SlBEL11 regulates flavonoid biosynthesis, thus fine-tuning auxin efflux to prevent premature fruit drop in tomato.

Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.

Enhanced photocatalytic ammonia oxidation activity and nitrogen selectivity over Ag/AgCl/N-TiO2 photocatalyst.

The removal of ammonia (NH3) emitted from agricultural and industrial activities is of great significance to protect human health and ecological environment. Photocatalytic NH3 oxidation to N2 under mild conditions is a promising strategy. However, developing visible light photocatalysts for NH3 oxidation is still in its infancy. Here, we fabricate N-TiO2 and Ag/AgCl/N-TiO2 photocatalysts by sol-gel and photodeposition methods, respectively. The introduction of N not only endows TiO2 with visible light response (absorption edge at 460 nm) but also results in the formation of heterophase junction (anatase and rutile). Thus, N-TiO2 shows 2.0 and 1.8 times higher than those over anatase TiO2 and commercial TiO2 for NH3 oxidation under full spectrum irradiation. Meanwhile, surface modification of Ag can simultaneously enhance visible light absorption (generating localized surface plasmon resonance effect) and charge separation efficiency. Therefore, the photocatalytic activity of Ag/AgCl/N-TiO2 is further improved. Furthermore, the presence of N and Ag also enhances the selectivity of N2 product owing to the change of reaction pathway. This work simultaneously regulates photocatalytic conversion efficiency and product selectivity, providing some guidance for developing highly efficient photocatalysts for NH3 elimination.

Prevalence and characteristics of comorbid stroke and traumatic brain injury in a real-world population: findings from a nationally representative cross-sectional survey in China.

BACKGROUND: In China, data on the prevalence and characteristics of comorbid stroke and traumatic brain injury (TBI) in real-world populations are still lacking but of paramount importance for the evidence-based prevention and control of the comorbidity of the two diseases. This study aimed to investigate the prevalence and characteristics of comorbid stroke and TBI in a real-world population. METHODS: In 2013, a nationally representative, door-to-door survey on stroke and TBI using a complex, multistage, probability sampling design was conducted among approximately 600,000 participants from 155 urban and rural areas in China (Ethic ID: KY2013-006-01). The weighted prevalence of comorbid stroke and TBI was estimated using individuals' final weight. A Poisson regression analysis was used to compare the rate ratio of the comorbidity prevalence among different subgroups of the population, including age, sex, place of residence, and geographic location subgroups. For analyses of associations between the comorbidities and predictors of interest, all other variables were adjusted for in a multinomial logistic regression model. RESULTS: Among the 596,536 people, 219 patients with comorbid stroke and TBI were identified. The point prevalence of comorbid stroke and TBI weighted to the China 2010 census population was 29.30 (95% CI: 22.69-37.84) per 100,000 population in China. The adjusted prevalence of post-TBI stroke in patients with previous TBI was significantly higher than that of post-stroke TBI in patients with previous stroke (6021.3 vs. 811.1 per 100,000 people; rate ratio: 11.001; 95% CI: 8.069-14.998). Patients with nonconcussion had significantly higher rates of both pre-stroke TBI (odds ratio: 4.694; 95% CI: 3.296-6.687) and post-stroke TBI (odds ratio: 6.735; 95% CI: 3.719-12.194) than patients with concussion. Compared to patients with ischaemic stroke, patients with subarachnoid haemorrhage (odds ratio: 2.044; 95% CI: 1.097-3.809) and intracerebral haemorrhage (odds ratio: 1.903; 95% CI: 1.296-2.795) had significantly higher rates of post-TBI stroke. CONCLUSIONS: The high prevalence of stroke among TBI patients is becoming a new public health issue. TBI patients, especially those with nonconcussion TBI, are more likely to develop comorbid stroke and TBI than stroke patients, especially ischaemic stroke patients.

Needs and views on healthy lifestyles for the prevention of dementia and the potential role for mobile health (mHealth) interventions in China: a qualitative study.

OBJECTIVES: Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study. DESIGN: Qualitative semi-structured interview study, using thematic analysis. SETTING: Primary and secondary care in Beijing and Tai'an, China. PARTICIPANTS: Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes. RESULTS: We performed 26 interviews with participants aged 55-86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional. CONCLUSIONS: The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD. TRIAL REGISTRATION NUMBER: ISRCTN15986016; Pre-results.

