A mitochondrion-targeted fluorescent probe based on ESIPT phthalimide for the detection of Hg2+ with large Stokes shift.

A novel mitochondrion-targeted Hg2+-specific fluorescent probe 1 based on ESIPT phthalimide was designed and synthesized for the first time. Owing to the blockage of the ESIPT process between the hydroxy group and the carbonyl oxygen of the imide by the diphenylphosphinothioate group, 1 was almost nonfluorescent. After reacting with Hg2+, 1 exhibited a dramatic fluorescence enhancement due to the recovery of the ESIPT process through Hg2+-induced desulfurization-hydrolysis of the diphenylphosphinothioate moiety and the cleavage of the P-O bond. 1 showed a large Stokes shift, rapid response and high sensitivity and selectivity for Hg2+ over other metal ions. Moreover, 1 was successfully employed to image Hg2+ in the mitochondria of living cells.

A Reaction-Based ESIPT Fluorescent Probe for the Detection of Hg2+ with Large Stokes Shift.

A novel reaction-based fluorescent probe 1 for Hg2+ was designed and synthesized. 1 was almost nonfluoresent due to inhibition of the ESIPT process between hydroxy group and imid carbonyl oxygen by diphenylphosphinothioate group. After reacting with Hg2+, the fluorescence intensity of 1 exhibited significant enhancement owing to recovery of the ESIPT process via Hg2+-promoted desulfurization-hydrolysis of the diphenylphosphinothioate moiety and cleavage of the P-O bond. 1 not only showed rapid response, high sensitivity, excellent selectivity for Hg2+ over other metal ions, but also could detect Hg2+ with large Stokes shift (165 nm), which was attributed to the ESIPT process. Moreover, the reaction mechanism was fully validated by absorption spectra, fluorescence spectra, fluorescence color as well as ESI-MS analysis. 1 is the reaction-based ESIPT fluorescent probe for the detection of Hg2+ with large Stokes shift, rapid response, high sensitivity and selectivity.

Identification of key DNA methylation changes on fasting plasma glucose: a genome-wide DNA methylation analysis in Chinese monozygotic twins.

BACKGROUND: Elevated fasting plasma glucose (FPG) levels can increase morbidity and mortality even when it is below the diagnostic threshold of type 2 diabetes mellitus (T2DM). We conducted a genome-wide DNA methylation analysis to detect DNA methylation (DNAm) variants potentially related to FPG in Chinese monozygotic twins. METHODS: Genome-wide DNA methylation profiling in whole blood of twins was performed using Reduced Representation Bisulfite Sequencing (RRBS), yielding 551,447 raw CpGs. Association between DNAm of single CpG and FPG was tested using a generalized estimation equation. Differentially methylated regions (DMRs) were identified using comb-P approach. ICE FALCON method was utilized to perform the causal inference. Candidate CpGs were quantified and validated using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data from twins. RESULTS: The mean age of 52 twin pairs was 52 years (SD: 7). The relationship between DNAm of 142 CpGs and FPG reached the genome-wide significance level. Thirty-two DMRs within 24 genes were identified, including TLCD1, MRPS31P5, CASZ1, and CXADRP3. The causal relationship of top CpGs mapped to TLCD1, MZF1, PTPRN2, SLC6A18, ASTN2, IQCA1, GRIN1, and PDE2A genes with FPG were further identified using ICE FALCON method. Pathways potentially related to FPG were also identified, such as phospholipid-hydroperoxide glutathione peroxidase activity and mitogen-activated protein kinase p38 binding. Three CpGs mapped to SLC6A18 gene were validated in a community population, with a hypermethylated direction in diabetic patients. The expression levels of 18 genes (including SLC6A18 and TLCD1) were positively correlated with FPG levels. CONCLUSIONS: We detect many DNAm variants that may be associated with FPG in whole blood, particularly the loci within SLC6A18 gene. Our findings provide important reference for the epigenetic regulation of elevated FPG levels and diabetes.

Insomnia symptoms are associated with an increased risk of type 2 diabetes mellitus among adults aged 50 and older.

PURPOSE: To evaluate the association of the different degrees of insomnia symptoms with subsequent incidence of type 2 diabetes mellitus (T2DM). METHODS: The data were extracted from Health and Retirement Study 2006-2014 waves. The association of insomnia symptoms with T2DM incidence was evaluated by the competing risk model with cumulative incidence function (death was considered a competing event) and Cox proportional hazard model with the Kaplan-Meier method. Population attributable fraction (PAF) was calculated. All analyses related to our study were conducted between November 2020 and January 2021. RESULTS: A total of 14,112 patients were included in this study, with an average follow-up of 6.4 years, and the incidence density was 17.9 per 1000 person-years. Insomnia symptoms were positively associated with T2DM incidence compared with those with no insomnia symptoms, regardless of competing risk model (≥ 1 symptoms: sub-distribution hazard ratio (SHR) 1.13; 95% confidence interval (CI) 1.02-1.26; P-trend = 0.012) and Cox proportional hazard model (≥ 1 symptoms: hazard ratio (HR) 1.13; 95% CI 1.02-1.26; P-trend = 0.013). The cumulative incidence function (Gray's test, p < 0.001) and Kaplan-Meier estimate (log-rank test, p < 0.001) also presented this positive relationship. This positive association was more apparent in women and participants with ages from 50 to 65 years. The PAF was 4.1% with 95% CI (0.7-7.9%). CONCLUSIONS: Insomnia symptoms may be an important risk factor for the development of T2DM, which is unbiased by the death competing risk. These findings suggest that management of sleep problems may be an important part of strategies to prevent T2DM.

