Muscle-specific overexpression of Atg2 gene and endurance exercise delay age-related deteriorations of skeletal muscle and heart function via activating the AMPK/Sirt1/PGC-1α pathway in male Drosophila.

Atg2 is a key gene in autophagy formation and plays an important role in regulating aging progress. Exercise is an important tool to resist oxidative stress in cells and delay muscle aging. However, the relationship between exercise and the muscle Atg2 gene in regulating skeletal muscle aging remains unclear. Here, overexpression or knockdown of muscle Atg2 gene was achieved by constructing the AtgUAS/MhcGal4 system in Drosophila, and these flies were also subjected to an exercise intervention for 2 weeks. The results showed that both overexpression of Atg2 and exercise significantly increased the climbing speed, climbing endurance, cardiac function, and lifespan of aging flies. They also significantly up-regulated the expression of muscle Atg2, AMPK, Sirt1, and PGC-1α genes, and they significantly reduced muscle malondialdehyde and triglyceride. These positive benefits were even more pronounced when the two were combined. However, the effects of Atg2 knockdown on skeletal muscle, heart, and lifespan were reversed compared to its overexpression. Importantly, exercise ameliorated age-related changes induced by Atg2 knockdown. Therefore, current results confirmed that both overexpression of muscle Atg2 and exercise delayed age-related deteriorations of skeletal muscle, the heart function, and lifespan, and exercise could also reverse age-related changes induced by Atg2 knockdown. The molecular mechanism is related to the overexpression of the Atg2 gene and exercise, which increase the activity of the AMPK/Sirt1/PGC-1α pathway, oxidation and antioxidant balance, and lipid metabolism in aging muscle.

The effect of continuous positive airway pressure on obstructive sleep apnea in children with syndromic craniosynostosis.

BACKGROUND: Obstructive sleep apnea (OSA) is common in children with syndromic craniosynostosis (SC). However, objective data on the treatment of OSA in children with SC remain inadequate. This study aimed to explore the efficacy of continuous positive airway pressure (CPAP) in the management of OSA in children with SC. METHODS: A retrospective study was performed in children with SC and OSA diagnosed by polysomnography (PSG), which was defined as an apnea hypopnea index (AHI) ≥ 1. Patients were included if they were treated with CPAP and had baseline PSG and follow-up sleep studies. Clinical and demographic data were collected from all enrolled subjects. RESULTS: A total of 45 children with SC and OSA were identified, with an average age of 6.8 ± 4.7 years. Among them, 36 cases had moderate to severe OSA (22 with severe OSA) and received CPAP therapy followed by post-treatment sleep studies. Notably, there was a significant reduction in the AHI observed after CPAP treatment (3.0 [IQR: 1.7, 4.6] versus 38.6 [IQR: 18.2, 53.3] events/h; P < 0.001). CONCLUSIONS: CPAP is effective and acceptable in treating severe OSA in children with SC.

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study.

PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.

Whole-genome metagenomic analysis of the oral microbiota in patients with obstructive sleep apnea.

