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Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
The hydrodynamic interactions (HIs) of two colloidal spheres characterized by the translation–translation (T–T) couplings have been studied under various confinements, but little is known regarding the HIs of anisotropic particles and rotational motions, which are common in nature and industry. Here, we study the T–T, rotation–rotation (R–R) and translation–rotation (T–R) hydrodynamic couplings of two colloidal ellipsoids sediment on the bottoms of channels in experiment, theory and simulation. We find that the degree of confinement and the particle shape anisotropy are critical tuning factors resulting in anomalous hydrodynamic and diffusive behaviours. The negative R–R coupling reflects the tendency of opposite rotations of two neighbouring ellipsoids. The positive T–R coupling reflects that an ellipsoid rotates away from the channel axis as another ellipsoid approaches. As the channel width increases, the positive T–T coupling changes to an abnormal negative coupling, indicating that the single-file diffusion can exist even in wide channels. By contrast, only positive T–T couplings were observed for spheres in channels. The T–T coupling increases with the aspect ratio p. The R–R coupling is the maximum at a moderate p ~ 2.8. The T–R coupling is the maximum at a moderate degree of confinement. The spatial range of HIs is longer than that of spheres and increases with p. We propose a simple model which reproduces some coupling phenomena between two ellipsoids, and it is further confirmed by low-Reynolds-number hydrodynamic simulation. These findings shed new light on anisotropic particle diffusion in porous media, transport through membranes, microfluidics and microrheology.
We aimed to investigate the associations between dietary branched-chain amino acids (BCAA) intake and long-term risks of CVD, cancer and all-cause mortality in nationwide survey participants aged ≥ 18.
This was a prospective cohort study. Dietary intakes of BCAA (leucine, isoleucine and valine) were determined from the total nutrient intake document. The main outcomes were CVD, cancer and all-cause mortality.
A nationally representative sample of US adults were recruited by the National Center for Health Statistics (NCHS) from 1988 to 1994.
A total of 14 397 adults aged ≥ 18 who participated in the United States National Health and Nutrition Examination Survey III (NHANES III) were included.
During 289 406 person-years of follow-up, we identified 4219 deaths, including 1133 from CVD and 926 from cancer. After multivariate adjustment, the hazard ratios (95 % confidence intervals) of all-cause mortality in the highest dietary BCAA and isoleucine intake quintile (reference: lowest quintiles) were 0·68 (0·48, 0·97) and 0·68 (0·48, 0·97), respectively. Each one-standard-deviation increase in total dietary BCAA or isoleucine intake was associated with an 18 % or 21 % decrease in the risk of all-cause mortality, respectively. The serum triglyceride (TAG) concentration was found to modify the association between the dietary BCAA intake and all-cause mortality (Pfor interaction = 0·008).
In a nationally representative cohort, higher dietary intakes of BCAA and isoleucine were independently associated with a lower risk of all-cause mortality, and these associations were stronger in participants with higher serum TAG concentrations.
Angiopoietin-like 4 (ANGPTL4) is a potent regulator of triacylglycerol metabolism but knowledge of the mechanisms underlying ANGPTL4 transcription in response to fatty acids is still limited in teleost. In this study, we explored the molecular characterization of ANGPTL4 and regulatory mechanisms of ANGPTL4 in response to fatty acids in large yellow croaker (Larimichthys crocea). Here, croaker angptl4 contained a 1416 bp open reading frame encoding a protein of 471 amino acids with highly conserved 12-amino acid consensus motif. Angptl4 was widely expressed in croaker, with the highest expression in the liver. In vitro, oleic and palmitic acids (OA and PA) treatments strongly increased angptl4 mRNA expression in croaker hepatocytes. Moreover, angptl4 expression was positively regulated by peroxisome proliferator-activated receptor family (PPAR-α, β and γ) and expression of pparγ was also significantly increased in response to OA and PA. Moreover, inhibition of PPARγ abrogated OA or PA-induced angptl4 mRNA expression. Beyond that, PA might increase angptl4 expression partly via the insulin signaling. Overall, the expression of ANGPTL4 is strongly upregulated by OA and PA via PPARγ in the liver of croaker, which contributes to improve the understanding of the regulatory mechanisms of ANGPTL4 in fish.
