Inonotus obliquus aqueous extract inhibits intestinal inflammation and insulin metabolism defects in Drosophila.

In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.

Hydrogen Sulfide Ameliorates Heart Aging by Downregulating Matrix Metalloproteinase-9.

PURPOSE: Aging contributes significantly to cardiovascular diseases and cardiac dysfunction, leading to the upregulation of matrix metalloproteinase-9 (MMP-9) in the heart and a significant decrease in hydrogen sulfide (H2S) content, coupled with impaired cardiac diastolic function. This study explores whether supplementing exogenous hydrogen sulfide during aging ameliorates the decline in H2S concentration in the heart, suppresses MMP-9 expression, and improves the age-associated impairment in cardiac morphology and function. METHODS: We collected plasma from healthy individuals of different ages to determine the relationship between aging and H2S and MMP-9 levels through Elisa detection and liquid chromatography-tandem mass spectrometry (LC/MC) detection of plasma H2S content. Three-month-old mice were selected as the young group, while 18-month-old mice were selected as the old group, and sodium hydrosulfide (NaHS) was injected intraperitoneally from 15 months old until 18 months old as the old + NaHS group. Plasma MMP-9 content was detected using Elisa, plasma H2S content, cardiac H2S content, and cystathionine gamma-lyase (CSE) activity were detected using LC/MC, and cardiac function was detected using echocardiography. Heart structure was assessed using hematoxylin and eosin staining, Masone staining was used to detect the degree of cardiac fibrosis, while western blot was used to detect the expression of MMP-9, CSE, and aging marker proteins. Knockdown of MMP-9 and CSE in H9c2 cells using small interfering RNA was carried out to determine the upstream-downstream relationship between MMP-9 and CSE. RESULTS: H2S content in the plasma of healthy individuals decreases with escalating age, whereas MMP-9 level rises with age progression. Aging leads to a decrease in H2S levels in the heart and plasma of mice, severe impairment of cardiac diastolic function, interstitial relaxation, and fibrosis of the heart. Supplementing with exogenous H2S can improve these phenomena. CONCLUSION: H2S maintains the structure and function of the heart by inhibiting the expression of MMP-9 during the aging process.

Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus.

Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.

Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction.

Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia.

This study aimed to determine whether trimethylamine N-oxide (TMAO) was involved in sympathetic activation in aging and the underlying mechanisms. Our hypothesis is TMAO reduces P2Y12 receptor (P2Y12R) and induces microglia-mediated inflammation in the paraventricular nucleus (PVN), then leading to sympathetic activation in aging. This study involved 18 young adults and 16 old adults. Aging rats were established by injecting D-galactose (D-gal, 200 mg/kg/d) subcutaneously for 12 weeks. TMAO (120 mg/kg/d) or 1% 3, 3-dimethyl-l-butanol (DMB) was administrated via drinking water for 12 weeks to investigate their effects on neuroinflammation and sympathetic activation in aging rats. Plasma TMAO, NE and IL-1ß levels were higher in old adults than in young adults. In addition, standard deviation of all normal to normal intervals (SDNN) and standard deviation of the average of normal to normal intervals (SDANN) were lower in old adults and negatively correlated with TMAO, indicating sympathetic activation in old adults, which is associated with an increase in TMAO levels. Treatment of rats with D-gal showed increased senescence-associated protein levels and microglia-mediated inflammation, as well as decreased P2Y12R protein levels in PVN. Plasma TMAO, NE and IL-1ß levels were increased, accompanied by enhanced renal sympathetic nerve activity (RSNA). While TMAO treatment exacerbated the above phenomenon, DMB mitigated it. These findings suggest that TMAO contributes to sympathetic hyperactivity in aging by downregulating P2Y12R in microglia and increasing inflammation in the PVN. These results may provide promising new target for the prevention and treatment of aging and aging-related diseases.

Decreased levels of hydrogen sulfide in the hypothalamic paraventricular nucleus contribute to sympathetic hyperactivity induced by cerebral infarction.

