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nts that meet a given patient's clinical needs.Gemcitabine (GEM) is one of the first choice drugs for treating bladder cancer. In this study, we loaded M1 macrophage-derived exosomes (M1-Exo) with GEM by ultrasonication technique to derive an M1-Exo-GEM drug delivery system, and then explored its effects on bladder cancer. After inducing M1 polarization of macrophages in vitro, ultracentrifugation was performed to obtain M1-Exo, followed by construction of M1-Exo-GEM via ultrasonication technique. Mouse bladder cancer MB49 cells were chosen for study. CCK-8, PI staining and flow cytometry (FCM) assays were employed to assess the cell viability and apoptosis level. Inflammatory cytokines were detected by ELISA, while the protein expressions of Bcl-2, Bax and Caspase-3 were examined through Western-Blotting. After injecting M1-Exo-GEM into the tumor-bearing mouse model, the pathological changes were observed by H&E staining, the cancer cell damage was detected by TUNEL staining, and the apoptosis pathway activation was analyzed through immunohistochemical (IHC) staining and protein expression assays for Caspase-3 and Bax. Our results showed that M1-Exo and GEM had cytotoxic effects on MB49 cells, which increased the apoptosis level and the inflammatory cytokine expressions. Compared to M1-Exo and GEM, M1-Exo-GEM was significantly more cytotoxic to MB49 cells while markedly up-regulating the expressions of inflammatory cytokines. In the tumor-bearing mouse model, M1-Exo-GEM significantly inhibited tumor growth and damaged tumor cells, which outperformed GEM. Meanwhile, it also increased the tissue levels of inflammatory cytokines. This study finds that the drug delivery system composed of M1-Exo and GEM can act synergistically with GEM to exert cytotoxicity and induce inflammatory damage of bladder cancer cells.Structural isolation of two unprecedented AIEE/ACQ type fluorophores based on N-methyl N-confused tripyrromonomethene analogues exhibiting selective F- anion-coordination-induced-enhanced emission (ACIEE) with a detection limit of 10-7 M is reported. The intrinsic relation between molecular structures/molecular arrangements with (without) anion binding have been revealed at a deeper level via spectroscopic measurements and DFT level theoretical studies.Cell death is an essential process that plays a vital role in restoring and maintaining skin homeostasis. It supports recovery from acute injury and infection and regulates barrier function and immunity. Cell death can also provoke inflammatory responses. Loss of cell membrane integrity with lytic forms of cell death can incite inflammation due to the uncontrolled release of cell contents. Excessive or poorly regulated cell death is increasingly recognised as contributing to cutaneous inflammation. Therefore, drugs that inhibit cell death could be used therapeutically to treat certain inflammatory skin diseases. Programmes to develop such inhibitors are already underway. In this review, we outline the mechanisms of skin-associated cell death programmes; apoptosis, necroptosis, pyroptosis, NETosis, and the epidermal terminal differentiation programme, cornification. We discuss the evidence for their role in skin inflammation and disease and discuss therapeutic opportunities for targeting the cell death machinery.Dye-decolorizing peroxidase (DyP), which can degrade anthraquinone dyes using H2O2, is an attractive prospect for potential biotechnological applications for environmental purification. We previously designed an artificial DyP with an optimal pH for reactive blue 19 (RB19) degradation shifting from pH 4.5 to 6.5. We then attempted to degrade RB19 using Escherichia coli expressing this mutant, but RB19 was degraded equally compared with bacteria expressing wild-type (WT) DyP because most DyP was expressed in a heme-free form. In this study, we attempted to design an artificial peroxidase based on cytochrome c (cyt c), whose heme is covalently bound to the protein. We found that cyt c can degrade RB19, but its ability at pH 7.0 was ∼60% of that of DyP from Vibrio cholerae at pH 4.5. To enhance this activity we constructed several mutants using three approaches. Initially, to improve reactivity with H2O2, Met80 was replaced with a noncoordinating residue, Ala or Val, but catalytic efficiency (kcat/Km) was increased by only ∼1.5-fold. To enhance the substrate binding affinity we introduced an additional Trp by replacing Pro76 (P76W). click here The catalytic efficiency of this mutant was ∼3-fold greater than that of WT cyt c. Finally, to form a hydrogen bond to axial histidine Gly29 was replaced with Asp (G29D). This mutant exhibited an ∼80-fold greater dye-decolorizing activity. Escherichia coli expressing the G29D mutant was unable to degrade RB19 in solution due to degradation of heme itself, but this study provides new insights into the design of artificial DyPs.

Surface modification of flow diverters (FDs) has been explored as a solution for reducing thrombotic risk of these devices, without necessarily using dual antiplatelet therapy (DAPT). If effective, this could pose a promising alternative for treatment of ruptured aneurysms not amenable to other modalities.

We performed a comprehensive search of PubMed, MEDLINE, and Embase databases following Preferred Reporting Items for Systematic reviews and Meta-analyzes guidelines. We included articles reporting use of surface-modified FDs for treatment of ruptured aneurysms. Demographics, subarachnoid hemorrhage (SAH) severity, aneurysm characteristics, devices used, periprocedural complications, angiographic outcomes, and mortality were extracted for sample size-based weighted analysis.

