Regioselective Synthesis of α-Quaternary Amino Acid Derivatives Enabled by Photoinduced Energy Transfer.

α-Quaternary amino acids have found application in many biologically relevant compounds and pharmaceuticals. Although there are many methods for the synthesis of α-quaternary amino acids, most of them are mainly realized with the aid of transition metals and complex ligands. We present herein a 2,7-Br-4CzIPN catalyzed regioselective alkylation of azlactones with redox-active esters via radical-radical couplings. Strikingly, this approach is devoid of any metal or additive and shows broad scope and superior sensitive functional group compatibility.

Visible-light-promoted regioselective hydrocarboxylation of allenes with formate salt and CO2.

Visible-light-promoted hydrocarboxylation of allenes with formate salt and CO2 was developed for the first time using commercially available [Ir(ppy)2(dtbbpy)]PF6 as a photocatalyst. This strategy provides an efficient and practical method to access ß,γ-unsaturated linear carboxylic acids in moderate yields with complete regioselectivity.

Effects of Antarctic Krill Meal in Diet on Reproductive Performance and Embryo Quality of Eriocheir sinensis.

A 60-day feeding trial was conducted to evaluate the impact of dietary Antarctic krill meal on the reproductive performance and embryo quality of the Chinese mitten crab, Eriocheir sinensis. Three diets were formulated, incorporating varying levels of Antarctic krill meal at 0% (Diet K0), 10% (Diet K10), and 20% (Diet K20), with a control group fed razor clam Sinonovacula constricta. Each diet was randomly assigned to three replicate tanks, each stocked with 5 males and 10 females. Male and female weights were 145.38 ± 8.01 and 102.57 ± 9.73 g, respectively. The results revealed no significant differences in weight gain rate, specific growth rate, and survival rate. However, the hepatopancreatic weight and hepatopancreas index of female crabs in each group decreased, while gonadal weight and gonadosomatic index increased significantly after 60 days, with Diet K20 showing the highest values. Egg production and fecundity of female crabs reached their peak in Diet K20, with no significant differences in reproductive indices among all groups. The phospholipid content in Diet K20 was significantly higher than in the other groups (P < 0.05). Cholesterol contents in Diet K0 and the control group were significantly higher than in Diet K10 and K20 (P < 0.05). No significant differences were observed in egg diameter, egg weight, moisture, crude protein, and crude fat between the groups. The content of C20 : 2 and C20 : 4n6 was highest in Diet K0, with a significant difference compared to Diet K10 (P < 0.05). However, no significant differences were found in the total content of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids among all groups. Based on the research findings, it is recommended that the optimal level of Antarctic krill meal in diets is 20%.

Characterization of pneumococcal serotype 7F in vaccine conjugation.

Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20.To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process.

Lithium Triethylborohydride (LiHBEt3)-Promoted Hydrosilylation of Allenes to Prepare (E)-Allylsilanes.

A transition-metal-free hydrosilylation of allenes is reported herein by using commercially available lithium triethylborohydride (LiHBEt3) as the catalyst. Both mono- and disubstituted allenes could be hydrosilylated with primary or secondary silanes effectively. This reaction represents an environmental and economic method to prepare (E)-allylsilanes in good yields along with decent selectivities.

Photoredox-Catalyzed Phosphonocarboxylation of Allenes with Phosphine Oxides and CO2.

Phosphonocarboxylation of allenes with diarylphosphine oxides and CO2 via visible-light photoredox catalysis was developed for the first time. This work provided practical and sustainable access to highly valuable but otherwise difficult-to-access linear allylic ß-phosphonyl carboxylic acids in moderate yields with exclusive regio- and stereoselectivity. This method was also characterized by step and atom economy and transition-metal free and mild conditions. Preliminary mechanistic studies suggested that allyl-methyl carbanion species are the key intermediates.

Preparation of (E)-1,3-Enyne Derivatives through Palladium Catalyzed Hydroalkynylation of Allenes.

A general and efficient palladium catalyzed hydroalkynylation of allenes was developed to produce synthetically versatile (E)-1,3-enyne derivatives with high regio- and stereoselectivity. This catalytic system proceeded under mild conditions and was compatible with a broad range of substrates, especially for allenes without electron-bias groups. This work further broadens the synthetic potential of these scaffolds in organic synthesis and medicinal chemistry.

Fingerprint detection in the mid-infrared region based on guided-mode resonance and phonon-polariton coupling of analyte.

