p-Cresol-Enabled Nickel-Catalyzed Intermolecular Redox-Economical Coupling of Allyl Alcohols with Alkynes through oxa-Nickelacycle.

An intermolecular redox-economical coupling reaction of allyl alcohols with alkynes, catalyzed by Ni-Brønsted acid cocatalysis, has been developed. This method allows for the synthesis of a diverse range of γ,δ-unsaturated ketones with yields ranging from 40% to 94%, while maintaining excellent compatibility with various functional groups. The transformation of the resulting product demonstrates the significant practical value of this method. Further mechanistic investigations have revealed that the reaction proceeds through the formation of an oxa-nickelacycle intermediate.

Intermolecular Carbophosphination of Alkynes with Phosphole Oxides via Ni-Al Bimetal-Catalyzed C-P Bond Activation.

Intermolecular carbophosphination reaction of alkynes or alkenes with unreactive C-P bonds remains an elusive challenge. Herein, we used a Ni-Al bimetallic catalyst to realize an intermolecular carbophosphination reaction of alkynes with 5-membered phosphole oxides, providing a series of 7-membered phosphepines in up to 94 % yield.

Ni-catalyzed benzylic ß-C(sp3)-H bond activation of formamides.

The development of transition metal-catalyzed ß-C-H bond activation via highly-strained 4-membered metallacycles has been a formidable task. So far, only scarce examples have been reported to undergo ß-C-H bond activation via 4-membered metallacycles, and all of them rely on precious metals. In contrast, earth-abundant and inexpensive 3d transition metal-catalyzed ß-C-H bond activation via 4-membered metallacycles still remains an elusive challenge. Herein, we report a phosphine oxide-ligated Ni-Al bimetallic catalyst to activate secondary benzylic C(sp3)-H bonds of formamides via 4-membered nickelacycles, providing a series of α,ß-unsaturated γ-lactams in up to 97% yield.

Mdm-MIR393b-mediated adventitious root formation by targeted regulation of MdTIR1A expression and weakened sensitivity to auxin in apple rootstock.

Adventitious root (AR) formation is of great significance for apple rootstock breeding. It is widely accepted that miR393 influences AR formation in many plant species; however, the molecular mechanism by which factors regulate AR formation remains insufficient. In this study, the evolutionary relationship of mdm-miR393 and candidate target genes MdTIR1/AFB was systematically identified, and the expression patterns were analysed. Multisequence alignment analysis of miR393 family members suggests that miR393 conservatively evolved between different species. The evolutionary relationship of the TIR1/AFBs can be divided into G1, G2 and G3 subgroups. During AR formation, the expression level of mdm-miR393a/b/c was significantly upregulated at 1 d and 7 d by exogenous auxin treatment. Furthermore, the expression levels of MdTIR1A, MdTIR1D, MdAFB1, MdAFB2, MdAFB3, MdAFB4 and MdAFB8 also appeared to be significantly changed by exogenous auxin induction. Subsequently, tissue-specific expression analysis showed that the expression levels of mdm-miR393 and MdTIR1/AFBs in different tissues exhibited significant differences. The promoter of mdm-miR393 contains multiple elements that respond to ABA, adversity and light signals; auxin treatment can activate the mdm-MIR393b promoter but is obviously inhibited by NPA treatment. The targeting relationship between mdm-MIR393b and MdTIR1A was verified by expression patterns, degradation group data, transient tobacco conversion results, and genes functions experiments. Heterologous overexpression of mdm-MIR393b (35S::mdm-MIR393b) decreased the number of ARs in the phenotype and reduced the expression level of the target gene NtTIR1 in tobacco. Compared to the wild type, the 35S::mdm-MIR393b transgenic plants demonstrated insensitivity to auxin. Furthermore, tir1 mutant exhibited reduced root system structure relative to the control. The above results illustrated that mdm-MIR393b is involved in mediating AR formation by targeted regulation of MdTIR1A expression in apple rootstock.

Construction 7-membered ring via Ni-Al bimetal-enabled C-H cyclization for synthesis of tricyclic imidazoles.

The construction of 7-membered ring via direct C7-H cyclization of benzoimidazoles with alkenes would provide a more atom- and step-economical route to tricyclic imidazoles and derivatives that widely exist in a broad range of bioactive molecules. However, transition metal-catalyzed C-H cyclization for medium-ring synthesis has been limited to reactive C-H bonds, instead, the activation of unreactive C-H bonds towards medium synthesis still remains an elusive challenge. Herein, we report a direct construction of 7-membered rings via Ni-Al co-catalyzed unreactive C7-H cyclization of benzoimidazoles with alkenes, providing a series of tricyclic imidazoles in 40-98% yield and with up to 95:5 er.

Carbamoyl Fluoride-Enabled Enantioselective Ni-Catalyzed Carbocarbamoylation of Unactivated Alkenes.