Early life exposure to famine was associated with adulthood metabolic syndrome and nonalcoholic fatty liver disease (NAFLD), and NAFLD was also affected by cardiometabolic traits. However, the role of cardiometabolic traits in the associations from famine exposure to NAFLD was largely unknown. This study aimed to investigate whether the relationship between early life famine exposure and adulthood NAFLD risk was mediated by cardiometabolic traits. Overall, 7578 subjects aged 56·0 (sd 3·7) years in the Dongfeng–Tongji cohort were included and classified into late-exposed (1952–1954), middle-exposed (1954–1956), early-childhood-exposed (1956–1958), fetal-exposed (1959–1961) and non-exposed (1962–1966, reference) group according to the birth year. NAFLD was diagnosed by experienced physicians via abdominal B-type ultrasound inspection. Mediation analysis was used to evaluate the mediating effects of cardiometabolic traits. Compared with those non-exposed, after multivariable adjustment, participants in fetal-exposed group (OR: 1·37; 95 % CI 1·08, 1·73) had 37 % higher risk to develop NAFLD, and the overall childhood-exposed group had marginally significant association with NAFLD (OR: 1·39; 95 % CI 0·99, 1·94). Stratification analysis found the famine–NAFLD associations more evident in women and those born in areas severely affected by famine. Mediation analysis showed that cardiometabolic traits such as total cholesterol, TAG glucose index, γ-glutamyl transpeptidase, alkaline phosphatase and alanine aminotransferase mediated 6·7–22·2 % of the relation from famine exposure to higher NAFLD risk. Early life exposure to famine was related to increased adulthood NAFLD risk, and this relationship was partly mediated by cardiometabolic traits.
No relevant studies have yet been conducted to explore which measurement can best predict the survival time of patients with cancer cachexia. This study aimed to identify an anthropometric measurement that could predict the 1-year survival of patients with cancer cachexia. We conducted a nested case–control study using data from a multicentre clinical investigation of cancer from 2013 to 2020. Cachexia was defined using the Fearon criteria. A total of 262 patients who survived less than 1 year and 262 patients who survived more than 1 year were included in this study. Six candidate variables were selected based on clinical experience and previous studies. Five variables, BMI, mid-arm circumference, mid-arm muscle circumference, calf circumference and triceps skin fold (TSF), were selected for inclusion in the multivariable model. In the conditional logistic regression analysis, TSF (P = 0·014) was identified as a significant independent protective factor. A similar result was observed in all patients with cancer cachexia (n 3084). In addition, a significantly stronger positive association between TSF and the 1-year survival of patients with cancer cachexia was observed in participants aged > 65 years (OR: 0·94; 95 % CI 0·89, 0·99) than in those aged ≤ 65 years (OR: 0·96; 95 % CI 0·93, 0·99; Pinteraction = 0·013) and in participants with no chronic disease (OR: 0·92; 95 % CI 0·87, 0·97) than in those with chronic disease (OR: 0·97; 95 % CI 0·94, 1·00; Pinteraction = 0·049). According to this study, TSF might be a good anthropometric measurement for predicting 1-year survival in patients with cancer cachexia.
Studies reported the effects of different types and different levels of abstraction of analogical stimuli on designers. However, specific, single visual analogical stimuli on the effects of designers have not been reported. We define this type of stimuli as specific analogical stimuli. We used the extended linkography method to analyze the facilitating and limiting effects of specific analogical stimuli and free association analogical stimuli (nonspecific analogical stimuli) on the students' creativity at different design levels. The results showed that: (1) Advanced students focused on exploring the depth of the design problem while beginning students tended to explore the breadth of the design problem. (2) Nonspecific analogical stimuli enhanced the creativity of beginning students. However, its impact on advanced students is less pronounced. (3) The specific analogical stimuli attract the students into design fixation. Furthermore, it has a more pronounced effect on advanced students. These results illustrate the differences in the effects of specific analogy stimuli on the students at different design levels. It clarifies the use of analogical stimuli in design and the teaching of analogical design methods in design education.
