[Anti-pyroptosis effect of Albiziae Cortex-Tribuli Fructus combination on hepatic stellate cell line LX2: based on network pharmacology].

Based on network pharmacology, molecular docking, and in vitro experimental verification, this study aims to explore the effect of Albiziae Cortex-Tribuli Fructus combination on HSC-LX2 pyroptosis. Specifically, the targets of Albiziae Cortex, Tribuli Fructus, and hepatic fibrosis were retrieved from an online database and CNKI, and "drug-component-target" network and "drug-component-target-disease" network were constructed. Protein-protein interaction(PPI) network was established based on STRING. Metascape was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and the mechanism of Albiziae Cortex-Tribuli Fructus combination against liver fibrosis was predicted. Molecular docking was used to verify some of the results of network pharmacology, and in vitro experiment was carried out to further verify the above conclusions. According to the results of network pharmacological analysis, 25 active components and 439 targets of Albiziae Cortex-Tribuli Fructus combination and 152 anti-liver fibrosis targets were screened out, including nucleotide-binding oligomerization domain and leucine-rich-repeat-and pyrin-domain-containing 3(NLRP3) and caspase-1. The key targets were involved in 194 KEGG pathways in which the NOD-like receptor signaling pathway topped. The binding common targets were related to pyroptosis. The results of in vitro experiment showed that the pair-containing serum reduced the proliferation rate of HSC-LX2 and the content of reactive oxygen species(ROS), interleukin-18(IL-18), and interleukin-1ß(IL-1ß)(P<0.05). Western blot and qRT-PCR suggested that the protein and gene expression of NLRP3, caspase-1, α-smooth muscle actin(α-SMA), and gasdermin D(GSDMD) in HSC-LX2 increased after AngⅡ stimulation, and the expression decreased after the intervention of pair-containing serum(P<0.05). In summary, the pair-containing serum can inhibit the classic pathway of pyroptosis, which may be the anti-liver fibrosis mechanism. This is consistent with the predicted results of network pharmacology.

Synergistic effect of activator nature and curing temperature on time-dependent rheological behavior of cemented paste backfill containing alkali-activated slag.

Cemented paste backfill (CPB) that contains alkali-activated slag (AAS) produces more desirable properties and performance (enhanced fluidity, higher strength, lower cost, and limited carbon emission) as compared with CPB made with cement. Significant efforts have been devoted to the study of the effect of the individual factor on the rheology of AAS-CPB. However, the synergistic effect of curing temperature, time, and activator nature is still unclear. Therefore, the current research aims to investigate the time-dependent rheology of AAS-CPB under the combined influence of curing temperature, silica modulus (Ms), and activator concentration (AC). The findings revealed that a higher curing temperature results in a reduction in fluidity and an increase in the thixotropy of CPB. The evolution of rheological parameters of AAS-CPB is more insensitive to the curing temperature as compared to that of OPC-CPB. During the initial 2 h, higher AC can weaken the rheological parameter. However, a more rapid growth rate of rheological properties was observed after 2 h. The rheological parameters of AAS-CPB with higher Ms are always lower than those of AAS-CPB with lower Ms at all temperatures studied. In addition, the discrepancy in the linear correlation between thixotropy and plastic viscosity for OPC-CPBs and AAS-CPBs indicates the different hydration rates of slag and Portland cement. These findings are beneficial in guiding the mix proportion design of AAS-CPB in mines with various underground temperatures.

Toll-like receptor 4 deficiency alleviates lipopolysaccharide-induced intestinal barrier dysfunction.

BACKGROUND: The intestinal tract is considered the body's "engine" and the most impacted organ during sepsis. In this study, we explored toll-like receptor 4 (TLR4) functions in sepsis-induced intestinal barrier dysfunction. METHODS: Wild-type and TLR4-knockout (KO) mice were used to establish a sepsis-induced dysfunctional intestinal barrier model via the intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Hematoxylin and eosin staining, Transmission electron microscope, enzyme linked immunosorbent assay, western blot, quantitative real-time polymerase chain reaction, TdT-mediated dUTP nick end labeling staining, 16 S rRNA gene sequencing were used to explore differences in inflammatory cytokines, apoptosis, tight junction (TJ) protein expression, and intestinal flora diversity between groups. RESULTS: TLR4-deficiency reduced procalcitonin and C-reactive protein to prevent sepsis, and also inhibited inflammatory response by decreasing interleukin (IL)- 1ß, IL-6 and tumor necrosis factor-α levels. Also, BAX/Bcl2 and cleaved-caspase 3 expressions were decreased in TLR4-KO mice to suppress the intestinal mucosal cell apoptosis. TJ proteins, including zonula occludens protein, Occludin and Claudin-5 were significantly increased and intestinal fatty acid binding protein, myosin light chain and myosin light chain kinase were reduced in TLR4-KO mice. Additionally, 16 S rRNA gene sequencing indicated that TLR4-deficiency improved flora diversity and altered normal and abnormal bacterial proportions. CONCLUSIONS: TLR4 deficiency alleviated LPS-induced intestinal barrier dysfunction by reducing inflammatory responses and apoptosis, impairing intestinal damage, and regulating intestinal flora disturbance.