Exploring the bidirectional associations between handgrip strength and depression in middle and older Americans.

OBJECTIVE: Current evidence on the relationship between decreased handgrip strength and depression risk is controversial, and there is limited study focus on the potential bidirectional associations between them. We aim to explore their bidirectional relationships. METHODS: This study used panel data from the Health and Retirement Study involving 17,713 aging Americans (≥50 years old) who participated in at least 2 waves. Smedley spring-type hand-held dynamometer was used to assess the handgrip strength. Depression was evaluated by the 8-item Center for Epidemiologic Studies-Depression (CESD) scale. Time-lagged general estimating equations (GEE) were used to assess the bidirectional association between handgrip strength and the depression risk. RESULTS: In the fully adjusted model, every 5 kg decreased handgrip strength was associated with a 6% (95%CI: 3%-9%) increased risk of depression. Compared with non-weakness participants, those with weakness had a higher depression risk (OR = 1.22, 95%CI: 1.09-1.36). Conversely, depression might associate with a 0.33 kg (95% CI: 0.09-0.56) decrease in handgrip strength and increased the risk of weakness by 18% (95% CI: 6%-33%). In addition, the results remained stable in the stratified analyses by gender and sex. Interestingly, the above-mentioned associations were also observed in overweight and obese participants. CONCLUSIONS: The present study found bidirectional associations between handgrip strength and depression risk. Our results indicated early interventions for depression and handgrip strength might achieve reciprocal benefits over time.

The use of oral contraceptive is inversely associated with the risk of type 2 diabetes mellitus among middle-aged women.

OBJECTIVE: To assess the cross-sectional association between oral contraceptive (OC) use and type 2 diabetes mellitus (T2DM) risk among US women. METHODS: The data was obtained from the National Health and Nutrition Examination Survey (NHANES 2007-2018). OC use was assessed by questionnaires and the diagnosis of T2DM was confirmed by the glycosylated hemoglobin, fasting blood glucose, and self-report. Binary logistic regression models and the restricted cubic spline model were adopted to evaluate whether OC use was associated with T2DM. RESULTS: Compared with non-users, the odds ratio (OR) with 95% confidence interval (CI) of T2DM risk for the OC users was 0.71 (0.57-0.89) in unadjusted Model. The association remained significant in fully adjusted models, and the OR with 95%CI was 0.78 (0.62-0.99). In the stratified analyses, there was an inverse association of OC use with T2DM risk when women were overweight. Dose-response analysis also revealed an inversely nonlinear relationship between the duration of OC use and T2DM (p-value for linearity = .589). CONCLUSIONS: Our findings suggested that OC use may be inversely associated with T2DM risk.

Associations of Dietary ω-3, ω-6 Fatty Acids Consumption with Sleep Disorders and Sleep Duration among Adults.

The relationship between ω-3 and ω-6 fatty acids consumption and sleep disorders or duration are controversial. Therefore, we used the data of the National Health and Nutrition Examination Survey 2007-2016 in this cross-sectional study to explore their relationships. ω-3 and ω-6 fatty acids consumption was assessed using two 24 h dietary recall interviews. Sleep disorders and sleep duration were based on self-reported data. Logistic regression models and restricted cubic spline analyses were used. Compared with tertile one, the odds ratios (ORs) and 95% confidence intervals (CIs) of sleep disorders for the second tertile of ω-6 fatty acid intake and the highest tertile of ω-6:ω-3 ratio were 1.30 (1.04-1.62) and 1.36 (1.08-1.70), respectively. Inverse U-shaped and linear dose-response relationships were observed between dietary ω-6 fatty acid intake and ω-6:ω-3 ratio and sleep disorders, respectively. In addition, ω-3 fatty acid consumption was adversely related to sleep disorders in men and the OR (95% CI) was 0.68 (0.49-0.95). Compared with normal sleep duration, ω-3 fatty acid consumption was negatively related to very short, short, and long sleep duration risk. The relative risk ratios (RRRs) were 0.53 (0.35-0.81), 0.79 (0.67-0.93), and 0.81 (068-0.98), respectively. The RRR of very short sleep for ω-6 fatty acid consumption was 0.57 (0.45-0.73). Our study indicates that ω-6 fatty acid consumption and the ω-6:ω-3 ratio are positively associated with the risk of sleep disorders, while the negative association between ω-3 fatty acids and sleep disorders may exist only in men. Furthermore, ω-3 and ω-6 fatty acid consumption are negatively related to the risk of non-normal sleep duration.

