Comprehensive bioremediation effect of phosphorus-mineralized bacterium Enterobacter sp. PMB-5 on cadmium contaminated soil-crop system.

Phosphate-mineralizing bacteria (PMBs) have been widely studied by inducing phosphate heavy metal precipitation, but current researches neglect to study their effects on soil-microbe-crop systems on cadmium (Cd) contaminated. Based on this, a strain PMB, Enterobacter sp. PMB-5, was inoculated into Cd contaminated pots to detect soil characteristics, Cd occurrence forms, soil biological activities, plant physiological and biochemical indicators. The results showed that the inoculation of strain PMB-5 significantly increased the available phosphorus content (85.97%-138.64%), Cd-residual fraction (11.04%-29.73%), soil enzyme activities (31.94%-304.63%), plant biomass (6.10%-59.81%), while decreased the state of Cd-HOAc (11.50%-31.17%) and plant bioconcentration factor (23.76%-44.24%). These findings indicated that strain PMB-5 could perform the function of phosphorus solubilization to realize the immobilization of Cd in the complex soil environment. Moreover, SEM-EDS, FTIR, XPS, and XRD analysis revealed that strain PMB-5 does not significantly alter the soil morphology, structure, elemental distribution, and chemical composition, which suggested that remediation of Cd contamination using strain PMB-5 would not further burden the soil. This research implies that PMB-5 could be a safe and effective bioinoculant for remediating Cd-contaminated soils, contributing to the sustainable management of soil health in contaminated environments.

Cadmium induced changes in rhizosphere microecology to enhance Cd intake by Ligusticum sinense cv. Chuanxiong.

As the most famous and widely used traditional Chinese medicine (TCM), Ligusticum sinense cv. Chuanxiong (L. Chuaniong) has been affected by cadmium (Cd) exceeding with high ability of Cd accumulation. There is relatively little research on Cd absorption and storage process in L. Chuanxiong, which is an important reason for the poor remediation efficiency. Hence, this study takes L. Chuanxiong as the point of penetration to explore how L. Chuanxiong affects rhizobacteria through root exudates to alter soil Cd intake, as well as to explore the migration and storage of Cd in its body with 0.10 (T0), 5.00 (T5), 10.00 (T10) mg/kg Cd contaminations. The results showed that the relative abundance of amino acids and phospholipids secreted from L. Chuanxiong root noticeably increased with increasing Cd levels, which directly activated soil Cd or extremely significantly (P < 0.01) recruited bacteria such as Bacillus, Arthrobacter to indirectly increase Cd availability. Under the interaction of root exudates and rhizobacteria, Cd bioavailability increased by 80.00% in rhizosphere soil and Cd accumulation in L. Chuanxiong increased 5.44-6.65 mg/kg. Cd subcellular distribution analysis demonstrated that Cd was mainly stored in the root (10-fold more than in the leaf), whose Cd content was cytoderm>cytoplasm>organelle in tissues. The sequential extraction results found that non-soluble phosphate and protein-chelated Cd dominated (85.00-90.00%) in the cell, while Cd cheated with alcohol soluble protein, amino acid salts, water-soluble organic acid in cell was minimal (5.50%). The phenomenon indicated that L. Chuanxiong fixed Cd in root (the medical part) with low translocation ability. This study can provide theoretical support for the high-quality production of L. Chuanxiong and other root medical plant in heavy metal influenced sites.

Morel (Morchella spp.) intake alters gut microbial community and short-chain fatty acid profiles in mice.

