Search

Background: The awareness of the association between the gut microbiota and human intelligence levels is increasing, but the findings are inconsistent. Furthermore, few research have explored the potential role of gut microbial metabolites in this association. This study aimed to investigate the associations of the gut microbiota and fecal metabolome with intelligence quotient (IQ) in preschoolers. Methods: The 16 S rRNA sequencing and widely targeted metabolomics were applied to analyze the gut microbiota and fecal metabolites of 150 children aged 3–6 years. The Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to assess the cognitive competence. Results: The observed species index, gut microbiome health index, and microbial dysbiosis index presented significant differences between children with full-scale IQ (FSIQ) below the borderline (G1) and those with average or above-average (all P < 0.05). The abundance of Acinetobacter, Blautia, Faecalibacterium, Prevotella_9, Subdoligranulum, Collinsella, Dialister, Holdemanella, and Methanobrevibacter was significantly associated with preschooler's WPPSI-IV scores (P < 0.05). In all, 87 differential metabolites were identified, mainly including amino acid and its metabolites, fatty acyl, and benzene and substituted derivatives. The differential fecal metabolites carnitine C20:1-OH, 4-hydroxydebrisoquine, pantothenol, creatine, N,N-bis(2-hydroxyethyl) dodecanamide, FFA(20:5), zerumbone, (R)-(-)-2-phenylpropionic acid, M-toluene acetic acid, trans-cinnamaldehyde, isonicotinic acid, val-arg, traumatin, and 3-methyl-4-hydroxybenzaldehyde were significantly associated with the preschooler's WPPSI-IV scores (P < 0.05). The combination of Acinetobacter, Isonicotinic acid, and 3-methyl-4-hydroxybenzaldehydenine may demonstrate increased discriminatory power for preschoolers in G1. Conclusion: This study reveals a potential association between gut microbiome and metabolites with IQ in preschoolers, providing new directions for future research and practical applications. However, due to limitations such as the small sample size, unclear causality, and the complexity of metabolites, more validation studies are still needed to further elucidate the mechanisms and stability of these associations. [ABSTRACT FROM AUTHOR]

Motivated by the recent rapid growth of research for algorithms to cluster multi-layer and temporal graphs, we study extensions of the classical Cluster Editing problem. In Multi-Layer Cluster Editing we receive a set of graphs on the same vertex set, called layers and aim to transform all layers into cluster graphs (disjoint unions of cliques) that differ only slightly. More specifically, we want to mark at most d vertices and to transform each layer into a cluster graph using at most k edge additions or deletions per layer so that, if we remove the marked vertices, we obtain the same cluster graph in all layers. In Temporal Cluster Editing we receive a sequence of layers and we want to transform each layer into a cluster graph so that consecutive layers differ only slightly. That is, we want to transform each layer into a cluster graph with at most k edge additions or deletions and to mark a distinct set of d vertices in each layer so that each two consecutive layers are the same after removing the vertices marked in the first of the two layers. We study the combinatorial structure of the two problems via their parameterized complexity with respect to the parameters d and k, among others. Despite the similar definition, the two problems behave quite differently: In particular, Multi-Layer Cluster Editing is fixed-parameter tractable with running time k O (k + d) s O (1) for inputs of size s, whereas Temporal Cluster Editing is W [ 1 ] -hard with respect to k even if d = 3 . [ABSTRACT FROM AUTHOR]

We characterize one-dimensional Euclidean preference profiles with a small number of alternatives and voters. We show that every single-peaked preference profile with two voters is one-dimensional Euclidean, and that every preference profile with up to five alternatives is one-dimensional Euclidean if and only if it is both single-peaked and single-crossing. By the work of Chen et al. (Social Choice and Welfare 48(2):409–432, 2017), we thus obtain that the smallest single-peaked and single-crossing preference profiles that are not one-dimensional Euclidean consist of three voters and six alternatives. [ABSTRACT FROM AUTHOR]

