Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis.

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

Regio- and Stereoselective Reductive Coupling of Alkynes and Crotononitrile.

A new regio- and stereoselective reductive coupling of alkynes and crotononitrile has been developed via visible light organophotoredox cobalt dual catalysis. A variety of enantioenriched homoallylic nitriles bearing a stereodefined trisubstituted alkene have been easily synthesized with good to excellent regio- (up to >20:1 rr), stereo- (>20:1 E/Z), and enantioselectivity (up to 98% ee) control under mild conditions. The corresponding nitrile products were smoothly converted into various chiral building blocks. Remarkably, a simple organic base together with water have been utilized as hydrogen sources in this photoinduced reductive reaction.

Boryl Radical Activation of Benzylic C-OH Bond: Cross-Electrophile Coupling of Free Alcohols and CO2 via Photoredox Catalysis.

A new strategy for the direct cleavage of the C(sp3)-OH bond has been developed via activation of free alcohols with neutral diphenyl boryl radical generated from sodium tetraphenylborate under mild visible light photoredox conditions. This strategy has been verified by cross-electrophile coupling of free alcohols and carbon dioxide for the synthesis of carboxylic acids. Direct transformation of a range of primary, secondary, and tertiary benzyl alcohols to acids has been achieved. Control experiments and computational studies indicate that activation of alcohols with neutral boryl radical undergoes homolysis of the C(sp3)-OH bond, generating alkyl radicals. After reducing the alkyl radical into carbon anion under photoredox conditions, the following carboxylation with CO2 affords the coupling product.

[Testosterone replacement therapy improves metabolic indexes of the patients with hypogonadism: A meta-analysis].

OBJECTIVE: To systematically evaluate the effect of testosterone replacement therapy (TRT) on metabolic indexes in patients with hypogonadism. METHODS: We searched the databases of CNKI, CBM, Wanfang Data, VIP, PubMed, Medline, Embase and Cochrane Library from the establishment to May 2021 for clinical randomized controlled trials (RCT) on the improvement of metabolic indexes of the patients with hypogonadism treated by TRT. According to the inclusion and excretion criteria, we screened the literature, extracted the data and evaluated the quality of the included RCTs, followed by statistical analysis with the STATA15.1 software. RESULTS: Totally 19 RCTs with 1 553 cases were included. Compared with placebo, TRT effectively reduced the levels of fasting plasma glucose (FPG) and fasting insulin (FINS), improved Homeostatic Model Assessment-insulin resistance (HOMA-IR), decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), increased the body mass index (BMI), lowered the waist circumference (WC), but elevated the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients. No statistically significant differences were observed in the improvement of glycosylated hemoglobin (HbA1c) and triglyceride (TG) between the TRT-treated patients and placebo controls. The results of Egger's and Begg's tests showed no significant publication bias among the studies. CONCLUSION: TRT can significantly improve metabolic indexes in patients with hypogonadism, though further studies are needed to confirm its long-term efficacy and safety in patients with metabolic disorders.

Highly Regio- and Enantioselective Reductive Coupling of Alkynes and Aldehydes via Photoredox Cobalt Dual Catalysis.

A Co-catalyzed highly regio- and enantioselective reductive coupling of alkynes and aldehydes has been developed under visible light photoredox dual catalysis. A variety of enantioenriched allylic alcohols have been obtained by using unsymmetrical internal alkynes and commercially available catalyst, chiral ligand, and reagents. It is noteworthy that this approach has considerable advantages, such as excellent regio- (>95:5 for >40 examples), stereo- (up to >95:5 E/Z), and enantioselectivity (92-99% ee, >35 examples) control, mild reaction conditions, broad substrate scope, and good functional group compatibility, making it a great improvement to enantioselective alkyne-aldehyde reductive coupling reactions.

[Ecologically suitable areas for growing Scutellaria baicalensis worldwide: an analysis based on GMPGIS].