PURPOSE: The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA). This study aimed to identify the variation of oral microbiota among patients with severe OSA, and the change of oral microbiota after treatment with continuous positive airway pressure (CPAP). METHODS: Participants were enrolled in the study from November 2020 to August 2021. Sleep parameters using full nocturnal polysomnography (PSG) were collected on healthy controls, patients with severe OSA, and patients with severe OSA after CPAP treatment for 3 months. Oral samples were also collected by rubbing disposable medical sterile swabs on the buccal mucosa. Routine blood tests and biochemical indicators were measured using the fully automated biochemical analyzer. Oral microbial composition of oral samples were determined using whole-genome metagenomic analysis in all participants. Correlations were analyzed between the oral microbiota and blood lipids. RESULTS: Study enrollment included 14 participants, 7 healthy controls and 7 patients with severe OSA. At the species level, the relative abundances of Prevotella, Alloprevotella, Bacteroides, Veillonella_tobetsuensis, Candidatus saccharimonas, and Leptotrichia in the groups with severe OSA were significantly lower than those in the healthy controls (P both < 0.05). The abundances of Capnocytophaga, Veillonella, Bacillus_anthracis, Eikenella, and Kingella were significantly higher whereas the abundances of Gordonia and Streptococcus were significantly lower in the group with severe OSA compared to the severe OSA-CPAP group (P < 0.05 for both). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), 4 pathways changed in the group with severe OSA compared with healthy controls (P both < 0.05). Pathways related to Novobiocin biosynthesis, 2-Oxocarboxylic acid metabolism, and Histidine metabolism were enriched in the patients with severe OSA. Nine pathways showed significant differences with regard to the relative abundances of phenylalanine metabolism; alanine, aspartate, and glutamate metabolism; one carbon pool by folate; monobactam biosynthesis; 2-oxocarboxylic acid metabolism; arginine biosynthesis and vitamin B6 metabolism; novobiocin biosynthesis; and arginine and proline metabolism, which were significantly higher in the group with severe OSA compared to the severe OSA-CPAP group (P both < 0.05). The Spearman correlation analysis between blood lipid parameters and oral microbiota components showed that negative correlations were observed between total cholesterol and Streptomyces (r = - 0.893, P = 0.007), and high-density lipoprotein cholesterol (HDL-C) and Gordonia (r = - 0.821, P = 0.023); positive correlations were observed between HDL-C and Candidatus saccharimonas (r = 0.929, P = 0.003), and low-density lipoprotein cholesterol (LDL-C) and Capnocytophaga (r = 0.893, P = 0.007). CONCLUSION: There was an apparent discrepancy of the oral microbiota and metabolic pathways between the group with severe OSA and controls, and CPAP significantly changed oral microbial abundance and metabolic pathways in patients with severe OSA. Correlation analysis showed that these oral bacteria were strongly correlated with the blood lipids level.

The Impact of Symptom Severity on Health-Related Quality of Life in People with Narcolepsy Type 1.

OBJECTIVE: To assess the impact of symptom severity on health-related quality of life (HRQoL) in people with narcolepsy type 1 (NT1). METHODS: A total of 174 people with NT1 were enrolled. They completed the Narcolepsy Severity Scale (NSS) and EQ-5D-3L consisting of five dimensions (EQ-5D utility values) and a visual analog scale (EQ-5D VAS). The relationship between severity of symptoms and HRQoL dimensions was evaluated by Pearson correlation analyses. Logistic regression was used to identify significant predictors of HRQoL. Nomogram was established based on results of independent predictors of factors on logistic regression analyses. RESULTS: The mean score for NSS, EQ-5D utility values, and EQ-5D VAS were 29.8 (10.08), 0.78 (0.09), and 64.30 (19.84) in people with NT1, respectively. NSS score showed a significant correlation with self-care (r = 0.157, p < .05), usual activities (r = 0.236, p < .01), pain/discomfort (r = 0.174, p < .05), anxiety/depression (r = 0.2, p < .01), and EQ-5D utility values (r = -.261, p < .01). EDS (excessive daytime sleep), cataplexy, hallucinations, paralysis, and disrupted nocturnal sleep (DNS) were significantly associated to EQ-5D VAS (r ranged from -0.154 to -0.354, p < .05). EDS (OR = -0.297) and DNS (OR = -0.16) were predictors of HRQoL. NSS score (OR = -0.360) and treatment (OR = 0.215) were predictors of the metrics of HRQoL. The C-indices of the nomogram were 0.726. CONCLUSION: The severity of symptoms could disrupt self-care and usual activities, and increase pain/discomfort and anxiety/depression. HRQoL might be improved by alleviating symptom severity.

Evolution and Analysis of Caffeic Acid Transferase (COMT) in Seed Plants.