• Histoplasmosis mainly involves the lung, with the uncommon disseminated forms involving other rare sites such as the epiglottis. • Metagenomic next-generation sequencing should be considered an important addition to improve the diagnostic yield for Histoplasma capsulatum. • Heightened suspicion of inborn errors of immunity is required for who develop disseminated histoplasmosis without acquired immune deficiency. Histoplasmosis is an endemic disease mainly occurring in North America and is rare in China. Confirmation of histoplasmosis should be based on a compatible clinical scenario and a positive culture or histopathology. However, there are still many cases that are misdiagnosed or missed, especially in individuals from non-endemic areas. In recent years, metagenomic next-generation sequencing (mNGS) has led to the accurate and timely diagnosis of some rare and complicated infectious diseases. We describe the case of a 27-year-old Chinese man who had chronic progressive pulmonary lesions without any symptoms for more than 1 year, until the lesions reached the epiglottis and led to progressive pharyngeal pain. There were no positive results from bronchoalveolar lavage fluid (BALF) and epiglottis tissue cultures, or from epiglottis and lung pathological examinations, but mNGS was able to identify Histoplasma capsulatum in the epiglottis tissues and BALF as the cause of the lesions. The patient was treated successfully with itraconazole. [ABSTRACT FROM AUTHOR]

Hepatitis B virus-associated (HBV(+)) hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer with poor clinical outcomes and treatment options. However, the underlying molecular mechanisms are still poorly understood. To explore potential key genes in the development of HBV(+)HCC, four series of data (GSE14520, GSE94660, GSE25599, and GSE55092) derived from Gene Expression Omnibus database were analyzed. Totally, 84 upregulated and 46 downregulated common differentially expressed genes (DEGs) were discovered. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that these DEGs were mainly enriched in cell division and DNA replication biological processes, nucleoplasm and microtubule cellular components, protein-binding molecular functions, and cell cycle and DNA replication pathways. Through protein–protein interaction analysis, 10 hub DEGs with the highest degree of connectivity were indicated, including TOP2A, CDC20, MAD2L1, BUB1B, RFC4, CCNB1, CDKN3, CCNB2, TPX2, and FEN1. Kaplan–Meier analysis revealed that high expression of TOP2A and CDC20 was associated with poor overall survival, relapse-free survival, and high serum alpha-fetoprotein level in HBV(+)HCC. In conclusion, TOP2A and CDC20 were two potential key genes for HBV(+)HCC. Their value in the diagnosis and treatment of HBV(+)HCC requires further investigation. [ABSTRACT FROM AUTHOR]

Given a task that requires some skills and a social network of individuals with different skills, the Team Formation problem asks to find a team of individuals that together can perform the task, while minimizing communication costs. Since the problem is NP-hard, we identify the source of intractability by analyzing its parameterized complexity with respect to parameters such as the total number of skills k , the team size l , the communication cost budget b , and the maximum vertex degree Δ. We show that the computational complexity strongly depends on the communication cost measure: when using the weight of a minimum spanning tree of the subgraph formed by the selected team, we obtain fixed-parameter tractability for example with respect to the parameter k . In contrast, when using the diameter as measure, the problem is intractable with respect to any single parameter; however, combining Δ with either b or l yields fixed-parameter tractability. [ABSTRACT FROM AUTHOR]

We show that one-dimensional Euclidean preference profiles can not be characterized in terms of finitely many forbidden substructures. This result is in strong contrast to the case of single-peaked and single-crossing preference profiles, for which such finite characterizations have been derived in the literature. [ABSTRACT FROM AUTHOR]

In the Shift Bribery problem, we are given an election, a preferred candidate p , and a budget. The goal is to ensure p 's victory by shifting p higher in some voters' preference orders. However, each such shift request comes at a price and we must not exceed the given budget. We study the parameterized computational complexity of Shift Bribery for a number of parameters and several classes of price functions: For the number of affected voters, Shift Bribery is W [ 2 ] -hard for Borda, Maximin, and Copeland. For the number of positions by which p is shifted in total, the problem is fixed-parameter tractable for Borda and Maximin, and is W [ 1 ] -hard for Copeland. For the budget, the results depend on the price function class. Finally, Shift Bribery tends to be tractable when parameterized by the number of voters, but the results for the number of candidates are more enigmatic. [ABSTRACT FROM AUTHOR]

We investigate the problem of deciding whether a given preference profile is close to having a certain nice structure, as for instance single-peaked, single-caved, single-crossing, value-restricted, best-restricted, worst-restricted, medium-restricted, or group-separable profiles. We measure this distance by the number of voters or alternatives that have to be deleted to make the profile a nicely structured one. Our results classify the problem variants with respect to their computational complexity, and draw a clear line between computationally tractable (polynomial-time solvable) and computationally intractable (NP-hard) questions. [ABSTRACT FROM AUTHOR]

