Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology.

BACKGROUND: Alcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated. PURPOSE: The purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD. METHODS: Network pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets. RESULTS: HSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro. CONCLUSION: This study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.

Regulation of Erythroid Differentiation via the HIF1α-NFIL3-PIM1 Signaling Axis Under Hypoxia.

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM: To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS: We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS: HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION: Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

Impact of landfill garbage on insect ecology and human health.

The landfill garbage includes organic and inorganic matter. The organic matter covers more than 50% of the total waste material. Due to improper management of landfill garbage, it causes serious risks to human health directly by the emission of toxic gasses. On the other hand, landfill sites are the natural habitat of several microbes and arthropods. The present discussion illustrates the impact of landfill garbage on insect ecology and human health. Here, we highlighted the arthropod density as well as diversity. Moreover, the population of insect vectors of various diseases, insect scavengers as well as pollinators has been pinpointed. It shows that landfill sites and adjacent areas are hotspots for a wide variety of arthropods. The proper management of landfill sites could reduce the population dynamics of various insect pests, and health risks could be decreased in low-and middle-income countries.

[Characteristics of Chemical Fractions of Dissolved Organic Matter in Road Runoff in Beijing].

The characteristics of DOM chemical fractions in road runoff with different traffic density were analyzed using excitation emission matrix spectroscopy (EEMs) technology, UV-vis spectra, and FTIR spectroscopy. The results showed that hydrophobic organics were the dominant components in DOM of road runoff, and hydrophobic neutral organics was the most abundant fraction. The hydrophilic organics in DOM of road runoff were mainly composed of protein-like substances. Both protein-like substances and fulvic-like acid substances were found in the hydrophobic organic matters. A high degree of aromatization and a low degree of humification were detected in hydrophobic organics, whereas the characteristics of hydrophilic organics were opposite. Some functional groups such as isomerized carboxyl and unsaturated C=C bonds were featured in acidic organics, and ether and ester groups, phenol, and alcohol were detected in alkaline and neutral organics. The substance composition and characteristics of DOM chemical fractions in road runoff were not affected by the traffic density. Traffic density influenced the quantity of substances in each chemical fraction only. With traffic density increasing, the matter content and the aromatization degree of DOM chemical fractions in road runoff increased, whereas the degree of humification decreased.

An effective live attenuated vaccine against Aeromonas veronii infection in the loach (Misgurnus anguillicaudatus).

Aeromonas veronii is a major pathogenic bacterium in humans and animals. When it causes outbreaks, there are enormous economic losses to the aquaculture industry. An effective live attenuated vaccine strain, ΔhisJ, was obtained in our previous studies by gene knockout in Aeromonas veronii TH0426 using the suicide vector pRE112. Here, we evaluated whether the live attenuated vaccine ΔhisJ was suitable for prevention of Aeromonas veronii infection by injection and immersion in loaches. Compared with that of the TH0426 wild-type strain, the virulence of the live vaccine was significantly weakened. Vaccine safety assessment results also indicated that 1 × 107 CFU/mL live vaccine was safe and did not induce clinical symptoms or obvious pathological changes. Additionally, after challenging loaches with Aeromonas veronii TH0426, the relative percent survival of the IN3 injection group was 65.66%, and that of the IM group was 50.78%. Our data show that the live attenuated vaccine ΔhisJ can improve the immune protection rate of loaches. Furthermore, increased enzyme activity parameters (SOD, LZM, ACP, and AKP) in the skin mucus, increased enzyme activity parameters (SOD, LZM, ACP, AKP, and GPx) in the serum, increased specific IgM antibodies and cytokine IL-1ß contents in the serum, and increased cytokine (IL-15, pIgR, IL-1ß, and TNF-α) expression in the liver and spleen were observed. These data are the first to indicate that the live attenuated vaccine ΔhisJ is suitable for the development of a safe and effective vaccine against Aeromonas veronii infection in loach aquaculture.

Self-transport of underwater bubbles on a microholed hydrophobic surface with gradient wettability.

Manipulation of underwater bubbles is of great importance in both scientific research and industrial applications. In this work, the motion of underwater bubbles on a microholed polydimethylsiloxane (PDMS) surface with gradient wettability is studied using a high-speed camera. It was found that underwater bubbles self-transported directionally from the smaller area fraction (SAF) to the larger area fraction (LAF) of the surface. Besides, the bubble motion was triggered by an effective depth range from hcr,min to hcr,max. Only the depth of the bubble was within the range when the self-transport motion occurred. Otherwise the bubble would adhere onto the surface eventually. The main cause for the motion is the trapped air inside the microholes, which generates the torque Tb and the retention force Fr driving the bubble directionally. The mathematical model is established to reveal the motion mechanism, which is verified by the experimental results. The outcomes of our work shed new light on the target transportation fields such as drug delivery and submarine gas collection.

Review on antibacterial characteristics of bridge engineering biomaterials.

This review summarizes the research on timber construction materials used in bridge construction. It focuses on the application of antiseptic treatments and the use of timber engineering materials in decks and bridges. This review also provides an overview on the future research and prospects of engineered timber materials.

Growth, Feed Utilization and Blood Metabolic Responses to Different Amylose-amylopectin Ratio Fed Diets in Tilapia (Oreochromis niloticus).

A feeding trial was conducted in tilapia to determine the growth performance, nutrient digestibility, digestive enzymes, and postprandial blood metabolites in response to different dietary amylose-amylopectin ratios. Five isonitrogenous and isolipidic diets containing an equal starch level with different amylose-amylopectin ratios of 0.11 (diet 1), 0.24 (diet 2), 0.47 (diet 3), 0.76 (diet 4) and 0.98 (diet 5) were formulated using high-amylose corn starch (as the amylose source) and waxy rice (as the amylopectin source). Each diet was hand-fed to six tanks of 15 fish each, three times a day over a 6-wk period. After the growth trial, a postprandial blood metabolic test was carried out. Fish fed diet 2 exhibited the highest percent weight gain and feed efficiency and protein efficiency ratio, whereas fish fed with diet 5 showed the lowest growth and feed utilization among treatments. The digestibility for starch in fish fed diet 1 and 2 was higher than those in fish fed with other diets (p<0.05). The highest activities for protease, lipase and amylase were found in fish fed the diet 2, diet 1, and diet 1 respectively among dietary treatments, while the lowest values for these indexes were observed in fish fed the diet 3, diet 5 and diet 4, respectively. The liver glycogen concentrations in fish fed diets 4 and 5 were found higher than in fish fed other diets (p<0.05). The feeding rate, hepatosomatic index, condition factor, and plasma parmeters (glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) did not differ across treatments. In terms of postprandial blood responses, peak blood glucose and triglycerides were lower after 3 or 6 h in the fish fed with diets 3-5 than in the fish fed diet 1, but delayed peak blood total amino acid time was observed in fish fed with the diets 1 or 2. The lowest peak values for each of the three blood metabolites were observed in fish fed diet 5. The results indicate that high-dietary amylose-amylopectin ratio could compromise growth, but help in reducing the blood glucose stress on fish caused by postprandial starch load.