Morels (Morchella spp.) are highly nutritious and consumed as both edible mushrooms and traditional Chinese medicine. This study aimed to investigate the effects of dietary supplementation with morel mushrooms on the gut bacterial microbiota and short-chain fatty acids (SCFAs) profiles in healthy mice. Healthy mice were randomly assigned to five groups: a control group (0% morel) and four intervention groups supplemented with different levels of morel mushrooms (5% for M5, 10% for M10, 15% for M15, and 20% for M20) over a period of 4 weeks. Fecal samples were collected at the end of the experiment to characterize the microbiota and assess the SCFAs levels. The morel intervention significantly altered the bacterial community composition, increasing Bacteroides, Lachnospiraceae NK4A136 group and Parabacteroides, while decreasing Staphylococcus and the Firmicutes to Bacteroidetes ratio (F/B ratio). Moreover, increased morel intake was associated with weight loss. All SCFAs content was upregulated in the morel-intervention groups. Potential SCFAs-producing taxa identified by regression analysis were distributed in the families Muribaculaceae, Lachnospiraceae, and in the genera Jeotgalicoccus, Gemella, Odoribacter, Tyzzerella 3 and Ruminococcaceae UCG-014. The functional categories involved with SCFAs-production or weight loss may contain enzymes such as beta-glucosidase (K05349), beta-galactosidase (K01190), and hexosaminidase (K12373) after morel intervention. The exploration of the impact of morel mushrooms on gut microbiota and metabolites contributes to the development of prebiotics for improving health and reducing obesity.

Polygonum Cuspidatum Alcohol Extract Exerts Analgesic Effects via the MAPK/ERK Signaling Pathway.

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.

Selenium metabolism heterogeneity in pan-cancer: insights from bulk and single-cell RNA sequencing.

BACKGROUND: Selenium, a natural microelement with both nutritional and toxicological properties, is intertwined with tumorigenesis and progression. However, it is not fully understood how selenium metabolism affects immune response and cancer biology. METHODS: We estimated selenium metabolism by Gene Set Enrichment Analysis (GSEA) to delineate the selenium metabolism landscape using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and a integrated pan-cancer single-cell dataset. We systematically explored the prognostic implications of selenium metabolism and selenium-related regulatory patterns. The therapeutic value of selenium metabolism was explored through machine learning and examined in several immunotherapy cohorts. The heterogeneity and underlying mechanism of selenium metabolism were investigated by cell‒cell communication analysis at the single-cell level. RESULTS: A GSEA analysis based on 86 genes was used to evaluate the selenium metabolism landscape. The selenium metabolism score exhibited prognostic value in predicting the lower risk of mortality, possibly due to its correlation with multiple cancer hallmarks, including a positive correlation with complement (R = 0.761, P < 0.001), inflammatory response (R = 0.663, P < 0.001), apoptosis (R = 0.626, P < 0.001), hypoxia (R = 0.587, P < 0.001), reactive oxygen species (ROS) (R = 0.558, P < 0.001), and interferon gamma response (R = 0.539, P < 0.001). We also observed heterogeneity in the relationship between selenium metabolism and immunity across different cancers. Based on selenium-related genes, we constructed a machine learning model with area under the ROC curve (AUC) of 0.82 in predicting immune checkpoint inhibitor (ICI)-based immunotherapy response. Single-cell selenium metabolism quantification revealed that adjacent and tumor tissues had higher selenium metabolism compared with normal tissues, especially in epithelial cells, fibroblasts and macrophages. The communication between high-selenium epithelium and high-selenium fibroblast was significantly higher than other cells, especially in cytokines, chemokines, collagen, Wnt, VEGF, IGF and FGF pathways. CONCLUSION: Our study provides a comprehensive landscape of selenium metabolism levels and diverse regulatory patterns in different cancers, deepening the understanding of selenium's roles in tumorigenesis and immunity.

Coaxial radiography guided puncture technique for percutaneous transforaminal endoscopic lumbar discectomy: A randomized control trial.

