[Quantitative study on the acupoint effects based on complex network analysis: with the examples of the textbook networks formed by Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion].

By extracting the acupoint names and their main indications from cases in Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion, the acupoints and their main indications are represented in a reduced dimension, establishing an "acupoint-indication" linkage. Using complex network detection results (node degree values), the specificity of acupoints was assessed. The small-world characteristics of the "acupoint-indication" network are utilized to analyze the consistency of acupoint selection in acupuncture prescriptions and strategies to avoid redundant acupoints. The results show that the "acupoint-indication" network formed by both texts exhibited an approximate "long-tail" distribution, with a large number of node degree values concentrated between 0 and 4 000, while a few nodes have degree values exceeding 10 000. There are significant differences in the number and distribution of nodes with degree values> 10 000 between the two texts. Chinese Acupuncture and Moxibustion Therapy includes 11 acupoints with multiple edges across the body, whereas Practical Acupuncture and Moxibustion contains only 2 such acupoints, located in the lower limbs. Clinically, some acupoints have a broad therapeutic effect and appear in numerous prescriptions. The division of acupoints based on node degree values can coarsely evaluate the body region specificity of acupoints' regulatory effects. The "acupoint-indication" network of Chinese Acupuncture and Moxibustion Therapy has a higher number of edges than that of Practical Acupuncture and Moxibustion, which might be related to the different historical contexts of the two texts. In the future, diagnostic and therapeutic patterns with historical continuity can be utilized to optimize acupuncture prescriptions.

Nanoscale zero-valent iron reverses resistance of Pseudomonas aeruginosa to chloramphenicol.

Zero-valent iron (ZVI) has been extensively studied for its capacity to remove various contaminants in the environments. However, whether ZVI affects bacterial resistance to antibiotics has not been fully explored. Herein, it was unexpected that, compared with microscale ZVI (mZVI), nanoscale ZVI (nZVI) facilitated the susceptibility of Pseudomonas aeruginosa (P. aeruginosa) to chloramphenicol (CAP), with a decrease in the minimal inhibitory concentration (MIC) of about 60 %, demonstrating a nanosize-specific effect. nZVI enhanced CAP accumulation in P. aeruginosa via inhibitory effect on efflux pumps activated by MexT, thus conferring the susceptibility of P. aeruginosa to CAP. Circular dichroism spectroscopy revealed that the structure of MexT was changed during the evolution. More importantly, molecular dynamic simulations uncovered that, once the structure of MexT changed, it would be more likely to interact with nZVI, resulting in more serious changes in its secondary structure, which was consistent with the increasing susceptibility of P. aeruginosa to CAP. Collectively, this study elucidated the size-specific effect and the underlying mechanism of ZVI on the bacterial evolution of susceptibility toward antibiotics, highlighting the potentials of nZVI-based technologies on the prevention of bacterial resistance to antibiotics, one of the most important issue for globally public health.

Sex-Specific Associations between Maternal Thyroid Peroxidase Antibodies and Cognitive Development in Preschool Children: A Prospective Cohort Study.

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (ß = -3.17, 95% CI: -5.82 to -0.52), fluid reasoning index (FRI) (ß = -4.49, 95% CI: -7.18 to -1.80), and FSIQ score (ß = -2.43, 95% CI: -4.77 to -0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Vaccines Induce Homeostatic Immunity, Generating Several Secondary Benefits.

The optimal immune response eliminates invading pathogens, restoring immune equilibrium without inflicting undue harm to the host. However, when a cascade of immunological reactions is triggered, the immune response can sometimes go into overdrive, potentially leading to harmful long-term effects or even death. The immune system is triggered mostly by infections, allergens, or medical interventions such as vaccination. This review examines how these immune triggers differ and why certain infections may dysregulate immune homeostasis, leading to inflammatory or allergic pathology and exacerbation of pre-existing conditions. However, many vaccines generate an optimal immune response and protect against the consequences of pathogen-induced immunological aggressiveness, and from a small number of unrelated pathogens and autoimmune diseases. Here, we propose an "immuno-wave" model describing a vaccine-induced "Goldilocks immunity", which leaves fine imprints of both pro-inflammatory and anti-inflammatory milieus, derived from both the innate and the adaptive arms of the immune system, in the body. The resulting balanced, 'quiet alert' state of the immune system may provide a jump-start in the defense against pathogens and any associated pathological inflammatory or allergic responses, allowing vaccines to go above and beyond their call of duty. In closing, we recommend formally investigating and reaping many of the secondary benefits of vaccines with appropriate clinical studies.