Caffeic acid transferase (COMT) is a key enzyme in the lignin and melatonin synthesis pathways and plays an important role in plant growth and development. All seed plants have two characteristics: they have vascular tissues, phloem, and xylem, and they can produce and reproduce seeds. In order to understand the distribution and evolution of COMTs in seed plants, we performed physicochemical property analysis, subcellular localization, phylogenetic analysis, conserved motif analysis, and protein interaction network analysis of 44 COMT homologs from 26 seed plants through in silico. The results showed that in seed plants, the structure of COMT genes tends to be stable in different plant taxa, while the relationship between the chromosomal positions of different COMT genes in the same plant was more intricate. The conserved distribution of COMT in seed plants reflected its highly specialized function.

Prevalence and factors associated with atrial fibrillation in older patients with obstructive sleep apnea.

PURPOSE: This study sought to identify the prevalence and factors associated with atrial fibrillation (AF) in older patients with obstructive sleep apnea (OSA) in China.  METHODS: This was an explorative cross-sectional study. Between January 2015 and October 2017, we continuously recruited 1285 older patients with OSA who underwent overnight polysomnography from sleep centers of multiple hospitals. They were assessed using 12-lead ECG or 24-h dynamic ECG, and their baseline demographics, clinical characteristics, sleep parameters, and medical history were determined. Multivariate binary logistic regression analysis was used to investigate the factors related to AF in these older patients with OSA. RESULTS: The clinician classified 122 (9.5%) patients as having AF. The prevalence of AF significantly increased with age (P < 0.05) but did not significantly differ between the mild, moderate, and severe OSA groups. Additionally, the prevalence of paroxysmal AF was 7.2% among the overall study population, and it increased with OSA severity or advanced age (P < 0.05). Persistent AF was noted in 2.3% participants, and the prevalence also increased with age. The logistic regression analysis showed that age (OR = 1.054, 95%CI: 1.027-1.018, P < 0.001), history of drinking (OR = 1.752, 95%CI: 1.070-2.867, P < 0.05), chronic heart disease (OR = 1.778, 95%CI: 1.156-2.736, P < 0.01), diabetes mellitus (OR = 1.792, 95%CI: 1.183-2.713, P < 0.01), and reduced diastolic function (OR = 2.373, 95%CI = 1.298-4.337, P < 0.01) were relevant to AF among participants with OSA. CONCLUSION: The prevalence of AF is significantly common in older patients with OSA. Age, history of drinking, chronic heart disease, diabetes mellitus, and reduced diastolic function are independently related to AF in these patients.

Impact of obstructive sleep apnea complicated with type 2 diabetes on long-term cardiovascular risks and all-cause mortality in elderly patients.

BACKGROUND: The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes. METHODS: From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events. RESULTS: A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08-2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23-3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17-2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17-5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08-3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29-3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03-5.71, P = 0.044) were at a higher risk for MACE by diabetes. CONCLUSION: OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk.

Noninvasive Measurements Predict Liver Fibrosis Well in Hepatitis C Virus Patients After Direct-Acting Antiviral Therapy.

