率为95.35%(95%CI:0.78,0.99)。ROC曲线分析结果显示,两者联合诊断直肠癌的AUC为0.968(95%CI:0.89,1.00)。两者联合诊断为T1期的准确率为94.12%(95%CI:0.76,0.94),T2期的准确率为90.91%(95%CI:0.72,0.92),T3期的准确率为100.00%(95%CI:0.99,1.00),T4期的准确率为100.00%(95%CI:0.99,1.00)。直肠癌组E_(max)、E_(mean)值较非直肠癌组高(P<0.05)。不同分期的杨氏模量值比较,差异有统计学意义(P<0.05),且TNM分期越晚,E_(max)、E_(mean)值越高。结论TRUS结合SWE诊断直肠癌及TNM分期的准确性较高,可为临床病变鉴别及病理程度提供一定参考依据。

Transplantation of vascular endothelial growth factor-modified neural stem/progenitor cells promotes the recovery of neurological function following hypoxic-ischemic brain damage

Neural stem/progenitor cell （NSC） transplantation has been shown to effectively improve neurological function in rats with hypoxic-isch- emic brain damage. Vascular endothelial growth factor （VEGF） is a signaling protein that stimulates angiogenesis and improves neural regeneration. We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neo- natal rats. We produced and transfected a recombinant lentiviral vector containing the VEGF165gene into cultured NSCs. The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage. Compared with the NSCs group, VEGF mRNA and protein expression levels were increased in the transgene NSCs group, and learning and memory abilities were significantly improved at 30 days. Furthermore, histopathological changes were alleviated in these animals. Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function, and that its therapeutic effectiveness is better than that of unmodified NSCs.

Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells

AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine(DAC) on telomerase activity in hepatocellular carcinoma(HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis.The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.RESULTS:The telomerase activity was significantly reduced in both cell lines treated with DAC,accompanied by downregulation of telomerase reverse transcriptase(hTERT).We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes,such as c-myc,p15,p16,p21,E2F1,and WT1.The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC,but not in HepG2 cells.However,p16 expression could be reactivated by demethylation of its promoter,and c-Myc expression was repressed in both cell lines.Moreover,DAC could enhance the sensitivity to the chemotherapeutic agents,such as cisplatin,by induction of apoptosis of HCC cells.CONCLUSION:The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.

非酒精性脂肪性肝病药物治疗学前沿与展望

尽管近年来非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)的发病率在不断增加,但是临床上仍缺乏公认的对NAFLD具有明显疗效的药物干预.目前治疗NAFLD的主要方法是改变生活方式,包括减肥和饮食调整.然而,这些治疗方法有时效果不佳,尤其是对于非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的患者.针对NAFLD的发病机制,多种药物已被用于治疗NASH的临床试验,部分展示了一定的临床价值.目前,欧美一些指南只推荐作为胰岛素增敏剂的吡格列酮和作为抗氧化剂的维生素E用于治疗NASH.包括他汀类药物和贝特类药物的降脂药、己酮可可碱、血管紧张素受体阻断剂、熊去氧胆酸、益生菌和合生素是目前潜在治疗NASH的有益药物,但来源于小样本量的随机双盲对照临床试验所获得的证据强度尚不足以至得到监管部门的批准.一些新兴的药物正在开发用于治疗NASH,例如奥贝胆酸、利拉鲁肽、elafibranor、c e n i c r i v i r o c、a r a m c h o l、成纤维细胞生长因子(FGF)-21或FGF-19类似物、IMM-124e、奥利司他、solithromycin, simtuzumab和GR-MD-02、remogliflozin etabonate、lipaglyn、SHP626、PXS4728A等已在临床试验中测试或正在完成试验.因此,本文主要针对NAFLD的肝脏脂肪蓄积和由此产生的代谢应激、氧化应激、肠道微生物紊乱、纤维化进程等药物治疗学前沿进展进行综述.