Piperine improves the health span of Drosophila melanogaster with age- and sex-specific effect.

Piperine, a dietary phytochemical isolated from the Piper species, has been used as a natural medicine for pain, flu, and fever in ancient China and India. Although the health benefits of piperine have been widely studied, research on its effect on aging is limited. This study aimed to determine whether piperine has the potential to mitigate aging-related changes in the fruit fly (Drosophila melanogaster), which is an excellent model organism for studies on aging. The experiments were conducted using the newly eclosed or 30-day-old D. melanogaster wild-type strain Cantonized-white. Piperine was dissolved in 99% ethanol and added to the sucrose-yeast medium at a final concentration of 10, 35, 70, or 100 µM. The study examined the effects of piperine supplementation on the lifespan of D. melanogaster and other physiological functions, such as fecundity, feeding, lipid content, and resistance to environmental stress. Log-rank tests, Shapiro-Wilk test, F-test, t-test, or Wilcoxon rank sum test were used to analyze the data. Piperine failed to change the lifespan and body weight, but increased the fecundity and decreased the feeding rate in one-week-old flies. However, when piperine was fed to 30-day-old flies, it increased the lifespan of male flies and the fecundity and feeding rate of female flies. These results indicate that piperine can improve the health of aged flies. The findings suggest that piperine has age-dependent and sex-specific anti-aging effects in fruit flies.

The association between BCG scars and self-reported chronic diseases: A cross-sectional observational study within an RCT of Danish health care workers.

INTRODUCTION: The live-attenuated vaccines Bacillus Calmette-Guérin (BCG) and Vaccinia have been associated with beneficial non-specific effects. We assessed the prevalence of BCG and Vaccinia vaccine scars in a cohort of Danish health care workers and investigated the association between the presence of vaccine scars and self-reported chronic diseases. METHODS: Cross-sectional study utilizing baseline data collected during 2020-2021 at enrollment in a BCG trial aiming to assess the effect of BCG vaccination on absenteeism and infectious disease morbidity during the SARS-COV-2 pandemic. In Denmark, Vaccinia was discontinued in 1977, and BCG was phased out in the early 1980s. We used logistic regression analysis (adjusted for sex, birth year, and smoking status) to estimate the association between scar status and chronic diseases, providing adjusted Odds Ratios (aORs) with 95 % Confidence Intervals, for participants born before 1977, and born from 1965 to 1976. RESULTS: The cohort consisted of 1218 participants (206 males; 1012 females) with a median age of 47 years (Q1-Q3: 36-56). Among participants born 1965-1976 (n = 403), who experienced the phase-outs, having BCG and/or Vaccinia scar(s) vs. having no vaccine scars yielded an aOR of 0.51 (0.29-0.90) of self-reported chronic disease; an effect primarily driven by BCG. In the same birth cohort, having vaccine scar(s) was most strongly associated with a lower prevalence of chronic respiratory and allergic diseases; the aORs being 0.39 (0.16-0.97) and 0.39 (0.16-0.91), respectively. CONCLUSION: Having a BCG scar was associated with a lower prevalence of self-reported chronic disease.

Confined Water Dominates Ion/Molecule Transport in Hydrogel Nanochannels.

