Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.
Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.
By using density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods, the sensing mechanism of a fluorescent probe 2-(2-hydroxyphenyl) benzothiazole (HBT) derivative HBTPP-S for hydrogen sulfide has been thoroughly studied. The thiolysis reaction has a moderate reaction barrier of 18.40 kcal mol, which indicates that the hydrogen sulfide sensing process has a favorable response speed. Because of the nonradiative donor-excited photoinduced electron transfer (d-PET, fluorophore as the electron donor) from the excited HBTPP group to the electron-withdrawing 2,4-dinitrophenyl group, as well as the inhibition of the proton transfer (PT) and the excited state intramolecular proton transfer (ESIPT) process by 2,4-dinitrophenyl group, the probe HBTPP-S is essentially nonfluorescent. On the other hand, the added hydrogen sulfide induces the thiolysis of the 2,4-dinitrophenyl ether bond, and then the thiolysis product HBTPP comes into existence. The theoretically simulated potential energy surface demonstrates that without the electron-withdrawing 2,4-dinitrophenyl group, the thiolysis product HBTPP undergoes the excited state intramolecular proton transfer (ESIPT) coupled twisted intramolecular charge transfer (TICT) processes in the first excited state. The absence of the d-PET and the process mentioned above may explain the significant fluorescent turn-on response and large Stokes shift of the thiolysis product HBTPP.
We report a new process to access highly enantioenriched sulfur-based heterocycles by an asymmetric catalytic thio-Diels-Alder reaction. Thiocarbonyls are challenging heterodienophiles in enantioselective Diels-Alder reactions, due to their inherent high reactivity and their poor ability to coordinate to chiral catalysts. We successfully circumvented these problems by employing a different strategy, which explores the use of in situ generated catalyst-bound dienes. Synthetically useful dihydrothiopyrans as well as other bi- and tricyclic sulfur-containing heterocycles are formed in high yields and high to excellent selectivities. DFT calculations were performed to examine the mechanism of the developed reaction. Furthermore, a series of synthetic transformations of the optically active sulfur-based heterocycles are presented.
Abstract. Black carbon (BC), water-insoluble organic carbon (OC), and mineral dust are important particles in snow and ice which significantly reduce albedo and accelerate melting. Surface snow and ice samples were collected from the Karakoram-Himalayan region of northern Pakistan during 2015 and 2016 in summer (six glaciers), autumn (two glaciers), and winter (six mountain valleys). The average BC concentration overall was 2130 ± 1560 ng g −1 in summer samples, 2883 ± 3439 ng g −1 in autumn samples, and 992 ± 883 ng g −1 in winter samples. The average waterinsoluble OC concentration overall was 1839 ± 1108 ng g −1 in summer samples, 1423 ± 208 ng g −1 in autumn samples, and 1342 ± 672 ng g −1 in winter samples. The overall concentration of BC, OC, and dust in aged snow samples collected during the summer campaign was higher than the concentration in ice samples. The values are relatively high compared to reports by others for the Himalayas and the Tibetan Plateau. This is probably the result of taking more representative samples at lower elevation where deposition is higher and the effects of ageing and enrichment are more marked. A reduction in snow albedo of 0.1-8.3 % for fresh snow and 0.9-32.5 % for aged snow was calculated for selected solar zenith angles during daytime using the Snow, Ice, and Aerosol Radiation (SNICAR) model. The daily mean albedo was reduced by 0.07-12.0 %. The calculated radiative forcing ranged from 0.16 to 43.45 W m −2 depending on snow type, solar zenith angle, and location. The potential source regions of the deposited pollutants were identified using spatial variance in wind vector maps, emission inventories coupled with backward air trajectories, and simple region-tagged chemical transport modeling. Central, south, and west Asia were the major sources of pollutants during the sampling months, with only a small contribution from east Asia. Analysis based on the Weather Research and Forecasting (WRF-STEM) chemical transport model identified a significant contribution (more than 70 %) from south Asia at selected sites. Research into the presence and effect of pollutants in the glaciated areas of Pakistan is economically significant because the surface water resources in the country mainly depend on the rivers (the Indus and its tributaries) that flow from this glaciated area.
Taiwan is widely considered to be a typical example of an arc‐continent collision surrounded by two opposite dipping subduction zones. The manner by which the interaction of the two neighboring slabs caused plate collision and mountain building is insufficiently understood. Various hypotheses have been proposed, but the geodynamic feasibility of those remains to be tested. Here we present 3‐D thermomechanical models to study the geodynamic evolution process of a Taiwan‐like setting after an initial transform fault was consumed. In our model setup, the boundary between the Eurasian plate and the South China Sea is northeast trending. The results show that all simulations result in toroidal mantle flow around the slab edges and that slab breakoff as well as a small‐scale mountain belt with high topography and crustal exhumation occurs in most cases. The Eurasian continental crust is exhumed in a dome‐like manner exposing higher‐grade metamorphic rocks, facilitated by high erosion rates and a weak continental lower crust rheology, but inhibited by the presence of a weak arc. A high topography within the orogen, as well as continental slab detachment, can develop for the convergence direction of N307° and large convergence rates. Our modeling results are thus generally consistent with the Eurasian slab‐tearing model proposed for Taiwan based on seismic tomographic studies, and we suggest that the main characteristic features in Taiwan can be explained by the combined effects of fast erosion, a weak lower crust, fast convergence, and a small convergence azimuth.
We report the preparation of biodegradable nanoscopic hydrogels and their application for targeted drug delivery. The nanogel is synthesized in a template-free method by photo-crosslinking salt-induced polymer assemblies. With convenient incorporation of targeted lactosyl moieties, the nanogels efficiently deliver doxorubicin to HepG2 cells through receptor-mediated internalization.
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