This paper explored the ecologically suitable areas for growing Scutellaria baicalensis using Geographic Information System for Global Medicinal Plants(GMPGIS), to figure out the resource distribution of S. baicalensis worldwide and provide a scientific basis for its scientific introduction. A total of 349 S. baicalensis sampling sites were selected all over the world for GMPGIS-based analy-sis of the ecologically suitable areas with six ecological factors including annual average temperature, average temperature during the coldest season, average temperature during the warmest season, average annual precipitation, average annual relative humidity, and annual average illumination and soil type as the ecological indexes. The results demonstrated that the ecologically suitable areas for growing S. baicalensis were mostly located in the Northern hemisphere, and the suitable areas in the United States, China, and Russia accounted for 19.25%, 18.66%, and 13.15% of the total area worldwide, respectively. In China, the Inner Mongolia, Heilongjiang province, and Yunnan province occupied the largest proportions of the total area, namely 14.28%, 8.72%, and 6.18%, respectively. As revealed by ecological factors of each sampling site, S. baicalensis was resistant to low temperature but not to high temperature. The adaptive range of average annual precipitation is narrower than that of average annual air humidity. The suitable soils were mainly inceptisol, alfisol, and fluvisol. High temperature and rainy climate or excessively high soil bulk density was not conducive to the growth of S. baicalensis. The adoption of GMPGIS enabled to obtain areas with the greatest ecological similarity for S. baicalensis, which were reliable data supporting the exploration of resource distribution and reasonable introduction of S. baicalensis.

Copper(II)-Assisted Ligand Fragmentation Leading to Three Families of Metallamacrocycle.

We present an unprecedented copper(II)-assisted organic ligand fragmentation process under basic conditions leading to several ligands within three families of metallamacrocycle, Cu6, Cu8, and Cu16. The sequential multistep reaction include (i) the deprotonation of the starting alcohol, 1,2-bis(3,5-dimethyl-pyrazol-1-yl)ethane-1,2-diol (H2bdped) to its diolate bdped followed by complexation through six bonds (µ6) to three copper atoms in a ring, (ii) the breaking of the ethane-pyrazole C-N bonds by the different solvent alcohols to form 1-(3,5-dimethyl-pyrazol-1-yl)-2-methoxyethane-1,2-diolate (dpmed) or 2-(3,5-dimethyl-pyrazol-1-yl)-2-hydroxyacetate (dpet), while retaining coordination to the copper centers and (iii) the final step to ethane-1,1,2,2-tetraolate, C2H2O44- (et). Importantly, the latter product, only observed on two previous occasions, occupies the core of Cu6 and Cu16 through exceptionally eight coordination bonds (µ8). Its alkyl esters, 2-alkoxyethane-1,1,2-triolate (met, eet, and pet), also occupy the central parts of Cu8 but forming six bonds (µ6) instead. The other product, 3,5-dimethylpyrazolate (dp), acts as peripheral bridges (µ2) but it is not involved in coordination if the starting salt is copper acetate, this may be a consequence of acetate being a better µ2-chelating ligand. In the presence of an oxidizing agent, K2Cr2O7, C2H2O44- (et) is oxidized to oxalate, C2O42- (ox). Thus, an additional µ3-hydroxide and µ4-oxalate in Cu16 widen the complexity of the structures, not to mention the range of coordination geometries of the copper centers, though in the present cases they can be classed in only two types: distorted square-planar and square-pyramid. In addition to single-crystal crystallography, the results from different techniques such as IR, ESI-MS, optical UV-vis, and SQUID magnetometry help in the characterization of these rare metallamacrocycles made from unexpected and in situ generated ligands. We believe the results of the organic transformations are highly relevant to von Liebig's benzil-benzilic acid rearrangement.

Pd/Cu Cocatalyzed Oxidative Tandem C-H Aminocarbonylation and Dehydrogenation of Tryptamines: Synthesis of Carbolinones.

The Pd/Cu cocatalyzed oxidative tandem C-H aminocarbonylation and dehydrogenation was developed, affording carbolinones with molecular oxygen as the terminal oxidant. Natural product strychnocarpine and its derivatives were prepared conveniently using this strategy.

