Search

Concise and scalable formal syntheses of (-)-quinocarcinamide and (-)-quinocarcin have been achieved in 9 steps with 9% overall yield from simple commercially available chemicals. The synthetic strategy features an ortho -regioselective Pictet-Spengler cyclization for the construction of the tetrahydroisoquinoline skeleton, a stereoselective formal intramolecular [3 + 2] cross cycloaddition of cyclopropane 1,1-diester with an imine for the construction of the 3,8-diazabicyclo[3.2.1]octane skeleton.

In this paper, a 53 Gbps widely tunable transmitter is experimentally demonstrated for the first time, to our knowledge. An InGaAlAs/InP multiple-quantum-well (MQW) wafer is used with an identical layer structure for both the V-coupled cavity laser (VCL) and the electro-absorption modulator (EAM). The VCL uses a shallow-etched waveguide to reduce loss, while the EAM uses a deep-etched waveguide to increase the 3-dB modulation bandwidth. With the temperature varying from 19.5 to 30°C, the transmitter achieves wavelength tuning of 42 channels with a spacing of 100 GHz, corresponding to a tuning range of 32.6 nm from 1538.94 to 1571.54 nm. The static extinction ratio (ER) for all channels is higher than 14 dB. The measured 3-dB electro-optic (E0) bandwidth of the transmitter is over 40 GHz, which fits well with the calculated 3-dB bandwidth. At a fixed peak-to-peak driving voltage of 2.4 V, all channels exhibit clearly an open eye diagram with a 53 Gbps non-return-to-zero (NRZ) signal, while the dynamic ER is higher than 4.5 dB.

Staphylococcus aureus ( S. aureus ) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b + F4/80 + macrophages, and validated a predominant distribution of SLC7A11 in F4/80 + cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo . Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata , Plutella xylostella , and Spodoptera frugiperda . Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors ( Sf RyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the Sf RyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We have developed a visible-light-mediated formal [4 + 2] cycloaddition of arylcyclobutylamines with olefins, using QXPT-NPhCN as an organic photocatalyst. The corresponding cycloadducts could be obtained from electron-deficient olefins, aryl olefins and exocyclic olefins. We found that the addition of K 3 PO 4 could significantly promote the cycloadditions. Using this method, 2-functionalized cyclohexylamines including the ones with spiro-skeletons can be expediently obtained. Based on the "3D-bioisostere" principle, we designed and synthesized three cyclohexylamine 2-sulfonylurea compounds.

The risk posed by heavy metals makes it difficult to dispose of sediment contaminants from dredging lakes in China. Black soldier fly ( Hermetia illucens ) can convert organic waste, such as restaurant waste and lake sediment, to high-value-added protein feed and fertilizer. Experimental groups were formed in this study to explore the conversion of heavy metals present in the mixture of restaurant waste and lake sediment by black soldier fly larvae (BSFL). The results demonstrated that BSFL could survive in pure sediment with an 84.76% survival rate. Relative to the substrate, BSFL could accumulate 70-90% zinc (Zn), chromium (Cr), copper (Cu), and 20-40% cadmium (Cd) and lead (Pb). The experimental group 2:3, with 40% lake sediment and 60% restaurant waste, was the best group after conversion for 15 days, which showed a 95.24% survival rate of BFSL, 82.20 mg average weight of BFSL, 8.92 mm average length of BFSL, with varying content of heavy metals such as Cu (43.22 mg/kg), Zn (193.31 mg/kg), Cd (1.58 mg/kg), Cr (25.30 mg/kg) Cr, and Pb (38.59 mg/kg) in BSFL. Furthermore, the conversion residue conforms to the relevant standards of organic fertilizer in China and can be used as organic fertilizer. Overall, the present study shows that black soldier flies can improve the resource utilization of lake sediment, especially by reducing the effect of heavy metals., Competing Interests: Author XX was employed by Changsha Zoomlion Environmental Industry Co., Ltd. Author ZW was employed by Hubei Provincial Key Lab for Quality and Safety of Traditional Chinese Medicine Health Food, Jing Brand Chizhengtang Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Yang, Wang, Xiao, Wang, Gong, Liu and Li.)

We developed a visible-light-mediated [3 + 2] cycloaddition of arylcyclopropylamine with structurally diverse olefins using QXPT-NPh as a highly efficient organic photoredox catalyst. We first achieved the use of various alkyl-substituted alkenes in intermolecular [3 + 2] cycloadditions with cyclopropylamine. We also developed a general and efficient strategy for the construction of structurally diverse cyclopentane-based spiro[4. n ] skeletons with 1,3-difunctional groups, which broadly exist in natural products and synthetic molecules. Furthermore, we proposed a hydrogen-bond mode between the arylcyclopropylamine and the photocatalyst QXPT-NPh .

