Tensile Stress-Activated and Exosome-Transferred YAP/TAZ-Notch Circuit Specifies Type H Endothelial Cell for Segmental Bone Regeneration.

The Ilizarov technique has been continuously innovated to utilize tensile stress (TS) for inducing a bone development-like regenerative process, aiming to achieve skeletal elongation and reconstruction. However, it remains uncertain whether this distraction osteogenesis (DO) process induced by TS involves the pivotal coupling of angiogenesis and osteogenesis mediated by type H endothelial cells (THECs). In this study, it is demonstrated that the Ilizarov technique induces the formation of a metaphysis-like architecture composed of THECs, leading to segmental bone regeneration during the DO process. Mechanistically, cell-matrix interactions-mediated activation of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) transcriptionally upregulates the expression of Notch1 and Delta-like ligand 4, which act as direct positive regulators of THECs phenotype, in bone marrow endothelial cells (BMECs) upon TS stimulation. Simultaneously, the Notch intracellular domain enhances YAP/TAZ activity by transcriptionally upregulating YAP expression and stabilizing TAZ protein, thus establishing the YAP/TAZ-Notch circuit. Additionally, TS-stimulated BMECs secrete exosomes enriched with vital molecules in this positive feedback pathway, which can be utilized to promote segmental bone defect healing, mimicking the therapeutic effects of Ilizarov technique. The findings advance the understanding of TS-induced segmental bone regeneration and establish the foundation for innovative biological therapeutic strategies aimed at activating THECs.

Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment.

Osteoarthritis (OA) is the most common age-related degenerative joint disease mainly characterized by the destruction of articular cartilage. Owing to its native avascular property, intrinsic repair of articular cartilage is very limited. Thus, a chondrogenic microenvironment in the joint is essential to the preservation of healthy chondrocytes and OA treatment. Recently, cartilage progenitor cells (CPCs)-based therapy is emerging as a promising strategy to repair degenerated and damaged articular cartilage. In this study, injectable hypoxia-preconditioned three-dimensional (3D) cultured CPCs-laden gelatin methacryloyl (GelMA) microspheres (CGMs) were constructed and characterized. Compared to normoxia-pretreated 3D CPCs and two-dimensional (2D) cultured CPCs, hypoxia-preconditioned 3D cultured CPCs exhibited enhanced cartilage extracellular matrix (ECM) secretion and greater chondrogenic ability. In addition, hypoxia-preconditioned 3D cultured CPCs more effectively maintained cartilage matrix metabolism balance and attenuated articular cartilage degeneration in subacute and chronic rat OA models. Mechanistically, our results demonstrated hypoxia-preconditioned 3D cultured CPCs exerted chondro-protective effects by inhibiting inflammation and oxidative stress via NRF2/HO-1 pathway in vitro and in vivo. Together, through the 3D culture of CPCs using GelMA microspheres (GMs) under hypoxia environment, our results proposed an efficient articular cartilage regeneration strategy for OA treatment and could provide inspiration for other stem cells-based therapies.

Blood Concentrations of Volatile Organic Compounds Among US Workers From Various Trades.

OBJECTIVE: This study aimed to examine blood benzene, toluene, ethylbenzene, o-xylene, and m-/p-xylene (BTEX) concentrations and their trends contrasting construction workers with workers in other occupations from 1999 to 2014 in the United States. Methods: Using data from the National Health and Nutrition Examination Survey, quantile regressions were performed to investigate associations between occupation and blood BTEX concentrations. Results: We found that high-risk and construction occupations were associated with increased blood concentrations of toluene, o-xylene, and m-/p-xylene at the 50-90th percentiles (P 50-90 ), and ethylbenzene at P 70-90 . Moreover, although blood concentrations of ethylbenzene, o-xylene, and m-/p-xylene trended down among all US workers, no decreasing trend was observed for benzene and toluene among construction workers. Conclusions: Future studies are warranted to address questions about specific tasks to better assess VOC exposure from various trades.

Influence on emergency digit replantation and outcome assessment after COVID-19 virus nucleic acid testing normalization.

Objective: The study aims to compare the implementation and prognosis of emergency digit replantation surgery before and after normalized corona virus disease 2019 (COVID-19) nucleic acid testing for patients taking emergency operation and to explore the influence of normalized COVID-19 nucleic acid testing on replantation surgery. Method: Normalized COVID-19 nucleic acid testing for patients taking emergency operation has been carried out since 1 August 2021 at our hospital, which means each patient who needs emergency surgical treatment has to obtain either positive or negative results of COVID-19 nucleic acid before entering the operating room. This research reviewed and compared the prognosis of the injured extremity that had emergency severed digit replantation between June and September 2021, at the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and analyzed the impact of normalized COVID-19 nucleic acid testing on the outcome of the replanted fingers of different severity using disability of arm-shoulder-hand (DASH) and hand injury severity scoring (HISS) scoring systems. Results: A total of 54 cases with 74 severed replanted phalanges were included replanted by the research group between 1 August and 30 September 2021, without any COVID-19 suspected/confirmed case detected. Compared with previous period (1 June to 31 July, 2021), although the interval between emergency visits and emergency replantation did increase significantly after normalized COVID-19 nucleic acid testing [(3.83 ± 0.94) to (1.77 ± 0.67) h, P < 0.05], we observed no significant difference in the improvement rate of the DASH scoring of the disabled upper extremity 3-month postoperatively (P = 0.538) nor in the complication rate (P = 0.344). Moreover, there was no significant difference in the improvement rate of the DASH scoring of the disabled upper extremity 3-month postoperatively in patients with different traumatic severities before and after normalized COVID-19 nucleic acid testing (moderate P = 0.269, severe P = 0.055, major P = 0.149). Conclusion: Despite the preoperative delay, the policy of COVID-19 nucleic acid testing normalization does not have explicit influence on the short-term outcomes of emergency digit replantation surgery. With this evidence, microsurgeons could pay attention to the patients' anxiety and spend more effort in comforting them during the prolonged preoperative wait. These insights may have implications for other emergency department resource management whenever a social crisis occurs.