Maintaining homeostasis is of utmost importance regarding human health. Several factors could protect human body's internal environment from harms and fluctuations from external environment. Regulation of physiological pH has a considerable role in maintaining human health and its metabolic functions. Several studies have shown that the interstitial body fluid pH around metabolic tissues is easily reduced due to weaker pH buffering capacity than that in the cytosol and blood circulation. Therefore, pH reduction in the interstitial fluid may cause the onset of metabolic dysfunctions. However, several dietary food components have potential benefits in maintaining the interstitial fluid pH to the normal range by improving buffering capacities, suppressing proton production, and activating proton transporters, which strengthen the effect of appropriate diet on metabolic health. Keeping deep insights about this aspect, we have summed up several facts and figures for maintaining human body homeostasis via regulation of physiological pH. Furthermore, we have discussed about different food categories and their potential renal acid load and its relation with maintaining homeostasis. Afterwards we have deeply discussed the potential beneficial role of healthy food components in different pathological conditions of human body. [ABSTRACT FROM AUTHOR]

Voter control problems model situations such as an external agent trying to affect the result of an election by adding voters, for example by convincing some voters to vote who would otherwise not attend the election. Traditionally, voters are added one at a time, with the goal of making a distinguished alternative win by adding a minimum number of voters. In this paper, we initiate the study of combinatorial variants of control by adding voters. In our setting, when we choose to add a voter v , we also have to add a whole bundle κ ( v ) of voters associated with v . We study the computational complexity of this problem for two of the most basic voting rules, namely the Plurality rule and the Condorcet rule. [ABSTRACT FROM AUTHOR]

We extend previous studies on “explaining” a nonnegative integer vector by sums of few homogeneous segments, that is, vectors where all nonzero entries are equal and consecutive. We study two NP-complete variants which are motivated by radiation therapy and database applications. In Vector Positive Explanation , the segments may have only positive integer entries; in Vector Explanation , the segments may have arbitrary integer entries. Considering several natural parameterizations such as the maximum vector entry γ and the maximum difference δ between consecutive vector entries, we obtain a refined picture of the computational (in-)tractability of these problems. For example, we show that Vector Explanation is fixed-parameter tractable with respect to δ , and that, unless NP ⊆ coNP / poly , there is no polynomial kernelization for Vector Positive Explanation with respect to the parameter γ . We also identify relevant special cases where Vector Positive Explanation is algorithmically harder than Vector Explanation . [ABSTRACT FROM AUTHOR]

We characterize single-crossing preference profiles in terms of two forbidden substructures, one of which contains three voters and six (not necessarily distinct) alternatives, and one of which contains four voters and four (not necessarily distinct) alternatives. We also provide an efficient way to decide whether a preference profile is single-crossing. [ABSTRACT FROM AUTHOR]

Bronchiolitis is one of the most common lower respiratory diseases in infants. A correlation between the severity of bronchiolitis and a co-infection with respiratory syncytial virus (RSV) as well as other viruses has not yet been elucidated. The purpose of this study was to clarify the impact of RSV co-infection with other viruses on the severity of bronchiolitis and airway inflammation. One hundred and twelve hospitalized children with clinical symptoms of bronchiolitis were prospectively enrolled in this study. Nasopharyngeal aspirates were analyzed to identify RSV, human bocavirus, human metapneumovirus and nine other respiratory viral pathogens. Inflammatory cell counting and concentrations of cytokines/chemokines were also evaluated. The severity of the disease was further determined on the basis of symptom score and duration of hospitalization. Viral pathogens were detected in 84 samples (75%). RSV was detected in 62 samples (55.36%), 31 of which also possessed other viruses. No difference was found between children with bronchiolitis that had RSV as the sole infecting viral agent and those that were infected with RSV and other viruses with respect to the prevalence of symptoms prior to admission to the hospital, the duration of hospitalization and the diagnosis of severe bronchiolitis. The median cellularity, concentrations of cytokines and cell counts of nasopharyngeal aspirates were similar between the two groups of children. The severity of bronchiolitis is not dependent on the co-infection of RSV with other respiratory viruses. [ABSTRACT FROM AUTHOR]

Background: While prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children. Methods: A total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR). Results: In GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (β = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (β = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (β = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR. Conclusions: Prenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs. [ABSTRACT FROM AUTHOR]