The medium-sized Ergu Fe–Zn polymetallic skarn deposit is located in the central Lesser Xing’an Range, NE China. The ore bodies are mainly hosted in the contact zone between granodiorite intrusions and lower Cambrian dolomitic crystalline limestones or skarns. To reveal the magmatic influence on the mineralization, resource potential and metallogenic geodynamic process of this deposit, a systematic study of the geology, petrology, zircon U–Pb dating, element geochemistry, amphibole geochemistry and Sr–Nd–Pb–Hf isotopes of the Ergu deposit intrusives was conducted. The results show the following: (1) The major rock types in the mine area are medium-grained granodiorite and porphyritic granite, and the rock related to mineralization is medium-grained granodiorite. Zircon U–Pb dating suggests that the granodiorite and porphyritic granite formed at 181.9–183.8 Ma and 182.7 Ma, respectively. Thus, an Early Jurassic magmatic event led to the formation of the Ergu deposit. (2) The granodiorite and porphyritic granite are high-K calc-alkaline I-type granites that formed by comagmatic evolution with varying degrees of fractional crystallization and were likely derived from partial melting of the lower crust. The Ergu deposit occurred in an active continental-margin tectonic setting. (3) The high water content (5.69 wt % H2O), high oxygen fugacity (ΔFMQ = +1.75 to +1.82) and intermediate-plutonic emplacement (3.13 km) of the granodioritic magma are key factors in the formation of the Ergu deposit. The porphyry granite is characterized by high water content (>4 wt % H2O), reduced oxygen fugacity (ΔFMQ = −0.47) and shallow emplacement (<3 km).
The aim of this study was to present the clinical characteristics and dynamic changes in laboratory parameters of the coronavirus disease 2019 (COVID-19) in Guangzhou, and explore the probable early warning indicators of disease progression.
We enrolled all the patients diagnosed with COVID-19 in the Guangzhou No. 8 People’s Hospital. The patients’ demographic and epidemiologic data were collected, including chief complaints, lab results, and imaging examination findings.
The characteristics of the patients in Guangzhou are different from those in Wuhan. The patients were younger in age, predominately female, and their condition was not commonly combined with other diseases. A total of 75% of patients suffered fever on admission, followed by cough occurring in 62% patients. Comparing the mild/normal and severe/critical patients, being male, of older age, combined with hypertension, abnormal blood routine test results, raised creatine kinase, glutamic oxaloacetic transaminase, lactate dehydrogenase, C-reactive protein, procalcitonin, D-dimer, fibrinogen, activated partial thromboplastin time, and positive proteinuria were early warning indicators of severe disease.
The patients outside epidemic areas showed different characteristics from those in Wuhan. The abnormal laboratory parameters were markedly changed 4 weeks after admission, and also were different between the mild and severe patients. More evidence is needed to confirm highly specific and sensitive potential early warning indicators of severe disease.
New zircon U–Pb ages and whole-rock chemical data from four adakitic and two non-adakitic igneous rocks as tectonic blocks in the southern West Junggar accretionary complexes, northwestern China and one gabbro enclave in adakitic block provide further constraints on the initial subduction and following rollback process of the Junggar Ocean as part of southern Palaeo-Asian Ocean. The oldest adakitic monzonite in Tangbale is intruded by the non-adakitic quartz monzonite at 549 Ma, and the youngest adakitic diorite in Tierekehuola formed at 520 Ma. The Ediacaran–Cambrian magmatism show a N-wards younger trend. The high-SiO2 adakitic rocks have high Sr (300–663 ppm) and low Y (6.68–12.2 ppm), with Sr/Y = 40–84 and Mg no. = 46–60, whereas the non-adakitic rocks have high Y (13.2–22.7 ppm) and Yb (2.32–2.92 ppm), with Mg no. = 36–40. The gabbro has high MgO (14.81–15.11 wt%), Co (45–48 ppm), Cr (1120–1360 ppm) and Ni (231–288 ppm), with Mg no. = 72–73. All the samples show similar large-ion lithophile element (LILE) and light rare earth element (LREE) enrichment and Nb, Ta, Ti and varying Zr and Hf depletion, suggesting that they were formed in a subduction-related setting. The adakitic rocks were produced by partial melting of subducted oceanic slab, but the melts were modified by mantle wedge and slab-derived fluids; the non-adakitic rocks were likely derived from partial melts of the middle-lower arc crust; and the gabbro originated from the mantle wedge modified by slab-derived fluids. The magmatism could have been generated during the Ediacaran initial subduction and Cambrian slab rollback of the Junggar Ocean.
