Association of the combination of obstructive sleep apnea risk and sleep duration with ideal cardiovascular health metrics in patients undergoing hemodialysis.

BACKGROUND: The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. METHODS: 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0-2,3-4, and 5-7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. RESULTS: After adjusting for covariates, short sleep duration (< 7 h) (OR = 0.53; 95% CI [ 0.30, 0.92]) and OSA risk (OR = 0.58; 95% CI [0.32, 0.83]) were negatively associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration and OSA risk, the odds of ideal CVH metrics were reduced by 72% (odds ratio 0.28 [95% CI 0.13, 0.60]). CONCLUSIONS: Short sleep duration and OSA risk are separately and jointly associated with poor CVH in hemodialysis patients. Suitable interventions for sleep may minimize the risk of developing cardiovascular disease.

Relationships between muscle strength, lung function, and cognitive function in Chinese middle-aged and older adults: A study based on the China health and retirement longitudinal study (CHARLS).

OBJECTIVE: As the population ages, concerns about cognitive decline have become increasingly relevant in medical consultations. This study aims to analyze the interaction between muscle strength, lung function, and cognitive function in Chinese middle-aged and older adults, providing a theoretical basis for better prevention of cognitive decline. METHODS: This study used data from the China Health and Retirement Longitudinal Study (CHARLS) wave 3, including 13 716 participants aged 45 years or older. Cognitive function was assessed through two dimensions, resulting in a total score ranging from 0 to 31 points, with higher scores indicating better cognitive function. Muscle strength was measured using normalized grip strength and chair-standing time, while lung function was evaluated using peak expiratory flow (PEF). RESULTS: Total cognitive function scores exhibited significant correlations with grip strength, chair-standing time, and PEF. Muscle strength and lung function demonstrated significant associations with cognitive function, with lung function emerging as a notable mediating factor. This relationship persisted even after adjusting for potential confounding variables. Specifically, PEF played a substantial mediating role in linking grip strength to cognitive function scores (estimated indirect effect = 0.0132, boot-strapped standard error = 0.0015, boot-strapped standard 95% confidence interval = 0.0104, 0.0162). Additionally, PEF served as a significant mediator in the association between chair-standing time and cognitive function scores (estimated indirect effect = -0.0204, boot-strapped standard error = 0.0023, boot-strapped standard 95% confidence interval = -0.0251, -0.0159). CONCLUSION: The study highlights the importance of addressing declines in muscle strength and lung function to identify risk factors associated with cognitive function. Understanding these relationships can provide insights into potential pathways linking these variables and may aid in better prevention of cognitive decline. Further long-term longitudinal cohort studies are needed to explore the causality between these factors.

Mediating effect of gait speed on the relationship between ankle-brachial index and mild cognitive impairment in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis are highly predisposed to arterial disease, poor physical performance, and cognitive impairment. However, the connection between them is not yet known. We aimed to investigate the mediating effect of physical performance on the relationship between arterial stiffness and mild cognitive impairment (MCI). METHODS: We conducted a multicenter cross-sectional study. The final analyzed hemodialysis patients comprised 616 subjects (men 391, women 225) from seven dialysis units in Shanghai, China. MCI was assessed by Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale. Arterial function was measured by ankle-brachial index (ABI) and branchial-ankle pulse-wave velocity (baPWV). Physical function was assessed by the Short Physical Performance Battery (SPPB). Logistic regression and mediation model were used to analysis. RESULTS: The mean age of the final analysis sample (n = 616) was 59.0 ± 12.0 years. Hemodialysis patients with MCI were more likely to have lower ABI (p < 0.001) and higher baPWV (p < 0.01). After adjusting for covariates, lower ABI (abnormal ≤0.9 and borderline 0.91-0.99) were positively associated with MCI (OR = 4.43, 95% CI = 1.89-10.39; OR = 4.83, 95% CI = 1.61-14.46). SPPB total score and its components standing balance, gait speed score were negatively associated with MCI. In the mediational model, gait speed played a mediating role (indirect effect ab = -0.21; 95% CI = -0.58 to -0.03) in the association of ABI (≤0.9) and MMSE, while standing balance and chair stands did not. CONCLUSIONS: Lower gait speed mediates a positive association between ABI and MCI in hemodialysis patients. Suitable interventions for physical performance, especially gait speed, may reduce the risk of MCI in hemodialysis patients.

Identification and expression analysis of Dazl homologue in Cynops cyanurus.