Current artificial nanochannels rely more on charge interactions for intelligent mass transport. Nevertheless, popular charged nanochannels would lose their advantages in long-term applications. Confined water, an indispensable transport medium in biological nanochannels, dominating the transport process in the uncharged nanochannels perfectly provides a new perspective. Herein, we achieve confined-water-dominated mass transport in hydrogel nanochannels (HNCs) constructed by in situ photopolymerization of acrylic acid (PAA) hydrogel in anodic alumina (AAO) nanochannels. HNCs show selectivity to Na+ transport and a high transport rate of molecules after introducing Na+/Li+, compared with other alkali metal ions like Cs+/K+. The mechanism given by ATR-FTIR shows that the hydrogen-bonding structure of confined water in HNCs is destabilized by Na+/Li+, which facilitates mass transport, but is constrained by Cs+/K+, resulting in transport inhibition. This work elucidates the relationship between confined water and mass transport in uncharged nanochannels while also presenting a strategy for designing functional nanochannel devices.

Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation.

BACKGROUND: Systematic characterization of how  genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing. RESULTS: We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic variants with cell type-specific effects are often accessible in multiple cell types. Furthermore, the transcription factors whose binding sites are perturbed by genetic variants tend to have higher expression levels in the cell types where the variants exert their effects, compared to the cell types where the variants have no impact. We further validate our findings with high-throughput reporter assays. Lastly, we identify the enriched cell types, candidate causal variants and genes, and cell type-specific regulatory mechanism underlying GWAS loci. CONCLUSIONS: Overall, genetic effects on gene regulation are highly context dependent. Our results suggest that cell type-dependent genetic effect is driven by precise modulation of both trans-factor expression and chromatin accessibility of cis-elements. Our findings indicate hierarchical collaboration among transcription factors plays a crucial role in mediating cell type-specific effects of genetic variants on gene regulation.

Zinc Cations Uniquely Stabilize Cell Membrane for Cell Cryopreservation.

We report, for the first time, merely using a small amount of (0.039% w/w) Zn(II) instead of very high concentration (25%-50% w/w) of conventional cryoprotective agents (CPAs), i.e., glycerol, during the cryopreservation of red blood cells (RBCs) can lead to a comparable post-thaw recovery rate of ∼95% while avoiding the tedious gradient washout process for the removal of CPA afterward. The result is remarkable, since Zn(II) does not have the ice-controlling ability reported to be critical for CPA. It benefits from its moderate interaction with lipid molecules, facilitating the formation of small and dynamic lipid clusters. Consequently, the membrane fluidity is maintained, and the cells are resilient to osmotic and mechanical stresses during cryopreservation. This study first reports the ion-specific effect on stabilizing the cell membrane; meanwhile, reversibly tuning the structure of biological samples against injuries during the cooling and rewarming provides a new strategy for cryopreservation.

Overall and Sex-Specific Effect of Berberine on Glycemic and Insulin-Related Traits: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Berberine is widely available as a nutraceutical supplement for improving glucose metabolism. Berberine affects sex hormones, raising the possibility that its effects on glycemic traits and insulin sensitivity have sex disparity which has been overlooked. OBJECTIVE: To assess the overall and sex-specific effects of berberine on glycemic- and insulin-related traits. METHODS: We identified randomized trials of berberine versus placebo from Medline, Embase, CNKI, clinical trial registries and previous systematic reviews. Mean differences were estimated using inverse-variance weighting with random effects models. Subgroup analyses were conducted by sex, diabetes diagnosis, trial duration, berberine dose and ethnicity. RESULTS: We identified 20 eligible studies (n = 1761). Berberine lowered fasting glucose (-0.52 mmol/L, 95% CI -0.72 to -0.33; 18 studies, n = 1522), HbA1c (-4.48 mmol/mol, 95% CI -6.53 to -2.44, 7 studies, n = 756), fasting insulin (-2.36 mU/L, 95% CI -3.64 to -1.08, 11 studies, n = 966), HOMA-IR (-0.85, 95% CI -1.16 to -0.53,12 studies, n = 1065), and 2-h postprandial glucose (-1.81 mmol/L, 95% CI -2.37 to -1.24, 4 studies, n = 501). Effects on fasting glucose and HOMA-IR showed potential differences by sex, with larger reductions in women than in men. Comparing 4 studies conducted in women to one study conducted in men, the mean difference was -0.21 mmol/L (95% CI -0.41 to -0.00) for fasting glucose and -0.97 (95% CI -1.84 to -0.10) for HOMA-IR. We also found larger reductions in fasting glucose in participants with diabetes and in Asians. CONCLUSION: Berberine is effective in improving glucose metabolism and may result in larger effects on fasting glucose in women, in people with diabetes and in Asians, but subgroup comparisons remain to be replicated given the limited number of studies. Berberine can be considered as a complementary intervention in individuals who may benefit from modest improvements in glucose metabolism and who prefer taking a nutraceutical. STUDY REGISTRATION: PROSPERO (CRD42022345172).