Methomyl is a widely used carbamate insecticide and environmental oestrogen that has adverse effects on the reproductive system. However, there have been no reports on the effect of methomyl on early embryos in mammals. In this study, we explored the effect of methomyl exposure on the quality of early embryonic development in mice and the possible mechanisms. During in vitro culture, different concentrations of methomyl (10, 20, 30 and 35 μM) were added to mouse zygote medium. The results showed that methomyl had an adverse effect on early embryonic development. Compared with the control group, the addition of 30 μM methomyl significantly reduced the rate of early embryo blastocyst formation. Methomyl exposure can increase oxidative stress and impair mitochondrial function, which may be the cause of blastocyst formation. In addition, we found that methomyl exposure promoted apoptosis and autophagy in mouse blastocysts. The toxic effect of methomyl on early embryos may be the result of oxidative stress induction. Taken together, our results indicate that methomyl can cause embryonic development defects in mice, thereby reducing the quality of early embryo development.
Bacterial dysentery (BD) brings a major disease burden to developing countries. Exploring the influence of temperature and its interaction with other meteorological factors on BD is significant for the prevention and early warning of BD in the context of climate change. Daily BD cases and meteorological data from 2008 to 2018 were collected in all nine prefecture-level cities in Jilin Province. A one-stage province-level model and a two-stage city-specific multivariate meta-pooled level distributed lag non-linear model were established to explore the correlation between temperature and BD, then the weather-stratified generalised additive model was used to test the interaction. During the study period, a total of 26 971 cases of BD were developed. The one-stage and two-stage cumulative dose-response ‘J’ curves overlapped, and results showed a positive correlation between temperature and BD with a 1–6 days lag effect. Age group ⩾5 years was found to be more sensitive to the effects. Moreover, there was a significant interaction between temperature, humidity and precipitation (P = 0.004, 0.002, respectively) on BD under high temperature (>0 °C), reminding residents and policymakers to pay attention to the prevention of BD in situations with both high temperature and humidity, high temperature and precipitation during the temperate monsoon climate.
The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort.
In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status.
Longitudinal population-based cohort.
17 262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China.
During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22–24 kg/m2, with BMI ≤ 18, 18–20, 20–22, 24–26, 26–28, 28–30 and >30 kg/m2, the hazard ratios for mortality in normotensive participants were 1·92 (95% CI 1·23, 3·00), 1·44 (95% CI 1·01, 2·05), 1·14 (95% CI 0·82, 1·58), 0·96 (95% CI 0·70, 1·31), 0·96 (95% CI 0·65, 1·43), 1·32 (95% CI 0·81, 2·14) and 1·32 (95% CI 0·74, 2·35), respectively, and in hypertensive participants were 1·85 (95% CI 1·08, 3·17), 1·67 (95% CI 1·17, 2·39), 1·29 (95% CI 0·95, 1·75), 1·20 (95% CI 0·91, 1·58), 1·10 (95% CI 0·83, 1·46), 1·10 (95% CI 0·80, 1·52) and 0·61 (95% CI 0·40, 0·94), respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity v. normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants.
Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.