The Dazl (deleted in azoospermia-like) gene encodes an RNA-binding protein containing an RNA recognition motif (RRM) and a DAZ motif. Dazl is essential for gametogenesis in vertebrates. In this study, we report the cloning of Dazl cDNA from Cynops cyanurus. Ccdazl mRNA showed a germline-specific expression pattern as expected. Ccdazl expression gradually decreased during oogenesis, suggesting that it may be involved in oocyte development. Phylogenetic analysis revealed that the Ccdazl protein shares conserved motifs/domains with Dazl proteins from other species. Cloning of Ccdazl provides a new tool to carry out comparative studies of germ cell development in amphibians.

Muscle mass rather than muscle strength or physical performance is associated with metabolic syndrome in community-dwelling older Chinese adults.

OBJECTIVE: The purpose of this study was to examine whether muscle mass, muscle strength, and physical performance were associated with metabolic syndrome (MetS) in community-dwelling older Chinese adults. METHODS: The study comprised of 1413 community-dwelling Chinese participants (577 men; mean ± standard deviation age: 71.3 ± 5.9) recruited from Tianjin and Shanghai, China who were invited to participate in a comprehensive geriatric assessment. The International Diabetes Federation metabolic syndrome guidelines were used to define MetS, including high waist circumference, elevated blood pressure, elevated fasting blood glucose, elevated triglycerides, and reduced HDL cholesterol. Muscle mass was measured by appendicular skeletal muscle mass/weight (ASM/weight), and ASM was measured by BIA. Muscle strength was measured using grip strength. Physical performance was represented by walking speed and the time up and go test (TUGT). RESULTS: The overall prevalence of MetS was 46.8% (34.1% in males and 55.5% in females). In the final logistic regression model, there was a significant, graded inverse association between muscle mass and MetS (p for trend = 0.014). Muscle strength and physical performance, including walking speed and TUGT, were not associated with overall MetS. In the components of MetS, muscle mass and grip strength were significantly inversely associated with high waist circumference and elevated blood pressure (p < 0.05), while physical performance was not associated with components of MetS. CONCLUSIONS: Compared with muscle strength and muscle function, muscle mass was inversely associated with MetS in a community-dwelling elderly Chinese population. Among muscle mass、muscle strength and physical performance, muscle mass appears to have the strongest association with MetS in the elderly.

[Effect of shear stress on eicosanoid metabolism in endothelial cells by metabolomics approach].

The article aims to study the effect and mechanism of shear stress on eicosanoids produced by the metabolism of polyunsaturated fatty acids in endothelial cells. First, human umbilical vein endothelial cells were treated by control (Static), laminar shear stress (LSS) and oscillatory shear stress (OSS) for 6 h. Then the endothelial cells were incubated with fresh M199 medium for 3 h, and the cell culture medium was collected. Ultra-performance liquid chromatography-mass spectrometer was used to detect the level of eicosanoid metabolites secreted by endothelial cells. The results showed that under different shear stress, the level of eicosanoid metabolites were changed significantly. We found 10 metabolites were significantly up-regulated by OSS compared with those in LSS group, including PGD2, PGE2, PGF2α and PGJ2 produced by cyclooxygenase; 11-HETE, 15-HETE, 13-HDoHE produced by lipoxygenase or spontaneous oxidation; 12,13-EpOME, 9,10-EpOME, 9,10-DiHOME produced by cytochrome P450 oxidase and soluble epoxide hydrolase. The transcription levels of these up-regulated eicosanoids metabolic enzyme-related genes were also increased in vitro and in vivo. These results indicate that OSS may promote the increase of metabolites by up-regulating the transcription level of metabolic enzyme-related genes, which playing a key role in the development of atherosclerosis. This study reveals the effect of shear stress on eicosanoid metabolism in endothelial cells, which provides a novel supplement to the systems biology approach to study systemic hemodynamics.

Total Synthesis of Dactylicapnosines A and B.

Dactylicapnosines A and B, two natural products from Dactylicapnos scandens, exhibited potent anti-inflammatory and analgesic activities both in vitro and in vivo. In this paper, we report our second-generation synthesis of dactylicapnosine A and the first total synthesis of dactylicapnosine B. Our synthetic route features acid-induced isomerization of o-quinone (16), Co-mediated regioselective ring contraction of p-quinone (8b), and oxidative methoxylation of enone (18). This modified sequence provides dactylicapnosine A in 14 steps with an overall yield of 12% from a known compound (14a) and also offers opportunities to synthesize dactylicapnosine-like analogues for biological investigations.

