Upper crustal deformation characteristics in the northeastern Tibetan Plateau and its adjacent areas revealed by GNSS and anisotropy data

The northeastern part of the Tibetan Plateau is a region where different tectonic blocks collide and intersect,and large earthquakes are frequent.Global Navigation Satellite System(GNSS)observations show that tectonic deformation in this region is strong and manifests as non-uniform deformation associated with tectonic features.S-wave splitting studies of near-field seismic data show that seismic anisotropy parameters can also reveal the upper crustal medium deformation beneath the reporting station.In this paper,we summarize the surface deformation from GNSS observations and crustal deformation from seismic anisotropy data in the northeastern Tibetan Plateau.By comparing the principal compressive strain direction with the fast S-wave polarization direction of near-field S-wave splitting,we analyzed deformation and its differences in surface and upper crustal media in the northeastern Tibetan Plateau and adjacent areas.The principal compressive strain direction derived from GNSS is generally consistent with the polarization direction of fast S-waves,but there are also local tectonic regions with large differences between them,which reflect the different deformation mechanisms of regional upper crustal media.The combination of GNSS and seismic anisotropy data can reveal the depth variation characteristics of crustal deformation and deepen understanding of three-dimensional crustal deformation and the deep dynamical mechanisms underlying it.it.

Contemporary crustal tectonic movement in the southern Sichuan-Yunnan block based on dense GPS observation data

We analyzed 360 permanent and campaign GPS data from 1999 to 2017 in the southern Sichuan-Yunan block, and obtained crustal horizontal deformation in this region.Then, we derived the strain rate using a multi-scale spherical wavelet method.Results reveal a complex pattern of tectonic movement in the southern Sichuan-Yunnan block.Compared to the stable Eurasian plate, the maximum rate of the horizontal deformation in the southern Sichuan-Yunnan block is approximately 22 mm/a.The Xiaojiang fault shows a significantly lower deformation—a left-lateral strike-slip movement of 9.5 mm/a.The Honghe fault clearly shows a complex segmental deformation from the north to south.The northern Honghe fault shows 4.3 mm/a right strike-slip with 6.7 mm/a extension; the southern Honghe fault shows 1.9 mm/a right strike-slip with 1.9 mm/a extension; the junction zone in the Honghe and Lijiang–Xiaojinhe faults shows an obvious clockwise-rotation deformation.The strain calculation results reveal that the maximum shear-strain rate in this region reaches 70 nstrain/a, concentrated around the Xiaojiang fault and at the junction of the Honghe and Lijiang–Xiaojinhe faults.We note that most of the earthquakes with magnitudes of 4 and above that occurred in this region were within the high shear strain-rate zones and the strain rate gradient boundary zone, which indicates that the magnitude of strain accumulation is closely related to the seismic activities.Comparison of the fast shear-wave polarization direction of the upper-crust with the upper-mantle anisotropy and the direction of the surface principal compressive strain rate obtained from the inversion of the GPS data reveals that the direction of the surface principal compressive strain is basically consistent with the fast shear-wave polarization direction of the upper crust anisotropy, but different from the polarization direction of the upper mantle.Our results support the hypothesis that the principal elements of the deformation mechanism in the southern Sichuan-Yunnan block are decoupling between the upper and lower crust and ductile flow in the lower crust.

Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy

An essential concept of cancer immunotherapy is that immunogenic cell death(ICD),characterized by the release of tumor-associated antigens(TAAs)and tumor-specific antigens(TSAs)like neoantigens,danger-associated molecular patterns(DAMPs),and pro-inflammatory cytokines,facilitates the presentation of TAAs and TSAs to adaptive immune cells,eliciting an emerging or reinstating a pre-existing anti-cancer immune response.

VISUALIZATION OF HEAD AND NECK CANCER MODELS WITH A TRIPLE FUSION REPORTER GENE

The development of experimental animal models for head and neck tumors generally rely on the biol uminescence imaging to achieve the dynamic monitoring of the tumor growth and metastasis due to the complicated anatomical structures.Since the bioluminescence imaging is largely affected by the intracellular luciferase expression level and external D-luciferin concentrations,its imaging accuracy requires further confirmation.Here,a new triple fusion reportelr gene,which consists of a herpes simplex virus type 1 thymidine kinase(TK)gene for radioactive imaging,a far-red fuorescent protein(mLumin)gene for fuorescent imaging,and a firefly luciferase gene for bioluminescence imaging,was introduced for in vrivo observation of the head and neck tumors through multi-modality imaging.Results show that fuorescence and bioluminescence signals from mLumin and luciferase,respectively,were clearly observed in tumor cells,and TK could activate suicide pathway of the cells in the presence of nucleotide analog-ganciclovir(GCV),demonstrating the effecti veness of individual functions of each gene.Moreover,subcutaneous and metastasis animal models for head and neck tumors using the fusion reporter gene-expressing cell lines were established,allowing multi-modality imaging in vio.Together,the established tumor models of head and neck cancer based on the newly developed triple fusion reporter gene are ideal for monitoring tumor growth,assessing the drug therapeutic efficacy and verifying the effec-tiveness of new treatments.

