Proinflammatory Diet Increases the Risk of Irritable Bowel Syndrome: A Prospective Study of 129,408 UK Biobank Participants and Mendelian Randomization Analysis.

BACKGROUND: Patients with irritable bowel syndrome (IBS) often have chronic low-grade inflammation in the intestinal mucosa. Some dietary components are known to be associated with inflammation. However, there is currently limited research on the relationship between dietary inflammatory potential and the risk of IBS. METHODS: A total of 129,408 participants in the UK Biobank were included in this study. Energy-Adjusted Dietary Inflammatory Index (E-DII) based on 26 nutrients and the Empirical Dietary Inflammatory Pattern (EDIP) based on 17 food groups were constructed, and on the basis of the tertiles, the continuous score was categorized into proinflammatory, neutral, and antiinflammatory categories. Associations between IBS and E-DII and EDIP were investigated by multivariable Cox proportional hazard models. Potential confounders including sociodemographic, lifestyle, body mass index (BMI), psychological state, type 2 diabetes, and thyroiditis were adjusted. In addition, subgroup analysis and sensitivity analysis were also performed. Finally, a two-sample Mendelian randomization (MR) analysis was employed to explore the independent causality of nutrients and dietary-derived serum antioxidants with IBS. RESULTS: In the cohort study, over a median follow-up period of 13.26 years, 2421(1.87%) participants developed IBS. In the E-DII categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with the antiinflammatory category (HR 1.15, 95% CI 1.03-1.28, p = 0.015, p trend = 0.017) and neutral category (HR 1.13, 95% CI 1.01-1.26, p = 0.030, p trend = 0.017). In the EDIP categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with antiinflammatory category (HR 1.19, 95% CI 1.06-1.33, p = 0.002, p trend = 0.002) but no significant association compared with neutral category (HR 1.10, 95% CI 0.99-1.23, p = 0.067, p trend = 0.002). In the MR analysis, genetically determined intake levels of 16 nutrients and 6 dietary sources of circulating antioxidants did not have a causal effect on IBS. CONCLUSIONS: Our findings indicate that proinflammatory dietary components are independent risk factors for IBS. However, there is no causal relationship between individual nutrient intake or serum antioxidants from dietary sources and IBS.

Association between pro-inflammatory diet and abdominal pain: cross-sectional and case-control study from UK biobank and NHANES 2017-2020.

BACKGROUND: There is a close association between diet and abdominal pain; however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet. METHODS: This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q), which including abdominal pain in the past 3 months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain. RESULTS: In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02-1.24; P = .022), 1.05 (95% CI 1.00-1.09; P = .030), 1.26 (95% CI 1.17-1.36; P < .001), and 1.10 (95% CI 1.00-1.20; P = .044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20-1.77;P < .001), 1.75 (95% CI 1.20-2.60; P = .005), 1.45 (95% CI 1.14-1.87; P = .003), and 1.18 (95% CI 0.82-1.72; P = .380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (P nonlinear <.001). CONCLUSION: Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.

Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress.

INTRODUCTION: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. METHODS AND RESULTS: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. CONCLUSIONS: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.

Paraventricular Nucleus Oxytocin Subsystems Promote Active Paternal Behaviors in Mandarin Voles.

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles (Microtus mandarinus) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT circuit enhanced/inhibited paternal care. This finding is a first step toward delineating the neuronal circuity underlying paternal care and may have implications for treating abnormalities in paternal care associated with paternal postpartum depression or paternal abuse.SIGNIFICANCE STATEMENT Paternal behavior is essential for offspring survival and development in some mammalian species. However, the circuit mechanisms underlying the paternal brain are poorly understood. We show that manipulation of paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) oxytocin (OT) projections as well as VTA to nucleus accumbens (NAc) DA projections promote paternal behaviors. Inhibition the PVN to VTA OT pathway reduces DA release in the NAc during pup licking and grooming. PVN to NAc OT circuit is also essential for paternal behaviors. Our findings identify two new neural circuits that modulate paternal behaviors.

Reduced Consolation Behaviors in Physically Stressed Mandarin Voles: Involvement of Oxytocin, Dopamine D2, and Serotonin 1A Receptors Within the Anterior Cingulate Cortex.

BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.

