Copper-catalyzed reactions of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct N-arylpyrazoles and diaryl sulfones.

Herein, an economical copper-catalyzed reaction of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct both N-arylpyrazoles and diaryl sulfones has been developed. Both the p-toluenesulfonyl anion and the 3-arylpyrazole intermediates were formed in situ from N-tosylhydrazones. Subsequently, the former reacted rapidly with diaryliodonium salts to give diaryl sulfones and aryl iodide intermediates, and the latter reacted with aryl iodide to give N-arylpyrazoles under copper-catalyzed conditions. Using unsymmetrical mesityl phenyliodonium salts as substrates, mesityl p-toluenesulfide was obtained as the major product. This reaction took full advantage of the "waste" part of substrates to form an extra diaryl sulfone.

Circular RNAs: novel regulators of resistance to systemic treatments in breast cancer.

Systematic treatments including chemotherapy, endocrine therapy, and HER2-targeted therapy are important therapeutic approaches to breast cancer. However, drug resistance is a major barrier to achieving a cure in breast cancer (BC) patients. Hence, it is urgent to gain insight into the drug-resistance mechanisms in order to improve the prognosis of BC patients. Genetic alternations, epigenetic alternations, and other non-genetic mechanisms such as BC stem-like cells, metabolic reprogramming, and tumor microenvironment contribute to drug resistance of BC. With the development of single-cell sequencing of circulating tumor cell and next-generation sequencing of matched pre- and post- progression tumor biopsies or ctDNA from BC patients with drug resistance, new mechanisms of resistance are being discovered. An increasing number of microRNAs and long non-coding RNAs have been found to be associated with the drug resistance of BC. However, there are few reports on the role of circular RNAs (circRNAs) as master regulators of drug resistance. Therefore, there is still much to say in the field of drug resistance-related circRNAs. In this review, we mainly focus on literature evidence for the detailed mechanisms associated with systematic treatments' resistance of BC and how circRNAs intensify or weaken drug resistance. Exogenous expression of tumor suppressive circRNAs or knockdown of oncogenic circRNAs has been verified to reverse drug resistance of BC cells, which highlights that circRNAs may function as potential biomarkers and/or therapeutic targets of BC. Treatment targeting abnormally expressed circRNAs alone or combined with other systemic treatments may be a promising approach to conquering drug resistance.

Synthesis, Characterization of Spirocyclic λ3 -Iodanes and Their Application to Prepare 4,1-Benzoxazepine-2,5-diones and 1,3-Diynes.

Herein, a [3+2] cycloaddition of aza-oxyallylic cations with ethynylbenziodoxolones for synthesis of new λ3 -iodanes containing spirocyclic 4-oxazolidinone has been developed. This cyclic λ3 -iodanes display stability in air and excellent solubility in organic solvent. Using them as substrate, both the 4,1-benzoxazepine-2,5-diones and symmetrical 1,3-diynes derivatives were afforded in high yield under copper(I)-catalyzed conditions.

A base-promoted cascade reaction of α,ß-unsaturated N-tosylhydrazones with o-hydroxybenzyl alcohols: highly regioselective synthesis of N-sec-alkylpyrazoles.

An efficient method for the synthesis of N-sec-alkylpyrazoles through a base-promoted cascade cyclization/Michael addition reaction of α,ß-unsaturated N-tosylhydrazones with ortho-hydroxybenzyl alcohols has been developed. The desired products containing di- or triaryl groups at the same carbon atom were afforded in good to excellent yields with excellent regioselectivities (>20 : 1). Moreover, a three-component reaction of ortho-hydroxybenzyl alcohols, α,ß-unsaturated N-tosylhydrazones and saturated N-tosylhydrazones also took place to afford pyrazoles in good yields. This reaction offers a new route to triarylmethanes with a simple operation and is applicable for large-scale synthesis.

Two Odorant-Binding Proteins of the Dark Black Chafer (Holotrichia parallela) Display Preferential Binding to Biologically Active Host Plant Volatiles.