BACKGROUND: The coaxial radiography-guided puncture technique (CR-PT) is a novel technique for endoscopic lumbar discectomy. As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction, the X-ray beam can be used to guide the trajectory angle, facilitating the choice of the puncture site and providing real-time guidance. This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique (AP-PT), especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process, high iliac crest, and narrowed intervertebral foramen. AIM: To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT. METHODS: In this parallel, controlled, randomized clinical trial, herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine. Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group. The CR-PT group underwent CR-PT, and the AP-PT group underwent AP-PT. The number of fluoroscopies during puncturing, puncture duration (min), surgery duration (min), VAS score during puncturing, and puncture success rate were recorded. RESULTS: Sixty-five participants were included, with 31 participants in the CR-PT group and 34 in the AP-PT group. One participant in the AP-PT group dropped out due to unsuccessful puncturing. The number of fluoroscopies [median (P25, P75)] was 12 (11, 14) in the CR-PT group vs 16 (12, 23) in the AP-PT group, while the puncture duration (mean ± SD) was 20.42 ± 5.78 vs 25.06 ± 5.46, respectively. The VAS score was 3 (2, 4) in the CR-PT group vs 3 (3, 4) in the AP-PT group. Further subgroup analysis was performed, considering only the participants with L5/S1 segment herniation: 9 patients underwent CR-PT, and 9 underwent AP-PT. The number of fluoroscopies was 11.56 ± 0.88 vs 25.22 ± 5.33; the puncture duration was 13.89 ± 1.45 vs 28.89 ± 3.76; the surgery duration was 105 (99.5, 120) vs 149 (125, 157.5); and the VAS score was 2.11 ± 0.93 vs 3.89 ± 0.6, respectively. All the above outcomes demonstrated statistical significance (P < 0.05), favoring the CR-PT treatment. CONCLUSION: CR-PT is a novel and effective technique. As opposed to conventional AP-PT, this technique significantly improves puncture accuracy, shortens puncture time and operation time, and reduces pain intensity during puncturing.

Osteoblast Biospecific Extraction Conjugated with HPLC Analysis for Screening Bone Regeneration Active Components from Moutan Cortex.

INTRODUCTION: The function of promoting bone regeneration of Moutan Cortex (MC), a traditional Chinese medicine, has been widely known but, the effective components of MC in promoting osteoblast-mediated bone regeneration were still unclear. OBJECTIVE: The method of osteoblast membrane bio-specific extraction conjugated with HPLC analysis was established to screen bone regeneration active components from MC. METHODS: The fingerprints, washing eluate and desorption eluate of MC extract were analyzed by the established HPLC-DAD method. The established MC3T3-E1 cells membrane chromatography method was used for the bio-specific extraction of MC. The isolated compounds were identified by MS spectrometry. The effects and possible mechanisms of the isolated compounds were evaluated by molecular docking, ALP activity, cell viability by MTT Assay and proteins expression by Western Blot Analysis. RESULTS: The active compound responsible for bone regeneration from MC was isolated using the established method of osteoblast membrane bio-specific extraction conjugated with HPLC analysis, and it was identified as 1,2,3,4,6-penta-O-ß-galloyl-D-glucose (PGG) by MS spectrometry. It was further demonstrated through molecular docking that PGG could fit well into the functional ALP, BMP2, and Samd1 binding pocket. The proliferation of osteoblasts was promoted, the level of ALP was increased, and the protein expression of BMP2 and Smad1 was increased as shown by further pharmacological verification. CONCLUSION: It was concluded that PGG, the bone regeneration active compound from MC, could stimulate the proliferation of osteoblasts to promote osteoblast differentiation, and its mechanism might be related to the BMP/Smad1 pathway.

Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

[Characteristics of acidification and the distribution of available phosphorus along soil depths in heavy clay soils in southern Henan Province, China]. / è±«å—é»æ¿åœŸå£¤åˆ†å±‚é ¸åŒ–å’Œè€•å±‚é€Ÿæ•ˆç£·åˆ†å¸ƒç‰¹å¾.