Self-Organization into Preferred Sites by MgII, MnII, and MnIII in Brucite-Structured M19 Cluster.

The search for functional materials, for example those aiming at microelectronics, magnetic recording, and catalysis, often ventures into mixed metal systems to achieve optimization of the properties. Thus, understanding site preference and self-organization is crucial but hard to implement. Herein, we present a system whereby MgII, MnII, and MnIII ions selectively locate exact positions within the Brucite-structured cluster, Mn13Mg6, [MnIII⊂MgII6⊂MnII9MnIII3( L)18(OH)12(N3)6](ClO4)6·12CH3CN, H L = 1-(hydroxymethyl)-3,5-dimethylpyrazolate). The MnIII being small (78 pm) takes up the core position; while 6 MgII (86 pm) are located in the inner ring, and the 9 large MnII (97 pm) and 3 MnIII occupy the outer ring. The factors (a) ionic radii, (b) regularity in coordination geometry, oxophilicity, and softness of MgII compared to MnII, and (c) Jahn-Teller distortion of MnIII may all be implicated synergistically. Electrospray ionization mass spectrometry reveals the M19 disc remains an integral unit when crystals are dissolved, and exchange between Mg and Mn occurs within the disc during its formation. Diamagnetic MgII doping insulates the magnetic exchange between the central MnIII and those in the outer ring, thus giving an overall antiferromagnetic exchange interaction between nearest-neighbors of the outer ring. The work reveals the underlying rule for site-preference of main group metal versus transition metal in disc-like Brucite-structured cluster and provides an elegant new avenue to assemble heterometallic clusters in a stepwise fashion.

Comparison of enzyme-linked immunosorbent assay with indirect immunofluorescence assay for the diagnosis of Mycoplasma pneumoniae infection.

BACKGROUND: The study aimed to compare enzyme-linked immunosorbent assay (ELISA) with indirect immunofluorescence assay (IFA) in the diagnosis of Mycoplasma pneumoniae infection. METHODS: From March 2016 to May 2017, 180 patients suspected with M. pneumoniae infection were enrolled. The SeroMP kit using ELISA and PNEUMOSLIDE kit using IFA were performed in parallel to detect the IgM antibodies against M. pneumoniae. Cohen's kappa statistics were used to assess the agreement between the ELISA and IFA assays, multivariate logistic regression analysis was used to evaluate risk factors for the discordance between the ELISA and IFA assays. RESULTS: The mean age of the enrolled subjects was 46.6 ± 21.1 years. For detection of M. pneumoniae infection, the positivities of the ELISA and IFA assays were 15.6% (95% CI: 11.0%, 21.6%) and 10.0% (95% CI: 6.4%, 15.3%), respectively. The total positivity was 19.4% (95% CI: 14.3%, 25.8%). The agreement between the ELISA and IFA assays was low (κ = 0.117, P < 0.001). Variables associated with discordant results between ELISA and IFA assays in multivariate analysis were as follows: male (OR: 0.366; 95% CI: 0.149, 0.899; P < 0.05), age (>33 years old; OR: 0.313; 95% CI: 0.129, 0.758; P < 0.05). CONCLUSION: In detection of M. pneumoniae infection, low agreement was found in IgM assays between the ELISA and IFA methods, female and younger age were significant risk factors for the discordance. A combination of ELISA and IFA tests would be recommended, in order to detect more patients suspected of M. pneumoniae infection in clinical practice.

[Study of extracting natural resources of Chinese medicinal materials planted area in Luoning of Henan province based on UAV of low altitude remote sensing technology and remote sensing image of satellite].

