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The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experiment results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats including reducing body weight (BW) gain, Lee’s index, food intake, inguinal white adipose tissue (IWAT) accumulation, blood lipid fasting insulin level and fasting blood glucose level, increasing the ratios of brown adipose tissue (BAT) mass to BW, and improving insulin sensitivity and liver function. In addition, mulberry leaf induced browning of IWAT by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated BAT by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT1) protein in both IWAT and BAT via a mechanism involving Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.
Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4–6 months, 7–12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.
Diverse and abundant fossil taxa have been described in the lower Cambrian Shipai Formation in the Three Gorges area of Hubei Province, South China, but the taxonomy and diversity of the co-occurring brachiopod fauna are still far from clear. Here we describe the brachiopod fauna recovered from the Shipai Formation in the Three Gorges area of South China, including representatives of the subphylum Linguliformea: linguloids (Lingulellotreta ergalievi, Eoobolus malongensis, and Neobolidae gen. indet. sp. indet.), and an acrotretoid (Linnarssonia sapushanensis); and representatives from the subphylum Rhynchonelliformea: the calcareous-shelled Kutorginates (Kutorgina sinensis, Kutorgina sp., and Nisusia liantuoensis). This brachiopod assemblage and the first occurrence of Linnarssonia sapushanensis shell beds permit correlation of the Shipai Formation in the Three Gorges area of Hubei Province with the Stage 4 Wulongqing Formation in the Wuding area of eastern Yunnan. This correlation is further strengthened by the first appearance datum (FAD) of the rhynchonelliform brachiopod Nisusia in the upper silty mudstone of both the Shipai and Wulongqing formations. The new well-preserved material, derived from siliciclastic rocks, also gives critical new insights into the fine shell structure of L. sapushanensis. Microstructural studies on micromorphic acrotretoids (like Linnarssonia) have previously been restricted to fossils that were acid-etched from limestones. This is the first study to carry out detailed comparative ultrastructural studies on acrotretoid shells preserved in siliciclastic rocks. This work reveals a hollow tube and solid column microstructure in the acrotretoid shells from the Shipai Formation, which is likely to be equivalent of traditional column and central canal observed in shells dissolved from limestones.
The high overall plant-based diet index (PDI) is considered to protect against type 2 diabetes in the general population. However, whether the PDI affects gestational diabetes mellitus (GDM) risk among pregnant women is still unclear. We evaluated the association between PDI and GDM risk based on a Chinese large prospective cohort – the Tongji Maternal and Child Health Cohort. Dietary data were collected at 13–28 weeks of pregnancy by a validated semi-quantitative FFQ. The PDI was obtained by assigning plant food groups positive scores while assigning animal food groups reverse scores. GDM was diagnosed by a 75 g 2-h oral glucose tolerance test at 24–28 weeks of gestation. Logistic regression models were fitted to estimate OR of GDM, with associated 95 % CI, comparing women in different PDI quartiles. Among the total 2099 participants, 169 (8·1 %) were diagnosed with GDM. The PDI ranged from 21·0 to 52·0 with a median of 36·0 (interquartile range (IQR) 33·0–39·0). After adjusting for social-demographic characteristics and lifestyle factors etc., the participants with the highest quartile of PDI were associated with 57 % reduced odds of GDM compared with women in the lowest quartile of PDI (adjusted OR 0·43; 95 % CI 0·24, 0·77; Pfor trend = 0·005). An IQR increment in PDI was associated with 29 % decreased odds of GDM (adjusted OR 0·71; 95 % CI 0·56, 0·90). Findings suggest that adopting a plant-based diet during pregnancy could reduce GDM risk among Chinese women, which may be valuable for dietary counselling during pregnancy.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