The dark black chafer (DBC), Holotrichia parallela, is an important pest of multiple crops. Insect host-searching behaviors are regulated by host plant volatiles. Therefore, a better understanding of the mechanism linking the chemosensory system to plant volatiles at the molecular level will benefit DBC control strategies. Based on antenna transcriptome data, two highly expressed antenna-specific odorant-binding proteins (HparOBP20 and 49) were selected to identify novel DBC attractants using reverse chemical ecology methods. We expressed these proteins, mapped their binding specificity, and tested the activity of the plant volatiles in the field. The ligands used in the binding specificity assays included 31 host-plant-associated volatiles and two sex pheromone components. The results showed that (1) HparOBP20 and 49 are involved in odor recognition; (2) these proteins bind attractive plant volatiles strongly and can therefore be employed to develop environmentally friendly DBC management strategies; and (3) the green-leaf volatile (Z)-3-hexenyl acetate shows a high binding affinity to HparOBP20 (Ki = 18.51 µM) and HparOBP49 (Ki = 39.65 µM) and is highly attractive to DBC adults, especially females. In the field test, a (Z)-3-hexenyl acetate trap caught an average of 13 ± 1.202 females per day, which was significantly greater than the corresponding male catch (F2,6 = 74.18, P < 0.0001). (Z)-3-Hexenyl acetate may represent a useful supplement to the known sex pheromone for DBC attraction. In the present study, the binding characteristics of two HparOBPs with host plant volatiles were screened, providing behaviourally active compounds that might be useful for DBC control, based on reverse chemical ecology.

The characteristics of konjac glucomannan octenyl succinate (KGOS) prepared with different substitution rates.

The characteristics of octenyl succinic anhydride (OSA)-modified polysaccharide could be affected by its degree of reaction. Four konjac glucomannan octenyl succinate (KGOS) samples were prepared with different substitution rates (SRs) of 1.151%, 1.514%, 1.753% and 2.247%. The critical micelle concentration (CMC) of the four KGOS materials decreased with increasing SR. Fourier transform infrared (FT-IR) spectroscopy indicated that the increase in SR had little effect on the type of acyl peak. The viscosity test indicated that with SR increase, the viscosity increased slightly at low rotational speed. The emulsion capacity (EC) and stability (ES) also increased with increasing SR, but the extent of increase was not obvious when the SR exceeded 1.753%. A similar pattern was found in confocal scanning laser microscopy (CSLM) observations and ES tests of KGOS nanoemulsions. Considering the characteristics of KGOS and the economic benefits, it is preferable to prepare KGOS with an SR of 1.514% and additions of alkalizing agent and OSA (in proportion to konjac glucomannan (KGM), w/w) of 2% and 3%, respectively, during the KGOS preparation.

Plant Volatiles Increase Sex Pheromone Attraction of Holotrichia parallela (Coleoptera: Scarabaeoidea).

Holotrichia parallela (Coleoptera: Scarabaeoidea) is a notorious pest of many crops. To improve the effectiveness of its female-produced sex pheromone (L-isoleucine methyl ester:(R)-(-)-linalool = 6:1), 14 plant volatiles, including dodecanoic acid, dodecanal, farnesol, α-farnesene, (Z)-3-hexen-1-ol, (E)-2-hexen-1-ol, (Z)-3-hexenyl acetate, (E)-2-hexenyl acetate, (R)-(+)-limonene, α-phellandrene, α-pinene, ocimene, methyl benzoate, and benzaldehyde, were individually evaluated using electroantennography and olfactometer assays. (E)-2-Hexenyl acetate and (Z)-3-hexenyl acetate were found to elicit the strongest responses in both males and females. Further testing of these two compounds in mixtures with the sex pheromone indicated that (E)-2-hexenyl acetate had a stronger synergistic effect than (Z)-3-hexenyl acetate. Field evaluations showed that mixtures of (E)-2-hexenyl acetate and the sex pheromone resulted in significantly higher catches than the sex pheromone alone. Using a 5:1 mixture of the sex pheromone and (E)-2-hexenyl acetate, the maximum number of females per trap per day was 14, showing a synergistic effect of a factor of four. For males, a 3:1 mixture of the sex pheromone and (E)-2-hexenyl acetate yielded a maximum number of 310 individuals per trap per day, equivalent to a synergistic effect of 175%. These results may provide the basis for the development of efficient pest management systems against H. parallela using plant volatiles and insect sex pheromones.