Mid-infrared absorption spectroscopy is an effective method for detecting analyte fingerprints without labeling, but the inherent loss of metals in current methods is a main issue. Here, a sensing scheme was proposed that uses an all-dielectric grating metasurface and angular scanning of polarized light, and then it was verified by numerical simulation. The proposed fingerprint detection scheme could effectively couple a guided-mode resonance spectrum peak with the characteristic peak of the analyte's phonon-polariton in the mid-infrared region, significantly enhancing the interaction between light and the analyte. The novel scheme would realize broadband enhancement to detect a variety of substances, and facilitate mid-infrared sensing and analysis of trace substances.

Optimal target localisation and eight-year outcome for subthalamic stimulation in patients with Parkinson's disease.

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a useful therapy to improve motor functions and reduce dependence on medication in patients with Parkinson's disease (PD). The purpose of the study is to assess the long-term clinical outcomes of STN-DBS and to determine the optimal placement of electrodes that for the most positive outcomes. METHODS: A consecutive series of 42 PD patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) before and after STN-DBS lead implantation. Postoperatively, patients were evaluated during both the medication 'ON' period (medication suppressed symptoms) and the medication 'OFF' period (when medication failed to suppress symptoms), and the results were compared to the baseline values prior to surgery. Follow-up assessments, focusing on motor functions, were performed 1, 3, 5, and 8 years after the initial implantation surgery. The locations of electrodes were measured and compared against the clinical outcomes. RESULTS: STN-DBS remarkably improved the UPDRS-II, -III, and -IV dyskinesia and motor fluctuation scores in the OFF-medication condition when compared to baseline values. In addition, the dose of levodopa needed to elicit an effect declined sharply in the OFF-medication condition. Over time, the axial signs progressively worsened even with continuous stimulation and a levodopa response. The location of electrodes correlated with the most beneficial outcomes was the dorsal STN margin. CONCLUSIONS: Our results confirm that overall, stimulation-induced motor improvement is still evident after 8 years. However, the primary best outcome declines with the progressive loss of favourable axial signs.

Opportunity for marine fisheries reform in China.

China's 13th Five-Year Plan, launched in March 2016, provides a sound policy platform for the protection of marine ecosystems and the restoration of capture fisheries within China's exclusive economic zone. What distinguishes China among many other countries striving for marine fisheries reform is its size-accounting for almost one-fifth of global catch volume-and the unique cultural context of its economic and resource management. In this paper, we trace the history of Chinese government priorities, policies, and outcomes related to marine fisheries since the 1978 Economic Reform, and examine how the current leadership's agenda for "ecological civilization" could successfully transform marine resource management in the coming years. We show how China, like many other countries, has experienced a decline in the average trophic level of its capture fisheries during the past few decades, and how its policy design, implementation, and enforcement have influenced the status of its wild fish stocks. To reverse the trend in declining fish stocks, the government is introducing a series of new programs for sustainable fisheries and aquaculture, with greater traceability and accountability in marine resource management and area controls on coastal development. As impressive as these new plans are on paper, we conclude that serious institutional reforms will be needed to achieve a true paradigm shift in marine fisheries management in China. In particular, we recommend new institutions for science-based fisheries management, secure fishing access, policy consistency across provinces, educational programs for fisheries managers, and increasing public access to scientific data.

Pyrazole synthesis via a cascade Sonogashira coupling/cyclization of N-propargyl sulfonylhydrazones.

An efficient approach for the preparation of pyrazoles via a Pd(ii)/Cu(i)-catalyzed Sonogashira coupling/cyclization of N-propargyl sulfonylhydrazones has been established. In this study, we firstly report the strategic use of a Sonogashira reaction to construct pyrazole rings in a one step operation. With a broad range of functional group tolerance, bioactive 3-CF3 pyrazoles can also be synthesized easily through this domino coupling/cyclization sequence.

Conjugated Microporous Polymer as Heterogeneous Ligand for Highly Selective Oxidative Heck Reaction.

A series of pyridine-type ligands containing C≡C bonds were designed and synthesized for selective oxidative Heck reaction. These ligands were utilized as functional units and integrated into the skeleton of conjugated microporous polymers. 6,6'-diiodo-2,2'-bipyridine and 1,3,5-triethynylbenzene were polycondensed via Sonogashira cross-coupling strategy to afford CMP-1 material. The resultant CMP-1 was used as a heterogeneous catalytic ligand for the PdII-catalyzed oxidative Heck reaction with high linear selectivity. The linear selectivity of CMP-1 is about 30 times higher than that of bipyridine-based monomer ligand. This work opens a new front of using CMP as an intriguing platform for developing highly efficient catalysts in controlling the regioselectivity in organic reactions.

