Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

IntroductionClonorchiasis remains a serious global public health problem, causing various hepatobiliary diseases. However, there is still a lack of overall understanding regarding the molecular events triggered by Clonorchis sinensis (C. sinensis) in the liver.MethodsBALB/c mouse models infected with C. sinensis for 5, 10, 15, and 20 weeks were constructed. Liver pathology staining and observation were conducted to evaluate histopathology. The levels of biochemical enzymes, blood routine indices, and cytokines in the blood were determined. Furthermore, alterations in the transcriptome, proteome, and metabolome of mouse livers infected for 5 weeks were analyzed using multi-omics techniques.ResultsThe results of this study indicated that adult C. sinensis can cause hepatosplenomegaly and liver damage, with the most severe symptoms observed at 5 weeks post-infection. However, as the infection persisted, the Th2 immune response increased and symptoms were relieved. Multi-omics analysis of liver infected for 5 weeks identified 191, 402 and 232 differentially expressed genes (DEGs), proteins (DEPs) and metabolites (DEMs), respectively. Both DEGs and DEPs were significantly enriched in liver fibrosis-related pathways such as ECM-receptor interaction and cell adhesion molecules. Key molecules associated with liver fibrosis and inflammation (Cd34, Epcam, S100a6, Fhl2, Itgax, and Retnlg) were up-regulated at both the gene and protein levels. The top three metabolic pathways, namely purine metabolism, arachidonic acid metabolism, and ABC transporters, were associated with liver cirrhosis, fibrosis, and cholestasis, respectively. Furthermore, metabolites that can promote liver inflammation and fibrosis, such as LysoPC(P-16:0/0:0), 20-COOH-leukotriene E4, and 14,15-DiHETrE, were significantly up-regulated.ConclusionOur study revealed that the most severe symptoms in mice infected with C. sinensis occurred at 5 weeks post-infection. Moreover, multi-omics analysis uncovered predominant molecular events related to fibrosis changes in the liver. This study not only enhances our understanding of clonorchiasis progression but also provides valuable insights into the molecular-level interaction mechanism between C. sinensis and its host liver

Incremental feedforward collective pitch control method for wind turbines

In recent years, wind turbines are becoming larger, which will exacerbate the complexity of loads Complex load change affect the output power quality and wind turbine service life so that must be studied. Pitch control is usually used to reduce wind turbine load. In this paper, based on the Light Detection and Ranging (LiDAR) technology and incremental feedforward control theory, an incremental feedforward collective pitch controller is proposed. The controller can be directly superimposed on the traditional collective pitch controller so that the incremental pitch angle can fully compensate wind influence. The effectiveness of the controller is verified by multi-software platform joint simulation and hardware-in-the-loop experiment. The results show that the controller can effectively reduce the wind turbine power and load fluctuation when the variation trend of wind speed in the rotor plane estimate by LiDAR data is the same as the actual wind speed

Petrogenesis of Garnet Clinopyroxenite and Associated Dunite in Hujialin, Sulu Orogenic Belt, Eastern China

The origin of ultramafic rocks, especially those in suture zones, has been a focus because they are not only important mantle sources of magma, but also provide substantial information on metamorphism and melt/fluid–peridotite interaction. Ultramafic rocks in Hujialin, in the central part of the Sulu orogen, include peridotite and pyroxenite. Although many papers on their origin and tectonic evolution have been published in the past few decades, these questions are still highly debated. Here, we present mineralogy, mineral composition, and bulk-rocks of these ultramafic rocks to evaluate their origin and tectonic evolution. The garnet clinopyroxenite is low in heavy rare-earth elements (HREE, 5.97–10.6 ppm) and has convex spoon-shaped chondrite-normalized REE patterns, suggesting the garnet formed later, and its precursor is clinopyroxenite. It is high in incompatible elements (i.e., Cs, Rb, Ba) and shows negative to positive U, Nb, and Ta anomalies, without pronounced positive Sr or Eu anomalies. Clinopyroxene in garnet clinopyroxenite contains high MgO (Mg# 0.90–0.97). The mineral chemistry and bulk-rock compositions are similar to those of reactive clinopyroxenite, suggesting that it originally formed via peridotite–melt interaction, and that such silicic and calcic melt might derive from the subducted Yangtze continent (YZC). Dunite contains olivine with high Fo (93.0–94.1), low NiO (0.11–0.29 wt.%) and MnO (≤0.1 wt.%), chromite with high Cr# (0.75–0.96), TiO2 (up to 0.88 wt.%), and Na2O (0.01–0.10 wt.%). It has negatively sloped chondrite-normalized REE patterns. Mineral chemistry and bulk rocks suggest dunite likely represent residual ancient lithosperic mantle peridotite beneath the North China Craton (NCC) that was overprinted by aqueous fluids. The lack of prograde and retrograde metamorphic minerals in dunite and irregular shaped mineral inclusions in chromite suggest dunite did not subduct to deep levels. Dunite mingled with garnet clinopyroxenite during exhumation of the latter at shallow depths. These ultramafic rocks, especially hydrated peridotite, may be important sources of Au for the Jiaodong gold province in the NCC

