Glyphosate spraying exacerbates nitrogen and phosphorus loss in karst slope farmland.

Glyphosate herbicide is an indispensable material in agricultural production. In order to explore the potential environmental effects of glyphosate application in karst slope farmland, this paper used a variable slope steel tank to simulate the surface microtopography and underground pore structure characteristics of karst slope farmland, and combined with artificial rainfall experiments to explore the migration path of glyphosate in karst slope farmland and the impact of spraying glyphosate on soil nitrogen and phosphorus loss. The results showed that under the condition of heavy rain, glyphosate in karst slope farmland was mainly transported and diffused by surface runoff, supplemented by underground runoff; secondly, in different hydrological paths, glyphosate directly affected the content of nitrogen and phosphorus in runoff, and all showed extremely significant positive correlation (p < 0.001). In addition, rainfall conditions such as rainfall intensity, rainfall duration, and runoff affected the content of nitrogen and phosphorus in runoff to varying degrees. In conclusion, the application of glyphosate significantly increased the content of nitrogen and phosphorus in different runoff and accelerated the loss of nitrogen and phosphorus from soil, which not only led to soil degradation, but also threatened the safety of aquatic ecosystem. Therefore, in the prevention and control of agricultural non-point source pollution, the threat of glyphosate to the surrounding aquatic ecosystem cannot be ignored, especially in karst areas with frequent rainstorms and serious water erosion, long-term monitoring and risk assessment of glyphosate are needed.

Exploring potential targets of HPV&BC based on network pharmacology and urine proteomics.

BACKGROUND: Bladder cancer (BC) caused by Human papillomavirus (HPV) infection remains a complex public health problem in developing countries. Although the HPV vaccine effectively prevents HPV infection, it does not benefit patients with BC who already have HPV. METHODS: Firstly, the differential genes of HPV-related BC patients were screened by transcriptomics, and then the prognostic and clinical characteristics of the differential genes were analyzed to screen out the valuable protein signatures. Furthermore, the compound components and targets of Astragali Radix (AR) were analyzed by network pharmacology, and the intersection targets of drug components and HPV_BC were screened out for pathway analysis. In addition, the binding ability of the compound to the Astragali-HPV_BC target was verified by molecular docking and virtual simulation. Finally, to identify potential targets in BC patients through urine proteomics and in vitro experiments. RESULTS: Eleven HPV_BC-related protein signatures were screened out, among which high expression of EGFR, CTNNB1, MYC, GSTM1, MMP9, CXCR4, NOTCH1, JUN, CXCL12, and KRT14 had a poor prognosis, while low expression of CASP3 had a poor prognosis. In the analysis of clinical characteristics, it was found that high-risk scores, EGFR, MMP9, CXCR4, JUN, and CXCL12 tended to have higher T stage, pathological stage, and grade. Pharmacological and molecular docking analysis identified a natural component of AR (Quercetin) and it corresponding core targets (EGFR). The OB of the natural component was 46.43, and the DL was 0.28, respectively. In addition, EGFR-Quercetin has high affinity. Urine proteomics and RT-PCR showed that EGFR was expressed explicitly in BC patients. Mechanism analysis revealed that AR component targets might affect HPV_BC patients through Proteoglycans in the cancer pathway. CONCLUSION: AR can target EGFR through its active component (Quercetin), and has a therapeutic effect on HPV_BC patients.

Dietary berberine against intestinal oxidative stress, inflammation response, and microbiota disturbance caused by chronic copper exposure in freshwater grouper (Acrossocheilus fasciatus).

Berberine (BBR) is known for its strong antioxidant, anti-inflammatory, and capacity to preserve intestinal microbiota balance in fish. This study aimed to investigate the protective effects of berberine against copper-induced toxicity in the intestine of freshwater grouper Acrossocheilus fasciatus. The experiment involved four groups: a control group, a Cu group exposed to 0.02 mg/L Cu2+, and two BBR groups fed with 100 or 400 mg/kg of berberine diets and exposed to the same Cu2+ concentration. Three replicates of healthy fish (initial weight 1.56 ± 0.10 g) were subjected to their respective treatments for 30 days. Results showed that none of the treatments significantly affected the survival rate, final weight, weight gain, and feed intake (P > 0.05). However, supplementation with 100 and 400 mg/kg of BBR significantly lowered the antioxidant activities, and glutathione peroxidase (gpx) and superoxide dismutase (sod) expression levels, as well as reduced malondialdehyde (MDA) content caused by Cu2+ exposure (P < 0.05). Berberine inclusion significantly downregulated proinflammatory factors NLR family pyrin domain containing 3 (nlrp3), interleukin 1 beta (il1ß), interleukin 6 cytokine family signal transducer (il6st) but upregulated transforming growth factor beta 1 (tgfß1) and heat shock 70 kDa protein (hsp70) expression. Moreover, berberine at both levels maintained the intestinal structural integrity and significantly improved gap junction gamma-1 (gjc1) mRNA level compared to the Cu group (P < 0.05). Based on 16S rDNA sequencing, the richness and diversity of intestinal microbiota in different groups were not significantly influenced. Berberine reduced the Firmicutes/Bacteroidota ratio and stifled the growth of some specific pathogenic bacteria such as Pseudomonas, Citrobacter, and Acinetobacter, while boosting the richness of potential probiotic bacteria, including Roseomonas and Reyranella compared with the Cu group. In conclusion, berberine showed significant protective effects against Cu2+-induced intestinal oxidative stress, inflammation response, and microbiota disturbance in freshwater grouper.