A carbamoyl fluoride-enabled enantioselective Ni-catalyzed carbocarbamoylation of unactivated alkenes was developed, providing a broad range of chiral γ-lactams bearing an all-carbon quaternary center in 45-96% yield and 38-97% ee.

Wet- versus dry-suction techniques for endoscopic ultrasound-guided fine-needle aspiration of solid lesions: a multicenter randomized controlled trial.

BACKGROUND: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen. METHODS: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality. RESULTS: Among the 269 patients with pancreatic (n = 161) and non-pancreatic (n = 108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9 % [95 % confidence interval (CI) 79.9 % - 89.0 %] vs. 73.2 % [95 %CI 67.1 % - 78.7 %]; P = 0.001), higher specimen adequacy (94.8 % vs. 78.8 %; P < 0.001), and less blood contamination (P < 0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6 %. CONCLUSIONS: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available.

Developmental population pharmacokinetics-pharmacodynamics and dosing optimization of cefoperazone in children.

OBJECTIVES: To evaluate the population pharmacokinetics of cefoperazone in children and establish an evidence-based dosing regimen using a developmental pharmacokinetic-pharmacodynamic approach in order to optimize cefoperazone treatment. METHODS: A model-based, open-label, opportunistic-sampling pharmacokinetic study was conducted in China. Blood samples from 99 cefoperazone-treated children were collected and quantified by HPLC/MS. NONMEM software was used for population pharmacokinetic-pharmacodynamic analysis. This study was registered at ClinicalTrials.gov (NCT03113344). RESULTS: A two-compartment model with first-order elimination agreed well with the experimental data. Covariate analysis showed that current body weight had a significant effect on the pharmacokinetics of cefoperazone. Monte Carlo simulation showed that for bacteria for which cefoperazone has an MIC of 0.5 mg/L, 78.1% of hypothetical children treated with '40 mg/kg/day, q8h, IV drip 3 h' would reach the pharmacodynamic target. For bacteria for which cefoperazone has an MIC of 8 mg/L, 88.4% of hypothetical children treated with 80 mg/kg/day (continuous infusion) would reach the treatment goal. A 160 mg/kg/day (continuous infusion) regimen can cover bacteria for which cefoperazone has an MIC of 16 mg/L. Nevertheless, even if using the maximum reported dose of 160 mg/kg/day (continuous infusion), the ratio of hypothetical children reaching the treatment target was only 9.9% for bacteria for which cefoperazone has an MIC of 32 mg/L. CONCLUSIONS: For cefoperazone, population pharmacokinetics were evaluated in children and an appropriate dosing regimen was developed based on developmental pharmacokinetics-pharmacodynamics. The dose indicated in the instructions (20-160 mg/kg/day) can basically cover the clinically common bacteria for which cefoperazone has an MIC of ≤16 mg/L. However, for bacteria for which the MIC is >16 mg/L, cefoperazone is not a preferred choice.

Dual-modal aptasensor for the detection of isocarbophos in vegetables.

An aptamer-based colorimetric-phosphorescent assay was developed for the detection of isocarbophos. The colorimetric assay relied on the aggregation of gold nanoparticles (AuNPs) caused by the competitive binding of aptamer between isocarbophos and AuNPs in the presence of a high salt concentration. The further addition of persistent luminescence nanorods (PLNRs) into the system showed the phosphorescence sensitively proportional to the concentration of isocarbophos, due to the inner filter effect between PLNRs and AuNPs. The assay showed good linearity within 50-500 µg/L and 5-160 µg/L, and limit of detection of 7.1 µg/L and 0.54 µg/L in colorimetry and phosphorescence mode, respectively. The feasibility of this approach for food analysis was demonstrated with the sensitive and selective determination of isocarbophos residues in vegetables.

Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury.

The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF-1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF-1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF-1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF-1 binding motifs in the 1,692-bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF-1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll-like receptor 4 pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. CONCLUSION: These findings provide a novel mechanism by which IRF-1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056-1070).

[Retracted] Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

Following the publication of this article, the authors find that they are not able to reproduce the results presented in this paper. Consequently, the authors have decided to retract this paper from publication. All of the authors agree to this retraction. The authors sincerely regret this decision, and apologize to the Editor and to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 33: 783-791, 2015; DOI: 10.3892/or.2014.3644].

Tlr22 structure and expression characteristic of barbel chub, Squaliobarbus curriculus provides insights into antiviral immunity against infection with grass carp reovirus.

