Nuclear Magnetic Resonance-Based Metabolomics and Risk of CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY: The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Liquid chromatography-mass spectrometry-based strategy for systematic profiling of chemical components and associated quantitative analysis of quality markers in Qi-Wei-Tong-Bi oral liquid.

Qi-Wei-Tong-Bi oral liquid (QWTB), a famous Chinese medicine preparation composed of seven crude drugs has a good therapeutic effect on rheumatoid arthritis and is widely used in China. However, its chemical composition and quality control have not been comprehensively and systematically investigated. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed for its chemical profiling. As a result, 100 components were chemically characterized. Additionally, high-performance liquid chromatography coupled with a quadrupole linear ion trap mass spectrometry method was developed to simultaneously quantify nine bioactive components (hyperoside, ononin, quercetin, sinomenine, magnoflorine, gallic acid, protocatechuic acid, monotropein, and cyclo-(Pro-Tyr)) in multiple-reaction monitoring mode. After successful validation in terms of linearity, precision, repeatability, and recovery, the assay method was applied for the determination of 10 batches of QWTB. The results showed that QWTB was enriched in sinomenine and magnoflorine with the highest amount up to hundreds or even thousands of µg/mL, while quercetin, ononin, cyclo-(Pro-Tyr), and hyperoside were much lower with the lowest content below 10 µg/mL. This study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even pharmacodynamic material basis studies of QWTB.

USP14 regulates heme metabolism and ovarian cancer invasion through BACH1 deubiquitination and stabilization.

The deubiquitinating enzyme USP14 has been established as a crucial regulator in various diseases, including tumors, neurodegenerative diseases, and metabolic diseases, through its ability to stabilize its substrate proteins. Our group has utilized proteomic techniques to identify new potential substrate proteins for USP14, however, the underlying signaling pathways regulated by USP14 remain largely unknown. Here, we demonstrate the key role of USP14 in both heme metabolism and tumor invasion by stabilizing the protein BACH1. The cellular oxidative stress response factor NRF2 regulates antioxidant protein expression through binding to the antioxidant response element (ARE). BACH1 can compete with NRF2 for ARE binding, leading to the inhibition of the expression of antioxidant genes, including HMOX-1. Activated NRF2 also inhibits the degradation of BACH1, promoting cancer cell invasion and metastasis. Our findings showed a positive correlation between USP14 expression and NRF2 expression in various cancer tissues from the TCGA database and normal tissues from the GTEx database. Furthermore, activated NRF2 was found to increase USP14 expression in ovarian cancer (OV) cells. The overexpression of USP14 was observed to inhibit HMOX1 expression, while USP14 knockdown had the opposite effect, suggesting a role for USP14 in regulating heme metabolism. The depletion of BACH1 or inhibition of heme oxygenase 1 (coded by HMOX-1) was also found to significantly impair USP14-dependent OV cell invasion. In conclusion, our results highlight the importance of the NRF2-USP14-BACH1 axis in regulating OV cell invasion and heme metabolism, providing evidence for its potential as a therapeutic target in related diseases.

Associations of lipoprotein subclasses with risk of all-cause and cardiovascular disease mortality in individuals with type 2 diabetes: A prospective cohort study.

AIM: Although lipoproteins are well-established risk factors for cardiovascular disease (CVD) mortality, conventional measurements failed to identify lipoprotein particle sizes. This study aimed to investigate associations of lipoprotein subclasses categorized by particle sizes with risk of all-cause and CVD mortality in individuals with type 2 diabetes. METHODS: This study included 6575 individuals with type 2 diabetes from the UK Biobank. Concentrations of very low-, low-, intermediate- and high-density lipoprotein [very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein and high-density lipoprotein (HDL)] particles in 14 subclasses and lipid constituents within each subclass were measured by quantitative nuclear magnetic resonance. Multivariable-adjusted Cox proportional-hazard regression models were used to estimate the hazard ratio (HR) for per standard deviation increment of log-transformed lipoprotein subclasses with risk of mortality. All p-values were adjusted by the false discovery rate method. RESULTS: During a median follow-up of 11.4 years, 943 deaths were documented, including 310 CVD deaths. Small HDL particles were inversely associated with CVD mortality, with HR (95% CI) of 0.78 (0.69, 0.87), whereas very large and large HDL particles were positively associated with CVD mortality with HR (95% CI) of 1.28 (1.12, 1.45) and 1.19 (1.05, 1.35), respectively. A similar pattern was observed for all-cause mortality [small HDL particle (HR, 95% CI): 0.79, 0.74-0.85; large HDL particle: 1.15, 1.07-1.24; very large HDL particle: 1.26, 1.17-1.36]. For VLDL and LDL, very small VLDL particle was positively, while medium LDL particle was inversely associated with all-cause mortality, but not associated with CVD mortality. The pattern of association with all-cause and CVD mortality for cholesterol and triglyceride within lipoprotein particles was similar to those for lipoprotein particles themselves. CONCLUSIONS: The associations between lipoprotein particles, particularly HDL particles, with all-cause and CVD mortality among patients with type 2 diabetes were significantly varied by particle sizes, highlighting the importance of particle size as a lipoprotein metric in mortality risk discrimination.