Maternal Exposure to Potentially Toxic Metals and Birth Weight: Preliminary Results from the DSAN-12M Birth Cohort in the Recôncavo Baiano, Brazil.

Prenatal exposure to potentially toxic metals (PTM) may impair fetal growth (FG). We investigated the relationship between maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) and birth weight (BW) of 74 newborns. Blood was collected during the second trimester of pregnancy to determine Pb (PbB) and Cd (CdB), while hair (MnH) and toenails (MnTn) were used for Mn. Samples were analyzed by graphite furnace atomic absorption spectrophotometry (GFAAS). Sociodemographic and BW data were collected from questionnaires and maternity records, respectively. The medians (P25th-P75th) of PbB, CdB, MnH, and MnTn were, respectively, 0.9 (0.5-1.8) µg/dL; 0.54 (0.1-0.8) µg/L; 0.18 (0.1-0.4) µg/g; and 0.65 (0.37-1.22) µg/g. The means (standard deviation) of birth weight according to sex were 3067 (426.3) and 3442 (431) grams, respectively, for girls and boys. MnTn presented an inverse correlation with the BW/gestational age ratio for girls (rho = -0.478; p = 0.018), suggesting the effect of sex modification. Although BW correlation with CdB was not statistically significant, hierarchical linear regression (beta = -2.08; 95% CI-4.58 to 0.41) suggested a fetotoxic effect. These results confirmed the threat PTMs may represent and the need for more extensive research to elucidate their role in inadequate FG in developing countries.

Household food insecurity levels in Ethiopia: quantile regression approach.

Introduction: Numerous natural and man-made factors have afflicted Ethiopia, and millions of people have experienced food insecurity. The current cut-points of the WFP food consumption score (FCS) have limitations in measuring the food insecurity level of different feeding patterns due to the diversified culture of the society. The aim of this study is to adapt the WFP food security score cut-points corrected for the different feeding cultures of the society using effect-driven quantile clustering. Method: The 2012, 2014, and 2016 Ethiopian socio-economic household-based panel data set with a sample size of 3,835 households and 42 variables were used. Longitudinal quantile regression with fixed individual-specific location-shift intercept of the free distribution covariance structure was adopted to identify major indicators that can cluster and level quantiles of the FCS. Result: Household food insecurity is reduced through time across the quintiles of food security score distribution, mainly in the upper quantiles. The leveling based on effect-driven quantile clustering brings 35.5 and 49 as the FCS cut-points corrected for cultural diversity. This corrected FCS brings wider interval for food insecure households with the same interval range for vulnerable households, where the WFP FCS cut-points under estimate it by 7 score. Education level, employment, fertilizer usage, farming type, agricultural package, infrastructure-related factors, and environmental factors are found to be the significant contributing factors to food security. On the other hand, the age of the head of the household, dependency ratio, shock, and no irrigation in households make significant contributions to food insecurity. Moreover, households living in rural areas and farming crops on small lands are comparatively vulnerable and food insecure. Conclusion: Measuring food insecurity in Ethiopia using the WFP FCS cut-off points underestimates households' food insecurity levels. Since the WFP FCS cut-points have universality and comparability limitations, there is a need for a universally accepted local threshold, corrected for local factors those resulted in different consumption patterns in the standardization of food security score. Accordingly, the quantile regression approach adjusts the WFP-FCS cut points by adjusting for local situations. Applying WFP cut-points will wrongly assign households on each level, so the proportion of households will be inflated for the security level and underestimated for the insecure level, and the influence of factors can also be wrongly recommended the food security score for the levels. The quantile clustering approach showed that cropping on a small land size would not bring about food security in Ethiopia. This favors the Ethiopian government initiative called integrated farming "ኩታ ገጠም እርሻ" which Ethiopia needs to develop and implement a system that fits and responds to this technology and infrastructure.