The acidification of agricultural soil in the southern part of the North China Plain has become more obvious, which is particularly true for the heavy clay soil types, such as yellow-cinnamon and lime concretion black soils. To understand the spatial variability of the pH value and nutrients on the vertical agricultural soil profile of heavy clay soils in this area, we measured pH values and available phosphorus (AP) in 63 farmland sample points from Xiping County in the southern Henan Province. Geostatistical methods and ArcGIS technology were used to map soil pH values along three soil depths (0-10, 10-20, and 20-30 cm) and the spatial distribution of soil AP in the tillage layer (0-20 cm). Furthermore, the correlation between pH and AP was analyzed. The results showed that mean pH values of typical yellow-cinnamon and typical fluvo-aquic soils from three soil layers were 4.98, 4.93, 5.31, and 5.46, 5.81, 6.26, respectively, which gradually increased with soil depths. However, there was no significant difference among the three soil layers. Mean pH values of typical lime concretion black soil from the three soil layers were 5.23, 5.43 and 6.03, respectively, and that of the 20-30 cm soil layer was significantly higher than that of the 0-10 cm (by 0.8-1 pH unit) and the 10-20 cm layers. The pH of the 20-30 cm soil layer of the calcareous lime concretion black and moist soils were also significantly higher than that of the 0-10 and 10-20 cm soil layers. The AP contents of the typical yellow-cinnamon, typical lime concretion black, moist, typical fluvo-aquic and calcareous lime concretion black soils in 0-20 cm soil layer were 8.85-54.75, 4.27-37.49, 8.22-51.80, 6.07-34.82, and 13.22-22.85 mg·kg-1, respectively. The results of the map indicated that the areas with low AP were distributed in the middle of the study area in blocks, and the areas with high AP were distributed around the study area in dots and flakes. The pH values of the typical yellow-cinnamon, typical lime concretion black, and moist soils positively correlated with the content of AP in the 0-20 cm soil layer. In conclusion, the heavy clay soil in southern Henan Province became stratified acidification, which slowed down along the soil depth. Soil AP contents in the tillage layer were distributed unevenly in the study area, and were affected by soil types and soil pH. These results would be useful for the improvement of heavy clay soil acidification in the southern part of the North China Plain.

Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens.

Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-b]indole derivatives represented by GP-1 demonstrated excellent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria but were limited by hERG inhibition and poor pharmacokinetics profile. To improve their drug-like properties, we designed a series of novel pyrimido[4,5-b]indole derivatives based on the tricyclic scaffold of GP-1 and the C-7 moiety of acorafloxacin. These efforts have culminated in the discovery of a promising compound 18r with reduced hERG liability and an improved PK profile. Compound 18r exhibited superior broad-spectrum in vitro antibacterial activity compared to GP-1, including a variety of clinical multidrug G- pathogens, especially Acinetobacter baumannii, and the in vivo efficacy was also demonstrated in a neutropenic mouse thigh model of infection with multidrug-resistant A. baumannii.

Identification of novel anti-inflammatory Nur77 modulators by virtual screening.

Orphan nuclear receptor Nur77 is a unique member of the NR4A nuclear receptor subfamily, which is critical for cellular processes especially the inflammatory responses. Many efforts have been made to discover novel scaffold small molecules targeting Nur77. Herein, we evaluated the previously reported binding sites in crystal structures of Nur77 with small molecules, and then discovered compound 13 as a hit of Nur77 via virtual screening targeting the best-scored binding site. Based on the results of fluorescence titration assay, structure-activity relationship (SAR) analysis was summarized for compound 13 and its analogs. Among these analogs, compound 13e displayed the most potent binding affinity (0.54 ± 0.02 µM). The binding mode of compound 13e was predicted via molecule docking. Moreover, 13e exhibited significant anti-inflammation activity in TNF-α induced HepG2 cell model. Taken together, these results provided a new insight into the understanding the functions of specific binding sites on Nur77 for small molecular compounds, and the development of new scaffold Nur77 modulators.

Discovery of novel reversible monoacylglycerol lipase inhibitors via docking-based virtual screening.

Monoacylglycerol lipase (MAGL) is the major enzyme that catalyzes the hydrolysis of monoacylglycerols (MAGs). MAGL is responsible for degrading 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain and specific tissues. The inhibition of MAGL could attenuate the inflammatory response. Here, we report a series of reversible non-covalent MAGL inhibitors via virtual screening combined with biochemical analysis. The hit, DC630-8 showed low-micromolar activity against MAGL in vitro, and exhibited significant anti-inflammatory effects.