Mechanochemical Release of Fluorophores from a "Flex-activated" Mechanophore.

Optical force probes that can release force-dependent and visualized signals with minimal changes in the polymer main chains under mechanical load are highly sought after but currently limited. In this study, we introduce a flex-activated mechanophore (FA) based on the Diels-Alder adduct of anthracene and dimethyl acetylenedicarboxylatea that exhibits turn-on mechanofluorescence. We demonstrate that when FA is incorporated into polymer networks or in its crystalline state, it can release fluorescent anthracenes through a retro-Diels-Alder mechanochemical reaction under compression or hydrostatic high pressure, respectively. The flex-activated mechanism of FA is successfully confirmed. Furthermore, we systematically modulate the force delivered to the mechanophore by varying the crosslinking density of the networks and the applied macroscopic pressures. This modulation leads to incremental increases in mechanophore activation, successive release of anthracenes, and quantitative enhancement of fluorescence intensity. The exceptional potential of FA as a sensitive force probe in different bulk states is highlighted, benefiting from its unique flex-activated mode with highly emissive fluorophore releasing. Overall, this report enriches our understanding of the structures and functions of flex-activated mechanophores and polymeric materials.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Overall lifestyles and socioeconomic inequity in mortality and life expectancy in China: the China health and nutrition survey.

BACKGROUND: socioeconomic inequity in mortality and life expectancy remains inconclusive in low- and middle-income countries, and to what extent the associations are mediated or modified by lifestyles remains debatable. METHODS: we included 21,133 adults from China Health and Nutrition Survey (1991-2011) and constructed three parameters to reflect participants' overall individual- (synthesising income, education and occupation) and area-level (urbanisation index) socioeconomic status (SES) and lifestyles (counting the number of smoking, physical inactivity and unhealthy diet and bodyweight). HRs for mortality and life expectancy were estimated by time-dependent Cox model and life table method, respectively. RESULTS: during a median follow-up of 15.2 years, 1,352 deaths were recorded. HRs (95% CIs) for mortality comparing low versus high individual- and area-level SES were 2.38 (1.75-3.24) and 1.84 (1.51-2.24), respectively, corresponding to 5.7 (2.7-8.6) and 5.0 (3.6-6.3) life-year lost at age 50. Lifestyles explained ≤11.5% of socioeconomic disparity in mortality. Higher lifestyle risk scores were associated with higher mortality across all socioeconomic groups. HR (95% CI) for mortality comparing adults with low individual-level SES and 3-4 lifestyle risk factors versus those with high SES and 0-1 lifestyle risk factors was 7.06 (3.47-14.36), corresponding to 19.1 (2.6-35.7) life-year lost at age 50. CONCLUSION: this is the first nationwide cohort study reporting that disadvantaged SES was associated with higher mortality and shorter life expectancy in China, which was slightly mediated by lifestyles. Risk lifestyles were related to higher mortality across all socioeconomic groups, and those with risk lifestyles and disadvantaged SES had much higher mortality risks.

Quality diet indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study.

There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.