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS-based untargeted metabonomics.

Background: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. Methods: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. Results: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". Conclusion: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

Association between changes in depressive symptoms and falls: The China health and retirement longitudinal study (CHARLS).

PURPOSE: This study aimed to investigate the impact of depressive symptoms and changes in depressive status on falls among middle-aged and older population in China. METHODS: We used two waves of interview data (time 1 [T1] and time 2 [T2], 2 years from T1) from a nationally representative sample of the China Health and Retirement Longitudinal Study (CHARLS), which included a total of 14,356 participants (male 6859; mean age: 59.5 ± 9.3 years). Depressive symptoms were assessed using the 10-item short form of the Center for Epidemiologic Studies Depression Scale (CES-D-10). Participants were categorized into four groups based on changes in their CES-D-10 scores over a 2-year follow-up period. Self-reported falls were evaluated, and logistic regression models and restricted cubic splines (RCS) were employed to examine the relationship between depressive symptoms and fallen. RESULTS: Participants who had experienced falls had higher CES-D-10 scores and were more likely to have depressive symptoms. Depressive symptoms at T1 were significantly associated with falls during the follow-up period. After adjusting for covariables, increasing CES-D-10 scores were associated with higher adjusted odds ratios (ORs) for falling prevalence: 1.230 (95 % CI, 1.041-1.453), 1.579 (95 % CI, 1.331-1.873), 1.745 (95 % CI, 1.472-2.070), and 2.366 (95 % CI, 1.972-2.838). Participants who experienced depressive symptoms at either T1 or T2, as well as those with persistent depressive symptoms from T1 to T2, were both at higher risk for future falls. The worsening of depressive symptoms significantly increased the likelihood of falls. CONCLUSION: This study revealed a significant association between depressive symptoms and changes in depressive status with subsequent falls in older adults. The heightened fall risk among individuals with depressive symptoms underscores the importance of addressing mental health as an integral part of comprehensive fall prevention strategies.

Comparison of Inflammatory Markers in the Diagnosis of Metabolic Syndrome in Hemodialysis Patients: A Multicenter Observational Study.

Objective: The purpose of this study is to observe the correlation between high sensitivity C-reactive protein (hs-CRP) and metabolic syndrome (MetS) in hemodialysis patients, determine its optimal cut-off point value, and compare the diagnostic ability of different inflammatory markers for MetS. Methods: This cross-sectional study finally included 860 long-term hemodialysis patients (male 524, average age 61.5 years) from seven dialysis centers in Shanghai, China. The International Diabetes Federation metabolic syndrome guidelines were used to define MetS, including high waist circumference, elevated blood pressure, elevated fasting blood glucose, elevated triglycerides, and reduced HDL cholesterol. Serum hs-CRP was determined by the immunonephelometric assay. The association with MetS was observed according to the quartile of inflammatory markers, and then the optimal cut-off point value of the hs-CRP was determined by ROC analysis. Results: The overall prevalence of MetS was 55.1% (46.6% in males and 68.5% in females). In the final logistic regression model, there was a significant, graded positive association between hs-CRP and MetS (p for trend = 0.010). The traditional inflammatory markers leukocytes, neutrophils, lymphocytes, monocytes and neutrophil-to-lymphocyte ratio (NLR) were not associated with MetS. The results of the ROC analysis showed that the optimal cut point value of hs-CRP for the diagnosis of MetS was 1.58 mg/L. In the components of MetS and hs-CRP was significantly positively associated with high waist circumference, elevated TG and low HDL (p < 0.05). Conclusion: The increase in hs-CRP concentration is significantly associated with the risk of MetS, and the diagnostic ability of hs-CRP for MetS is better than traditional inflammatory markers.

Alteration of plasma metabolic profile and physical performance combined with metabolites is more sensitive to early screening for mild cognitive impairment.