Petrogenesis of Garnet Clinopyroxenite and Associated Dunite in Hujialin, Sulu Orogenic Belt, Eastern China

The origin of ultramafic rocks, especially those in suture zones, has been a focus because they are not only important mantle sources of magma, but also provide substantial information on metamorphism and melt/fluid–peridotite interaction. Ultramafic rocks in Hujialin, in the central part of the Sulu orogen, include peridotite and pyroxenite. Although many papers on their origin and tectonic evolution have been published in the past few decades, these questions are still highly debated. Here, we present mineralogy, mineral composition, and bulk-rocks of these ultramafic rocks to evaluate their origin and tectonic evolution. The garnet clinopyroxenite is low in heavy rare-earth elements (HREE, 5.97–10.6 ppm) and has convex spoon-shaped chondrite-normalized REE patterns, suggesting the garnet formed later, and its precursor is clinopyroxenite. It is high in incompatible elements (i.e., Cs, Rb, Ba) and shows negative to positive U, Nb, and Ta anomalies, without pronounced positive Sr or Eu anomalies. Clinopyroxene in garnet clinopyroxenite contains high MgO (Mg# 0.90–0.97). The mineral chemistry and bulk-rock compositions are similar to those of reactive clinopyroxenite, suggesting that it originally formed via peridotite–melt interaction, and that such silicic and calcic melt might derive from the subducted Yangtze continent (YZC). Dunite contains olivine with high Fo (93.0–94.1), low NiO (0.11–0.29 wt.%) and MnO (≤0.1 wt.%), chromite with high Cr# (0.75–0.96), TiO2 (up to 0.88 wt.%), and Na2O (0.01–0.10 wt.%). It has negatively sloped chondrite-normalized REE patterns. Mineral chemistry and bulk rocks suggest dunite likely represent residual ancient lithosperic mantle peridotite beneath the North China Craton (NCC) that was overprinted by aqueous fluids. The lack of prograde and retrograde metamorphic minerals in dunite and irregular shaped mineral inclusions in chromite suggest dunite did not subduct to deep levels. Dunite mingled with garnet clinopyroxenite during exhumation of the latter at shallow depths. These ultramafic rocks, especially hydrated peridotite, may be important sources of Au for the Jiaodong gold province in the NCC

Effect of Silica Fume and Polyvinyl Alcohol Fiber on Mechanical Properties and Frost Resistance of Concrete

To improve the mechanical properties and frost resistance of concrete, silica fume, and polyvinyl alcohol fiber compounded in concrete. The mechanical and frost resistance of concrete were comprehensively analyzed and evaluated for strength change, mass loss, and relative dynamic elastic modulus change by compressive strength test, flexural strength test, and rapid freeze-thaw test. The results showed that with the incorporation of silica fume and polyvinyl alcohol fiber, the compressive and flexural strengths of concrete were improved, and the decrease in mass loss rate and relative dynamic elastic modulus of concrete after freeze-thaw cycles were significantly reduced, which indicated that the compounding of silica fume and polyvinyl alcohol fiber improved the frost resistance of concrete. When the content of silica fume was 10% and the volume content of polyvinyl alcohol fiber was 1%, the comprehensive mechanical performance and frost resistance of concrete is the best. The compressive strength increased by 26.6% and flexural strength increased by 29.17% compared to ordinary concrete. Based on the test data, to study the macroscopic damage evolution of concrete compound silica fume and polyvinyl alcohol fiber under repeated freeze-thaw conditions. The Weibull distribution probability model and GM (1, 1) model were established. The average relative errors between the predicted and actual data of the two models are small and very close. It is shown that both models can reflect well the development of concrete damage under a freeze-thaw environment. This provides an important reference value and theoretical basis for the durability evaluation and life prediction of compound silica fume and polyvinyl alcohol fiber concrete in cold regions