Uranium is a radioactive heavy metal and a significant public health concern; however, its associated underlying toxicological mechanisms remain largely unknown. In this work, the uptake and efflux processes of uranium in CHO-k1 cells were studied and the cytotoxicity effects were explored. It was found that both the uptake and efflux processes took place rapidly and half of the internalized uranium was expelled within 8 h. The uranium exposure caused a decrease of cell viability and adhesion ability in a dose-dependent manner and blocked the cell cycle at the G1 stage. In addition, gene expression analysis revealed relative changes in the transcription of metabolism related genes. Further studies revealed that the cytotoxicity of uranium could be alleviated by exposing cells to a lower temperature or by the addition of amantadine-HCl, an endocytosis inhibitor. Interestingly, after uranium exposure, needle-like precipitates were observed in both intracellular and extracellular regions. These findings collectively suggest that the cellular transport of uranium is a rapid process that disturbs cell metabolism and induces cytotoxicity, and this impact could be reduced by slowing down endocytic processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Subdural anaplastic large-cell lymphoma (SALCL) is an extremely rare subtype of primary central nervous system (CNS) lymphoma. Here, we report a very rare subdural lymphoma case, which was misdiagnosed as a subacute epidural hematoma based on the radiological examination., Patient Concerns: We present the case of an 82-year-old patient who presented with a 2-day history of headache and consciousness disorder following head injury. Computed tomography of the head revealed a fusiform isodense/slightly dense shadow under the right temporoparietal occipital cranial plate, suggesting a subacute epidural hematoma. It was initially misdiagnosed as a right traumatic subacute epidural hematoma with hemiplegia of the left limb. According to the patient's condition, an emergency craniotomy was performed to remove the hematoma. However, it was found that the lesion was located under the dura mater and was yellowish-brown with yellowish-brown liquid inside. The appearance of the lesion looked like bean curd residue. Histopathological examination diagnosed ALCL., Diagnosis: SALCL presenting as a subacute epidural hematoma on imaging., Interventions: Operation., Outcomes: The patient died 1 month after being discharged automatically., Conclusions: This report shows a rare radiography presentation of SALCL. SALCL can mimic the appearance of an epidural hematoma and should be regarded as a differential diagnosis even in patients with a history of craniocerebral injury and the "typical" imaging appearance of an epidural hematoma. The report is hoped to provide a scientific reference for the clinical diagnosis of subdural lymphoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

We report herein a highly efficient strategy for construction of a bridged oxa-[3.2.1]octane-embedded 5-7-6 tricyclic carbon skeleton through [3 + 2] IMCC (intramolecular [3 + 2] cross-cycloaddition), and the substituents and/or stereochemistries on C-4, C-6, C-7 and C-10 fully match those in the rhamnofolane, tigliane and daphnane diterpenoids. Furthermore, ring-opening of the bridged oxa-[3.2.1]octane via C-O bond cleavage was also successfully achieved., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An efficient construction of an aza-[5.7.6.5] tetracyclic core structure of calyciphylline D-type Daphniphyllum alkaloids has been achieved. The synthetic route features a diastereoselective cyclopropanation, efficient construction of the core bridged 8-aza-[3.2.1]octane skeleton through a [3 + 2] IMCC strategy, oxidative dearomatization of phenol, and gram-scale preparation in each step.