We propose a scheme for a Bell–Bloom atomic magnetometer based on a single beam. In our approach, the light is periodically modulated synchronously with Larmor precession. As a result, the light that interacts with atoms is alternately polychromatic and monochromatic. When the light is polychromatic, the ±1st sidebands of the light are optically resonant with the atoms, and the atoms are polarized by pumping. When the light is monochromatic, a differential detection technique extracts the Faraday-rotation signal of the light, and the polarization of the light is probed. We demonstrate an experimental implementation of the Bell–Bloom magnetometer that achieves a sensitivity for magnetic-field detection of 0.25 pT/Hz1/2 at 1 Hz. Our scheme is suitable for developing compact, miniaturized magnetometers. [ABSTRACT FROM AUTHOR]

We report on research into a microfabricated 87Rb vapor cell with differential detection. Elliptically polarized light is used to interact with alkali atoms to generate coherent population trapping (CPT) resonance, and the CPT signal is obtained by detecting the Faraday rotation effect with differential detection technology. To move closer to an actual chip-scale atomic clock (CSAC), we reduce the volume of the experimental apparatus and use a divergent laser beam to interact with the atoms. We obtain the short-term frequency stability of the CSAC based on the differential detection scheme and compare it with that of a conventional CSAC. The results show that the frequency stability is more than two times better than that of current commercial CSAC devices with the same power consumption and volume. [ABSTRACT FROM AUTHOR]

The relationship between prenatal physical activity (PA) and adverse birth outcomes is still inconclusive. We aimed to investigate the association between PA during pregnancy and adverse birth outcomes by using data from the Guangxi Zhuang birth cohort (GZBC) in China. A total of 11,292 mother-infant pairs were included from GZBC in China. The information on PA status, intensity, adequacy, and volume and birth outcomes were collected. Multivariable linear and logistic regression models were applied to analyze the effects of PA during pregnancy on birth weight z-scores (BW z-scores) and gestational age and risk of small-for-gestational age (SGA) and preterm birth (PTB), respectively. Cubic spline analysis was conducted to detect a nonlinear dose-response of total weekly activity metabolic equivalents (MET) and birth outcomes. Compared to no regular PA during pregnancy, moderate and high-intensity PA (MVPA) was associated with increase BW z-scores (β = 0.08, 95%CI: 0.002, 0.15, p =.044) and associated with a marginal significant decrease in risk of PTB (OR = 0.73, 95%CI: 0.51, 1.05, p =.093). However, PA had no relationship with gestational age and risk of SGA, and Nonlinear relationships were not observed between total weekly activity MET and risk of SGA and PTB. These finding shows that PA during pregnancy may increase the BW z-score and reduce risk of PTB, supporting the guidelines that pregnant women should be encouraged to engage in appropriate physical activity during pregnancy in China. [ABSTRACT FROM AUTHOR]

Maternal environmental metal exposure is common, but long-term prospective epidemiological evidence of its impact on children's intellectual development is still insufficient. Data on maternal plasma metal levels and child intelligence were obtained for 211 3–6-year-old children from Guangxi Zhuang Birth Cohort. ICP-MS was employed to detect 17 metals, including 7 essential metals (Mn, Fe, Co, Ni, Cu, Zn, Mo) and 10 non-essential metals (As, Rb, Sr, Cd, Sb, Cs, Ba, W, Pb, U), in maternal plasma samples obtained before 13 weeks of gestation during the initial maternity checkup. Child intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. The GLM, RCS and mixture models were used to assess the associations of maternal plasma metal levels with child intelligence quotient (IQ) scores. The GLM analysis revealed that U had a significant adverse effect on child IQ scores in high-dose exposure groups (−9.236 [-18.644, −4.936], p = 0.006) after adjusting for covariates, while Sb showed a linear adverse effect on children's intelligence in the adjusted model (−4.028 [-7.432, −0.626], p = 0.021). BKMR modeling indicated that overall IQ scores decreased as concentrations of non-essential metals mixtures increased after adjusting for essential metal mixtures, consistent with findings from the WQS (β [95% CI], −8.463 [-14.449, −2.476], p = 0.007) and Qgcomp models (−7.003 [-12.928, −1.078], p = 0.022). Among the non-essential metals, U had the highest negative weight at 37.96%, followed by Pb (23.35%) and Sb (16.91%). Furthermore, potential interactions were observed between metals (Pb and U) and Sb in the study findings. Reducing exposure to non-essential metal mixtures, especially U, Sb and Pb, during early pregnancy and ensuring adequate intake of specific essential metal elements could be a critical intervention in addressing childhood intellectual impairment. [Display omitted] • Early pregnancy single Sb and U exposure was related to childhood IQ. • Non-essential metals mixture exposure in early pregnancy was associated with a risk of childhood IQ decline. • U (37.96%), Pb (23.35%) and Sb (16.91%) were the main contributors to the risk of childhood intelligence. • Essential metals intervene in the detrimental effects of non-essential metal mixtures on children's intelligence. [ABSTRACT FROM AUTHOR]