[Advances in hydrogen sulfide and hydrogen sulfide-releasing drugs].

Hydrogen sulfide (H(2)S) is considered as a new member of gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO). H2S exerts important biological effects in mammals, which has drawn more and more attention in recent years. It is proved that H(2)S has a role in the regulation of physiological and pathophysiological processes in the cardiovascular system and the nervous system. Several cardiovascular and nervous diseases are connected to H(2)S. H(2)S-releasing agents (also known as H(2)S donors) have been widely used not only as useful research tools but also potential therapeutic agents. In this review, we provide an overview of the chemistry and biology of H(2)S, and summarize the chemistry and biological activity of some natural and synthetic H(2)S donors. We introduce the developments of currently available H(2)S-releasing drugs including H(2)S-non-steroidal anti-inflammatory drugs, H(2)S-nervous system drugs and NO-H(2)S-releasing drugs. We hope this review will be a value reference in the development of H(2)S-releasing drugs in the treatment of cardiovascular and nervous diseases.

Transcriptome and tissue-specific expression analysis of Obp and Csp genes in the dark black chafer.

The dark black chafer, Holotrichia parallela, is an economically important pest in China and worldwide. Traps based on chemical communication are being developed as an alternative control measure to pesticides for this pest, and studies to reveal chemical communication mechanisms in this pest are highly desirable. To systematically analyze genes potentially involved in chemical communication in this pest, we generated a comprehensive transcriptome with combined samples derived from multiple tissues and developmental stages. A total of 43,967 nonredundant sequences (unigenes) with average length of 806 bp were obtained. These unigenes were annotated into different pathways using gene ontology analysis and cluster analysis of orthologous groups of proteins, and kyoto encyclopedia of genes and genomes. In total, 25 transcripts encoding odorant-binding proteins (OBPs) and 16 transcripts encoding chemosensory proteins (CSPs) were identified based on homology searches. Tissue-specific expression profile indicates that OBP17 and CSP7 are likely responsible for male sex pheromone recognition, whereas OBP1-4, OBP9, OBP13-14, OBP17-18, OBP20, OBP22, OBP25, CSP1-7, CSP11, and CSP12-15 are likely responsible for chemical communication between the beetle and environments. Our data shall provide a foundation for further research on the molecular aspects of chemical communication of this insect, and for comparative genomic studies with other species.

Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma.

Conventional liver targeted system focuses on delivering drugs to liver, bringing toxicity on hepatic normal tissues. The purpose of this study is to construct a new system capable of specially targeting to hepatic carcinoma instead of the whole liver. Based on the fact that nanoparticles (NPs) bound with either biotin or avidin tend to accumulate in tumors and avidin-attached reagents were quickly eliminated from blood circulation and assembled in liver, trans-resveratrol loaded chitosan nanoparticles (CS-NPs), CS-NPs with the surface modified either by biotin (B-CS-NPs) or by both biotin and avidin (A-B-CS-NPs) were prepared and their physiochemical properties were investigated. The in vitro release profiles of the three NPs all conformed to bioexponential equation. Pharmacokinetic experiment indicated that A-B-CS-NPs rapidly assembled in liver after injection, with the highest liver targeting index of 2.70, while the modification of biotin attenuated the liver targeting ability of NPs. Inhibitory study on HepG2 cells declared that compared to trans-resveratrol solution and CS-NPs, both B-CS-NPs and A-B-CS-NPs significantly improved the anticancer activity. When incubated with HepG2 cells at high concentration for longer time, A-B-CS-NPs exhibited superior cytotoxicity than B-CS-NPs. This study exclaims that A-B-CS-NPs may be a potent drug delivery vector specially targeting to hepatic carcinoma.

[Tumor suppressor role of chromatin-remodeling factor ARID1A].

