Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

TGF-ß1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM+ B cells apoptosis via Bax/Bcl2-Caspase3 pathway.

Transforming growth factor ß1 (TGF-ß1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-ß1 expression via activating Tregs. Besides, recombinant porcine TGF-ß1 decreased the percentage of CD21+ B cells within the lymphocyte population in vitro. We further found that TGF-ß1 reduced the IgA-secreting B cell numbers and also inhibited plasma cell differentiation. Additional investigations revealed that TGF-ß1 induced the apoptosis of IgM+ B cells in both peyer's patches (PPs) and peripheral blood (PB) through the activation of the Bax/Bcl2-Caspase3 pathway. Conversely, the application of the TGF-ß1 signaling inhibitor SB431542 significantly antagonized the TGF-ß1-induced reduction of IgA secretion and B cell apoptosis and restored plasma cell differentiation. Collectively, TGF-ß1 plays an important role in regulating the survival and differentiation of porcine IgA-secreting B cells through the classical mitochondrial apoptosis pathway. These findings will facilitate future mucosal vaccine designs that target the regulation of TGF-ß1 for the control of enteric pathogens in the pig industry.

Spot Detection for Laser Sensors Based on Annular Convolution Filtering.

Spot detection has attracted continuous attention for laser sensors with applications in communication, measurement, etc. The existing methods often directly perform binarization processing on the original spot image. They suffer from the interference of the background light. To reduce this kind of interference, we propose a novel method called annular convolution filtering (ACF). In our method, the region of interest (ROI) in the spot image is first searched by using the statistical properties of pixels. Then, the annular convolution strip is constructed based on the energy attenuation property of the laser and the convolution operation is performed in the ROI of the spot image. Finally, a feature similarity index is designed to estimate the parameters of the laser spot. Experiments on three datasets with different kinds of background light show the advantages of our ACF method, with comparison to the theoretical method based on international standard, the practical method used in the market products, and the recent benchmark methods AAMED and ALS.

Enantioselective Synthesis of Chiral Amides by a Phosphoric Acid Catalyzed Asymmetric Wolff Rearrangement.

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α-aryl-α-diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes. The phosphoric acid not only accelerates ketene capture by amines to form a single configuration of aminoenol intermediates but also promotes an enantioselective proton-transfer reaction of the intermediates to yield the products. Mechanistic studies elucidated the reaction pathway and explained how the catalyst expedited the transformation and controlled the enantioselectivity.

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds.

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

Preparation and identification of monoclonal antibodies against porcine CD103.

Dendritic cells (DCs) play an important role in activating, regulating, and maintaining the immune response. CD103+ DCs, one of the DC subpopulations, mainly function in the mucosal immune response. They are responsible for capturing and carrying antigens to the relevant lymph nodes to activate the downstream immune responses. However, there is limited available information regarding the function of CD103+ DCs in the porcine mucosal immune response. In this study, two monoclonal antibodies (mAbs) against porcine CD103 were prepared, and their applications were evaluated by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and flow cytometry. The produced mAbs (7F3 and 9H3) were both IgG1 subtype with κ chains in the light chain. The 7F3 recognizes a linear epitope (PDLRPRAQVYFSDLE) while 9H3 recognizes another linear epitope (QILDEGQVLLGAVGA). The prepared mAbs could be used in vivo to detect the cells expressing CD103 molecules, giving wide applications of both mAbs. In conclusion, this study successfully prepared 2 mAbs against CD103 protein, and they showed applicability in vivo experiments, which will provide the basis for the study of porcine mucosal immunity. KEY POINTS: • Preparation of monoclonal antibodies against porcine CD103 molecule • Analysis of the distribution of CD103 protein on different cells is possible • Exploration of the CD103+ DCs function in porcine mucosal immunity is possible.

Intrathecal therapy for tuberculous meningitis: propensity-matched cohort study.