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.

Discovery of 4-Methylquinazoline Based PI3K Inhibitors for the Potential Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, and its molecular pathogenesis remains poorly understood. Recently, emerging evidence demonstrates that the PI3K signaling transduction pathway is linked to the pathology of IPF. In this work, we rationally designed a new series of 4-methylquinazoline derivatives as highly potent PI3K inhibitors that significantly suppress the phosphorylation of the main PI3K downstream effectors and displays marked antiproliferative activity in mouse MLg2908 lung fibroblasts. In a bleomycin-induced mouse pulmonary fibrosis model, 5d from the series improved mouse lung function and slowed the progression of pulmonary fibrosis. Overall, this work promises a therapeutic potential for PI3K inhibitors to treat IPF.

Fe3O4 nanoparticle-coated mushroom source biomaterial for Cr(VI) polluted liquid treatment and mechanism research.

Agrocybe cylindracea substrate-Fe3O4 (ACS-Fe3O4), a Fe3O4 nanoparticle-coated biomaterial derived from agriculture waste from mushroom cultivation, was developed to remove hexavalent chromium (Cr(VI)) from liquid. After modification, material surface became uneven with polyporous and crinkly structure which improved Cr-accommodation ability in a sound manner. Optimized by the Taguchi method, Cr(VI) removal percentage was up to 73.88 at 240 min, 40°C, pH 3, Cr(VI) concentration 200 mg l-1, dosage 12 g l-1, rpm 200. The efficient Cr(VI) removal was due to the combined effect of adsorption and redox. In addition, verification test using tannery wastewater, with removal percentage of Cr(VI) and total Cr reaching 98.35 and 95.6, provided further evidence for the efficiency and feasibility of ACS-Fe3O4. The effect of storage time of the material on Cr(VI) removal was small, which enhanced its value in practical application. Results indicated that metal removal was mainly influenced by solution concentration, adsorbent dosage and treatment time. The experimental data obtained were successfully fitted with the Langmuir isotherm model. Thermodynamic study indicated the endothermic nature of the process. The results confirmed that ACS-Fe3O4 as novel material derived from waste, with long-term stability, could be applied for heavy metal removal from wastewater and waste cycling.

Aerobic granules cultivated with simultaneous feeding/draw mode and low-strength wastewater: Performance and bacterial community analysis.

Sequence batch reactors (SBR) with simultaneous feeding/draw mode and low-strength wastewater were used for the cultivation of aerobic granules, and analysis of bacterial community diversity were conducted. Results revealed that the ratio of chemical oxygen demand/total nitrogen removal amount for R1 with real wastewater and R2 with synthetic wastewater decreased from 9.9 to 8.7 and, 29.9 to 21.1, respectively, when volumetric exchange ratio (VER) decreased from 90% (stage I) to 50% (stage II), indicating that organic matter in real and low-strength wastewater was fully utilized with lower VER by denitrifying bacteria. Relative abundances of the genus Dechloromonas, Pseudomonas, Bacillus in R1, which are responsible for denitrifying phosphorus removal, were much higher than that in R2, accounting for the high efficiency of nitrogen and phosphorus removal from real wastewater with low influent C/N ratio of 3.6 on average. These results provide useful information for improving wastewater treatment efficiency in the future.

Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors.

A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.

Tanshinone IIA Attenuates Sevoflurane Neurotoxicity in Neonatal Mice.

BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics. METHODS: To test this hypothesis, neonatal C57 mice (P6) were exposed to 3% sevoflurane for 2 hours with or without Tan IIA pretreatment at a dose of 10 mg/kg or 20 mg/kg for 3 consecutive days. Cognitive behavior tests such as open field tests and fear conditioning were performed to evaluate locomotor and cognitive function at P31 and P32. At P8, other separate tests, including TdT mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, and electron microscopy, were performed. The mean differences among groups were compared using 1-way analysis of variance followed by Bonferroni post hoc multiple comparison tests. RESULTS: Repeated exposure to sevoflurane leads to significant cognitive impairment in mice, which may be explained by increased apoptosis, overexpression of neuroinflammatory markers, and changes in synaptic ultrastructure. Interestingly, preadministration of Tan IIA ameliorated these neurocognitive deficits, as shown by increased freezing percentages on the fear conditioning test (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, mean difference, 19, 99% confidence interval for difference, 6.4-31, P < .0001, n = 6). The treatment also reduced the percentage of TUNEL-positive nuclei (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 2.6, 0.73-4.5, P = .0004, n = 6) and the normalized expression of cleaved caspase-3 (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 0.27, 0.02-0.51, P = .0046, n = 5). Moreover, it attenuated the production of the neuroinflammatory mediators interleukin (IL)-1ß and IL-6 (normalized sevoflurane versus sevoflurane+Tan IIA [20 mg/kg]: IL-1ß: 0.75, 0.47-1.0; P < .0001; IL-6: 0.66, 0.35-0.97; P < .0001; n = 10 per group). Finally, based on measurements of postsynaptic density, the treatment preserved synaptic ultrastructure (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, 42, 20-66; P < .0001; n = 12 per group). CONCLUSIONS: These results indicate that Tan IIA can alleviate sevoflurane-induced neurobehavioral abnormalities and may decrease neuroapoptosis and neuroinflammation.

Application of acclimated sewage sludge as a bio-augmentation/bio-stimulation strategy for remediating chlorpyrifos contamination in soil with/without cadmium.

This experiment was performed to investigate the effects of acclimated sewage sludge (ASS) and sterilized ASS on the fates of chlorpyrifos (CP) in soil with or without cadmium (Cd), as well as the improvement of soil biochemical properties. Results showed that both ASS and sterilized ASS could significantly promote CP dissipation, and the groups with ASS had the highest efficiency on CP removal, whose degradation rates reached 71.3%-85.9% at the 30th day (40.4%-50.2% higher than non-sludge groups). Besides, the degradation rate of CP was not severely influenced by the existence of Cd, and the population of soil microorganism dramatically increased after adding sludge. The soil enzyme activities (dehydrogenase, acid phosphatase and FDA hydrolase activities) ranked from high to low were as follows: groups with sterilized ASS>groups with ASS>groups without sludge. Simultaneously, 16S rRNA gene sequencing revealed that ASS changed bacterial community structure and diversity in soil. In addition, alkali-hydrolyzable nitrogen and Olsen- phosphorus increased after application of sludge, indicating that the addition of ASS (or sterilized ASS) could effectively improve soil fertility.

In vivo anti-Trichophyton Activities of Seed Oil Obtained from Caraganakorshinskii Kom.

AIM: The objective of this study was to evaluate the effects of seed oil of Caragana korshinskii Kom. against Trichophyton mentagrophytes on an in vivo guinea pig model of dermatophytosis. METHODS: The skin of albino guinea pigs was infected with T. mentagrophytes, and the animals were divided into five groups: negative control (NC group), positive control (PC group), vehicle control, CK50% group (received topical 50% seed oil of C.korshinskii), and CK100% group (received topical 100% seed oil of C.korshinskii). Evaluation of clinical efficacy was performed 72 h after the completion of a 10-day treatment regimen. Skin biopsy samples were processed for histopathological examination. RESULTS: The infected untreated control guinea pigs showed patches of hair loss and ulcerated or scaly skin. Lower clinical scores indicate improved efficacy compared with NC. The lesion scores significantly declined in the CK50%, CK100%, and PC groups in comparison with the NC group. The CK50% group (45.31%) and the CK100% group (75%) showed clinical efficacy compared with the PC group (78.13%). In addition, no fungal elements, inflammation, or tissue destruction was observed in any of the PAS-stained sections of the infected skin in the groups treated with CK100% or 1% terbinafine. CONCLUSION: Seed oil of C.korshinskii demonstrated high antifungal efficacy in experimental dermatophytosis.