The mammalian SWI/SNF complex is one of ATP-dependent chromatin-remodeling complexes, which plays important roles in cell proliferation, differentiation, development and tumor suppression. ARID1A (AT-rich interactive domain-containing protein 1A) is a large subunit of SWI/SNF complex, and also an ARID family member with non- sequence-specific DNA binding activity. ARID1A is a tumor suppressor gene which is frequently mutated in many cancers, such as ovarian, bladder and gastric cancers. ARID1A can suppress cell proliferation through the up-regulation of p21 and the down-regulation of E2F-responsive genes. These findings on ARID1A and its role of tumor suppression contribute to understanding the mechanism of cancer development and developing new therapy for cancer.It is introduced in the review that ARID1A basic characteristic, related to cancer development, and biological role for full understanding of ARID1A.

[Discoverer of genetic principle for antibody diversity--Susumu Tonegawa].

Susumu Tonegawa is a Japanese molecular biologist who won the Nobel Prize for Physiology or Medicine in 1987 for his discovery of "the genetic principle for generation of antibody diversity". Susumu Tonegawa is also famous for his important contributions on neuroscience, who explored the molecular and cellular mechanisms underlying learning and memory. In this article, the life and research on Susumu Tonegawa was introduced.

Synthesis and antibacterial activity of new fluoroquinolones containing a cis- or trans-cyclohexane moiety.

New quinolone derivatives bearing a cis- or trans-cyclohexane side chain at the C-7 position have been synthesized and evaluated for their antibacterial activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using the agar dilution method. The activities of compound 53 against these three bacteria were superior to those of the reference drug lomefloxacin. Compounds bearing a cis-cyclohexane side chain generally exhibited greater antibacterial activity than their corresponding trans-isomers.

4-Chloro-phenyl 2-oxo-2H-chromene-3-carboxyl-ate.

In title compound, C(16)H(9)ClO(4), the coumarin ring system is approximately planar [maximum deviation = 0.056 (1) Å] and is oriented with respect to the benzene ring at an angle of 22.60 (7)°. Inter-molecular C-H⋯O hydrogen bonding is present in the crystal.

[3-Bromo-meth-yl-1-(4-methyl-phenyl-sulfon-yl)azetidin-3-yl]methanol.

The asymmetric unit of the title compound, C(12)H(16)BrNO(3)S, contains two independent mol-ecules. In each mol-ecule, the azetidine four-membered ring adopts a nearly planar conformation, the maximum deviations being 0.087 (3) and 0.079 (3) Å. The mean azetidine plane is twisted by 75.2 (2) and 73.6 (2)° with respect to the plane of the benzene ring in the two independent mol-ecules. The crystal packing is stabilized by O-H⋯O hydrogen bonds.

Deltaline from Delphinium delavayi Franch.

THE TITLE COMPOUND [SYSTEMATIC NAME: 6ß,10-dihy-droxy-1α,14α,16ß-trimeth-oxy-4-methyl-7ß,8-(methyl-enedi-oxy)-20-ethyl-aconitan-6-yl acetate], C(27)H(41)NO(8), is a C(19)-diterpenoid alkaloid and a major diterpenoid alkaloid component of the roots of Delphinium delavayi Franch. var. pogonanthum (Hand.-Mazz.) W. T. Wang. The mol-ecule has a lycoctonine carbon-atom skeleton with four six-membered rings and three five-membered rings among; three of the six-membered rings adopt chair conformations with the fourth adopting a boat conformation while all of the five-membered rings exhibit envelope conformations. Inter-molecular O-H⋯O hydrogen bonding is present in the crystal structure.

[The progress of TMPRSS2-ETS gene fusions and their mechanism in prostate cancer].

The gene fusions between transmembrane protease serine 2 (TMPRSS2) and E26 (ETS) transcription factors are present in over 50% of patients with prostate cancer. TMPRSS2-ERG is the most common gene fusion type. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. Both androgen receptor binding and genotoxic stress induce chromosomal proximity and TMPRSS2-ETS gene fusions. TMPRSS2-ERG gene fusion functions as a biomarker for prostate cancer, which can be easily detected in urine. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions.