PhI(OAc)2-mediated aminoacyloxylation of ß,γ-unsaturated hydrazones using Togni reagent II as an acyloxyl precursor.

A metal-free protocol for the direct construction of C(sp2)-N and C-O bonds via a PhI(OAc)2-mediated dehydrogenative aminoacyloxylation of ß,γ-unsaturated hydrazones with Togni reagent II is reported. Initiated by the carboxyl-containing species generated in situ from Togni reagent II, this method offers a new solution for regioselective functionalization at a remote site on ß,γ-unsaturated hydrazones, thus providing a straightforward method for the synthesis of acyloxyl-substituted pyridazines. This reaction features a broad substrate scope and mild conditions.

Annulative Aminosulfonylation of Unactivated Alkenes for Accessing Pyrazolines via Multicomponent SO2 Insertion.

A direct arylsulfonylation of ß,γ-unsaturated hydrazones method, in which sulfonated pyrazolines are accessed by a three-component reaction of ß,γ-unsaturated hydrazones, DABSO, and aryldiazonium tetrafluoroborates, has been developed without external oxidants or catalysts. This transformation is triggered by the formation of arylsulfonyl radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO, and is enabled by controllable generation of C center radical, in which DABSO was utilized as the sulfone source and an oxidant in this radical-mediated cascaded reaction. A wide range of substrates can be applied in this process to afford pyrazolines in good yield, and it is amenable for gram-scale synthesis.

Cyclin-dependent kinase 5 negatively regulates antiviral immune response by disrupting myeloid differentiation primary response protein 88 self-association.

As a member of the pattern recognition receptors (PRRs) involving in the innate immune system, Toll-like receptors (TLRs) can sense a wide range of microbial pathogens and combat infections by producing antimicrobial products, inflammatory cytokines, and chemokines. All TLRs, with the exception of TLR3, activate a signalling cascade via the myeloid differentiation primary response gene 88 (MyD88). Therefore, the activation of MyD88-dependent signalling pathway must be finely controlled. Herein, we identified that cyclin-dependent kinase 5 (CDK5) negatively regulated TLR-MyD88 signalling pathway by targeting MyD88. Overexpression of CDK5 reduced the production of interferons (IFNs), while a deficiency in CDK5 increased the expression of IFNs in response to vesicular stomatitis virus (VSV) infection. Mechanistically, CDK5 suppressed the formation of MyD88 homodimers, resulting in the attenuated production of IFNs induced by VSV infection. Surprisingly, its kinase activity does not play a role in this process. Therefore, CDK5 can act as an internal regulator to prevent excessive production of IFNs by restricting TLR-MyD88-induced activation of antiviral innate immunity in A549 cells.

Synthesis of α-allenic aldehydes/ketones from homopropargylic alcohols using a visible-light irradiation system.

A visible-light irradiation tandem oxidative aryl migration/carbonyl formation reaction, mediated by K2S2O8 and visible-light photoredox catalysis, has been discovered. The presented transformation provides a straightforward access to important α-allenic aldehyde/ketone derivatives from readily available homopropargylic alcohol derivatives in a regioselective manner of 1,4-aryl shift concomitant with carbonyl formation. The operational simplicity and broad substrate scope demonstrate the great potential of this method for the synthesis of highly functional α-allenic aldehyde/ketone derivatives.

Catalytic Oxidative Carbene Coupling of α-Diazo Carbonyls for the Synthesis of ß-Amino Ketones via C(sp(3))-H Functionalization.

A catalytic domino oxidative carbene coupling (OCC) of α-diazo carbonyls has been established by treatment with N,N-dimethylanilines and carboxylic acids (or N-methylaniline) via direct C(sp(3))-H functionalization under convenient conditions. The reaction pathway is proposed to proceed through the sequence of carbene formation, enolization, and nucleophilic addition. The reaction enables de-diazotized carbo-oxygenation and carbo-amination of α-diazo carbonyls and provides practical access to α-(acyloxy)-ß-amino ketones and α,ß-diamino ketones.

[Analysis of characteristics of acute poisoning caused by various poisons in Guangxi, China].

