Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against non-alcoholic fatty liver disease.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on NAFLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on NAFLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of NAFLD. In addition, this study revealed that in addition to the canonical TGF-ß/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in NAFLD progression. Conclusions: Ursolic acid could improve immune inflammation in NAFLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Gentiopicroside improves non-alcoholic steatohepatitis by activating PPARα and suppressing HIF1.

Gentiopicroside (GPS) is a highly water-soluble small-molecule drug and the main bioactive secoiridoid glycoside of Gentiana scabra that has been shown to have hepatoprotective effects against non-alcoholic steatohepatitis (NASH), a form of non-alcoholic fatty liver disease (NAFLD) that can progress to cirrhosis and hepatocellular carcinoma. However, the effects of GPS on NASH and the underlying mechanisms remain obscure. Firstly, a high-fat, high-cholesterol (HFHC) diet and a high-sugar solution containing d-fructose and d-glucose were used to establish a non-alcoholic steatohepatitis (NASH) mice model. Secondly, we confirmed GPS supplementation improve metabolic abnormalities and reduce inflammation in NASH mice induced by HFHC and high-sugar solution. Then we used metabolomics to investigate the mechanisms of GPS in NASH mice. Metabolomics analysis showed GPS may work through the Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway and glycine, serine, and threonine metabolism. Functional metabolites restored by GPS included serine, glycine, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Western blot and qRT-PCR analysis confirmed GPS improve NASH by regulating PPARα and Hypoxia-Inducible Factor-1α (HIF-1α) signaling pathways. In vitro, studies further demonstrated EPA and DHA enhance fatty acid oxidation through the PPARα pathway, while serine and glycine inhibit oxidative stress through the HIF-1α pathway in palmitic acid-stimulated HepG2 cells. Our results suggest GPS's anti-inflammatory and anti-steatosis effects in NASH progression are related to the suppression of HIF-1α through the restoration of L-serine and glycine and the activation of PPARα through increased EPA and DHA.

Causal effects of gut microbiome on autoimmune liver disease: a two-sample Mendelian randomization study.

BACKGROUND: Epidemiological studies have indicated a potential link between the gut microbiome and autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The relationship between the gut microbiome and autoimmune liver disease is still uncertain due to confounding variables. In our study, we aim to shed light on this relationship by employing a two-sample Mendelian randomization approach. METHODS: We conducted a two-sample Mendelian randomization (MR) study using the R package "TwoSampleMR". The exposure data consisted of genetic variants associated with 194 bacterial traits obtained from the MiBioGen consortium. Summary statistics for AILD were obtained from the GWAS Catalog website. Furthermore, a series of sensitivity analyses were performed to validate the initial MR results. RESULTS: There were two, four and three bacteria traits associated with an increased risk of AIH. PBC, and PSC respectively. In contrast, there were five, two and five bacteria traits associated with a decreased risk for AIH, PBC and PSC. Notably, the genus_Clostridium_innocuum_group showed a negative association with AIH (OR = 0.67, 95% CI: 0.49-0.93), and the genus_Actinomyces was found to be genetically associated with a decreased risk of PSC (OR = 0.62, 95% CI: 0.42-0.90). CONCLUSIONS: Our study identified the causal impact of specific bacterial features on the risk of AILD subtypes. Particularly, the genus_Clostridium_innocuum_group and the genus_Actinomyces demonstrated significant protective effects against AIH and PSC respectively. These findings provide further support for the potential use of targeted probiotics in the management of AILD.

Test Pilot and Airline Pilot Differences in Facing Unexpected Events.

BACKGROUND: Unexpected events in flight might decrease the transparency of the flying process and weaken the pilot's perception of the current state, or even erode manipulating skills. However, during the flight test of a new or modified aircraft, to verify the boundaries of aircraft aerodynamic performance and handling stability, unexpected events may be encountered that need to be handled by the test pilot. Therefore, studying the differences between test pilots and airline pilots could help improve flight safety.METHODS: Two kinds of physiological parameters, eye blink rate and average fixation duration and task-related performance of test pilots and airline pilots, were analyzed in three abnormal scenarios. A total of 16 pilots participated. The study was carried out in an A320 flight simulator.RESULTS: The differences were significant for both test pilots and airline pilots in eye blink rate and average fixation duration. Furthermore, the reaction time of test pilots (Mean = 23.38 s) was significantly shorter than airline pilots (Mean = 42.63 s) in Unreliable Airspeed condition, and the pitch angle deviations between them were significant in both Wind Shear and Unreliable Airspeed condition.DISCUSSION: The uncertainty of environmental change could create more severe pressure and mental workload influence than actual system failure. For airline pilots, compared with test pilots, the importance of practicing manual flight should still be emphasized. Improving reactions to unexpected ambient conditions and unannounced fault status could also contribute to flight safety.Zheng Y, Lu Y, Jie Y, Zhao Z, Fu S. Test pilot and airline pilot differences in facing unexpected events. Aerosp Med Hum Perform. 2023; 94(1):18-24.

