Research Note: Metabolomics revealed the causes of the formation of chicken structural blue earlobes.

The earlobes of chickens exhibit a range of colors, but there has been relatively little research on the formation of structural blue earlobes. Previous results showed that the structural color earlobes were related to the interplay between melanin and collagen in light reflection. To investigate the metabolic differences in these earlobe colors, we conducted nontargeted liquid chromatograph mass spectrometer (LC-MS) for metabolomic sequencing on structural blue (Green and Blue groups) and nonstructural color (Black group) earlobes tissue of Jiangshan black-bone chickens. The content detection in earlobe tissues of different groups shows that there were significant differences in melanin and collagen content between the Black and Green group. The metabolome identified a total of 6,102 mass spectroscopic peaks and ultimately identified 919 annotated metabolites. Variable importance in the projection (VIP) analysis identified the common differential expressed metabolites (DMs) "Tyr Thr Ala Glu" among the 3 groups. By combining those DMs with differentially expressed genes (DEGs) in our previous transcriptome data from the same sample, and associated with KEGG pathway analysis, multiple pathways related to melanogenesis and collagen metabolism were enriched across the 3 groups. By analyzing the metabolites and genes in these pathways, as well as the interaction network diagram of DEGs, we identified some key genes, Wnt Family Member 6 (WNT6), Transcription Factor 7 (TCF7), Proopiomelanocortin (POMC) and Calcium/Calmodulin Dependent Protein Kinase II Alpha (CAMK2A), and some key DMs like DG (11M3/9M5/0:0) and gentisic acid. The differential gene expression and metabolic levels affect the production of melanin and collagen, leading to differences in the content in melanin and the thickness of the collagen layer between earlobe colors, while the thickness of the collagen layer could affect light scattering, ultimately resulting in different colored earlobes in Jiangshan black-bone chickens.

A longitudinal study of the mediator role of physical activity in the bidirectional relationships of cognitive function and specific dimensions of depressive symptoms.

BACKGROUND: The bidirectional relationship between cognitive function and depressive symptoms has been extensively reported. However, the potential mechanisms are still not clear. We aim to longitudinally investigate whether physical activity mediates the bidirectional relationships between cognitive function and specific dimensions of depressive symptoms. METHODS: Data from 6,787 individuals aged ≥50 of 2014/15 (T1), 2016/17 (T2), and 2018/19 (T3) waves of the English Longitudinal Study of Ageing (ELSA). Cognitive function was assessed by domains of memory, orientation in time, and executive function. Physical activity was measured with the intensity and frequency of participation. Specific dimensions of depressive symptoms were assessed by the 8-item Center for Epidemiologic Studies Depression Scale, distinguishing between cognitive-affective and somatic symptoms. Cross-lagged panel models were used to investigate the mediating role of physical activity in the bidirectional relationships between cognitive function and two dimensions of depressive symptoms. RESULTS: Poorer cognitive function was indirectly associated with worse cognitive-affective symptoms (indirect effect = -0.002, 95%CI: -0.004, -0.001) through lower physical activity levels. Poorer cognitive function was also indirectly associated with worse somatic symptoms (indirect effect = -0.003, 95%CI: -0.006, -0.002) through lower physical activity levels, and the reverse mediation was observed as well (indirect effect = -0.002, 95%CI: -0.004, -0.001). LIMITATIONS: There is no distinction between potential within-person and between-person effects. CONCLUSIONS: Collaborative interventions of physical activity are beneficial in protecting cognitive function and mental health in older adults.

Transcriptome and proteome revealed the differences in 3 colors of earlobe in Jiangshan Black-bone chicken.