Study of SPRC Impact Resistance Based on the Weibull Distribution and the Response Surface Method

Silica-fume–polyvinyl-alcohol-fiber-reinforced concrete (SPRC) is a green and environmentally friendly composite material incorporating silica fume and polyvinyl alcohol fiber into concrete. To study the impact resistance of SPRC, compressive-strength and drop hammer impact tests were conducted on SPRC with different silica-fume and polyvinyl-alcohol-fiber contents. The mechanical and impact resistance properties of the SPRC were comprehensively analyzed in terms of the compressive strength, ductility ratio and impact-energy-dissipation variation. Based on the impact resistance of the SPRC, the impact life of SPRC with different failure probabilities was predicted by incorporating the Weibull distribution model, and an impact damage evolution equation for SPRC was established. The impact life of SPRC under the action of silica-fume content, polyvinyl-alcohol-fiber content and failure probability was analyzed in depth by the response surface method (RSM). The research results show that, when the content of silica fume is 10% and the content of polyvinyl alcohol fiber is 1%, the compressive strength and impact resistance of SPRC are the best. The RSM response model can effectively predict and describe the impact life of SPRC specimens under the action of three factors

Identification and Evolution of the Noncoordination Coupling Relationship between Tourism Poverty Alleviation and Ecological Environments in Poor Mountainous Areas

Tourism poverty alleviation and ecological environments are closely associated with each other’s dissipation structure, which contains various coordinated and noncoordinated coupling states. Based on the perspective of reverse thinking and problem diagnosis, this paper constructs a bridge from uncoordinated pathology to coordinated development. From the perspective of incongruity, the framework model and evaluation index system of tourism poverty alleviation and ecological environments incongruity coupling coordination driving mechanism are constructed. Also, the variation coefficient method is used to calculate the weight of each evaluation index and the coupling relationship and evolution of tourism poverty alleviation and ecological environments in Liupanshui city are analyzed by the noncoordination coupling function. The results suggest the following: (1) During the study period, the poverty alleviation level of tourism in Liupanshui city presents a continuous growth curve. Meanwhile, ecological environment development level depicts rapid growth initially and then slows down and improves further. In this way, it shows different stage characteristics from the tourism poverty alleviation level. (2) The discordant coupling between tourism poverty alleviation and ecological environments in Liupanshui city shows a decreasing curve. So, the noncoordinated development relationship between tourism poverty alleviation and ecological environments is significant

Six bufadienolides derivatives are the main active substance against human colorectal cancer HCT116 cells of Huachansu injection

Background: Huachansu injection (HCS) is an aqueous extract preparation of Traditional Chinese Medicine (TCM) toad skin (Bufo melanosticus or B. bufo gargarizans). As a national second-class and self-developed TCM preparation, it is widely used to treat human colorectal cancer (CRC), yet its substantial toxic side effects, such as vascular irritation reaction, drug fever, and allergic reactions, pose a considerable challenge during clinical use. In-depth research on the material basis of HCS' traditional efficacy is essential for developing more effective and less toxic medicine. Identifying the main components responsible for the efficacy of HCS is crucial in determining its material basis and explaining any adverse reactions. Purpose: The purpose of this study is to clarify the main active components of HCS as a growth inhibitory agent against CRC HCT116 cells and to further understand the material basis of its anti-CRC properties. Methods: Sulforhodamine B (SRB) assay was used to screen the compound with strong inhibitory activity against HCT116 cells from 44 compounds isolated from aqueous extracts of toad skin (B. melanosticus). The screened compounds as standard and MeOH extracts from HCS were determined by HPLC coupled with triple quadrupole mass spectrometry. The partial MeOH extract was subjected to HPLC system using solvents in a gradient of increasing polarity, yielding 12 fractions in total (HCS1 to HCS12). Besides, the screened active compounds were knocked out from HCS to obtain a fraction as a negative control, and the knocked-out components were collected as one fraction using semi-preparative HPLC. Those fractions were submitted to HPLC-MS/MS or HPLC-DAD system to determine the presence or absence of the screened compounds. In addition, cytotoxicity of those prepared fractions against CRC HCT116 cells was evaluated to determine the effect of the screened compounds in the anti-CRC of HCS. Results: Six compounds, namely arenobufagin, telocinobufagin, gamabufalin, hellebrigenin, 19-hydroxylbufagin and argentinogenin, were screened for their inhibitory activity (with an IC50 value of less than 400 nM), and were present in HCS at a total-mass-percentage of 1.35×10−3 % in HCS MeOH extract. In addition, those 6 compounds were mainly distributed in HCS8, which also showed the strongest inhibitory activity against HCT116 cells. And the results of multicomponent knockout assay indicated the negative control lost its anti-CRC activity significantly, while the activity can be restored after those 6 compounds were added to the negative control. Conclusions: Those six bufadienolides derivatives are responsible for the anti-CRC HCT116 cells activity of HCS, and are the main components of HCS on anti-CRC. Through this research, we can more clearly understand the main anti-CRC active components in HCS, and the work also lays the foundation for the development of more effective and less toxic medicine from HCS