The widespread occurrence of late Mesozoic volcanic rocks in SE China is associated with widespread mineralization. Most geologists have accepted the model of Pacific plate subduction beneath the eastern Asian continent, but there are still controversies, especially the initial timing of the tectonic transition. In order to understand the tectonic evolution of the palaeo-Pacific plate subduction, an integrated study of zircon U–Pb, Lu–Hf isotope compositions and whole-rock geochemistry was carried out for Mesozoic volcanic rocks in eastern Fujian Province. According to the field observations and zircon U–Pb ages, these volcanic rocks can be divided into three phases: an early stage of Late Jurassic volcanic rocks (Phase 1, 159–153 Ma), a late stage of Late Jurassic volcanic rocks (Phase 2, 152–146 Ma) and an early stage of Early Cretaceous volcanic rocks (Phase 3, 143–139 Ma). Overall, these volcanic rocks are composed of intermediate–acid pyroclastic rocks and lava, with high SiO2, Na2O, K2O and Al2O3 contents, belonging to the high-K calc-alkaline and peraluminous series, with enrichment in large ion lithophile and light rare earth elements but depletion in high-field-strength elements and heavy rare earth elements. However, the Phase 1 and 2 volcanic rocks contain different zircon Hf isotopic compositions and whole-rock geochemistry to the Phase 3 volcanic rocks, implying that they have a different petrogenesis. Our study combined with previous research shows that the decreasing zircon ϵHf(t) values of the Middle–Late Jurassic volcanic rocks indicate a decreasing mantle-derived material contribution. On the contrary, the majority of the Early Cretaceous volcanic rocks have variable ϵHf(t) values, requiring varied degrees of involvement of juvenile components in their origin. Thus, we consider that the Late Jurassic volcanic rocks were generated in a compressional tectonic environment during the early stage (> 146 Ma) of palaeo-Pacific subduction. In contrast, the Cretaceous volcanic rocks were formed in an extensional tectonic setting during a later stage (< 143 Ma) of subduction.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
Physics-informed neural networks (PINNs) were recently proposed in  as an alternative way to solve partial differential equations (PDEs). A neural network (NN) represents the solution, while a PDE-induced NN is coupled to the solution NN, and all differential operators are treated using automatic differentiation. Here, we first employ the standard PINN and a stochastic version, sPINN, to solve forward and inverse problems governed by a non-linear advection–diffusion–reaction (ADR) equation, assuming we have some sparse measurements of the concentration field at random or pre-selected locations. Subsequently, we attempt to optimise the hyper-parameters of sPINN by using the Bayesian optimisation method (meta-learning) and compare the results with the empirically selected hyper-parameters of sPINN. In particular, for the first part in solving the inverse deterministic ADR, we assume that we only have a few high-fidelity measurements, whereas the rest of the data is of lower fidelity. Hence, the PINN is trained using a composite multi-fidelity network, first introduced in , that learns the correlations between the multi-fidelity data and predicts the unknown values of diffusivity, transport velocity and two reaction constants as well as the concentration field. For the stochastic ADR, we employ a Karhunen–Loève (KL) expansion to represent the stochastic diffusivity, and arbitrary polynomial chaos (aPC) to represent the stochastic solution. Correspondingly, we design multiple NNs to represent the mean of the solution and learn each aPC mode separately, whereas we employ a separate NN to represent the mean of diffusivity and another NN to learn all modes of the KL expansion. For the inverse problem, in addition to stochastic diffusivity and concentration fields, we also aim to obtain the (unknown) deterministic values of transport velocity and reaction constants. The available data correspond to 7spatial points for the diffusivity and 20 space–time points for the solution, both sampled 2000 times. We obtain good accuracy for the deterministic parameters of the order of 1–2% and excellent accuracy for the mean and variance of the stochastic fields, better than three digits of accuracy. In the second part, we consider the previous stochastic inverse problem, and we use Bayesian optimisation to find five hyper-parameters of sPINN, namely the width, depth and learning rate of two NNs for learning the modes. We obtain much deeper and wider optimal NNs compared to the manual tuning, leading to even better accuracy, i.e., errors less than 1% for the deterministic values, and about an order of magnitude less for the stochastic fields.
