Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma

Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was discussed.Methods: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by WB.Results: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated markers.Conclusions: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and invasion.Our study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds:A large-scale,retrospective study

Objective:Hepatocellular carcinoma(HCC)is a lethal global disease that requires an accurate diagnosis.We assessed the potential of 5 serum biomarkers(AFP,AFU,GGT-II,GPC3,and HGF)in the diagnosis of HCC.Methods:In this retrospective study,we measured the serum levels of each biomarker using ELISAs in 921 participants,including 298 patients with HCC,154 patients with chronic hepatitis(CH),122 patients with liver cirrhosis(LC),and 347 healthy controls from 3 hospitals.Patients negative for hepatitis B surface antigen and hepatitis C antibody(called"NBNC-HCC")and patients positive for the above indices(called"HBV-HCC and HCV-HCC")were enrolled.The selected diagnostic model was constructed using a training cohort(n=468),and a validation cohort(n=453)was used to validate our results.Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.Results:Theα-L-fucosidase(AFU)/α-fetoprotein(AFP)combination was best able to distinguish NBNC-HCC[area under the curve:0.986(95%confidence interval:0.958–0.997),sensitivity:92.6%,specificity:98.9%]from healthy controls in the test cohort.For screening populations at risk of developing HCC(CH and LC),the AFP/AFU combination improved the diagnostic specificity for early-stage HCC[area under the curve:0.776(0.712–0.831),sensitivity:52.5%,specificity:91.6%in the test group].In all-stage HBV-HCC and HCV-HCC,AFU was also the best candidate biomarker combined with AFP[area under the curve:0.835(0.784–0.877),sensitivity 69.1%,specificity:87.4%in the test group].All results were verified in the validation group.Conclusions:The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.

Ⅲ Ⅳ型肝门胆管癌不同切除方式对预后的影响

目的:比较Ⅲ、Ⅳ型肝门胆管癌(hilar cholangiocarcinoma,HC)手术治疗方式及疗效。方法:回顾性分析自2010年1月至2015年12月就诊于天津医科大学肿瘤医院行手术治疗的50例Ⅲ、Ⅳ型HC患者的临床资料。结果:50例HC患者获得随访,中位随访时间为27个月。其中围肝门局限肝切除组13例,中位无复发时间为6个月,1、2年无复发率分别为30.8%、23.1%;中位生存时间为20个月,1、2年生存率分别为76.9%、38.5%;扩大肝切除组37例,中位无复发时间为14个月,1、2年无复发率分别为59.5%、32.4%;中位生存时间为37个月,1、2年生存率分别为83.8%、51.4%。扩大肝切除组无复发时间及生存时间均长于围肝门局限肝切除组(P<0.05),1、2年无复发生存率及总生存率也更高(P<0.05),但是两组并发症发生率及病死率并无显著差异(P>0.05)。结论:扩大肝切除术是延缓Ⅲ、Ⅳ型HC患者早期复发、改善生存预后的安全术式。

Ultrasensitive detection of aliphatic nitro-organics based on“turn-on”fluorescent sensor array

The broad class of explosives includes nitro aromatics as well as challenging aliphatic nitro-organics whose detection is important from counter-terrorism and national security perspectives.Here we report a turn-on fluorescent sensor array based on aggregation-induced emission(AIE)fluorophores as receptors.To achieve a good sensing system with fast response,good sensitivity and low detection limit,three receptors with abundant chemical diversities for target analytes were synthesized.The turn-on response of the individual receptor showed highly variable and cross-reactive analyte-dependent changes in fluorescence.The excellent ability to identify a variety of explosives,especially the challenging aliphatic nitro-organics(2,3-dimethyl-2,3-dinitrobutane(DMNB),1,3,5-trinitro-1,3,5-triazinane(RDX),cyclotetramethylene tetranitramine(HMX)and entaerythritol tetranitrate(PETN)),was demonstrated in qualitative and quantitative analyses with 100%accuracy.The fluorescence signal amplification in the presence of explosives allows for application of these receptors in a sensor microarray suitable for high-throughput screening.These results suggested that the cross-reactive sensor array based on AIE fluorophores could find a wide range of applications for sensing various analytes or complex mixtures.

A multiple coupling approach to produce high-performance SERS substrates

Creating hotspots with significantly enhanced electromagnetic(EF) field, efficiently placing target molecules in hotspot region, and achieving uniform and reproducible Raman signals are three critical issues for developing high-performance SERS substrates. In this work, large area gold nanoparticle cluster pillar array with a gold mirror at bottom was facilely fabricated by combined use of nanosphere lithography and self-assembly approach. It is both theoretically and experimentally found that through multiple coupling interactions, the electromagnetic fields at interparticle gaps within the gold clusters were significantly enhanced in our three-dimentional(3D) pillar array substrates, which can result in one order of magnitude stronger as compared with random gold clusters on a two-dimentional planar case.Due to the periodic stucture, our substrates also possess the capbility of producing highly uniform and reproducible SERS signals. Attractively, in our case, a photoresponsive polymer was used for the formation of pillar array structure. Its unique photoinduced deformation makes it possible to reversibly open and close the gaps of the closely packed Au NP array, thus enabling efficient placement or entrapment of probe molecules into hotspot sites between adjacent nanoparticles.

