RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

RhIII-promoted directed C-H N-heteroarylation of 2-pyridones.

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

Detection Enhancement of One Multifunctional Cd-Metal-Organic Framework toward Tetracycline Antibiotics by Simply Mixing Eu3+ in Suspension.

It is necessary to find more simple methods to improve the detection selectivity and sensitivity of antibiotics. Herein, we constructed a novel three-dimensional (3D) Cd-MOF LCU-117 assembled from p-terphenyl-4,2″,5″,4'-tetracarboxylic acid, which showed a special 3D helical structure with carboxylic acid ligands and nitrogen-containing ligands crossing each other vertically. Luminescence measurements indicated that LCU-117 has high selectivity and sensitivity toward Eu3+ through the ratiometric effect. Meanwhile, this complex itself could detect antibiotics oxytetracycline (OTC) through the turn-off mechanism. When Eu3+ was added in suspensions of LCU-117 (noted as Eu3+@LCU-117), the detection toward OTC was enhanced significantly and visually. The sensing mechanism was investigated in detail by various measurements and theoretical calculations. LCU-117 has a good effect on the logic gate, potential fingerprint detection, and mixed-matrix membranes (MMMs). The practical application for monitoring OTC in water samples also provided a satisfactory result.

One-Pot Construction of Heteroarylation/Esterification Products of Acrylic Acids via Iridium(III)-Catalyzed C-H Activation.

A carboxylate-assisted iridium(III)-catalyzed regioselective C(sp2)-H heteroarylation/esterification reaction of acrylic acid is disclosed herein for the first time. This catalytic protocol tolerates various α-substituted, ß-substituted, and α, ß-disubstituted acrylic acids as well as heteroaromatic boronates well. The resulting 3,4-dihydro-2H-pyran-6-carboxylic acid derivative 3r highlighted the AIE-active luminophore with multiple emission signal properties and a high quantum yield of 28%, exhibiting the potential application of this methodology for the synthesis of nitrogen-containing organic functional materials.

AIE-active aurones for circularly polarized luminescence and trace water detection.

AIE-active phenyl- and [2.2]paracyclophanyl-based aurones (2-Ph and 2-PCP) were synthesized and investigated with different structures and photophysical properties. The results illustrated that the PCP ring can provide chirality, electron-donating ability and steric hindrance. Accordingly, (Rp)/(Sp)-2-PCP exhibit high sensitivity in trace water detection and aggregation-induced CPL with enhanced quantum yields and luminescence dissymmetry factors.

RhIII-Catalyzed C-H N-Heteroarylation and Esterification Cascade of Carboxylic Acid with Organoboron Reagents and 1,2-Dichloroethane in One-Pot Synthesis.

A RhIII-catalyzed C(sp2)-H N-heteroarylation and esterification cascade of aryl carboxylic acids with N-heteroaromatic boronates and 1,2-dichloroethane in a one-pot synthesis has been disclosed. The strong coordinating ability of ortho- and meta-substituted pyridine boronates and pyrazoles as well as unsubstituted pyrimidine allows them to serve as the coupling partners. This protocol allows late-stage modification of the key precursor of roflumilast and compounds of pharmaceutical interest, which highlights the potential application of this synthetic method.

The synthesis of aryl-heteroaryl derivatives via the RhIII-catalyzed heteroarylation of arenes and heteroaromatic boronates.

An efficient RhIII-catalyzed strategy for constructing aryl-heteroaryl derivatives with removable ketoxime ether auxiliaries via direct C-H heteroarylation based on arenes and heteroaromatic boronates has been disclosed. This protocol could tolerate various pyridine, pyrimidine, pyrazole, thiophene, and furan heteroaromatic boronates well, providing the desired products with high reactivities and excellent regioselectivity. The easy synthetic accessibility may offer potential for application in the synthesis of heterocyclic drug molecules containing aryl-heteroaryl motifs.

3D Boranil Complexes with Aggregation-Amplified Circularly Polarized Luminescence.

The development of small organic CPL-active molecules with large luminescent dissymmetry factors is highly demanded due to their promising applications in chiroptical devices and sensors. This work describes the design and synthesis of a new family of CPL-active BF2 complexes, (Rp)/(Sp)-3a-3e, which were constructed by fusing a N̂O-chelated BF2 complex with [2.2]paracyclophane. These complexes display aggregation-amplified CPL with moderate dissymmetry factors values and moderate quantum yields both in solution and in the solid state. In addition, these photophysical properties were rationalized via X-ray diffraction and TD-DFT calculations.

RhIII-Catalyzed Direct Heteroarylation of C(sp3)-H and C(sp2)-H Bonds in Heterocycles with N-Heteroaromatic Boronates.