Paroxysmal sympathetic hyperactivity (PSH) is a common clinical feature secondary to ischemic stroke (IS), but its mechanism is poorly understood. We aimed to investigate the role of H2S in the pathogenesis of PSH. IS patients were divided into malignant (MCI) and non-malignant cerebral infarction (NMCI) group. IS in rats was induced by the right middle cerebral artery occlusion (MCAO). H2S donor (NaHS) or inhibitor (aminooxy-acetic acid, AOAA) were microinjected into the hypothalamic paraventricular nucleus (PVN). Compared with the NMCI group, patients in the MCI group showed PSH, including tachycardia, hypertension, and more plasma norepinephrine (NE) that was positively correlated with levels of creatine kinase, glutamate transaminase, and creatinine respectively. The 1-year survival rate of patients with high plasma NE levels was lower. The hypothalamus of rats with MCAO showed increased activity, especially in the PVN region. The levels of H2S in PVN of the rats with MCAO were reduced, while the blood pressure and renal sympathetic discharge were increased, which could be ameliorated by NaHS and exacerbated by AOAA. NaHS completely reduced the disulfide bond of NMDAR1 in PC12 cells. The inhibition of NMDAR by MK-801 microinjected in PVN of rats with MCAO also could lower blood pressure and renal sympathetic discharge. In conclusion, PSH may be associated with disease progression and survival in patients with IS. Decreased levels of H2S in PVN were involved in regulating sympathetic efferent activity after cerebral infarction. Our results might provide a new strategy and target for the prevention and treatment of PSH.

InR and Pi3K maintain intestinal homeostasis through STAT/EGFR and Notch signaling in enteroblasts.

To maintain the integrity of the adult gut, the proliferation and differentiation of stem cells must be strictly controlled. Several signaling pathways control the proliferation and differentiation of Drosophila intestinal epithelial cells. Although the modulatory effects of insulin pathway components on cell proliferation have been characterized, their specific role in which cell type and how these components interact with other regulatory signaling pathways remain largely unclear. In this study, we found that InR/Pi3K has major functions in enteroblasts (EBs) that were not previously described. The absence of InR/Pi3K in progenitors leads to a decrease in the number of EBs, while it has no significant effect on intestinal stem cells (ISCs). In addition, we found that InR/Pi3K regulates Notch activity in ISCs and EBs in an opposite way. This is also the reason for the decrease in EB. On the one hand, aberrantly low levels of Notch signaling in ISCs inhibit their proper differentiation into EBs; on the other hand, the higher Notch levels in EBs promote their excessive differentiation into enterocytes (ECs), leading to marked increases in abnormal ECs and decreased proliferation. Moreover, we found that Upd/JAK/STAT signaling acts as an effector or modifier of InR/Pi3K function in the midgut and cooperates with EGFR signaling to regulate cell proliferation. Altogether, our results demonstrate that InR and Pi3K are essential for coordinating stem cell differentiation and proliferation to maintain intestinal homeostasis.

Association between screen time and physical activity on mental health among preschoolers: a cross-sectional study from Southwest China.

BACKGROUND: Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures. METHODS: A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers' MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities. RESULTS: A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers' MHP for comparisons of different levels of screen time (< 2 h/day, 2-4 h/day,≥4 h/day) show that screen time positively associated with MHP after adjusting for confounders (P < 0.05), but the association was not significant among girls with screen time ≥ 4 h/day. In addition, increased engagement in physical activity was reversely linked to MHP (P < 0.05). A stronger association between MHP and MVPA was observed in boys, however, this association was weakened when the total time spent engaging in MVPA exceeded two hours per day (P < 0.05). CONCLUSION: Less physical activity and more screen time positively relate to MHP, but the relationship differs by type of physical activity, total time, and gender. These findings provide novel insights and evidence supporting for guidelines on physical activity, screen time, and improvement of mental health for preschoolers.

Construction of an enteral nutrition evaluation system for critically ill patients based on the Delphi method.