BACKGROUND: Short-time usage of direct-acting antiviral agents (DAA) limited knowledge regarding histological outcomes and predictive values of noninvasive measurements in patients with hepatitis C virus (HCV) after sustained virologic response (SVR) with DAA. AIMS: This study aimed to indicate histological changes and assess predictive value of noninvasive measurements for fibrosis in these patients. METHODS: HCV patients who achieved SVR by DAA were identified. Pre- and post-SVR clinical and histological data were collected. RESULTS: Of patients, 83% (33/40), 38% (15/40) and 83% (33/40) achieved inflammation improvement, fibrosis regression and histological improvement, respectively. Liver stiffness measurements (LSM), APRI, and FIB-4 could predict post-SVR fibrosis well without significant differences. Areas under receiver operating characteristic curves of LSM, APRI, and FIB-4 were 0.78, 0.81, and 0.87 for post-SVR advanced fibrosis (≥ F4) and 0.86, 0.86, and 0.85 for post-SVR cirrhosis (≥ F5), respectively. Pre-SVR LSM, APRI, and FIB-4 values were significantly lower in patients with fibrosis regression (P = 0.003-0.012), while FIB-4 was significantly lower in patients with histological improvement (P = 0.012-0.033). Patients with higher pre-SVR Ishak scores tended to have bigger decline in APRI (P = 0.025) and FIB-4 (P = 0.024) after SVR. CONCLUSIONS: DAA could improve liver inflammation and fibrosis of HCV patients in a short time after SVR. LSM, APRI, and FIB-4 predict fibrosis well even after SVR by DAA. Most of the cutoff values for advanced fibrosis (≥ F4) and cirrhosis (≥ F5) of these noninvasive measurements decreased significantly after SVR, maybe because of the inflammation improvement.

Risk factors for familial clustering of hepatitis C virus infection in a Chinese Han population: a cross-sectional study.

BACKGROUND: Hepatitis C is a curable disease, but reinfection from household contact may occur in patients who have achieved sustained viral response (SVR). METHODS: A total of 997 ethnic Han HCV treatment-naïve adult patients were enrolled in a cross-sectional study with stratified sampling based on the populations of five geographic regions across China to examine the genetic and physiological parameters associated with the phenomenon of HCV familial clustering. RESULTS: Of the total 997 patients, there were 59 patients who had at least one family member with HCV infection according to patient self-report. Comparison between patients with and without HCV familial clustering by univariate regression analysis showed that genotype 2, sexual transmission, long-term exposure to HCV patients, monthly family income per person less than 2000 yuan, farming occupation, and the southern and northern regions were associated with HCV familial clustering. Blood transfusion was negatively associated with HCV familial clustering. Multivariate logistic regression analysis suggested that long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was negatively associated, which meant that blood transfusion was not the main transmission route in HCV familial clustering. CONCLUSION: Long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was not the main transmission route in HCV familial clustering. To reduce reinfection from household contacts, education and awareness of HCV transmission routes and familial clustering should be strengthened, especially among HCV patients' family members, low-income families and non-blood transmission hepatitis C patients.

Relationship between the Level of Circulating Endothelial Micro-Particles in the Blood and Blood Lipid Content in Uyghur and Han Patients with Acute Coronary Syndrome.

BACKGROUND: The aim of this study was to analyze the relationships between the endothelial cell micro-particles (EMPs) blood level and the blood lipid in Uygur and Han patients with acute coronary syndrome (ACS) in order to provide a theoretical basis for the pathogenesis study of ACS. METHODS: 100 ACS patients (50 cases for each ethnic group) were selected as the patient group from January 2012 to August 2013 from the Cardiology Sector of the People's Hospital of the Xinjiang Uygur Autonomous Region, and 100 healthy subjects (50 cases for each ethnic group) were selected as the control group. Blood samples were collected. Flow cytometry was used to detect the EMP levels. An automatic biochemical analyzer was used to detect the levels of the blood lipids and the related indicators. RESULTS: The EMP levels in the patient group of both ethnicities were higher than those in the control group (p < 0.05), although no statistically significant differences were found in the EMP levels between Uygur and Han in the patient groups, nor in the control group (p > 0.05). Multiple linear regression analysis showed significant correlations between the EMP levels and the blood lipid related indexes (p < 0.05), with a degree of correlation of 86.70%. Path analysis indicated that the EMP level was mainly affected by high density lipoprotein cholesterol (HDL-C) (p < 0.05). CONCLUSIONS: The EMP level in the blood of ACS patients is significantly higher than in the control group, and the levels between HDL-C and EMPs are negatively correlated. The pathogenesis of ACS could be associated with the increase of the EMP level in the blood, and HDL-C might affect the level of circulating EMPs.

