Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China.

BACKGROUND: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. METHODS: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. FINDINGS: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. CONCLUSIONS: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.

Enantioselective Total Syntheses of the Cephalotaxus Alkaloids (-)-Fortuneicyclidins A and B and (-)-Cephalotine B.

Fortuneicyclidins A and B are a pair of recently isolated Cephalotaxus alkaloids with an unprecedented rearranged polycyclic skeleton possessing multiple complex stereocenters and functionalization. In this work, highly stereocontrolled asymmetric total syntheses for title alkaloids were outlined. Key features include an underexplored Ir-catalyzed α-allylation of aldehyde to strategically install a vicinal N-substituted quaternary center and a tertiary stereocenter, Heck and RCM reactions to construct the critical polycyclic framework rapidly, two different tandem oxidation-transannular aldol cyclization processes, one through ozonolysis and another via Swern oxidation, to forge the last ring for fortuneicyclidins A and B, respectively. In this approach, the challenging C-2 hydroxyl group can be installed stereospecifically.

Enantioselective Total Synthesis of the Cephalotaxus Alkaloid (-)-Cephalotine A.

Cephalotine A, a recently isolated Cephalotaxus alkaloid, was first synthesized enantioselectively through three critical reactions. SmI2 -mediated radical cyclization of lactone and aldehyde to forge the final ring system, Chang's iridium-catalyzed C-H amidation to construct pyrrolidone stereoselectively, and Carreria's dual Ir/amine catalyzed allylation to install the vicinal tertiary stereocenters.

Total Syntheses of Cinchona Alkaloids via Photoredox-Catalyzed Deoxygenative Arylation.

Metallaphotoredox-enabled deoxygenative arylation of alcohols is a recently developed robust synthetic strategy for sp2-sp3 coupling by MacMillan. Inspired by this method, we report herein its first utilization in natural product total synthesis through realizing the coupling of 4-bromo-quinoline or 4-bromo-6-methoxyquinoline with quincorine or quincoridine, respectively. The alcohols were de novo synthesized in racemic form by a key step of the intramolecular Diels-Alder reaction or in an enantioselective manner by Ir/amine dual-catalyzed allylation. All members of the cinchona alkaloids could be prepared efficiently.

Catalytic, Asymmetric Total Synthesis of (+)-α-, (+)-ß-, (+)-γ-, and (-)-δ-Lycorane.

The first collectively asymmetric total synthesis of all members of lycorane, including (+)-α, (+)-ß, (+)-γ, and (-)-δ, in a catalytic manner has been achieved. The cornerstone of this synthesis features an asymmetric, stereodivergent Ir/amine dual catalytic α-allylation of 2-phthalimidoacetaldehyde.

Genetic Characteristics and Pathogenicity of a Novel Porcine Epidemic Diarrhea Virus with a Naturally Occurring Truncated ORF3 Gene.

Porcine epidemic diarrhea virus (PEDV) is the major pathogen that causes diarrhea and high mortality in newborn piglets, with devastating impact on the pig industry. To further understand the molecular epidemiology and genetic diversity of PEDV field strains, in this study the complete genomes of four PEDV variants (HN2021, CH-HNYY-2018, CH-SXWS-2018, and CH-HNKF-2016) obtained from immunized pig farms in central China between 2016 to 2021 were characterized and analyzed. Phylogenetic analysis of the genome and S gene showed that the four strains identified in the present study had evolved into the subgroup G2a, but were distant from the vaccine strain CV777. Additionally, it was noteworthy that a new PEDV strain (named HN2021) belonging to the G2a PEDV subgroup was successfully isolated in vitro and it was further confirmed by RT-PCR that this isolate had a large natural deletion at 207-373 nt of the ORF3 gene, which has never been reported before. Particularly, in terms of pathogenicity evaluation, colostrum deprivation piglets challenged with PEDV HN2021 showed severe diarrhea and high mortality, confirming that PEDV HN2021 was a virulent strain. Hence, PEDV strain HN2021 of subgroup G2a presents a promising vaccine candidate for the control of recurring porcine epidemic diarrhea (PED) in China. This study lays the foundation for better understanding of the genetic evolution and molecular pathogenesis of PEDV.

Ir-Catalyzed Asymmetric Total Syntheses of Bisdehydrotuberostemonine D, Putative Bisdehydrotuberostemonine E and Structural Revision of the Latter.

