Recent Progress towards Transition-Metal-Catalyzed Synthesis of Fluorenes.

Fluorenes are a commonly encountered structural motif in materials science, pharmaceutical chemistry, and organic synthesis. Among various strategies towards the synthesis of this unique structure, transition metal-catalyzed functionalization has emerged as one of the most efficient methods. This Minireview presents an overview of the recent advances in this emerging area by highlighting the reactions' specificity and applicability and, where possible, provides a mechanistic rationale.

Gold Catalysis, Asymmetric Friedel-Crafts Alkylation Cascade for One-Pot Synthesis of Chiral Dihydrocarbazoles and Dihydrodibenzofurans.

A one-pot gold-catalyzed acyl migration followed by ytterbium-catalyzed asymmetric Friedel-Crafts alkylation is disclosed, leading to the rapid synthesis of chiral dihydrocarbazoles and dihydrodibenzofuran in generally moderate to good overall yields with good to excellent enantioselectivities. The gold-catalyzed acyl migration of propargyl acetates generates α-ylidene-ß-diketones with high E/Z ratios, which are then subjected to the ytterbium-catalyzed asymmetric Friedel-Crafts alkylation without any purification. Importantly, this protocol provides a new type of substrate for asymmetric Friedel-Crafts alkylation.

Clinical characteristics and effective treatments of scrub typhus-associated hemophagocytic lymphohistiocytosis in children.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon and life-threatening disorder that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus). Here, we describe the clinical features, laboratory parameters, management, and outcome of 16 children with scrub typhus-associated HLH. All patients satisfied the HLH-2004 diagnostic criteria. All patients had fever of unknown origin and multisystem damage. Raised hepatic transaminases and abnormalities in routine blood test were observed in all children. Imaging tests showed abnormalities in 10 cases. Six patients were treated with intravenous azithromycin for 5 days, and 10 with intravenous chloramphenicol for 7-10 days because of non-response to 3-day azithromycin treatment. Five patients were treated with intravenous albumin and 3 with intravenous immunoglobulin. Two patients with severe symptoms (shortness of breath, cyanosis) were treated with dexamethasone (0.3 mg/kg/d). Fifteen patients recovered completely after 8-22 days of treatment. One patient died. The occurrence of severe complications draws attention to the need for early diagnosis and effective treatment. Anti-rickettsial antibiotic treatment (azithromycin or chloramphenicol) without the need for chemotherapy may be beneficial in such cases, instead of treatment according to the 2004 HLH protocol.

Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress.

Elevated plasma levels of homocysteine have been implicated in neurodevelopmental and neurodegenerative disorders in human studies. Although the molecular mechanisms underlying the effects of homocysteine (Hcy) cytotoxicity on the nervous system are not yet fully unknown, induction of DNA interstrand cross-links and inhibition of neural stem cells (NSCs) survival may be involved. The objective of our study was to investigate the effects of Hcy on DNA interstrand cross-links in NSCs, and to explore its possible mechanisms. We also found that Hcy induced cell DNA damage on a dose-dependent manner and evoked reactive oxidative species (ROS) production, leading to elevated apoptosis in NSCs. Moreover, Hcy exposure activated the Fanconi anemia (FA) pathway, which was characterized by increases in monoubiquitination of Fanci and Fancd2 and enhancement of the interaction between above two proteins. On contrary, N-Acety-l-Cysteine (NAC) decreased Hcy-evoked ROS production and significantly ameliorated DNA damage and improved cell survival. These data suggest that Hcy may play a role in the pathogenesis of neurological diseases via a molecular mechanism that induces DNA interstrand cross-links via oxidative stress and involves in negative regulation of NSCs survival.

Atom-Economic Synthesis of Fully Substituted 2-Aminopyrroles via Gold-Catalyzed Formal [3+2] Cycloaddition between Ynamides and Isoxazoles.

A concise and flexible synthesis of fully substituted 2-aminopyrroles via gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles has been developed. Under mild reaction conditions, various 2-aminopyrrole derivatives were obtained in good to excellent yields, thus providing an efficient and atom-economic way for the construction of fully substituted 2-aminopyrroles.

Atom-economic generation of gold carbenes: gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles.

The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N-O or N-N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N-O or N-N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air ("open flask").

Pachyman treatment improves CD4+CD25+ Treg counts and serum interleukin 4 and interferon γ levels in a mouse model of Kawasaki disease.

The aim of this study was to explore the effect of pachyman, a mushroom extract, on CD4+CD25+ regulatory T cells (Tregs), serum interleukin 4 (IL-4) and interferon γ (IFN-γ) levels in a mouse model of Kawasaki disease. Lactobacillus casei cell wall extract was diluted to 1 mg/ml in PBS and administered to mice by intraperitoneal injection to establish a model of Kawasaki disease. Sixty female mice were used in this study, 40 of which were randomly assigned to a model (normal saline by gavage, n=20) or experimental group (200 mg/kg/day pachyman by gavage, n=20). The remaining 20 mice were disease and treatment-free, and were used as the control group. Compared to the control mice, mice in the model group exhibited a significantly lower percentage of CD4+CD25+ Tregs and significantly higher serum IL-4 and IFN-γ levels (P<0.05). However, CD4+CD25+ Tregs significantly increased and IL-4 and IFN-γ levels significantly decreased in experimental mice following pachyman treatment (P<0.05). Further analysis showed a negative correlation between CD4+CD25+ Tregs and IL-4/IFN-γ levels (P<0.05). In conclusion, pachyman improves immune function in a mouse model of Kawasaki disease by upregulating CD4+CD25+ Tregs, which may inhibit the cytokine secretion of Th1 and Th2 cells.

