CircRNA在肺癌诊断与发生发展及耐药中的作用进展

肺癌在全球范围内的致死率一直居高不下。近年来针对多种分子分型的靶向药物已成为中晚期肺癌治疗的新有效手段,但是肺癌在早期诊断以及长期有效的治疗上仍然面临着严峻的挑战。环状RNA(circular RNA,circRNA)是一类具有环形结构的独特RNA分子,具有优异的稳定性以及表达特异性。越来越多的研究发现circRNA在肿瘤中表达异常,这种异常表达不仅与肿瘤的恶性相关,同时可以参与调控肿瘤进展,为肿瘤的诊断与治疗提供了新的思路。因此,本文就circRNA在肺癌中的表达、诊断、预后价值以及发生发展机制展开综述,以期为肺癌的早期诊断与治疗寻找新的靶点。

Multiple valence states of Fe boosting SERS activity of Fe_(3)O_(4) nanoparticles and enabling effective SERS-MRI bimodal cancer imaging

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment.Herein,an optimized strategy for designing a Fe_(3)O_(4)-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering(SERS)and magnetic resonance imaging(MRI)is introduced.Excellent SERS activity of ultrasmall Fe_(3)O_(4) nanoparticles(NPs)was discovered,and a 5×10^(-9)M limit of detection for crystal violet molecules was successfully obtained.The high-efficiency interfacial photon-induced charge transfer in Fe_(3)O_(4) NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe,which was observed using ultraviolet-visible diffuse reflectance spectroscopy.Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe_(3)O_(4) NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination.The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Feg Og-based bioprobe with high sensitivity and good specificity.Notably,Fe_(3)O_(4)-based bioprobes simultaneously exhibited T,-weighted MRI contrast enhancement with an active targeting capability for tumors in vivo.To the best of our knowledge,this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro,which has been previously realized only using semiconductor-metal complex materials.The non-metallic materials with SERS-MRI dual-modal imaging established in this report are a promising cancer diagnostic platform,which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.

In-orbit performance of LE onboard Insight-HXMT in the first 5 years

Purpose The low-energy X-ray telescope(LE)is a main instrument of the Insight-HXMT mission and consists of 96 swept charge devices covering the 1–10 keV energy band.The energy gain and resolution are continuously calibrated by analyzing Cassiopeia A(Cas A)and blank sky data,while the effective areas are also calibrated with the observations of the Crab Nebula.In this paper,we present the evolution of the in-orbit performances of LE in the first 5 years since launch.Methods The Insight-HXMT data analysis software package(HXMTDAS)is utilized to extract the spectra of Cas A,blank sky,and Crab Nebula using different good time interval selections.We fit a model with a power-law continuum and several Gaussian lines to different ranges of Cas A and blank sky spectra to get peak energies of their lines through xspec.After updating the energy gain calibration in CALibration DataBase(CALDB),we rerun the Cas A data to obtain the energy resolution.An empirical function is used to modify the simulated effective areas so that the background-subtracted spectrum of the Crab Nebula can best match the standard model of the Crab Nebula.Results The energy gain,resolution,and effective areas are calibrated every month.The corresponding calibration results are duly updated in CALDB,which can be downloaded and used for the analysis of Insight-HXMT data.Simultaneous observations with NuSTAR and NICER can also be used to verify our derived results.Conclusion LE is a well-calibrated X-ray telescope working in 1–10 keV band.The uncertainty of LE gain is less than 20eV in 2–9 keV band,and the uncertainty of LE resolution is less than 15eV.The systematic errors of LE,compared to the model of the Crab Nebula,are lower than 1.5%in 1–10 keV.