To study the role of orexin A in the reproductive regulation of Mongolian sheep, ovine ovarian granulosa cells were cultured in vitro. The cells were divided into groups after luteinization, the experimental group was given orexin A and the transcriptome was sequenced together with that of the control group. The different genes related to reproduction were screened out. qRT-PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the selected genes and detect the effect on progesterone secretion. In total, 123 differentially expressed genes were obtained by sequencing. Six genes with high expression related to reproduction (PRRT2, ABCG1, SOX4, TBX3, ID1 and ATP8) were screened. The results of qRT-PCR were consistent with those of sequencing; western blot and ELISA were used to verify the protein levels of steroidogenic acute regulatory protein (StAR) and its related PRRT2 and ABCG1, and to detect their effect on progesterone secretion. Validation results were consistent with those of qRT-PCR and sequencing. The experimental group was given orexin A and compared with the control group. Expression of PRRT2 protein was significantly increased (P < 0.05), ABCG1 protein expression was significantly decreased (P < 0.05), StAR expression was significantly increased (P < 0.05), and progesterone secretion was significantly increased (P < 0.05). The results showed that orexin A promoted the expression of StAR by upregulating PRRT2 and downregulating ABCG1, therefore affecting secretion of progesterone. Gene expression characteristics of orexin A affecting progesterone secretion were preliminarily explored; this study provides a theoretical basis for further study on signalling pathways and reproductive regulation in Mongolian sheep.
This paper considers the estimation of dynamic causal effects using a proxy structural vector-autoregressive model with possibly nonstationary regressors. We provide general conditions under which the asymptotic normal approximation remains valid. In this case, the asymptotic variance depends on the persistence property of each series. We further provide a consistent asymptotic covariance matrix estimator that requires neither knowledge of the presistence properties of the variables nor pretests for nonstationarity. The proposed consistent covariance matrix estimator is robust and is easy to implement in practice. When all regressors are indeed stationary, the method becomes the same as the standard procedure.
Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesised that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT), AMP-activated protein kinase–acetyl coenzyme A carboxylase and Janus kinase 2 (JAK2)–signal transducer and activator of transcription (STAT) signalling pathways in both strains. Hypoglycaemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K–AKT signalling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin–genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared with the A strain. Moreover, a more active JAK2–STAT signalling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.
Fat-soluble vitamins during pregnancy are important for fetal growth and development. The present study aimed at exploring the association between vitamin A, E and D status during pregnancy and birth weight. A total of 19 640 women with singleton deliveries from a retrospective study were included. Data were collected by the hospital electronic information system. Maternal serum vitamin A, E and D concentrations were measured during pregnancy. Logistic regression was performed to estimate the association between the vitamin status and low birth weight (LBW) or macrosomia. Women with excessive vitamin E were more likely to have macrosomia (OR 1·30, 95 % CI 1·07, 1·59) compared with adequate concentration. When focusing on Z scores, there was a positive association between vitamin E and macrosomia in the first (OR 1·07, 95 % CI 1·00, 1·14), second (OR 1·27, 95 % CI 1·11, 1·46) and third (OR 1·28, 95 % CI 1·06, 1·54) trimesters; vitamin A was positively associated with LBW in the first (OR 1·14, 95 % CI 1·01, 1·29), second (OR 1·31, 95 % CI 1·05, 1·63) and third (OR 2·00, 95 % CI 1·45, 2·74) trimesters and negatively associated with macrosomia in the second (OR 0·79, 95 % CI 0·70, 0·89) and third (OR 0·77, 95 % CI 0·62, 0·95) trimesters. The study identified that high concentrations of vitamin E are associated with macrosomia. Maintaining a moderate concentration of vitamin A during pregnancy might be beneficial to achieve optimal birth weight. Further studies to explore the mechanism of above associations are warranted.
This paper studies asymptotic properties of a posterior probability density and Bayesian estimators of spatial econometric models in the classical statistical framework. We focus on the high-order spatial autoregressive model with spatial autoregressive disturbance terms, due to a computational advantage of Bayesian estimation. We also study the asymptotic properties of Bayesian estimation of the spatial autoregressive Tobit model, as an example of nonlinear spatial models. Simulation studies show that even when the sample size is small or moderate, the posterior distribution of parameters is well approximated by a normal distribution, and Bayesian estimators have satisfactory performance, as classical large sample theory predicts.