OBJECTIVE: To investigate the characteristics of acute poisonings caused by various poisons in Guangxi, China. METHODS: A retrospective investigation was performed in 5859 cases of acute poisonings who were admitted to 63 hospitals in 11 cities, as well as 531 types of poisons involved. The poisons were categorized into 6 groups; each group of cases was stratified by the rural or urban settings, frequency of poisoning, and cause of poisoning to analyze the numbers of cases and constituent ratios. RESULTS: Most types of poisons (68.74%) belonged to drugs (217 types) and pesticides (148 types). Most cases of poisonings (61.63%) were caused by pesticides (n = 2547) and chemicals (n = 1064). Pesticides, poisons of plant origins, and poisons of animal origins were responsible for most of the cases in rural settings; 88.46%, 79.10%, and 66.74% of the cases of these poison categories happened in rural settings. Chemicals, drugs, and other poisons were responsible for most of the cases in urban settings; 70.20%, 61.74%, and 63.73% of the cases of these poison categories happened in urban settings. The numbers of cases in 5-year-poisoning groups were the highest in all categories of poisons, accounting for 85.24%, 88.57%, 55.16%, 70.79%, 68.36%, and 66.44%of cases of respective categories. Most cases of poisonings by chemicals, poisons of animal origin, and other poisons were accident-related (86.24%, 72.66%, and 46.71%of the poison categories). Most cases of poisonings by pesticides and drugs were suicide-related (59.39% and 33.52% of the poison categories). Most cases by poisons of plant origin were caused by accidental ingestion (70.36% of the poison category). CONCLUSION: Most of the acute poisonings in Guangxi area are caused by pesticides and chemicals; the most common causes of poisoning are accidents, accidental ingestion, and suicide. There are significant differences in the causes of acute poisonings between the urban and rural settings.

[Analysis of the characteristics of toxins in 6005 cases of acute poisoning in Guangxi].

OBJECTIVE: To investigate the toxin characteristics of toxins in patients of acute poisoning in the Guangxi area. METHODS: A retrospective study was conducted. The data of acute poisoning cases and the causative toxins collected from 63 hospitals of Guangxi, including 36 city hospitals, 12 county hospitals, and 15 township health centers from January 2005 to December 2009 were collected. The data were descriptively analyzed and classified by year. RESULTS: A total of 6005 cases with acute poisoning induced by 532 kinds of poisons were enrolled. The 532 kinds of toxin were classified by high-occurrence (producing poisoning for 5 continuous years), low-occurrence (leading to poisoning for 2-4 continuous years) and newly occurred categories (leading to poisoning only in 1 year). The numbers of poisons of these 3 categories accounted for 10.15% (54 kinds), 29.70% (158 kinds), 60.15% (320 kinds) of total number of poisons, respectively. There were 4688 (78.07%), 780 (12.99%), and 537 (8.94%) cases for each category respectively. And the poisoning cases of each toxin involved from 8 to 837, 2 to 25, and 1 to 69 cases respectively. 77.78% (42/54) of high-occurrence poisons affect more than 20 cases, and 89.87% (142/158), 98.75% (316/320) of low-occurrence and new-occurrence poisons involved less than 10 cases. In the dynamic analyses for 5 years, frequency of toxin caused by high-occurrence, low-occurrence and newly occurred poisons in 5 years were 5 times, 2.6 times, and 1 time, respectively. The number of poisons caused by the high-occurrence toxin each year were same, but the average-annual growth rates of poison numbers caused by the low-occurrence and new-occurrence poisons each year were 17.61% and 20.10%. The average-annual growth rates of poisoning cases caused by the 3 categories of poisons were 14.08%, 16.53%, 31.96%, and the average-annual growth rates of poisoning cases caused by each categories were 10.28%, 1.13%, 11.45%, respectively. CONCLUSIONS: In the high-occurrence category, the poison species was least, the poisoning cases were most, the variety of the affected cases by each poison was largest, and the case involved by each toxin was increased by year. But in the newly occurred category, the poison constituent ratio was largest, but the poisoning population was the least, the disparity of each poison was least, and the toxin increased and the population affected each year were elevated. The characteristics of low-occurrence poison were between high-occurrence poison and newly occurred poison.

[The comparative analysis of acute poisoning characteristics between cities and rural areas in Guangxi].