BACKGROUND: This study aimed to construct an enteral nutrition evaluation system for critically ill patients using the Delphi method to direct the formulation of enteral nutrition support strategies and reduce interruption to enteral feeding. METHODS: We used domestic and foreign databases to obtain and analyze the literature and form "The Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients." The Delphi method was used to conduct two rounds of expert opinion consultation, combined with the suggestions from the research group to finalize the nutrition evaluation content of the system. RESULTS: After two rounds of expert consultation, a nutrition evaluation system was formed around three dimensions: before the start, during, and after the end of nutritional support. The effective recovery rates of the two rounds of expert consultation were 90.0% (18/20) and 100.0% (18/18), respectively. Authority coefficients were 0.865 and 0.908, while Kendall coordination coefficients were 0.108 ( P < 0.05) and 0.115 ( P < 0.001), respectively. Finally, the full enteral nutrition evaluation system for critically ill patients was constructed based on the Delphi method, including three primary items and seven secondary and 28 tertiary indicators. CONCLUSION: The established "Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients" has high consistency from expert opinions and reliability, which can provide a practical evaluation tool for the process of enteral nutrition for severe patients.

Monounsaturated and polyunsaturated fatty acids concerning prediabetes and type 2 diabetes mellitus risk among participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to March 2020.

Objective: Unsaturated fatty acids (UFA) may be related to glycometabolism. While associations between UFA intake (especially their subtype) and prediabetes or type 2 diabetes mellitus (T2DM) need to be further studied. In this study, we aimed to evaluate the potential relation of UFA with prediabetes and T2DM. Methods: A total of 16,290 adults aged older than 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2005 to March 2020 were included in the present analysis. Dietary intake was assessed by two day, 24-hour dietary recalls and daily intake of total monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA); four specific fatty acids of MUFA and seven specific fatty acids of PUFA were calculated. Prediabetes and T2DM were diagnosed by fasting glucose, glycohemoglobin, and self-reported medication or insulin. Rao-Scott modified chi-square tests, the Taylor series linearization method, and multivariable logistic regression analyses were applied to analyze the associations of dietary MUFA and PUFA intake with diabetes risk. Results: Of the participants, 44.34% had prediabetes and 13.16% had T2DM patients. From multivariate analysis, we found that intake of MUFA, PUFA, and some subtypes was negatively associated with the risk of prediabetes and T2DM in Americans. Compared with adults in the lowest tertile, those in the highest MUFA (PUFA) tertile had an approximately 50% (49%) and 69% (68%) lower risk of prediabetes and T2DM, respectively. Moreover, the effects of the subtypes of MUFA and PUFA on prediabetes and T2DM were different. Higher intakes of MFA 18:1, MFA 20:1, PFA 18:2, and PFA 18:3 and higher tertile intakes of MFA 16:1 and PFA 20:4 were related to a lower risk of prediabetes and T2DM. Similarly, the effects of MUFA, PUFA, and subtype on prediabetes and T2DM varied among different age groups, being weakened along with age. Conclusion: Our study suggested that total MUFA and PUFA intake might be essential in preventing prediabetes and T2DM, especially in Americans. However, this protective effect may decrease with age. Moreover, the effects of the specific UFA on prediabetes and T2DM need further consideration.

Seroprevalence and Molecular Characterization of Brucella abortus from the Himalayan Marmot in Qinghai, China.

Objective: Brucellosis is a serious public health issue in Qinghai (QH), China. Surveying the seroprevalence and isolation of B. abortus strains from marmots is key to understanding the role of wildlife in the maintenance and spread of brucellosis. Methods: In this study, a set of methods, including a serology survey, bacteriology, antibiotic susceptibility, molecular genotyping (MLST and MLVA), and genome sequencing, were employed to characterize the two B. abortus strains. Results: The seroprevalence of brucellosis in marmots was 7.0% (80/1146) by serum tube agglutination test (SAT); one Brucella strain was recovered from these positive samples, and another Brucella strain from a human. Two strains were identified as B. abortus bv. 1 and were susceptible to all eight drugs examined. The distribution patterns of the accessory genes, virulence associated genes, and resistance genes of the two strains were consistent, and there was excellent collinearity between the two strains on chromosome I, but they had significant SVs in chromosome II, including inversions and translocations. MLST genotyping identified two B. abortus strains as ST2, and MLVA-16 analysis showed that the two strains clustered with strains from northern China. WGS-SNP phylogenetic analysis showed that the strains were genetically homogeneous with strains from the northern region, implying that strains from a common lineage were spread continuously in different regions and hosts. Conclusion: Seroprevalence and molecular clues demonstrated frequent direct or indirect contact between sheep/goats, cattle, and marmots, implying that wildlife plays a vital role in the maintenance and spread of B. abortus in the Qinghai-Tibet Plateau.

