Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage.

OBJECTIVE: To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage. METHODS: Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0.3 g Hb/kg/day or an equivalent volume of saline. The in vivo left ventricle function, cardiac enzyme release, histopathological changes, apoptosis and inflammation were also measured. RESULTS: High-altitude hypoxia induced significant cardiac damage, as demonstrated by impaired cardiac function and increased proapoptotic, proinflammatory and pro-oxidant markers. Pretreatment with CO-HBOC significantly improved cardiac performance, reduced cardiac enzyme release and limited myocardial apoptosis. The increased inflammatory response was also suppressed. In addition to the preserved mitochondrial structure, hypobaric hypoxia-induced mitochondrial oxidative damage was remarkably attenuated. Moreover, these antiapoptotic and antioxidative effects were accompanied by an upregulated phosphorylation of Akt, ERK and STAT3. CONCLUSION: This study demonstrated that CO-HBOC provides a promising protective effect on high-altitude hypoxia-induced myocardial injury, which is mediated by the inhibition of inflammation and mitochondrial oxidative damage.

[The Protective Effect of Tanshinone IIA on Oxygen-glucose Deprivation and Reperfusion Injury of MicrogliaThrough the NLRP3 Inflammatory Signaling Pathway].

OBJECTIVES: To investigate the protective effect of Tanshinone IIA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. METHODS: The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 ug/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA. In TSA 0 (also called OGD group), 0.5, 1.0, 2.0 ug/mL groups, expression levels of NLRP3 and caspase-1 were detected by Western blot, while IL-1ß and IL-18 in culture medium of those groups were detected by ELISA assay. RESULTS: The highest expression level of NLRP3 came to 12 h of reperfusion. The maximum effective concentration of TSA was 2.0 ug/mL. The expression levels of NLRP3, caspase-1, IL-1ß and IL-18 decreased with the increase of TSA concentration. CONCLUSIONS: TSA can inhibit the expression of protein and cytokines of NLRP3 inflammatory signaling pathway in OGD/R BV-2 cells, which may be one of the molecular mechanisms of the protective effect of TSA on OGD/R cells.

The effects of psychological safety and employee voice behavior on flight attendants' mindful safety practices adoption.

Introduction: Flight attendants, as the front-line staff in the cabin, play a crucial role in improving air travel safety. This research explores how psychological safety affects flight attendants' adoption of mindful safety practices through voice participation. This mechanism also identifies ethical leadership and traditionality as two moderators. Methods: A self-reported questionnaire was used to collect data from 621 flight attendants in Chinese private commercial airline companies. PLS-SEM (partial least square structured equation modeling) is used to examine the hypotheses proposed in the present study. Results: After data analysis, the results reveal that the underlying mechanism covering both mediating and moderating effects through which flight attendants' voluntary and extra-role safety behavior could be improved. Discussion: The findings extend the existing literature regarding the antecedents of flight attendants' mindful safety practices adoption and obstacles to employee voice participation. Managerial implications are also provided in the commercial aviation industry and discussed along with future research directions.

USP18 overexpression protects against spinal cord ischemia/reperfusion injury via regulating autophagy.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases. OBJECTIVE: The present study was designed to assess the effects and mechanisms of USP18 on SCII. METHODS: By inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy. RESULTS: USP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro. CONCLUSIONS: In summary, USP18 overexpression protects against SCII via regulating autophagy.

Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aß Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery.

Objective: Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. Methods: In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aß protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. Results: The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aß protein levels increased significantly at T1-T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aß protein levels at T1-T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1-T2. Conclusion: The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aß protein expression without causing hypoglycemia. Clinical Trial Registration: This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021).

Hypoxia Acclimation Protects against Heart Failure Postacute Myocardial Infarction via Fundc1-Mediated Mitophagy.

Mitochondrial dysfunction is the main cause of heart failure (HF) postacute myocardial infarction (AMI). Hypoxia acclimation (HA) reduces efficiently the area of AMI caused by ischemia and/or reperfusion and delays HF. Here, we examined whether HA improves mitochondrial structure and function through the hypoxic autophagy receptor FUNDC1 to prevent HF post-AMI. Male adult mice were acclimated in a low-pressure hypoxic animal chamber (11% oxygen (O2)) for 8 h/day for 28 days, and then, an induced HF post-AMI model via left anterior descending (LAD) artery ligation was structured to explore the efficacy and mechanism of HA. Our results showed that HA exposure can improve cardiac structure and function in mice with HF post-AMI and protected myocardial mitochondrial morphology and function. Further studies showed that HA increased the expression of Fundc1 protein and its associated mitophagy protein LC3 in myocardial tissue after infarction. We then established a cellular model of oxygen glucose deprivation (OGD) in vitro, and knockdown of FUNDC1 attenuated the protective effect of HA exposed on cardiomyocyte mitochondria and increased cardiomyocyte apoptosis. In conclusion, the protective effect of HA on HF post-AMI is achieved by regulating Fundc1-mediated mitophagy in myocardial tissue. FUNDC1-mediated mitophagy could be a promising strategy to treat cardiovascular diseases, including HF.

The Wnt pathway regulator expression levels and their relationship to bone metabolism in thoracolumbar osteoporotic vertebral compression fracture patients.