Six studies comprising 59 patients with 64 aneurysms were included. Mean patient age was 56.6 ± 6.3 years and 60.6% (95% confidence interval [CI], 46.7-72.9%) were women. The anterior circulation was the location in 60.4% (95%CI, 4 hemorrhagic complications. A considerable proportion of aneurysms were nonsaccular. Rates of complete occlusion were high and retreatment were low. Importantly, no statistically significant difference was found between SAPT and DAPT with respect to complications and mortality.

Surface-modified FD treatment of ruptured aneurysms resulted in high rates of thromboembolic complications and acceptable rates of hemorrhagic complications. A considerable proportion of aneurysms were nonsaccular. Rates of complete occlusion were high and retreatment were low. Importantly, no statistically significant difference was found between SAPT and DAPT with respect to complications and mortality.Water-soluble polymers (WSPs) have unique properties that are valuable in diverse applications ranging from home and personal care products to agricultural formulations. For applications that result in the release of WSPs into natural environments or engineered systems, such as agricultural soils and wastewater streams, biodegradable as opposed to nonbiodegradable WSPs have the advantage of breaking down and, thereby, eliminating the risk of persistence and accumulation. In this Commentary, we emphasize central steps in WSP biodegradation, discuss how these steps depend on both WSP properties and characteristics of the receiving environment, and highlight critical requirements for testing WSP biodegradability.Chlorine dioxide (ClO2) is a very selective oxidant that reacts with electron-rich moieties such as activated amines and thus can degrade specific N-containing micropollutants. N-containing heterocycles (NCHs) are among the most frequent moieties of pharmaceuticals. In this study, the reactions of ClO2 with ritalinic acid and cetirizine, two abundant micropollutants, and model compounds representing their NCH moiety were investigated. The pH-dependent apparent reaction rates of all NCHs with ClO2 were measured and modeled. This model showed that neutral amines are the most important species having reaction rates between 800 and 3200 M-1 s-1, while cationic amines are not reactive. Ritalinic acid, cetirizine, and their representative model compounds showed a high stoichiometric ratio of ≈5 moles ClO2 consumption per degraded ritalinic acid and ≈4 moles ClO2 consumption per degraded cetirizine, respectively. Investigation of chlorine-containing byproducts of ClO2 showed that all investigated NCHs mostly react by electron transfer and form above 80% chlorite. The reactions of the model compounds were well comparable with cetirizine and ritalinic acid, indicating that the model compounds indeed represented the reaction centers of cetirizine and ritalinic acid. Using the calculated apparent reaction rate constants, micropollutant degradation during ClO2 treatment of surface water was predicted for ritalinic acid and cetirizine with -8 to -15% and 13 to -22% error, respectively. The results indicate that in ClO2-based treatment, piperidine-containing micropollutants such as ritalinic acid can be considered not degradable, while piperazine-containing compounds such as cetirizine can be moderately degraded. This shows that NCH model compounds could be used to predict micropollutant degradation.The efficient palladium-catalyzed synthesis of esters from readily available arenes has been developed. These C-H bond esterifications were achieved relying on the regioselective thianthrenation to generate the aryl-TT salts, which were treated as reactive electrophilic substrates to couple with phenol formate and N-hydroxysuccinimide (NHS) formate giving access to phenol esters and NHS esters, respectively, in the absence of carbon monoxide. A wide range of functional esters could be prepared with high efficiency under this redox-neutral palladium-catalytic condition. Late-stage functionalization and investigations of synthetic applications demonstrated the potential application of the established platform and these products.We investigate the flow evolution of a linear and a branched wormlike micellar solution with matched rheology in a Taylor-Couette (TC) cell using a combination of particle-tracking velocimetry, birefringence, and turbidity measurements. Both solutions exhibit a stress plateau within a range of shear rates. Under startup of a steady shear rate flow within the stress plateau, both linear and branched samples exhibit strong transient shear thinning flow profiles. However, while the flow of the linear solution evolves to a banded structure at longer times, the flow of the branched solution transitions to a curved velocity profile with no evidence of shear banding. Flow-induced birefringence measurements indicate transient birefringence banding with strong micellar alignment in the high shear band for the linear solution. The transient flow-induced birefringence is stronger for the branched system at an otherwise identical Wi. At longer times, the birefringence bands are replaced by a chaotic flow reminiscent of elastic instabilities. Visualization of the flow-induced turbidity in the velocity gradient-vorticity plane reveals quasi-steady banding with a turbidity contrast between high and low shear bands in the linear solution. However, the turbidity evolves uniformly within the gap of the TC cell for the branched solution, corroborating the non-banded quasi-steady velocimetry results. Finally, we show that while elastic instabilities in the linear solution emerge in the high shear band, the flow of branched solution at high Wi becomes unstable due to end effects, with growing end regions that ultimately span the entire axial length of the TC cell.