Association between daily screen time and risk of stroke among middle-aged and elderly people: research based on China health and nutrition survey.

Background: We aimed to explore the independent associations between screen time and the risk of stroke among Chinese adults based on the China Health and Nutrition Survey (CHNS). Methods: Data on Chinese adults aged older than 40 years from the CHNS in during 2004-2009 were selected. A total of 4,587 individuals were included in 2009, including screen time and the risk of stroke. Simultaneously, we traced the previous screen time to 2004 for those with outcome measures in 2009 (n = 2,100). Basic information, lifestyle, and screen behavior were obtained through face-to-face interviews and self-completed questionnaires. Anthropometric data collected included blood pressure, body weight, height, hip circumference, and waist circumference. Fasting blood was obtained for measurements of lipid and glucose levels. Cross-sectional analysis and cohort analysis were both performed using multivariate logistic regression. Results: Of all participants, 3,004 (65.49%) participants spent more than 2 h per day on screen time. Taking the men who spent less than 2 h on screen per day as reference, the crude odds ratio (OR) of the high risk of stroke was 1.53 [95% confidence interval (CI), 1.20-1.95] for the men who spent 2-3 h per day on screen and 2.37 (95% CI, 1.78-3.16) for the men who spent more than 3 h per day on screen. This difference remained significant after adjusting for confounding factors. No association was observed among women. However, in the cohort analysis with screen time in 2006 as the independent variable, the association between screen time and stroke risk was found both in men [OR, 1.83 (95% CI, 1.19-2.82)] and women [OR, 1.48 (95% CI, 1.10-1.99)]). Conclusion: We found that the high screen time was associated with an increased stroke risk, which was pronounced in men, warranting a universal need to limit screen time in order to improve health.

The association between maternal healthy lifestyle factors during pregnancy and the neonatal anthropometric indicators based on a prospective cohort study.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the associations between a combined healthy lifestyle during the second and third trimesters and offspring anthropometric outcomes in China. METHODS AND STUDY DESIGN: We examined these associations among 548 participants from nine community health centers and three hospitals in the North China cohort. A pregnant women's healthy lifestyle score (HLS) was constructed based on six lifestyle factors: smoking, alcohol consumption, physical activity, sedentary behavior, diet, and gestational weight gain. Anthropometric indicators at birth like birth weight (BW), head circumference (HC), and birth length (BL) were collected, and weight to head circumference ratio (WHC, kg/m), body mass index (BMI, kg/m2) and Ponderal Index (PI, kg/m3) were calculated. Multivariate linear and logistic regression models were used to examine the effects of HLS during the second and third trimesters on anthropometric outcomes at birth, respectively. RESULTS: In fully adjusted models, we found a negative association between second and third-trimester HLS and offspring HC and a positive relationship between second-trimester HLS and BL (p<0.05). Neonates with mothers in the highest HLS tertile had a 5.6% relatively lower HC and 2.3% relatively longer body length than women in the lowest tertile. Each additional unit in third-trimester HLS had an associated decrease in HC by 0.96 cm. None of the associations between HLS and BW, WHC, BMI, and PI of offspring were observed. CONCLUSIONS: A healthy lifestyle score may significantly impact offspring head circumference and body length, supporting the important role of healthy lifestyles in improving the health of offspring.

Native circulating Brucella melitensis lineages causing a brucellosis epidemic in Qinghai, China.

Since 2010, the cases and incidences of human brucellosis have been increasing annually in Qinghai (QH) Province. Molecular epidemiology and phylogenetic analyses of strains from this region are crucial to better understand the transmission of the disease and the evolutionary patterns of Brucella strains. In this study, classical bio-typing assay, multilocus variable-number tandem repeat analysis, and the whole-genome sequencing-single-nucleotide polymorphism approach were used to illustrate the epidemiological and evolutionary patterns of Brucella melitensis. A total of 54 B. melitensis bv. 3 strains were isolated and molecularly characterized, with all strains belonging to the East Mediterranean lineages. Cross-regional transmission events (i.e., between counties) were caused by common sources of infection, suggesting that predominant circulating genotypes are endemic in different regions. Strengthening surveillance in animal brucellosis and controlling infected animals' cross-border movement are necessary. Two strains isolated from humans and marmots were clustered in the same sub-clade, implying the possible existence of direct and/or indirect contact between sheep (and goats) and wildlife (marmots), but this needs to be verified by further investigations. The global-scale phylogenetic analysis indicated that 54 strains sorted into six subclades, four of which formed independent lineages, suggesting that the increase in the incidence rate of human brucellosis may be caused by local circulating lineages. Further strengthening the serology and pathogen surveillance of animals (wildlife) and humans will contribute to an in-depth understanding of the transmission chain of human brucellosis in this region.