Preweaning Paternal Deprivation Impacts Parental Responses to Pups and Alters the Serum Oxytocin and Corticosterone Levels and Oxytocin Receptor, Vasopressin 1A Receptor, Oestrogen Receptor, Dopamine Type I Receptor, Dopamine Type II Receptor Levels in Relevant Brain Regions in Adult Mandarin Voles.

Although maternal separation and neonatal paternal deprivation (PD) have been found to exert a profound and persistent effects on the physiological and behavioural development of offspring, whether preweaning PD (PPD; from PND 10 to 21) affects maternal and parental responses to pups and the underlying neuroendocrine mechanism are under-investigated. Using monogamous mandarin voles (Microtus mandarinus), the present study found that PPD increased the latency to approach a pup-containing ball, decreased the total durations of sniffing and contacting a pup-containing ball and walking and increased the total duration of inactivity in both sexes. Moreover, PPD decreased serum oxytocin levels and increased corticosterone levels, but only in females. Furthermore, in both males and females, PPD decreased the expression of oxytocin receptor mRNA and protein in the medial preoptic area (MPOA), nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), but increased it in the medial amygdala (MeA) and decreased the expression of oestrogen receptor mRNA and protein in the MPOA. PPD increased the expression of dopamine type I receptor in the NAcc, but decreased it in the mPFC. PPD decreased dopamine type II receptor (D2R) in the NAcc both in males and females, but increased D2R in the mPFC in females and decreased D2R protein expression in males. Moreover, PPD decreased vasopressin 1A receptor (V1AR) in the MPOA, MeA and mPFC, but only in males. Our results suggest that the reduction of parental responses to pups induced by PPD may be associated with the sex-specific alteration of several neuroendocrine parameters in relevant brain regions.

Pulmonary Cryptococcosis: comparison of Cryptococcal antigen detection and radiography in Immunocompetent and Immunocompromised patients.

BACKGROUND: We compared the cryptococcal antigen detection and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed. The aim of our study was to determine whether the patient's immune status and radiography affect the detection of cryptococcal antigen. METHODS: According to whether they took immunosuppressive drugs or not, seventy and eight adult patients with pulmonary cryptococcosis were divided into two groups: the immunocompetent group and the immunocompromised group. According to the detection of CrAg, each group was divided into the CrAg+ group and the CrAg- group. Then, clinical records, laboratory examinations and computed tomography findings were collected and analyzed. RESULTS: No difference was found in baseline characteristics, clinical symptoms, and laboratory investigations. By comparing CrAg detection in these two groups, it was found that the number of CrAg+ cases in the immunocompetent group was more than that in the immunocompromised group. And in the immunocompetent group, diffuse lesions were more common in CrAg+ group and limited lesions were more frequently observed in CrAg- group. CONCLUSIONS: The patient's immune status and radiography would affect the detection of cryptococcal antigen. And serum CrAg could be a useful tool for the diagnosis of pulmonary cryptococcosis in immunocompetent patients with extensive lung involvement.

Role of oxytocin in the medial preoptic area (MPOA) in the modulation of paternal behavior in mandarin voles.

Parental care plays an important role in individual survival and development in mammals. Many studies have focused on the mechanisms underlying maternal behavior. However, the underlying neural mechanisms of paternal behavior are less understood. Using monogamous mandarin voles (Microtus mandarinus), the present study found that fathers initiated more paternal behavior and the virgin male showed more infanticide. Moreover fathers had shorter latency to approach a pup at the postnatal day (PND) 10 than PND1, PND20 than nonfathers. Fathers had a shorter latency to take care of unfamiliar pups than nonfathers. They had higher levels of paternal behavior at PND 10 than PND1 and PND20 toward the mandarin vole pups. Fathers had a significantly higher serum concentration of oxytocin (OT) than virgin males. Both RT-PCR and Western blot results indicated that the levels of the oxytocin receptor (OTR) in the medial preoptic area (MPOA) of fathers were significantly higher than in virgin males, but the levels of vasopressin 1a receptor (V1AR) mRNA and protein expression in the MPOA did not show significant differences. Microinjection of an oxytocin receptor antagonist into the MPOA significantly reduced the total duration of paternal behavior and increased the latency to approach the pup and initiate paternal behavior. Our results indicated that OT plays a key role in the modulation of paternal behavior via the MPOA.

Study on the Mechanism of Curcumin Regulating Lung Injury Induced by Outdoor Fine Particulate Matter (PM2.5).