CXCL12 and its receptors regulate granulosa cell apoptosis in PCOS rats and human KGN tumor cells.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder accompanied by chronic low-grade inflammation; its etiology is still undefined. This study investigated the expression of CXCL12, CXCR4, and CXCR7 in PCOS rats and their role in regulation of apoptosis. To accomplish this, we established an in vivo PCOS rat model and studied KGN cells (human ovarian granulosa cell line) in vitro. In PCOS rats, the ovarian expression of CXCL12, CXCR4, and CXCR7 was reduced, and the apoptosis rate of granulosa cells was increased, accompanied by decreased expression of BCL2 and increased expression of BAX and cleaved CASPASE3 (CASP3). We further showed that recombinant human CXCL12 treatment upregulated BCL2, downregulated BAX, and cleaved CASP3 in KGN cells to inhibit their apoptosis in a concentration-dependent manner; moreover, the effect of CXCL12 was weakened by CXCR4 antagonist AMD3100 and anti-CXCR7 neutralizing antibody. In conclusion, PCOS rats showed decreased CXCL12, CXCR4, and CXCR7 expression and increased apoptosis rate of ovarian granulosa cells. Further, in human KGN cells, CXCL12 regulated the expression of BAX, BCL2, and cleaved CASP3 to inhibit apoptosis through CXCR4- and CXCR7-mediated signal transmission. These findings may provide a theoretical and practical basis for illuminating the role of proinflammatory cytokines in the pathogenesis of PCOS.

Quantifying the influencing factors and multi-factor interactions affecting cadmium accumulation in limestone-derived agricultural soil using random forest (RF) approach.

Cadmium (Cd) is a highly toxic heavy metal that occurs widely in the environment and poses extensive threats to human health, animals, and plants. This study aims to identify and apportion multi-source and multi-phase Cd pollution from natural and anthropogenic inputs using ensemble models that include random forest (RF) in agricultural soils on Karst areas. The contributions of natural and anthropogenic factors to Cd accumulation were quantitatively assessed using the RF machine learning method. The results revealed that the main influencing factors were pH, organic carbon (Corg), and elevation. Moreover, the interaction effects of pH and Corg on distance and elevation were also quantified and visualised. It is observed that pH and Corg had stronger effects on soil Cd concentration than that of distance when pH > 7.02 and Corg > 1.53. In other words, higher Cd content in the soil along roadways may be caused by the interaction of distance, pH and Corg, with pH and Corg playing the dominant role in our case. Moreover, the maximum contribution of a single factor, elevation, to Cd concentration was about 0.13 mg/kg, and its interactions reached 1.082 mg/kg and 0.83 mg/kg, respectively, when combined with pH and Corg at 194.0 m. However, with increasing elevation, pH and Corg gradually took over the leading roles. This result not only gives us a quantitative understanding of the relationship between the factors that affect soil cadmium accumulation, but also provides an accurate method for source apportionment of heavy metals in soil.

Effective Internal and External Modulation of Nontraditional Intrinsic Luminescence.

The rational modulation of the nontraditional intrinsic luminescence (NTIL) of nonconventional luminophores remains difficult, on account of the limited understanding on the structure-property relationships and emission mechanisms. Herein, the effective modulation of NTIL is demonstrated based on a group of nonaromatic anhydrides and imides. Mutual bridging of isolated subgroups effectively promotes intramolecular through-space conjugation (TSC), leading to red-shifted emission, enhanced efficiency, and prolonged persistent room-temperature phosphorescence (p-RTP). The substitution of heteroatoms from oxygen to nitrogen drastically changes the TSC and enhances intermolecular interactions, resulting in enhanced emission efficiency. In addition, upon freezing, compression, or embedding into polymer matrices, the emission intensity and color remain well regulated. These results shed new light on the rational modulation of the NTIL and p-RTP of nonconventional luminophores.

Epigenetic Regulation of Transition Among Different Pluripotent States: Concise Review.

The extraordinary progress of pluripotent stem cell research provides a revolutionary avenue to understand mammalian early embryonic development. Besides well-established conventional mouse and human embryonic stem cells, the discoveries of naive state human stem cell, two-cell-like cell, and the newly defined "extended pluripotent" stem cell and "expanded potential" stem cell with bidirectional chimeric ability have greatly broadened the horizons of more pluripotent states recaptured and maintained in dish, infinitely approaching the totipotent blastomere state. Although all these pluripotent cell types can self-renew and have the ability to differentiate into all the three germ layers, accumulating evidence suggests that these pluripotent states display distinct epigenetic characters. More strikingly, epigenetic reprogramming, including DNA methylation, histone modification, and chromatin remodeling, is required to reset the cell fate commitment, suggesting that epigenetic mechanisms may play an active and important role in the maintenance and transition among these pluripotent states. Here, we have reviewed studies on various pluripotent states, with a highlight on the epigenetic regulation during the interconversion. Stem Cells 2019;37:1372-1380.

