Characterization of PYL gene family and identification of HaPYL genes response to drought and salt stress in sunflower.

In the context of global climate change, drought and soil salinity are some of the most devastating abiotic stresses affecting agriculture today. PYL proteins are essential components of abscisic acid (ABA) signaling and play critical roles in responding to abiotic stressors, including drought and salt stress. Although PYL genes have been studied in many species, their roles in responding to abiotic stress are still unclear in the sunflower. In this study, 19 HaPYL genes, distributed on 15 of 17 chromosomes, were identified in the sunflower. Fragment duplication is the main cause of the expansion of PYL genes in the sunflower genome. Based on phylogenetic analysis, HaPYL genes were divided into three subfamilies. Members in the same subfamily share similar protein motifs and gene exon-intron structures, except for the second subfamily. Tissue expression patterns suggested that HaPYLs serve different functions when responding to developmental and environmental signals in the sunflower. Exogenous ABA treatment showed that most HaPYLs respond to an increase in the ABA level. Among these HaPYLs, HaPYL2a, HaPYL4d, HaPYL4g, HaPYL8a, HaPYL8b, HaPYL8c, HaPYL9b, and HaPYL9c were up-regulated with PEG6000 treatment and NaCl treatment. This indicates that they may play a role in resisting drought and salt stress in the sunflower by mediating ABA signaling. Our findings provide some clues to further explore the functions of PYL genes in the sunflower, especially with regards to drought and salt stress resistance.

Changes in frailty and incident cardiovascular disease in three prospective cohorts.

BACKGROUND AND AIMS: Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, previous studies only focused on baseline frailty status, not taking into consideration the changes in frailty status during follow-up. The aim of this study was to investigate the associations of changes in frailty status with incident CVD. METHODS: This study used data of three prospective cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), and Health and Retirement Study (HRS). Frailty status was evaluated by the Rockwood frailty index and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty status at baseline and the second survey which was two years after the baseline. Cardiovascular disease was ascertained by self-reported physician-diagnosed heart disease (including angina, heart attack, congestive heart failure, and other heart problems) or stroke. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. RESULTS: A total of 7116 participants from CHARLS (female: 48.6%, mean age: 57.4 years), 5303 from ELSA (female: 57.7%, mean age: 63.7 years), and 7266 from HRS (female: 64.9%, mean age: 65.1 years) were included according to inclusion and exclusion criteria. The median follow-up periods were 5.0 years in the CHARLS, 10.7 years in the ELSA, and 9.5 years in the HRS. Compared with stable robust participants, robust participants who progressed to pre-frail or frail status had increased risks of incident CVD (CHARLS, HR = 1.84, 95% CI: 1.54-2.21; ELSA, HR = 1.53, 95% CI: 1.25-1.86; HRS, HR = 1.59, 95% CI: 1.31-1.92). In contrast, frail participants who recovered to robust or pre-frail status presented decreased risks of incident CVD (CHARLS, HR = 0.62, 95% CI: 0.47-0.81; ELSA, HR = 0.49, 95% CI: 0.34-0.69; HRS, HR = 0.70, 95% CI: 0.55-0.89) when compared with stable frail participants. These decreased risks of incident CVD were also observed in pre-frail participants who recovered to robust status (CHARLS, HR = 0.66, 95% CI: 0.52-0.83; ELSA, HR = 0.65, 95% CI: 0.49-0.85; HRS, HR = 0.71, 95% CI: 0.56-0.91) when compared with stable pre-frail participants. CONCLUSIONS: Different changes in frailty status are associated with different risks of incident CVD. Progression of frailty status increases incident CVD risks, while recovery of frailty status decreases incident CVD risks.

Exploration for the reference interval of C-reactive protein in the Chinese longevity people over 90 years of age.