Dickeya zeae is a globally important bacterial pathogen that has been reported to cause severe soft rot diseases in several essential food crops, including bananas, rice, maize, and potatoes. Carvacrol, a hydrophobic terpene component, is found in aromatic plants of the Labiatae family and various essential oils. However, little work has been done on its antimicrobial potential against D. zeae. This study aimed to evaluate the antimicrobial activity and the functional mechanism of carvacrol against D. zeae. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of carvacrol against D. zeae were 0.1 mg/mL and 0.2 mg/mL, respectively. Carvacrol affected the cell membrane of D. zeae, as revealed by decreased intracellular ATP concentration, nucleic acid leakage, and decreased membrane potential. Scanning electron microscopy (SEM) micrographs confirmed that D. zeae cell membranes were damaged by carvacrol. Furthermore, a significant inhibition of D. zeae swimming motility and biofilm formation was observed following treatments with carvacrol at sub-inhibitory concentrations, indicating a significantly negative effect on these virulence factors. Accordingly, the tissue infection test revealed that carvacrol significantly reduced the pathogenicity of D. zeae. In a pot experiment, inoculated banana seedlings displayed remarkably lesser disease symptoms following treatment with carvacrol, and the control efficiency for banana soft rot was 32.0% at 14 days post-inoculation. To summarize, carvacrol exhibits strong antimicrobial activity against D. zeae and great potential applications in the control of D. zeae-associated crop diseases., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An online monitoring technology of Pu-239 aerosol based on aerosol direct introduction device, membrane desolvation nebuliser and ICP-MS was established for workplaces of reprocessing plants. Briefly, 0.8 l min -1 Pu-239 aerosol from the workplace was introduced into the aerosol direct introduction device where the air was replaced by Argon, and then the aerosol was introduced into the ICP-MS for measurement. To determine the activity of Pu-239 aerosol, 1.10E-3 Bq ml -1 Pu-242 standard solution generated by a membrane desolvation nebuliser was used. The introduction efficiency of the nebuliser was determined by sampling the aerosol generated from the nebuliser with Lead Standard Solution by glass fiber filter, which was (26.82 ± 3.33) %. The mass bias between Pu-239 and Pu-242 for the ICP-MS measurement was determined by Pu-239 and Pu-242 standard solutions generated by the nebuliser, and mass discrimination correction factor for Pu-239/Pu-242 was 0.972 ± 0.010. The limit of detection (LOD) and limit of quantification (LOQ) of this system were calculated according to the ISO 20 899:2018, which were 2.24E-05 Bq m -3 and 7.45E-05 Bq m -3 with 1 min measurement. The main interference which was from U-238 was determined by U-238 standard solution generated by the nebuliser, and the interferences of U-238 to 239 was (8.50 ± 1.05) E-05. According to the counts of U-238 from several workplaces of reprocessing plant where this system was tested, 239 counts rate from the interferences of U-238 of those workplaces were at the same level of the system background counts, which meant that the LOD above was suitable for those places.

Rice husk is a widespread agriculture waste in rice-farming country. High silica content in rice husk prevent its efficient utilization. So in this work, concept of poly-generation was introduced to improve its utilization value. This study provided CO-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous SiO 2 as four end products for first time via combination of acid washing and activated carbon catalyst. Specifically, acid washing effectively decreasedsoluble ash, which altered pyrolysis paths, increased volatiles release and reduced impurities in bio-char. After catalytic pyrolysis, phenol content of 65.56% and CO of 56.09 vol% were detected in bio-oil and syngas from AWRH. For solid products, acid washing benefited both bio-char and silica. A low-cost porous carbon with developed pores and rich surface functional groups was prepared for water absorption. And high purity amorphous SiO 2 was recycled from alkali etching solution. Finally, a green process with no waste emission was proposed., (Copyright © 2019. Published by Elsevier Ltd.)

Perchlorate is a low molecular weight highly soluble anion. It occurs naturally in the environment, primarily near potash deposits and in arid regions. The determination of perchlorate in human milk is of interest in vulnerable populations such as infants and pregnant women. In this study, a sensitive and selective isotope dilution ion chromatography/tandem mass spectrometry (ID IC-MS/MS) method was developed and validated for the determination of perchlorate in human milk samples collected from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. The limit of detection (LOD) was 0.27 µg·kg -1 for human milk. A total of 439 human milk samples were analysed with measurable levels of perchlorate in most of the milk samples, and the mean value was 7.62 ± 32.7 µg·kg -1 . This project provided important information related to perchlorate levels in human milk collected across Canada and the extent to which pregnant women and their infants may be exposed to perchlorate. A dietary exposure assessment was also conducted in infants based on the measured values in human milk. The mean perchlorate probable daily intakes (PDIs) for infants consuming human milk were 0.31 ± 0.07 μg/kg bw/day for infants under 1 year and 0.17 ± 0.10 μg/kg bw/day for infants between 1 and 3 years old. None of the estimates exceeded the FAO/WHO provisional maximum tolerable daily intake (PMTDI) of 10 μg/kg bw/day.