BACKGROUND: Epidemiological studies have shown that exposure to PM induces oxidative stress, leading to a variety of health problems. In particular, PM2.5 contains a lot of substances harmful to the human body and penetrates into the lungs to induce lung injury. At the same time, there is increasing evidence that oxidative stress also affects the severity of lung injury. However, there is still no good way to reduce or eliminate these hazards. In the future, more experimental research is needed to further confirm the mechanisms of these hazards and formulate effective preventive measures and treatment plans for their hazard mechanisms. Curcumin has been reported to reduce oxidative stress and inflammatory damage and protect organs. OBJECTIVE: To investigate whether curcumin can play a protective role against PM2.5-induced oxidative stress and inflammatory damage by inducing expression of the HO-1/CO/P38 MAPK pathway. METHODS: In this experiment, PM2.5 was dropped into the trachea to establish a lung injury model in mice. 28 SPF-grade male Kunming mice were randomly divided into 4 groups: normal control group, saline control group, PM2.5 treatment group, and curcumin intervention group. Albumin (ALB), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were measured in alveolar lavage fluid (BALF) to assess lung tissue damage. Colorimetric detection of oxidative stress indicators such as MDA, GSH-PX, T-AOC, and CAT in the lung tissue was performed. The levels of IL-6 and TNF-α in the lung tissue were determined by ELISA. Histopathological examination was used for the assessment of alveolar epithelial damage. The protein expression of the HO-1/P38 MAPK pathway in the lung tissue was determined by Western blot and immunohistochemistry. Endogenous CO was detected by spectrophotometry. The results showed that the expression of the HO-1/CO/P38 MAPK protein in the lung tissue was significantly increased in the curcumin intervention group compared with the PM2.5 treatment group, and it was statistically significant (P < 0.05). Compared with the PM2.5 treatment group, the curcumin intervention group can reduce the amount of ALB, LDH, and ALP in BALF; reduce the levels of MDA, IL-1, and TNF-α in the lung tissue; and improve GSH-PX, T-AOC, and CAT levels, but there is no statistical difference (P > 0.05). CONCLUSION: We found that PM2.5 can cause lung damage through oxidative stress and inflammatory responses. Oxidative stress and inflammatory responses increase the expression of HO-1/CO/P38 MAPK. The intervention of curcumin can further increase the expression of HO-1/CO/P38 MAPK.

Pre-weaning paternal deprivation impairs social recognition and alters hippocampal neurogenesis and spine density in adult mandarin voles.

Disruption of the early social environment, such as maternal separation or early deprivation, can impair cognitive function, alter offspring neurogenesis and restrict dendritic architecture in the hippocampus. However, whether paternal deprivation during the pre-weaning period affects adult neurogenesis, synaptogenesis and social recognition remains unclear in monogamous species. In the present study, mandarin vole (Microtus mandarinus) pups were deprived of fathers during postnatal day 14-21. Then social recognition, hippocampal neurogenesis and spine density, basal levels of corticosterone (CORT) and oxytocin (OT) were examined at adulthood. We found that paternal deprivation impaired social recognition at adulthood. In addition, paternal deprivation significantly reduced 5-bromo-2-deoxyuidine (BrdU) immunoreactive cells (p < 0.01) and Brdu/Neun-labeled cells (p < 0.05) in the dentate gyrus compared to those of biparental care group in females, but not in males (p > 0.05). Meanwhile, paternal deprivation group had fewer double-staining cells with BrdU and the immature neuron marker doublecortin than biparental care group both in male (p < 0.01) and female (p < 0.05) voles. Paternal deprivation also decreased the number of dendritic spines in the dentate gyrus at adulthood. Paternal deprivation reduced circulating levels of OT and increased CORT only in females. These results demonstrated that impaired social recognition induced by paternal deprivation may be linked with alterations in neurogenesis and spine densityof the dentate gyrus and levels of OT and CORT, especially in females.

Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals.

Comparison of the associations between Life's Essential 8 and Life's Simple 7 with depression, as well as the mediating role of oxidative stress factors and inflammation: NHANES 2005-2018.