[Effect of Tetrastigma hemsleyanum on sepsis and mechanism based on network pharmacology and experimental verification].

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1ß, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1ß, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lß, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.

Electroacupuncture at Zusanli Alleviates Sepsis by Regulating the TLR4-MyD88-NF-Kappa B Pathway and Diversity of Intestinal Flora.

Background: Electroacupuncture (EA) at the Zusanli acupoint (ST36) has shown therapeutic potential for sepsis due to its ability to limit inflammation and to regulate gastrointestinal tract symptoms. However, the mechanisms contributing to the effects of EA at ST36 on sepsis and connections with the intestinal flora remain unclear. This study was designed to explore the effects of EA at ST36 on Toll-like receptor 4 signaling and the intestinal flora. Methods: ICR mice were randomly divided into 4 groups: control group, model group, EA group, and sham EA group. EA at ST36 was performed at 2.5 mA and 2 to 100 Hz, and the 30 min of dense wave was achieved over 5 days. A sepsis model was built by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/mL). The levels of expression of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and IL-10 were detected by enzyme-linked immunosorbent assays, and lactate dehydrogenase (LDH) levels in serum were measured by biochemical tests. Expression levels of Bax, Bcl2, cleaved caspase-3, Toll-like receptor (TLR4), nuclear factor-kappa B (NF-κB), and myeloid differentiation factor 88 (MyD88) were assessed by the Western blotting. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to evaluate apoptosis. The intestinal microecology was assessed via 16S rRNA gene sequencing. Results: EA at ST36 reduced the expression of IL-1ß, IL-6, and TNF-α and increased the expression of IL-10 to inhibit the inflammatory response. EA at ST36 also inhibited apoptosis, as measured by TUNEL staining, and decreased the Bax/Bcl2 ratio and levels of caspase-3 and cleaved caspase-3, as well as LDH release. Our results suggest that alleviation of sepsis may correlate with the downregulation of levels of TLR4, NF-κB, and MyD88. Importantly, EA at ST36 improved the diversity of the intestinal flora and increased the abundance of Firmicutes and Actinobacteria. Conclusion. EA at ST36 prevented sepsis from worsening by inhibiting inflammation and apoptosis, which correlated with the regulation of the TLR4/NF-κB/MyD88 signaling axis and modulation of the intestinal flora.

Tetrastigma hemsleyanum Diels et Gilg ameliorates lipopolysaccharide induced sepsis via repairing the intestinal mucosal barrier.

OBJECTIVE: Sepsis causes excessive systemic inflammation and leads to multiple organ dysfunction syndrome (MODS). The intestine plays a key role in the occurrence and development of sepsis. Tetrastigma hemsleyanum Diels et Gilg (San ye qing, SYQ), a precious Chinese medicine, has been widely used for centuries due to its high traditional value, such as a remarkable anti-inflammatory effect. However, the role of SYQ in intestinal permeability during the development of sepsis needs to be discovered. METHODS: Mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate intestinal mucosal barrier function damage in sepsis. Pathological section, inflammatory cytokines, tight junctions, cell apoptosis, and intestinal flora were detected to evaluate the protective effect of SYQ on intestinal mucosal barrier injury in LPS-induced septic mice. RESULTS: The results showed that SYQ treatment obviously attenuated LPS-induced intestinal injury and reduced the production of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Besides, SYQ also up-regulated the expressions of tight junctions, including Zonula occludens 1 (ZO-1), Claudin-5, and Occludin along with a decreased in the levels of myosin light chain kinase (MLCK) and myosin light chain (MLC). In addition, SYQ down-regulated the expression of Bax/Bcl2 as well as that of cleaved caspase-3 to prevent the cells from undergoing apoptosis. Further, SYQ restored the diversity of the intestinal flora, increased the abundance of Firmicutes, and decreased the abundance of Bacteroidota. CONCLUSIONS: The study indicated that SYQ exerted its protective effect on intestinal mucosal barrier injury in LPS-induced septic mice by reducing inflammatory response, improving the tight junction protein expression, inhibiting cell apoptosis, and adjusting the intestinal flora structure.