The earlobe is a featherless, exposed thickening located beneath the ear canal of chickens, which plays a visual signaling role in age, performance, mental vitality, reproduction, and other aspects. However, despite its importance, there have been few studies on the color differences and formation mechanisms of chicken earlobes, particularly the structurally blue earlobes characteristic of the Jiangshan black-bone chicken. In this study, we explored the physiological mechanisms that may influence the formation of differently colored earlobes using 3 types of earlobes from Jiangshan black-bone chickens: light peacock green (Green group), dark peacock green (Blue group), and dark reddish purple (Black group). All 3 earlobe colors exhibited positive melanin Masson-Fontana staining, and the thickness of collagen fibers in the dermis decreased in the order of Green, Blue, and Black groups. A total of 1,953 differentially expressed genes (DEGs) were detected in the 3 earlobes through mRNA sequencing, among which the GO term "collagen trimer" was significantly enriched in DEGs between groups. Additionally, 716 differentially expressed proteins (DEPs) were identified in the 3 earlobes using 4D-DIA proteomics, with the term "collagen fibril organization" being significantly enriched in DEPs between the Green and Black groups. Integrated analysis of transcriptome and proteome data revealed that 12 DEGs and DEPs were commonly differentially expressed between the Green and Black groups, including the gene LUM (corneal keratan sulfate proteoglycan), which was significantly enriched in the "collagen fibril organization" GO term. In conclusion, our study suggests that LUM plays a crucial role in the formation of peacock green earlobes in Jiangshan black-bone chickens. The high level of LUM in peacock green (Green and Blue groups) may affect collagen nanostructures, leading to a stronger effect of melanin-supported dermal collagen on the production of non-iridescent structural colors through coherent scattering, resulting in a bright structural blue color in Jiangshan black-bone chickens. In contrast, the low expression of LUM in dark reddish purple (Black group) reduces the reflection of non-iridescent structural colors, making the earlobe color appear almost black, similar to melanin.

Association of diabetes mellitus with gait and falls in community-dwelling older adults: Serial mediation of vision and cognition.

BACKGROUND/OBJECTIVE: Diabetes mellitus (DM) is associated with walking performance, but potential underlying mechanisms of this association remain unclear. The present study aims to disentangle the pathways linking DM to gait and falls through the serial mediation effect of vision and cognition among the older population. METHODS: Data were taken from wave 9 (2018-2019) of the English Longitudinal Study of Aging (ELSA), including 5496 participants aged 60 years and older. DM was identified based on medical diagnosis and laboratory tests. Vision and falls were self-reported. Cognition was evaluated using questionnaire. Gait speed was measured by the "timed walking test". Serial mediation analysis was performed using Mplus 8.3. RESULTS: DM was associated with impaired gait speed (c = 0.085, P < 0.05) and falls (c = 0.061, P < 0.05). The serial mediation model revealed that vision and cognition significantly mediated the association of DM with impaired gait speed, with 17.97% and 23.60% of the total effects explained by vision and cognition respectively, and 3.37% explained by the path through vision and then cognition. Similarly, vision and cognition significantly mediated the association of DM with falls, with 14.99% and 6.67% of the total effects explained by vision and cognition respectively, and 1.67% explained by the path through vision and then cognition. CONCLUSIONS: These findings contribute to deeper understanding of the mechanism underlying the association of DM with walking performance. Evaluation and intervention targeted at vision and the cognition may be beneficial for improving gait or reducing falls in older adults with DM.