OBJECTIVE: To compare the acute-poisoning characteristics between city and rural areas of Guangxi Province in order to provide clinical data for the formation of treatment strategies of acute poisoning in Guangxi. METHODS: Data of acute poisoning patients as treated in 36 municipal and 12 county hospitals, and also 15 rural clinics in 11 cities of Guangxi during 2005 to 2009 were collected and analyzed according to poisoning population, poisoning site, poisoning process, and poisoning degree. RESULTS: By analysing 3678 and 2153 cases of acute poisoning patients in rural and urban areas, the gender [χ (2) = 5.53, P < 0.05], age [χ (2) = 21.04, P < 0.01], professions [χ (2) = 3156.83, P < 0.01], poisoning site [χ (2) = 429.26, P < 0.01], poisoning cause [χ (2) = 363.06, P < 0.01], poison variety [χ (2) = 1713.12, P < 0.01], poisoning degree [χ (2) = 35.25, P < 0.01] were shown to be significantly different between rural and urban areas. In the rural areas, poisoning occurred predominantly in male (48.10% vs. 44.91%), age between 20-60 years (69.39% vs. 67.53%) and over 61 years old (11.17% vs. 8.69%), farmers by occupation (74.84% vs. 2.79%), home (80.64% vs. 78.07%), sites of labor (11.83% vs. 3.07%) and other sites (4.08% vs. 2.97%), and the chief causes were professional (3.10% vs. 1.30%), taken by mistake (21.85% vs. 20.91%), homicide (0.30% vs. 0.28%), and suicide (39.07% vs. 18.77%), and by pesticide (60.94% vs. 12.13%), plant (7.08% vs. 2.88%) and animal poisons (7.73% vs. 6.56%), belonging to severe poisoning (25.86% vs. 19.04%) were higher than those in town. In the town, poisoning occurred predominantly in female (55.09% vs. 51.90%), age below 19 years old (23.78% vs. 19.44%), unemployed (33.35% vs. 13.76%), student (17.53% vs. 8.43%), industrial workers (31.95% vs. 2.69%), executives (10.84% vs. 0.22%) and other professional (3.53% vs. 0.05%); occurred in schools (8.78% vs. 0.82%), restaurants (5.48% vs. 1.55%), place of entertainment (1.63% vs. 1.09%), by accidental (52.23% vs. 31.27%), therapeutic (4.46% vs. 2.56%), and other reasons (2.04% vs. 1.85%); by chemicals (33.19% vs. 8.55%), medicines (24.31% vs. 9.12%), and other types of poison (20.92% vs. 6.59%); light and medium degree of poisoning (44.87% vs. 41.22%, 36.09% vs. 32.93%) were higher than those in rural areas. CONCLUSION: Regarding the acute poisoning in Guangxi, the composition of population, the poisoning sites and causes, the types of poisons, the poisoning degree are distinctly different between urban and rural areas.

LTB4 can directly stimulate human osteoclast formation from PBMC independent of RANKL.

Leukotriene B4, as a kind of 5-lipoxygenase metabolite of arachidonic acid, is known to influence osteoclast formation and bone resorption. In order to determine whether Leukotriene B4 could directly stimulate human osteoclast differentiation and activation independent of RANKL (ODF), three different concentrations of Leukotriene B4 (10(-9)M, 10(-8)M, 10(-7)M) were added to the culture of CD14+ monocyte fraction of peripheral blood mononuclear cell (PBMC) in the presence of macrophage colony-stimulating factor (M-CSF). Under these conditions, Leukotriene B4 could induce multinucleated cells, which were positive for Tartrate-resistant acidic phosphatase (TRAP) staining and capable of bone resorption. Addition of osteoprotegerin (OPG) to PBMC cultures does not abrogate osteoclast formation induced by LTB4. Osteoclastogenesis induced by Leukotriene B4 were dose-dependently increased and weaker than that of RANKL. These results indicated that Leukotriene B4, elevated in many inflammatory diseases, is directly capable of inducing osteoclast formation by a RANKL-independent mechanism.

[Significance and role of increased expression of extracellular matrix metalloproteinase induced in the aseptic loosening of prostheses].

OBJECTIVE: To investigate the expression of extracellular matrix metalloproteinase induced (EMMPRIN) in the interface tissue, and explore the role of EMMPRIN in the aseptic loosening of prostheses. METHODS: Immunohistochemistry was performed to characterize the EMMPRIN-expressing cells at sites of interface tissue around aseptic loosened hip prostheses in 16 cases. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the existence of EMMPRIN mRNA in interface tissue samples. And it was followed up by computer assisted image analysis in order to detect the A values of their expression. Synovium of hip joint of 8 femoral neck fracture were in control group. RESULTS: Strong immunostaining of EMMPRIN was found in the macrophages and fibroblasts of lining-like layers and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. Expression of EMMPRIN was significantly higher in interface tissue than the control synovium (z=-3.252, P=0.001). RT-PCR of interface tissue samples disclosed the presence of EMMPRIN mRNA of 14 cases. In interface tissue, the A value of EMMPRIN increased significantly compared to control synovium (P<0.01). CONCLUSION: Over-expression of EMMPRIN up-regulates the production of matrix metalloproteinase (MMPs) in the interface tissue. And it can promote the bone destruction around prostheses. Thereby it may be one of methods to prevent and treat aseptic loosening of prostheses by repression the biology activity of EMMPRIN.