Nucleophilic functionalization of thianthrenium salts under basic conditions.

In recent years, S-(alkyl)thianthrenium salts have become an important means of functionalizing alcohol compounds. However, additional transition metal catalysts and/or visible light are required. Herein, a direct thioetherification/amination reaction of thianthrenium salts is realized under metal-free conditions. This strategy exhibits good functional-group tolerance, operational simplicity, and an extensive range of compatible substrates.

Mitigation of uranium toxicity in rice by Sphingopyxis sp. YF1: Evidence from growth, ultrastructure, subcellular distribution, and physiological characteristics.

Uranium (U) contamination of rice is an urgent ecological and agricultural problem whose effective alleviation is in great demand. Sphingopyxis genus has been shown to remediate heavy metal-contaminated soils. Rare research delves into the mitigation of uranium (U) toxicity to rice by Sphingopyxis genus. In this study, we exposed rice seedlings for 7 days at U concentrations of 0, 10, 20, 40, and 80 mg L-1 with or without the Sphingopyxis sp. YF1 in the rice nutrient solution. Here, we firstly found YF1 colonized on the root of rice seedlings, significantly mitigated the growth inhibition, and counteracted the chlorophyll content reduction in leaves induced by U. When treated with 1.1 × 107 CFU mL-1 YF1 with the amendment of 10 mg L-1 U, the decrease of U accumulation in rice seedling roots and shoots was the largest among all treatments; reduced by 39.3% and 32.1%, respectively. This was associated with the redistribution of the U proportions in different organelle parts, leading to the alleviation of the U damage to the morphology and structure of rice root. Interestingly, we found YF1 significantly weakens the expression of antioxidant enzymes genes (CuZnSOD,CATA,POD), promotes the up-regulation of metal-transporters genes (OsHMA3 and OsHMA2), and reduces the lipid peroxidation damage induced by U in rice seedlings. In summary, YF1 is a plant-probiotic with potential applications for U-contaminated rice, benefiting producers and consumers.

Polystyrene microplastics enhanced the toxicity of cadmium to rice seedlings: Evidence from rice growth, physiology, and element metabolism.

Microplastics (MPs) and cadmium (Cd) are toxic to rice; however, the effects and mechanisms of their combined exposure are unclear. The combined exposure effects of polystyrene microplastics (PS-MPs) with different particle sizes (1-10 µm, 50-150 µm) and concentrations (50, 500 mg·L-1) and Cd on rice were explored. PS-MPs combined with Cd amplifies the inhibition of each individual exposure on the height and biomass of rice seedlings, and they showed antagonistic effects. PS-MPs reduced the content of chlorophyll and increased the content of carotenoid rice seedlings significantly. High concentrations of PS-MPs enhanced the inhibition of Cd on chlorophyll content. Cd, PS-MPs single and combined exposures significantly altered the antioxidant enzyme (POD, CAT, SOD) activities in rice seedlings. Under PS-MPs exposure, overall, the MDA content in shoots and roots exhibited opposite trends, with a decrease in the former and an increase in the latter. In comparison with Cd treatment, the combined exposures' shoot and root MDA content was reduced. Cd and PS-MPs showed "low concentration antagonism, high concentration synergism" on the composite physiological indexes of rice seedlings. PS-MPs significantly increased the Cd accumulation in shoots. PS-MPs promoted the root absorption of Cd at 50 mg·L-1 while inhibited at 500 mg·L-1. Cd and PS-MPs treatments interfered with the balance of microelements (Mn, Zn, Fe, Cu, B, Mo) and macroelements (S, P, K, Mg, Ca) in rice seedlings; Mn was significantly inhibited. PS-MPs can enhance of Cd's toxicity to rice seedlings. The combined toxic effects of the two contaminants appear to be antagonistic or synergistic, relying on the particle size and concentration of the PS-MPs. Our findings offer information to help people understanding the combined toxicity of Cd and MPs on crops.

Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens.

RATIONALE: Effective treatment for lung cancer requires accuracy in subclassification of carcinoma subtypes. OBJECTIVES: To identify microRNAs in bronchial brushing specimens for discriminating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and for further differentiating squamous cell carcinoma (SQ) from adenocarcinoma (AC). METHODS: Microarrays were used to screen 723 microRNAs in laser-captured, microdissected cancer cells from 82 snap-frozen surgical lung specimens. Quantitative reverse-transcriptase polymerase chain reaction was performed on 153 macrodissected formalin-fixed, paraffin-embedded (FFPE) surgical lung specimens to evaluate seven microRNA candidates discovered from microarrays. Two microRNA panels were constructed on the basis of a training cohort (n = 85) and validated using an independent cohort (n = 68). The microRNA panels were applied as differentiators of SCLC from NSCLC and of SQ from AC in 207 bronchial brushing specimens. MEASUREMENTS AND MAIN RESULTS: Two microRNA panels yielded high diagnostic accuracy in discriminating SCLC from NSCLC (miR-29a and miR-375; area under the curve [AUC], 0.991 and 0.982 for training and validation data set, respectively) and in differentiating SQ from AC (miR-205 and miR-34a; AUC, 0.977 and 0.982 for training and validation data set, respectively) in FFPE surgical lung specimens. Moreover, the microRNA panels accurately differentiated SCLC from NSCLC (AUC, 0.947) and SQ from AC (AUC, 0.962) in bronchial brushing specimens. CONCLUSIONS: We found two microRNA panels that accurately discriminated between the three subtypes of lung carcinoma in bronchial brushing specimens. The identified microRNA panels may have considerable clinical value in differential diagnosis and optimizing treatment strategies based on lung cancer subtypes.

Advances in investigating microcystin-induced liver toxicity and underlying mechanisms.

Microcystins (MCs) are a class of biologically active cyclic heptapeptide pollutants produced by the freshwater alga Microcystis aeruginosa. With increased environmental pollution, MCs have become a popular research topic. In recent years, the hepatotoxicity of MCs and associated effects and mechanisms have been studied extensively. Current epidemiological data indicate that long-term human exposure to MCs can lead to severe liver toxicity, acute toxicity, and death. In addition, current toxicological studies on the liver, a vital target organ of MCs, indicate that MC contamination is associated with the development of liver cancer, nonalcoholic fatty liver, and liver fibrosis. MCs produce hepatotoxicity that affects the metabolic homeostasis of the liver, induces apoptosis, and acts as a pro-cancer factor, leading to liver lesions. MCs mainly mediate the activation of signaling pathways, such as the ERK/JNK/p38 MAPK and IL-6-STAT3 pathways, which leads to oxidative damage and even carcinogenesis. Moreover, MCs can act synergistically with other pollutants to produce combined toxicity. However, few systematic reviews have been performed on these new findings. This review systematically summarizes the toxic effects and mechanisms of MCs on the liver and discusses the combined liver toxicity effects of MCs and other pollutants to provide reference for subsequent research. The toxicity of different MC isomers deserves further study. The detection methods and limit standards of MCs in agricultural and aquatic products will represent important research directions in the future. Standard protocols for fish sampling during harmful algal blooms or to evaluate the degree of MC toxicity in nature are lacking. In future, bioinformatics can be applied to offer insights into MC toxicology research and potential drug development for MC poisoning. Further research is essential to understand the molecular mechanisms of liver function damage in combined-exposure toxicology studies to establish treatment for MC-induced liver damage.

Progress in Understanding the Role and Therapeutic Targets of Polarized Subtypes of Macrophages in Pulmonary Fibrosis.

Pulmonary fibrosis represents the advanced phase of diverse pulmonary ailments, and at present, a definitive cure for these ailments is lacking. Furthermore, underlying mechanisms causative of these ailments remain elusive. Macrophages are immune cells that resist external stimuli in the early stages after birth. These cells can polarize into the classically (M1) and alternatively (M2) activated macrophages. When stimulated owing to the presence of toxic factors, M1 macrophages produce several pro-inflammatory factors, which mediate the inflammatory injury response of the alveolar tissue. The secretion of diverse growth factors by M2 macrophages contributes to the pathogenesis of aberrant alveolar structural fibrosis and remodeling. The abnormal activity of M2 macrophages is considered a critical factor in the formation of pulmonary fibrosis. In this mini-review, to highlight the clinical implications of research studies, we summarize the role and therapeutic targets of polarized subtypes of macrophages in pulmonary fibrosis and the role of targeting macrophages for the treatment of pulmonary fibrosis.

Strontium alleviated the growth inhibition and toxicity caused by cadmium in rice seedlings.

Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.

Magnoflorine attenuates inflammatory responses in RA by regulating the PI3K/Akt/NF-κB and Keap1-Nrf2/HO-1 signalling pathways in vivo and in vitro.

BACKGROUND: As a prolonged autoimmune disorder, rheumatoid arthritis (RA) is characterised by synovial hyperplasia and the erosion of bone and cartilage. Magnoflorine (MAG) is the main component purified from Clematis manshurica Rupr. Recent studies have shown that MAG has anti-inflammatory, antioxidant, and immunosuppressive effects, which are relevant to anti-RA activities. OBJECTIVE: The current investigation was conducted to explore the anti-RA effects of MAG and to discover the possible molecular mechanisms. METHODS: In vitro experiments, CCK-8, wound healing, and transwell assays were utilized to evaluate the anti-proliferative, anti-migratory, and anti-invasive activities of MAG, respectively. The rate of cell distribution and cell apoptosis were evaluated by flow cytometry. ROS generation was detected by DCFH-DA staining. Western blotting, quantitative real-time polymerase chain reaction assay, and immunofluorescent staining were employed to test the anti-RA effect of MAG as well as to explore the potential mechanisms by evaluating related gene and protein expression. For in vivo experiments, an adjuvant-induced arthritis (AIA) rat model was established. The related parameters were measured in rats. Then, rats were sacrificed, and ankle joints were collected for histopathological analysis and observation. RESULTS: MAG significantly decreased the proliferation, migration, invasion, and reactive oxygen species levels in IL-1ß-treated MH7A cells. Furthermore, MAG promoted cell apoptosis by increasing Bax levels and decreasing Bcl-2 levels. MAG also induced cell cycle arrest. Inflammatory cytokines (iNOS, COX-2, IL-6, and IL-8) and MMPs (MMP-1, 2, 3, 9, and 13) were reduced by MAG treatment. Molecular analysis revealed that MAG exerted anti-RA effects by partly inhibiting the PI3K/Akt/NF-κB signalling axis and activating the Keap1-Nrf2/HO-1 signalling pathway. In vivo studies have revealed that MAG treatment substantially improved severe symptoms in AIA rats, and these curative effects were linked to the attenuation of inflammatory responses. CONCLUSION: These results first suggested that MAG exhibits anti-arthritic effects in IL-1ß-treated MH7A cells and AIA rat models. Thus, MAG may be used as a new drug to treat RA clinically.