Hydrogen sulfide ameliorates endothelial dysfunction in aging arteries by regulating ferroptosis.

Aging causes vascular endothelial dysfunction. We aimed to investigate the causes of vascular endothelial dysfunction during aging using plasma and renal arteries from patients who underwent nephrectomy and animal models. The results showed that the endogenous H2S-producing enzyme cystathione-γ-lyase (CSE) protein expression was downregulated in renal artery tissue, plasma H2S levels were reduced. Moreover, elevated lipid peroxidation and iron accumulation levels led to ferroptosis and endothelial diastolic function in the renal arteries was impaired in the elderly group. H2S enhanced the endogenous CSE expression in the elderly group, promoted endogenous H2S production, decreased lipid peroxide expression, and inhibited ferroptosis, which in turn improved vascular endothelial function in the elderly group. In animal models, we also observed the same results. In addition, we applied NaHS, Ferrostatin-1 (ferroptosis inhibitor) and erastin (ferroptosis inducer) to incubate renal arteries of SD rats. The results showed that NaHS enhanced ferroptosis related proteins expression, inhibited ferroptosis and improved vascular endothelial function. We demonstrated that endothelial dysfunction associated with aging is closely related to reduced endogenous H2S levels and ferroptosis in vascular endothelial cells. Notably, H2S reduced lipid peroxidation levels in vascular endothelial cells, inhibited ferroptosis in vascular endothelial cells, and improved endothelial dysfunction.

Hydrogen sulfide ameliorates senescence in vascular endothelial cells through ameliorating inflammation and activating PPARδ/SGLT2/STAT3 signaling pathway.

Mounting evidence demonstrates that hydrogen sulfide (H 2S) promotes anti-inflammatory molecules and inhibits pro-inflammatory cytokines in endothelial cells (ECs). This study aims to investigate the favorable action of H 2S on endothelial function in senescence by inhibiting the production of inflammatory molecules. Senescent ECs exhibit a reduction in H 2S, endothelial nitric oxide synthase (eNOS) and peroxisome proliferator-activated receptor δ (PPARδ), coupled with increased inflammatory molecules, sodium glucose transporter type 2 (SGLT2) and phosphorylation of STAT3, which could be reversed by the administration of a slow but sustained release agent of H 2S, GYY4137. Decreased production of eNOS and upregulated p-STAT3 and SGLT2 levels in senescent ECs are reversed by replenishment of the SGLT2 inhibitor EMPA and the PPARδ agonist GW501516. The PPARδ antagonist GSK0660 attenuates eNOS expression and increases the production of p-STAT3 and SGLT2. However, supplementation with GYY4137 has no beneficial effect on GSK0660-treated ECs. GYY4137, GW501516 and EMPA preserve endothelial-dependent relaxation (EDR) in D-gal-treated aortae, while GSK0660 destroys aortic relaxation even with GYY4137 supplementation. In summary, senescent ECs manifest aggravated the expressions of the inflammatory molecules SGLT2 and p-STAT3 and decreased the productions of PPARδ, eNOS and CSE. H 2S ameliorates endothelial dysfunction through the anti-inflammatory effect of the PPARδ/SGLT2/p-STAT3 signaling pathway in senescent ECs and may be a potential therapeutic target for anti-ageing treatment.

Alginate-based edible coating with oregano essential oil/ß-cyclodextrin inclusion complex for chicken breast preservation.