A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.

Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.

Mortality due to primary brain tumours in China and detection rate in people with suspected symptoms: a nationally representative cross-sectional survey.

BACKGROUND AND PURPOSE: Epidemiological data on primary brain tumours (PBTs) are lacking due to the difficulty in case ascertainment among the population. Thus, we aimed to estimate mortality due to PBTs in China nationwide and the detection rate in people with suspected symptoms. METHODS: A multistage, complex sampling survey regarding mortality due to PBTs in Chinese individuals was carried out by reviewing all causes of death within a year. The detection rates in people with suspected symptoms were estimated based on PBT symptom screening and neurologist reviews and compared between groups by logistic regression analysis. RESULTS: Weighted mortality due to PBT was 1.6 (0.8-3.3) per 100,000 population in Chinese individuals, 1.8 (0.7-4.6) per 100,000 population in men, and 1.5 (0.5-4.5) per 100,000 population in women. Among 14,990 people with suspected symptoms, the PBT detection rate was 306.9 (95% CI 224.7-409.3) per 100,000 population in the total population, 233.0 (95% CI 135.7-373.1) per 100,000 population in men, and 376.9 (95% CI 252.4-546.3) per 100,000 population in women. People with an unsteady gait (OR 2.46; 95% CI 1.09-5.51; P=0.029), visual anomalies (3.84; 1.88-7.85; P<0.001), and headache (2.06; 1.10-3.86; P=0.023) were more likely to have a brain tumour than those without corresponding symptoms, while people with dizziness/vertigo were less likely to have a brain tumour than those without corresponding symptoms (0.45; 0.23-0.87; P=0.017). CONCLUSIONS: Mortality due to PBT in China was low, with a nationwide estimate of 21,215 (10,427-43,165) deaths attributable to PBTs annually. However, the detection rate of PBTs can be greatly improved based on symptom screening in the population.

Prevalence, Incidence, and External Causes of Traumatic Spinal Cord Injury in China: A Nationally Representative Cross-Sectional Survey.

BACKGROUND AND PURPOSE: The epidemiological characteristics of traumatic spinal cord injury (TSCI) in China are unclear. Thus, we aimed to study prevalence, incidence, and external causes of TSCI in China nationwide. METHODS: In 2013, we conducted a nationally representative, door-to-door epidemiological survey on TSCI in China using a complex, multistage, probability sampling design. RESULTS: In China, the point prevalence of TSCI standardized to the China census population 2010 was 569.7 (95% CI: 514.2-630.4) per 1,000,000 in the population, 753.6 (95% CI: 663.3-854.3) per 1,000,000 among men, and 387.7 (95% CI: 324.8-461.1) per 1,000,000 among women. The incidence of TSCI standardized to the China census population 2010 was 49.8 (95% CI: 34.4-70.7) per 1,000,000 per year in the population, 63.2 (95% CI: 38.9-98.5) per 1,000,000 among men, and 36.9 (95% CI: 19.5-65.9) per 1,000,000 among women. Among the 415 TSCI events in 394 prevalent cases, the top three injury causes were falls (55.2%), motor vehicle collisions (MVCs) (26.5%), and strike injuries (10.1%), while other injury causes including gunshot and explosion accounted for 8.2%. Among the 394 prevalent cases, the mean age of patients at the time of injury was 43.7 ± 17.1 years; the male-to-female ratio was 1.86:1. CONCLUSION: It is estimated that there are 759,302 prevalent patients with TSCI in total and 66,374 new TSCI cases annually in China. Falls and MVCs are still 2 major external causes for TSCI in China.

Modelling biological age based on plasma peptides in Han Chinese adults.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis.