Two-dimensional layered nanomaterials fortumor diagnosis and treatment

With the evolution of nanomedicine,the past decades witnessed diversified nanomaterials as marvelous antitumor tools ushering in a new era of tumor diagnosis and treatment.Among them,two-dimensional layered nano-material as an emerging class of nanomaterials has one dimension less than 100 nm,showing a high specific area and the thinnest sheet-like structure(Liu S,Pan X,Liu H.Twodimensional nanomaterials for photothermal therapy.Angew Chem Int Ed 2020;59:5890–900).The discovery of graphene drove the exploration of various new two-dimensional layered nanomaterials for tumor diagnosis and treatment including graphene-based nanomaterials,black phosphorus(BP),transition metal dichalcogenides(TMDs),layered double hydroxides(LDHs),and bismuth oxyhalides(BiOX,X=F,Cl,Br,I)(Ma H,Xue MQ.Recent advances in the photothermal applications of two-dimensional nanomaterial:photothermal therapy and beyond.J Mater Chem 2021;9:17569).On the one hand,they exhibit strong near-infrared(NIR)absorption and the capacity of optimizing corresponding properties by adjusting the crystal structure.On the other hand,they own unique strengths such as fantastic physicochemical properties(graphene-based nanomaterials),high loading capacity(BP),distinct phase-dependent optical properties(TMDs),a specific chemical response to the tumor microenvironment(LDHs),and large X-ray attenuation coefficient(BiOX).Herein,we briefly introduce three typical two-dimensional layered nanomaterials,their prospects and future research priorities in tumor diagnosis and treatment are concluded.

基于效用决策理论下广州市养老服务模式变化趋势研究

'人口老龄化'是中国当前面临的一大社会发展难题,为更好迎接及应对老龄化社会的到来,本文以广州市为研究对象,提出了六种既适合当前社会,又符合未来老年人事业发展的六种养老模式。论文运用个人消费效用决策理论构建养老服务体系决策模型,通过文献检索、调查问卷、访谈、专家讨论等研究方法确定模型中的各项权重值,计算出'当前、未来五年、未来十年'三个时间节点六种养老服务模式的18个效用值。通过横向、纵向比较,分析出目前及预测未来广州市的养老服务模式的重心及发展趋势,构建一个适应广州市老年人事业未来发展的动态养老服务模式。此研究不仅具有很强实践性,而且还为全国其他城市的养老服务事业发展预测提供前瞻性的借鉴意义。

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China’s first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band(1-250 ke V) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 Me V. It was designed to perform pointing, scanning and gamma-ray burst(GRB)observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed.Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.

The enhanced X-ray Timing and Polarimetry mission—eXTP

In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment.

Insight-HXMT observations of the first binary neutron star merger GW170817

Finding the electromagnetic （EM） counterpart of binary compact star merger, especially the binary neutron star （BNS） merger, is critically important for gravitational wave （GW） astronomy, cosmology and fundamental physics. On Aug. 17, 2017, Advanced LIGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart, GRB 170817A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope （HE） onboard Insight-HXMT （Hard X-ray Modulation Telescope） is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart （SSS17a/AT2017gfo） with very large collection area （M000 cm2） and microsecond time resolution in 0.2-5 MeV. In addition, Insight-HXMT quickly implemented a Target of Opportunity （TOO） observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy （0.2-5 MeV） radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817A. Meanwhile, Insight-HXMT/HE provides one of the most stringent constraints （-10-7 to 104 erg/cm2/s） for both GRB170817A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event.

The Low Energy X-ray telescope (LE) onboard the Insight-HXMT astronomy satellite

The Low Energy X-ray telescope(LE) is one of the three main instruments of the Insight-Hard X-ray Modulation Telescope(Insight-HXMT). It is equipped with Swept Charge Device(SCD) sensor arrays with a total geometrical area of 384 cm^2 and an energy band from 0.7 to 13 ke V. In order to evaluate the particle induced X-ray background and the cosmic X-ray background simultaneously, LE adopts collimators to define four types of Field Of Views(FOVs), i.e., 1.6°×6°, 4°×6°, 50°-60°×2°-6 oand the blocked ones which block the X-ray by an aluminum cover. LE is constituted of three detector boxes(LEDs) and an electric control box(LEB) and achieves a good energy resolution of 140 e V@5.9 ke V, an excellent time resolution of 0.98 ms, as well as an extremely low pileup(<1%@18000 cts/s). Detailed performance tests and calibration on the ground have been performed,including energy-channel relation, energy response, detection efficiency and time response.

