In vitro/ in vivo evaluation of double crosslinked bone glue with different degrees.

Successful bone fragment fixation is a crucial factor in bone fracture healing, the fixation of crushed bone fragments could hinder bone fracture healing. Thus, ideal bone glues to effectively adhere and splice comminuted bone fragments are needed in clinical. Herein, an osteoinductive and biodegradable double cross-linked bone glue (GelMA-oDex-AMBGN) was constructed through Schiff's base reaction between commercial GelMA (with different substitution degrees of amino groups) and Odex mixed with amine-modified mesoporous bioactive glass nanoparticles (AMBGN), followed by crosslink with blue light irradiation. The GelMA-oDex-AMBGN bone glue successfully adhered and spliced the comminuted bone fragments of isolated rat skulls. GelMA-oDex-AMBGN promoted the proliferation of 3T3 cells and enhanced the expression of osteogenic proteins Runx2 and OCN in vitro. In rat cranial critical-sized defect models, GelMA-oDex-AMBGNs with different substitution degrees significantly increased the new bone contents at the fracture defect sites and promoted bone tissue regeneration in vivo. In conclusion, the double cross-linked bone glue (GelMA-oDex-AMBGN) was successfully constructed and can induce bone regeneration. Additionally, there was no significant difference in osteogenic activity among GelMA-oDex-AMBGNs with different substitution degrees and the equal content of AMBGN.

Long-term effects of PM2.5 components on hypertension: A national analysis in China.

BACKGROUND: Evidence is less about the associations between fine particulate matter (PM2.5) components and hypertension. We aimed to examine the long-term effects of PM2.5 components on prevalence of hypertension, diastolic blood pressure (DBP) and systolic blood pressure (SBP). METHODS: We included participants between March 1, and July 31, 2021, from 13 provinces in China. Geocoded residential address was used for exposure assignment. Mixed-effect regression was used to assess 3-year average concentrations of PM2.5 and its components (black carbon, organic matter, nitrate, ammonium, and sulfate) on prevalence of hypertension, DBP and SBP with covariate-adjusted. SHapley Additive exPlanation was used to compare the contribution of PM2.5 components to hypertension, DBP, and SBP. Sex and age subgroup were also analyzed. RESULTS: We enrolled a total of 113,159 participants aged ≥18 years. Long-term exposure to PM2.5 and its components (black carbon, organic matter, nitrate, ammonium, and sulfate) had associations with prevalence of hypertension, with the Odds Ratios and 95% confidence interval (CI) of 1.06 (95%CI: 1.03-1.09), 1.07 (95%CI: 1.04-1.09), 1.07 (95%CI: 1.04-1.10), 1.05 (95%CI: 1.01-1.08), 1.03 (95%CI: 1.00-1.06), and 1.03 (95%CI: 1.00-1.04), respectively. Effects of that except for black carbon on DBP with per interquartile upticks of concentration were 0.23 (95%CI: 0.11-0.35), 0.17 (95%CI: 0.04-0.29), 0.35 (95%CI: 0.21-0.48), 0.40 (95%CI: 0.28-0.52), and 0.25 (95%CI: 0.13-0.26), respectively. Ammonium was associated with SBP, corresponding to an increase of 0.18 (95%CI: 0.01-0.35). Males had higher risks of DBP (Z = 2.54-6.08, P < 0.001). Older people were substantially more affected by PM2.5 and its components. Nitrate showed the highest contribution to hypertension, DBP and SBP compared with other components. CONCLUSIONS: Long-term exposure to PM2.5 and its components had adverse consequences on prevalence of hypertension, DBP and SBP, especially for males and older people. Nitrate contributed the highest to hypertension, DBP and SBP. Findings may have implications for pollution and hypertension control.

Magnoflorine Alleviates "M1" Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome.

Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by "M1" polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce "M1" polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What's more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with "M1" polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates "M1" polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment.

Palladium-Catalyzed Allylic Substitution Reaction of Benzothiazolylacetamide with Allylic Alcohols in Water.

An efficient tetrakis(triphenylphosphine)palladium- and Brønsted acid catalyzed allylic substitution reaction of benzothiazolylacetamide with allylic alcohols in water has been developed, and the corresponding allylated products were afforded in good to excellent (up to 99%) yields with high regioselectivities. This straightforward protocol exhibits good functional group tolerance and scalability.

Chiral phosphoric acid catalyzed enantioselective N-alkylation of indoles with in situ generated cyclic N-acyl ketimines.

A chiral SPINOL derived phosphoric acid-catalyzed asymmetric N-alkylation reaction of indoles with cyclic α-diaryl-substituted N-acyl imines, which are generated in situ from 3-aryl 3-hydroxyisoindolinones, has been demonstrated. The transformation proceeds smoothly with a broad range of indoles and isoindolinone alcohols. A variety of indole derived N-alkylated tetrasubstituted chiral aminals were afforded in moderate to good yields (50-79%) with excellent enantioselectivities (up to 98% ee).