The Associations of Iron Related Biomarkers with Risk, Clinical Severity and Mortality in SARS-CoV-2 Patients: A Meta-Analysis.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly around the world and has led to millions of infections and deaths. Growing evidence indicates that iron metabolism is associated with COVID-19 progression, and iron-related biomarkers have great potential for detecting these diseases. However, the results of previous studies are conflicting, and there is not consistent numerical magnitude relationship between those biomarkers and COVID-19. Thereby, we aimed to integrate the results of current studies and to further explore their relationships through a meta-analysis. We searched peer-reviewed literature in PubMed, Scopus and Web of Science up to 31 May 2022. A random effects model was used for pooling standard mean difference (SMD) and the calculation of the corresponding 95% confidence interval (CI). I2 was used to evaluate heterogeneity among studies. A total of 72 eligible articles were included in the meta-analysis. It was found that the ferritin levels of patients increased with the severity of the disease, whereas their serum iron levels and hemoglobin levels showed opposite trends. In addition, non-survivors had higher ferritin levels (SMD (95%CI): 1.121 (0.854, 1.388); Z = 8.22 p for Z < 0.001; I2 = 95.7%, p for I2 < 0.001), lower serum iron levels (SMD (95%CI): −0.483 (−0.597, −0.368), Z = 8.27, p for Z < 0.001; I2 = 0.9%, p for I2 =0.423) and significantly lower TIBC levels (SMD (95%CI): −0.612 (−0.900, −0.324), Z = 4.16, p for Z < 0.001; I2 = 71%, p for I2 = 0.016) than survivors. This meta-analysis demonstrates that ferritin, serum iron, hemoglobin and total iron banding capacity (TIBC) levels are strongly associated with the risk, severity and mortality of COVID-19, providing strong evidence for their potential in predicting disease occurrence and progression.

Simazine perturbs the maturational competency of mouse oocyte through inducing oxidative stress and DNA damage.

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

Does older subjective age predict poorer cognitive function and higher risk of dementia in middle-aged and older adults?

As a biopsychosocial marker of aging, subjective age (i.e., the age individuals feel regardless of their actual age) was related to many health issues in the elderly. The purpose of this study is to investigate whether subjective age is associated with subsequent cognition and dementia risk in middle-aged and older adults. Samples were drawn from the English Longitudinal Study of Ageing (ELSA). Participants reported their subjective ages at the baseline (2004/2005), and their cognitive functions were measured after 10 years (2014/2015). Newly diagnosed dementias were recorded between 2006/2007 to 2014/2015. Overall, 6,475 adults aged 50 years or older were included in the current analyses. The relationship between subjective age reported at baseline and cognition assessed ten years later was modeled using multiple linear regression models. Compared to participants who reported a younger subjective age, those who reported an older subjective age were more likely to have poorer cognition after ten years (ß = -0.705, P = .002 for memory, ß = -1.567, P = .001 for executive function). A Cox proportional hazard regression model suggested that older subjective age was an independent risk factor for incident dementia (HR = 1.737, 95% CI =1.060-2.848). Other than chronological age, subjective age could also be considered as an important predictor for the development of cognitive dysfunction.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of COVID-19: a multicenter retrospective cohort study of 4086 cases in China.

To establish an effective nomogram for predicting in-hospital mortality of COVID-19, a retrospective cohort study was conducted in two hospitals in Wuhan, China, with a total of 4,086 hospitalized COVID-19 cases. All patients have reached therapeutic endpoint (death or discharge). First, a total of 3,022 COVID-19 cases in Wuhan Huoshenshan hospital were divided chronologically into two sets, one (1,780 cases, including 47 died) for nomogram modeling and the other (1,242 cases, including 22 died) for internal validation. We then enrolled 1,064 COVID-19 cases (29 died) in Wuhan Taikang-Tongji hospital for external validation. Independent factors included age (HR for per year increment: 1.05), severity at admission (HR for per rank increment: 2.91), dyspnea (HR: 2.18), cardiovascular disease (HR: 3.25), and levels of lactate dehydrogenase (HR: 4.53), total bilirubin (HR: 2.56), blood glucose (HR: 2.56), and urea (HR: 2.14), which were finally selected into the nomogram. The C-index for the internal resampling (0.97, 95% CI: 0.95-0.98), the internal validation (0.96, 95% CI: 0.94-0.98), and the external validation (0.92, 95% CI: 0.86-0.98) demonstrated the fair discrimination ability. The calibration plots showed optimal agreement between nomogram prediction and actual observation. We established and validated a novel prognostic nomogram that could predict in-hospital mortality of COVID-19 patients.

Association of Coffee, Decaffeinated Coffee and Caffeine Intake from Coffee with Cognitive Performance in Older Adults: National Health and Nutrition Examination Survey (NHANES) 2011-2014.