Regulation of decorin by ursolic acid protects against non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) has become a global health issue, which poses additional financial burden to public health care. However, no specific pharmacological therapy is recommended in current guidelines. Ursolic acid (UA) has been proven to perform multiple biological activities, thereby having a broad application prospect in healthcare field. Thus, this current research was conducted to investigate the protective mechanisms of UA on NASH. Integrative genomic analyses were performed to identify characteristic genes for NASH, and human proteomics chip was applied to seek out differentially binding proteins for UA. The combining bioinformatic analyses revealed 529 and 502 differentially expressed genes for NASH and UA, respectively. And further enrichment analyses indicated that IGF-IR signaling pathway was intimately involved in the therapeutic effects of UA on NASH. Experimental studies displayed that UA up-regulated the decorin expression to activate IGF-IR signaling as well as to inhibit HIF-1 signaling, resulting in alleviation on metabolic dysfunction, liver steatosis, inflammation and hypoxia in high-fat-fed mice. And additionally, these results were confirmed by lipotoxic and decorin-interference cell model. Taken together, we found that UA could regulate IGF-IR and HIF-1 signaling pathways via decorin to provide dual protective functions on metabolic dysfunction and liver hypoxia, and therefore turned to be an effective option for the treatment of NASH.

Gentiana scabra Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has become a progressive metabolic disease that is emerging as a global epidemic. Considering that the complex pathogenesis has not been fully elucidated, barely specific pharmacological therapy is recommended in current guidelines. Gentiana scabra (GS) is a commonly used herb in Tibetan medicine, which has received much attention in recent years due to its diverse pharmacological properties, including anti-inflammation, anti-oxidation, and anti-fibrosis. However, the therapeutic mechanisms are still unclear. Our investigation demonstrated a regulatory effect of GS on pro-inflammatory macrophages, which was extensively investigated in NAFLD that revealed intimate participation in the disease evolution, and the non-canonical IKK family member TANK-binding kinase 1 (TBK1) was involved in this process. Plasmid vectors for shTBK1 and amlexanox (AML), an inhibitor of TBK1, were used in this study to verify the mechanisms of TBK1 both in vitro and in vivo, while a co-culture system for hepatocytes and BMDMs was constructed to confirm the critical role of macrophages for inflammatory cascade. The results revealed that metabolic burden up-regulated the phosphorylation of TBK1, resulting in activation of NF-κB signaling pathway, and consequently caused an elevated expression of MCP1 to induce the macrophage recruitment and accelerate the inflammatory cascade. In contrast, GS could inhibit the TBK1 phosphorylation and the MCP1 expression to restrain the recruitment of pro-inflammatory macrophages, so as to provide curative effects on metabolic dysfunction and inflammation. Considering that GS is non-toxic and can be used as a kind of tea for long-term drinking, we propose it may be an effective option for the prevention and treatment of NAFLD, which deserves further exploration and application, and may provide new insights to improve the current standardized intervention strategy.

Regulation of MFN2 by berberine alleviates obesity exacerbated colitis.

Obesity has become a global health issue, which can cause metabolic abnormalities systemically leading to increased morbidity of series diseases. At present, researches have presented obesity is a high-risk factor for colitis, and berberine shows positive therapeutic effect on colitis. Thus, we explored the beneficial effects and potential mechanisms of berberine on obesity-exacerbated colitis in this article. High-fat diet (HFD) exacerbated dextran sulfate sodium (DSS) induced colitis mice model was applied, the results showed that HFD promoted DSS-induced weight loss and inflammatory manifestations in intestine. The results of cytokines in serum and mRNA expression of inflammatory indicators in colon showed that HFD increased all their levels evidently, and the outcomes of Western blot analyses presented that HFD downregulated the MFN2 expression, inhibited the phosphorylation of AMPK as well as upregulated the BIP/Grp78 expression, while berberine could significantly reverse all these situations. In vitro, we stimulated Caco-2 cells with palmitic acid (PA) to replicate the lipotoxicity damage in the intestine, and the results presented that intervention therapy of berberine effectively enhanced the MFN2 expression, inhibited the mRNA levels of inflammatory factors, and reversed the PA induced protein level changes of AMPK and BIP/Grp78. In general, we proposed that berberine could regulate MFN2 to alleviate obesity exacerbated colitis.