Herein, we disclose a RhIII-catalyzed heteroarylation of C(sp3)-H and C(sp2)-H bonds in heterocycles with organoboron reagents. This protocol displays high efficiency and excellent functional group tolerance. A range of heterocyclic boronates with strong coordinating atoms, including pyridine, pyrimidine, pyrazole, thiophene, and furan derivatives, can be extensively served as the coupling reagents. The direct heteroarylation method could supply potential application in terms of the synthesis of drug molecules with multiple heterocycles.

Differences in the intestinal microbiota between insecticide-resistant and -sensitive Aedes albopictus based on full-length 16S rRNA sequencing.

The intestinal symbiotic bacteria of Aedes albopictus play a potential role in host resistance to insecticides. In this study, we sequenced the full-length of 16S rRNA and analyzed the differences in the intestinal microbiota between deltamethrin-resistant and -sensitive Ae. albopictus. Symbiotic bacteria were cultured and analyzed using six types of culture media in aerobic and anaerobic environments. We found significant differences in the diversity and abundance of the intestinal microbiota of the two strains of Ae. albopictus. The symbiotic bacteria cultured in vitro were found to be mainly facultative anaerobes. The cultured bacteria such as Serratia oryzae and Acinetobacter junii may function to promote the development of insecticide resistance. This work indicates that intestinal bacteria may contribute to the enhancement of insecticide resistance of Ae. albopictus It also highlights the analytical advantage of full-length 16S rRNA sequencing to study the intestinal microbiota of mosquitoes.

Effects of imperatorin on apoptosis and synaptic plasticity in vascular dementia rats.

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin-Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy.

RhIII-Catalyzed C-H (Het)arylation/Vinylation of N-2,6-Difluoroaryl Acrylamides.

RhIII-catalyzed sp2 C-H cross-coupling of acrylamides with organoboron reactants has been accomplished using a commercially available N-2,6-difluoroaryl acrylamide auxiliary. A broad range of aryl and vinyl boronates as well as a variety of heterocyclic boronates with strong coordinating ability can serve as the coupling partners. This transformation proceeds under moderate reaction conditions with excellent functional group tolerance and high regioselectivity.

Analysis of Epidemiological Changes and Prevention Effects for Malaria in Weifang, Shandong Province, China from 1957 to 2017.

BACKGROUND: We aimed to conduct a retrospective analysis of the epidemiological changes and prevention effects for malaria in Weifang, Shandong Peninsula, China from 1957 to 2017. METHODS: The malaria data from a web-based reporting system were analyzed to explore malaria epidemiological characteristics and prevention effects in Weifang. RESULTS: Overall, 1, 704, 890 malaria cases were reported in Weifang from 1957 to 2017, of which two major malaria epidemics occurred in 1961 (827.28/10, 000) and 1971 (366.14/10, 000). Prior to 1997, all malaria patients (1, 704, 829) were infected with Plasmodium vivax (P. vivax). After 2007, the cases of Plasmodium falciparum (P. falciparum) showed an upward trend (76.8%). The reported cases after the 21st century were mainly imported cases, and the last indigenous case was a patient that infected with P. vivax in 2006. Overall, 36 imported cases were reported from 2010 to 2017, of which 88.9% were acquired in Africa. Except for one 32-year-old woman, the rest were male (97.2%), in which laborers and farmers represented the vast majority (66.6%). From 1987 to 2017, there were 1, 224, 474 cases of fever with blood tests, and the average blood test rate was 4.9%. From 1957 to 2017, a total of 1, 704, 890 malaria patients were treated, 96 cases were treated during resting phase from 1987 to 2017. CONCLUSION: Weifang should continue to strengthen the management of the migrant population, making blood tests for fever patients and patient treatment as important means of malaria control and monitoring.

Elimination of Lymphatic Filariasis in Shandong Province, China, 1957-2015.

China used to be one of the most heavily endemic countries for lymphatic filariasis (LF) in the world. Bancroftian filariasis, which is caused by the filarioid nematode Wuchereria bancrofti, is the only filariasis in Shandong Province. A total of 864 endemic counties (cities) in 16 provinces/autonomous regions/municipalities with a total population of 330 million people were at risk of infection. Shandong Province was a highly LF-endemic area in the 1950s, the epidemiological investigation of LF conducted in 1957 indicated that the disease was endemic in 74 counties and the highest microfilaria rate was up to 26%. There were ∼5 million people in the province infected with LF; among which almost 2.5 million people had lymphedema, elephantiasis, or hydrocele. Through vigorous prevention and scientific research, Shandong Province was the first to propose to treat LF with fortified diethylcarbamazine salt, more than 25 million people in the province had taken the salt, and more than 3 million people took intermittent medication. After more than 50 years of unremitting efforts, Shandong Province basically eliminated LF in 1983 and became the first province in China that successfully eradicated LF in 2004, which has played an important role in accelerating the elimination of filariasis in the country in 2007 and has made tremendous contributions to social and economic development of China. Since 1980, Shandong Province has carried out extensive international cooperation as the WHO Collaborating Center for Lymphatic Filariasis. This article is intended to share the experience in eliminating LF to other parts of the world and improve public health capacity in regions such as Africa and Oceania where the disease is still endemic for interest.