The aim of this study was to examine the association of coffee, caffeinated coffee, decaffeinated coffee and caffeine intake from coffee with cognitive performance in older adults. we used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Coffee and caffeine intake were obtained through two 24-hour dietary recalls. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test and Digit Symbol Substitution Test (DSST). Binary logistic regression and restricted cubic spline models were applied to evaluate the association of coffee and caffeine intake with cognitive performance. A total of 2513 participants aged 60 years or older were included. In the fully adjusted model, compared to those reporting no coffee consumption, those who reported 266.4-495 (g/day) had a multivariate adjusted odd ratio (OR) with 95% confidence interval (CI) of 0.56(0.35-0.89) for DSST test score, compared to those reporting no caffeinated coffee consumption, those who reported ≥384.8 (g/day) had a multivariate-adjusted OR (95% CI) of 0.68(0.48-0.97) for DSST test score, compared to the lowest quartile of caffeine intake from coffee, the multivariate adjusted OR (95% CI) of the quartile (Q) three was 0.62(0.38-0.98) for the CERAD test score. L-shaped associations were apparent for coffee, caffeinated coffee and caffeine from coffee with the DSST test score and CERAD test score. No significant association was observed between decaffeinated coffee and different dimensions of cognitive performance. Our study suggests that coffee, caffeinated coffee and caffeine from coffee were associated with cognitive performance, while decaffeinated coffee was not associated with cognitive performance.

Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae.

We report a case of a 63-year-old female patient who developed a recurrent urinary tract infection (UTI) with extensively drug-resistant Klebsiella pneumoniae (ERKp). In the initial two rounds of phage therapy, phage resistant mutants developed within days. Although ERKp strains were completely resistant to sulfamethoxazole-trimethoprim, the combination of sulfamethoxazole-trimethoprim with the phage cocktail inhibited the emergence of phage resistant mutant in vitro, and the UTI of patient was successfully cured by this combination. Thus, we propose that non-active antibiotic and bacteriophage synergism (NABS) might be an alternative strategy in personalized phage therapy.

Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011-2014.

BACKGROUND: Current evidence on the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance is inconsistent. Therefore, the aim is to explore the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in the U.S. noninstitutionalized population of older adults. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Intakes of ω-3 and ω-6 fatty acids were obtained through two 24-h dietary recalls and were adjusted by energy. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning sub-test, Animal Fluency test and Digit Symbol Substitution Test (DSST). For each cognitive test, people who scored lower than the lowest quartile in each age group were defined as having low cognitive performance. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance. RESULTS: A total of 2496 participants aged 60 years or older were included. In the full-adjusted model, the odds ratios (ORs) with 95% confidence interval (CI) of CERAD test score, Animal Fluency test score and DSST test score were 0.58 (0.38-0.88), 0.68 (0.47-0.99) and 0.59 (0.37-0.92) for the highest versus lowest tertile of dietary ω-3 fatty acids intake, respectively; the ORs with 95% CI of CERAD test score, Animal Fluency test score and DSST test score were 0.48 (0.31-0.75), 0.60 (0.40-0.92) and 0.50 (0.34-0.75) for the highest versus lowest tertile of dietary ω-6 fatty acids intake, respectively. The association between ω-6: ω-3 ratio and cognitive performance was not statistically significant in three tests. In dose-response relationship analysis, L-shaped associations were apparent for ω-3 and ω-6 fatty acids intake with CERAD test score, Animal Fluency test score and DSST test score. CONCLUSIONS: Dietary ω-3 and ω-6 fatty acids intake might be inversely associated with low cognitive performance.

A Novel Approach Based on Bipartite Network Recommendation and KATZ Model to Predict Potential Micro-Disease Associations.

