Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis.

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein-based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein-based material P1 is comprised of a ß-sheet-forming peptide KLVFF, pro-apoptotic protein BAK, and GFP along with targeting moieties. The self-assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria-dependent apoptosis through Bcl-2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1-expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide-based enzyme-catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.

Sensitive detection of single-nucleotide polymorphisms by conjugated polymers for personalized treatment of hypertension.

Genetic variants among individuals have been associated with ineffective control of hypertension. Previous work has shown that hypertension has a polygenic nature, and interactions between these loci have been associated with variations in drug response. Rapid detection of multiple genetic loci with high sensitivity and specificity is needed for the effective implementation of personalized medicine for the treatment of hypertension. Here, we used a cationic conjugated polymer (CCP)-based multistep fluorescence resonance energy transfer (MS-FRET) technique to qualitatively analyze DNA genotypes associated with hypertension in the Chinese population. Assessment of 10 genetic loci using this technique successfully identified known hypertensive risk alleles in a retrospective study of whole-blood samples from 150 patients hospitalized with hypertension. We then applied our detection method in a prospective clinical trial of 100 patients with essential hypertension and found that personalized treatment of patients with hypertension based on results from the MS-FRET technique could effectively improve blood pressure control rate (94.0% versus 54.0%) and shorten the time duration to controlling blood pressure (4.06 ± 2.10 versus 5.82 ± 1.84 days) as compared with conventional treatment. These results suggest that CCP-based MS-FRET genetic variant detection may assist clinicians in rapid and accurate classification of risk in patients with hypertension and improve treatment outcomes.

Dithiol-Activated Bioorthogonal Chemistry for Endoplasmic Reticulum-Targeted Synergistic Chemophototherapy.

The controlled intracellular release of nitrite is still an unmet challenge due to the lack of bio-friendly donors, and the antitumor effect of nitrite is limited by its physiologically inert activity. Herein, we designed benzothiadiazole-based organic nitrite donors that are stable against bio-relevant species but selectively respond to dithiol species through SN Ar/intramolecular cyclization tandem reactions in the aqueous media. The bioorthogonal system was established to target the endoplasmic reticulum (ER) of liver cancer HepG2 cells. The nitrite and nonivamide were coupled to induce elevation of intracellular levels of calcium ions as well as reactive oxygen/nitrogen species, which resulted in ER stress and mitochondrial dysfunction. We demonstrated that a combination of photoactivation and "click to release" strategy could enhance antitumor effect in cellular level and show good potential for cancer precision therapy.

Selective Fluorescence Imaging of Cancer Cells Based on ROS-Triggered Intracellular Cross-Linking of Artificial Enzyme.

Inside living cells, regulation of catalytic activity of artificial enzymes remains challenging due to issues such as biocompatibility, efficiency, and stability of the catalyst, by which the practical applications of artificial enzymes have been severely hindered. Here, an artificial enzyme, PTT-SGH, with responsiveness to reactive oxygen species (ROS), was obtained by introducing a catalytic histidine residue to pentaerythritol tetra(3-mercaptopropionate) (PTT). The artificial enzyme formed large aggregates in cells via the intracellular ROS-mediated oxidation of thiol groups. The process was significantly facilitated in tumor cells because of the higher ROS concentration in the tumor microenvironment. The catalytic activity of this artificial enzyme was intensively enhanced through deprotonation of cross-linked PTT-SGH, which showed typical esterase activities. Selective fluorescence imaging of tumor cells was achieved using the artificial enzyme to trigger the cleavage of the ester bond of the caged fluorophore inside living cells.

Appraising regional anthropogenic heat flux using high spatial resolution NTL and POI data: A case study in the Beijing-Tianjin-Hebei region, China.