Inhibition of HAdV-14 induced apoptosis by selenocystine through ROS-mediated PARP and p53 signaling pathways.

BACKGROUND: Human Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells. METHODS: The experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential. RESULTS: In the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways. CONCLUSION: SeC might provide an effective selenium species with antiviral properties for the therapies against HAdV-14.

[Post-stroke shoulder-hand syndrome of phlegm-stasis obstruction treated with the combined therapy of eye acupuncture, Tengliao and rehabilitation training: a multi-central randomized controlled trial].

OBJECTIVE: To assess the efficacy on relieving pain and improving the range of motion of shoulder joint in post-stroke shoulder-hand syndrome of phlegm-stasis obstruction in treatment of the combined therapy of eye acupuncture, Tengliao (Chinese herbal warm dressing technique) and rehabilitation training (eye acupuncture + Tengliao + rehabilitation) as compared with the combined treatment of Tengliao and rehabilitation training (Tengliao + rehabilitation) and the simple rehabilitation training (rehabilitation). METHODS: A total of 356 patients with post-stroke shoulder-hand syndrome of phlegm-stasis obstruction were randomized into an eye acupuncture + Tengliao + rehabilitation group (group A, 122 cases, 2 cases dropped off), a Tengliao + rehabilitation group (group B, 120 cases, 3 cases dropped off) and a rehabilitation group (group C, 114 cases, 1 case dropped off). In the group C, the basic treatment was combined with routine rehabilitation training. In the group B, on the base of the treatment as the group C, Tengliao was exerted. A medical bag composed of over 20 Chinese herbal materials was heated and dressed at the affected area, 30 min each time, 5 times weekly. In the group A, besides the treatment as the group B, eye acupuncture was applied to heart region, kidney region, upper jiao region and lower jiao region, 30 min each time, 5 times weekly. The treatment lasted 28 days in all of three groups. Separately, before treatment, in 7, 14, 21 and 28 days of treatment, as well as in 14 days after treatment of follow-up, the score of visual analogue scale (VAS) for pain, the score of guides to evaluation of permanent impairment (GEPI) and the score of National Institutes of Health stroke scale (NIHSS) were observed in each group. RESULTS: The scores of VAS, GEPI and NIHSS were all improved with the treatment lasting in the three groups (P<0.000 1). In 7, 14, 21 and 28 days of treatment and in follow-up as well, VAS scores in the group A were all lower than the group C (P<0.05). After 14 days of treatment, GEPI score showed increasing trend, while NIHSS score showed decreasing trend in the group A compared with the group B. Before treatment, GEPI score was lower and NIHSS score was higher in the group A compared with the group C (P<0.05). It was suggested that the illness was slightly serious in the group A. After propensity score matching, in 14, 21 and 28 days as well as in follow-up, GEPI scores in the group A were higher than the group C respectively (P<0.05). Regarding NIHSS score at each time point, the difference had no statistical significance between the group A and the group C (P>0.05). CONCLUSION: The combined therapy of eye acupuncture, Tengliao and rehabilitation training obtains a better efficacy on post-stroke shoulder-hand syndrome of phlegm-stasis obstruction as compared with rehabilitation training.

Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation.

Sho-saiko-to is a well-known traditional Chinese medicine compound and is considered to have therapeutic effects against many diseases, including thyroid cancer (TC). However, the mechanisms and therapeutic targets of Sho-saiko-to against TC remain unclear. In this study, network pharmacology, molecular docking, and cell experiments were combined to predict and verify the targets and mechanisms of the active ingredients of Sho-saiko-to against TC. The results demonstrated that the main chemical ingredients of Sho-saiko-to could suppress the viability and proliferation of TC cells, promote apoptosis through the caspase3 pathway, and induce autophagy through the PI3K-AKT pathway. In addition, Sho-saiko-to could also induce the redifferentiation of anaplastic thyroid cancer. Our study provides a novel approach for treating differentiated thyroid cancer (DTC) or radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC).

Wheat grain phenolics: a review on composition, bioactivity, and influencing factors.

Wheat (Triticum aestivum L.) is a widely cultivated crop and one of the most commonly consumed food grains in the world. It possesses several nutritional elements. Increasing attention to wheat grain phenolics bioactivity is due to the increasing demand for foods with natural antioxidants. To provide a comprehensive understanding of phenolics in wheat grain, this review first summarizes the phenolics' form and distribution and the phenolic components identified in wheat grain. In particular, the biosynthesis path for phenolics is discussed, identifying some candidate genes involved in the biosynthesis of phenolic acids and flavonoids. After discussing the methods for determining antioxidant activity, the effect of genotypes, environmental conditions, and cultivation systems on grain phenolic component content are explored. Finally, the bioavailability of phenolics under different food processing method are reported and discussed. Future research is recommended to increase wheat grain phenolic content by genetic engineering, and to improve its bioavailability through proper food processing. © 2021 Society of Chemical Industry.

Integrative RNA-Seq and ATAC-Seq Analysis Reveals the Migration-Associated Genes Involved in Antitumor Effects of Herbal Medicine Feiyanning on Lung Cancer Cells.

Lung cancer is one of the leading causes of cancer-associated death in the world. It is of great importance to explore new therapeutic targets. Traditional Chinese medicine formula Feiyanning has been clinically administered in China for more than a decade and raised attention due to its anticancer effect in lung cancer. However, the underlying molecular mechanisms remain to be elucidated. In the present study, we carried out cellular and molecular assays to examine the antitumor activities and understand the mechanism of the Feiyanning formula in lung cancer cells. The cellular viability of Feiyanning-treated lung cancer cells was evaluated by Cell Counting Kit-8. The effect of the Feiyanning formula on cellular migration and invasion of lung cancer cells was examined by wound healing and transwell assays. Transcriptome and chromatin accessibility analysis by RNA-seq and ATAC-seq was performed to investigate the underlying molecular mechanisms. Our results revealed that the Feiyanning formula inhibited the cellular activities of proliferation, migration, and invasion in non-small cell lung cancer cell lines A549, H1975, and 95D. Furthermore, we observed that the transcriptional activity of the migration-associated genes was downregulated upon Feiyanning formula treatment in non-small cell lung cancer cells. The chromatin accessibility of the Feiyanning-treated lung cancer genome tended to decrease, and the regulation of the cellular component movement biological process and PI3K-AKT pathway were enriched among these altered genomic regions. Taken together, the present study suggested that Feiyanning formula exerted the antitumor effects by modulating the expression and chromatin accessibility levels of migration-associated genes.

Omega-3 fatty acid supplementation is associated with favorable outcomes in patients with sepsis: an updated meta-analysis.

OBJECTIVES: The efficacy of omega-3 fatty acids in the treatment of sepsis is controversial. We conducted an updated meta-analysis to clarify the efficacy of omega-3 fatty acids in patients with sepsis. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with sepsis. RESULTS: Twenty eligible RCTs involving 1514 patients were included in the meta-analysis. Omega-3 fatty acid supplementation was linked to reductions of mortality (I2 = 0, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.69-0.97), the duration of mechanical ventilation (DMV; I2 = 74%, weighted mean difference [WMD] = -2.20, 95% CI = -4.00 to -0.40), and intensive care unit (ICU) length of stay (LOS; I2 = 91%, WMD = -3.86, 95% CI = -5.72 to -2.01). Subgroup analysis illustrated that mortality was significantly reduced in patients with sepsis and gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29-0.86, I2 = 0). CONCLUSION: Omega-3 fatty acid supplementation might be associated with reduced mortality in patients with sepsis, especially those with gastrointestinal dysfunction. Furthermore, omega-3 fatty acid administration could shorten DMV and ICU LOS.

Exogenous Melatonin Modulates the Physiological and Biochemical Mechanisms of Drought Tolerance in Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn).