The first total syntheses of bisdehydrotuberostemonine D (8) and putative bisdehydrotuberostemonine E (9), two novel pyrrole Stemona alkaloids, along with the synthesis of bisdehydrotuberostemonine (3) have been completed in 12-13 steps. Our strategy harnesses the power of transition-metal-catalyzed reactions employing Ir, Ru, and Pd, in particular Ir-catalyzed asymmetric allylation of aldehydes, two distinct protocols recently developed by Carreira and Krische, respectively. The threefold use of Ir catalysis, first in the stereodivergent construction of two contiguous stereocenters at C (9,10) and then in rapid formation of the two γ-butyrolactone motifs, enabled the route's efficiency. Through this work, the originally assigned structure of bisdehydrotuberostemonine E (9) should be revised as 18α-bisdehydrotuberostemonine D (8*).

Asymmetric Total Synthesis of (+)-Quinocarcinamide.

The first asymmetric total synthesis of (+)-quinocarcinamide (3), an enantiomer of the natural oxidation product from antitumor antibiotic (-)-quinocarcin (1), is described. Key steps include an iridium-catalyzed asymmetric allylic amidation of racemic alcohol 9, olefin cross-metathesis followed by a SN2' to forge tetrahydroisoquinoline, and stereocontrolled 1,3-dipolar cycloaddition between a facilely generated azomethine ylide and tert-butyl acrylate to construct the diazabicyclo[3.2.1]octane ring.

Gram-Scale, Seven-Step Total Synthesis of (-)-Colchicine.

Herein we report a streamlined, gram-scale total synthesis of (-)-colchicine that takes only 7 easy steps, with an overall yield of 27-36%. To warrant the synthetic efficiency and practicality of (-)-colchicine, we tactically utilized a modified version of a powerful Ir-catalyzed amidation reported by Carreira to install the key chiral C-7 acetamido group, Suzuki and biomimetic phenol oxidative coupling, and Banwell-inspired cyclopropane ring cleavage to construct (-)-colchicine precisely and rapidly. Remarkably, a described strategy also can shorten the synthesis of allocolchicinoid to 4 steps.

Synthetic Studies toward Parvistemoline Using Asymmetric Ir/Amine-Catalyzed Allylation.

The common, key tricyclic core of stemona alkaloids parvistemonine (1) and parvistemoline (2), whose synthetic efforts have not reported yet, was constructed through a new strategy in which three contiguous stereogenic centers were set by using Carreira's asymmetric Ir/amine-catalyzed allylation of aldehyde with α-vinylfurfuryl alcohol and Ellman's sulfinamide chiral auxiliary, respectively. The furan ring was especially designed to act as the precursor of the butyrolactone while establishing the significant chirality.

Enantioselective Iridium-Catalyzed Allylic Alkylation of Racemic Branched Alkyl-Substituted Allylic Acetates with Malonates.

The regio- and enantioselective allylic substitution of branched alkyl-substituted allylic acetates employing malonates has been achieved through a process that calls for Krische's π-allyliridium C,O-benzoate catalyst. The protocol reported herein can be applied to a diverse set of branched alkyl substrates that are generally not well tolerated in the other two types of Ir-catalyzed allylation.

Morinda officinalis polysaccharides improve meat quality by reducing oxidative damage in chickens suffering from tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is the common leg disease in commercial broilers. However, the effects of TD on meat quality and the protective of Morinda officinalis polysaccharide (MOP) are largely unknown. Three hundred broiler chicks (one-day-old) were equally allocated into control (CON), TD and MOP-treated groups for 15 days. The results indicated that TD influenced morphology and meat quality-related parameters of the breast muscle, and changed the activity and mRNA expression of antioxidant enzymes in plasma and breast muscles. Moreover, metabolomics profiling of breast muscle revealed that the main altered metabolites 4-guanidinobutyric acid and chenodeoxycholic acid, which are related to meat quality and oxidative stress. Additionally, 500 mg/L MOP effectively restored the content of meat metabolites and oxidative damage. These findings suggest that oxidative damage caused by TD may affect meat quality in broilers by changing the content of breast muscle metabolites and that MOP supplementation has a restorative effect.

Electrically precise control of the spin polarization of electronic transport at the single-molecule level.

Compared with the conventional magnetic means (such as ferromagnetic contacts), controlling a spin current by electrical methods could largely reduce the energy consumption and dimensions of nano-devices, which has become a focus of research in spintronics. Inspired by recent progress in the synthesis of an iron-based metal-organic nanostructure, we investigate the spin-dependent electronic transport of the molecule of Fe3-terpyridine-phenyl-phenyl-terpyridine-Fe3 (Fe3-TPPT-Fe3) through first-principles calculations, and propose a three-terminal device without ferromagnetics. By applying a gate voltage, not only the spin polarization can be switched between 100% and -100% to achieve a dual-spin filter, but also its fine regulation can be realized, where the transmission with any ratio of spin-up to spin-down electron numbers is achievable. Analysis shows that the particular transmission spectra are the key mechanism, where two peaks reside discretely on both sides of the Fermi level with opposite spins. Such a feature is found to be robust to the number of Fe atoms and TPPT chain length, suggesting that it is an intrinsic feature of such systems and very conducive to practical applications. The electrical control (such as an electric field) of spin polarization is realized at the single-molecule level, showing great application potential.