A sodium alginate (SA) edible coating containing oregano essential oil (OEO)/ß-cyclodextrin (ß-CD) inclusion complexes (SA/OEO-MP coating) was developed to extend the shelf life of fresh chicken breast during refrigeration storage. First, OEO was inserted into the hydrophobic interior of ß-CD to form an inclusion complex (OEO-MP) that maintained its excellent antioxidant and antibacterial activities. The formed OEO-MP was characterized using fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). In addition, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) results demonstrated that ß-CD could improve the thermal stability of OEO. The encapsulation efficiency reached 71.6 %, and OEO was released continuously from the OEO-MP. The lipid oxidation, total viable count (TVC) and sensory properties of chicken breasts were regularly monitored when OEO-MP was incorporated into the SA coating for chicken breast preservation. Compared with the uncoated group, the SA/OEO-MP-coated groups showed significantly reduced increases in pH, thiobarbituric acid reactive substances (TBARS), total volatile base nitrogen (TVB-N), and TVC, especially in the SA/OEO-MP1 group. In summary, the SA/OEO-MP coating could preserve the chicken breast by reducing lipid oxidation and inhibiting the proliferation of microorganisms. It would be developed as a prospective edible packaging for chicken preservation.

UAV Trajectory Design and Power Optimization for Terahertz Band-Integrated Sensing and Communications.

Sixth generation (6G) wireless networks require very low latency and an ultra-high data rate, which have become the main challenges for future wireless communications. To effectively balance the requirements of 6G and the extreme shortage of capacity within the existing wireless networks, sensing-assisted communications in the terahertz (THz) band with unmanned aerial vehicles (UAVs) is proposed. In this scenario, the THz-UAV acts as an aerial base station to provide information on users and sensing signals and detect the THz channel to assist UAV communication. However, communication and sensing signals that use the same resources can cause interference with each other. Therefore, we research a cooperative method of co-existence between sensing and communication signals in the same frequency and time allocation to reduce the interference. We then formulate an optimization problem to minimize the total delay by jointly optimizing the UAV trajectory, frequency association, and transmission power of each user. The resulting problem is a non-convex and mixed integer optimization problem, which is challenging to solve. By resorting to the Lagrange multiplier and proximal policy optimization (PPO) method, we propose an overall alternating optimization algorithm to solve this problem in an iterative way. Specifically, given the UAV location and frequency, the sub-problem of the sensing and communication transmission powers is transformed into a convex problem, which is solved by the Lagrange multiplier method. Second, in each iteration, for given sensing and communication transmission powers, we relax the discrete variable to a continuous variable and use the PPO algorithm to tackle the sub-problem of joint optimization of the UAV location and frequency. The results show that the proposed algorithm reduces the delay and improves the transmission rate when compared with the conventional greedy algorithm.

Validation of a novel nutrition risk screening tool in stroke patients.

BACKGROUND AND OBJECTIVES: We aimed to apply a novel nutrition screening tool to stroke patients and assess its reliability and validity. METHODS AND STUDY DESIGN: Cross-sectional data among 214 imaging-confirmed stroke patients were collected between 2015 and 2017 in two public hospitals in Hebei, China. Delphi consultation was conducted to evaluate the items in the NRS-S scale. Anthropometric indices including body mass index (BMI), triceps skin fold thickness (TSF), upper arm circumference (AMC) and mid-arm muscle circumference (MAMC) were measured. Internal consistency reliability, test-retest reliability, construct validity and content validity were assessed. In order to estimate content validity, two rounds Delphi consultation of fifteen experts were conducted to evaluate the items in the Nutrition Risk Screening Scale for Stroke (NRS-S). RESULTS: High internal consistency was indicated by Cronbach's alpha of 0.632 and a split-half reliability of 0.629; test-retest reliability of NRS-S items ranged from 0.728 to 1.000 (p<0.0001), except for loss of appetite (0.436, p<0.001) and gastrointestinal symptoms (0.213, p=0.042). Content validity index of 0.89 indicated robust validity of the items. Regarding construct validity, the Kaiser-Meyer-Olkin value was 0.579, and the result of the Bartlett test of sphericity was 166.790 (p<0.001). Three factors were extracted by exploratory factor analysis, which contributed to 63.079% of the variance. Confirmatory factor analysis was performed on the questionnaire, finding the p-value of the model to be 0.321, indicating a high model fitting index. CONCLUSIONS: A novel stroke-specific nutritional risk screening tool demonstrated a relatively high reliability and validity in its clinical application.