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58-0.84; P < 0.01), whereas carriers of ε4 allele were of increased risk of AD (OR = 3.62; 95% CI: 3.03-4.32; P < 0.05), compared to these of ε3 allele. Circulating TC was significantly reduced in carriers of ε2 allele (WMD = - 0.29 mmol/L; 95% CI: -0.54 to -0.03; P < 0.05) and increased in carriers of ε4 allele (WMD = 0.42 mmol/l; 95% CI: 0.001-0.84; P < 0.05). In addition, carriers of ε4 allele had reduction in circulating HDL-C (WMD = - 0.04 mmol/L; 95% CI: - 0.07 to -0.001; P < 0.05). In comparing allele ε2 with ε3, the predicted OR of having AD for 1 mg/dL increment in circulating TC was 0.97 (95% CI: 0.86-0.98; P < 0.05). Comparing allele ε4 with ε3, the predicted OR for a 1 mg/dL increment in TC was 1.08 (95% CI: 1.05-17.58; P < 0.05), and reduction in HDL-C was 2.30 (95% CI: 1.51-43.99; P < 0.05). Our findings demonstrate that high circulating TC and reduced HDL-C levels might be potential risk factors of the development of AD.

Annual rates of and factors influencing inpatient and outpatient transient ischaemic attacks in Chinese population: a nationally representative cross-sectional survey.

OBJECTIVES: To investigate the rates and influencing factors of transient ischaemic attack (TIA) inpatient admissions and outpatient visits in China. SETTING: A door-to-door survey of 178 059 families from 155 urban and rural areas in 31 provinces in China, 2013. PARTICIPANTS: Total 596 536 people were assessed in the annual rate analysis, and 829 TIA patients were assessed in the influencing factor analysis. MAIN OUTCOME MEASURES: The weighted annual rates of TIA inpatient admissions and outpatient visits and the factors influencing inpatient admissions and outpatient visits for TIA patients. RESULTS: The weighted annual inpatient admission rate per TIA patient was 25.8 (95% CI: 18.4 to 36.2) per 100 000 in the population, whereas the weighted annual inpatient admission rate for patients with TIAs was 32.5 (95% CI: 23.3 to 38.9) per 100 000 in the population. The weighted annual outpatient visit rate per TIA patient was 34.4 (95% CI: 26.2 to 45.1) per 100 000 in the population, whereas the weighted annual outpatient visit rate for patients with TIAs was 149.6 (95% CI: 127.0 to 165.5) per 100 000. The inpatient rate was higher for men than for women (OR: 2.24; 95% CI: 1.40 to 3.59; p=0.001), for TIA patients with stroke than for patients with isolated TIAs (2.93; 2.01 to 4.25; p<0.001), for TIA patients with hypertension than for TIA patients without hypertension (2.60; 1.65 to 4.11; p<0.001). The outpatient rate was higher for TIA patients with stroke than for patients with isolated TIAs (1.88; 1.33 to 2.64; p<0.001), for TIA patients with dyslipidaemia than for TIA patients without dyslipidaemia (1.92; 1.30 to 2.83; p=0.001). CONCLUSIONS: The annual rates of TIA inpatient admissions and outpatient visits in population are low, probably due to the lack of access to inpatient and outpatient services experienced by the majority of TIA patients in the population, and individuals' socio-demographic characteristics, disease histories and stroke prognosis may be associated with inpatient and outpatient TIAs.

Jidong cognitive impairment cohort study: objectives, design, and baseline screening.

The risk of dementia increases in patients with cognitive impairment. However, it is not clear what factors contribute to the onset of dementia in those with cognitive impairment. In this prospective cohort study, we will investigate the every-five-year incidence of cognitive impairment and prognostic factors for cognitive impairment. The Jidong cognitive impairment cohort was established from April 2012 to August 2015, during which we recruited 5854 healthy participants (55.1% male) older than 45 years (mean, 57 years). Participants received a health examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Cognitive impairment was evaluated using the Mini-Mental State Examination, and was defined as a Mini-Mental State Examination score of less than 24. Dementia was assessed using the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth edition), the International Working Group criteria, and the Mini-Mental State Examination score. The follow-up will continue until December 2024, during which a prognostic model will be constructed. The primary outcome is the presence/absence of dementia and the secondary outcome is quality of life. Baseline screening results showed the following: (1) Cognitive impairment was apparent in 320 participants (5.5%). These participants will be excluded from the Jidong cohort study, and the remaining participants will be followed up. (2) Of the 320 participants with cognitive impairment, there was a significantly higher prevalence of illiteracy than other education levels (35.9%, P < 0.05). Age, arterial hypertension, alcohol consumption, and passive smoking differed significantly between the cognitive impairment and healthy groups (P < 0.05). Multivariate logistic regression models showed that age (odds ratio [OR] = 1.059, 95% confidence interval [CI]: 1.044-1.074) and arterial hypertension (OR = 1.665, 95% CI: 1.143-2.427) were risk factors for mild cognitive impairment. With the increase of educational level (illiteracy, primary school, junior high school, high school, university, and above), cognitive impairment gradually decreased (OR < 1, P < 0.05). (3) This cohort study has initially screened for several risk factors for cognitive impairment at baseline, and subsequent prospective data will further describe, validate, and evaluate the effects of these risk factors on cognitive impairment and dementia. These results can provide clinical evidence for the early prevention of cognitive impairment and dementia. The study was approved by the Ethics Committee of Kailuan General Hospital of Tangshan City and the Medical Ethics Committee, Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation on July 12, 2013 (approval No. 2013 YILUNZI 1).

