Characteristic gene expression in the liver monocyte-macrophage-DC system is associated with the progression of fibrosis in NASH

BackgroundThe monocyte-macrophage-dendritic cell (DC) (MMD) system exerts crucial functions that may modulate fibrogenesis in nonalcoholic steatohepatitis (NASH). In this study, we explored the cell characteristics, distribution and developmental trajectory of the liver MMD system in NASH mice with fibrosis and clarified characteristic genes of the MMD system involved in liver fibrosis progression in NASH mice and patients.MethodsSingle cells in liver tissue samples from NASH and normal mice were quantified using single-cell RNA sequencing (scRNA-seq) analysis. Differentially expressed genes (DEGs) in the MMD system by pseudotime analysis were validated by tyramide signal amplification (TSA)-immunohistochemical staining (IHC) and analyzed by second harmonic generation (SHG)/two-photon excitation fluorescence (TPEF).ResultsCompared with control mice, there were increased numbers of monocytes, Kupffer cells, and DCs in two NASH mouse models. From the transcriptional profiles of these single cells, we identified 8 monocyte subsets (Mono1-Mono8) with different molecular and functional properties. Furthermore, the pseudotime analysis showed that Mono5 and Mono6 were at the beginning of the trajectory path, whereas Mono2, Mono4, Kupffer cells and DCs were at a terminal state. Genes related to liver collagen production were at the late stage of this trajectory path. DEGs analysis revealed that the genes Fmnl1 and Myh9 in the MMD system were gradually upregulated during the trajectory. By TSA-IHC, the Fmnl1 and Myh9 expression levels were increased and associated with collagen production and fibrosis stage in NASH mice and patients.ConclusionsOur transcriptome data provide a novel landscape of the MMD system that is involved in advanced NASH disease status. Fmnl1 and Myh9 expression in the MMD system was associated with the progression of NASH fibrosis

Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase

How do urban residents use energy for winter heating at home? A large-scale survey in the hot summer and cold winter climate zone in the Yangtze River region

The increasing demand for improving indoor thermal environment in the hot summer and cold winter climate zone (HSCW) in the Yangtze River region in China poses enormous challenges in terms of energy policy and design solutions for this unique region. A comprehensive understanding of people’s habits and behaviors involving winter heating is imperative for decision making for urban heating infrastructure investment strategies that significantly impact the decarbonization of heating. However, there are little studies of a large-scale survey to gain such knowledge acrose the region. The aim of this study is to develop a rigorous survey method in order to obtain reliable data for analysis. Five municipal/capital cities across the upper, middle and downstream Yangtze River were surveyed based on 30 randomly generated locations in each city. A total of 8481 valuable samples were obtained in the survey conducted in the winter from November 2017 to March 2018. It is revealed that air conditioning/air source heat pumps are the predominant systems, accounting for 63% and 58% for bedroom and living room heating respectively. The use patterns of heating are diverse featuring ‘part-time-part-space’ systems in accordance with the occupancy patterns. There is significant evidence of the habit of opening a window to provide a gap for fresh air irrespective of whether the heating is in use. Two-step cluster analysis is employed to subdivide occupants’ heating-related behaviors into three clusters to characterize households. This study fills the knowledge gap of winter-heating-related behaviors. The research outcomes will benefit building energy simulations for energy prediction and help policy makers making decisions on providing strategic guidance in terms of winter heating solutions in this region

Phosphorylated Trehalose Suppresses the Denaturation of Myofibrillar Proteins in Peeled Shrimp (Litopenaeus vannamei) during Long-Term Frozen Storage

The protective effects of phosphorylated trehalose on the quality and characteristics of peeled shrimp (Litopenaeus vannamei) were determined. Quality changes in treated samples were evaluated by assessing the physicochemical properties of myofibrillar proteins (MP) and compared to fresh water-, sodium tripolyphosphate-, and trehalose-treated samples during 12 weeks of frozen storage. The sensitivity of MP to oxidation and denaturation was increased during frozen storage. Phosphorylated trehalose significantly improved the quality of shrimp by increasing water-holding capacity. Further analysis showed that the addition of phosphorylated trehalose reduced the decrease in soluble MP content, Ca2+-ATPase activity, and total sulfhydryl contents and also effectively inhibited the increase in the surface hydrophobicity of MP. In addition, atomic force microscopy and hematoxylin and eosin staining revealed that phosphorylated trehalose preserved the integrity of the myofibril microstructure. Thermal stability results further confirmed that the denaturation temperature and denaturation enthalpy of MP were improved by phosphorylated trehalose. Overall, phosphorylated trehalose suppresses the denaturation of MP in peeled shrimp during long-term frozen storage