Bacterial soft rot caused by Dickeya zeae MS1 (Erwinia chrysanthemi) is one of the most devastating banana diseases worldwide. However, knowledge of the development and ecological interactions of D. zeae MS1 biofilm is limited. Here, we visualized the development and architecture of D. zeae MS1 biofilm using confocal laser scanning microscopy, and we evaluated the ability of D. zeae MS1 to form biofilms under different environmental conditions (carbon sources, temperatures, pH levels and mineral elements) using a microtiter plate assay. We found that the development of D. zeae MS1 biofilm could be categorized into four phases and that mature biofilm consisted of a highly organized architecture of both bacterial cells and a self-produced matrix of extracellular polysaccharides. Furthermore, sucrose was the most suitable carbon source for supporting the growth of biofilm cells and that 32 °C and pH 7.0 were the most favorable of the temperatures and pH levels examined. Meanwhile, the addition of Ca 2+ , Fe 2+ , K + and Na + enhanced the formation of biofilm in minimal medium cultures, whereas 2.5 mM Cu 2+ and Mn 2+ was inhibitory. A better understanding of biofilm formation under different environmental parameters will improve our knowledge of the growth kinetics of D. zeae MS1 biofilm.

In order to determine the baseline levels of perchlorate in major brands of baby food, 200 baby food products were collected from retail stores in Ottawa, Canada and analysed for perchlorate in 2010. The seven food groups tested were fruit, juices, vegetables, meat, yogurt, mixed (vegetable mixed with meat) and other (e.g. vegetable mixed with meat and cereal, cheese, egg,). Samples were extracted with a mixture of methanol and 1% acetic acid (4:1, v/v). Determination was conducted by stable isotope dilution ion chromatography tandem mass spectrometry (ID-IC-MS/MS). The complexity of different food matrices required additional method validation. The perchlorate levels in 46 samples were found to be lower than the quantification limit (0.2 ng g -1 ). The perchlorate levels in the other 154 baby food samples were also low; about 96.7% of the baby foods had perchlorate levels less than 10 ng g -1 (ranged from 0.2 to 22.4 ng g -1 , median1.35 ng g -1 ); only 5 samples had perchlorate levels higher than 10 ng g -1 . Dietary exposure to perchlorate from analysed baby food was conservatively estimated to range from 0.007 to 0.121 µg/kg bw/d based on the mean intake for children (1-5 years old).

(-)-Englerin A was synthesized in 20 steps from the commercially available material ( R)-(+)-limonene. In addition, (-)-englerin B, (+)-orientalol E/F and (-)-oxyphyllol were obtained from the intermediate in the route. The key steps include a hydroxyl-directing stereoselective and regioselective intramolecular cyclopropanation and a multi-gram-scale stereoselective formal intramolecular [3 + 2] cross cycloaddition ([3 + 2]-IMCC) of a cyclopropane 1,1-diester with a carbonyl. A precursor of 7,10-diastereoisomer of englerins was also obtained.

A novel Lewis acid-catalyzed [3+2] intramolecular cross-cycloaddition (IMCC) between aziridine 2,2-diesters and conjugated dienes has been developed. This is the first regiospecific IMCC of intramolecular 1,3-dipolar cycloadditions of azomethine ylides with carbon=carbon double bonds, and supplies a general and efficient strategy for construction of structurally complex and diverse aza-[n.2.1] skeletons. The [3+2]IMCC could be carried out under mild conditions and in gram scale. More importantly, 3-alkyl-substituted aziridines were also successful. The excellent structural diversity, the facile operation and the versatile post-modifications will support the applications of the [3+2]IMCC in natural products synthesis and drugs discovery., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aiming to develop efficient and general strategies for construction of complex and diverse polycyclic skeletons, we have successfully developed [4+3]IMPC (intramolecular parallel cycloaddition) of cyclopropane 1,1-diesters with [3]dendralenes. With a combination of the [4+3]IMPC and subsequent [4+n] cycloadditions, trans-[5.3.0]decane skeleton and its corresponding structurally complex and diverse polycyclic variants could be constructed efficiently. This novel [4+3] cycloaddition reaction mode of donor-acceptor cyclopropanes proceeds as a result of the ring-strain relief of a trans-[3.3.0]octane. We strongly believe that the developed methods will demonstrate potential applications in natural products synthesis and drug discovery., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Controlling the fibril-formation process of collagen in vitro to fabricate novel biomaterials is a new area in the field of collagen research. This study aimed to determine the effect of ultrasonication on collagen fibril formation and the properties of the resulting collagen gels. Native collagen, extracted from the skin of grass carp, self-assembled under ultrasonic conditions (at different ultrasonic power and duration). The self-assembly kinetics, fibrillar morphology, and physical and cell growth-promoting properties of the collagen gels were analyzed and compared. The results showed that the self-assembly rate of collagen was increased by ultrasonication at the nucleation stage. The resulting fibrils exhibited smaller diameters and D-periodicity lengths than that of the untreated collagen samples (p<0.05). The viscoelasticity and textural properties of collagen gels also changed after ultrasonication at the nucleation stage. Texture profile analysis and cell proliferation assays showed that ultrasonication produced softer collagen gel colloids, which were more suitable for cell proliferation than the untreated collagen gels., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A tandem isomerization/intramolecular [3 + 2] cross-cycloaddition (IMCC) of cyclopropane 1,1-diesters with α,β-unsaturated ketones/aldehydes under a cooperative catalysis of photo and Lewis acids has been successfully developed. This supplied a general and efficient strategy for construction of medium-sized carbocyclic (8-, 9-, and 10-membered) skeletons as well as such carbocycle-based bridged oxa-bicyclo[n.2.1] (n = 4-6) skeletons.

