S-alkyl Dithiocarbamates Synthesis through Electrochemical Multicomponent Reaction of Thiols, Hydrogen Sulfide, and Isocyanides.

Dithiocarbamates synthesis is extremely important in plenty of biomedical and agrochemical applications, especially fungicide development, but remains a great challenge. In this work, we have successfully developed a multicomponent reaction protocol to convert H2S into S-alkyl dithiocarbamates under constant current conditions. No additional oxidants nor additional catalysts are required, and due to mild conditions, the reactions display a broad substrate scope, including varieties of thiols or disulfides.

Photoinduced efficient synthesis of cyanoalkylsulfonylated oxindoles via sulfur dioxide insertion.

A visible-light-promoted radical cascade reaction of N-arylacrylamide and cyclobutanone oxime esters with sulfur dioxide insertion is established. Mainly through the exploration of the visible light wavelength, it is found that the light source has a certain influence on the formation of cyanoalkylsulfonylated oxindoles, furnishing a range of sulfones in good to excellent yields. This protocol presents good functional group compatibility and does not require transition metals, photosensitizers, external bases, or oxidants.

Enhanced T-cell proliferation and IL-6 secretion mediated by overexpression of TRIM21 in oral lesions of patients with oral lichen planus.

BACKGROUNDS: To explore the expression and functions of the tripartite motif-containing protein 21 (TRIM21) in oral lichen planus(OLP) lesions. METHODS: Paraffin sections of buccal mucosa samples from 15 cases of reticular oral lichen planus (OLP) patients and 10 healthy controls were used for immunohistochemistry to determine expression and distribution of TRIM21. Buccal mucosae from 11 OLP patients and seven healthy controls were analyzed by qPCR to quantify its gene expression. Peripheral blood mononuclear cells and CD3+ cells from four pairs of age- and sex-matched OLP patients and healthy controls were isolated for immunocytochemistry and culture. Following lentivirus-mediated overexpression of TRIM21 gene in CD3+ cells, CCK-8 was applied to evaluate cell proliferation. Cytokines including IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the supernatants were measured by the cytometric bead array and verified by ELISA. RESULTS: A larger number of TRIM21-positive cells infiltrating the lamina propria were observed in OLP lesions by immunohistochemistry than those of healthy controls. Significantly higher transcription of TRIM21 was revealed by qPCR. TRIM21 overexpression in CD3+ cells significantly enhanced the proliferation and IL-6 secretion in CD3+ cells from 12 to 72 hours. CONCLUSION: Overexpressed TRIM21 in OLP may be a primary proinflammatory molecule rather than a secondary and inducible regulatory factor in immunopathogenesis of OLP.

Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis.

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Ultrasound-assisted bromination of indazoles at the C3 position with dibromohydantoin.

Bromoaryl compounds have attracted great attention in organic chemistry, especially for the synthesis of pharmaceutical intermediates. Herein, we demonstrated a novel and efficient bromination protocol of indazoles via C-H bond cleavage to give site-specific 3-bromide products that could be further employed as synthetic blocks to prepare drugs. The reaction used DBDMH as a bromine source, tolerated a wide range of indazoles, and finished in 30 min under mild, ultrasound-assisted conditions. Besides, preliminary mechanistic studies revealed that this approach was not a radical process.

Visible-Light Photosynthesis of CHF2 /CClF2 /CBrF2 -Substituted Ring-fused Quinazolinones in Dimethyl Carbonate.

With eco-friendly and sustainable CO2 -derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2 /CClF2 /CBrF2 -substituted ring-fused quinazolinones.

Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia.