Two cadmium(II) coordination polymers as multi-functional luminescent sensors for the detection of Cr(VI) anions, dichloronitroaniline pesticide, and nitrofuran antibiotic in aqueous media.

Two ternary cadmium(II) coordination polymers, with the formulas being {[Cd(tptc)0.5(bpz)(H2O)]·0.5H2O}n (CP 1), and [Cd(tptc)0.5(bpy)]n (CP 2), were designed through mixed ligands strategy. Benefiting from the excellent chemical stability and luminescent property, two Cd(II) CPs possessing efficient multi-functional fluorescent responses toward Cr(VI) anions, 2,6-dichloro-4-nitroaniline pesticide, and nitrofuran antibiotic in aqueous media with high sensitivity, selectivity, and excellent recyclable behaviors with the detection limits (LODs) are 235 ppb for CrO42- anion, 343 ppb for Cr2O72- anion, 112 ppb for DCN pesticide, 62 ppb for NFT antibiotic for CP 1, and 173 ppb for CrO42- anion, 270 ppb for Cr2O72- anion, 638 ppb for DCN pesticide, 184 ppb for NFT antibiotic for CP 2, respectively. Besides, the mechanisms of luminescence quenching were revealed from the viewpoint of internal filter effect (IFE) and photoinduced electron transfer (PET).

Investigation of mosquito larval habitats and insecticide resistance in an area with a high incidence of mosquito-borne diseases in Jining, Shandong Province.

BACKGROUND: To investigate mosquito larval habitats and resistance to common insecticides in areas with high incidence rates of mosquito-borne diseases in Jining, Shandong Province, and to provide a scientific basis for the future prevention and control of mosquito-borne diseases and the rational use of insecticides. METHODS AND RESULTS: From June to September 2018, mosquito habitat characteristics and species compositions in Jintun town were studied through a cross-sectional survey. Larvae and pupae were collected in different habitats using the standard dipping technique. A total of 7,815 mosquitoes, comprising 7 species from 4 genera, were collected. Among them, Culex pipiens pallens (n = 5,336, 68.28%) was the local dominant species and found in all four habitats (rice paddies, irrigation channels, water containers, drainage ditches). There were 1,708 Cx. tritaeniorhynchus (21.85%), 399 Anopheles sinensis (5.11%), 213 Armigeres subalbatus (2.72%), 124 Aedes albopictus (1.59%), and 35 other (Cx. bitaeniorhynchus and Cx. halifaxii) (0.45%) mosquito samples collected. Spearman correlation analysis was employed to evaluate the relationship between larval density and the physicochemical characteristics of the breeding habitat. It was found that the larval density of Cx. tritaeniorhynchus correlated positively with water depth (r = 0.927 p = 0.003), the larval density of An. sinensis correlated positively with dissolved oxygen (DO) (r = 0.775 p = 0.041) and the larval density of Cx. p. pallens correlated positively with ammonia nitrogen (r = 0.527 p = 0.002). Resistance bioassays were carried out on the dominant populations of Cx. p. pallens: mosquitoes presented very high resistance to cypermethrin and deltamethrin, moderate resistance to dichlorvos (DDVP), and low resistance to Bacillus thuringiensis israelensis (Bti), with decreased susceptibility to propoxur. CONCLUSION: We showed that mosquito species vary across habitat type and that the mosquito larval density correlated positively with certain physicochemical characteristics in different habitats. In addition, Cx. p. pallens developed different levels of resistance to five insecticides. Vector monitoring should be strengthened after an epidemic, and further research should be conducted to scientifically prevent and kill mosquitoes.

Toward the Elimination of Malaria in China: A Retrospective Analysis of Malaria-Endemic Characteristics and Prevention Effects in Yantai, Shandong Province, 1951 to 2017.