Evaluation of the safety of sclerotomy incision in patients with choroidal colobomas with/without associated microcornea.

PURPOSE: Whether the position of the ora serrata is normal in patients with choroidal colobomas remains unknown. The aim of this study was to measure the distance between the ora serrata and limbus in these patients and define safe sclerotomy sites for standard three-port pars plana vitrectomy. METHODS: Twelve patients with choroidal colobomas with normal corneas (Group 1) and 11 patients with choroidal colobomas with microcornea (Group 2) were included in the study. Twelve patients with simple retinal detachment served as control subjects. All participants underwent vitrectomy. The distance between the limbus and ora serrata, corneal diameter, and ocular axial length were measured. RESULTS: The average corneal diameter was 10.9 mm in Group 1, 7.9 mm in Group 2, and 11.4 mm in the control group. The average distance between the limbus and ora serrata was 6.3 mm in Group 1, 7.6 mm in Group 2, and 6.2 mm in the control group. There were significant differences in the distance between the limbus and ora serrata among the 3 groups (analysis of variance test, P < 0.05). CONCLUSION: Our study confirmed that it is safe to perform a sclerotic puncture 4 mm posterior to the limbus for vitrectomy in patients with choroidal colobomas with or without microcornea.

How Does Digital Leadership Foster Employee Innovative Behavior: A Cognitive-Affective Processing System Perspective.

Employee innovative behavior is crucial for organizations to engage in innovative activities and gain competitive advantages in the context of digital transformation. Despite many studies having focused on the relationship between leadership and employee innovative behavior, the role of digital leadership and the underlying mechanisms for employee innovative behavior remain unclear. Using the cognitive-affective processing system framework, the study investigated the dual mediating role of psychological empowerment and affective commitment between digital leadership and employee innovative behavior and the moderating role of a proactive personality in such relationships. Employing data from 359 employees, the study conducted structure equation modeling to examine the hypotheses. The results show that digital leadership influences employee innovative behavior through psychological empowerment but not affective commitment. Furthermore, a proactive personality does not moderate the direct effect of digital leadership on psychological empowerment and affective commitment or the indirect effect of digital leadership on employee innovative behavior. Theoretical and practical implications are discussed.

Short-Term Efficacy of Tenofovir Alafenamide in Acute-On-Chronic Liver Failure: A Single Center Experience.

Background: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). Methods: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. Results: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P < .001), higher HBV-DNA undetectability rates (P < .001), and lower HBV DNA levels (P < .001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P = .003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P = .023 and P < .0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P = .038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P > .05). Conclusions: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.

Muscle Psn gene combined with exercise contribute to healthy aging of skeletal muscle and lifespan by adaptively regulating Sirt1/PGC-1α and arm pathway.

The Presenilin (Psn) gene is closely related to aging, but it is still unclear the role of Psn genes in skeletal muscle. Here, the Psn-UAS/Mhc-GAL4 system in Drosophila was used to regulate muscle Psn overexpression(MPO) and muscle Psn knockdown(MPK). Drosophila were subjected to endurance exercise from 4 weeks to 5 weeks old. The results showed that MPO and exercise significantly increased climbing speed, climbing endurance, lifespan, muscle SOD activity, Psn expression, Sirt1 expression, PGC-1α expression, and armadillo (arm) expression in aged Drosophila, and they significantly decreased muscle malondialdehyde levels. Interestingly, when the Psn gene is knockdown by 0.78 times, the PGC-1α expression and arm expression were also down-regulated, but the exercise capacity and lifespan were increased. Furthermore, exercise combined with MPO further improved the exercise capacity and lifespan. MPK combined with exercise further improves the exercise capacity and lifespan. Thus, current results confirmed that the muscle Psn gene was a vital gene that contributed to the healthy aging of skeletal muscle since whether it was overexpressed or knocked down, the aging progress of skeletal muscle structure and function was slowed down by regulating the activity homeostasis of Sirt1/PGC-1α pathway and Psn/arm pathway. Exercise enhanced the function of the Psn gene to delay skeletal muscle aging by up regulating the activity of the Sirt1/PGC-1α pathway and Psn/arm pathway.