BACKGROUND: Older individuals tend to develop chronic inflammation. As a commonly used nonspecific inflammatory marker, C-reactive protein (CRP) can predict metabolic syndrome, cardiovascular diseases, etc. However, little is known about CRP levels in longevity people. OBJECTIVES: Investigate the distribution and correlates of CRP and provide a reference for the establishment of normal interval values in Chinese longevity people over 90 years of age. METHODS: We performed a correlation analysis to evaluate the correlation between CRP levels and longevity based on the basic demographic characteristics, anthropometric measurements and blood data of 4,418 participants in the 2015 China Health and Retirement Longitudinal Study and 636 participants in an ongoing longitudinal study of natural longevity people in Guangxi. On this basis, the CRP reference interval for longevity was explored. RESULTS: The CRP concentration was significantly different among the three age groups, with a median of 3.80 mg/L for those older than 90 years, which was significantly higher than that for those aged 45-64 years (median 1.20 mg/L, p < 0.001) and 65-89 years (median 1.30 mg/L, p < 0.001). Body mass index, waist circumference, the waist-to-height ratio, systolic blood pressure, diastolic blood pressure, and fasting and postprandial blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol levels were positively correlated with CRP levels, while fasting high-density lipoprotein cholesterol was negatively correlated with CRP levels. The CRP reference interval (RI) value in longevity people was 0.25-9.22 mg/L. CONCLUSION: The concentrations of CRP increased with advancing age, and the CRP reference interval was different between older and younger adults.

Financing constraints and impact on corporate performance growth: Study in China listed logistics enterprises.

Based on 2010-2019 Chinese logistics listed companies as research samples, the paper used the binary Logit model measuring degree of financing constraints. The Kernel density function and Markov chain model are used to forecast China listed companies financing logistics dynamic constraints and business performance growth. Furthermore the stock of knowledge was chosen as a threshold variable to explore the impact of financing constraints on corporate performance growth of listed logistics enterprises. We find that the degree of financing constraints of logistics enterprises in our country has not been significantly eased. Corporate performance has not changed significantly and there are no obvious spatial gap and polarization with the passage of time. The impact of financing constraints on the corporate performance growth of logistics enterprises in China has a double threshold effect of knowledge stock, and has an inhibitory effect that first increases and then decreases. This is because in the short term, the investment of knowledge stock by enterprises can crowd out more corporate liquidity, and in the long run, it is related to the conversion rate of the knowledge stock itself. Because of the uneven regional distribution of resources and differences in the degree of economic development, there is a growing disincentive effect in central China as the stock of knowledge accumulates.

Predictive value of preoperative magnetic resonance imaging structural and diffusion indices for the results of trigeminal neuralgia microvascular decompression surgery.

PURPOSE: To explore the predictive value of preoperative magnetic resonance imaging structural and diffusion indices of the spinal trigeminal tract (SpTV) on the results of microvascular decompression (MVD) in patients with trigeminal neuralgia (TN). METHODS: This retrospective study included patients diagnosed with TN and treated with MVD in the Jining First People's Hospital between January 2020 and January 2021. The patients were divided into good and poor results groups according to postoperative pain relief. Logistic regression analysis was performed to explore independent risk factors for poor results of MVD, and their predictive value was examined using receiver operating characteristic (ROC) curves. RESULTS: A total of 97 TN cases were included, 24 cases with a poor result and 73 with a good result. They were comparable in demographic characteristics. Fractional anisotropy (FA) was lower (P < 0.001), and radial diffusivity (RD) was higher (P < 0.001) in the poor result group compared to the good result group. Patients in the good result group showed a higher proportion of grade 3 neurovascular contact (NVC) (39.7% vs. 16.7%, P = 0.001) and a lower RD (P < 0.001). The multivariate analysis showed that the RD of SpTV (OR = 0.000016, 95% CI: 0.000-0.004, P < 0.001) and NVC (OR = 8.07, 95% CI: 1.67-38.93, P = 0.009) were independently associated with poor results. The area under the curve (AUC) of RD and NVC were 0.848 and 0.710, and their combination achieved an AUC of 0.880. CONCLUSION: NVC and RD of SpTV are independent risk factors for poor results after MVD surgery, and combining the NVC and RD might achieve relatively high predictive value for poor results.

The relationship between sleep duration and activities of daily living (ADL) disability in the Chinese oldest-old: A cross-sectional study.