Cloning and identification of a novel human glioma differentiation related gene GDR1

In order to identify the genes associated with glioblastoma differentiation, some ESTs, expressed differentially in the control cell and the differentiated human glioblastoma cell line BT-325 induced by the all-trans retinoid acid, have been isolated by the method of DDRT-PCR. Of the 46 ESTs sequenced, 19 are from new genes. A full-length 1 535-bp cDNA, termed gene GDR1, has been isolated from the human cDNA library using the probe designed according to one of the novel ESTs, HGBB098. The open reading frame of GDR1 gene encodes a putative protein containing 334 amino acid residues. Blast against the current GenBank DMA and protein sequence database did not reveal significant homology with any known proteins. RT-PCR shows that GDR1 mRNA level increased in the differentiated BT-325 cells after being treated with RA. The different expression patterns of GDR1 mRNA in human tissues have been detected through the multiple tissue Northern blot hybridization.

Gram-scale fabrication of patchy nanoparticles with tunable spatial topology and chemical functionality

Patchy particles,defined as particles with one or more well-defined patches,have attracted much attention due to their anisotropic and.directional interactions.The anisotropic nature of the patchy particle surface enables a certain degree of control over the assembly,process.Enormous efforts have been carried out to design and explore the properties of patchy particles and their collective behaviour.However,the techniques to fabricate patchy particles are still limited in terms of tunability and scalability.In this work,an effective method of fabricating patchy particles with tunable spatial topology and chemical composition of patches is presented.The number,distribution and size of the patches can be tailored by adjusting the packing of the colloidal particles and the processing condition.The active secondary reaction on the polydopamine(PDA)-coated surface and silica surface could functionalize the obtained patchy particles with desired properties to meet different requirements.As a proof of principle,the PDA-coated patches were modified with thiol-based dye via the Michael reaction and the silica surfaces were functionalized with amine-terminated alkoxysilanes via the silane coupling reaction have been demonstrated.Furthermore,the unique properties of PDA,such as reductive ability,powerful'adhesive capability and carbonizable feature,have also been proven to fabricate metallic nanoparticle-decorated patchy particles and anisotropic carbon nanocapsules.The well-defined patchy particles are templated from colloidal crystal and their gram-scale fabrication is easily achieved.These results indicate that our strategy will help access the transformative potential of patchy particles in the rational design and large-scale production of functional materials.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination:A prospective Chinese cohort study

Background:Vaccination has been shown effective in controlling the global coronavirus disease 2019(COVID-19)pandemic and reducing severe cases.This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis(RA).Methods:A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status.Each of them was examined every 3 to 6 months.In the vaccination group,disease activity was compared before and after vaccination.The rates of flare defined as disease activity scores based on 28-joint count(DAS28)>3.2 withΔDAS28≥0.6 were compared between vaccination and non-vaccination groups.Results:A total of 202 eligible RA patients were enrolled.Of these,98 patients received no vaccine shot(non-vaccination group),and 104 patients received two doses of vaccine(vaccination group).The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days,respectively.The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar.At enrollment,gender,RA disease course,seropositivity,and disease activity were comparable across the two groups.Flare was observed in five(4.8%)of the vaccination group patients and nine(9.2%)of the non-vaccination group patients at post-vaccination assessment(P=0.221).In terms of safety,29(27.9%)patients experienced adverse events(AEs)after vaccination.No serious AEs occurred.Conclusions:COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity.Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Block copolymer assisted topochemical polymerization:A facile and efficient route to robust polymeric nanoporous membranes decorated with versatile amino acids

Based on block copolymer assisted topochemical polymerization,a new strategy for facilely producing robust nanoporous membranes with controlled incorporation of functional groups onto nanopores is developed.As exemplified by preparing nanoporous polypyrrole decorated with amino acids,this strategy exhibits a high degree of freedom for tailoring the surface functionality in the created pores.

Direct identification of HMX via guest-induced fluorescence turn-on of molecular cage

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine(HMX) is one of the most widely used powerful explosives. The direct and selective detection of HMX, without the requirement of specialized equipment, remains a great challenge due to its extremely low volatility, unfavorable reduction potential and lack of aromatic rings. Here, we report the first chemical probe of direct identification of HMX at ppb sensitivity based on a designed metal-organic cage(MOC). The cage features two unsaturated dicopper units and four electron donating amino groups inside the cavity, providing multiple binding sites to selectively enhance host-guest events. It was found that compared to other explosive molecules the capture of HMX inside the cavity would strongly modulate the emissive behavior of the host cage, resulting in highly induced fluorescence “turn-on”(160 folds). Based on the density functional theory(DFT) simulation, the mutual fit of both size and binding sites between host and guest leads to the synergistic effects that perturb the ligand-to-metal charge-transfer(LMCT) process, which is probably the origin of such selective HMX-induced turn-on behavior.