An Eu(III)-functionalized Sr-based metal-organic framework for fluorometric determination of Cr(III) and Cr(VI) ions.

An Eu(III)-functionalized strontium-organic framework (Eu3+@Sr-MOF) was synthesized by encapsulating Eu3+ ions into the pores of Sr-MOF via postsynthetic modification (PSM) and fully characterized by XRD, SEM, EDS, FTIR, and TGA. The luminescent properties of Eu3+@Sr-MOF were measured and investigated in detail, which demonstrated that Eu3+@Sr-MOF not only possessed excellent water and chemical stabilities in a wide pH range (5-10) but also displayed red luminescence with excitation/emission maxima at 332/617 nm. The Eu3+@Sr-MOF can be considered as a highly selective and sensitive recyclable luminescence probe for sensing Cr(III) and Cr(VI) based on strong luminescence quenching effects; it can be recycled at least five times. The luminescence probe for Cr3+, CrO42-, and Cr2O72- shows low detection limits (0.15 µM, 0.17 µM, and 0.13 µM, respectively), relatively broad linear ranges (0.6-150 µM, 0.1-200 µM and 0.4-180 µM, respectively), and high quenching constants KSV. The signals can be observed by the naked eye under UV light of 365 nm. The method was applied to the determination of total Cr in environmental water samples. Graphical abstract.

Ultrastable Triazine-Based Covalent Organic Framework with an Interlayer Hydrogen Bonding for Supercapacitor Applications.

Covalent organic frameworks (COFs) with redox-active units are a class of ideal materials for electrochemical-energy-storage devices. A novel two-dimensional (2D) PDC-MA-COF with redox-active triazine units was prepared via aldehyde-amine condensation reaction by using 1,4-piperazinedicarboxaldehyde (PDC) and melamine (MA) as structural units, which possessed high specific surface area (SBET = 748.2 m2 g-1), narrow pore width (1.9 nm), large pore volume (1.21 cm3 g-1), and high nitrogen content (47.87%), for pseudocapacitance application. The interlayer C-H···N hydrogen bonding can "lock" the relative distance between two adjacent layers to avoid an interlayer slip, which is more conducive to maintaining the ordered pore structure of the COF and improving a fast charge transfer between the electrode interface and triazine units. The PDC-MA-COF exhibited an excellent electrochemical performance with the highest specific capacitance of 335 F g-1 along with 19.71% accessibility of the redox-active triazine units in a three-electrode system and 94 F g-1 in a two-electrode system at 1.0 A g-1 current density. Asymmetric supercapacitor of PDC-MA-COF//AC assembled using PDC-MA-COF and activated carbon (AC) as positive and negative electrode materials, respectively, exhibited a high energy density of 29.2 W h kg-1 with a power density of 750 W kg-1. At the same time, it also showed an excellent cyclic stability and could retain 88% of the initial capacitance after 20 000 charge-discharge cycles, which was better than those of the most of the analogous materials reported previously. This study provided a new strategy for designing redox-active COFs for pseudocapacitive storage.

Pharmacologic Effect of Miao Medicine Illicium simonsii Maxim. on Collagen-Induced Arthritis in Rats.

OBJECTIVES: To study the pharmacologic effect and mechanism of action of Miao medicine Illicium simonsii Maxim. (ISM) in treating rheumatoid arthritis. METHODS: Sixty rats were randomly divided to six groups: normal control (normal), collagen-induced arthritis (CIA) model (model), CIA + tripterygium glycosides (TG), CIA + ISM high dose oral (ISM-H), CIA + ISM low-dose oral (ISM-L), and CIA + ISM topical application (ISM-T). The treatment doses were selected based on published reports and folk medicine practice. The outcome measurements included paw swelling, joint pathology, organ index, blood count, T helper 17 (Th17) cell count, and interleukin-6 (IL-6) level. RESULTS: Compared to the CIA model group, all treatment groups showed a significant reduction in paw swelling, blood vessel pathology, Th17 cell count, and IL-6 levels (p < 0.05 or p < 0.01). All treatment groups showed alleviated foot swelling and lower total number of white blood cells, and these effects were observed earlier with oral ISM than topical ISM. The effect of ISM was weaker than that of TG. In addition, less organ damage was observed with topical ISM than oral ISM but better than TG. CONCLUSIONS: These results suggest that, by downregulating Th17 cells, ISM inhibits the production of Il-6, thereby alleviating the proliferation of endothelial and rheumatoid-like cells and leukocytosis in CIA rats, ultimately eliminating foot swelling.