Assessment of Elemental Components in Atmospheric Particulate Matter from a Typical Mining City, Central China: Size Distribution, Source Characterization and Health Risk.

Atmospheric particulate matters in nine size fractions were sampled at Huangshi city, Hubei province. Elemental concentrations occurred unimodal size distribution for Zn, Pb and Ni, dimodal distribution for Ca, S, Fe and Ti, and trimodal distribution for Cl, K, Mn, Cu and Cr. Enrichment factor and principal component analysis identified the main sources from crustal material, biomass burning, waste incineration, vehicular and industrial emission. As for the non-carcinogenic health risk through inhalation, there were certain potential risks for Mn and Sb for children, and Pb for children and adults in PM2.5. It showed certain potential risks for Mn, Sb and Pb for children and adults in PM10. As for the carcinogenic health risk through inhalation, Cr in PM2.5 and Ni, Co and Cr in PM10 indicated unacceptable risk for children and adults. Meanwhile, Co and Ni in PM2.5 represented acceptable risk for children.

Atmospheric Concentrations and Air-Soil Exchange of Polycyclic Aromatic Hydrocarbons (PAHs) in Typical Urban-Rural Fringe of Wuhan-Ezhou Region, Central China.

During the summer of 2015, polycyclic aromatic hydrocarbons (PAHs) in the atmosphere were collected by passive air samplers in typical urban-rural fringe of Wuhan-Ezhou region, Central China. The results showed that 16 kinds of PAHs were ubiquitous with the concentrations of ∑16PAHs from 14.69 to 136.30 ng·m-3 and the mean concentration of 43.03 ng·m-3. Phenanthrene (Phe), fluoranthene (Fla) and pyrene (Pyr) were major components, which accounted for 81% of ∑16PAHs. PAHs atmospheric concentrations presented obvious spatial variation, being significantly related to geographical environment and influenced by anthropogenic activity. Air-soil exchange status of PAHs was discussed according to the fugacity fraction (ff). The results showed that HMW-PAHs behaved as net deposition, while LMW-PAHs were more likely to establish dynamic equilibrium between atmosphere and soil than MMW-PAHs and HMW-PAHs. For some PAHs, such as acenaphthylene (Acy) and anthracene (Ant), the soil acted as second sources of them.

A new dual-peptide strategy for enhancing antioxidant activity and exploring the enhancement mechanism.

The development of a new generation antioxidant peptides with high free radical scavenging rates is highly desirable, but remains a great challenge. Herein, a new dual-peptide development strategy based on plant and animal proteins has been proposed to enhance the antioxidant activity of peptides. Sea cucumber peptide and pine nut peptide were selected to assemble the dual-peptides, namely, VTPYKDHCH and VTPYQDHCH. The in vitro antioxidant activity of the dual-peptides was confirmed to be much higher than that of the individual peptides VTPY, KDHCH, and QDHCH according to the DPPH and ABTS radical scavenging and EPR experiments. The antioxidant activity of the dual-peptides was also further confirmed via cell experiments. Moreover, circular dichroism (CD), Raman spectrum and 1H NMR spectrum were recorded to determine the enhancement mechanism, which showed that the enhancement activity was derived from the increase in the random crimp degree of the secondary structure after the two different proteins were bound together. Our findings are expected to establish a new dual-peptide strategy for the enhancement of antioxidant activity based on plant and animal sources and encourage the further exploration of dual-peptides for functional applications.

Characterization of carbonaceous fractions in PM2.5 and PM10 over a typical industrial city in central China.

