pH-Responsive NIR-II phototheranostic agents for in situ tumor vascular monitoring and combined anti-vascular/photothermal therapy.

Developing nanoplatforms integrating superior fluorescence imaging ability in second near-infrared (NIR-II) window and tumor microenvironment responsive multi-modal therapy holds great potential for real-time feedback of therapeutic efficacy and optimizing tumor inhibition. Herein, we developed a pH-sensitive pyrrolopyrrole aza-BODIPY-based amphiphilic molecule (PTG), which has a balanced NIR-II fluorescence brightness and photothermal effect. PTG is further co-assembled with a vascular disrupting agent (known as DMXAA) to prepare PTDG nanoparticles for combined anti-vascular/photothermal therapy and real-time monitoring of the tumor vascular disruption. Each PTG molecule has an active PT-3 core which is linked to two PEG chains via pH-sensitive ester bonds. The cleavage of ester bonds in the acidic tumor environment would tricker releases of DMXAA for anti-vascular therapy and further assemble PT-3 cores into micrometer particles for long term monitoring of the tumor progression. Furthermore, benefiting from the high brightness in the NIR-II region (119.61 M-1 cm-1) and long blood circulation time (t1/2 = 235.6 min) of PTDG nanoparticles, the tumor vascular disrupting process can be in situ visualized in real time during treatment. Overall, this study demonstrates a self-assembly strategy to build a pH-responsive NIR-II nanoplatform for real-time monitoring of tumor vascular disruption, long-term tracking tumor progression and combined anti-vascular/photothermal therapy.

Spatiotemporal variation analysis of global XCO2 concentration during 2010-2020 based on DINEOF-BME framework and wavelet function.

Combining with Carbon dioxide column concentration (XCO2) remote sensing data, it is of great scientific significance to obtain XCO2 long time series data with high precision and high spatio-temporal coverage. In this study, the combination framework of DINEOF and BME were employed to integrate the XCO2 data of GOSAT, OCO-2 and OCO-3 satellites for generating global XCO2 data from January 2010 to December 2020, with the average monthly space coverage rate of more than 96 %. Through cross-validation and comparison of The Total Carbon Column Observing Network (TCCON) XCO2 data and DINEOF-BME interpolation XCO2 products, it is verified that DINEOF-BME method has better interpolation accuracy, and the coefficient of determination of interpolated XCO2 products and TCCON data is 0.920. The long time series of global XCO2 products showed a wave rising trend, with a total increase of ~23 ppm; obviously seasonal characteristics were also detected with the highest XCO2 value in spring and the lowest in autumn. According to the zonal integration analysis, the values of XCO2 in the northern hemisphere is higher than the southern hemisphere during January-May and October-December, while the values of XCO2 in the southern hemisphere is higher than the northern hemisphere during June-September, which accords with the seasonal law. Through EOF mapping, the first mode accounted for 88.93 % of the total variability, and its variation trend is consistent with that of XCO2 concentration, which verifies the variation rule of XCO2 from the time and space pattern. Through wavelet analysis, the time scale corresponding to the first main cycle of XCO2 change is 59-month, which has obvious regularity on the time scale. DINEOF-BME technology framework has good generality, while XCO2 long time series data products and the spatio-temporal variation of XCO2 revealed by the research provide a solid theoretical basis and data support for related research.

Pyrrolopyrrole aza-BODIPY-based NIR-II fluorophores for in vivo dynamic vascular dysfunction visualization of vascular-targeted photodynamic therapy.

Real-time monitoring vascular responses is crucial for evaluating the therapeutic effects of vascular-targeted photodynamic therapy (V-PDT). Herein, we developed a highly-stable and bright aggregation induced emission (AIE) fluorophore (PTPE3 NP) for dynamic fluorescence (FL) imaging of vascular dysfunction beyond 1300 nm window during V-PDT. The superior brightness (ϵmaxΦf>1000 nm ≈ 180.05 M-1 cm-1) and high resolution of PTPE3 NP affords not only high-clarity images of whole-body and local vasculature (hindlimbs, mesentery, and tumor) but also high-speed video imaging for tracking blood circulation process. By virtue of the NPs' prolonged blood circulation time (t1/2 ≈ 86.5 min) and excellent photo/chemical (pH, RONS) stability, mesenteric and tumor vascular dysfunction (thrombosis formation, vessel occlusion, and hemorrhage) can be successfully visualized during V-PDT by FL imaging for the first time. Furthermore, the reduction of blood flow velocity (BFV) can be monitored in real time for precisely evaluating efficacy of V-PDT. These provide a powerful approach for assessing vascular responses during V-PDT and promote the development of advanced fluorophores for biological imaging.