Pilots' Visual Scanning Behaviors During an Instrument Landing System Approach.

BACKGROUND: Since eye movement can provide a reliable index of the attention allocation, which can assist in understanding pilots' cognitive state, this study investigated the effect of pilots' experience and the autopilot mode on their attention allocation on the Primary Flight Display (PFD) and Multi-Function Display (MFD) during an approach task.METHODS: There were 16 pilots who were classified into two levels of aviation expertise depending on the flight hours, and required to fly an Instrument Landing System approach. Their visual scanning behaviors were recorded through an eye tracker and analyzed based on fixation number and dwell time.RESULTS: The results revealed that the pilot experience level, instrument panel and autopilot mode all had significant impact on the fixation time ratio and dwell time. The pilots fixated most often on the PFD and had shorter dwell time. Furthermore, they had a lower fixation number and shorter dwell time on the PFD and MFD when the autopilot was off that they should allocate visual resources to the others (e.g., out-of-the-window) and obtain more information to maintain overall situation awareness under higher time pressure. Compared to pilots with more expertise, pilots with less expertise had an increased fixation number and decreased dwell time on the airspeed after turning off the autopilot.DISCUSSION: The present study indicated that the pilots had different visual scanning modes according to the flight mode and their experience. We expect that pilots' visual scanning behaviors during tasks will help the training and the design of the human-machine interaction.Lu Y, Zheng Y, Wang Z, Fu S. Pilots' visual scanning behaviors during an instrument landing system approach. Aerosp Med Hum Perform. 2020; 91(6):511-517.

Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis.

BACKGROUND: Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM: To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS: We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS: Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION: JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.

Predicting Workload Experienced in a Flight Test by Measuring Workload in a Flight Simulator.

BACKGROUND: In order to determine the minimum flight crew number and show compliance with airworthiness regulations, the workload of flight crew should be measured in various flight scenarios both in a simulator and in flight tests demonstrating compliance. However, the complexity, environment, and safety considerations of flight tests require pilots to take more responsibility and be more careful with decisions and actions with higher stress, and it might be inappropriate to carry out flight tests in a high-risk abnormal situation. Therefore, it is necessary to assess workload measures in a simulator to predict workload experienced during a flight test.METHODS: Two subjective workload measurements and three psychophysiological measurements were compared both in a simulator and in a flight test among three flight scenarios. The scenarios were carried out in an ARJ21-700 full-flight simulator and a corresponding aircraft, and a total of 17 pilots participated.RESULTS: Both flight scenarios and flight environment had a significant influence on NASA-TLX, eye blink rate, and heart rate. Additionally, the NASA-TLX (R = 0.864) and heart rate differences (R = 0.840) presented strong correlations between the simulator and flight test.DISCUSSION: NASA-TLX and heart rate could be used in simulators and flight tests as consistent measures of workload. Furthermore, in order to reduce the quantity and risk of compliance during a flight test, the best strategy is to combine the results of the NASA-TLX scales and HR-D together in a flight simulator to predict workload experienced in a flight test.Zheng Y, Lu Y, Jie Y, Fu S. Predicting workload experienced in a flight test by measuring workload in a flight simulator. Aerosp Med Hum Perform. 2019; 90(7):618-623.

Systems pharmacology-based exploration reveals mechanisms of anti-steatotic effects of Jiang Zhi Granule on non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi Granule (JZG), a clinically used herbal formula, is developed in accordance with traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD. In previous studies, the anti-steatotic effects of JZG against NAFLD have been demonstrated, and in this study, a systems pharmacology approach was used to explore the pharmacological mechanisms of JZG by predicting the active compounds within the herbal formula and their corresponding therapeutic targets. Its therapeutic efficacy was confirmed in the beginning of this study, and JZG was shown to significantly improve hepatic dysfunction and lipid droplet accumulation in PA-treated hepatocytes. Systems pharmacology was then performed to identify the active compounds in as well as to predict the therapeutic targets of this Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of the anti-steatotic effects of JZG against NAFLD might be associated with lipid droplet degradation via autophagy, and a series of in vitro and in vivo validation experiments was subsequently performed to confirm that JZG could activate autophagy though the mTOR signalling to improve NAFLD.