A novel Lewis acid catalyzed formal intramolecular [3 + 3] cross-cycloaddition (IMCC) of cyclopropane 1,1-diesters has been successfully developed. This supplies an efficient and conceptually new strategy for construction of bridged bicyclo[2.2.2]octane skeletons. This [3 + 3]IMCC could be run up to gram scale and from easily prepared starting materials. This [3 + 3]IMCC, together with our previously reported [3 + 2]IMCC strategy, can afford either the bicyclo[2.2.2]octane or bicyclo[3.2.1]octane skeletons from the similar starting materials by regulating the substituents on vinyl group.

A Lewis acid catalyzed intramolecular [3 + 2] cross cycloaddition of cobalt-alkynylcyclopropane 1,1-diesters with carbonyls has been successfully developed. Together with simple and efficient postcycloadditions of the cobalt-alkyne moiety, a general and efficient strategy for construction of structurally complex and diverse medium-sized skeletons and related polycycles was supplied successfully.

A triflic acid-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles was developed. This reaction was expeditious, and the scope of the substituents in both cyclopropanes and nitriles was broad. This supplies an efficient and practical method for the synthesis of 1-pyrrolines.

A novel Lewis acid promoted formal intramolecular [3 + 2] parallel/cross-cycloaddition of cyclopropane 1,1-diesters with allenes has been successfully developed, in which the two C═C of allenes were involved respectively. This provides a general and efficient strategy for the construction of structurally diverse [4.3.0]nonane and [3.2.1]octane skeletons.

Objective: To compare the effectiveness of the traditional center of tibial plateau as the entry point and digital technology in the design of intramedullary tibial nail point positioning method in total knee arthroplasty (TKA)., Methods: Between October 2011 and October 2012, 60 cases undergoing unilateral TKA and meeting the selection criteria were randomly divided into 2 groups: in group A (30 cases), the tibial plateau center as the entry point of tibial intramedullary positioning was used; in group B (30 cases), Mimics 10.01 software to simulate the guide rod point of tibial intramedullary positioning was used. There was no significant difference in gender, age, etiology, disease duration, sides, and preoperative knee range of motion, Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) between 2 groups (P > 0.05). Postoperative X-ray films were taken to measure the tibiofemoral angle and tibial angle; knee range of motion, and HSS and WOMAC scores were used to assess the activity of knee., Results: The entry point of group B was located in front of the center of tibial plateau, which was inconsistent with the traditional entry point. The incision healed by first intention in all patients of 2 groups. The patients were followed up 6 to 12 months (mean, 8.6 months). The X-ray measurement at 1 week after operation showed no significant difference in tibiofemoral angle between 2 groups (t = -6.65, P = 0.72), but the anteroposterior and lateral tibial angles of group A were significantly lower than those of group B (P < 0.05). The knee range of motion, HSS score, and WOMAC score of 2 groups were significantly higher at 3 and 6 months after operation when compared with preoperative values (P < 0.05), and the values at 6 months were significantly increased than those at 3 months after operation (P < 0.05). HSS score and WOMAC score had no significant difference between 2 groups at 3 months after operation (P > 0.05), but the scores of group B were significantly higher than those of group A at 6 months (P < 0.05). The knee range of motion of group B was significantly better than that of group A at 3 months after operation (t = 2.13, P = 0.04), but no significant difference was found between 2 groups at 6 months (t = 0.58, P = 0.56)., Conclusion: Compared with the traditional intramedullary guide rod insertion point positioning, digital individualized design of entry point positioning has the advantages of more accurate lower limb force line, better recovery of knee function, and earlier 90 degrees activities, but the long-term effectiveness needs further observation.

Background: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health., Methods: Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the study's Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies., Results: Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada., Conclusions: The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals., (© 2013 John Wiley & Sons Ltd and Her Majesty the Queen in Right of Canada. Reproduced with the permission of the Minister of Health.)