OBJECTIVE: The study aimed to determine the safety and efficacy of intrathecally administered isoniazid (INH) and prednisolone in addition to systemic anti-TB therapy and compare it with systemic anti-TB therapy alone in adult patients with tuberculous meningitis (TBM). METHODS: In this retrospective study, patients were categorized into two groups: Group A patients received systematic anti-TB therapy alone, Group B patients received IT INH (50 mg) and prednisolone (25 mg) twice a week together with the same standard systemic anti-TB therapy as Group A, in addition to the standard systemic anti-TB therapy. Functional outcomes were compared between the two groups in a prosperity-matched cohort using propensity score matching (PSM) method. RESULTS: A total of 198 patients with TBM were enrolled. After PSM, 30 patients from each group were analyzed, so that there was no significant difference in the characteristics of the two groups. Mortality at follow-up was significantly lower among patients receiving additional IT therapy (4/30, 13.3%) compared with matched patients receiving systemic anti-TB therapy alone (11/30, 36.7%, P value = 0.037). CONCLUSIONS: In this propensity score-matched cohort, the addition of IT INH and prednisolone to systemic anti-TB therapy could be effective for the better outcome among adult TBM patients. Further large-scale, prospective, and randomized controlled trials are warranted to the best timing and indication of IT therapy.

Discovery of degradable niclosamide derivatives able to specially inhibit small cell lung cancer (SCLC).

Small cell lung cancer (SCLC) is exceedingly tough to treat and easy to develop resistance upon long use of the first-line drug carboplatin or radiotherapy. Novel medicines effective and specific against SCLC are greatly needed. Herein, we focused on the discovery of such a medicine by exploring a drug niclosamide with repurposing strategy. Initial screening efforts revealed that niclosamide, an anthelmintic drug, possessed the in vitro anticancer activity and an obvious sensitivity towards SCLC. This observation inspired the evaluation for two different kinds of niclosamide derivatives. 2 with a degradable ester as a linker exhibited the comparable activity but slightly inferior selectivity to SCLC, by contrast, the cytotoxicities of 4 and 5 with non-degradable ether linkages completely disappeared, clearly validating the importance of 2-free hydroxyl group or 2-hydroxyl group released in the antitumor activity. Mechanism study unfolded that, similar to niclosamide, 2 inhibited growth of cancer cells via p 53 activation and subsequent underwent cytochrome c dependent apoptosis. Further structural modification to afford phosphate sodium 8 with significantly enhanced aqueous solubility (22.1 mg/mL) and a good selectivity towards SCLC demonstrated more promising druggability profiles. Accordingly, niclosamide as an attractive lead hold a huge potential for developing targeted anti-SCLC drugs.

Enantioselective Diarylcarbene Insertion into Si-H Bonds Induced by Electronic Properties of the Carbenes.

Catalytic enantioselection usually depends on differences in steric interactions between prochiral substrates and a chiral catalyst. We have discovered a carbene Si-H insertion in which the enantioselectivity depends primarily on the electronic characteristics of the carbene substrate, and the log(er) values are linearly related to Hammett parameters. A new class of chiral tetraphosphate dirhodium catalysts was developed; it shows excellent activity and enantioselectivity for the insertion of diarylcarbenes into the Si-H bond of silanes. Computational and mechanistic studies show how the electronic differences between the two aryls of the carbene lead to differences in energies of the diastereomeric transition states. This study provides a new strategy for asymmetric catalysis exploiting the electronic properties of the substrates.

Insertion of Alkylidene Carbenes into B-H Bonds.

We have developed a protocol for insertion of alkylidene carbenes into the B-H bonds of amine-borane adducts, enabling, for the first time, the construction of C(sp2)-B bonds by means of carbene-insertion reactions. Various acyclic and cyclic alkenyl borane-amine adducts were prepared from readily accessible starting materials in good to high yields and were subsequently subjected to a diverse array of functional group transformations. The unprecedented spiro B-N heterocycles prepared in this study have potential utility as building blocks for the synthesis of pharmaceuticals. Preliminary mechanistic studies suggest that insertion of the alkylidene carbenes into the B-H bonds of the amine-borane adducts proceeds via a concerted process involving a three-membered-ring transition state.

[on oligozoospermia and asthenospermia].