Aerosol samples of PM2.5 and PM10 were collected every 6 days from March 2012 to February 2013 in Huangshi, a typical industrial city in central China, to investigate the characteristics, relationships, and sources of carbonaceous species. The PM2.5 and PM10 samples were analyzed for organic carbon (OC), elemental carbon (EC), char, and soot using the thermal/optical reflectance (TOR) method following the IMPROVE_A protocol. PM2.5 and PM10 concentrations ranged from 29.37 to 501.43 µg m-3 and from 50.42 to 330.07 µg m-3, with average levels of 104.90 and 151.23 µg m-3, respectively. The 24-h average level of PM2.5 was about three times the US EPA standard of 35 µg m-3, and significantly exceeds the Class II National Air Quality Standard of China of 75 µg m-3. The seasonal cycles of PM mass and OC concentrations were higher during winter than in summer. EC and char concentrations were generally highest during winter but lowest in spring, while higher soot concentrations occurred in summer. This seasonal variation could be attributed to different seasonal meteorological conditions and changes in source contributions. Strong correlations between OC and EC were found for both PM2.5 and PM10 in winter and fall, while char and soot showed a moderate correlation in summer and winter. The average OC/EC ratios were 5.11 and 4.46 for PM2.5 and PM10, respectively, with individual OC/EC ratios nearly always exceeding 2.0. Higher char/soot ratios during the four seasons indicated that coal combustion and biomass burning were the major sources for carbonaceous aerosol in Huangshi. Contrary to expectations, secondary organic carbon (SOC) which is estimated using the EC tracer method exhibited spring maximum and summer minimum, suggesting that photochemical activity is not a leading factor in the formation of secondary organic aerosols in the study area. The contribution of SOC to OC concentration for PM2.5 and PM10 were 47.33 and 45.38%, respectively, implying that SOC was an important component of OC mass. The serious air pollution in haze-fog episode was strongly correlated with the emissions of pollutants from biomass burning and the meteorological conditions.

Dicarboxylic acids and related compounds in fine particulate matter aerosols in Huangshi, central China.

PM2.5 (particulate matter with an aerodynamic diameter <2.5 µm) samples were collected in Huangshi, central China, from March 2012 to February 2013 and were analyzed for dicarboxylic acids (diacids) and related compounds (DARCs). Oxalic acid (C2; 416 ng m-3) was the most abundant species, followed by phthalic (Ph; 122 ng m-3), terephthalic (tPh; 116 ng m-3), succinic (C4; 70.4 ng m-3), azelaic (C9; 67.9 ng m-3), and adipic (C6; 57.8 ng m-3) acids. Relatively high abundances of Ph and tPh differed from the distribution in urban and marine aerosols, indicating contributions from nearby anthropogenic sources. Glyoxylic acid (ωC2; 41.4 ng m-3) was the dominant oxoacid, followed by 9-oxononanoic (ωC9; 40.8 ng m-3) and pyruvic (Pyr; 24.1 ng m-3) acids. Glyoxal (Gly; 35.5 ng m-3) was the dominant α-dicarbonyl. Highest average concentrations were found for C2, ωC2, and C9 in autumn, for C4, for Pyr and C6 in spring, for Ph, ωC9, and Gly in summer, whereas the lowest values were observed in winter. Seasonal variations and correlation coefficients of DARCs demonstrate that both primary emissions and secondary production are important sources. Principal component analysis of selected DARCs species suggests that a mixing of air masses from anthropogenic and biogenic sources contribute to the Huangshi aerosols. Implications: Both primary emissions and secondary production are important sources of diacids and related compounds in PM2.5 from Huangshi, central China. Principal component analysis of selected diacids in Huangshi aerosols suggests that mixing of air masses from anthropogenic and biogenic sources contribute to ambient aerosols in central China.

[Characteristics and Sources of Elements of a PM10 Measurements from a Typical Industrial City in Eastern Hubei Province].

In order to investigate the characteristics and sources of elements in atmospheric aerosols (PM10) measurements, samples were collected between April 2012 and February 2013 in Huangshi, a typical industrial city in the east of Hubei province, China. These samples were analyzed for seventeen elements using wavelength dispersive X-ray fluorescence spectrometry. In addition, the pollution characteristics of fourteen elements were analyzed by an enrichment factor (EF) method, and the sources of these elements were studied by a principal component analysis (PCA) and positive matrix factorization (PMF) method. The result from the EF indicated that the concentration of the seventeen elements in the PM10 measurements varied from 0.01-9.83 µg·m-3. The elemental concentration of S was the highest and Ni and V was the lowest during the monitoring period in Huangshi. Daily levels of Pb and Cd exceeded the annual reference values set by the National Ambient Air Quality Standard (GB3095-2012) by 36.4% and 89.1%, respectively. An analysis of EF showed that Ti, V, Mn, and Ni elements were mildly enriched, indicating they were affected by both natural and anthropogenic sources. Ca, Cr, and Ba elements were moderately enriched and Cu, Zn, Pb, Sn, Sb, and Fe were highly enriched or hyper accumulated, suggesting they are mainly sourced from human activities. There were four sources significantly contributing to the elements in the PM10measurement, which were determined using PCA and PMF analysis. These were soil and fugitive dust, coal combustion, industry exhausts, and motor vehicle emissions. The results of the two models supported each other and had good consistency.