BACKGROUND: Remimazolam is a new ultrashort acting benzodiazepine anesthetic which has predictable sedative duration and rapid recovery in gastrointestinal endoscopy. Propofol is a commonly used intravenous anesthetic in clinical work which also has rapid action, short action time and rapid recovery. To date, there have been relatively few articles comparing the two for general anesthesia induction. So, we conducted a randomized trial to evaluate whether remimazolam is superior to propofol during anesthesia induction in terms of efficacy and safety. METHODS: One hundred and eighty nine ASA I or II patients scheduled for elective surgery were divided into four groups: remimazolam 0.2 mg/kg (R1 group), 0.3 mg/kg (R2 group), 0.4 mg/kg (R3 group), and propofol group (P group). All patients were anesthetized with single shots of experimental drugs during induction period. Efficacy was measured by completing the induction of anesthesia without rescue sedation; and safety was defined as no severe adverse events. RESULTS: Success induction rates in remimazolam groups were 89% (R1 group), 94% (R2 group) and 100% (R3 group) while success induction rate in P group was 100%. Hypotension rates during induction were lower in R1 group (13%) and R2 group (24%) compared with P group (44%). Hypotension rate in R3 group (34%) was similar to propofol (44%). Injection site pain in group P was 27% while no pain was observed in remimazolam groups. CONCLUSIONS: Remimazolam is a safe and effective sedative drug during induction with less adverse effects for general anesthesia in ASA I or II patients.

Influence of alternated drying and wetting on the characteristics of soil preferential flow formation in Honghe Arid Valley.

To clarify the effects of alternation of drying and wetting on the formation of soil preferential flow in arid valley, taking the wasteland in the arid valley of Honghe River as the research object, we analyzed the soil preferential flow characteristics before and after the simulation of drying and wetting alternation based on dyeing tracer method, water breakthrough curve, and image processing technology. The results showed that, under the simulated alternation of drying and wetting, the matrix flow occurred in the 0-10 cm soil layer, the dyeing depth reached 35 cm, the horizontal width of the preferred path was only 3-10 cm, and the dyeing area curve fluctuated little. Simulated alternation of drying and wetting led to significant increases in the steady effluent, macropores number, and macroporosity. In the 0-20 cm soil layer, the steady effluent after alternation of drying and wetting was about 0.27 cm3·s-1 higher than that non-alternation of drying and wetting, macropores number in dyeing area was about 1.4 times higher, and the macroporosity was 13.4% higher. The macropores number was positively correlated with stable flow rate. After simulated alternation of drying and wetting, the number of macropores from large to small was 0.6-0.8 mm＞0.8-1.0 mm＞1.0-1.5 mm＞1.5-2.0 mm＞2.0-3.7 mm, while under non-alternation of drying and wetting, it was 0.8-1.0 mm＞0.6-0.8 mm＞1.0-1.5 mm＞2.0-3.7 mm＞1.5-2.0 mm. The macropores number in each pore size range was significantly correlated with the dyeing area ratio. After simulated alternation of drying and wetting, the correlation increased, and the dominant factor affecting the occurrence of preferential flow changed from the macropores number in the pore size range of 1.5-2.0 mm to that of 0.8-1.0 mm. Therefore, the alternation of drying and wetting would affect the characteristics of macropores, which caused the soil to be more prone to preferential flow and with higher magnitude.

Mixed and inhomogeneous expression profile of Th1/Th2 related cytokines detected by cytometric bead array in the saliva of patients with oral lichen planus.

OBJECTIVE: The aim of this study was to measure T helper (Th) 1/Th2-related cytokine expression in saliva from patients with oral lichen planus (OLP), compared with healthy controls (HC group) and controls with recurrent aphthous ulcers (RAU group). STUDY DESIGN: Saliva was collected from 41 patients with OLP, 14 HCs, and 14 controls with RAU for Th1/Th2-related cytokines analysis with cytometric bead array. Disease activity in OLP was recorded by reticulation/keratosis, erythema, and ulceration scores. RESULTS: Interleukin (IL)-6, IL-10, interferon-γ (IFN-γ), and IFN-γ/IL-4 in saliva were significantly higher in the OLP group than in the HC group. A positive and significant correlation among IL-6, IL-10, and reticulation/keratosis, erythema, and ulceration scores in the OLP group was revealed. Significantly increased IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-α and IFN-γ/IL-4 were found in the RAU group. CONCLUSIONS: Salivary cytokine profiles analyzed by cytometric bead array may provide a convenient research approach to OLP. Data indicated complicated Th1/Th2-related cytokine profile changes, rather than simple dominance model, in OLP. IL-10 and especially IL-6 may provide a surrogate endpoint for monitoring OLP.