Pn wave velocity and anisotropy underneath the central segment of the North-South Seismic Belt in China

We present a Pn wave velocity and anisotropy model of the central segment of the North-South Seismic Belt in China, where there are numerous stable basins and active faults, making this segment attractive for extensive studies. The model was obtained by a tomographic analysis of 49,973 Pn wave phase readings collected by the China Earthquake Networks Center and temporary stations in Yunnan and Sichuan. The tomographic velocity model shows that the average Pn wave velocity is 8.06km/s; prominent high-velocity (high-V) anomalies are visible under the Sichuan Basin, the Zoige Basin and the Ordos block, which clearly outline their tectonic mar- gins. A pronounced low-velocity (low-V) zone is observed from the Songpan-Ganzi block to the Chuan-Dian and Daliangshan blocks, suggesting the presence of hot material upwelling. The station delay data show a gradual variation from negative to positive values, possibly reflecting a crustal thickness variation from the southwest to the northeast of the study area. A correlation between the Pn wave anisotropy and the distribution of velocity anomalies is observed: anisotropy is relatively weaker in the high-V anomaly zones beneath stable basins, while it is stronger in the low-V anomaly zones and the high-to-low-V anomaly transition zones. The high-resolution velocity and anisotropy tomographic model that we obtained could also provide a better understanding of the study area seismicity, since the occurrence of strong earthquakes seems to be related to the presence and strength of lateral heterogeneities at the uppermost mantle level

Improvement of a highly sensitive and specific whole-cell biosensor by adding a positive feedback amplifier

In this study, we designed a Cd2+ whole-cell biosensor with both positive and negative feedback cascade amplifiers in Pseudomonas putida KT2440 (LTCM) based on our previous design with only a negative feedback amplifier (TCM). The results showed that the newly developed biosensor LTCM was greatly improved compared to TCM. Firstly, the linear response range of LTCM was expanded while the maximum linear response range was raised from 0.05 to 0.1 μM. Meanwhile, adding a positive feedback amplifier further increased the fluorescence output signal of LTCM 1.11–2.64 times under the same culture conditions. Moreover, the response time of LTCM for detection of practical samples was reduced from 6 to 4 h. At the same time, LTCM still retained very high sensitivity and specificity, while its lowest detection limit was 0.1 nM Cd2+ and the specificity was 23.29 (compared to 0.1 nM and 17.55 in TCM, respectively). In summary, the positive and negative feedback cascade amplifiers effectively improved the performance of the biosensor LTCM, resulting in a greater linear response range, higher output signal intensity, and shorter response time than TCM while retaining comparable sensitivity and specificity, indicating better potential for practical applications

Progress on additive manufacturing of 600 ℃ high-temperature titanium alloys

Key components used in the high-pressure compressor of advanced aero engines operating in the 550-600 ℃ range have an urgent demand for 600 ℃ high-temperature titanium alloy. However，the use of casting，forging，and other traditional processing techniques is not sufficient to meet the requirements for gradient or composite structures，functional integration components and complex components that are difficult to form. Additive manufacturing is an advanced manufacturing technology that offers unique advantages such as material design-manufacturing integration and complex design-customization integration. It provides a new approach to the development of new materials and technologies of 600 ℃ high-temperature titanium alloy. Currently，attention is being paid to the processing of 600 ℃ high-temperature titanium alloy by using additive manufacturing techniques at home and abroad，focusing on the relationship among materials，processing，structures，and properties. Firstly，this paper reviews the research on 600 ℃ high-temperature titanium alloy in brief，introduces the microstructure characteristics of deposited and post-treated states of 600 ℃ high-temperature titanium alloy under different additive manufacturing processes，and analyzes key properties such as tensile properties，creep properties，thermal fatigue properties，and antioxidant properties. Then，the research progress of composite materials based on 600 ℃ high-temperature titanium alloy and gradient structure built by additive manufacturing is discussed. Finally，the prospects are provided for research directions including the development of 600 ℃ high-temperature titanium alloy materials for additive manufacturing，exploration of hybrid manufacturing processes，defect control，and establishment of performance evaluation standards

Understanding the Impact of Bismuth Heterovalent Doping on the Structural and Photophysical Properties of CH3NH3PbBr3 Halide Perovskite Crystals with Near-IR Photoluminescence

A comprehensive study unveiling the impact of heterovalent doping with Bi3+ on the structural, semiconductive, and photoluminescent properties of a single crystal of lead halide perovskites (CH3NH3PbBr3) is presented. As indicated by single-crystal XRD, a perfect cubic structure in Bi3+-doped CH3NH3PbBr3 crystals is maintained in association with a slight lattice contraction. Time-resolved and power-dependent photoluminescence (PL) spectroscopy illustrates a progressively quenched PL of visible emission, alongside the appearance of a new PL signal in the near-infrared (NIR) regime, which is likely to be due to energy transfer to the Bi sites. These optical characteristics indicate the role of Bi-3 dopants as nonradiative recombination centers, which explains the observed transition from bimolecular recombination in pristine CH3NH3PbBr3 to a dominant trap-assisted monomolecular recombination with Bi3+ doping. Electrically, it is found that the mobility in pristine perovskite crystals can be boosted with a low Bi3+ concentration, which may be related to a trap-filling mechanism. Aided by temperature (7)-dependent measurements, two temperature regimes are observed in association with different activation energies (E-a) for electrical conductivity. The reduction of E-a at lower T may be ascribed to suppression of ionic conduction induced by doping. The modified electrical properties and NIR emission with the control of Bi3+ concentration shed light on the opportunity to apply heterovalent doping of perovskite single crystals for NIR optoelectronic applications

Light-responsive prodrug-based supramolecular nanosystems for site-specific combination therapy of cancer