This article covers challenges and trends in the determination of some major food chemical contaminants and allergens, which-among others-are being monitored by Health Canada's Food Directorate and for which background levels in food and human exposure are being analyzed and calculated. Eleven different contaminants/contaminant groups and allergens have been selected for detailed discussion in this paper. They occur in foods as a result of: use as a food additive or ingredient; processing-induced reactions; food packaging migration; deliberate adulteration; and/or presence as a chemical contaminant or natural toxin in the environment. Examples include acrylamide as a food-processing-induced contaminant, bisphenol A as a food packaging-derived chemical, melamine and related compounds as food adulterants and persistent organic pollutants, and perchlorate as an environmental contaminant. Ochratoxin A, fumonisins, and paralytic shellfish poisoning toxins are examples of naturally occurring toxins whereas sulfites, peanuts, and milk exemplify common allergenic food additives/ingredients. To deal with the increasing number of sample matrices and analytes of interest, two analytical approaches have become increasingly prevalent. The first has been the development of rapid screening methods for a variety of analytes based on immunochemical techniques, utilizing ELISA or surface plasmon resonance technology. The second is the development of highly sophisticated multi-analyte methods based on liquid chromatography coupled with multiple-stage mass spectrometry for identification and simultaneous quantification of a wide range of contaminants, often with much less requirement for tedious cleanup procedures. Whereas rapid screening methods enable testing of large numbers of samples, the multi analyte mass spectrometric methods enable full quantification with confirmation of the analytes of interest. Both approaches are useful when gathering surveillance data to determine occurrence and background levels of both recognized and newly identified contaminants in foods in order to estimate human daily intake for health risk assessment.

Build a bridge: The first catalytic intramolecular [3+2] cycloaddition of monodonor-monoacceptor cyclopropanes (see scheme) provides a general and efficient strategy for construction of structurally diverse acetal[n.2.1] and 1,4-dioxygen-substituted cyclic skeletons, which are widely distributed in biologically important natural products., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly efficient and convenient method for the synthesis of 1,2,4,5-tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones has been developed. This reaction proceeded under mild conditions without the assistance of any metal, acid, or base.

TrdL, encoding a flavin-dependent oxidoreductase in the tirandamycin gene cluster, was inactivated to afford a ΔtrdL mutant, the fermentation of which yielded a new intermediate, tirandamycin E (5), and an additional early intermediate, tirandamycin F (6), if XAD-16 resin was introduced. TrdL was overexpressed in E. coli, and the protein was shown to efficiently catalyze the transformations from 5 to tirandamycin A (1) and from 6 to tirandamycin D (4), demonstrating its function as a 10-hydroxy dehydrogenase.

Tirandamycins are bacterial RNA polymerase inhibitors holding great potential for antibacterial agent design. To elucidate the biosynthetic machinery and generate new derivatives, the tirandamycin biosynthetic gene cluster was cloned and sequenced from marine-derived Streptomyces sp. SCSIO1666. The biosynthetic gene cluster of tirandamycin spans a DNA region of ∼56kb and consists of 15 open reading frames (ORFs) which encode three type I polyketide synthases (TrdAI, AII, AIII), one non-ribosomal peptide synthetase (TrdD), one phosphopantetheinyl transferase (TrdM), one Type II thioesterase (TrdB), one FAD-dependent oxidoreductase (TrdL), one cytochrome P450 monooxygenase (TrdI), three proteins related to resistance and regulations (TrdHJK), and four proteins with unknown function (TrdCEFG). To investigate the roles of the genes played in the biosynthetic machinery, seven genes (trdAI and trdBDFHIK) were inactivated via in frame replacement with an apramycin gene cassette using λ-RED recombination technology. The ΔtrdAI and ΔtrdD mutants targeting the ketosynthase and adenylation domain of TrdAI and TrdD, respectively, abolished the production of tirandamycins, confirming their involvement in the tirandamycin biosynthesis. TrdH showed high homology to LuxR family transcriptional regulatory proteins, disruption of which abolished the production of tirandamycins, indicating that TrdH is a positive regulator for tirandamycin biosynthesis. On the other hand, TrdK showed high homology to TetR-family transcriptional regulatory proteins, disruption of which significantly increased the yields of tirandamycins almost one-fold, implicating that TrdK is a negative regulator for tirandamycin biosynthesis. Disruption of the gene trdI resulted in the accumulation of the intermediate tirandamycin C (3) and a trace amount of new product tirandamycin C2 (5). A model of tirandamycin biosynthesis was proposed based on bioinformatics analyses, gene inactivation experiments and intermediates isolated from the mutants. These findings set the stage for further study of the tirandamycin biosynthetic mechanism and rationally engineer new tirandamycin analogues., (Copyright © 2011 Elsevier Inc. All rights reserved.)