In this study, three strains of lactobacilli and bifidobacteria originally isolated from healthy infants, were tested for their abilities to activate RAW264.7 cells. Gene expression and cytokine production of interleukin-10 (IL-10) of RAW264.7 cells were evaluated. The activation of extracellular regulated protein kinases 1/2 (ERK1/2), p38, and nuclear factor-κB (NK-κB) were also assessed. These results suggest lactobacilli and bifidobacteria in infants may promote production of IL-10 in macrophages, conferring a protective effect in hosts suffering from inflammation. Dimerization of TLR2 and MyD88 and subsequent phosphorylation of the key downstream signaling molecules, such as MAPKs and NK-κB, may be one of the key underlying mechanisms of activation of macrophages by these microbes. Bifidobacteria and lactobacilli induced macrophages to secrete IL-10 in a different manner, which may relate to their abilities to activate key signaling pathways mediated by TLR2 and MyD88. Lactobacilli and bifidobacteria derived from infant intestines may activate macrophages and lead to different IL-10 secretion [ABSTRACT FROM AUTHOR]

In this study, the difference detection magnetic optical rotation (MOR) Ramsey-coherent population trapping (CPT) interference fringe signal was taken as the object for research. By solving the optical Bloch equations, the analytic function solution was obtained. An experimental platform was also used to obtain the MOR Ramsey-CPT interference fringe signal experimentally. The experimental results match the results for the calculation of the analytic function. Use of the analytic function solution is convenient and effective for studying the Ramsey-CPT interference phenomenon. [ABSTRACT FROM AUTHOR]

Ethnic differences in the level of thyroid hormones exist among individuals. The American Thyroid Association (ATA) recommends that an institution or region should establish a specific thyroid hormone reference value for each stage of pregnancy. To date, a limited number of studies have reported the level of thyroid hormones in Chinese minorities, and the exact relationship between BMI and thyroid function in pregnant women is ill. This study was performed to establish trimester-specific reference ranges of thyroid hormones in Zhuang ethnic pregnant women and explore the role of body mass index (BMI) on thyroid function. A total of 3324 Zhuang ethnic health pregnant women were recruited in this Zhuang population-based retrospective cross-sectional study. The values of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were determined by automatic chemiluminescence immunoassay analyzer. Multivariate linear regression and binary logistic regression were constructed to evaluate the influence of BMI on the thyroid function. The established reference intervals for the serum thyroid hormones in three trimesters were as follows: TSH, 0.02–3.28, 0.03–3.22, and 0.08-3.71 mIU/L; FT4, 10.57–19.76, 10.05–19.23, and 8.96–17.75 pmol/L; FT3, 3.51–5.64, 3.42–5.42, and 2.93–5.03 pmol/L. These values were markedly lower than those provided by the manufacturers for nonpregnant adults which can potentially result in 6.10% to 19.73% misclassification in Zhuang pregnant women. Moreover, BMI was positively correlated with isolated hypothyroxinemia (OR=1.081, 95% CI=1.007–1.161), while the correlation between the BMI and subclinical hypothyroidism was not statistically significant (OR=0.991, 95% CI=0.917–1.072). This is the first study focusing on the reference ranges of thyroid hormones in Guangxi Zhuang ethnic pregnant women, which will improve the care of them in the diagnosis and treatment. We also found that high BMI was positively associated with the risk of isolated hypothyroxinemia. [ABSTRACT FROM AUTHOR]

