Molecular engineering and bioimaging applications of C2-alkenyl indole dyes with tunable emission wavelengths covering visible to NIR light.

As an important member of dyes, small-molecule fluorescent dyes show indispensable value in biomedical fields. Although various molecular dyes have been developed, full-color dyes covering blue to red region derived from a single chromophore are still in urgent demand. In this work, a series of dyes based on C2-alkenyl indole skeleton were synthesized, namely AI dyes, and their photophysical properties, cytotoxicity, and imaging capacity were verified to be satisfactory. Particularly, the maximal emission wavelengths of these dyes could cover a wide range from visible to NIR light with large Stokes shifts. Besides, the optical and structural discrepancies between the C2- and C3- alkenyl AI dyes were discussed in detail, and the theoretical calculations were conducted to provide insights on such structure-activity relationship. Finally, as a proof-of-concept, a fluorescent probe AI-Py-B capable of imaging endogenous ONOO- was presented, demonstrating the bioimaging potentials of these alkenyl indole dyes. This work is anticipated to open up new possibilities for developing dye engineering and bio-applications of natural indole framework.

The association between dietary patterns with type 2 diabetes mellitus and pre-diabetes in the Henan rural cohort study.

OBJECTIVE: We aimed to investigate whether dietary patterns were associated with the risk of type 2 diabetes mellitus (T2DM) or pre-diabetes in adults of rural area in Henan. DESIGN: Cross-sectional study. Principal component analysis was used to identify dietary patterns, while multivariate logistic regression analysis and restricted cubic spline regression models were used to analyse the association between dietary patterns and both pre-diabetes and T2DM. SETTING: Rural area of Henan province, China. PARTICIPANTS: A total of 38 779 adults aged 18-79 years were recruited from the Henan rural cohort study as the subjects. RESULTS: The prevalence of pre-diabetes and T2DM in rural Henan was 6·8 % and 9·4 %, respectively. A total of three dietary patterns were assessed in the present study. Dietary pattern I with a high intake of red meat and white meat; dietary pattern II with a high intake of grains, nuts, milk and eggs and dietary pattern III with a high intake of vegetables, staple food and fruits. The highest quintile (Q5) of pattern III could reduce 32·7 % risk of pre-diabetes. The Q5 of pattern II showed a 15·5 % decreased risk of T2DM, in a U-shaped dose-response manner; meanwhile, the Q5 of pattern III was significantly associated with reduced risks of T2DM (OR: 0·582, 95 % CI (0·497, 0·682)). CONCLUSIONS: Pattern III is beneficial for reducing risk of pre-diabetes or T2DM. Though a higher consumption of 'grains-nuts-egg' may associate with a reduced risk of T2DM, excessive intakes should be avoided. This study may provide a reference for the prevention of diabetes on dietary precautions.

The association between frequency of away-from home meals and type 2 diabetes mellitus in rural Chinese adults: the Henan Rural Cohort Study.

PURPOSE: There is a paucity of data on the association between away-from home meals (AFHs) and type 2 diabetes mellitus (T2DM). The aim of this cross-sectional study was to explore the dose-response relationship between AFHs and T2DM in a Chinese population. METHODS: A total of 29,910 participants were enrolled from the Henan Rural Cohort Study. Information on the weekly frequency of AFHs was collected by face-to-face questionnaires. Logistic regression and restricted cubic splines were used to estimate the relationship between the frequencies of AFHs and T2DM. Mediation analysis was performed to examine the contribution of body mass index (BMI) to the frequency of AFH-related T2DM. RESULTS: Compared with those who reported 0 AFHs per week, those who consumed ≥ 11 AFHs/week were associated with a 39% increase in the prevalence of T2DM. A nonlinear dose-response relationship between the frequency of AFHs and T2DM was found. Compared with the 0 AFHs/week group, in males, the multivariate odds ratios (OR) and 95% confidence interval (95% CI) of the groups with 11 or more AFHs/week for T2DM were 1.36 (1.01-1.84). However, no such association was found in females. BMI partly mediated the effects of the frequency of AFHs on T2DM, and the proportion explained was 23.4%. CONCLUSIONS: A relationship between the frequency of AFHs and T2DM was observed in the rural Chinese population. An excessive frequency of AFHs was likely to increase the prevalence of T2DM. Meanwhile, BMI partially mediates the effects of the frequency of AFHs on T2DM. TRIAL REGISTRATION: The Henan Rural Cohort Study, ChiCTR-OOC-15006699, Registered 6 July 2015, https://www.chictr.org.cn/showproj.aspx?proj=11375 .