[Phenotypic variations in cones and seeds of natural Cupressus chengiana populations in China]. / 岷江柏天然种群种实表型变异特征.

A total of 13 phenotypic traits from 11 natural populations of Cupressus chengiana were investigated by using nested analysis, variation coefficient, phenotypic traits differentiation coefficient, and un-weighted pair-group method by arithmetic averages (UPGMA) cluster analysis. Phenotypic variations among and within populations of C. chengiana were discussed, the relationship among phenotypic traits and that between phenotypic traits and environmental factors were analyzed, and the 11 populations were divided. The results showed that there was significant difference in phenotypic variation both between and within populations. Variation within populations (49.7%) was greater than that between populations (28.6%). The mean coefficient of phenotypic differentiation between populations was 43.4% suggesting the differentiation between populations was relatively larger. The average variation coefficient of cone mass was the highest (37.2%), followed by seed mass in single cone, and that of cone length was the smallest (8.0%) indicating the cone length was the most stable phenotypic trait. The phenotypic diversity was greatest in Kangding County and smallest in Wudu County. The mean annual temperature of the hottest month and mean annual precipitation of growing season were the main environmental factors on phenotypic diversity in cones and seeds of C. chengiana in the study region. According to the 13 phenotypic traits, the 11 populations could be divided into two groups and three subgroups, which showed how C. chengiana distributed in three watersheds. Phenotypic traits in cones and seeds of C. chengiana populations were the best in Daduhe River watershed, and those were the worst in Minjiang River watershed.

[Concentration and Size Distribution of Bioaerosols in Indoor Environment of University Dormitory During the Plum Rain Period].

Bioaerosols of university dormitory can spread through air and cause a potential health risk for student staying in indoor environment. To quantify the characteristics of bioaerosols in indoor environment of university dormitory, concentration and size distribution of culturable bioaerosols were detected during the plum rain period, the correlations of culturable bioaerosol with concentration of particulate matter, the ambient temperature and relative humidity were analyzed using Spearman's correlation coefficient and finally the changes of size distribution of culturable bioaerosol caused by activities of students were detected. The results showed that the mean concentrations of culturable airborne bacteria and fungi were (2133 +/- 1617) CFUm' and (3111 +/- 2202) CFU x m(-3). The concentrations of culturable airborne bacteria and fungi exhibited negative correlation with PM1, PM2.5, and PM10, respectively. The respirable fractions of bacteria exhibited positive correlation with PM2.5, and the respirable fractions of fungi exhibited significant positive correlation with PM10. Ambient temperature had positive correlation with culturable airborne bacteria and fungi, and relative humidity had negative correlation with culturable airborne bacteria and fungi. In the afternoon, concentrations of culturable airborne fungi in indoor environment of university dormitory significantly increased, and the size distribution of culturable hioaerosols was different in the morning and afternoon.

Polycyclic aromatic hydrocarbons (PAHs) in atmospheric dustfall from the industrial corridor in Hubei Province, Central China.

Thirty atmospheric dustfall samples collected from an industrial corridor in Hubei Province, central China, were analyzed for 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs) to investigate their concentrations, spatial distributions, sources, and health risks. Total PAH concentrations (ΣPAHs) ranged from 1.72 to 13.17 µg/g and averaged 4.91 µg/g. High molecular weight (4-5 rings) PAHs averaged 59.67% of the ΣPAHs. Individual PAH concentrations were not significantly correlated with total organic carbon, possibly due to the semi-continuous inputs from anthropogenic sources. Source identification studies suggest that the PAHs were mainly from motor vehicles and biomass/coal combustion. The incremental lifetime cancer risks associated with exposure to PAHs in the dustfall ranged from 10(-4) to 10(-6); these indicate potentially serious carcinogenic risks for exposed populations in the industrial corridor.