BACKGROUND: Cardiovascular health (CVH) is closely associated with depression. However, Life's Essential 8 (LE8), a novel CVH measure, has not yet been clearly linked to depression. This study aims to explore the association between LE8 and depression, compare its advantages over Life's Simple 7 (LS7), and investigate the mediating effects of oxidative stress and inflammation. METHODS: This study investigated cross-sectional data of adults aged 20 and above from National Health and Nutrition Examination Survey (NHANES) 2005 to 2018. The LE8 score (ranging from 0 to 100) was derived from the American Heart Association's definition, based on the unweighted average of 8 metrics, classified as low cardiovascular health (CVH) (0-49), moderate CVH (50-79), and high CVH (80-100). Similar to LE8, LS7 scores were categorized into inadequate (0-7), average (8-10), or optimal (11-14) after calculating the unweighted mean of each component. Depression was diagnosed using the Patient Health Questionnaire (PHQ-9), with a score of ≥10 defining depression. Adjusted for sociodemographic factors and other risk factors for depression, weighted logistic regression and restricted cubic spline analysis were used to explore the correlation. Receiver operating characteristic (ROC) curves were used to study the associations between CVH scores and depression. Subsequently, subgroup analysis and sensitivity analysis were conducted, followed by an exploration of the mechanisms involved. RESULTS: A total of 7 cycles from 2005 to 2018 contained complete data. Weighted logistic regression showed that both LS7 and LE8 were significantly associated with depression. Specifically, for LE8, after adjustment, the risk of depression decreased by 52 % for moderate CVH compared to low CVH (OR: 0.48, 95 % CI: 0.41-0.57, P < 0.0001), while the risk decreased by 80 % for high CVH (OR: 0.20, 95 % CI: 0.15-0.26, P < 0.0001, Ptrend < 0.0001). For LS7, after adjustment, compared with inadequate CVH, the risk of depression decreased by 49 % for average CVH (OR: 0.51, 95 % CI: 0.34-0.78, P = 0.002), and by 55 % for optimal CVH (OR: 0.45, 95 % CI: 0.27-0.74, P = 0.002, Ptrend < 0.0001). Area under ROC curves for predicting depression were 0.672 (95 % CI, 0.66-0.684; P < 0.001) and 0.605 (95 % CI, 0.59-0.619; P < 0.001) for LE8 and LS7 (PDeLong < 0.001), respectively. Sensitivity analysis demonstrated the robustness of the association. GGT and WBC jointly mediated 9.62 % of this association (all P < 0.001). LIMITATIONS: The cross-sectional study cannot infer causality. CONCLUSIONS: The association between Life's Essential 8 and depression was stronger and more practical. Oxidative stress and inflammation mediate this association. Individuals with extremely poor cardiovascular health have a 7-fold increased risk of depression, highlighting the necessity of maintaining at least moderate cardiovascular health.

Associations of exposure to volatile organic compounds with sleep health and potential mediators: analysis of NHANES data.

Objective: The effect of environmental pollution on sleep has been widely studied, yet the relationship between exposure to volatile organic compounds (VOCs) and sleep health requires further exploration. We aimed to investigate the single and mixed effect of urinary VOC metabolites on sleep health and identify potential mediators. Methods: Data for this cross-sectional study was collected from the National Health and Nutrition Examination Surveys (NHANES) (2005-2006, 2011-2014). A weighted multivariate logistic regression was established to explore the associations of 16 VOCs with four sleep outcomes. Following the selection of important VOCs through the least absolute shrinkage and selection operator (LASSO) regression, principal component analyses (PCA), weight quantile sum (WQS), and Bayesian kernel machine regression (BKMR) analyses were conducted to explore the associations between exposure to single and mixed VOCs and sleep outcomes, as well as identify the most contributing components. A mediation analysis was performed to explore the potential effect of depression scores. Results: Of the 3,473 participants included in the study, a total of 618 were diagnosed with poor sleep patterns. In logistic regression analyses, 7, 10, 1, and 5 VOCs were significantly positively correlated with poor sleep patterns, abnormal sleep duration, trouble sleeping, and sleep disorders, respectively. The PCA analysis showed that PC1 was substantially linked to a higher risk of poor sleep patterns and its components. The WQS model revealed a positive association between VOC mixture of increased concentrations and poor sleep patterns [OR (95% CI): 1.285 (1.107, 1.493)], abnormal sleep duration [OR (95% CI): 1.154 (1.030, 1.295)], trouble sleeping [OR (95% CI): 1.236 (1.090, 1.403)] and sleep disorders [OR (95% CI): 1.378 (1.118, 1.705)]. The BKMR model found positive associations of the overall VOC exposure with poor sleep patterns, trouble sleeping, and sleep disorders. PCA, WQS, and BKMR models all confirmed the significant role of N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) in poor sleep patterns and its components. The depression score was a mediator between the positive VOC mixture index and the four sleep outcomes. Conclusion: Exposure to single and mixed VOCs negatively affected the sleep health of American population, with AMCC playing a significant role. The depression score was shown to mediate the associations of VOC mixtures with poor sleep patterns and its components.