Asymmetric Total Syntheses of (-)-Fennebricin A, (-)-Renieramycin J, (-)-Renieramycin G, (-)-Renieramycin M, and (-)- Jorunnamycin A via C-H Activation.

Collective total synthesis of five tetrahydroisoquinoline alkaloids including the first total synthesis of (-)-fennebricin A and (-)-renieramycin J has been accomplished. The synthesis features employing a single common amino acid to symmetrically construct the pentacycle of title alkaloids. The palladium-catalyzed arylation of alanine-derived amide developed by Yu was tactically utilized to afford unnatural amino acid building block rapidly and practically. The structure of synthetic (-)-renieramycin M has been confirmed by single crystal X-ray analysis for the first time.

Construction and immunogenicity of a gE/gI/TK-deleted PRV based on porcine pseudorabies virus variant.

Pseudorabies (PR) caused by re-emerging pseudorabies virus (PRV) variant has outbroken among PRV vaccine-immunized swine herds on many Chinese pig farms, with severe socioeconomic consequences since late 2011. Here, a gE/gI/TK-deleted recombinant virus (rPRV NY-gE-/gI-/TK-) was constructed based on PRV NY strain from 2012 through homologous DNA recombination and gene-editing technology termed clustered regularly interspaced palindromic repeats (CRISPR)/associated (Cas9) system. The rPRV NY-gE-/gI-/TK- strain showed similar growth kinetics to the parental PRV NY strain in vitro, and was safe for mice. Sixty mice were injected subcutaneously (s.c.) twice with 106.0 TCID50 of rPRV NY-gE-/gI-/TK- and DMEM, respectively, with two-week interval. The levels of PRV gB antibodies and neutralizing antibodies against PRV NY in mice immunized with rPRV NY-gE-/gI-/TK- were higher than those in the DMEM control group. The number of T lymphocyte subclasses CD3+, CD4+ and CD8+ in rPRV NY-gE-/gI-/TK--immunized mice was higher than that in DMEM-injected mice. After challenge with 106.0 TCID50 PRV NY at 42 dpi, all rPRV NY-gE-/gI-/TK--immunized mice survived without exhibiting any pathological lesions in different tissues and intranuclear eosinophilic inclusions of the brain, and the viral genomic copy numbers in various organs of mice were obviously lower than DMEM group. These results showed the rPRV NY-gE-/gI-/TK- could be a promising next-generation vaccine to control now epidemic PR in China.

Catalytic, Enantioselective Formal Synthesis of Monoterpene Indole Alkaloid (-)-Alstoscholarine.

A catalytic, enantioselective formal synthesis of monoterpene indole alkaloid (-)-alstoscholarine is described. The synthesis employs an Ir-amine dual catalyzed asymmetric allylation of aldehyde 8 with 3-indolyl vinyl carbinol derivative 7 to furnish chiral aldehyde 6 as a key asymmetric step. Other key reactions include the construction of the 2-ketopyrrole moiety by Nicolaou's method and Tf2O promoted Pictet-Spengler cyclization to access Zhu's intermediate 3.

Tabernabovines A-C: Three Monoterpenoid Indole Alkaloids from the Leaves of Tabernaemontana bovina.

Three monoterpenoid indole alkaloids (MIAs), tabernabovines A-C (1-3), were isolated from Tabernaemontana bovina. They were elucidated by spectroscopic data and computational calculations. Unlike precursors of MIAs, strictosidine and alstrostine A, alkaloid 1 consists of tryptamine and secologanin in a 2:1 ratio. Alkaloid 2 is a cage compound, and 3 possesses a bridged ring. Tabernabovine A exhibited inhibitory activity against NO production with IC50 44.1 µM compared to l-NMMA with IC50 of 48.6 µM.

Iridium-Catalyzed Enantioselective Allylation of Aryl Enamides and Enecarbamates.

Aromatic enamide and enecarbamate as a novel type of nucleophile in the asymmetric allylation of branched, racemic allylic alcohols to give homoallylic ketones has been described. Enabled by Carreira's chiral Ir (P, olefin) complex, the reactions proceed in good yields with excellent enantioselectivities.

Enantioselective Ir-Catalyzed Allylic Alkylation of Racemic Allylic Alcohols with Malonates.

Ir-catalyzed enantioselective allylic alkylation of branched racemic allylic alcohols with malonates is described. Enabled by Carreira's chiral Ir/(P, olefin) complex, the method described allows allylic substitution with various aromatic alcohols and malonates with excellent enantioselectivity. The malonates could be used directly as efficient nucleophiles without the need of preactivation.