Association between daily egg intake and lipid profiles in adults from the Henan rural cohort study.

BACKGROUND AND AIMS: The association between daily egg intake and dyslipidemia remains a contentious issue. Therefore, our study was aimed to explore the relation of daily egg intake to lipid profile; and whether the association was mediated by body mass index (BMI). METHODS AND RESULTS: A total of 39,021 participants (18-79 years) were enrolled from the Henan Rural Cohort Study. Data on egg consumptions and blood lipid indices were collected with standardized processes. Logistic regression and restricted cubic splines were used to estimate the odds ratio (OR) and 95% confidence intervals (95% CI). Mediation analysis using bootstrap was performed to examine the contribution of BMI to daily egg intake and HDL-C. The participants were divided into 3 egg intake groups (＜26.79 g/d, 26.79-62.50 g/d, ＞62.5 g/d). According to our results, comparing with the low daily egg consumption group, medium and high egg intake tertiles were related with increased high-TC (ORmedium = 1.546, 95%CI (1.417,1.688); ORhigh = 1.902,95%CI (1.703, 2.124)), high LDL-C (ORmedium = 1.224, 95%CI (1.121, 1.337); ORhigh = 1.368,95%CI (1.220, 1.534)) and non-HDL-C(ORmedium = 1.486,95%CI(1.358,1.625); ORhigh = 1.715,95%CI (1.499, 1.888)), as well as inversely associated with high-TG (ORmedium = 0.825, 95% CI(0.778, 0.875); ORhigh = 0.778,95%CI(0.718,0.844)) and low HDL-C (ORmedium = 0.914, 95%CI (0.858, 0.973); ORhigh = 0.756,95%CI(0.693,0.825)). Moreover, mediation analysis showed that both of BMI and WC partly mediated the relationship between daily egg intake and HDL-C. CONCLUSIONS: Our results suggested that the daily egg intake may have a role in effect on lipid profiles, and the effect of daily egg intake on HDL-C may be partly mediated by BMI and WC.

Reproducibility and validity of an FFQ in the Henan Rural Cohort Study.

OBJECTIVE: The present study aimed to evaluate the validity and reproducibility of a thirteen-item FFQ regarding identification of dietary conditions in a rural population in China. DESIGN: A reproducibility study repeated the first FFQ (FFQ1) approximately 4 weeks later (FFQ2). A validity study evaluated the mean of three consecutive 24 h diet recalls as the reference measure. SETTING: Cross-sectional study. PARTICIPANTS: Residents of a rural area in Henan Province, which is located in the central region of China. RESULTS: A total of 295 individuals participated in the reproducibility study. In addition, 123 people agreed to participate in the validity study. Spearman's correlation coefficients between the two FFQ ranged from 0·06 (vegetables) to 0·58 (eggs). Spearman's correlation coefficients between the two methods of collection ranged from 0·01 for cereal to 0·49 for staple foods. The mean of the intraclass correlation coefficients of the two FFQ (FFQ1 v. FFQ2) was 0·19. Bland-Altman analysis indicated good agreement for most food groups across the range of intake for the two studies. CONCLUSIONS: The study demonstrated that our FFQ design could be used as a representative tool to conduct a dietary evaluation of a rural population.