Tartary buckwheat is one of the nutritious minor cereals and is grown in high-cold mountainous areas of arid and semi-arid zones where drought is a common phenomenon, potentially reducing the growth and yield. Melatonin, which is an amphiphilic low molecular weight compound, has been proven to exert significant effects in plants, under abiotic stresses, but its role in the Tartary buckwheat under drought stress remains unexplored. We evaluated the influence of melatonin supplementation on plant morphology and different physiological activities, to enhance tolerance to posed drought stress by scavenging reactive oxygen species (ROS) and alleviating lipid peroxidation. Drought stress decreased the plant growth and biomass production compared to the control. Drought also decreased Chl a, b, and the Fv/Fm ratio by 54%, 70%, and 8%, respectively, which was associated with the disorganized stomatal properties. Under drought stress, H2O2, O2•-, and malondialdehyde (MDA) contents increased by 2.30, 2.43, and 2.22-folds, respectively, which caused oxidative stress. In contrast, proline and soluble sugar content were increased by 84% and 39%, respectively. However, exogenous melatonin (100 µM) could improve plant growth by preventing ROS-induced oxidative damage by increasing photosynthesis, enzymatic antioxidants (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), secondary metabolites like phenylalanine ammonialyase, phenolics, and flavonoids, total antioxidant scavenging (free radical DPPH scavenging), and maintaining relative water content and osmoregulation substances under water stress. Therefore, our study suggested that exogenous melatonin could accelerate drought resistance by enhancing photosynthesis and antioxidant defense in Tartary buckwheat plants.

Discovery and identification of proangiogenic chemical markers from Gastrodiae Rhizoma based on zebrafish model and metabolomics approach.

INTRODUCTION: Angiogenesis is closely related to a variety of diseases, and therapies based on angiogenesis are intensely investigated. Studies have shown that the use of Gastrodiae Rhizoma (GR, Gastrodia elata) can benefit the treatment of ischemic cardiovascular diseases and atherosclerosis by stimulating angiogenesis. OBJECTIVE: This study tested the angiogenesis effects of a group of chemical markers isolated from GR. MATERIAL AND METHODS: Zebrafish model was used to evaluate angiogenesis by setting four groups: blank control group, model group, positive control group and treatment group (0.1, 1, and 100 µg/mL RGP). The Gray correlation analysis (GCA) was implemented to calculate the correlation coefficients of each compound between the peak area in liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) and the bioactivity, the top ten components with the correlation degree > 0.9 were listed. RESULTS AND DISCUSSION: The optimum final concentration of GR on proangiogenesis effect was determined to be 100 µg/mL. Ten compounds, including gastrodin, parishin E, stigmasterol, p-hydroxybenzyl alcohol, citric acid, etc., were identified to have high correlation coefficients with proangiogenic activity. Furthermore, the network pharmacologic analysis of these compounds revealed that the compounds systematically regulate the formation of new blood vessels via networked vital targets and signalling pathways. CONCLUSION: GR can promote the growth of blood vessels, ten chemical components discovered contribute to this proangiogenesis activity. These chemical markers of GR thus provide a foundation for further studies on medicinal substances and quality evaluation of GR, also providing a scientific basis for modern interpretation of the processing theory of traditional Chinese medicine.

The reduction of allograft arteriosclerosis in intestinal transplant is associated with sphingosine kinase 1/sphingosine-1-phosphate signaling after fish oil treatment.

BACKGROUND: Transplant arteriosclerosis is a major cause of late intestinal allograft dysfunction. However, little is known about the immunologic and molecular mechanisms underlying it, and no effective treatment is available. This study aimed to investigate the role of sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) in transplant arteriosclerosis and find out whether fish oil (FO) attenuates allograft arteriosclerosis through S1P signaling. METHODS: A rat model with orthotopic intestinal transplantation was conducted in this study. Animals received daily FO supplementation after intestinal transplant. The allogeneic recipients by phosphate-buffered saline or corn oil treatment served as controls. The allograft arteriosclerosis was characterized, and the expression of SPHK1 and S1P receptors (S1P1, S1P2, and S1P3) was determined on day 190 posttransplant. RESULTS: The allogeneic controls presented transplant vasculopathy in mesenteric vessels, including intimal thickening, fibrosis, and leukocyte infiltration. The transplant arteriosclerosis was markedly reduced in FO-fed animals. The pression of SPHK1 and its activity were significantly augmented, and the expression of S1P1 and S1P3 messenger RNA was up-regulated in the allogeneic controls. FO supplementation suppressed the activation of SPHK1 and led to a decrease in the expression of S1P1 and S1P3 in these tissues in transplant arteriosclerosis. CONCLUSIONS: These results demonstrate that the activation of SPHK1/S1P signaling plays a possible role in the pathogenesis of transplant arteriosclerosis. The reduction of allograft arteriosclerosis by FO may be associated with down-regulation of SPHK1/S1P signaling. Understanding the role of FO for SPHK1/S1P may help us to identify considerable therapeutic targets for transplant arteriosclerosis.

Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

BACKGROUND: The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.