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1,3,5-tris（3,3,3-trifluoropyl）-1,3,5-trimethylcyclotrisiloxane （D3F） and hexamethylcyclotrisiloxane were used as raw materials to synthesize fluorosilicone copolymer with high molecular weight. The effects of reaction time and reaction temperature on molecular weight of the products and monomer ratio on chain segment content of the copolymers were studied. The structure of the copolymer was characterized by infrared spectroscopy and nuclear magnetic resonance spectroscopy, and its molecular weight was determined by Ubbelohde viscometer. The results showed that the proportion of chain segment content in fluorosilicone rubber was closer to that of feed when D3F amount was high. With increase of reaction temperature and time, molecular weight of the fluorosilicone copolymer first increased and then decreased. Molecular weight of fluorosilicone copolymer could be effectively increased by stopping heating at an approp-riate node in the reaction process. When the reaction temperature was 90 ℃, reaction time was 10 min and mole fraction of D3F was 80%, molecular weight of fluorosilicone copolymer reached the maximum, and the viscosity average molecular weight was 8.2×105.

Three novel ent-kaurane diterpenes, namely sigesbeckin A–C (1–3), in conjunction with eight previously identified analogues (4–11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain. [ABSTRACT FROM AUTHOR]

Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1s expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer.

Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry including full scan, auto‐MS2 and target‐MS2, was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19‐epi‐scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target‐MS2 mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box‐Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post‐handling processes, were subsequently investigated. The results indicated that target‐MS2 mode could improve the quantitative capability of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry for structure‐complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra‐high‐performance liquid chromatography [ABSTRACT FROM AUTHOR]