The effect of Le Fort III procedure in the treatment of obstructive sleep apnea in children with syndromic craniosynostosis.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with syndromic craniosynostosis (SC). The efficacy of the Le Fort III procedure in managing OSA in children with SC remains a subject of ongoing debate. This study aimed to explore the efficacy of Le Fort III procedure in the management of OSA in children with SC. METHODS: A retrospective study was performed in children with SC and OSA diagnosed by polysomnography, which was defined as an apnea-hypopnea index ≥ 1 event/h. Patients meeting the inclusion criteria were those who underwent Le Fort III surgery and had both baseline polysomnography and follow-up sleep studies. Relevant clinical and demographic data were collected from all individuals who participated in the study. RESULTS: Overall, 45 children with OSA and SC were identified, with a mean age of 6.8 ± 4.7 years. Twenty-five received the Le Fort III procedure and follow-up sleep studies. The Le Fort III procedure resulted in a significant reduction in apnea-hypopnea index (6.0 [2.6, 10.1] vs 37.6 [20.9, 48.0] events/h; P < .001). However, normalization of OSA was only achieved in 1 patient (4%). CONCLUSIONS: The Le Fort III procedure is efficacious in the treatment of OSA in children with SC. However, despite the observed improvement, residual OSA following treatment remains common. CITATION: Chang Y, Zhang W, Li M, et al. The effect of Le Fort III procedure in the treatment of obstructive sleep apnea in children with syndromic craniosynostosis. J Clin Sleep Med. 2024;20(8):1301-1311.

Activation of GPR3-ß-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.

Kupffer cells are liver resident macrophages and play critical role in fatty liver disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) in Kupffer cells stimulates glycolysis and protects mice from obesity and fatty liver disease. GPR3 activation induces a rapid increase in glycolysis via formation of complexes between ß-arrestin2 and key glycolytic enzymes as well as sustained increase in glycolysis through transcription of glycolytic genes. In mice, GPR3 activation in Kupffer cells results in enhanced glycolysis, reduced inflammation and inhibition of high-fat diet induced obesity and liver pathogenesis. In human fatty liver biopsies, GPR3 activation increases expression of glycolytic genes and reduces expression of inflammatory genes in a population of disease-associated macrophages. These findings identify GPR3 activation as a pivotal mechanism for metabolic reprogramming of Kupffer cells and as a potential approach for treating fatty liver disease.

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C-/- mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Targeting VPS18 hampers retromer trafficking of PD-L1 and augments immunotherapy.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive antitumor clinical outcomes. However, the limited response rates suggest the incomplete understanding of PD-L1 regulation. Here, we demonstrate that vacuole protein sorting 11 and 18 (VPS11/18), two key players in vesicular trafficking, positively regulate PD-L1 and confer resistance to immune checkpoint blockade therapy. VPS11/18 interact with PD-L1 in endosome recycling accompanied by promoting PD-L1 glycosylation and protein stability. VPS18 deficiency enhances antitumor immune response. Pharmacological inhibition by VPS18 inhibitor RDN impaired PD-L1 member trafficking and protein stability. Combination treatment of RDN and anti-cytotoxic T lymphocyte-associated antigen 4 synergistically enhances antitumor efficacy in aggressive and drug-resistant tumors. RDN exerted lung-preferred distribution and good bioavailability, suggesting a favorable drug efficacy. Together, our study links VPS18/11-mediated trans-Golgi network recycling of PD-L1 and points to a promising treatment strategy for the enhancement of antitumor immunity.

Clinical features, polysomnography, and genetics association study of restless legs syndrome in clinic based Chinese patients: A multicenter observational study.

STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.