Objective: To investigate the relationship between sleep duration and activities of daily living (ADL) disability, and to explore the optimal sleep duration among oldest-old Chinese individuals. Methods: In this cross-sectional study, 1,798 participants (73.2% female) were recruited from Dongxing and Shanglin in Guangxi Zhuang Autonomous Region, China in 2019. The restricted cubic spline function was used to assess the dose-response relationship between sleep duration and ADL disability, and the odds ratios (ORs) of the associations were estimated by logistic regression models. Results: The overall prevalence of ADL disability was 63% (64% in females and 58% in males). The prevalence was 71% in the Han population (72% in females and 68% in males), 60% in the Zhuang population (62% in females and 54% in males) and 53% in other ethnic population (53% in females and 53% in males). A nonlinear relationship between sleep duration and ADL disability was observed. Sleep duration of 8-10 hours was associated with the lowest risk of ADL disability. Sleep duration (≥12 hours) was associated with the risk of ADL disability among the oldest-old individuals after adjusting for confounding factors (OR = 1.47, 95% CI [1.02, 2.10], p < 0.05). Conclusion: Sleep duration more than 12 hours may be associated with an increased risk of ADL disability in the oldest-old individuals, and the optimal sleep duration among this population could be 8-10 h.

The general law of plasma proteome alterations occurring in the lifetime of Chinese individuals reveals the importance of immunity.

BACKGROUND: Aging is characterized by a continuous loss of protein homeostasis. A closer examination of peripheral blood, which houses proteins from nearly all tissues and cells, helped identify several biomarkers and other aspects of aging biology. To further explore the general law of aging and identify key time nodes and associated aging biology, we collected 97 plasma samples from 253 healthy individuals aged 0-100 years without adverse outcomes to conduct nano-Ultra High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (nano-UHPLC-MS/MS) and weighted gene co-expression network analysis (WGCNA). RESULTS: Through biological processes and key biological pathways identified in discrete age group modules, our analyses highlighted a strong correlation between alterations in the immune system and aging process. We also identified hub genes associated with distinct age groups that revealed alterations not only in protein expression but also in signaling cascade. Among them, hub genes from age groups of 0-20 years old and 71-100 years old are mostly involved in infectious diseases and the immune system. In addition, CDC5L and HMGB2 were the key transcription factors (TFs) regulating genes expression in people aged between 51-60 and 71-100 years of age. They were shown to not only be independent but also mutually regulate certain hub gene expressions. CONCLUSIONS: This study reveals that the plasma proteome undergoes a complex alteration over the lifetime of a human. In this process, the immune system is crucial throughout the lifespan of a human being. However, the underlying mechanism(s) regulating differential protein expressions at distinct ages remains to be elucidated.

Plasma neurofilament light chain: A biomarker predicting severity in patients with acute ischemic stroke.

Neurofilament light chain (NfL) levels have proved to be a good biomarker in cerebrospinal fluid (CSF) correlating with the degree of neuronal injury and neurodegeneration. However, little is known about the value of plasma neurofilament light chain (pNfL) levels in predicting the clinical prognosis of patients with acute cerebral infarction. This study aimed to explore whether pNfL could be used as a biomarker to predict the severity of the outcomes of acute ischemic stroke (AIS). Patients with AIS were included from the Department of Neurology of the First People's Hospital of Bengbu City from January 2018 to May 2019, as well as health control (HC). The plasma levels of NfL in patients with AIS (n = 60) at 2 days, 7 days, and 6 months after stroke, as well as in HCs (n = 60) were measured by electrochemiluminescence immunoassay(ECL) on the Meso Scale Discovery platform. Stroke severity was analyzed at admission using the National Institutes of Health Stroke Scale score. Functional outcomes were assessed at different times using the modified Rankin Scale (mRS) and Barthel Index. The mean level of pNfL in patients with ischemic stroke (IS) at 2 days (225.86 pg/L) after stroke was significantly higher than that in HC (107.02 pg/L) and gradually increased 7 days after stroke (316.23 pg/L) (P < .0001). The mean level of pNfL in patients with IS at 6 months after stroke was 173.38 pg/L, which was still significantly higher than that of HC. The levels of pNfL at 7 days after stroke independently predicted modified Rankin Scale scores (mRS) (R = 0.621, P < .001), Barthel Index (R = -0.716, P < .001), and National Institutes of Health Stroke Scale (R = -0.736, P < .001). The diagnostic severity and prognosis were evaluated by ROC curve, an area under the receiver operator curve of 0.812 (P = .001, 95% CI: 0.69-0.93) at 7 days. Plasma NfL levels reflect neuronal injury after AIS. It changes with time and has a certain relationship with prognosis and may be a promising biomarker for predicting the severity of neuroaxonal injury in patients with acute IS.