Time-Resolved Photoelectron Spectroscopy Studies of Isoxazole and Oxazole.

The excited state relaxation pathways of isoxazole and oxazole upon excitation with UV-light were investigated by nonadiabatic ab initio dynamics simulations and time-resolved photoelectron spectroscopy. Excitation of the bright ππ*-state of isoxazole predominantly leads to ring-opening dynamics. Both the initially excited ππ*-state and the dissociative πσ*-state offer a combined barrier-free reaction pathway, such that ring-opening, defined as a distance of more than 2 Å between two neighboring atoms, occurs within 45 fs. For oxazole, in contrast, the excited state dynamics is about twice as slow (85 fs) and the quantum yield for ring-opening is lower. This is caused by a small barrier between the ππ*-state and the πσ*-state along the reaction path, which suppresses direct ring-opening. Theoretical findings are consistent with the measured time-resolved photoelectron spectra, confirming the timescales and the quantum yields for the ring-opening channel. The results indicate that a combination of time-resolved photoelectron spectroscopy and excited state dynamics simulations can explain the dominant reaction pathways for this class of molecules. As a general rule, we suggest that the antibonding σ*-orbital located between the oxygen atom and a neighboring atom of a five-membered heterocyclic system provides a driving force for ring-opening reactions, which is modified by the presence and position of additional nitrogen atoms.

Competition between ring-puckering and ring-opening excited state reactions exemplified on 5H-furan-2-one and derivatives.

The influence of ring-puckering on the light-induced ring-opening dynamics of heterocyclic compounds was studied on the sample 5-membered ring molecules γ-valerolactone and 5H-furan-2-one using time-resolved photoelectron spectroscopy and ab initio molecular dynamics simulations. In γ-valerolactone, ring-puckering is not a viable relaxation channel and the only available reaction pathway is ring-opening, which occurs within one vibrational period along the C-O bond. In 5H-furan-2-one, the C=C double bond in the ring allows for ring-puckering which slows down the ring-opening process by about 150 fs while only marginally reducing its quantum yield. This demonstrates that ring-puckering is an ultrafast process, which is directly accessible upon excitation and which spreads the excited state wave packet quickly enough to influence even the outcome of an otherwise expectedly direct ring-opening reaction.

The effect of ICSI in infertility couples with non-male factor: a systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes. METHODS: The literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate. RESULTS: Four RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83-1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66-1.64), implantation rate (RR = 1.12, 95% CI: 0.67-1.86), and live birth rate (RR = 1.17, 95% CI: 0.43-3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03-1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01-1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77-0.94), implantation rate (RR = 0.78, 95% CI: 0.65-0.95), and live birth rate (RR = 0.86, 95% CI: 0.79-0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93-1.04). CONCLUSION: ICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.

Photoactivated Fluorescence Enhancement in F,N-Doped Carbon Dots with Piezochromic Behavior.

Photoactivation in CdSe/ZnS quantum dots (QDs) on UV/Vis light exposure improves photoluminescence (PL) and photostability. However, it was not observed in fluorescent carbon quantum dots (CDs). Now, photoactivated fluorescence enhancement in fluorine and nitrogen co-doped carbon dots (F,N-doped CDs) is presented. At 1.0 atm, the fluorescence intensity of F,N-doped CDs increases with UV light irradiation (5 s-30 min), accompanied with a blue-shift of the fluorescence emission from 586 nm to 550 nm. F,N-doped CDs exhibit photoactivated fluorescence enhancement when exposed to UV under high pressure (0.1 GPa). F,N-doped CDs show reversible piezochromic behavior while applying increasing pressure (1.0 atm to 9.98 GPa), showing a pressure-triggered aggregation-induced emission in the range 1.0 atm-0.65 GPa. The photoactivated CDs with piezochromic fluorescence enhancement broadens the versatility of CDs from ambient to high-pressure conditions and enhances their anti-photobleaching.

Long-term incense use and the risk of end-stage renal disease among Chinese in Singapore: the Singapore Chinese health study.