Ion-Specific Nanoconfinement Effect in Multilayered Graphene Membranes: A Combined Nuclear Magnetic Resonance and Computational Study.

Ion adsorption within nanopores is involved in numerous applications. However, a comprehensive understanding of the fundamental relationship between in-pore ion concentration and pore size, particularly in the sub-2 nm range, is scarce. This study investigates the ion-species-dependent concentration in multilayered graphene membranes (MGMs) with tunable nanoslit sizes (0.5-1.6 nm) using nuclear magnetic resonance and computational simulations. For Na+-based electrolytes in MGMs, the concentration of anions in graphene nanoslits increases in correlation with their chaotropic properties. As the nanoslit size decreases, the concentration of chaotropic ion (BF4-) increases, whereas the concentration of kosmotropic ions (Cit3-, PO43-) and other ions (Ac-, F-) decreases or changes slightly. Notably, anions remain more concentrated than counter Na+ ions, leading to electroneutrality breakdown and unipolar anion packing in MGMs. A continuum modeling approach, integrating molecular dynamic simulation with the Poisson-Boltzmann model, elucidates these observations by considering water-mediated ion-graphene non-electrostatic interactions and charge screening from graphene walls.

Is Peer Influence Gender and Age Specific? Findings From a Sample of Justice-Involved Individuals.

Peer influence is generally understood to be one of the primary predictors of crime and delinquency. It is unclear, however, whether the mechanism that connects peer association, endorsement of deviant values, and delinquent behavior applies equally across different age and sex groups. This study examined age- and gender-specific susceptibility to delinquent and prosocial peer influence using a sample of justice-involved individuals. Based on multigroup structural equation modeling, the author found the nexus among peer association, endorsement of deviant values, and violent delinquency varied across gender and age groups. Among adult male respondents, delinquent peers strengthened deviant culture whereas prosocial peers inhibited that culture. Among juvenile respondents, deviant culture was not inhibited by relationships with prosocial peers. The results for adult females showed no significant influence by either delinquent or prosocial peers.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Dose-specific efficacy of adipose-derived mesenchymal stem cells in septic mice.

BACKGROUND: Mesenchymal stem cells (MSCs) therapy for sepsis has been extensively studied in the past decade; however, the treatment regimen and mechanism of action of MSCs remain elusive. Here, we attempted to understand the efficacy and mechanism of action of MSCs on rescuing mice with sepsis. METHODS: A mouse model of sepsis was produced by cecal ligation and puncture (CLP). Allogeneic adipose-derived MSCs (ADSCs) were administered by intravenous infusion at 6 h after CLP, and dose-related effects of ADSCs on these mice were determined by survival rate, histopathological changes, biochemical and coagulation parameters, bacterial load, and plasma levels of endotoxin and inflammatory cytokines. The tissue distribution of intravenously infused ADSCs in septic mice was investigated by pre-labeling ADSCs with the lipophilic membrane dye PKH26. RNA sequencing analysis was performed to assess the transcriptional changes in peripheral blood mononuclear cells (PBMCs) and the liver. RESULTS: A significant therapeutic effect of ADSCs at a dose of 2 × 107 cells/kg in septic mice was evidenced by a remarkable reduction in mortality (35.89% vs. 8.89% survival rate), blood bacterial burden, systemic inflammation, and multiple organ damage. In contrast, ADSCs at a lower dose (1 × 107 cells/kg) failed to achieve any beneficial outcomes, while ADSCs at a higher dose (4 × 107 cells/kg) caused more early death within 24 h after CLP, retaining a steady survival rate of 21.42% thereafter. PKH26-labeled ADSCs were predominantly localized in the lungs of septic mice after intravenous infusion, with only a smaller proportion of PKH26-positive signals appearing in the liver and spleen. RNA sequencing analysis identified that insufficient phagocytic activity of PBMCs in addition to a hyperactivation of the hepatic immune response was responsible for the ineffectiveness of low-dose ADSCs therapy, and acute death caused by high-dose ADSCs infusion was associated with impaired coagulation signaling in PBMCs and exacerbated hepatic hypoxic injury. CONCLUSIONS: Our findings demonstrate a dose-specific effect of ADSCs on the treatment of sepsis due to dose-related interactions between exogenous stem cells and the host's microenvironment. Therefore, a precise dosing regimen is a prerequisite for ADSCs therapy for sepsis.