Grass carp reovirus (GCRV) is the most virulent agent to Grass carp, Ctenopharyngodon idella, and causes a severe infectious disease called hemorrhagic disease of grass carp. Generally, barbel chub, Squaliobarbus curriculus, a genetically closely related species to grass carp, exhibits significant resistance against GCRV infection compared to grass carp. To investigate whether the Toll-like receptor 22 (tlr22) has got a vital role against the GCRV infection, the full cDNA sequence of tlr22 from barbel chub (Sctlr22) was cloned by RACE-PCR, and the structure and expression feature were studied. The complete cDNA sequence of Sctlr22 has a size of 3504 bp, encoding for 960 amino acid residues. Sctlr22 possesses typical structural features of the tlrs family, including 19 leucine rich repeats (LRRs), a transmembrane (TM) and a Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis revealed that barbel chub Tlr22 was clustered together with the Tlr22 of grass carp (Citlr22). Structurally, barbel chub Tlr22 have two different structure in LRRs domain and TIR domain with grass carp (Susceptible to GCRV), but was similar to that of Danio rerio and Cyprinus carpio (Resistance to GCRV). Quantitative RT-PCR analysis has shown that Sctlr22 is prominently expressed in immune relevant tissues such as head kidney and spleen. After GCRV infection, Sctlr22 expression level was up-regulated in four tested tissues and the highest expression of Sctlr22 appeared fast and higher than Citlr22. The interferon-ß (ifn-ß) expression level in CIK cells over-expressing fused cDNA encoding the LRR domain of Sctlr22 to the transmembrane and TIR domain of Citlr22 was significantly higher than that cells overexpressing Citlr22 after GCRV infection. The virus titer was significantly reduced compared to Citlr22 over-expressing cells. These results suggested that Sctlr22 seems to play a vital role in the immune response against GCRV.

Malaria from hyperendemicity to elimination in Hekou County on China-Vietnam border: an ecological study.

BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China-Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952-2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) -0.6845 (95% CI -0.7978, -0.6845) for national GDP, -0.7014 (-0.8093, -0.7014) for national urbanization rate and -0.5563 (-0.7147, -0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County.

Ligand-Accelerated Direct C-H Arylation of BINOL: A Rapid One-Step Synthesis of Racemic 3,3'-Diaryl BINOLs.

An ortho-selective rhodium-catalyzed direct C-H arylation of 1,1'-bi-2-naphthol (BINOL), to deliver the widely used but not easily available 3,3'-diaryl BINOL, has been developed. This highly efficient one-step synthetic approach is the shortest route to date and is greatly facilitated by the newly developed ligand system comprising tBu2 PCl, Ph2 -cod, and Cy3 P⋅HBF4 . In addition, the same procedure can facilitate the challenging syntheses of 3-bulkyaryl BINOLs in good to excellent yields.

Determination of Silicon in Gasoline by Directly Measuring under Organic Phase Using Inductively Coupled Plasma Optical Emission Spectroscopy.

A simple and accurate method was developed for determining silicon in gasoline using inductively coupled plasma optical emission spectroscopy (ICP-OES). For sample inroduction a Burgener nubulizer and a Cyclonic spray chamber were used. A gasoline sample was diluted with isooctane and then introduced into the cooled spray chamber of the ICP-OES. Good linearity was achieved in the silicon concentration range 0.1 - 10.0 mg x kg(-1), and the correlation coefficient was 0.999 96. The detection limit for silicon was 0.012 mg x kg(-1) and the silicon recoveries from gasoline samples were 95.8% - 98.4%, with relative standard deviations of less than 3.0% The method was proved to be simple, reliable and highly sensitive, and suitable for determining silicon in samples of motor gasoline, ethanol-gasoline and methanol-gasoline fuel mixtures those containing not more than 15% (V/V) oxygenates.

Estimating municipal solid waste generation by different activities and various resident groups in five provinces of China.

The quantities and composition of municipal solid waste (MSW) are important factors in the planning and management of MSW. Daily human activities were classified into three groups: maintenance activities (meeting the basic needs of food, housing and personal care, MA); subsistence activities (providing the financial support requirements, SA); and leisure activities (social and recreational pursuits, LA). A model, based on the interrelationships of expenditure on consumer goods, time distribution, daily activities, residents groups, and waste generation, was employed to estimate MSW generation by different activities and resident groups in five provinces (Zhejiang, Guangdong, Hebei, Henan and Sichuan) of China. These five provinces were chosen for this study and the distribution patterns of MSW generated by different activities and resident groups were revealed. The results show that waste generation in SA and LA fluctuated slightly from 2003 to 2008. For general waste generation in the five provinces, MA accounts for more than 70% of total MSW, SA approximately 10%, and LA between 10% and 16% by urban residents in 2008. Females produced more daily MSW than males in MA. Males produced more daily MSW than females in SA and LA. The wastes produced at weekends in MA and LA were far greater than on weekdays, but less than on weekdays for SA wastes. Furthermore, one of the model parameters (the waste generation per unit of consumer expenditure) is inversely proportional to per-capita disposable income of urban residents. A significant correlation between gross domestic product (GDP) and waste generation by SA was observed with a high coefficient of determination.

Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

This study was mainly focused on the development of a dual-ligand liposomal delivery system for targeting the delivery of paclitaxel (PTX) to lung cancer. The specific ligand peptide HAIYPRH (T7) and the cationic cell-penetrating peptide TAT were connected with phospholipid via a polyethylene glycol (PEG) spacer to prepare the dual-ligand liposomes (T7/TAT-LP-PTX). Physicochemical characterizations of T7/TAT-LP-PTX, such as particle size, ζ potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the T7/TAT-LP endocytosed by the A549 cells was 2.26-, 3.48- and 8.56-fold higher than TAT-LP, T7-LP and LP, respectively. The IC50 values of TAT-LP-PTX, T7-LP-PTX and LP-PTX were much higher than those of T7/TAT-LP-PTX, respectively. The homing specificity of T7/TAT-LP was evaluated on the tumor spheroids, which revealed that T7/TAT-LP was more efficaciously internalized in tumor cells than TAT-LP, T7-LP and LP, respectively. Compared to LP, TAT-LP and T7-LP, T7/TAT-LP showed the strongest cell uptake property, and the highest accumulation ability in tumor spheroids in vitro. In the in vivo study, the T7/TAT-LP-PTX exhibited the best inhibitory effect of tumor growth for A549-bearing mice. Collectively, these results suggested that T7/TAT-LP-PTX is a promising drug delivery system for the treatment of lung cancer.

[Expression of biomarkers related with bone marrow cells in patients with acute myelogenous leukemia].

This study was aimed to investigate the expression of biomarkers (PTEN, mTOR, NF-kB, CD44, PI3K) related with bone marrow cells in patients with acute myelogenous leukemia. The immunohistochemical method was used to detect the expression of PTEN, mTOR, NF-kB, CD44, PI3K in 20 patients. The AML patients were divided into remission group and non-remission group after calculating the percentage of leukemia cells in bone marrow. The results showed that by optical microscopy, the positive expression rates of PTEN, mTOR, NF-kB, CD44 and PI3K in remission group were 33.3%, 33.3%, 77.8%, 22.2%, 0, respectively; meanwhile, in non-remission group, the positive expression rates of above-menthioned biomarkers were 63.6%, 18.2, 90.9, 63.6%, 0, respectively. The percentage and mean OD for PTEN and CD44 were statistically different between the two groups (P < 0.05), but for mTOR, NF-kB and PI3K were not statistically differenly (P > 0.05). It is concluded that the high expression of PTEN and CD44 can be regarded as an important index for diagnosis and prognosis in acute myelogenous leukemia.

[Clinical manifestations and gene mutations of a Chinese family with MYH9-related syndrome].

OBJECTIVE: To explore the method for early diagnosis and pathogenesis of MYH9-related syndrome through analysis of the clinical manifestation and gene mutation of a Chinese family with MYH9-related syndrome. METHODS: Peripheral blood samples were collected from a three-generation Chinese family with MYH9-related syndrome (11 individuals, including 3 patients) and 100 healthy individuals. Polymerase chain reaction (PCR) amplification and direct sequencing of DNA were performed to analyze mutations of MYH9 gene. RESULTS: Thrombocytopenia, increased volume of platelet, and granulocyte inclusion bodies were found in the patients with MYH9-related syndrome via a peripheral blood test. A missense mutation of a base pair (G-A) in exon 30 was revealed by PCR amplification and direct sequencing of MYH9 of the proband. That lead to Asp-Asn substitution at position 1424 (D1424N mutation). The mutation was the same as in other patients with MYH9-related syndrome. It was not found in healthy people from the Chinese family or in the other 100 healthy individuals. CONCLUSIONS: Patients with MYH9-related syndrome show diverse symptoms. Mutation of MYH9 gene may be the molecular mechanism of MYH9-related syndrome, and D1424N mutation of MYH9 has not been reported in Chinese people. Early diagnosis of MYH9-related syndrome can be carried out by investigating family history and making early examinations.

A simple stochastic model with environmental transmission explains multi-year periodicity in outbreaks of avian flu.

Avian influenza virus reveals persistent and recurrent outbreaks in North American wild waterfowl, and exhibits major outbreaks at 2-8 years intervals in duck populations. The standard susceptible-infected- recovered (SIR) framework, which includes seasonal migration and reproduction, but lacks environmental transmission, is unable to reproduce the multi-periodic patterns of avian influenza epidemics. In this paper, we argue that a fully stochastic theory based on environmental transmission provides a simple, plausible explanation for the phenomenon of multi-year periodic outbreaks of avian flu. Our theory predicts complex fluctuations with a dominant period of 2 to 8 years which essentially depends on the intensity of environmental transmission. A wavelet analysis of the observed data supports this prediction. Furthermore, using master equations and van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how the outbreak period varies with the environmental transmission.