Association between dietary patterns and dyslipidemia in adults from the Henan Rural Cohort Study.

BACKGROUND AND OBJECTIVES: The aim of the study was to explore the association between dietary patterns and lipid levels in Henan rural area. METHODS AND STUDY DESIGN: Fasting blood samples, information on dietary intakes (with food frequency questionnaires) and other data were collected from the Henan Rural Cohort Study. Principal component analysis was used to identify the dietary patterns. Binary logistic regression and restricted cubic spline regression models were performed to obtain odds ratios (ORs) and 95% confidence intervals (95%CI). The study recruited 38,983 available participants aged from 18 to 79 from rural areas in Henan province. RESULTS: The study showed that, three patterns were identified by higher factor loadings: namely the "meat" (high intakes of red meat, white meat and fish), "grain-egg-nut complex" (high intakes of nuts, milk, eggs, grains and beans), and "vegetablesstaple food-fruits" pattern (high intakes of vegetables, staple food and fruits). "Grain-egg-nut complex" pattern was significantly positively related to the risk of dyslipidemia (OR: 1.10; 95% CI: 1.05-1.16, p<0.05). The multivariable- adjusted ORs across tertiles of each dietary pattern were significantly associated with each component of dyslipidemia indexes. CONCLUSIONS: Grain-egg-nut complex dietary pattern was positively associated with dyslipidemia. All three dietary patterns were associated with blood lipid profiles aberrations.

Vegetable Oil or Animal Fat Oil, Which is More Conducive to Cardiovascular Health Among the Elderly in China?

Our present study aimed to investigate the relationship between cooking oil types and atherosclerotic cardiovascular disease (ASCVD) and to reveal which cooking oil is more beneficial to cardiovascular health in older Chinese. This study relies on cross-section data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in the 2018 wave. A total of 15,874 elderly Chinese over 65 years old were included in our analysis. Logistic regression analysis was used to assess the association between cooking oil types and ASCVD. Of the 15,874 elderly people, 13,709 cooked with vegetable/gingili oil, with an average age [SD] of 84.47 [11.51] years; 1533 cooked with lard/other animal fat oils, with an average age [SD] of 85.90 [11.72] years. 3918 of those who cooked with vegetable/gingili oil had ASCVD, and 249 of those who cooked with lard/other animal fat oils had ASCVD. The prevalence of ASCVD in vegetable/gingili oil users (31.68%) was higher than that in lard/other animal fat oil users (17.46%). Compared with lard/other animal fat users, the multivariate-adjusted model indicated that vegetable oil/sesame oil users were significantly associated with a higher risk of ASCVD (OR = 2.19; 95%CI, 1.90-2.53). Our study found that cooking with lard/other animal fat oil is more beneficial to cardiovascular health in older Chinese. Dietary guidelines should seriously consider the health effects of substituting vegetable/gingili oil for lard/other animal fat oil for different populations.

Association between ambient PM2.5 and outpatient visits of children's respiratory diseases in a megacity in Central China.

Objective: To explore the relationship between ambient PM2.5 level and outpatient visits of children with respiratory diseases in a megacity, Zhengzhou, in central China. Methods: We collected daily outpatient visit data, air pollutant data, and meteorological data at the monitoring points of Zhengzhou from the time period 2018 to 2020 and used Spearman's rank correlation to analyze the correlation between children's respiratory outpatient visits and air pollutants and meteorological factors. Generalized additive models were used to analyze the association between PM2.5 exposures and children's respiratory outpatient visits. A stratified analysis was further carried out for the seasons. Results: From 2018 to 2020, the total number of outpatients with children's respiratory diseases was 79,1107, and the annual average concentrations of PM2.5, PM10, SO2, NO2, CO, and O3-8h in Zhengzhou were respectively 59.48 µg/m3, 111.12 µg/m3, 11.10 µg/m3, 47.77 µg/m3, 0.90 mg/m3 and 108.81 µg/m3. The single-pollutant model showed that the risk of outpatient visits for children with respiratory disease increased by 0.341% (95%CI: 0.274-0.407%), 0.532% (95%CI: 0.455-0.609%) and 0.233% (95%CI: 0.177-0.289%) for every 10 µg/m3 increase in PM2.5 with a 3-day lag, 1-day lag, and 1-day lag respectively for the whole year, heating period, and non-heating period. The multi-pollutant model showed that the risk of PM2.5 on children's respiratory disease visits was robust. The excess risk of PM2.5 on children's respiratory disease visits increased by 0.220% (95%CI: 0.147-0.294%) when SO2 was adjusted. However, the PM2.5 effects were stronger during the heating period than during the non-heating period. Conclusion: The short-term exposure to PM2.5 was significantly associated with outpatient visits for children's respiratory diseases. It is therefore necessary to strengthen the control of air pollution so as to protect children's health.