Mixed exposure to phthalates and organic UV filters affects Children's pubertal development in a gender-specific manner.

BACKGROUND: Previous studies showed phthalates and UV filters are endocrine-disruptive and associated with puberty. However, few studies have examined effects of mixed exposure. METHODS: Six phthalate metabolites and 12 organic UV filters were detected among 223 school-age children. Puberty development was evaluated at baseline and after 18 months of follow-up. Ordered logistic regression models, least absolute shrinkage and selection operator (LASSO) regression and quantile-based g-computation (qgcomp) were used to evaluate relationships between phthalate metabolites or UV filters exposure and pubertal development. RESULTS: Six phthalate metabolites and 5 UV filters were detectable in urine samples. In boys, BP-3 and 4'-MAP were negatively associated with genital (ORBP-3 = 0.52, (0.27, 0.93), OR4'-MAP = 0.45, (0.25, 0.74)) and pubic hair development (ORBP-3:0.24, (0.05, 0.76), OR4'-MAP:0.24, (0.05, 0.77)). In girls, MEP levels were associated with advanced breast development (OR: 1.29, (1.04, 1.64)). LASSO regression identified BP-3, 4'-MAP, and OD-PABA for inverse associations with pubertal development in boys. MEP was related to an increase in girls' breast development (OR: 1.64, (1.08, 2.63)). Overall mixture was related to a 70% reduction in boys' genital development stage, with a larger effect size than a single chemical in qgcomp. Mixed exposure was associated with girls' earlier puberty onset (OR: 2.61, (1.06, 6.42)). CONCLUSIONS: Our results suggested higher levels of phthalate metabolites and UV filters were associated with delayed pubertal development in boys but with earlier puberty in girls. Higher effect size of joint exposure than single chemicals suggested phthalates and UV filters might have synergistic effects on puberty and distort adolescent endocrine function together.

Sex-specific effect of urinary metabolites of polycyclic aromatic hydrocarbons on thyroid profiles: results from NHANES 2011-2012.