Autophagy activation by Jiang Zhi Granule protects against metabolic stress-induced hepatocyte injury.

AIM: To elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury. METHODS: An in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 µg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62. Western blot analyses were performed to examine the expression of LC3-II/LC3-I, p62, mTOR and PI3K, while mitochondrial integrity and oxidative stress were observed by fluorescence staining of JC-1 and reactive oxygen species. C57BL/6 mice were divided into three groups: control group (n = 10), high fat (HF) group (n = 13) and JZG group (n = 13); and, histological staining was carried out to detect inflammation and lipid content in the liver. RESULTS: The cell trauma induced by PA was aggravated in a dose- and time-dependent manner, and hepatic function was improved by JZG. PA had dual effects on autophagy by activating autophagy induction and blocking autophagic flux. The PI3K-AKT-mTOR signaling pathway and the fusion of isolated hepatic autophagosomes and lysosomes were critically involved in this process. JZG activated autophagy progression by either induction of autophagosomes or co-localization of autophagosomes and lysosomes as well as degradation of autolysosomes to protect against PA-induced hepatocyte injury, and protected mitochondrial integrity against oxidative stress in PA-induced mitochondrial dysfunction. In addition, JZG ameliorated lipid droplets and inflammation induced by HF diet in vivo, leading to improved metabolic disorder and associated liver injury in a mouse model of non-alcoholic fatty liver disease (NAFLD). CONCLUSION: Metabolic stress-induced hepatocyte injury exhibited dual effects on autophagy and JZG activated the entire process, resulting in beneficial effects in NAFLD.

Flight Crew Workload Evaluation Based on the Workload Function Distribution Method.

BACKGROUND: The minimum flight crew on the flight deck should be established according to the workload for individual crewmembers. Typical workload measures consist of three types: subjective rating scale, task performance, and psychophysiological measures. However, all these measures have their own limitations. To reflect flight crew workload more specifically and comprehensively within the flight environment, and more directly comply with airworthiness regulations, the Workload Function Distribution Method, which combined the basic six workload functions, was proposed. METHODS: The analysis was based on the different conditions of workload function numbers. Each condition was analyzed from two aspects, which were overall proportion and effective proportion. Three types of approach tasks were used in this study and the NASA-TLX scale was implemented for comparison. RESULTS: Neither the one-function condition nor the two-function condition had the same results with NASA-TLX. However, both the three-function and the four- to six- function conditions were identical with NASA-TLX. Further, the significant differences were different on four to six conditions. The overall proportion was insignificant, while the effective proportions were significant. DISCUSSION: The results show that the conditions with one function and two functions seemed to have no influence on workload, while executing three functions and four to six functions had an impact on workload. Besides, effective proportions of workload functions were more precisely compared with the overall proportions to indicate workload, especially in the conditions with multiple functions.Zheng Y, Lu Y, Jie Y, Fu S. Flight crew workload evaluation based on the workload function distribution method. Aerosp Med Hum Perform. 2017; 88(5):481-486.

Acupuncture and Lifestyle Modification Treatment for Obesity: A Meta-Analysis.

Obesity is an epidemic health hazard associated with many medical conditions. Lifestyle interventions are foundational to the successful management of obesity. However, the body's adaptive biological responses counteract patients' desire to restrict food and energy intake, leading to weight regain. As a complementary and alternative medical approach, acupuncture therapy is widely used for weight control. The objective of this study was to assess the efficacy of acupuncture treatment alone and in combination with lifestyle modification. We searched the MEDLINE, EMBASE, CENTRAL and Chinese Biomedical Literature Databases for relevant publications available as of 24 October 2015 without language restriction. Eligible studies consisted of randomized controlled trials for acupuncture with comparative controls. A total of 23 studies were included with 1808 individuals. We performed meta-analyses of weighted mean differences based on a random effect model. Acupuncture exhibited a mean difference of body mass index reduction of 1.742[Formula: see text]kg/m2 (95% confidence interval [Formula: see text]) and 1.904[Formula: see text]kg/m2 (95% confidence interval [Formula: see text]) when compared with untreated or placebo control groups and when lifestyle interventions including basic therapy of both treatment and control groups. Adverse events reported were mild, and no patients withdrew because of adverse effects. Overall, our results indicate that acupuncture is an effective treatment for obesity both alone and together with lifestyle modification.