Accumulating evidence indicates that the microbes colonizing human bodies have crucial effects on human health and the discovery of disease-related microbes will promote the discovery of biomarkers and drugs for the prevention, diagnosis, treatment, and prognosis of diseases. However clinical experiments of disease-microbe associations are time-consuming, laborious and expensive, and there are few methods for predicting potential microbe-disease association. Therefore, developing effective computational models utilizing the accumulated public data of clinically validated microbe-disease associations to identify novel disease-microbe associations is of practical importance. We propose a novel method based on the KATZ model and Bipartite Network Recommendation Algorithm (KATZBNRA) to discover potential associations between microbes and diseases. We calculate the Gaussian interaction profile kernel similarity of diseases and microbes based on validated disease-microbe associations. Then, we construct a bipartite graph and execute a bipartite network recommendation algorithm. Finally, we integrate the disease similarity, microbe similarity and bipartite network recommendation score to obtain the final score, which is used to infer whether there are some novel disease-microbe interactions. To evaluate the predictive power of KATZBNRA, we tested it with the walk length 2 using global leave-one-out cross validation (LOOV), two-fold and five-fold cross validations, with AUCs of 0.9098, 0.8463 and 0.8969, respectively. The test results also show that KATZBNRA is more accurate than two recent similar methods KATZHMDA and BNPMDA.

AGE-RELATED MACULAR DEGENERATION AND THE RISK OF ALL-CAUSE AND CARDIOVASCULAR MORTALITY: A Meta-Analysis of Cohort Studies.

PURPOSE: We evaluated the association between age-related macular degeneration (AMD) and the risk of all-cause and cardiovascular mortality by meta-analyses of data from prospective studies. METHODS: A literature search was performed in PubMed, Web of Science, Embase, Cocharne Library, and China National Knowledge Infrastructure for relevant articles published up to December 2016. We estimated hazard ratios with 95% confidence intervals with fixed-effect models and conducted meta-regression to explore the potential sources of heterogeneity. Small-study effect was estimated by Egger's test and funnel plot. RESULTS: We identified 13 population-based prospective cohort studies that examined the relationship between AMD and all-cause and cardiovascular mortality. Overall, the hazard ratios (95% confidence intervals) of all-cause mortality and cardiovascular mortality associated with any AMD were 1.15 (1.05-1.27) and 1.05 (95% confidence intervals: 0.87-1.26), respectively. The risk of all-cause mortality and cardiovascular mortality associated with early AMD were 1.08 (1.00-1.18) and 1.05 (0.89-1.24), and the associations with late AMD were 1.23 (1.11-1.36) and 1.28 (1.04-1.57), respectively. No evidence of small-study effect was found. CONCLUSION: This meta-analysis indicated that AMD, especially late AMD, was associated with increased risk of all-cause mortality and cardiovascular mortality based on comparisons with people who did not have AMD and who were of similar age and sex.

[Construction of recombinant adenovirus vector co-expressing VEGF165 and SDF-1 genes and its expression in ischemic cerebral tissue of rats].

OBJECTIVE: To construct a recombinant adenoviral vector carrying and co-expressing vascular endothelial growth factor 165 (VEGF165) and stromal cell derived factor 1 (SDF-1) and explore its co-expression in ischemic brain tissue in rats. METHODS: The VEGF165 and SDF-1 genes were directionally connected with internal ribosome entry site (IRES). And the double gene co-expression recombinant shuttle plasmid pDC316-VEGF165-IRES-SDF-1 was built with homologous recombination. The resultant plasmid pDC316-VEGF165-IRES-SDF-1 and backbone plasmid pBHGlox_E1, 3Cre were transfected into HEK293 cells by liposome and the recombinant adenoviral particles capable of infection were acquired. With the rounds of amplification, the purified adenoviral vector Ad5-VEGF165-IRES-SDF-1 was obtained with a titer of up to 1×10(10) IU/ml. The rat model of middle cerebral artery occlusion (MCAO) was established by intra-luminal suturing. And the viral vectors were transfused into the lateral ventricle by a stereotactic microinjection. The expressions of VEGF165 and SDF-1 in ischemic brain tissue were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: The results of PCR, double enzyme digestion and gene sequencing showed that both the recombinant plasmid and the constructed adenoviral vector were expressed. And the adenoviral vector Ad5-VEGF165-IRES-SDF-1 could mediate a co-expression of VEGF165 and SDF-1 in ischemic cerebral tissue. CONCLUSION: The recombinant adenoviral vector carrying VEGF165 and SDF-1 are successfully constructed. And Ad5-VEGF165-IRES-SDF-1 may mediate a co-expression of VEGF165 and SDF-1 in ischemic cerebral tissue of rats.