Cloning the sterol carrier protein 2 genes of Japanese toad （Bufo japonicus formosus） and Chinese toad （Bufo gargarizans） and its tissue expression analysis

In this study,to clarify the bioactive polypeptides included in the skins and secretions of Bufo,we screened the Japanese toad(Bufo japonicus formosus) skin cDNA library by colony polymerase chain reaction(PCR),and obtained a transcript of 1 075 bp consisting of 1 37 bp 5′ untranslated region(UTR),515 bp 3′ UTR and a 423 bp open reading frame(ORF) encoding a polypeptide of 140 amino acid residues(GenBank accession number: KF359945).Homolog analysis showed a 70%–96% homology with sterol carrier protein-2(SCP-2) present in other animals,which is implicated in lipid metabolism of other organisms.The gene SCP-2 of Chinese toad(B.gargarizans) was cloned from a first strand cDNA of Bufo skin(GenBank accession number: KF381341) via PCR,whose encoding polypeptide has only one amino acid difference from that of Japanese toad.Tissue distribution analysis showed that SCP-2 expressed in all organs tested,though in the liver and spleen it manifested lower expression than in other organs.These findings might indicate SCP-2 being one of the active ingredients in toad skin.These findings may in turn have implications for further drug development from traditional Chinese medicine sources.

Laser frequency offset-locking using electromagnetically induced transparency spectroscopy of (85)Rb in magnetic field

We have experimentally offset-locked the frequencies of two lasers using electromagnetically induced transparency（EIT） spectroscopy of ^（85）Rb vapor with a buffer gas in a magnetic field at room temperature. The magnetic field is generated by a permanent magnet mounted on a translation stage and its field magnitude can be varied by adjusting the distance between the magnet and Rb cell, which maps the laser locking frequency to the space position of the magnet. This frequency-space mapping technique provides an unambiguous daily laser frequency detuning operation with high accuracy.A repeatability of less than 0.5 MHz is achieved with the locking frequency detuned up to 184 MHz when the magnetic field varies from 0 up to 80 G.

Correlation analysis of CRP/ALB and P-CRP in the prognosis of non-small cell lung cancer

Objective:The purpose of this study was to investigate the relationship between preoperative C-reactive protein/albumin ratio(CRP/ALB),platelet count and C-reactive protein product(P-CRP)and clinical prognosis in patients with non-small cell lung cancer.Methods:From January 2015 to December 2015,284 patients who underwent surgery for lung cancer in the First Affiliated Hospital of Bengbu Medical College were selected.According to their 3-year and 5-year survival conditions,ROC curves were drawn and the best cut-off value was determined.According to the cut-off value,the patients were divided into high CRP/ALB group,low CRP/ALB group,high P-CRP group and low P-CRP group.Survival curves were described by Kaplan-Meier method and compared by Log-rank test.The univariate and multivariate analyses were performed with the Cox proportional hazard model to evaluate the prognostic factors.Results:Survival analysis showed that there was no significant difference in 3-year survival rate between high CRP/ALB and P-CRP groups and low CRP/ALB and P-CRP groups,while the 5-year survival rate in high CRP/ALB and P-CRP groups was significantly lower than that in low CRP/ALB and P-CRP groups.Cox proportional hazard model showed that CRP/ALB,age,smoking history,lymph node metastasis and TNM stage were risk factors for 5-year survival rate.Conclusion:as a prognostic index based on inflammation,preoperative CRP/ALB level can better reflect the prognosis of patients than P-CRP.

Network pharmacology study on the mechanism of the tong xie yao fang in treating irritable bowel syndrome

Objective:The purpose of this study was to explore the effective compounds and molecular mechanism of Tong Xie Yao Fang(TXYF)in the treatment of Irritable Bowel Syndrome(IBS)based on network pharmacology.Method:The effective components in TXYF were screened using the TCMSP database,and the targets were predicted and analyzed with the PharmMapper server.The potential targets were imported into the MAS 3.0 database for target annotation and analysis.Finally,the KEGG database was used for pathway analysis.Result:Forty-three compounds were identified in the TXYF,corresponding to 247 targets.Among these,a total of 33 targets were found to be closely related to IBS.Pathway enrichment analysis identified 22 significant pathways to be associated with TXYF and its treatment.The results showed that components such as polyphenols,flavonoids,and terpenoids can enhance the immune function and alter hypoxia-induced stress by regulating cell proliferation,oxidative reactions,endocrine metabolism,and inflammatory reactions.Conclusion:The mechanism of TXYF in treating IBS is closely related to metabolic reactions,cell proliferation,inflammatory reactions,immune regulation,and endocrine hormone metabolism.

Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice

Retinal angiogenesis is a critical process for normal retinal function.However,uncontrolled angiogenesis can lead to pathological neovascularization(NV),which is closely related to most irreversible blindness-causing retinal diseases.Understanding the molecular basis behind pathological NV is important for the treatment of related diseases.Twist-related protein 1(TWIST1)is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition(EMT)in many human cancers.Our previous study showed that Twist1 expression is elevated in pathological retinal NV.To date,however,the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated.To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV,we generated an inducible vascular endothelial cell(EC)-specific Twist1 transgenic mouse model(Tg-Twist1iEC+).Whole-mount retinas from Tg-Twist1iEC+mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature,as well as aneurysm-like pathological retinal NV.Furthermore,overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity,thus leading to uncontrolled retinal angiogenesis.TWIST1 promoted pathological NV by activating the Wnt/β-catenin signaling pathway and inducing the expression of NV formation-related genes,thereby acting as a‘valve’in the regulation of pathological angiogenesis.This study identified the critical role of TWIST1 in retinal pathological NV,thus providing a potential therapeutic target for pathological NV.

A sensitive detection of high Rydberg atom with large dipole moment

We report a sensitive detection of high Rydberg atom with large dipole moment utilizing its deflection near a pair of parallel cylindrical copper rods which are oppositely charged. When the low-field seeking state Rydberg atoms fly across the gradient electric field formed by the pair of rods, they will be pushed away from the rods while the high-field seeking state ones will be attracted towards the rods. These atoms will form different patterns on an ion imaging system placed downwards at the end of the rods. The spatial distribution of the deflected atoms on the imaging system is also simulated, in good agreement with the experimental results, from which we can deduce the quantum state information of the excited atoms. This state resolvable Rydberg atom detection can be used for the dynamics research of the dipole-dipole interaction between atoms with large dipole moments.

Effects of Elevated CO_2 on Growth, Carbon Assimilation, Photosynthate Accumulation and Related Enzymes in Rice Leaves during Sink-Source Transition

To study the effects of growing rice （Oryza sativa L.） leaves under the treatment of the short-term elevated CO2 during the period of sink-source transition, several physiological processes such as dynamic changes in photosynthesis, photosynthate accumulation, enzyme activities （sucrose phosphate synthase （SPS）, and sucrose synthase （SS））, and their specific gene （spsl and RSusl） expressions in both mature and developing leaf were measured. Rice seedlings with fully expanded sixth leaf （marked as the source leaf, L6） were kept in elevated （700 μmol/mol） and ambient （350 mol/L） CO2 until the 7th leaf （marked as the sink leaf, L7） fully expanded. The results demonstrated that elevated CO2 significantly increased the rate of leaf elongation and biomass accumulation of L7 during the treatment without affecting the growth of L6. However, in both developing and mature leaves, net photosynthetic assimilation rate （A）, all kinds of photosynthate contents such as starch, sucrose and hexose, activities of SPS and SS and transcript levels of spsl and RSusl were significantly increased under elevated CO2 condition. Results suggested that the elevated CO2 had facilitated photosynthate assimilation, and increased photosynthate supplies from the source leaf to the sink leaf, which accelerated the growth and sink-source transition in new developing sink leaves. The mechanisms of SPS regulation by the elevated CO2 was also discussed.

Enhanced thermoelectric performance of CoSbS_(0.85)Se_(0.15) by point defect

In this study, we report the effect of Zn doping on the thermoelectric properties of CO1-xZnxSbS0.85Se0.15 solid solutions （x = 0, 0.02, 0.05, 0.08）. The results show the dimensionless figure of merit （zT） increases from 0.17 to 0.34 at 875 K for Co0.95Zn0.05SbS0.85Se0.15 sample, due to the noticeable decrease in the lattice thermal conductivity by introducing point defect, which is further confirmed by an analysis based on the Debye-Callaway- Klemens model. Meanwhile, the thermoelectric power factor is maintained at high temperatures. This work highlights the important role of point defect in improving the thermoelectric performance of CoSbS-based compounds.