Fluorescent and quantitative mitochondrial redox imaging of tumor targeted by Octa-RGD probe

Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor biomarker.Metabolism investigation also plays important roles in tumor theranostics.Devel-oping simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment,however,the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so far.Here,we developed an octavalent fuo-rescent probe Octa-R.GD by convenient genetic method,based on one tetrameric far-red fluo-rescent protein(fRFP)linked with RGD pept ides.We validated its inter gin targeting by confocal imaging in vitro.Then we screened a variety of tumor cells,and differentiated their binding affinity based on the fuorescence of the probe via flow cytometry.Among these cells,CNE-2 cells had the highest uptake of the probe,while B16 cells had the lowest,corresponding with their intergin expression levels.Next,the fuorescent and metabolic imaging was performed in HT1080(intergin postive)tumor,where nicotinamide adenine dinudeotide hydrogen(NADH),flavo-protein(Fp)and fRFP fuorescent signals were collected.The tumor from mice intravenously injected with Octa RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH)and fRFP signal,than those with fRFP protein.It suggested that integrin targeting may have influence on the target cell metabolism,and further demonstrated Octa-R.GD probe facilitated its uptake in the targeted tumor in vrivo.This paper developed a useful probe,which can bind integrins speci-cally and e±ciently in tumor cells,and together with tumor metabolic information,it may provide new insight for RGD targeting-based cancer therapeutics.

KillerRed protein based in vivo photodynamic therapy and corresponding tumor metabolic imaging

Photodynamic therapy(PDT)gains wide attention as a useful therapeutic method for cancer.It is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species(ROS),which induce cellular toxicity and regulate the redox potential in tumor cells.Nowadays,genetic photosensitizers of low toxicity and easy production are required to be developed.KillerRed,a unique red fluorescent protein exhibiting excellent phototoxic properties,has the potential to act as a photosensitizer in the application of tumor PDT.Meantime,the course of tumor redox metabolism during this treatment was rarely investigated so far.Thus here,we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen(NADH)and flavoprotein(Fp),two important metabolic coenzymes of tumor cells.Results showed the tumor growth had been significantly inhibited by KillerRedbased PDT treatment compared to control groups.A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors.The Fp signal was elevated by nearly 4.5-fold,while the NADH signal decreased by 66%after light irradiation,indicating that Fp and NADH were oxidized in the course of KillerRedbased PDT.Furthermore,we also observed correlation between the fluorescence distribution of KillerRed and NADH.It suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.

Comparison of caspase-3 activation in tumor cells upon treatment of chemotherapeutic drugs using capillary electrophoresis

Caspases play important roles in cell apoptosis.Meas-urement of the dynamics of caspase activation in tumor cells not only facilitates understanding of the molecular mechanisms of apoptosis but also contributes to the development,screening,and evaluation of anticancer drugs that target apoptotic pathways.The fluorescence resonance energy transfer(FRET)technique provides a valuable approach for defining the dynamics of apop-tosis with high spatio-temporal resolution.However,FRET generally functions in the single-cell level and becomes ineffective when applied in the high throughput detection of caspase activation.In the cur-rent study,a FRET sensor was combined with capillary electrophoresis(CE)to achieve a high throughput method for cellular caspase detection.The FRET-based CE system is composed of a homemade CE system and a laser source for detecting the dynamics of caspase-3 in various cells expressing sensors of caspase-3 that have been treated with anticancer drugs,such as cell cycle-independent drug cisplatin and specific cell cycle drugs camptothecin and etoposide,as well as their combination with tumor necrosis factor(TNF).A posi-tive correlation between the caspase-3 activation ve-locity and drug concentration was observed when the cells were treated with cisplatin,but cells induced by camptothecin and etoposide did not show any apparent correlation with their concentrations.Moreover,differ-ent types of cells presented distinct sensitivities under the same drug treatment,and the combination treat-ment of TNF and anticancer drugs significantly accel-erated the caspase-3 activation process.Its high throughput capability and detection sensitivity make the FRET-based CE system a useful tool for investi-gating the mechanisms of anticancer drugs and anti-cancer drug screening.

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Autologous tumor cells and cell-derived secretions(CDS)can induce antitumor immune responses.The conditions in which cells are cultured and treated impact CDS,and cellular insults alter their composition and function.In this study,we generated CDS from tumor cells exposed to normal culture conditions,hypoxia,cisplatin,radiotherapy,photodynamic therapy,or hypochlorous acid(HOCl).In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia,cisplatin,radiotherapy or photodynamic therapy.To improve HOCl-CDS activity at the tumor site,we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold.When injected intratumorally,the HOCl-CDS hydrogel promoted tumor cell death,cytotoxic T lymphocyte infiltration,and tumor-associated macrophage reprogramming towards an M1 phenotype.The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma.Furthermore,hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade.These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.