TMEM97 is transcriptionally activated by YY1 and promotes colorectal cancer progression via the GSK-3ß/ß-catenin signaling pathway.

Transmembrane protein 97 (TMEM97) is a conserved integral membrane protein highly expressed in various human cancers, including colorectal cancer (CRC), and it exhibits pro-tumor roles in breast cancer, gastric cancer, and glioma. However, whether TMEM97 participates in CRC progression is not fully understood. The expression of mRNA and protein was evaluated by real-time qPCR, western blotting, immunofluorescent, and immunohistochemical staining. TMEM97 functions in cell proliferation, apoptosis, migration, and invasion were assessed by CCK-8, flow cytometry, and transwell assays. The roles of TMEM97 in CRC cells in vivo was investigated using a subcutaneous xenograft model. The transcriptional regulation of TMEM97 was explored by luciferase reporter and ChIP assays. The silencing of TMEM97 inhibited migration and invasion of CRC cells in vitro and led to suppressed growth and enhanced apoptosis in CRC cells and xenografts, whereas overexpression of TMEM97 displayed opposite effects. Mechanistically, TMEM97 knockdown caused a reduction of the proliferating marker PCNA and an increase of pro-apoptotic proteins (cleaved caspase 8/3/7 and cleaved PARP) in CRC cells. TMEM97 also positively regulated the ß-catenin signaling pathway in CRC cells and xenografts by modulating the phosphorylated-GSK-3ß and active (non-phospho) ß-catenin levels. Interestingly, YY1, a well-recognized oncogenic transcription factor, was identified to bind to the TMEM97 promoter and enhance its transcriptional activity, and silencing of TMEM97 abolished YY1-mediated pro-tumor effects on CRC cells. Our results suggest that TMEM97 is transcriptionally activated by YY1 and promotes CRC progression via the GSK-3ß/ß-catenin signaling pathway, providing that TMEM97 might be a novel therapeutic target for preventing CRC development.

The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment.

Type 2 diabetes mellitus (T2DM) is a classic metaflammatory disease, and the inflammatory states of the pancreatic islet and insulin target organs have been well confirmed. However, abundant evidence demonstrates that there are countless connections between these organs in the presence of a low degree of inflammation. In this review, we focus on cell-cell crosstalk among local cells in the islet and organ-organ crosstalk among insulin-related organs. In contrast to that in acute inflammation, macrophages are the dominant immune cells causing inflammation in the islets and insulin target organs in T2DM. In the inflammatory microenvironment (IME) of the islet, cell-cell crosstalk involving local macrophage polarization and proinflammatory cytokine production impair insulin secretion by ß-cells. Furthermore, organ-organ crosstalk, including the gut-brain-pancreas axis and interactions among insulin-related organs during inflammation, reduces insulin sensitivity and induces endocrine dysfunction. Therefore, this crosstalk ultimately results in a cascade leading to ß-cell dysfunction. These findings could have broad implications for therapies aimed at treating T2DM.

Inclisiran inhibits oxidized low-density lipoprotein-induced foam cell formation in Raw264.7 macrophages via activating the PPARγ pathway.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a well-known proprotein convertase that influences foam cell formation and modulates atherosclerosis. Inclisiran is a novel chemosynthetic small interfering RNA that inhibits PCSK9 synthesis. This study aimed to explore the effect of inclisiran on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation in Raw264.7 macrophages and to investigate the underlying mechanisms. Raw264.7 cells were treated with ox-LDL to induce the formation of macrophage-derived foam cells. Oil Red O staining and high-performance liquid chromatography were performed to detect lipid accumulation and cholesterol levels. Dil-ox-LDL uptake assay, CCK-8, RT-qPCR, and Western blotting analysis were performed to examine ox-LDL uptake, cell viability, and expression of scavenger receptor-related factors. Inclisiran reduced lipid accumulation in ox-LDL-treated macrophages in a dose-dependent manner. Inclisiran significantly inhibited the levels of total cholesterol, free cholesterol, and cholesterol ester in the supernatant of Raw264.7 cells. Inclisiran reduced ox-LDL uptake and increased Raw264.7 cell viability. Meanwhile, inclisiran downregulated the expression of SR-A, LOX-1, and CD36 and upregulated SR-BI, ApoE, and ABCA1. Furthermore, inclisiran increased PPARγ activity and decreased NF-κB activity. An inhibitor of PPARγ (T0070907) reversed the beneficial effects of inclisiran on ox-LDL uptake, NF-κB inactivation, and cytokine expression. In conclusion, these data suggested that inclisiran inhibited the formation of macrophage-derived foam cells by activating the PPARγ pathway.HighlightsInclisiran reduces lipid accumulation in Raw264.7 cells;Inclisiran reduces ox-LDL uptake and increases Raw264.7 cell viability;Inclisiran inhibits foam cell formation by activating the PPARγ pathway.

Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis.

Genes related to human longevity have not been studied so far, and need to be investigated thoroughly. This study aims to explore the relationship among ABO gene variants, lipid levels, and longevity phenotype in individuals (≥90yrs old) without adverse outcomes. A genotype-phenotype study was performed based on 5803 longevity subjects and 7026 younger controls from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Four ABO gene variants associated with healthy longevity (rs8176719 C, rs687621 G, rs643434 A, and rs505922 C) were identified and replicated in the CLHLS GWAS data analysis and found significantly higher in longevity individuals than controls. The Bonferroni adjusted p-value and OR range were 0.013-0.020 and 1.126-1.151, respectively. According to the results of linkage disequilibrium (LD) analysis, the above four variants formed a block on the ABO gene (D'=1, r2range = 0.585-0.995). The carriers with genotypes rs687621 GG, rs643434 AX, or rs505922 CX (prange = 2.728 x 10-107-5.940 x 10-14; ORrange = 1.004-4.354) and haplotype CGAC/XGXX (p = 2.557 x 10-27; OR = 2.255) had a substantial connection with longevity, according to the results of genetic model analysis. Following the genotype and metabolic phenotype analysis, it has been shown that the longevity individuals with rs687621 GG, rs643434 AX, and rs505922 CX had a positive association with HDL-c, LDL-c, TC, TG (prange = 2.200 x 10-5-0.036, ORrange = 1.546-1.709), and BMI normal level (prange = 2.690 x 10-4-0.026, ORrange = 1.530-1.997). Finally, two pathways involving vWF/ADAMTS13 and the inflammatory markers (sE-selectin/ICAM1) that co-regulated lipid levels by glycosylation and effects on each other were speculated. In conclusion, the association between the identified longevity-associated ABO variants and better health lipid profile was elucidated, thus the findings can help in maintaining normal lipid metabolic phenotypes in the longevity population.

Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and meta-analysis.

Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I2 statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09-2.42], Phet = 0.377, Pz = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07-3.83], Phet = 0.085, Pz = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43-3.02], Phet < 0.001, Pz < 0.001) and in EA (OR = 2.01, 95% CI [1.53-2.66], Phet = 0.541, Pz < 0.001). Moreover, stratification by ethnicity revealed that IL-1B (-511) was associated with a decreased risk of T2DM in the dominant model (OR=0.76, 95% CI [0.59-0.97], Phet = 0.218, P z = 0.027) and codominant model (OR = 0.73, 95% CI [0.54-0.99], Phet = 0.141, Pz = 0.040) in the East Asian (EA) subgroup. Our results suggest that the IL-1RN 2* allele and 2*2* homozygous polymorphism are strongly associated with increasing T2DM risk and that the IL-1B (-511) T allele polymorphism is associated with decreasing T2DM risk in the EA subgroup.

Investigation of the Reference Interval Values of Fasting Plasma Glucose, Blood Pressure, and Blood Lipids in the Longevity People Aged 90 Years Old and Above.