Developing a Measurement for Task Complexity in Flight.

INTRODUCTION: Task complexity is regarded as an essential metric that is related to a pilot's performance and workload. Normally, pilots follow Standard Operating Procedures (SOPs) during a flight. In this study, we developed a measurement named Task Complexity in Flight (TCIF) to represent the task complexity in the SOPs. METHODS: The TCIF measurement combined four complexity components into one index: actions logic complexity (ALC), actions size complexity (ASC), information control exchange complexity (ICEC), and control mode complexity (CMC).To verify the measurement, we calculated 11 tasks during the takeoff and landing phases from the SOPs, and invited 10 pilots to perform the same tasks in a flight simulator. After flight, the TCIF results were compared with two workload measurements: the Bedford scale and heart rate. RESULTS: The results of TCIF and the 4 components of the 11 tasks were calculated. Further, the TCIF results showed a significant correlation with the Bedford scores (R=0.851) and were also consistent with the difference in heart rate (R=0.816). Therefore, with the increased TCIF results, both the Bedford scale and the difference in heart rate increased. DISCUSSION: TCIF was proposed based on the flight operating conditions. Although additional studies of TCIF are necessary, the results of this study suggest this measurement could effectively indicate task complexity in flight, and could also be used to guide pilot training and task allocation on the flight deck.

Short-term effects of intragastric balloon in association with conservative therapy on weight loss: a meta-analysis.

Obesity is an epidemic chronic disease which is a risk factor for a number of serious medical conditions. Intragastric balloon, as an alternative, non-surgical treatment approach for the management of obesity, was rejected in previous evidence-based reviews. The object of this review is updating the data and confirming the safety and efficacy of the procedure. In this review, systematic literature retrieve of MEDLINE, EMBASE, CENTRAL and other information sources was performed from inception to December 2014. The quality of selected studies was assessed and meta-analyses of weighted mean differences were made using the inverse variance method. Meta-analyses presented significant effect sizes of -8.9 kg, -3.1 kg/m(2) and -21.0% for SMG as well as of -1.5 kg and -1.2 kg/m(2) for LSG, favoring the intervention group. Safety analysis showed that minor complications occurred at a high rate in intervention group, however, no serious or fatal complication was reported in these studies. In conclusion, the current review presents that short-term efficacy for 6 months treatment of intragastric balloon in association with conservative therapy is clinically significant.

Expertise and responsibility effects on pilots' reactions to flight deck alerts in a simulator.

INTRODUCTION: Flight deck alerts provide system malfunction information designed to lead corresponding pilot reactions aimed at guaranteeing flight safety. This study examined the roles of expertise and flight responsibility and their relationship to pilots' reactions to flight deck alerts. METHODS: There were 17 pilots composing 12 flight crews that were assigned into pairs according to flight hours and responsibilities. The experiment included 9 flight scenarios and was carried out in a CRJ-200 flight simulator. Pilot performance was recorded by a wide angle video camera, and four kinds of reactions to alerts were defined for analysis. RESULTS: Pilots tended to have immediate reactions to uninterrupted cautions, with a turning off rate as high as 75%. However, this rate decreased sharply when pilots encountered interrupted cautions and warnings; they also exhibited many wrong reactions to warnings. Pilots with more expertise had more reactions to uninterrupted cautions than those with less expertise, both as pilot flying and pilot monitoring. Meanwhile, the pilot monitoring, regardless of level of expertise, exhibited more reactions than the pilot flying. In addition, more experienced pilots were more likely to have wrong reactions to warnings while acting as the monitoring pilot. CONCLUSIONS: These results suggest that both expertise and flight responsibility influence pilots' reactions to alerts. Considering crew pairing strategy, when a pilot flying is a less experienced pilot, a more experience pilot is suggested to be the monitoring pilot. The results of this study have implications for understanding pilots' behaviors to flight deck alerts, calling for specialized training and design of approach alarms on the flight deck.