[Gene polymorphisms of Toll-like receptors in Chinese Han children with sepsis in Wenzhou].

OBJECTIVE: Sepsis remains a serious clinical problem because of high morbidity and mortality. The importance of Toll-like receptors (TLRs) for the induction of immune responses against sepsis was demonstrated in humans. The present study aimed to probe the gene polymorphisms of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg753Gln) in patients with sepsis among Chinese Han children in Wenzhou, and investigate the correlation with sepsis. METHOD: This study was conducted as a case-control study. Using polymerase chain reaction and DNA sequencing, gene polymorphisms of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg753Gln) in 59 children with sepsis, 38 children with severe sepsis (including 20 septic shock) and 57 healthy controls were analyzed. Hardy-Weinberg method of statistics was used to compare the frequency of genotypes alleles among three groups. RESULT: The mutant genotypes of TLR4 gene (Asp299Gly and Thr399Ile) were not found among sepsis, septic shock and control groups. In severe sepsis group, the Arg753Gln TLR2 polymorphism occurred in 2 out of 38 severe sepsis patients and both of the subjects with the TLR2 Arg753Gln polymorphism had fatal staphylococcal infections. CONCLUSION: TLR4 gene (Asp299Gly and Thr399Ile) polymorphisms may not be correlated with susceptibility to sepsis among Chinese Han children in Wenzhou. The fact that only 2 out of 38 severe sepsis patients had Arg753Gln TLR2 polymorphism suggests that a larger sample size is needed because of the rarity of the TLR2 allele among Chinese Han children in Wenzhou.

[Clinical analysis of community-acquired Pseudomonas aeruginosa septic shock].

OBJECTIVE: This study sought to analyze the clinical manifestations and intervention of fulminant septic shock in community-acquired Pseudomonas aeruginosa septicemia. METHODS: We retrospectively reviewed the medical records for diagnosis, antibiotic therapy, clinical course of septic shock, respiratory support, laboratory data etc. RESULTS: Eight of nine cases with P. aeruginosa septic shock died. Fever (nine cases) and cough (three cases) or diarrhea (3 cases) were the 2 most common initial symptoms, three cases developed skin gangrenosum later. Pseudomonas aeruginosa infection was not considered in any of the cases before death or blood culture showed positive result. Only 3 cases were initially treated with susceptible antibiotic regimen but no anti pseudomonas combination therapy was applied, susceptible antibiotic monotherapy was applied in 7 cases after transfer to the ICU. The mean latency of shock occurrence was 5.1 hours (range 0 to 21 hours) after admission, the mean duration from the occurrence of shock to death was 13.8 hours (range, 1 - 32 hours). All the patients were transfer red to ICU for shock, the appropriate resuscitation of shock patients was delayed by 49.3 minutes (range 25 - 80 minutes) by transfer. Only two cases were diagnosed and treated for shock on admission; after transferred to ICU, only 5 patients were diagnosed as having shock, and only 3 received anti-shock treatment. Eight of the patients died of persistent shock. In 6 patients who died, mechanical ventilation was not applied until cardiac arrest occurred. All the patients had hypoalbuminaemia, elevated serum C-reactive protein concentration, leukopenia and 6 cases had DIC. CONCLUSION: The initial presentation of the cases with community-acquired Pseudomonas aeruginosa septicemia was nonspecific with fever and cough or diarrhea. Clinicians often underestimated the severity of the infection, few patients received effective antimicrobial therapy. The authors suggest that an anti-pseudomonas antibiotic should be included in the initial empiric antibiotic regimen to cover P. aeruginosa high-risk patients; the front-line clinician should be educated for early recognition and aggressive resuscitation of P infection. aeruginosa septicemia.

[Three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation].

OBJECTIVE: To recognize the clinical features of the enterovirus 71 (EV71) infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness. METHODS: We retrospectively reviewed the medical records of the three cases with EV71 infection for clinical manifestation, laboratory data, medications, outcome etc. RESULTS: All the cases were infants and they all died. These infants had no skin or mucosal lesions, however, they had sudden onset of cyanosis and tachypnea 1 to 2 days after the onset of the febrile disease with vomiting. All these 3 cases were misdiagnosed and were treated for shock on admission. Pulmonary hemorrhage was not considered in any of the cases on admission. All the cases received tracheal intubation when foamy secretions were discharged from mouth and nose of the patients and notable cyanosis was noted. After intubation, all had pink foamy fluid flew out from the endotracheal tube. The patients had hyperglycemia and limb weakness, two had tachycardia, and hypertension was found in one case. Chest X-ray showed bilateral or unilateral widespread air space opacity, but the cardiac size and shape were normal. All the patients had leucocytosis. EV71 infection was confirmed by detection of specific sequences of the virus in throat swab and tracheal secretions samples and in one case in cerebrospinal fluid sample. CONCLUSION: Pulmonary edema or pulmonary hemorrhage occurred in the 3 cases with EV71-infected infants. The initial presentation was often nonspecific with fever and vomiting, and sudden appearances of cyanosis, tachypnea, tachycardia, hypertension or hypotension, limb weakness may suggest pulmonary edema or hemorrhage. Excessive fluid resuscitation may deteriorate the illness, on the contrary, fluid restriction and inotropic agents, and early intubation with positive pressure mechanical ventilation may be the proper treatment.