The study is aimed to effectively obtain the planting area of traditional Chinese medicine resources. The herbs used as the material for traditional Chinese medicine are mostly planted in natural environment suitable mountainous areas. The UAV low altitude remote sensing data were used as the samples and the GF-2 remote sensing images were applied for the data source to extract the planting area of Salvia miltiorrhiza and Artemisia argyi in Luoning county combined with field investigation. Remote sensing satellite data of standard processing obtain specific remote sensing data coverage. The UAV data were pre-processed to visually interpret the species and distribution of traditional Chinese medicine resources in the sample quadrat. Support vector machine( SVM) was used to classify and estimate the area of traditional Chinese medicine resources in Luoning county,confusion matrix was used to determine the accuracy of spatial distribution of traditional Chinese medicine resources. The result showed that the application of UAV of low altitude remote sensing technology and remote sensing image of satellite in the extraction of S. miltiorrhiza and other varieties planting area was feasible,it also provides a scientific reference for poverty alleviation policies of the traditional Chinese medicine Industry in local areas.Meanwhile,research on remote sensing classification of Chinese medicinal materials based on multi-source and multi-phase high-resolution remote sensing images is actively carried out to explore more effective methods for information extraction of Chinese medicinal materials.

Intermolecular C-H Amidation of (Hetero)arenes to Produce Amides through Rhodium-Catalyzed Carbonylation of Nitrene Intermediates.

Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium-catalyzed three-component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene-intermediates and direct C-H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N2 as the only by-product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh-nitrene intermediate.

A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree.

Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically heterogeneous group of inherited neuropathies. Here, we report a five-generation family of eight affected individuals with CMT disease type 2, CMT2. Genome-wide linkage analysis showed that the disease phenotype is closely linked to chromosomal region 10p13-14, which spans 5.41 Mb between D10S585 and D10S1477. DNA-sequencing analysis revealed a nonsense mutation, c.1455T>G (p.Tyr485(∗)), in exon 8 of dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1) in all eight affected individuals, but not in other unaffected individuals in this family or in 250 unrelated normal persons. DHTKD1 mRNA expression levels in peripheral blood of affected persons were observed to be half of those in unaffected individuals. In vitro studies have shown that, compared to wild-type mRNA and DHTKD1, mutant mRNA and truncated DHTKD1 are significantly decreased by rapid mRNA decay in transfected cells. Inhibition of nonsense-mediated mRNA decay by UPF1 silencing effectively rescued the decreased levels of mutant mRNA and protein. More importantly, DHTKD1 silencing was found to lead to impaired energy production, evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels. In conclusion, our data demonstrate that the heterozygous nonsense mutation in DHTKD1 is one of CMT2-causative genetic alterations, implicating an important role for DHTKD1 in mitochondrial energy production and neurological development.

Aerobic oxidation of alcohols and the synthesis of benzoxazoles catalyzed by a cuprocupric coordination polymer (Cu(+)-CP) assisted by TEMPO.

A Cu(+)-CP based on the tetranuclear unit {[(HSQPA)2Cu4(bipy)4]·2H2O}n·2nH2O has been constructed through Cu(2+) salt, 2-(sulfonylquinlium-8-yloxy)phthalic acid (H3SQPA), and 4,4'-bipyridine (bipy). This Cu(+)-CP combined with 2,2,6,6-tetramethylpiperidine-1-oxyl as the cocatalyst is an effective catalyst for aerobic oxidation of alcohols and the synthesis of benzoxazoles and can be recycled at least four times without losing its catalytic activity.

Preparative Isolation of Two Prenylated Biflavonoids from the Roots and Rhizomes of Sinopodophyllum emodi by Sephadex LH-20 Column and High-Speed Counter-Current Chromatography.

Two prenylated biflavonoids, podoverines B-C, were isolated from the dried roots and rhizomes of Sinopodophyllum emodi using a Sephadex LH-20 column (SLHC) and high-speed counter-current chromatography (HSCCC). The 95% ethanol extract was partitioned with ethyl acetate in water. Target compounds from the ethyl acetate fraction were further enriched and purified by the combined application of SLHC and HSCCC. n-Hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v) was chosen as the two phase solvent system. The flow rate of mobile phase was optimized at 2.0 mL·min(-1). Finally, under optimized conditions, 13.8 mg of podoverine B and 16.2 mg of podoverine C were obtained from 200 mg of the enriched sample. The purities of podoverines B and C were 98.62% and 99.05%, respectively, as determined by HPLC. For the first time, podoverins B and C were found in the genus Sinopodophyllum. Their structures were determined by spectroscopic methods (HR-ESI-MS, ¹H-NMR, (13)C-NMR, HSQC, HMBC). Their absolute configurations were elucidated by comparison of their experimental and calculated ECD spectra. The cytotoxic activities were evaluated against MCF-7 and HepG2 cell lines. The separation procedures proved to be practical and economical, especially for trace prenylated biflavonoids from traditional Chinese medicine.

Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels.

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

N-Heterocyclic carbene (NHC)-modulated Pd/Cu cocatalyzed three-component synthesis of 2,6-diarylquinolines.

Two new NHC adducts of cyclopalladated ferrocenylpyrazine complexes 1-2 have been prepared and characterized. An efficient NHC-modulated Pd/Cu cocatalyzed three-component coupling reaction for the synthesis of 2,6-diarylquinolines from aminobenzyl alcohols, aryl ketones, and arylboronic acids in air is described. The reaction involves oxidation, cyclization and Suzuki reactions. The luminescence of the resulting arylquinolines 3-30 was also investigated.

Vanadium-catalyzed oxidative Strecker reaction: α-C-H cyanation of para-methoxyphenyl (PMP)-protected primary amines.

We describe an oxidative Strecker reaction that allows for direct cyanation of para-methoxyphenyl (PMP)-protected primary amines. A vanadium(V) complex was used as the catalyst and TBHP as the oxidant. The cyanation occurs at the α-C position bearing either an alkyl or an aromatic group. This method provides a direct access to α-aminonitrile from amines with one-carbon extension.

Long Non-coding RNA COX10-AS1 Promotes Glioma Progression by Competitively Binding miR-1-3p to Regulate ORC6 Expression.

Glioma is one of the most common and difficult to cure malignant primary tumors of the central nervous system. Long non-coding RNA (lncRNA) has been reported to play important functions in biological processes of many tumors, including glioma. In our study, we aimed to reveal the role and molecular mechanisms of lncRNA COX10-AS1 in regulating the progression of glioma. First of all, we showed that lncRNA COX10-AS1 was significantly increased in glioma tissues and cell lines, and high-expressed COX10-AS1 was associated with a poor prognosis in glioma patients. Moreover, through performing the functional experiments, including CCK-8, colony formation and Transwell assays, we confirmed that COX10-AS1 ablation curbed cell proliferation, migration and invasion in glioblastoma (GBM) cells. In addition, we uncovered that there existed a regulatory relationship that COX10-AS1 upregulated OCR6 by sponging miR-1-3p in GBM cells, and the following rescue assays demonstrated that both miR-1-3p downregulation and origin recognition complex subunit 6 (ORC6) overexpression rescued cell viability, migration and invasion in the COX10-AS1-deficient GBM cells. Consistently, we also verified that COX10-AS1 promoted tumorigenesis of the GBM cells in vivo through modulating the miR-1-3p/ORC6 axis. On the whole, our findings indicated a novel ceRNA pattern in which COX10-AS1 elevated OCR6 expression via sponging miR-1-3p, therefore boosting tumorigenesis in glioma, and we firstly discussed the underlying mechanisms by which the COX10-AS1/miR-1-3p/ORC6 axis affected the progression of glioma.

The adult, pupa, and larva of a new species of Gnaptorina Reitter, 1887 (Coleoptera, Tenebrionidae, Blaptini) from the Tibetan Plateau, with molecular phylogenetic inferences.

The adult, pupa and larva of a new species, Gnaptorina (Gnaptorina) lhorongica Li, sp. nov., from northeastern Xizang, China are described and illustrated. The species was identified using molecular phylogenetic analyses based on three mitochondrial fragments and one nuclear gene fragment (COI, Cytb, 16S, and 28S-D2). The taxonomic status of the new species is confirmed using a combination of molecular and morphological datasets. This study provides valuable molecular and morphological data for phylogenetic studies of the tribe Blaptini.