Objective: Unbiased metabolic profiling has been initiated to identify novel metabolites. However, it remains a challenge to define reliable biomarkers for rapid and accurate diagnosis of mild cognitive impairment (MCI). Our study aimed to evaluate the association of serum metabolites with MCI, attempting to find new biomarkers and combination models that are distinct for MCI. Methods: A total of 380 participants were recruited (mean age: 72.5 ± 5.19 years). We performed an untargeted metabolomics analysis on older adults who underwent the Mini-Mental State Examination (MMSE), the Instrumental Activities of Daily Living (IADL), and physical performance tests such as hand grip, Timed Up and Go Test (TUGT), and walking speed. Orthogonal partial least squares discriminant analysis (OPLS-DA) and heat map were utilized to distinguish the metabolites that differ between groups. Results: Among all the subjects, 47 subjects were diagnosed with MCI, and methods based on the propensity score are used to match the MCI group with the normal control (NC) group (n = 47). The final analytic sample comprised 94 participants (mean age: 75.2 years). The data process from the metabolic profiles identified 1,008 metabolites. A cluster and pathway enrichment analysis showed that sphingolipid metabolism is involved in the development of MCI. Combination of metabolite panel and physical performance were significantly increased discriminating abilities on MCI than a single physical performance test [model 1: the area under the curve (AUC) = 0.863; model 2: AUC = 0.886; and model 3: AUC = 0.870, P < 0.001]. Conclusion: In our study, untargeted metabolomics was used to detect the disturbance of metabolism that occurs in MCI. Physical performance tests combined with phosphatidylcholines (PCs) showed good utility in discriminating between NC and MCI, which is meaningful for the early diagnosis of MCI.

Single-cell transcriptomic analysis of honeybee brains identifies vitellogenin as caste differentiation-related factor.

The honeybee (Apis mellifera) is a well-known eusocial insect. In honeybee colonies, thousands of sterile workers, including nurse and forager bees, perform various tasks within or outside the hive, respectively. The queen is the only fertile female and is responsible for reproduction. The queen and workers share similar genomes but occupy different caste statuses. We established single-cell transcriptomic atlases of brains from queens and worker subcastes and identified five major cell groups: Kenyon, optic lobe, olfactory projection, glial, and hemocyte cells. By dividing Kenyon and glial cells into multiple subtypes based on credible markers, we observed that vitellogenin (vg) was highly expressed in specific glial-cell subtypes in brains of queens. Knockdown of vg at the early larval stage significantly suppressed the development into adult queens. We demonstrate vg expression as a "molecular signature" for the queen caste and suggest involvement of vg in regulating caste differentiation.

Comparison of three nutritional screening tools for detecting sarcopenia in patients with maintenance hemodialysis.

Background: Malnutrition, dynapenia, and sarcopenia are prevalent conditions among patients with maintenance hemodialysis (MHD). They are related to numerous adverse health outcomes. The aim of this study was to compare the effect of three nutritional screening tools on predicting the risk of dynapenia and sarcopenia in patients with MHD. Methods: From July 2020 to April 2021, a total of 849 patients with MHD were enrolled at seven different healthcare facilities in Shanghai, China in this multi-center cross-sectional study. Geriatric nutritional risk index (GNRI), malnutrition inflammation score (MIS), and creatinine (Cr) index were used for nutritional assessment. The cutoff values of muscle mass and strength to define dynapenia, pre-sarcopenia, and sarcopenia were based on the consensus by the Asia Working Group of Sarcopenia in 2019. Results: Among 849, almost 60% were malnourished with the majority suffering from dynapenia (27.7%), followed by sarcopenia (22.7%), and pre-sarcopenia (6.2%).The area under the receiver-operating characteristic curve for GNRI was 0.722 [95% confidence interval (CI) = 0.684-0.760] and 0.723 (95% CI = 0.663-0.783) in predicting sarcopenia and pre-sarcopenia. The GNRI [odds ratio (OR) =6.28, 95% CI: 4.05-9.73], MIS (OR =1.91, 95% CI: 1.31-2.78), and the Cr index (OR =2.73, 95% CI: 1.71-4.34) were all significantly associated with the risk of sarcopenia. More importantly, the sarcopenia predictability of the GNRI appears greater than the MIS and Cr index, while MIS was similar to the Cr index. Similarly, the superiority of GNRI prediction was also found in pre-sarcopenia, but not in dynapenia. Conclusion: All the three nutritional screening tools were significantly associated with an increased risk of sarcopenia. The sarcopenia predictability of the GNRI was greater than the MIS and Cr index.

First report of haemosporidia and associated risk factors in red junglefowl (Gallus gallus) in China.