The current study aims to evaluate the associations between 10 urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid profiles. The levels of 10 PAH metabolites and thyroid profiles were obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Spearman analysis was utilized to evaluate the correlation coefficients among these 10 PAH metabolites. Multivariate linear and logistic regression models assessed the relationship between urinary PAH metabolite levels, thyroid hormones, and thyroid autoantibodies after adjusting potential confounders. Stratified analysis by gender was performed to evaluate sex-specific effect of urinary metabolites of PAH on thyroid profiles. One thousand six hundred forty-five eligible adult participants with complete research data were enrolled. Of note, the concentrations of the majority of urinary PAH metabolites were remarkedly higher in females compared with males. 2-hydroxyfluorene (2-FLU) was associated with higher total triiodothyronine (T3) levels in whole population (ß = 2.113, 95% CI 0.339-3.888). In males, positive associations were observed in 1-hydroxynaphthalene (1-NAP) and free thyroxine (T4) (ß = 0.0002, 95% CI 0.0000-0.0004). 2-FLU was also found positively associated with total T3 (ß = 2.528, 95% CI 0.115-4.940) in male subjects. While in female participants, 2-hydroxynaphthalene (2-NAP) was associated with free T3 (ß = 0.002, 95% CI 0.000-0.005). 2-FLU was associated with total T3 (ß = 2.683, 95% CI 0.038-5.328), free T3 (ß = 0.050, 95% CI 0.012-0.087), and total T4 (ß = 0.195, 95% CI 0.008-0.382). 2-Hydroxyphenanthrene (2-OHP), 1-hydroxypyrene (1-HP), and 9-hydroxyfluorene (9-FLU) were all positively related to total T3 levels, and the corresponding coefficients were 16.504, 6.587, and 3.010. 9-FLU was also associated with free T3 (ß = 0.049, 95% CI 0.008-0.090). No statistical significances were found between PAH metabolite levels and increased prevalence of increased thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) when PAH metabolites were treated as continuous variables. Meanwhile, in the quartile analyses, increased prevalence of elevated TgAb was observed in participants with quartile 2 2-NAP compared with lowest quartile (OR = 1.753, 95% CI 1.021-3.008). Male subgroup analyses indicated that increased prevalence of elevated TgAb was observed in higher quartile of 1-NAP, 2-NAP, and 3-hydroxyfluorene (3-FLU). Increased prevalence of elevated TPOAb was associated with higher 2-NAP quartile. However, in subgroup analysis of females, no statistical significances were found between PAH quartiles and increased TgAb/TPOAb. Significant correlations were found among these 10 PAH metabolites. In conclusion, the cross-sectional study indicated that exposure to PAH might disturb the concentrations of thyroid hormones and thyroid autoantibodies. It is noteworthy that significant differences existed in males and females. Further prospective research is warranted to explore the causal relationship and underlying mechanism of PAH exposure on thyroid dysfunction.

High-fructose corn syrup intake increases hepatic mitochondrial DNA copy number and methylation in adolescent rats.

High-fructose corn syrup (HFCS) is consumed worldwide. However, it has been demonstrated that an increased intake of sweetened beverages, including those sweetened using fructose, is associated with the development of childhood obesity. It is unknown why the negative effects of fructose are stronger in young persons than in elderly individuals. In recent years, mitochondria have been identified as 1 of the targets of the negative effects of fructose; they possess their own genome called mitochondrial DNA (mtDNA), which encodes genes involved in metabolic functions. We hypothesized that HFCS intake affects mtDNA in the livers of rats, and that the intensity of these effects is age-dependent. The experimental period was divided into 3 parts: childhood and adolescence (postnatal day [PD] 21-60), young adulthood (PD61-100), and adulthood (PD101-140). Rats in the different age groups were assigned to receive either water (control group [CONT]) or a 20% HFCS solution (HFCS). The hepatic mtDNA copy number of the HFCS group was higher than that of the CONT group in childhood and adolescence. In addition, the mtDNA methylation level was increased in the HFCS group in the same experimental period. No significant differences were observed between the CONT and HFCS groups during the other experimental periods. We demonstrated that HFCS has the strongest effect on mtDNA during childhood and adolescence, suggesting a need to analyze the HFCS intake of young people.

Detection of simple proteins by direct surface-enhanced Raman scattering based on the Hofmeister ion-specific effect.

Surface-enhanced Raman scattering (SERS) spectroscopy has unique advantages in detecting biomolecules, but label-free determination of proteins with low scattering cross-sections remains challenging. In this study, such proteins' SERS signals have been optimized using the Hofmeister effect between protein molecules and CsI solution at physiological concentrations (A 100 mmol/L Cesium iodide, CsI). Cs+ as chaotro cation ion has a complex interaction mechanism with protein, can not only deprive hydrated water molecules on the surface of protein but also penetrate into the hydrophobic interior of protein. In addition to the above advantages, I- in excess CsI solution with appropriate concentration can removes the interference of citric acid-based impurities on the surface of silver nanoparticles, and Cs+ in excess CsI solution attracts the aggregation of negatively charged silver nanoparticles and cause local electromagnetic field enhancement to achieve high sensitivity in protein detection. This has been combined with principal component analysis to perform a comprehensive analysis of several proteins. Molecular dynamics simulations have been performed to study the mechanism of interaction between CsI and proteins. In addition, the vibrational peak of water has been used as an internal standard to quantify the protein content, and a good linear relationship between peak intensity and concentration was obtained.