Experimental Study on the Mechanics and Impact Resistance of Multiphase Lightweight Aggregate Concrete

Multiphase lightweight aggregate concrete (MLAC) is a green composite building material prepared by replacing part of the crushed stone in concrete with other coarse aggregates to save construction ore resources. For the best MLAC performance in this paper, four kinds of coarse aggregate—coal gangue ceramsite, fly ash ceramsite, pumice and coral—were used in different dosages (10%, 20%, 30% and 40%) of the total coarse aggregate replacement. Mechanical property and impact resistance tests on each MLAC group showed that, when coal gangue ceramsite was 20%, the mechanical properties and impact resistance of concrete were the best. The compressive, flexural and splitting tensile strength and impact energy dissipation increased by 29.25, 19.93, 13.89 and 8.2%, respectively, compared with benchmark concrete. The impact loss evolution equation established by the two-parameter Weibull distribution model effectively describes the damage evolution process of MLAC under dynamic loading. The results of a comprehensive performance evaluation of four multiphase light aggregate concretes are coal gangue ceramsite concrete (CGC) > fly ash ceramsite concrete (FAC) > coral aggregate concrete (CC) > pumice aggregate concrete (PC)

Body mass index and weight loss as risk factors for poor outcomes in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis

AbstractObjective The association between nutritional status and prognosis of idiopathic pulmonary fibrosis (IPF) remains unclear. This systematic review and meta-analysis aimed to explore the effect of body mass index (BMI) and weight loss on the prognosis of IPF patients.Methods We accumulated studies on IPF, BMI, and weight loss from databases including PubMed, Embase, Web of science, Scopus, Ovid and Cochrane Library up to 4 August 2023. Using Cox proportional hazard regression model for subgroup analysis, hazard ratio (HR) and 95% confidence intervals (CI) for BMI in relation to mortality, acute exacerbation (AE), and hospitalization in IPF patients were calculated, and HR, odds ratio (OR), and 95% CI for weight loss corresponding to IPF patient mortality were assessed. Sensitivity analysis was peformed by eliminating every study one by one, and publication bias was judged by Egger’s test and trim-and-fill method.Results A total of 34 eligible studies involving 18,343 IPF patients were included in the meta-analysis. The pooled results by univariate Cox regression analysis showed that baseline BMI was a predictive factor for IPF mortality (HR = 0.93, 95%CI = [0.91, 0.94]). Furthermore, the results by the multivariable regression model indicated that baseline BMI was an independent risk factor for predicting IPF mortality (HR = 0.94, 95%CI = [0.91, 0.98]). Weight loss was identified as a risk factor for IPF mortality (HR = 2.74, 95% CI = [2.12, 3.54]; OR = 4.51, 95% CI = [1.72, 11.82]) and there was no predictive value of BMI for acute exacerbation (HR = 1.00, 95% CI= [0.93, 1.07]) or hospitalization (HR = 0.95, 95% CI = [0.89, 1.02]).Conclusion Low baseline BMI and weight loss in the course of IPF may indicate a high risk of mortality in patients with IPF, so it is meaningful to monitor and manage the nutritional status of IPF patients, and early intervention should be conducted for low BMI and weight loss