BACKGROUND: Avian haemosporidia infect both domestic and wild birds, causing anemia, acute tissue degeneration, and depopulation in wild birds. Poultry and wild birds have been reported as common reservoirs of haemosporidia, but limited information is available for red junglefowl (Gallus gallus) in China. The present study investigated the prevalence and molecular characterization of haemosporidia in red junglefowl. METHODS: Blood samples were collected from 234 red junglefowl from Jinghong City of Yunnan Province, and genomic DNA was extracted from these samples. The prevalence of haemosporidia was determined by nested PCR targeting the mitochondrial cytochrome b (cytb) gene. Molecular characterization was investigated based on phylogenetic analysis of cytb sequences, and associated risk factors were analyzed using the Chi-square (χ2) test. RESULTS: The overall prevalence of haemosporidia was 74.8% (175/234), and three species were identified, namely Haemoproteus enucleator, Leucocytozoon californicus, and Plasmodium juxtanucleare. The prevalence of haemosporidia in adult fowl (81.1%, 107/132) was significantly higher (χ2 = 6.32, df = 1, P = 0.012) than that in juveniles (66.7%, 68/102). Three novel haemosporidian lineages were revealed. CONCLUSIONS: This study examined the prevalence and identified species of avian haemosporidians in red junglefowl, providing new information on the molecular epidemiology and geographical distribution of haemosporidian parasites. Our results indicated high prevalence and diverse species distribution of these haemosporidians in red junglefowl. To the best of our knowledge, this is the first record of haemosporidian infection in red junglefowl in China.

Relationship between physical performance and mild cognitive impairment in elderly hemodialysis patients is modified by the presence of diabetes: A multicenter cross-sectional study.

Objective: The purpose of this study was to observe the relationship between physical performance and mild cognitive impairment (MCI) in the presence or absence of type 2 diabetes in elderly hemodialysis patients. Methods: In this multicenter cross-sectional study, 396 clinically stable and aged ≥60 years hemodialysis patients (255 men; mean age: 68.3 ± 5.9 years) were included from seven dialysis units in Shanghai, China. The Chinese version of the Modified Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale were utilized to assess MCI. The performance-based assessments consisted of three physical tests, grip strength (GS), Timed Up and Go Test (TUGT), and 4-m walking test, which respectively represent muscle strength, mobility, and walking speed (WS). Logistic regression and multivariate linear regression were used for analysis. Results: Hemodialysis patients with diabetes had a high prevalence of MCI (20.6%). The odds ratio (OR) of MCI for the interacted items [(TUGT) * (diabetes) and (WS) * (diabetes)] was significant (p < 0.05). In diabetes patients, TUGT was positively associated with MCI, and WS was negatively associated with MCI after adjusting covariates [OR = 0.129; 95% confidence interval (CI) = 0.028-0.704, p = 0.021]. However, no significant association was found between physical performance and MCI in the non-diabetes hemodialysis patients (p > 0.05). Further analysis showed that TUGT was negatively associated with attention and calculation and language. WS was positively associated with recall and language in diabetic hemodialysis patients. Conclusions: Physical performance was associated with MCI in diabetic hemodialysis patients rather than the non-diabetes group. Whether increasing mobility or WS can positively influence MCI in individuals with type 2 diabetes requires further study.

Different stages of chronic kidney disease are associated with physical performance in adults over 60 years.

Objective: The purpose of this study was to determine the association between different stages of chronic kidney disease (CKD) and sarcopenia and its components in the Chinese older population. Methods: The study comprised of 2,213 participants aged ≥ 60 years (1,025 men; mean age: 70.7 years) recruited from Shanghai who were invited to participate in a comprehensive geriatric assessment. Sarcopenia was defined according to the AWGS 2019 consensus update on sarcopenia diagnosis criteria. The glomerular filtration rate (GFR) was estimated using the equation that originated from the CKD-EPI equation, the stages of CKD are classified according to the Kidney Disease-Improving Global Outcomes (KDIGO). Results: The overall prevalence of sarcopenia was 19.0%, which increased with the severity of CKD. The prevalence of sarcopenia in patients with CKD 3-4 and kidney failure was significantly higher than that in normal and CKD 1-2 (p < 0.05). In logistic regression analysis model, compared with normal and CKD 1 patients, kidney failure was significantly associated with the increased risk of sarcopenia and low grip strength (p < 0.05); CKD 2, CKD 3-4 and kidney failure groups were significantly associated with an increased risk of low walking speed (p < 0.05), respectively; while the association between CKD and muscle mass was not shown. Conclusions: In our study, only decreased physical performance, as represented by walking speed, was significantly associated with increased CKD severity. This may improve the evidence for the prevention and intervention of sarcopenia in patients with CKD.