OBJECTIVE: To investigate of the Wnt pathway serum regulator expression levels and their relationship with bone metabolism (BM) in thoracolumbar osteoporotic vertebral compression fracture (OVCF) patients. METHODS: In this study, 40 healthy controls (group A), 33 osteoporotic patients (group B), and 47 thoracolumbar OVCF patients (group C) were recruited as the study cohort during the same period. The Wnt pathway serum regulator levels, bone density, BM-related inflammatory cytokines, bone formation markers, and bone resorption markers were compared among the three groups, and the correlation between the Wnt pathway serum regulators and BM was analyzed. RESULTS: The ß-catenin levels, the BALP, the densities at the femoral neck and lumbar spine, and the PINP, IL-10, OPG and BGP in groups B and C were lower than they were in group A, and the above indices in group C were lower than they were in group B (P < 0.05). Groups B and C showed higher CDKK-1, RANKL, TRACP-5b, ß-CTX, IL-2, IL-6, MMP-2, MMP-9, Leptin, and TNF-α levels than group A, and the above indicators in group C were higher than they were in group B (P < 0.05). A Pearson's correlation analysis showed that the MMP-2, MMP-9, RANKL, ß-CTX, and TRACP-5b levels were negatively correlated with ß-catenin (r < 0, P < 0.05) and were positively correlated with DKK-1 (r > 0, P < 0.05). The BGP, PINP, OPG, and BALP levels were positively correlated with ß-catenin (r > 0, P < 0.05) and were negatively correlated with DKK-1 (r < 0, P < 0.05). CONCLUSION: Patients with thoracolumbar OVCF have abnormal Wnt pathway serum regulator expression levels, low bone density, and abnormal BM, and the patients' Wnt/ß-catenin and DKK-1 levels are closely related to BM, so they may be potential targets for the prevention and treatment of metabolic bone diseases.

Spinal WNT pathway contributes to remifentanil induced hyperalgesia through regulating fractalkine and CX3CR1 in rats.

BACKGROUND: Tremendous experimental and clinical studies identify that remifentanil anesthesia might elicit postoperative opioid-induced hyperalgesia (OIH) and aggravate nociceptive hypersensitivity, whereas definite mechanisms remain equivocal. WNT signaling and fractalkine pathway have been manifested to participate in varieties of pain pathogenesis, respectively, but no report is on whether they could lead to OIH. This study intended to investigate the effect of WNT3a/ß-catenin on fractalkine and its receptor CX3CR1 in OIH in rats model of incision pain. METHODS: A WNT scavenger Fz-8/Fc and a neutralizing antibody against CX3CR1 (anti-CX3CR1) were injected intrathecally after remifentanil infusion. Exogenous WNT agonist delivery was utilized in naïve rats. PWT and PWL were documented for postsurgical 48h to assess mechanical and thermal hyperalgesia. Also, expressions of WNT3a, FZ1, FZ8, ß-catenin, fractalkine and CX3CR1 in spinal dorsal horn were measured by Western blot and RT-qPCR after nociceptive testing. RESULTS: We found that postsurgical mechanical and thermal hyperalgesia could be engendered after remifentanil exposure, which was accompanied by a dramatical rise of spinal WNT3a, FZ8, ß-catenin, fractalkine and CX3CR1 levels. Moreover, OIH was attenuated by intrathecal application of Fz-8/Fc and anti-CX3CR1. Up-regulation of spinal fractalkine and CX3CR1 expression after remifentanil anesthesia was reversed by Fz-8/Fc. Also, WNT agonist administration could directly generate hypernociception and elevate fractalkine/CX3CR1 level in naïve rats, which was prevented by anti-CX3CR1. CONCLUSION: These present findings demonstrated that the involvement of spinal WNT3a/FZ8/ß-catenin in OIH through modulating fractalkine/CX3CR1 in rats.

Land suitability assessment on a watershed of Loess Plateau using the analytic hierarchy process.

In order to reduce soil erosion and desertification, the Sloping Land Conversion Program has been conducted in China for more than 15 years, and large areas of farmland have been converted to forest and grassland. However, this large-scale vegetation-restoration project has faced some key problems (e.g. soil drying) that have limited the successful development of the current ecological-recovery policy. Therefore, it is necessary to know about the land use, vegetation, and soil, and their inter-relationships in order to identify the suitability of vegetation restoration. This study was conducted at the watershed level in the ecologically vulnerable region of the Loess Plateau, to evaluate the land suitability using the analytic hierarchy process (AHP). The results showed that (1) the area unsuitable for crops accounted for 73.3% of the watershed, and the main factors restricting cropland development were soil physical properties and soil nutrients; (2) the area suitable for grassland was about 86.7% of the watershed, with the remaining 13.3% being unsuitable; (3) an area of 3.95 km(2), accounting for 66.7% of the watershed, was unsuitable for forest. Overall, the grassland was found to be the most suitable land-use to support the aims of the Sloping Land Conversion Program in the Liudaogou watershed. Under the constraints of soil water shortage and nutrient deficits, crops and forests were considered to be inappropriate land uses in the study area, especially on sloping land. When selecting species for re-vegetation, non-native grass species with high water requirements should be avoided so as to guarantee the sustainable development of grassland and effective ecological functioning. Our study provides local land managers and farmers with valuable information about the inappropriateness of growing trees in the study area along with some information on species selection for planting in the semi-arid area of the Loess Plateau.