West Junggar in the southwestern Central Asian Orogenic Belt is a critical area for the study of the Junggar oceanic basin and may also reveal tectonic evolutionary events before the final closure of the Palaeo-Asian Ocean. The sedimentary formations and paragenetic associations of the Upper Carboniferous Chengjisihanshan Formation in southern West Junggar jointly reveal a back-arc basin setting with zircon U–Pb ages of 313–310 Ma for the basaltic rocks. Geochemically, the basaltic rocks are tholeiitic with low SiO2 (47.76–52.06 wt %) and K2O (0.05–0.74 wt %) but high MgO (6.55–7.68 wt %) contents and Mg no. (52.9–58.9) values. They display slightly flat rare earth element patterns with weak positive Eu anomalies, and show enrichments in large ion lithophile elements relative to high field strength elements with negative Nb and Ta anomalies, exhibiting both N-MORB-like and arc-like signatures, similar to the back-arc basin basalt from the Mariana Trough. The high positive zircon εHf(t) and bulk εNd(t) values as well as high initial Pb isotopes, together with relatively high Sm/Yb and slightly low Th/Ta ratios imply a depleted spinel lherzolitic mantle source metasomatized by slab-derived fluids. The field and geochemical data jointly suggest that the volcanic rocks within the Chengjisihanshan Formation were formed in an intra-oceanic back-arc basin above the northwestward subduction of the Junggar oceanic lithosphere in southern West Junggar. The confirmation of the Late Carboniferous back-arc basin basalts, together with other geological observations, indicate that an arc-basin evolutionary system still existed in southern West Junggar at c. 310 Ma, and the Junggar Ocean closed after Late Carboniferous time.
Time-resolved particle image velocimetry measurements were performed in smooth-walled open channels to investigate the contributions of very large-scale motions (VLSMs) to the turbulence characteristics in open channel flows. The focal point is to clarify the free surface effects on the characteristics of VLSMs and the contributions of VLSMs to the unique statistical features in open channel flows (i.e., the turbulent kinetic energy (TKE) redistribution and smaller wake strength of the mean velocity profile). The resulting wavelength of VLSMs in present smooth-walled open channels is approximately
is water depth), which is comparable to that in pipe and closed channels while smaller than that in rough-walled open channels, and they are shown to make a great contribution to turbulence statistics with over 50 % of streamwise turbulence intensity, Reynolds shear stress and negative net force coming from VLSMs in the outer layer. Compared with other wall-bounded flows, VLSMs maintain higher strength in the outer layer of open channel flows with non-negligible strength even in the near surface region (
), indicating that the free surface seems to sustain/promote VLSMs. This strength difference of VLSMs closely relates to the TKE redistribution and smaller wake strength of the mean velocity in the outer layer of open channel flows. The higher streamwise turbulence intensity is mainly contributed from the higher strength of VLSMs therein. The decelerating role of VLSMs combining with their higher strength is vital for shaping the mean velocity profile, which therefore is speculated to make a great contribution to the smaller wake strength phenomenon.
Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Both short- and long-term effects of fertilizers on crops and soils are often studied only in arid or paddy soils, whereas less is known about the long-term effects in paddy-upland rotations, particularly with multiple crops and frequent tillage in subtropical areas. Therefore, an 18-year field experiment was initialized to assess the effects of different types of fertilization (no fertilizer; chemical fertilizer (CF); and manure in combination with CF (MCF)) on yield and soil chemical and microbial properties in a crop rotation involving rice (Oryza sativa L., summer), rapeseed (Brassica campestris L., winter), tobacco (Nicotiana tabacum L., the following summer), and hairy vetch (Vicia villosa Roth, the following winter). MCF caused higher yields of rapeseed grains and tobacco leaves than CF after 3 or 4 years of implementing the experiment, while rice yields varied little between MCF and CF, with one exception in 2011. Compared with the initial soil properties, providing soil with MCF increased organic matter (OM), while the opposite trend was found with CF. Higher microbial biomasses, enzyme activities, bacterial operational taxonomic units, and richness and diversity indexes of bacterial communities were found in soils receiving MCF, implying the improvement of soil microbial properties in the paddy-upland rotation system with multiple crops and frequent tillage. The experimental soils under varying fertilization were dominated by four bacterial phyla (Proteobacteria, Acidobacteria, Actinobacteria, and unclassified groups), which accounted for approximately 70% of the 16S rDNA sequences. Among the top 20 predominant bacteria, 14 were commonly found in all soil samples irrespective of which fertilizer treatment was implemented. Thus, the presence of those bacteria was stable in the soil and to some extent was influenced by fertilization. Most of them were facultative anaerobic bacteria, which can adapt to both anaerobic paddy soil and aerobic drylands. The dominant bacteria at various taxonomic levels found in soils might reflect multiple soil processes such as OM turnover, nutrient cycling, physical structure formation, and xenobiotic detoxification.