Rapid urbanization and the aggregation of human activities in cities have resulted in large amounts of anthropogenic heat (AH) emission, which affects urban climate. Quantifying and assessing the AH emission values accurately and analyzing their spatial distribution characteristics is important to understand the energy exchange processes of urban areas. In this study, the high spatial resolution anthropogenic heat flux (AHF) quantification and spatial distribution analysis were conducted using multi-source data in the Beijing-Tianjin-Hebei region (BTH region) of China. First, the AH emission in district and city level were estimated using inventory method based on energy consumption and socio-economic statistical data; Then, AHF spatial quantification models were constructed based on high spatial resolution nighttime light (NTL) data and Point of interests (POI) data, and 130 m × 130 m gridded AHF quantification result in BTH region was realized; Finally, the potential numerical and spatial distribution patterns of AHF were analyzed using various indicators including contribution rate and aggregation index. The results show that: (1) The parameterized index constructed based on NTL and POI data shows a strong correlation with AHF, with R2 ranging from 0.79 to 0.94 and a mean absolute error (MAE) value of 0.72 w·m-2, which can be applied to the quantification of gridded AHF values with high resolution. The highest total AHF in the study area is 214 w·m-2, and the average value is 2.24 w·m-2. (2) Considering the sources of AHF, industrial emission sources in BTH region contribute the most to the total AHF, but commercial building emission sources in Beijing have a higher contribution, which can reach 33.8%. (3) Different types of AHF have different spatial aggregation levels. Commercial building emission and human metabolic emission have the highest aggregation level, and transportation emission has the lowest aggregation level.

Near-Infrared-Light Remote-Controlled Activation of Cancer Immunotherapy Using Photothermal Conjugated Polymer Nanoparticles.

Remote control of the therapeutic process is an ideal strategy for maximizing efficacy and avoiding side effects, especially for cancer immunotherapy. Herein, a conjugated polymer nanoparticles (CPNs)-mediated optogenetic system for in situ activation of immunotherapy under near-infrared laser irradiation is reported. This system is composed of photothermal CPNs and interferon-gamma (IFN-γ) plasmid driven by heat shock promoter HSP70. The photothermally responsive CPNs serve as a photo-heat nanotransducer to trigger the gene transcription of IFN-γ cytokine. The secreted IFN-γ from cancer cells can sufficiently elicit surrounding tumor-associated macrophages activation through IFN-γ-JAK-STAT1 transcription-factor signaling pathway and finally induce cancer cell killing by immunotherapy. Therefore, this synergetic optogenetic system provides a promising approach to remotely control the process of cancer immunotherapy.

Mapping China's time-series anthropogenic heat flux with inventory method and multi-source remotely sensed data.

Mapping time-series anthropogenic heat flux (AHF) is of great significance for understanding the process of urbanization and its impact on urban environment and climate. By collecting energy consumption data and socioeconomic statistics, combined with multi-source remotely sensed data, this study mapped the surface AHF in China with a high spatial resolution of 500 m × 500 m from 2000 to 2016 with 4 years of interval through constructing AHF estimation scheme. The main conclusions are: (1) There is a strong correlation between the vegetation adjusted nighttime light urban index (VANUI) and AHF. The highest coefficient of determination (R2) of VANUI and AHF is 0.97 in partition of northwest region (NWR). The average R2 value in partitions is 0.76, which shows that VANUI can well reflect the spatial differentiation characteristics of anthropogenic heat emissions. In addition, the fitting R2 value of the AHF estimation result and the AHF calculated by the inventory method is between 0.7 and 0.9, which indicates that the AHF estimation model constructed by VANUI can obtain reliable AHF estimation results. (2) In 2000-2016, the composition of AHF value changed a lot. The most obvious change is the AHF of 2-5 W·m-2, with a total increase of 21.53%. The area ratio of the low-value AHF of 0-2 W·m-2 showed a decreasing trend, from 91.93% in 2000 to 50.45% in 2016. Due to the increase of AHF, the reduced area has evolved to a high anthropogenic heat emission area. By constructing the AHF estimation model, this study acquired the time-series AHF with good accuracy and time-variation consistency in China from 2000 to 2016, which can effectively serve the research on urban environment and climate.