Objectives: To study the epidemiological characteristics of malaria and the effects of comprehensive malaria control implementation in Yantai, as well as to provide a scientific basis for future malaria elimination. Materials and Methods: A retrospective analysis was conducted to explore the epidemiological changes and prevention effects in Yantai from 1951 to 2017. The malaria data before 2004 were collected from paper-based annual reports, and data after 2004 came from the Infectious Diseases Information Reporting Management System. Results: A total of 81,286 malaria cases were identified in Yantai from 1957 to 2017, with two peaks occurring in 1966 (120.93/100,000) and 1970-1972 (366.12/100,000). From 1951 to 2003, the case classification was mainly Plasmodium vivax (99.80%); the first case attributed to Plasmodium falciparum occurred in 2004, and P. falciparum became the main cause of malaria after 2011. All cases reported since 2010 have been imported cases, and the last indigenous case was caused by P. vivax in 2008. A total of 129 imported cases were reported from 2010 to 2017, most of which originated in Africa (93.80%), mainly in men aged 30-49 years (68.28%). From 1951 to 1973, 73,868 cases of malaria were diagnosed with clinical symptoms, and from 1974 to 2017, 818,943 cases in fever patients were diagnosed with blood tests. Conclusions: To achieve the goal of eliminating malaria by 2020, Yantai should continue to strengthen the management of migrant population, including improving malaria surveillance for returnees and immigrants from overseas endemic areas, and continue to increase the training of medical personnel to improve their diagnostic ability.

Trends in insecticide resistance in Culex pipiens pallens over 20 years in Shandong, China.

BACKGROUND: Culex pipiens pallens is the most abundant Culex mosquito species in northern China and is an important vector of bancroftian filariasis and, potentially, West Nile virus. Insecticides, particularly pyrethroids, are widely used for adult mosquito control. Insecticide resistance has become common in several mosquito species, and vector control is the main method currently available to prevent disease transmission. The voltage-gated sodium channel (Vgsc) gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). METHODS: Culex pipiens pallens larvae were collected from May to November over two decades, from 1992 to 2018, in four cities in Shandong Province, China. The World Health Organization (WHO) standard resistance bioassay was applied to test the resistance levels of Cx. p. pallens larvae to five different insecticides and to test deltamethrin resistance in adults, using the F1 generation. Mutations at Vgsc codon 1014 were also screened in 471 adult samples collected in 2014 to determine the association between kdr mutations and phenotypic resistance. RESULTS: Larval resistance against deltamethrin showed an increasing trend from the 1990s until 2018, which was statistically significant in all populations; resistance to cypermethrin increased significantly in mosquitoes from the Zaozhuang population. However, larval resistance to other insecticides remained relatively stable. Larval resistance against deltamethrin was consistent with adult bioassays in 2014, in which all tested populations were highly resistant, with mortality rates ranging from 39.4 to 55.23%. The L1014S and L1014F mutations were both observed in five Cx. p. pallens populations, with L1014F significantly associated with deltamethrin resistance. CONCLUSIONS: The long-term dataset from Shandong demonstrates major increases in pyrethroid resistance over a 20-year period. The L1014F kdr mutation may be considered a viable molecular marker for monitoring pyrethroid resistance in Cx. p. pallens.

Understanding the regulation of overwintering diapause molecular mechanisms in Culex pipiens pallens through comparative proteomics.

To reveal overwintering dormancy (diapause) mechanisms of Culex pipiens pallens (L.), global protein expression differences at three separate time points represent nondiapause, diapause preparation and overwintering diapause phases of Cx. pipiens pallens were compared using iTRAQ. Cx. pipiens pallens females accumulate more lipid droplets during diapause preparation and overwintering diapause maintenance than during the nondiapause phase. A total of 1030 proteins were identified, among which 1020 were quantified and compared. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Domain and Clusters of Orthologous Groups (COG) analyses revealed key groups of proteins, pathways and domains differentially regulated during diapause preparation and overwintering diapause maintenance phases in this mosquito, including major shifts in energy production and conversion, fatty acid metabolism, the citrate (TCA) cycle, and the cytoskeletal reorganization pathway. Our results provide novel insight into the molecular bases of diapause in mosquitoes and corroborate previously reported diapause-associated features in invertebrates. More interestingly, the phototransduction pathway exists in Cx. pipiens pallens, in particular, actin, rather than other proteins, appears to have substantial role in diapause regulation. In addition, the differential changes in calmodulin protein expression in each stage implicate its important regulatory role of the Cx. pipiens pallens biological clock. Finally, 24 proteins were selected for verification of differential expression using a parallel reaction monitoring strategy. The findings of this study provide a unique opportunity to explore the molecular modifications underlying diapause in mosquitoes and might therefore enable the future design and development of novel genetic tools for improving management strategies in mosquitoes.

Rhodium-Catalyzed Direct Ortho C-H Arylation Using Ketone as Directing Group with Boron Reagent.

A general method for selective ortho C-H arylation of ketone, with boron reagent enabled by rhodium complexes with excellent yields, is developed. The transformation is characterized by the use of air-stable Rh catalyst, high monoarylation selectivity, and excellent yields of most of the substrates.