Single and mixed effects of multiple volatile organic compounds exposure on hematological parameters in the U.S. adult population.

BACKGROUND: Most research exploring the correlation between volatile organic compounds (VOCs) and hematological parameters have focused on single VOCs. Our study aimed to explore the single and combined effects of VOCs on hematological parameters through three statistical models. METHODS: Data from 4 cycles of the National Health and Nutrition Examination Survey (NHANES) were used in this study. The correlations between single exposure to 16 VOCs and hematological parameters in the general population were assessed by weighted multiple linear regression. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were used to explore the relationship between the combined important VOCs selected by the least absolute shrinkage and selection operator (LASSO) and hematological parameters, as well as the effects of smoking status on them. RESULTS: A total of 4089 adults were included in the study. We found that a variety of VOCs were significantly associated with hematological parameters. Among them, N-acetyl-S-(benzyl)-l-cysteine (BMA) was significantly negatively correlated with white blood cell (WBC), red blood cell (RBC), lymphocyte, and neutrophil counts. N-acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine (HPMMA) was significantly positively correlated with WBC, monocyte, lymphocyte, and neutrophil counts. In the WQS analysis, the WQS index of the VOCs mixtures was positively correlated with WBC (ß: 0.031; P < 0.001), monocyte (0.023; P = 0.021), and neutrophil (0.040; P = 0.001) counts, while negatively associated with RBC (-0.013; P < 0.001) counts. The BKMR model revealed that combined exposure to VOCs levels ≥70th percentile was significantly associated with lower RBC counts, and BMA was identified as the dominant contributor. Smoking significantly influenced the relationship between VOCs and hematological parameters. CONCLUSIONS: Our study indicated the effects of single and overall VOCs exposure on hematological parameters and suggested the hematotoxicity as well as pro-inflammatory effects of VOCs, which had strong public health implications for reducing the potential health hazards of VOCs exposure to the hematologic system.

Association between Life's Essential 8 and Infertility as Well as the Mediating Effects of Oxidative Stress and Inflammatory Factors Among U.S. Women Aged 18-45 Years.

Management of cardiovascular disease in pregnancy is important, yet the association between cardiovascular health and infertility is rarely reported. In this study, we aimed to explore the association between Life's Essential 8 (LE8), a novel cardiovascular health (CVH) measure, and infertility, and to investigate potential mediating mechanisms. This study investigated cross-sectional data from the 2013-2018 National Health and Nutrition Examination Survey. LE8 score (ranging from 0 to 100) was calculated as the unweighted average of eight CVH metrics. The association between LE8 and infertility was explored through weighted multiple logistic regression. Restricted cubic splines were used to explore nonlinear correlation. In addition, mediation analysis was conducted to investigate the role of oxidative stress and inflammatory markers systematically. After strict exclusion criteria, 1703 American women aged 18-45 years were included. After full adjustment, the LE8 score showed a negative correlation with infertility [per 1 SD increase, OR = 0.675, 95% CI: 0.553-0.824], with a linear dose-response relationship (non-linear P = 0.122). Similar linear negative correlations were found between health factor scores and infertility, with higher body mass index and glucose scores having a significantly lower risk of infertility. Stratified analyses showed a stronger inversed relationship between LE8 and infertility in younger populations. Moreover, mediation analysis revealed that uric acid concentration and lymphocyte count mediated the effect of LE8 on infertility (P < 0.05). LE8 and its subscale scores were linearly and negatively associated with infertility, which may be mediated in part through uric acid and lymphocyte count. Focusing on weight management and glycemic control can effectively reduce the risk of infertility.

5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice.

Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.

GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

Type II diabetes mellitus increases the risk of inflammatory bowel disease in a prospective cohort study.