PURPOSE: To our knowledge, the normal fasting plasma glucose (FPG), blood pressure (BP), and blood lipids (BL) interval values have not been well-established in the longevity population. This study aims to provide a reference for the establishment of normal BP, FPG, and BL interval values in the longevity people in China. PATIENTS AND METHODS: A total of 7417 people were selected from the natural longevity cohort in Guangxi, with an age range of 20-110 years old, including 7093 classified as the non-longevity (20-89 years old) (94.02%) and 324 classified as the longevity (≥90 years old) (5.98%); there were 4309 men (58.1%) and 3108 women (41.9%). FPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels were defined as desirable levels when they were below the 75th percentile (P75), borderline levels from the 75th to 90th percentile (P75-P90), and high levels above P90; triglyceride (TG) levels above P90 were defined as high; and high-density lipoprotein cholesterol (HDL-C) levels below the 5th percentile (P5) were defined as low levels. RESULTS: The reference interval values of FPG in the longevity were as follows: desirable levels <6.15 mmol/L, borderline levels 6.15-7.45 mmol/L, high levels ≥7.45 mmol/L. Reference interval values of systolic blood pressure (SBP) were as follows: desirable levels <160.00 mmHg, borderline levels 160.00-174.50 mmHg, high levels ≥175.00 mmHg. DBP reference interval values were as follows: desirable levels <88.00 mmHg, borderline levels 88.00-90.00 mmHg, high levels ≥90.00 mmHg. TC reference interval values were as follows: desirable levels <5.59 mmol/L, borderline levels 5.59-6.45 mmol/L, high levels ≥6.45 mmol/L. LDL-C reference interval values were as follows: desirable levels <3.30 mmol/L, borderline levels 3.30-3.85 mmol/L, high levels ≥3.85 mmol/L. TG reference interval values were as follows: desirable levels <2.82 mmol/L, high levels ≥2.82 mmol/L. HDL-C reference interval values were as follows: low levels <0.80 mmol/L, desirable levels ≥0.80 mmol/L. CONCLUSION: The reference interval values of BP, FPG, and BL are different between the longevity population and the non-longevity population, and the interval values change with increasing age.

A description of the relationship in healthy longevity and aging-related disease: from gene to protein.

Human longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer's disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

Copper exposure association with prevalence of non-alcoholic fatty liver disease and insulin resistance among US adults (NHANES 2011-2014).

BACKGROUND: Excessive copper (Cu) has risky effect on insulin resistance (IR), oxidative stress and inflammation. Instead, some studies reported serum Cu to be protective for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to reevaluate the evidence for a potential risky correlation of serum Cu to NAFLD in large-scale and non-institutionalized American subjects. METHODS: A cross-sectional study of 3211 subjects was from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and cubic spline-based curve-fitting analyses were used to estimate the independent risky effect of Cu to hepatic steatosis index (HSI), US fatty liver index (USFLI) and NAFLD and their dose-effect relationship. Moreover, this association was analyzed in stratification of HOMA-IR, Metabolic syndrome (MetS) and severity of NAFLD, besides age and gender. RESULTS: The average level of serum Cu was 18.67 µmol/L and the prevalence of NAFLD was 54.53% and 32.60%, respectively defined by HSI and USFLI. Generally, the level of Cu was higher in females than males. Serum Cu was positively associated with higher HSI, USFLI index and risk of NAFLD. In fully adjusted models, compared with the lowest quartile, the risk of NAFLD increased 97% in the highest quartile of Cu. Interestingly, stratified analysis showed that the risky effect of Cu to NAFLD was more prominent in the middle-aged, females and subjects with improved status of IR (lower HOMA-IR and non-Mets) compared with their counterparts. Moreover, we further found that circulating copper was correlated to severity of NAFLD only in males. CONCLUSION: Excess serum Cu is significantly associated with risk of NAFLD, which is prominent in females, middle-aged and subjects with improved status of IR, and seems to be related to the severity of NAFLD, additionally. It is necessary to be cautious of the toxic effect of Cu and prospective cohort and mechanism studies are needed to verify the causal effect of Cu to NAFLD.

Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective.

Patients with type-2 diabetes mellitus (T2DM) display chronic low-grade inflammation induced by activation of the innate immune system. Toll-like receptor (TLR)4 is a pattern recognition receptor that plays a vital part in activation of the innate immune system. Results from animal and computer-simulation studies have demonstrated that targeting TLR4 to block the TLR4-nuclear factor-kappa B (NF-κB) pathway reduces the inflammatory response and complications associated with T2DM. Therefore, TLR4-targeted therapy has broad prospects. Here, we reviewed the role of TLR4 in inflammation during chronic hyperglycemia in T2DM and its therapeutic prospects.

iTRAQ-based proteome profiling of hyposaline responses in zygotes of the Pacific oyster Crassostrea gigas.