Anionic passivation layer-assisted trapping of an icosahedral Ag_(13)kernel in a truncated tetrahedral Ag_(89)nanocluster

Isolating reductive silver kernel from shell is a challenging task but is quite important to understand the embryonic form during the formation of silver nanoclusters.The intercalation of suitable anionic species may be of benefit for passivating then capturing such highly active kernel.Herein,we successfully isolated a novel silver thiolate nanocluster[Ag_(13)@Ag_(76)S_(16)(Cyh S)_(42)(p-NH_(2)-Ph As O_(3))_(4)]^(3+)(SD/Ag89 a,Cyh SH=cyclohexanethiol)that contains a well-isolated icosahedral Ag_(13) kernel passivated by four Ag S_(4)^(7-) tetrahedra and four p-NH_(2) Ph As O_(3)^(2-) piercing from outer Ag_(72) shell.Of note,this Ag_(13) kernel is the largest isolable subvalent silver kernel beneath the silver shell with extremely legible core-shell boundary ever before and represents a precise embryonic model formed in the reducing Ag(I)to Ag(0)followed by aggregating to large silver nanoparticles.The reductive role of DMF and the introduction of anionic passivation layer(APL)synergistically modulate the reduction kinetics,facilitating the capture of ultrasmall subvalent silver kernel.SD/Ag89 a emits in near infrared(NIR)region(λ_(em)=800 nm)at low temperature.The synthetic strategy shown in this work opens up new opportunities for precisely capturing and recognizing diverse reductive silver kernels in different systems.

Core engineering of paired core-shell silver nanoclusters

Unlike the facile modulation of surface structure through protecting ligands,the core shielded by outer shell of silver nanoclusters is still hard to be controlled.Ligand effects may seep into the incipient growth of silver core.However,the comparable cases to validate such hypothesis are currently lacking.Herein,we shed light on two core-shell silver nanoclusters,Ag_(7)S_(6)@Ag_(48)(SD/Ag55b,SD=SunDi)and Ag_(6)S_(6)@Ag_(48)(SD/Ag54b),differing in only one silver atom in the core which varies from a pentagon-bipyramidal Ag_(7)to an octahedral Ag_(6)while keeping the Ag_(48)shielding shell almost the same.Although no direct bonding between alkynes and silver core is observed in them,we propose that the ligand effect still exerts profound influences on the size and geometry of silver core.The solution behaviours and complete ligand-exchange reaction of SD/Ag55b in CH_(2)Cl_(2)are investigated using electrospray ionization mass spectrometry.Due to more and stronger argentophilic interactions,SD/Ag55b exhibits room-temperature phosphorescence with a 40 nm red-shift compared to that of SD/Ag54b in CH_(2)Cl_(2).This work not only presents effective fabrication of silver nanoclusters via synergism of dithiophosphate and alkyne ligands,but also provides us a pair of comparable examples to understand substitution group effect of protecting ligand on the core structures and properties.

Effectiveness of indoor residual spraying on malaria control: a systematic review and meta-analysis

Background:Indoor residual spraying(IRS)is one of the key interventions recommended by World Health Organization in preventing malaria infection.We aimed to conduct a systematic review and meta-analysis of global studies about the impact of IRS on malaria control.Method:We searched PubMed,Web of Science,Embase,and Scopus for relevant studies published from database establishment to 31 December 2021.Random-effects models were used to perform meta-analysis and subgroup analysis to pool the odds ratio(OR)and 95%confidence interval(CI).Meta-regression was used to investigate potential factors of heterogeneity across studies.Results:Thirty-eight articles including 81 reports and 1,174,970 individuals were included in the meta-analysis.IRS was associated with lower rates of malaria infection(OR=0.35,95%CI:0.27-0.44).The significantly higher effectiveness was observed in IRS coverage≥80%than in IRS coverage<80%.Pyrethroids was identified to show the greatest performance in malaria control.In addition,higher effectiveness was associated with a lower gross domestic product as well as a higher coverage of IRS and bed net utilization.Conclusions:IRS could induce a positive effect on malaria infection globally.The high IRS coverage and the use of pyrethroids are key measures to reduce malaria infection.More efforts should focus on increasing IRS coverage,developing more effective new insecticides against malaria,and using multiple interventions comprehensively to achieve malaria control goals.