On-demand release of chemotherapeutic drugs from their prodrugs triggered by light irradiation has been attracting great attention for effective cancer treatment. Herein, we prepared prodrug based supramolecular nanoparticles (HA−aPS−aCPT) composed of (1) β-cyclodextrin conjugated hyaluronic acid polymer (HA−CD), (2) adamantane-modified camptothecin prodrug (aCPT) caged via reactive oxygen species (ROS) responsive thioketal linker, and (3) adamantane modified photosensitizer (aPS), for combination photodynamic therapy and light-controlled chemotherapy. aCPT could release free camptothecin by the cleavage of ROS-sensitive thioketal linker. aPS is employed to produce ROS under light irradiation. HA−aPS−aCPT nanoparticles are formed by supramolecular means with excellent colloidal stability and monodispersity in aqueous solution. Confocal imaging and flow cytometric analysis confirm the selective uptake of HA−aPS−aCPT nanoparticles via CD44 receptor-mediated endocytosis by MDA-MB-231 cells, on account of the targeting capability of hyaluronic acid. Cell viability assays show that HA−aPS−aCPT nanoparticles possess minimal cytotoxicity in the dark, while presenting high cellular toxicity under light irradiation. In vivo experiments exhibit selective accumulation of HA−aPS−aCPT nanoparticles in MDA-MB-231 tumor of nude mice. Significant tumor regression is observed when light irradiation is applied after intravenous injection of HA−aPS−aCPT nanoparticles. Thus, HA−aPS−aCPT nanoparticles demonstrate a great potential for on-demand combination photodynamic therapy and chemotherapy of tumor.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.National Research Foundation (NRF)Published versionThis work was financially supported by the Singapore National Research Foundation under its Investigatorship (NRF-NRFI2018-03, Y.Z.) and Competitive Research Program (NRF-CRP26-2021-0002, Y.Z.). This work was also supported by the Fundamental Research Funds for the Central Universities (YD9990002021, D.W.)

A hypoxia-responsive albumin-based nanosystem for deep tumor penetration and excellent therapeutic efficacy

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia-responsive human serum albumin (HSA)-based nanosystem (HCHOA) is reported, prepared by cross-linking the hypoxia-sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)-conjugated HSA (HC) and oxaliplatin prodrug-conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100–150 nm. When exposed to the hypoxic tumor microenvironment, the nanosystem can quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with a diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles can be recovered for bioimaging. At the same time, the production of singlet oxygen is increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, combined photodynamic therapy and chemotherapy is realized to display superior antitumor efficacy in vivo. Based on this simple strategy, it is possible to achieve the dissociation of hypoxic-responsive nanosystem to enhance the tumor penetration and therapeutic effect.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)Accepted versio

MetalOrganic Framework Derived Multicomponent Nanoagent as a Reactive Oxygen Species Amplifier for Enhanced Photodynamic Therapy

Intracellular antioxidants such as glutathione (GSH) play a critical role in protecting malignant tumor cells from apoptosis induced by reactive oxygen species (ROS) and in mechanisms of multidrug and radiation resistance. Herein, we rationally design two multicomponent self-assembled photodynamic therapy (PDT) nanoagents, that is, Glup-MFi-c and Glud-MFo-c, which consist of respective GSH-passivation and GSH-depletion linkers in metal−organic frameworks encapsulated with photosensitizers for a deeply comprehensive understanding of GSH-based tumor PDT. Multicomponent coordination, π−π stacking, and electrostatic interactions among metal ions, photosensitizers, and bridging linkers under the protection of a biocompatible polymer generate homogeneous nanoparticles with satisfied size, good colloid stability, and ultrahigh loading capacity. Compared to the GSH-passivated Glup-MFi-c, the GSH-depleted Glud-MFo-c shows pH-responsive release of photosensitizer and [FeIII(CN)6] linker in tumor cells to efficiently deplete intracellular GSH, thus amplifying the cell-killing efficiency of ROS and suppressing the tumor growth in vivo. This study demonstrates that Glud-MFo-c acts as a ROS amplifier, providing a useful strategy to deeply understand the role of GSH in combating cancer.Ministry of Education (MOE)National Research Foundation (NRF)Accepted versionThis research is supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03), the Singapore Academic Research Fund (RT12/19), the National Natural Science Foundation of China (31471268), and the National Key Research and Development Program of China (Stem Cell and Translational Research, 2016YFA0101202)

Smart Nanoreactors for pH-Responsive Tumor Homing, Mitochondria-Targeting, and Enhanced Photodynamic-Immunotherapy of Cancer

Photodynamic therapy (PDT) is an oxygen-dependent light-triggered noninvasive therapeutic method showing many promising aspects in cancer treatment. For effective PDT, nanoscale carriers are often needed to realize tumor-targeted delivery of photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to reactive oxygen species (ROS). Second, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in the majority of solid tumors is important for optimizing PDT efficacy. Furthermore, as PDT is a localized treatment method, achieving systemic antitumor therapeutic outcomes with PDT would have tremendous clinical values. Aiming at addressing the above challenges, we design a unique type of enzyme-encapsulated, photosensitizer-loaded hollow silica nanoparticles with rationally designed surface engineering as smart nanoreactors. Such nanoparticles with pH responsive surface coating show enhanced retention responding to the acidic tumor microenvironment and are able to further target mitochondria, the cellular organelle most sensitive to ROS. Meanwhile, decomposition of tumor endogenous H₂O₂ triggered by those nanoreactors would lead to greatly relieved tumor hypoxia, further favoring in vivo PDT. Moreover, by combining our nanoparticle-based PDT with check-point-blockade therapy, systemic antitumor immune responses could be achieved to kill nonirradiated tumors 1–2 cm away, promising for metastasis inhibition