Low salinity treatment is proven to be the practical polyploidy inducing method for shellfish with advantages of lower cost, higher operability and reliable food security. However, little is known about the possible molecular mechanism of hypotonic induction. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) based proteomic profiling was pursued to investigate the responses of zygotes of the Pacific oyster Crassostrea gigas to low salinity. A total of 2235 proteins were identified and 87 proteins were considered differentially expressed, of which 14 were up-regulated and 69 were down-regulated. Numerous functional proteins including ADP ribosylation factor 2, DNA repair protein Rad50, splicing factor 3B, tubulin-specific Chaperone D were significantly changed in abundance, and were involved in various biology processes including energy generation, vesicle trafficking, DNA/RNA/protein metabolism and cytoskeleton modification, indicating the prominent modulation of cell division and embryonic development. Parallel reaction monitoring (PRM) analyses were carried out for validation of the expression levels of differentially expressed proteins (DEPs), which indicated high reliability of the proteomic results. Our study not only demonstrated the proteomic alterations in oyster zygotes under low salinity, but also provided, in part, clues to the relatively lower hatching rate and higher mortality of induced larvae. Above all, this study presents a valuable foundation for further studies on mechanisms of hypotonic induction.

Differential expression profiles of microRNAs in highly and weakly invasive/metastatic pancreatic cancer cells.

Pancreatic cancer is the eighth-leading cause of cancer-associated mortality worldwide. To date, the cellular and molecular mechanisms associated with the invasion and metastasis of pancreatic cancer remain unclear. To examine these mechanisms, a microRNA (miRNA/miR) microarray with 1,965 genes was hybridized with labeled miRNA probes from invasive PC-1.0 and non-invasive PC-1 cells for molecular profiling analysis. In addition, reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was utilized to validate the microarray results. Online miRNA target prediction algorithms online were used to predict the target genes of the differentially expressed miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) term enrichment analysis were performed for the potential targets of the differentially expressed miRNAs. The results demonstrated that 54 miRNAs were differentially expressed, of which 33 were upregulated and 21 were downregulated in the PC-1.0 cell line compared with the PC-1 cell line. A total of 6 upregulated miRNAs (miR-31, -34a, -181a, -181b, -193a-3p, and -193b) and 4 downregulated miRNAs (miR-221, -222, -484, and -502-3p) were selected from these 54 miRNAs and validated by RT-qPCR. The differentially expressed miRNAs were further validated by RT-qPCR in the human pancreatic cancer cell lines AsPC-1 (highly invasive) and CAPAN-2 (less invasive). The results revealed that 2 upregulated miRNAs (miR-34a and -193a-3p) and 4 downregulated miRNAs (miR-221, -222, -484, and -502-3p) exhibited a consistent expression pattern between the PC-1.0/PC-1 and AsPC-1/CAPAN-2 pancreatic cancer cells. The GO and KEGG enrichment analysis indicated that the mRNAs potentially targeted by miRNAs were involved in a range of biological functions. These results suggest that different miRNA expression profiles occur between highly and weakly invasive and metastatic pancreatic cancer cell lines, and may affect a variety of biological functions in pancreatic cancer.

Transcriptomic analysis of Crassostrea sikamea × Crassostrea angulata hybrids in response to low salinity stress.

Hybrid oysters often show heterosis in growth rate, weight, survival and adaptability to extremes of salinity. Oysters have also been used as model organisms to study the evolution of host-defense system. To gain comprehensive knowledge about various physiological processes in hybrid oysters under low salinity stress, we performed transcriptomic analysis of gill tissue of Crassostrea sikamea ♀ × Crassostrea angulata♂ hybrid using the deep-sequencing platform Illumina HiSeq. We exploited the high-throughput technique to delineate differentially expressed genes (DEGs) in oysters maintained in hypotonic conditions. A total of 199,391 high quality unigenes, with average length of 644 bp, were generated. Of these 35 and 31 genes showed up- and down-regulation, respectively. Functional categorization and pathway analysis of these DEGs revealed enrichment for immune mechanism, apoptosis, energy metabolism and osmoregulation under low salinity stress. The expression patterns of 41 DEGs in hybrids and their parental species were further analyzed by quantitative real-time PCR (qRT-PCR). This study will serve as a platform for subsequent gene expression analysis regarding environmental stress. Our findings will also provide valuable information about gene expression to better understand the immune mechanism, apoptosis, energy metabolism and osmoregulation in hybrid oysters under low salinity stress.