Observation of HOCl generation associated with diabetic cataract using a highly sensitive fluorescent probe.

Diagnosis of diabetic cataract (DC) in the early stage is of great significance for drug intervention and surgery circumvention for DC patients. However, the lack of reliable imaging tools greatly limits the diagnosis of early DC. In this context, a fluorescent probe BBPy for hypochlorous acid (HOCl) is presented based on the oxidation of phenothiazine. The probe displays apparent emission enhancement at 562 nm toward HOCl with high selectivity, superb sensitivity (detection limit: 12.6 nM), and rapid response (within seconds). Using the probe, the HOCl generation in diabetic human lens epithelial cells was monitored, as well as the HOCl down-regulation during antioxidant treatment. Therefore, it is proposed that HOCl can be a promising biomarker for DC and fluorescence imaging technique can be regarded as a candidate tool for DC diagnosis.

A ratiometric fluorescent probe for monitoring pH fluctuations during autophagy in living cells.

We present a ratiometric fluorescent probe for monitoring pH featuring superb photostability and chemostability. The down-regulation of the intracellular pH during autophagy in living cells induced by various stimuli, including several drugs and starvation, was quantified, which could provide instructive value to construct autophagy models to study the related pathological processes.

Molecular Fluorescent Probes for Imaging and Evaluation of Hypochlorite Fluctuations during Diagnosis and Therapy of Osteoarthritis in Cells and in a Mouse Model.

The early diagnosis of osteoarthritis (OA) can halt or delay the progression of the disease, and it is essentially beneficial to its treatment. However, biomarkers with sufficient sensitivity for dynamically identifying early OA are still yet to be determined. The overproduced hypochlorous acid (HOCl) has been proposed as an obvious symptom in early OA. Herein, based on the oxidation reaction of the sulfur atom in phenothiazine into sulfoxide, we design and synthesize a phenothiazine-derived coumarin fluorescent probe PDC for the detection of ClO- in cells and in an OA mouse model. The probe PDC exhibits excellent selectivity and sensitivity for ClO- detection with a limit of detection as low as 16.1 nM. Taking advantage of the probe PDC, we visualize and evaluate the level changes of ClO- in macrophage cells, which is stimulated by various inflammatory factors. The anti-inflammatory and therapeutic effects of selenocysteine and methotrexate in inflamed cells are also confirmed. Finally, with in vivo imaging of ClO- concentration changes in OA BALB/c mouse models, we successfully inspected the relationship between OA phenotypes and the burst of ClO-. We suggest that abnormal changes in HOCl concentration may be considered as a new biomarker for the early OA diagnosis.

Observation of peroxynitrite overproduction in cells during 5-fluorouracil treatment via a ratiometric fluorescent probe.

We describe a colorimetric and fluorescent probe 3a to detect cellular peroxynitrite with high selectivity and sensitivity. 3a was successfully applied in the bioimaging of exogenous and endogenous peroxynitrite in living cells. The up-regulation of peroxynitrite in cancer cells and normal cells during 5-fluorouracil treatment was finally monitored.