A facile fabrication route for binary transition metal oxide-based Janus nanoparticles for cancer theranostic applications

Janus nanoparticles （JNPs） have multiple configurations for molecular imaging, targeting, and therapeutic effects on cancers; these properties have made these particles attractive for biomedical applications. Nonetheless, smart strategies for the controlled synthesis in a liquid phase and exploration of the appropriate applications of JNPs remain a challenge. In this study, a unique liquid-phase method was applied to fabricate Mn3O4-TiO2/ZnO/Fe3O4 multifunctional binary transition metal oxide-based JNPs, using the concept of epitaxial growth and lattice mismatch among synthesized materials. Transmission electron microscopy and scanning transmission electron microscopy results revealed that the created materials are embedded in the form of dimers with good dispersion and homogeneous growth in a nonpolar solvent. Pluronic F-127-coated MnBO4- TiO2 JNPs were utilized as a contrast agent in T1-weighted magnetic resonance imaging （MRI） and in photodynamic therapy （PDT） for cancers in vitro and in vivo. In vivo T1-weighted MRI of the heart, liver, and kidneys in mice after intravenous injection of the nanoparticles revealed high sensitivity and biocompatibility of as-synthesized Mn3O4--TiO2 JNPs. Results of synchrotron X-ray fluorescence microscopy mapping showed the stability of the nanocomposites and efficiency of penetration into the cytoplasm and perinuclear area. Inorganic TiO2 photosensitizers showed promising tumor ablation performance in PDT in vitro and in vivo at low intensity of UV irradiation （5.6 mW.cm-2） because of their ultrasmall size and photodegradable stability. These results reveal that multifunctional Mn3O4-TiO2 JNPs enhance a T1-weighted MRI contrast and have excellent properties for PDT and therefore, may be a novel agent for cancer theranostics.

Controllable synthesis of layered black bismuth oxidechloride nanosheets and their applications in internal tumor ablation

The recently emerging bismuth oxyhalide(BiOX)nanomaterials are promising indirect band gap photosensitizer for ultraviolet(UV)light-triggered phototherapy due to their unique layered nanosheet structure.However,the low absorption and poor photothermal conversion efficiency have always impeded their further applications in cancer clinical therapy.Herein,BiOCl rich in oxygen vacancies has been reported to have fullspectrum absorption properties,making it possible to achieve photothermal property under near-infrared laser.Under 808nm irradiation,the photothermal conversion efficiency of black BiOCl nanosheets(BBNs)is up to 40%.BBNs@PEG can effectively clear primary subcutaneous tumors and prevent recurrence,achieving good synergistic treatment effect.These results not only broke the limitation of UV on the BiOCl material and provided a good template for other semiconductor materials,but also represent a promising approach to fabricate BBN@PEG a novel,potent and multifunctional theranostic platform for precise photothermal therapy and prognostic evaluation.

Identification of transcriptional isoforms associated with survival in cancer patient

The Cancer Genome Atlas(TCGA) project produced RNA-Seq data for tens of thousands of cancer and non-cancer samples with clinical survival information,providing an unprecedented opportunity for analyzing prognostic genes and their isoforms.In this study,we performed the first large-scale identification of transcriptional isoforms that are specifically associated with patient prognosis,even without gene-level association.These specific isoforms are defined as Transcripts Associated with Patient Prognosis(TAPPs).Although a group of TAPPs are the principal isoforms of their genes with intact functional protein domains,another group of TAPPs lack important protein domains found in their canonical gene isoforms.This dichotomy in the distribution of protein domains may indicate different patterns of TAPPs association with cancer.TAPPs in protein-coding genes,especially those with altered protein domains,are rich in known cancer driver genes.We further identified multiple types of cancer recurrent TAPPs,such as DCAF17-201,providing a new approach for the detection of cancer-associated events.In order to make the wide research community to study prognostic isoforms,we developed a portal named GESUR(http://gesur.cancer-pku.cn/),which illustrates the detailed prognostic characteristics of TAPPs and other isoforms.Overall,our integrated analysis of gene expression and clinical parameters provides a new perspective for understanding the applications of different gene isoforms in tumor progression.