Isolation and initial characterization of a vasa homolog in Cynops cyanurus.

The vasa mRNA encodes a putative RNA helicase that belongs to the DEAD-box protein family. Vasa protein is a conserved germ cell marker ranging from fruit fly to human. In this study, we cloned the full-length vasa cDNA from the ovary of newt Cynops cyanurus and examined its expression in embryos and adult tissues. The predictive C. cyanurus Vasa protein sequence shares eight conserved regions with Vasa proteins from other vertebrates. The C. cyanurus vasa mRNA expression is restricted to testis and ovary. During oogenesis, vasa mRNA shows highest expression in the early stages of oocytes. However, it rapidly down-regulates during embryogenesis. These findings suggest that Vasa may be involved in early germ cell specification/initiation in C. cyanurus.

Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation.

[Figure: see text].

Redox environment metabolomic evaluation (REME) of the heart after myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is closely related to oxidative stress. However, the redox environment of the heart has not been evaluated thoroughly after MIRI, which limits precise redox intervention. In this study, we developed the redox environment metabolomic evaluation (REME) method to analyze the redox metabolites of the heart after MIRI. Based on the targeted metabolomics strategy, we established a detection panel for 22 redox-related molecules, including the major redox couples nicotinamide adenine dinucleotide (NADH/NAD+), nicotinamide adenine dinucleotide phosphate (NADPH/NADP+), and glutathione/glutathione disulfide (GSH/GSSG), reactive oxygen and nitrogen species-related molecules, and some lipid peroxidation products. The high sensitivity and specificity of the method make it suitable for evaluating the endogenous redox environment. The REME method showed that the heart tissue in a MIRI mouse model had a different redox profile from that in the control group. Different redox species changed in different ways. The ratios of GSSG/GSH and NADP+/NADPH increased, but the levels of both NAD+ and NADH decreased in the risk area of the infarcted heart after reperfusion. In addition, some reactive nitrogen species-related metabolites (tetrahydrobiopterin, arginine, and S-nitrosoglutathione) decreased and some lipid peroxides (4-hydroxy-2-nonenal, 4-hydroxy-2-hexenal, and benzaldehyde) increased. The redox metabolites GSH, GSSG, NADPH, NAD+, S-nitrosoglutathione, arginine, and tetrahydrobiopterin had a positive correlation with the ejection fraction and a negative correlation with the level of lactate dehydrogenase in plasma. In summary, we achieved a comprehensive, systemic understanding of the changes in the redox environment after MIRI. Our REME method could be used to evaluate the redox environment in other processes.

Association Between Physical Performance and Cognitive Function in Chinese Community-Dwelling Older Adults: Serial Mediation of Malnutrition and Depression.

PURPOSE: We aimed to propose a serial mediational model to further analyze the relationship between poor physical performance, malnutrition, depression and cognitive impairment in Chinese community-dwelling older adults. PATIENTS AND METHODS: This study consisted of 1386 community-dwelling Chinese older adults aged 65 years and older in Shanghai, China. Mild cognitive impairment (MCI) was assessed by the Mini-Mental State Examination (MMSE) and Instrumental Activities Of Daily Living (IADL). Physical performance was assessed by short physical performance battery (SPPB). Malnutrition was defined with the Mini Nutritional Assessment (MNA). Depressive symptoms were evaluated by the 30-item Geriatric Depression Scale (GDS). Serial multiple mediator models were used. RESULTS: The mean age of the final analysis sample was 73.62±6.14, and 57.6% (n=809) were females. The prevalence of MCI was 14.35% (n=199). Physical performance (p<0.001), nutritional status (p=0.025), and depressive symptoms (p=0.002) were correlated with MCI. The serial mediational model revealed that MNA and GDS scores significantly mediated association of SPPB and MMSE scores (c'=0.4728, p<0.001). Furthermore, depressive symptoms significantly mediated the association of physical performance and cognition (p=0.0311), while malnutrition had no independent mediating effect between these two factors (p=0.794). CONCLUSION: Our study examined the serial multiple mediation roles of nutritional status and depressive symptoms on the relationship between physical performance and cognitive function in community-dwelling Chinese older adults. Older adults who were in poor physical condition tend to have worse nutritional status, more severe depression, and poorer cognitive function.