GeographicalDifference, Rural-urban Transition and Trend in Stroke Prevalence in China: Findings from a National Epidemiological Survey of Stroke in China.

Accurate and up-to-date provincial and regional-level stroke prevalence estimates are important for research planning and targeted strategies for stroke prevention and management. However, recent and comprehensive evaluation is lacking over the past 30 years in China. This study aimed to examine the geographical variations in stroke prevalence based on data from the National Epidemiological Survey of Stroke in China (NESS-China) and demonstrate urban-rural transition and trend over three decades. The stroke prevalence (prevalence day, August 31, 2013) was estimated using the world standard population. The stroke prevalence was 873.4 per 100,000 population, and varied from 218.0 in Sichuan to 1768.9 in Heilongjiang. Stroke prevalence exhibited a noticeable north-south gradient (1097.1, 917.7, and 619.4 in the north, middle, and the south, respectively; P < 0.001) and showed a 2.0-fold, 1.5-fold, and 1.2-fold increase in rural areas in the north, the middle, and the south, respectively, from 1985 to 2013. Overall, stroke prevalence was higher in the rural regions than in the urban (945.4 versus 797.5, P < 0.001) regions. However, the converse was depicted in 12 provinces. A noticeable geographical variation in stroke prevalence was observed and was evolving overtime in China. It is imperative that effective public health policies and interventions be implemented, especially in those regions with higher prevalence.

Type 2 Diabetes Mellitus is Associated with the Immunoglobulin G N-Glycome through Putative Proinflammatory Mechanisms in an Australian Population.

Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.

Suboptimal health status as an independent risk factor for type 2 diabetes mellitus in a community-based cohort: the China suboptimal health cohort study.

BACKGROUND: The prevalence of diabetes, constituted chiefly by type 2 diabetes mellitus (T2DM), is a global public health threat. Suboptimal health status (SHS), a physical state between health and disease, might contribute to the progression or development of T2DM. METHODS: We conducted a prospective cohort study, based on the China Suboptimal Health Cohort Study (COACS), to understand the impact of SHS on the progress of T2DM. We examined associations between SHS and T2DM outcomes using multivariable logistic regression models and constructed predictive models for T2DM onset based on SHS. RESULTS: A total of 61 participants developed T2DM after an average of 3.1 years of follow-up. Participants with higher SHS scores had more T2DM outcomes (p = 0.036). Moreover, compared with the lowest quartile of SHS scores, participants with fourth, third, and second quartile SHS scores were found to be associated with a 1.7-fold, 1.6-fold, and 1.5-fold risk of developing T2DM, respectively. The predictive model constructed with SHS had higher discriminatory power (AUC = 0.848) than the model without SHS (AUC = 0.795). CONCLUSIONS: The present study suggests that a higher SHS score is associated with a higher incidence of T2DM. SHS is a new independent risk factor for T2DM and has the capability to act as a predictive tool for T2DM onset. The evaluation of SHS combined with the analysis of modifiable risk factors for SHS allows the risk stratification of T2DM, which may consequently contribute to the prevention of T2DM development. These findings might require further validation in a longer-term follow-up study.

Hyperuricemia is Associated with Immunoglobulin G N-Glycosylation: A Community-Based Study of Glycan Biomarkers.