BACKGROUND: Inflammatory bowel disease is a common digestive disorder and diabetes can lead to intestinal dysfunction. Patients with inflammatory bowel disease in combination with diabetes present a higher rate of hospitalization and consumption of medical resources, yet the association between type 2 diabetes and Inflammatory bowel disease remains unknown. METHODS: We studied 313,008 participants from the UK Biobank, including 5891 patients with type 2 diabetes at baseline. Multivariate Cox proportional risk models were constructed to examine the risks associated with type 2 diabetes and inflammatory bowel disease and its subtypes (Crohn's disease, ulcerative colitis). Potential confounders including sociodemographic, lifestyle, physical body indicators, psychological state, hypertension, and thyroid-related disorders were adjusted. Propensity score matching was also performed to analyze their sensitivity. RESULTS: Of a total of 313,008 participants included in the study, 5891 (1.88 %) were diagnosed with type 2 diabetes mellitus at baseline and 1829 (0.58 %) of the entire cohort developed inflammatory bowel disease during follow-up, with a median follow-up time of 13.72 years. Patients with type 2 diabetes had a higher cumulative risk of inflammatory bowel disease compared to the non-type 2 diabetes population (inflammatory bowel disease: 1.24% vs. 0.57%, p < 0.001; Crohn's disease: 0.46% vs. 0.15%, p < 0.001; ulcerative colitis: 0.73% vs. 0.35%, p < 0.001). Multivariate Cox regression analysis showed that type 2 diabetes was independently associated with inflammatory bowel disease (Hazard Ratio: 1.61 [95% Confidence Interval: 1.26-2.06], p < 0.001), Crohn's disease (Hazard Ratio: 2.10 [95% Confidence Interval: 1.39-3.17], p < 0.001) and ulcerative colitis (Hazard Ratio: 1.58 [95% Confidence Interval: 1.15-2.18], p = 0.005). In a propensity-matched analysis, type 2 diabetes still showed its ability to predict the risk of inflammatory bowel disease (Hazard Ratio: 2.09 [95% Confidence Interval: 1.55-2.83], p < 0.001), Crohn's disease (Hazard Ratio: 3.49 [95% Confidence Interval: 2.00 to 6.09], p < 0.001), and ulcerative colitis (Hazard Ratio: 1.76 [95% Confidence Interval: 1.20 to 2.56], p = 0.003) of robustness. CONCLUSION: In patients with type 2 diabetes mellitus, the risk of inflammatory bowel disease is higher, and the presence of gastrointestinal symptoms in patients with type 2 diabetes requires vigilance for the possibility of inflammatory bowel disease in clinical practice.

Efficacy of Polyethylene Glycol Electrolyte Powder Combined With Linaclotide for Colon Cleansing in Patients With Chronic Constipation Undergoing Colonoscopy: A Multicenter, Single-Blinded, Randomized Controlled Trial.

INTRODUCTION: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation (CC). METHODS: This single-blinded, randomized, controlled, and multicenter study was conducted from July 2021 to December 2022 at 7 hospitals. Patients with CC who underwent colonoscopies were enrolled and randomly assigned to 4 groups with split-PEG regimens: 4L-PEG group, 4L-PEG+1d-Lin group, 3L-PEG+1d-Lin group, and 3L-PEG+3d-Lin group. The primary outcome was rates of adequate bowel preparation, defined as a total BBPS score ≥6 and a score ≥2 for each segment. Secondary outcomes were adverse effects, sleep quality, willingness to repeat the colonoscopy, adenoma detection rate, and polyp detection rate. RESULTS: Five hundred two patients were enrolled. The rates of adequate bowel preparation (80.0% vs 60.3%, P < 0.001; 84.4% vs 60.3%, P < 0.001) and the total Boston Bowel Preparation Scale (BBPS) scores (6.90 ± 1.28 vs 6.00 ± 1.61, P < 0.001; 7.03 ± 1.24 vs 6.00 ± 1.61, P < 0.01) in the 4L-PEG+1d-Lin group and the 3L-PEG+3d-Lin group were superior to that in the 4L-PEG group. Compared with the 4L-PEG group, the 4L-PEG+1d-Lin group (66.7% vs 81.7%, P = 0.008) and the 3L-PEG+3d-Lin group (75.0% vs 81.7%, P = 0.224) had a lower percentage of mild adverse events. No statistically significant difference in willingness to repeat the colonoscopy, sleep quality, polyp detection rate, or adenoma detection rate was observed among groups. DISCUSSION: PEG combined with linaclotide might be an effective method for bowel preparation before colonoscopy in patients with CC.