No abstract

The dramatically increasing demands in enzyme-like catalytic biosynthesis and biotherapeutics have promoted thrilling innovations to engineer artificial enzymes (AEs), [1][2][3][4][5][6][7][8] especially the haloperoxidase (HPO)-like AEs that can generate potent reactive oxygen species (ROS), [9][10][11][12] including • OH, • O 2 -, and HClO/HBrO, for antibacterial and antitumor applications. [13][14][15][16][17][18][19][20][21] Despite the fast flourishment of HPO-like AEs, further enhancing their biocatalytic performances is still a confusing black box since their electronic structures of metal centers and ROScatalytic mechanisms remain largely unclear. [22] The grand challenge is to develop new ideas and precise theoretical guidance for the de novo design of HPOlike AEs and clarify the corresponding electronic structures and catalytic behaviors of metal centers. [23,24] In particular, the vanadium oxide (V 2 O 5 ) is one of the most representative nanomaterials that displays HPO-like activities, which shows broad application potentials from killing pathogenic cells to preventing marine biofouling by catalyzing H 2 O 2 to potent ROS. Compared to natural HPO, the V 2 O 5 -based AEs provide a costeffective, stable, and broad reaction condition pathway. However, the currently reported strategies, [25,26] such as size tuning, modification of composition, and crystal facets engineering, present limited effects on further enhancing the biocatalytic performances of V 2 O 5 -based AEs. Pathways that can efficiently augment the intrinsic ROS-catalytic activities of metal centers in V 2 O 5 -based AEs are still missing.In V 2 O 5 -based AEs, the V centers possess depressed d electrons density due to its coordination with neighboring electronegative oxygen atoms, [27,28] which causes the V-d 2 z electrons (this d 2 z orbital is perpendicular to the basal plane) to become more accessible to form head-on-head sigma bonds with O-p z orbital. Therefore, the V centers in V 2 O 5 possess strong interaction with H 2 O 2 and suppressed dissociation of oxygenintermediates, [25] consequently resulting in reduced reaction dynamics. The de novo design of the d electrons of V centers to modulate the adsorption-energy between the H 2 O 2 and metal sites is essential for further enhancing their intrinsic ROS-catalytic activities. [29] One approach to weaken the accessibility of d 2 z electrons of metal centers is the filling of d yz orbitals near Nanomaterials-based artificial enzymes (AEs) have flourished for more than a decade. However, it is still challenging to further enhance their biocatalytic performances due to the limited strategies to tune the electronic structures of active centers. Here, a new path is reported for the de novo design of the d electrons of active centers by modulating the electron transfer in vanadium-based AEs (VO x -AE) via a unique Zn-O-V bridge for efficient reactive oxygen species (ROS)-catalysis. Benefiting from the electron transfer from Zn to V, the V site in VO x -AE exhibits a lower valence state tha...

ABSTRACT

The inflammatory response, manifested by serum levels of inflammatory factors and nuclear accumulation of activated NF-κB P65, was more serious in the IH group than in the SH and control group, and was dependent on hypoxia levels. This reaction increased initially and then decreased, which indicates the presence of compensatory mechanisms and an adaptive response to such stressors in the body. Notably, the correlation of NFκB activation to production of inflammatory factors under intermittent hypoxia implies an important role of this transcription factor in inflammation-induced cardiovascular damage occurring during obstructive sleep apnoea (OSA), which has a typical breathing pattern of intermittent hypoxia.

Background: This study aimed to assess the different types of port-wine stain (PWS) skin lesions quantitatively using high-frequency ultrasound (US) and shear wave elastography (SWE) before and after treatment, and investigate the feasibility and application value of high-frequency US and SWE in PWSs.Methods: A total of 195 PWS patients with 238 skin lesions before treatment and 72 follow-up PWS patients with 90 skin lesions were assessed using high-frequency US and SWE. The skin lesions were divided into four groups: pink-type, purple-type, thickened-type, and nodular-type PWSs. Gray-scale US was used to observe normal skin, observe the skin changes of lesions, and assess the skin thickness. The thickened skin was calculated. Power Doppler (PD) signal grades were used to assess the skin blood signals. SW velocity (in m/s) and Young's elastic modulus (in kPa) were used to assess the stiffness of normal skin and skin lesions.The heightened SWE was also calculated. Results:The dermis hypoechogenicity, thickness of thickened skin, and skin PD signal grades were significantly higher in all PWS-type groups compared with the normal-skin group (all P<0.05). The thickened skin and skin PD signal grades in the nodular-type and thickened-type group were significantly thicker and higher than those in the pink-type and purple-type group (all P<0.05). The PD signal grades in the purple-type was significantly higher than that in the pink-type group (P<0.05). All SWE values of PWS lesions were significantly higher in the transverse section than those in the longitudinal section (all P<0.05). The differences in heightened E mean , E min , C mean , and C min between each PWS group and the normal-skin group were not significant. The heightened E max and C max in the nodular-type PWS group was significantly higher than those in the normal-skin group and pinktype, and purple-type PWS groups (all P<0.05). The heightened E max and C max were significantly higher in the thickened-type PWS group than those in the normal-skin group (all P<0.05). In the evaluation of therapeutic effects, the ratio of dermis hypoechogenicity in pink-type lesions significantly decreased, and thickened skins in all groups were significantly thinned (all P<0.05). The differences of PD signal grades, heightened E max , and C max in all groups between pre-treatment and post-treatment showed no significance.Conclusions: High-frequency US and SWE show feasibility and application values assessing PWS skin lesions. Their features include dermis hypoechogenicity, thicker skin, higher PD signal grades, higher E max , and higher C max . Thicker skin is thus the best feature for assessing therapeutic effect.