Recombinant adeno-associated virus serotype 1-vascular endothelial growth factor promotes neurogenesis and neuromigration in the subventricular zone and rescues neuronal function in ischemic rats.

OBJECTIVE: Vascular endothelial growth factor (VEGF) enhances neurogenesis in ischemic brains. However, in most circumstances, endogenous VEGF expression is limited and insufficient to prevent brain damage. We transferred the VEGF gene into brain tissue with recombinant adeno-associated virus serotype 1 (rAAV1) vectors and determined the effect of VEGF expression on neurogenesis and recovery of neurological function after brain ischemia. METHODS: Two groups (n = 32) of Sprague Dawley rats received intraventricular injection of AAV1-VEGF or AAV1-lacZ. Twenty-one days after gene transfer, rats underwent transient middle cerebral artery occlusion, and neurological severity score was measured 1, 2, 3, 7, 14, and 21 days later. Immunostaining was used to identify the quantity and distribution of VEGF expression. Double-immunofluorescence for doublecortin and bromodeoxyuridine or neuronal nuclei was performed to detect neurogenesis and the migration of neural progenitor cells. RESULTS: VEGF expression reduced the size of cerebral infarction and improved neurological function. It also enhanced the proliferation of neural progenitor cells in the subventricular zone and promoted their migration to the ischemic lesion. Neural precursors in the subgranular zone of the dentate gyrus were also increased; however, most of these cells did not move to the ischemic lesion and integrated with their region of origin. CONCLUSION: rAAV1-mediated expression of VEGF in the rat brain reduces the size of the infarcted lesion and promotes recovery of neurological function, likely by enhancing neurogenesis in the subventricular zone and promoting neural precursor migration to brain tissue around the core of the ischemic lesion.

Worldwide trends in dairy production and consumption and calcium intake: is promoting consumption of dairy products a sustainable solution for inadequate calcium intake?

BACKGROUND: Adequate calcium intake is critical for good health. Inadequate calcium intake is a worldwide problem and is more serious in countries where consumption of dairy products is low. OBJECTIVE: To analyze worldwide trends in production and consumption of dairy products and in calcium intake. METHODS: Data were taken from Food and Agriculture Organization food balance sheets, from published studies, and from surveys of four countries with large populations and large dairy production (China, India, the United States, and Russia). Linear regression models were fitted to estimate average annual changes and to project future trends. RESULTS: Overall global dairy production and supply (total and per capita) have increased since 1980, especially in developing countries. There are large between-region and between-country differences in the levels of production, supply, and consumption and in the trends. In 1997 India surpassed the United States to become the largest dairy producer. Consumption of dairy products in China has more than tripled since 1982 and has increased sevenfold among urban residents. The increase has been more dramatic during recent years. In spite of increases in dairy production and consumption in China and India, calcium intake has decreased in these countries. The average daily per capita consumption of dairy products was more than 200 g in the United States in 1999-2004 but less than 27g in China in 2002; the average daily per capita intake of calcium was 962 mg in US men and 756 mg in US women in 1999-2004, but less than 400 mg in China in 2002. CONCLUSIONS: Global production and supply of dairy products have been increasing since 1980, which has an impact on the environment. Dairy consumption and calcium intake remain low in most countries examined as compared with recommended amounts of dairy products and calcium. Promotion of consumption of dairy products does not necessarily increase total calcium intake.