There has been increasing concern over the contamination of drinking water and food with perchlorate. Studies have reported perchlorate in a variety of foods, including lettuce, milk, fruits, and juices. In this study, 150 food samples were analyzed by ion chromatography tandem mass spectrometry (IC-MS/MS) to determine the concentrations of perchlorate in imported and domestic fruits and vegetables available from retail outlets in Ottawa, Canada. Perchlorate was found in most of the tested food types with concentrations appearing to vary by commodity and country of origin. Levels ranged from nondetectable to 536 microg/kg, with Guatemalan cantaloupes (156 +/- 232 microg/kg), United States spinach (133 +/- 24.9 microg/kg), Chilean green grapes (45.5 +/- 13.3 microg/kg), and United States Romaine lettuce (29.1 +/- 10.5 microg/kg) having the highest concentrations. Dietary exposure to perchlorate from analyzed fruits and vegetables was estimated to be approximately 36.6 and 41.1 ng/kg bw/day for toddlers (1-4 yrs) and children (5-11yrs), respectively.

Catalyzed by N-heterocyclic carbenes (NHCs), domino ring-opening/redox amidation/cyclization reactions of the readily available formylcyclopropane 1,1-diesters with 2-chloro-1H-indole-3-carboaldehydes were reported. This methodology provides an efficient and direct construction of a 6-5-6 tricyclic hydropyrido[1,2-a]indole skeleton, which can be potentially applied for the synthesis of several types of polycyclic indole alkaloids.

The first Friedel-Crafts reaction initiated by the direct generation of a carbocation at the C3 position of MCP 1,1-diesters through distal-bond cleavage was presented. The described method supplied a new synthetic strategy to prepare indene and hydronaphthalene derivatives in moderate to excellent yields under mild conditions.

Trivalent arsenicals have high affinity for thiols (such as free cysteines) in proteins. We describe here the use of this property to develop a collision-induced dissociation (CID) tandem mass spectrometry (MS/MS) technique for the identification of reactive cysteines in proteins. A trivalent arsenic species, dimethylarsinous acid (DMA (III)), with a residue mass (103.9607) and mass defect distinct from the normal 20 amino acids, was used to selectively label reactive cysteine residues in proteins. The CID fragment ions of the arsenic-labeled sequences shifted away from the more abundant normal fragments that would otherwise overlap with the ions of interest. Along with the internal and immonium ions, the arsenic-labeled fragment ions served as MS/MS signatures for identification of the binding sites and for assessment of the relative reactivity of individual cysteine residues in a protein. Using this method, we have identified two highly reactive binding sites in rat hemoglobin (Hb): Cys-13alpha and Cys-125beta. Cys-13alpha was bound to DMA (III) in the Hb of rats fed with arsenic, and this binding was responsible for arsenic accumulation in rat blood, while Cys-125beta was found to bind to glutathione in rat blood. This study revealed the relative reactivity of the cysteines in rat Hb in the following decreasing order: Cys-13alpha >> Cys-111alpha > Cys-104alpha and Cys-13alpha >> Cys-125beta > Cys-93beta. Arsenic-labeling is easy and fast for identification of active binding sites without enzymatic digestion and acid hydrolysis, and useful for characterization and identification of metal binding sites in other proteins.

Background: Determination of arsenic species in saliva is potentially useful for biomonitoring of human exposure and studying arsenic metabolism. Arsenic speciation in saliva has not been reported previously., Methods: We separated arsenic species in saliva using liquid chromatography (LC) and quantified them by inductively coupled plasma mass spectrometry. We further confirmed the identities of arsenic species by LC coupled with electrospray ionization tandem mass spectrometry. These methods were successfully applied to the determination of arsenite (As(III)), arsenate (As(V)), and their methylation metabolites, monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)), in >300 saliva samples collected from people who were exposed to varying concentrations of arsenic., Results: The mean (range) concentrations (microg/L) in the saliva samples from 32 volunteers exposed to background levels of arsenic were As(III) 0.3 [not detectable (ND) to 0.7], As(V) 0.3 (ND to 0.5), MMA(V) 0.1 (ND to 0.2), and DMA(V) 0.7 (ND to 2.6). Samples from 301 people exposed to increased concentrations of arsenic in drinking water showed detectable As(III) in 99%, As(V) in 98%, MMA(V) in 80%, and DMA(V) in 68% of samples. The mean (range) concentrations of arsenic species in these saliva samples were (in microg/L) As(III) 2.8 (0.1-38), As(V) 8.1 (0.3-120), MMA(V) 0.8 (0.1-6.0), and DMA(V) 0.4 (0.1-3.9). Saliva arsenic correlated with drinking water arsenic. Odds ratios for skin lesions increased with saliva arsenic concentrations. The association between saliva arsenic concentrations and the prevalence of skin lesions was statistically significant (P <0.001)., Conclusions: Speciation of As(V), As(III), MMA(V), and DMA(V) in human saliva is a useful method for monitoring arsenic exposure.