Silver(I)-Catalyzed Tandem Sigamatropic Rearrangement/1,3-H Shift/6π Aza-electrocyclization of N-Propargylic Hydrazones: A Mild Synthetic Route to 1,6-Dihydropyridazines.

A highly efficient AgOTf catalyzed [3,3] sigmatropic rearrangement/1,3-H shift/6π aza-electrocyclization cascade reaction of N-propargylic hydrazones has been developed. This method provides a new mild synthetic route to various polysubstituted 1,6-dihydropyridazines including the 3-CF3-substituted ones with high selectivity.

Characteristics of subthalamic oscillatory activity in parkinsonian akinetic-rigid type and mixed type.

OBJECTIVE: To explore neurons with ß oscillatory activity in the subthalamic nucleus (STN) in relation to parkinsonian motor signs. METHODS: We studied 27 patients with Parkinson's disease (PD) who underwent electrode implantation for STN deep brain stimulation. Thirteen patients were classified as akinetic-rigid (AR) type and 14 patients were classified as mixed type. Microelectrode recording was performed in the STN and the electromyogram (EMG) was simultaneously recorded. Single-unit and spectral analyses were performed. Coherence analysis was used to explore the relationship between ß oscillatory activity and EMG activity. Unpaired t-test and chi-square were used to compare the differences between the two PD types. RESULTS: Of 130 neurons identified in the AR type, 43.8% were ß oscillatory neurons (mean: 21.3 ± 6.87 Hz, ßFB) and 0.8% were tremor frequency oscillatory neurons (4-6 Hz, TFB). Of 102 neurons identified in the mixed type, 19.6% were ß oscillatory neurons and 26.5% were TFB oscillatory neurons. There was a significant difference in proportion of neurons with ßFB and TFB oscillations between the two PD groups. Additionally, 12% of the ßFB oscillatory neurons were coherent with limb EMG of the AR type, but there was no coherence in the mixed type. Most oscillatory neurons were localized in the dorsal portion of the STN. CONCLUSION: The STN ßFB oscillatory neurons correlate with parkinsonian rigidity-bradykinesia. The high proportion of ßFB oscillatory neurons found in the AR type of PD is indirect evidence for their importance in generating motor impairment.

Effects of vitrification protocol on the lactate dehydrogenase and total atpase activities of chinese mitten crab Eriocheir sinensis embryos.

BACKGROUND: Vitrification is the most promising option for the cryopreservation of fish embryos but requires high concentrations of potentially toxic cryoprotectants that can also cause cell injury, and affect cell division, enzymatic activities and cell metabolism. The effect of cryopreservation on the enzyme activity in crustacean embryos has not been reported. OBJECTIVES: The aim of this study was to investigate the effects of a vitrification protocol on the enzyme activity of different stages of Eriocheir sinensis embryos. The goal was to select an appropriate stage and vitrifying solution for the cryopreservation of embryos from this crustacean. MATERIALS AND METHODS: Embryos from E.sinensis at five development stages (cleavage, blastula, gastrula, eyed stage and heart beating stage) were submitted to six kinds of cryoprotectant incorporation protocol with a five stepwise method. Six vitrifying solutions were prepared by combining cryoprotectants PG, MeOH, Me(2)SO and DMF in different proportions (A: 20 % PG + 20 % DMF; B: 20 % MeOH+20 % DMF; C: 20 % PG+20 % MeOH; D:20 % PG+10 % MeOH+10 % DMF; E:20 % Me2SO+20 % PG;F:20 % Me(2)SO+20 % MeOH). After incubation in the six kinds of vitrification solutions, embryos were loaded into cryo-tubes and plunged into liquid nitrogen. The activities of two cytoplasmic enzymes, LDH and total ATPase were analyzed in control embryos, those subjected to the cryoprotectant solutions and in frozen/thawed embryos. RESULTS: The cryoprotectant incorporation protocol had important effects on the enzymatic activities, and different vitrifying solutions had distinct effects on the enzymatic activities. The early stage embryo was sensitive to the toxic effect of the cryoprotectants, with a significant drop in total ATPase in comparison with fresh, control embryos. Enzymatic activities dropped significantly after vitrification, indicating cell damage and loss of cytoplasmic enzymes. CONCLUSION: The composition of vitrifying solutions had different effects on the loss of the enzyme activity, and the later stage embryo was more resistant to the effect of vitrification.