This study was designed to validate thrombospondin 1 (TSP-1), vascular endothelial-cadherin complex (VE-cad), insulin-like growth factor 2 (IGF-2), and amyloid precursor protein (APP) and assess their diagnostic value in ventricular septal defect (VSD). We investigated the serum levels of TSP-1, VE-cad, IGF-2, and APP by enzyme-linked immunosorbent assay in a hospital-based case-control study that included 40 VSD children and 40 healthy controls. Logistic regression analysis was applied to evaluate the relationship of the proteins and VSD, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the significant proteins. The serum levels of TSP-1, VE-cad, and IGF-2 were significantly higher in VSD patients than those in healthy controls ( p < 0.05). Multivariate logistic regression analysis demonstrated that high levels of TSP-1, VE-cad, and IGF-2 were significantly associated with an increased risk of VSD [TSP-1 (OR 26.91, 95% CI 6.60-72.66, p < 0.001), VE-cad (OR 11.91, 95% CI 3.90-36.36, p < 0.001), IGF-2 (OR 3.25, 95% CI 1.25-8.43, p = 0.015)]. Areas under the ROC curve for TSP-1, VE-cad, and IGF-2 were 0.985, 0.838, and 0.658, respectively. These data demonstrated that TSP-1, VE-cad, and IGF-2 were significantly associated with risk of VSD and manifested diagnostic values, which may provide new evidence for understanding the etiology and promote the early diagnosis and prevention of VSD. [ABSTRACT FROM AUTHOR]

The partition of graphs into 'nice' subgraphs is a central algorithmic problem with strong ties to matching theory. We study the partitioning of undirected graphs into same-size stars, a problem known to be NP-complete even for the case of stars on three vertices. We perform a thorough computational complexity study of the problem on subclasses of perfect graphs and identify several polynomial-time solvable cases, for example, on interval graphs and bipartite permutation graphs, and also NP-complete cases, for example, on grid graphs and chordal graphs. [ABSTRACT FROM AUTHOR]

Purpose: Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells. Methods: Human colorectal cancer cell lines (HCT-116 and HT-29) were treated with sodium butyrate at concentrations ranging from 0.5–5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining), and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot. Results: Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II), beclin-1, and autophagocytosis-associated protein (Atg)3. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin) and genetic (siRNA targeting BIP and CHOP) methods, the induction of BIP, PDI, IRE1a, and LC3-II was blocked, but PARP cleavage was markedly enhanced. Discussion: Taken together, these results suggested that sodium butyrate-induced autophagy was mediated by endoplasmic reticulum stress, and that preventing autophagy by blocking the endoplasmic reticulum stress response enhanced sodium butyrate-induced apoptosis. These results provide novel insights into the anti-tumor mechanisms of butyric acid. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a common toxic mycotoxin and is detectable in pregnant women. Animal studies have revealed that AFB1 caused the lysis of erythrocytes and a decrease in hemoglobin. We conducted a prospective cohort study in Guangxi, China, in order to evaluate the association between AFB1 exposure and anemia in pregnant women during the entire pregnancy. A total of 616 pregnant women from the Guangxi Zhuang Birth Cohort were included in the study. Serum AFB1-albumin (AFB1-ALB) adduct levels were measured. The effect of AFB1-ALB adducts on hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed by using multivariable linear regression. The risks of anemia from AFB1-ALB adduct exposure were assessed by multivariable logistic regression. We found that the AFB1-ALB adduct was significantly associated with a decrease in Hb (β = −4.99, 95% CI: −8.42, −1.30), MCV (β = −4.58, 95% CI: −7.23, −1.94), MCH (β = −1.86, 95% CI: −2.87, −0.85), and MCHC (β = −5.23, 95% CI: −8.28, −2.17) in the first trimester with the third tertile of AFB1-ALB adducts when compared with the first tertile. Furthermore, the third tertile of the AFB1-ALB adduct significantly increased the risk of anemia by 2.90 times than compared to the first tertile in the first trimester (OR = 3.90, 95% CI: 1.67, 9.14). A significant positive does–response relationship existed between AFB1-ALB adduct levels and anemia risk (Ptrend = 0.001). When dividing anemia types, we only found that the third tertile of AFB1-ALB adduct increased the risk of microcytic hypochromic anemia (MHA) in the first trimester (OR = 14.37, 95% CI: 3.08, 67.02) and second trimester (OR = 4.75, 95% CI: 1.96, 11.51). These findings demonstrate the correlation between maternal AFB1 exposure during early pregnancy and risk of anemia, especially MHA, and during different trimesters in Southern China. More efforts should be made to diminish AFB1 exposure for pregnant women. [ABSTRACT FROM AUTHOR]