BACKGROUND: Experimental studies have shown that exposure to incense burning may have deleterious effects on kidney function and architecture. However, the association between chronic exposure to incense smoke and risk of end-stage renal disease (ESRD) has not been reported in epidemiologic studies. METHODS: We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese men and women of 45-74 years of age in Singapore during recruitment from 1993 to 1998. Information on the practice of incense burning at home, diet, lifestyle and medical history was collected at baseline interviews. ESRD cases were identified through linkage with the nationwide Singapore Renal Registry through 2015. We used Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% confidence interval (CI) of ESRD associated with domestic incense burning. RESULTS: Among cohort participants, 76.9% were current incense users. After an average 17.5 years of follow-up, there were 1217 incident ESRD cases. Compared to never users, the multivariable-adjusted HR for ESRD risk was 1.05 (95% CI, 0.80 to 1.38) for former users and 1.26 (95% CI, 1.02 to1.57) for current users of incense. In analysis by daily or non-daily use and duration, the increased ESRD risk was observed in daily users who had used incense for > 20 years; HR was 1.25 (95% CI, 1.07 to 1.46). Conversely, the risk was not increased in those who did not use incense daily or who had used daily but for ≤20 years. CONCLUSIONS: Our findings demonstrate that long-term daily exposure to domestic incense burning could be associated with a higher risk of ESRD in the general population.

Cellular pharmacokinetics and pharmacodynamics mechanisms of ginkgo diterpene lactone and its modulation of P-glycoprotein expression in human SH-SY5Y cells.

Ginkgo diterpene lactone (GDL) is the raw material for ginkgo diterpene lactone meglumine injection, which is used for treating cerebral ischemia. The aims of this study were to explore the cellular pharmacokinetics of GDL in whole cells and subcellular fractions, and detect cellular pharmacodynamics on the human SH-SY5Y cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Firstly, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the amount of ginkgolide A (GA), B (GB) and K (GK) in cellular/subcellular samples. Then, phosphatidylserine and mitochondria membrane potential were assayed to evaluate the extent of apoptosis effect. The study showed that the cellular/subcellular accumulation of GA and GB were increased in a concentration-dependent manner; the levels of GA and GB in cytosol were the highest among these subcellular organelles. Meanwhile, GDL also attenuated the OGD/R-induced increases in the percentage of apoptotic and mitochondria membrane potential. In addition, verapamil increased the rate and amount of GA and GB entering cellular/subcellular compartments through inhibition of P-glycoprotein activity, and promoted the protective effect of GDL. The present study reports the cellular pharmacokinetics profiles of GA and GB in normal and OGD/R-induced SH-SY5Y cells in vitro for the first time, which provided valuable information for clinical safety application.

Competitive Protein Binding Assay of Naproxen by Human Serum Albumin Functionalized Silicon Dioxide Nanoparticles.

We have developed a new competitive protein binding assay (CPBA) based on human serum albumin functionalized silicon dioxide nanoparticles (nano-SiO2-HSA) that can be used for naproxen determination in urine. Compared with a conventional multi-well reaction plate, nano-SiO2 with a high surface-area-to-volume ratio could be introduced as a stationary phase, markedly improving the analytical performance. Nano-SiO2-HSA and horseradish peroxidase-labeled-naproxen (HRP-naproxen) were prepared for the present CPBA method. In this study, a direct competitive binding to nano-SiO2-HSAwas performed between the free naproxen in the sample and HRP-naproxen. Thus, the catalytic color reactions were investigated on an HRP/3,3'5,5'-tetramethylbenzidine (TMB)/H2O2 system by the HRP-naproxen/nano-SiO2-HSA composite for quantitative measurement via an ultraviolet spectrophotometer. A series of validation experiments indicated that our proposed methods can be applied satisfactorily to the determination of naproxen in urine samples. As a proof of principle, the newly developed nano-CPBA method for the quantification of naproxen in urine can be expected to have the advantages of low costs, fast speed, high accuracy, and relatively simple instrument requirements. Our method could be capable of expanding the analytical applications of nanomaterials and of determining other small-molecule compounds from various biological samples.

[Rapid identification of chemical components in compound Nanxing acesodyne plaster by UPLC-Q-TOF-MS/MS].

The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 µm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.