Supramolecular photosensitizers using extended macrocyclic hosts for photodynamic therapy with distinct cellular delivery.

The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HB⊂AnBox4+ and HB⊂ExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HB⊂AnBox4+ and HB⊂ExAnBox4+ have different delivery effects at the cellular level.

An AHP-based regional COVID-19 vulnerability model and its application in China.

Since the COVID-19 outbreak, four cities-Wuhan, Beijing, Urumqi and Dalian-have experienced the process from outbreak to stabilization. According to the China Statistical Yearbook and China Center for Disease Control records, regional, pathological, medical and response attributes were selected as regional vulnerability factors of infectious diseases. Then the Analytic Hierarchy Process (AHP) method was used to build a regional vulnerability index model for the infectious disease. The influence of the COVID-19 outbreak at a certain place was assessed computationally in terms of the number of days of epidemic duration and cumulative number of infections, and then fitted to the city data. The resulting correlation coefficient was 0.999952. The range of the regional vulnerability index for COVID-19 virus was from 0.0513 to 0.9379. The vulnerability indexes of Wuhan, Urumqi, Beijing and Dalian were 0.8733, 0.1951, 0.1566 and 0.1119, respectively. The lack of understanding of the virus became the biggest breakthrough point for the rapid spread of the virus in Wuhan. Due to inadequate prevention and control measures, the city of Urumqi was unable to trace the source of infection and close contacts, resulting in a relatively large impact. Beijing has both high population density and migration rate, which imply that the disease outbreak in this city had a great impact. Dalian has perfect prevention and good regional attributes. In addition, the regional vulnerability index model was used to analyze other Chinese cities. Accordingly, the regional vulnerability index and the prevention and control suggestions for them were discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40808-021-01244-y.

CeO2 immobilized on magnetic core-shell microparticles for one-pot synthesis of imines from benzyl alcohols and anilines: Support effects for activity and stability.

Four types of core-shell materials with magnetic Fe3O4 microparticles as the core were prepared through different approaches using dopamine, glucose, tetrabutyl orthotitanate (TBOT), and tetraethyl orthosilicate (TEOS) as the shell precursor, respectively. CeO2 nanoparticles (NPs) was successfully immobilized onto these supports to fabricate efficient catalysts for the tandem catalytic synthesis of imines from benzyl alcohols and anilines at low temperature under air atmosphere. The as-prepared catalysts were detailedly characterized by TEM, EDX, XRD, FT-IR, XPS VSM, ICP, and CO2-TPD. Interestingly, these prepared catalysts showed higher catalytic activity than reported CeO2 catalysts. Most attractively, the catalyst with a shell ofnitrogen-doped-carbon derived from dopamine exhibited the best catalytic property, and outstanding stability and recyclability in the cycle experiment. According to the XPS and CO2-TPD characterization, the enhanced performance of Fe3O4@CN@CeO2 composites can be attributed to two reasons as follows: (1) the immobilization of CeO2 improved its alkalinity at low reaction temperature, and alkalinity is beneficial to promote the oxidation of alcohols to benzaldehyde, which is the rate-determining step for this tandem reaction; (2) the doped nitrogen generated Lewis basic site could satisfactorily stabilize Ce3+/Ce4+ pair of CeO2, which determined the catalytic activity and stability of CeO2 based catalysts for this tandem reaction. Moreover, the prepared catalysts could be facilely recovered from the reaction mixture with an external magnet. This work may provide a useful strategy for constructing CeO2 based catalysts for green and sustainable catalysis.