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G N-glycans play a role in hyperuricemia in the general population. This cross-sectional study enrolled 635 participants (208 men and 427 women), ages ≥18 years, from a community-based population in Beijing, China. The IgG N-glycan composition of serum was analyzed by an ultraperformance liquid chromatography method. The prevalence of hyperuricemia observed in this sample was 5.98% (14.9% in men and 1.6% in women). Serum uric acid level was positively correlated with glycan peaks (GP)1, GP2, GP4, GP6, GP10, and GP11, whereas it was negatively correlated with GP12, GP13, GP14, GP15, GP18, and GP20. The combination of GP9, GP10, body mass index, and gender distinguished individuals with hyperuricemia from subjects without hyperuricemia, with an area under the curve value of 0.849 (95% confidence interval: 0.784-0.915). These findings collectively suggest a possible link between hyperuricemia and IgG N-glycans, which might be potentially mediated through inflammation-related mechanisms. Additional research on glycan biomarkers in independent and community-based population samples might allow the development of glycan diagnostics for hyperuricemia and gout in the future.

The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia.

BACKGROUND: Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. METHODS: Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20-68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography. RESULTS: Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644-0.740). CONCLUSIONS: Our findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.

Type 2 Diabetes Mellitus: Integrative Analysis of Multiomics Data for Biomarker Discovery.

Increased fasting plasma glucose (FPG) is an independent risk factor for type 2 diabetes mellitus (T2DM). The development of systems biology technologies for integration of multiomics data is crucial for predicting increased FPG levels. In this case-control study, immunoglobulin (Ig) G glycosylation profiling and genome-wide association analyses were performed on 511 participants, and among them 76 had increased FPG (aged 47.6 ± 6.14 years), and 435 had decreased or fluctuant FPG (aged 47.9 ± 6.08 years). We identified nine single nucleotide polymorphisms (SNPs) in five genes (RPL7AP27, SNX30, SLC39A12, BACE2, and IGFL2) that were significantly associated with increased FPG (odds ratios 1.937-2.393). Moreover, of the 24 glycan peaks (GPs), GPs 3, 8, and 11 presented positive trends with increased FPG levels, whereas GPs 4 and 14 presented negative trends. A significant improvement of predictive power was observed when adding 24 IgG GPs to 9 SNPs with the area under the curve increased from 0.75 to 0.81. This report shows that the combination of candidate SNPs with IgG glycomics offers biomarker potentials for T2DM. The substantial predictive power obtained from integrating genomics and glycomics biomarkers suggests the feasibility of applying such multiomics strategies to enable predictive, preventive, and personalized medicine for T2DM.

Ischemic stroke is associated with the pro-inflammatory potential of N-glycosylated immunoglobulin G.

BACKGROUND: Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension. METHODS: The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n = 78) and cerebral arterial stenosis (CAS) (n = 75) and controls (n = 77) were analyzed by ultra-performance liquid chromatography. RESULTS: Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver-operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732-0.872) and controls (AUC, 0.740; 95% CI, 0.661-0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r = 0.566, p < 0.001). CONCLUSION: Our findings indicated that loss of galactose and sialic acid, as well as addition of bisecting GlcNAc, might involve in pro- or anti-inflammatory IgG functionality and further contribute to the pathogenesis of IS. IgG glycan profiles may be developed as clinical useful biomarkers for chronic disease in the future.

Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts.

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.

An Updated Systematic Review and Meta-analysis of Association Between Adiponectin Gene Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a significant contributor to global health burden. Adiponectin gene single nucleotide polymorphisms (SNPs) have been associated with CAD susceptibility, but with inconsistent results across the studies. We present, in this study, an updated meta-analysis to discern the genetic susceptibility of adiponectin SNPs in relation to CAD. PubMed and EMBASE databases were used to identify the relevant published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios and 95% confidence intervals were generated to assess the strength of the associations. Thirty-five articles with a total of 28,947 participants (mean age 55.3 years, 11,632 cases/17,315 controls, 19,443 males/8353 females, and 1151 persons with unspecified gender data) were included. The dominant, recessive, and additive models were applied. We found that the SNPs +45T>G (rs2241766), -4034A>C (rs822395), and -11391G>A (rs17300539) were linked to CAD development. In addition, +276G>T (rs1501299) SNP was associated with a decreased susceptibility to CAD among Caucasians. We did not find an association between the CAD susceptibility and the -11377C>G (rs266729) SNP. These observations offer new potential genetic biomarker candidates in relation to CAD, and warrant further research in independent world populations.