Analysis of Pre-Earthquake Space Electric Field Disturbance Observed by CSES

In order to explore the abnormal disturbance of the space electric field caused by earthquakes using the electric field data of the ULF and VLF frequency bands of the electric field observed by the ZH-1 satellite, and taking the Mw7.7 earthquake in the Caribbean Sea in the southern sea area of Cuba on 29 January 2020 as an example, the signal-to-noise ratio of the NAA and NLK artificial source VLF transmitting stations in the Northern Hemisphere and the height of the lower ionosphere was calculated. The disturbance of the electric field in the ULF band was extracted using the S-G filtering method. The results indicate that: (1) The ionospheric anomaly caused by this earthquake appeared 20 days before the earthquake, and before the earthquake, there were significant anomalous changes in all parameters within the pregnant seismic zone. The signal-to-noise ratios of the NAA and NLK artificial source transmitter stations decreased by 30%, and the height of the low ionosphere decreased by 5–10 km, while there were anomalous perturbations in several orbits of the ULF electric field, and the magnitude of the perturbations exceeded three times the standard deviation. (2) The SNR of the artificial source transmitting stations before and after the earthquake was significantly reduced in the third period before the earthquake and recovered after the earthquake. (3) The low ionospheric height appears to be reduced before the earthquake and recovers after the earthquake. (4) The decrease in the S/N ratio occurred simultaneously with the decrease in ionospheric height 15 days–10 days before the earthquake. This provides a reference for extracting pre-earthquake ionospheric precursor anomalies

Analysis of Pre-Earthquake Space Electric Field Disturbance Observed by CSES

In order to explore the abnormal disturbance of the space electric field caused by earthquakes using the electric field data of the ULF and VLF frequency bands of the electric field observed by the ZH-1 satellite, and taking the Mw7.7 earthquake in the Caribbean Sea in the southern sea area of Cuba on 29 January 2020 as an example, the signal-to-noise ratio of the NAA and NLK artificial source VLF transmitting stations in the Northern Hemisphere and the height of the lower ionosphere was calculated. The disturbance of the electric field in the ULF band was extracted using the S-G filtering method. The results indicate that: (1) The ionospheric anomaly caused by this earthquake appeared 20 days before the earthquake, and before the earthquake, there were significant anomalous changes in all parameters within the pregnant seismic zone. The signal-to-noise ratios of the NAA and NLK artificial source transmitter stations decreased by 30%, and the height of the low ionosphere decreased by 5–10 km, while there were anomalous perturbations in several orbits of the ULF electric field, and the magnitude of the perturbations exceeded three times the standard deviation. (2) The SNR of the artificial source transmitting stations before and after the earthquake was significantly reduced in the third period before the earthquake and recovered after the earthquake. (3) The low ionospheric height appears to be reduced before the earthquake and recovers after the earthquake. (4) The decrease in the S/N ratio occurred simultaneously with the decrease in ionospheric height 15 days–10 days before the earthquake. This provides a reference for extracting pre-earthquake ionospheric precursor anomalies

Properties of Dietary Flavone Glycosides, Aglycones, and Metabolites on the Catalysis of Human Endoplasmic Reticulum Uridine Diphosphate Glucuronosyltransferase 2B7 (UGT2B7)

Flavone glycosides, their aglycones, and metabolites are the major phytochemicals in dietary intake. However, there are still many unknowns about the cellular utilization and active sites of these natural products. Uridine diphosphate glucuronosyltransferases (UGTs) in the endoplasmic reticulum have gene polymorphism distribution in the population and widely mediate the absorption and metabolism of endogenous and exogenous compounds by catalyzing the covalent addition of glucuronic acid and various lipophilic chemicals. Firstly, we found that rutin, a typical flavone O-glycoside, has a stronger UGT2B7 binding effect than its metabolites. After testing a larger number of flavonoids with different aglycones, their aglycones, and metabolites, we demonstrated that typical dietary flavone O-glycosides generally have high binding affinities towards UGT2B7 protein, but the flavone C-glycosides and the phenolic acid metabolites of flavones had no significant effect on this. With the disposition of 4-methylumbelliferone examined by HPLC assay, we determined that 10 μM rutin and nicotifiorin could significantly inhibit the activity of recombinant UGT2B7 protein, which is stronger than isovitexin, vitexin, 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid. In addition, in vitro experiments showed that in normal and doxorubicin-induced lipid composition, both flavone O-glycosides rutin and flavone C-glycosides isovitexin at 10 μM had no significant effect on the expression of UGT1A1, UGT2B4, UGT2B7, and UGT2B15 genes for 24 h exposure. The obtained results enrich the regulatory properties of dietary flavone glycosides, aglycones, and metabolites towards the catalysis of UGTs and will contribute to the establishment of a precise nutritional intervention system based on lipid bilayers and theories of nutrients on endoplasmic reticulum and mitochondria communication