Surface molecularly imprinted polymer of solanesol (SA-SMIP) was prepared by reversed phase suspension polymerization using modified titanium dioxide (TiO2) as carrier, and operation conditions were investigated and optimized. Structures of modified TiO2 and SA-SMIP obtained at optimal conditions were characterized by Fourier transform infrared spectrometer adopting original TiO2 and non-surface molecularly imprinted polymer as reference. The SA-SMIP synthesized under optimal conditions displayed an excellent recognition of SA from the mixture of SA and triacontanol. The maximum separation degree of SA was 2.90. Finally, the adsorption kinetics and isotherm were investigated and analyzed. Adsorption kinetics results indicated that the adsorption of SA-SMIP to SA was a pseudo-second order process, and the adsorption of beginning and later stages was controlled by homogeneous particle diffusion and adsorption reaction process, respectively. Adsorption isotherm results documented hereby were two sorts of bonding sites, complete imprinted cavities and defective imprinted cavities. The adsorption for two bonding sites could be well lined up with the Langmuir model.
Recently, we introduced an epoxy group to mebendazole by a reaction with epichlorohydrin and obtained two isoforms, mebendazole C1 (M-C1) and mebendazole C2 (M-C2). The in vitro effects of mebendazole derivatives at different concentrations on Echinococcus multilocularis protoscoleces and metacestodes as well as cytotoxicity in rat hepatoma (RH) cells were examined. The results demonstrated that the solubility of the two derivatives was greatly improved compared to mebendazole. The mortality of protoscoleces in vitro reached to 70–80% after 7 days of exposure to mebendazole or M-C2, and M-C2 showed higher parasiticidal effects than mebendazole (P > 0.05). The parasiticidal effect of M-C1 was low, even at a concentration of 30 µm. The percentage of damaged metacestodes that were treated with mebendazole and M-C2 in vitro at different concentrations were similar, and M-C1 exhibited insignificant effects on metacestodes. Significant morphological changes on protoscoleces and metacestodes were observed after treatment with mebendazole and M-C2. In addition, the introduction of an epoxy group to mebendazole also reduced its cytotoxicity in RH cells. Our results demonstrate that the introduction of an epoxy group not only improved the solubility of mebendazole, but also increased its parasiticidal effects on E. multilocularis and reduced its cytotoxicity in RH cells.
Previous studies in schizophrenia revealed abnormalities in the cortico-cerebellar-thalamo-cortical circuit (CCTCC) pathway, suggesting the necessity for defining thalamic subdivisions in understanding alterations of brain connectivity.
To parcellate the thalamus into several subdivisions using a data-driven method, and to evaluate the role of each subdivision in the alterations of CCTCC functional connectivity in patients with schizophrenia.
There were 54 patients with schizophrenia and 42 healthy controls included in this study. First, the thalamic structural and functional connections computed, based on diffusion magnetic resonance imaging (MRI, white matter tractography) and resting-state functional MRI, were clustered to parcellate thalamus. Next, functional connectivity of each thalamus subdivision was investigated, and the alterations in thalamic functional connectivity for patients with schizophrenia were inspected.
Based on the data-driven parcellation method, six thalamic subdivisions were defined. Loss of connectivity was observed between several thalamic subdivisions (superior-anterior, ventromedial and dorsolateral part of the thalamus) and the sensorimotor system, anterior cingulate cortex and cerebellum in patients with schizophrenia. A gradual pattern of dysconnectivity was observed across the thalamic subdivisions. Additionally, the altered connectivity negatively correlated with symptom scores and duration of illness in individuals with schizophrenia.
The findings of the study revealed a wide range of thalamic functional dysconnectivity in the CCTCC pathway, increasing our understanding of the relationship between the CCTCC pathway and symptoms associated with schizophrenia, and further indicating a potential alteration pattern in the thalamic nuclei in people with schizophrenia.
A nonlinear station-keeping control method for a multi-vectored propeller airship under unknown wind field with thrust saturation is developed, which is composed of three modules: nonlinear model predictive controller (NMPC), disturbance observer (DOB) and tracking differentiator (TD). The nonlinear kinematics and dynamics models are introduced, and the wind effect is considered by the wind-induced aerodynamic force. Based on both models, an explicit NMPC is designed. Then a nonlinear DOB is introduced to estimate the wind disturbance. A TD, showing the relationship between the maximum propulsion force and the maximum flight acceleration, is proposed to handle the thrusts’ amplitude saturation. Stability analysis shows that the closed-loop system is globally asymptotically stable. Simulations for a multi-vectored propeller airship are conducted to demonstrate the robustness and effectiveness of the proposed method.