Adaptive alterations on gill Na⁺, K⁺-ATPase activity and mitochondrion-rich cells of juvenile Acipenser sinensis acclimated to brackish water.

Understanding the physiological changes and osmoregulatory strategy is critical for anadromous species to adapt to large changes between freshwater and marine environments. In this study, juvenile Chinese sturgeon (Acipenser sinensis) were acclimated for 2 months to freshwater (FW, c. 0‰) and brackish water (BW, 15‰). Blood was assessed for changes in osmolality and ions. Gill tissue was assayed for Na(+), K(+)-ATPase (NKA) activity and immunohistochemical analysis on mitochondria-rich cells (MRCs). Serum osmolality and ions concentrations (Na(+), Cl(-) and K(+)) examined, except K(+), increased significantly in those specimens adapted to BW. However, the variations were within the range of effective hyperosmotic adaptation. The specific activity of gill NKA of juveniles adapted to BW was significantly higher (c. 1.6 times) than that of fish adapted to FW. MRCs were mainly presented in the interlamellar region of the filament and at the base of the lamella in either FW- or BW-acclimated individuals. In BW, the number and size of MRCs on filaments greatly increased. However, there was no significant difference in the number and size of the MRCs at the lamella region. Results show that juvenile Chinese sturgeon keep osmotic homeostasis in hyperosmotic environments by increasing gill NKA activity and MRCs' size and number, which is similar to other sturgeons and euryhaline teleosts.

Synthesis of 4-Arylidenepyrazolones by a Gold-Catalyzed Cyclization/Arylidene Group Transfer Cascade of N-Propioloyl Hydrazones.

An efficient gold-catalyzed cyclization/arylidene group transfer cascade reaction of N-propioloyl hydrazones has been developed. This method provides a novel approach for the synthesis of various functionalized 4-arylidenepyrazolones.

Chromatographic resolution of closely related species in pharmaceutical chemistry: dehalogenation impurities and mixtures of halogen isomers.

In recent years, the use of halogen-containing molecules has proliferated in the pharmaceutical industry, where the incorporation of halogens, especially fluorine, has become vitally important for blocking metabolism and enhancing the biological activity of pharmaceuticals. The chromatographic separation of halogen-containing pharmaceuticals from associated isomers or dehalogenation impurities can sometimes be quite difficult. In an attempt to identify the best current tools available for addressing this important problem, a survey of the suitability of four chromatographic method development platforms (ultra high-performance liquid chromatography (UHPLC), core shell HPLC, achiral supercritical fluid chromatography (SFC) and chiral SFC) for separating closely related mixtures of halogen-containing pharmaceuticals and their dehalogenated isosteres is described. Of the 132 column and mobile phase combinations examined for each mixture, a small subset of conditions were found to afford the best overall performance, with a single UHPLC method (2.1 × 50 mm, 1.9 µm Hypersil Gold PFP, acetonitrile/methanol based aqueous eluents containing either phosphoric or perchloric acid with 150 mM sodium perchlorate) affording excellent separation for all samples. Similarly, a survey of several families of closely related halogen-containing small molecules representing the diversity of impurities that can sometimes be found in purchased starting materials for synthesis revealed chiral SFC (Chiralcel OJ-3 and Chiralpak IB, isopropanol or ethanol with 25 mM isobutylamine/carbon dioxide) as well as the UHPLC (2.1 × 50 mm, 1.8 µm ZORBAX RRHD Eclipse Plus C18 and the Gold PFP, acetonitrile/methanol based aqueous eluents containing phosphoric acid) as preferred methods.

Silver(I)-catalyzed annulation for the regioselective synthesis of N-imino-γ-carbolinium ylides from hydrazones of indole-3-carbonyl derivatives and propargylic alcohols.

A regioselective efficient synthetic approach to N-imino-γ-carbolinium ylides via AgOTf-catalyzed iminoannulation has been developed. This transformation proceeds via a silver(i) triflate-catalyzed consecutive Friedel-Crafts reaction/N-C bond formation sequence between the readily available indole derivatives and propargylic alcohols.

Selective synthesis of 4-(sulfonyl)-methyl-1H-pyrazoles and (E)-4,5-dihydro-1H-pyrazoles from N-allenic sulfonylhydrazones.

Selective synthesis of 4-(sulfonyl)-methyl-1H-pyrazoles and (E)-4,5-dihydro-1H-pyrazoles from N-allenic sulfonylhydrazones with sulfonyl group migrations has been developed. A key feature of these reactions is that the migrations of the sulfonyl groups to different positions can be controlled by changing the Lewis acids.