Humidity Stability of 2D Dion–Jacobson-Phase Perovskites with Hydrophobic Groups in Diammonium Spacers

Two-dimensional (2D) Dion–Jacobson-phase layered perovskites have received widespread attention for their better stability and superior photoelectric properties. In this work, the structure, optical properties, and stability of CHBMAPbI4, OBEAPbI4, and BDAPbI4 with different spacer cations were investigated. The structural changes during moisture erosion were detected based on the X-ray diffraction (XRD) patterns and ultraviolet–visible (UV–vis) diffuse reflectance spectra; the results demonstrate that CHBMAPbI4 with 1,3-cyclohexyl groups and OBEAPbI4 with alkoxy groups remained stable in high-humidity environments, while CHBMAPbI4 was more stable due to the weaker polarity of 1,3-cyclohexyl groups, suggesting that the hydrophobic functional groups in diammonium spacers play a role in improving the humidity stability of perovskites

Effects of Chemical Fertilizer Reduction Combined with Synergist on Soil Physicochemical Properties, Yield and Quality of Chinese Flowering Cabbage

【Objective】This study was conducted to investigate the effects of chemical fertilizer reduction combined with synergist on soil physicochemical properties, yield and quality of Chinese flowering cabbage in Huizhou, Guangdong Province, so as to provide a theoretical basis and technical support for chemical fertilizer reduction in vegetable fields.【Method】Taking the representative vegetable crop Chinese flowering cabbage in South China as the research object, four treatments of local fertilization level (T1, CK), local fertilization level+ synergist application (T2), 20% fertilizer reduction (T3) and 20% fertilizer reduction + synergist application (T4) were set up by field plot experiment. Soil physicochemical properties, microbial biomass, acid phosphatase activity, and crop yield and quality were measured and compared between treatments.【Result】The results showed that compared to T1 (CK), the soil capillary capacity, field capacity, non-capillary porosity, and total porosity in T3 treatment were increased by 13.3%, 43.1%, 29.4%, and 9.2%, respectively, and the soil non-capillary porosity and total porosity of T4 treatment were increased by 42.1% and 13.0%, respectively. Compared to T1 (CK), the soil pH value in T3 treatment was increased by 15.9%, whereas the other soil fertility indexes were not changed significantly. Under T4 treatment, soil pH value was increased by 13.4%, soil alkali-hydrolyzable nitrogen and available potassium contents were significantly increased by 33.3% and 15.8%, respectively. Compared to T1 (CK), the soil microbial biomass C (SMBC) and N (SMBN) contents and acid phosphatase activity in T3 treatment were increased by 35.6%, 43.1%, and 15.5%, respectively, whereas the SMBC, SMBN, and soil microbial biomass P (SMBP) contents and acid phosphatase activity in T4 treatment were increased by 78.1%, 111.2%, 49.1%, and 24.3%, respectively. Compared to T1 (CK), the N, P, and K absorption amounts of cabbage in T3 treatment were increased by 22.1%, 11.3%, and 17.9%, respectively, whereas those in T4 treatment were significantly increased by 33.0%, 28.5%, and 30.0%, respectively. Compared to T1 (CK), cabbage yield was increased by 19.4%, nitrate content was decreased by 13.6%, and Vc content was increased by 2.2% in T3 treatment. Cabbage yield was significantly increased by 28.1%, nitrate content was decreased by 12.1%, and Vc content was increased by 4.2% in T4 treatment.【Conclusion】Chemical fertilizer reduction combined with synergist application can increase soil fertility, microbial biomass and acid phosphatase activity, improve cabbage yield and quality