Thioredoxin (Trx) plays an important role in achieving redox balances in cells and protecting the cells from oxidative damage. However, little is known about how arsenic affects Trx chemically. It is conceivable that trivalent arsenicals may bind to Trx, which has a highly conserved -CysGlyProCys- sequence. The objective of this study is to characterize the binding of seven arsenic species with Trx from E. coli and humans, using two mass spectrometry techniques. The arsenic-Trx complexes and the free arsenicals were well separated by size-exclusion liquid chromatography (LC) and detected with inductively coupled plasma mass spectrometry (ICPMS). The LC/ICPMS analyses showed that the trivalent arsenic species were able to form complexes with both human and E. coli Trx. Determination of binding constants indicated that affinity to Trx was higher for monomethylarsonous acid (MMA(III)) and phenylarsine oxide (PhAs(III)) than inorganic arsenite (iAs(III)) and dimethylarsinous acid (DMA(III)), probably because MMA(III) and PhAs(III) were able to form stable complexes by binding to two vicinal cysteines in the -CysGlyProCys- region of the Trx. The complexes of arsenicals with both human and E. coli Trx were further characterized by nano-electrospray tandem mass spectrometry. Binding stoichiometries for different arsenic species were consistent with the available cysteine residues in the Trx. Mass spectral evidence also suggests that the pentavalent arsenicals could be reduced by Trx. This study provides the first detailed chemical characterization of the interactions between Trx and arsenic species., (Copyright 2007 John Wiley & Sons, Ltd.)

Children's exposure to arsenic and chromium from playground equipment constructed with chromated copper arsenate (CCA)-treated wood is a potential concern because of children's hand-to-mouth activity. However, there exists no direct measure of Cr levels on the hands of children after playing in such playgrounds. In this study we measured both soluble and total Cr on the hands of 139 children playing in playgrounds, eight of which were constructed with CCA-treated wood and eight of which were not. Children's age and duration of play were recorded. The hands of each child were washed after play with 150 mL deionized water, which was collected in a bag and subsequently underwent analysis of Cr and 20 other elements, using inductively coupled plasma mass spectrometry. Total average Cr on the hands of 63 children who played in CCA playgrounds was 1,112 +/- 1,089 ng (median, 688; range 78-5,875). Total average Cr on the hands of 64 children who played in non-CCA playgrounds was 652 +/- 586 ng (median, 492; range 61-3,377). The difference between the two groups is statistically significant (p < 0.01). Cr levels were highly correlated to both Cu (r = 0.672) and As (r = 0.736) levels in CCA playgrounds (p < or = 0.01), but not non-CCA playgrounds (r = 0.252 and 0.486 for Cu and As, respectively). Principal-component analysis indicates that Cr, Cu, and As are more closely grouped together in CCA than in non-CCA playgrounds. These results suggest that the elevated levels of Cr and As on children's hands are due to direct contact with CCA wood.

[reaction: see text]. A directed library of anilinogeranyl diphosphate analogues of the isoprenoid farnesyl diphosphate has been prepared by solid-phase organic synthesis using a traceless linker strategy in moderate yield in three steps: reductive amination, bromination, and treatment with ((n-Bu)4N)3HP2O7.

The appearance of 8-oxo-2'-deoxyguanosine (8-oxodG) was examined immunohistochemically using an 8-oxodG-monoclonal antibody in 28 cases of arsenic-related human skin tumors and in 20 cases of arsenic-unrelated human skin cancer to determine if the induction of oxidative stress participates in skin tumorigenesis caused by arsenics. The rate of 8-oxodG-positive was significantly higher in arsenic-related human skin cancer (28 of 28, 100%) than in arsenic-unrelated human skin cancer (3 of 20, 15%, P<0.01 by Chi2 test). Moreover, in all the arsenic-related skin samples, 8-oxodG was detected not only in tumor tissues but also in keratosis and normal tissues. These results suggest that the induction of oxidative stress may play an important role in arsenic carcinogenesis.