OBJECTIVE: To observe the clinical effect of Yihechun Capsules (YHC) on oligozoospermia and asthenospermia. METHODS: A total of 181 male patients with infertility were randomly divided into a YHC+Levocarnitine (LC) group (n = 93, including 42 cases of oligozoospermia, 20 cases of asthenospermia and 31 cases of oligoasthenospermia) and an LC control group (n = 88, including 39 cases of oligozoospermia, 22 cases of asthenospermia and 27 cases of oligoasthenospermia), the former treated with YHC (ï¼»0.3 g per capsuleï¼½, once 4 capsules, bid, 30 minutes after meal) combined with LC oral liquid (2－3 g/d, tid, at mealtime) and the latter with LC oral liquid only (2－3 g/d, tid, at mealtime). After 3 months of treatment, comparisons were made between the two groups of patients in sperm concentration, the percentages of grade a and grade a+b sperm, and the rate of pregnancy. RESULTS: Of the 181 patients, 5 in the YHC+LC group and 2 in the LC control group failed to complete the course of treatment. There were no statistically significant differences between the two groups of patients in the baseline sperm concentration and the percentages of grade a and grade a+b sperm (P > 0.05), wich were all markedly increased in both the YHC+LC and the LC control groups (P < 0.05) after 3 months of treatment. And the patients of the YHC+LC group, compared with the controls, showed even more significant increases, as the oligozoospermia patients in sperm concentration (ï¼»21.07 ± 6.98ï¼½ vs ï¼»16.56 ± 1.82ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»27.53 ± 3.34ï¼½% vs ï¼»26.88 ± 1.35ï¼½%, P < 0.05) and grade a+b sperm (ï¼»53.32 ± 3.16ï¼½% vs ï¼»52.63 ± 2.48ï¼½%, P < 0.05), the asthenospermia patients in sperm concentration (ï¼»26.36 ± 3.37ï¼½ vs ï¼»24.42 ± 2.21ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»25.28 ± 4.64ï¼½% vs ï¼»21.32 ± 3.28ï¼½%, P < 0.05) and grade a+b sperm (ï¼»49.19 ± 2.87ï¼½% vs ï¼»45.64 ± 1.78ï¼½%, P < 0.05), and the oligoasthenospermia patients in sperm concentration (ï¼»19.38 ± 3.39ï¼½ vs ï¼»18.75 ± 1.35ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»22.65 ± 4.81ï¼½% vs ï¼»21.31 ± 2.42ï¼½%, P < 0.05) and grade a+b sperm (ï¼»48.74 ± 5.61ï¼½% vs ï¼»44.36 ± 1.32ï¼½%, P < 0.05). The pregnancy rate was dramatically higher in the YHC+LC than in the LC control group (36.4% ï¼»32/88ï¼½ vs 15.1% ï¼»13/86ï¼½, P < 0.01). CONCLUSIONS: Yihechun Capsules combined with Levocarnitine oral liquid is evidently effective for the treatment of oligozoospermia and asthenospermia.

PCR-based reverse genetics strategy for bluetongue virus recovery.

BACKGROUND: Bluetongue virus (BTV), an emerging insect vector mediated pathogen affecting both wild ruminants and livestock, has a genome consisting of 10 linear double-stranded RNA genome segments. BTV has a severe economic impact on agriculture in many parts of the world. Current reverse genetics (RG) strategy to rescue BTV mainly rely on in vitro synthesis of RNA transcripts from cloned complimentary DNA (cDNA) corresponding to viral genome segments with the aid of helper plasmids. RNA synthesis is a laborious job which is further complicated with a need for expensive reagents and a meticulous operational procedure. Additionally, the target genes must be cloned into a specific vector to prepare templates for RNA transcription. RESULT: In this study, we have developed a PCR based BTV RG system with easy two-step transfection. Viable viruses were recovered following a first transfection with the seven helper plasmids and a second transfection with the 10 PCR products on the BSR cells. Further, recovered viruses were characterized with indirect immunofluorescence assays (IFA) and gene sequencing. And the proliferation properties of these viruses were also compared with wild type BTV. Interestingly, we have identified that viruses containing the segment 2 of the genome from reassortant BTV, grew slightly slower than the others. CONCLUSION: In this study, a convenient PCR based RG platform for BTV is established, and this strategy could be an effective alternative to the original available BTV rescue methods. Furthermore, this RG strategy is likely applicable for other Orbiviruses.

Nummular Headache: 2 Cases With Good Beta Blocker Responses and a Narrative Review.

OBJECTIVE: To report 2 new nummular headache (NH) cases and review the clinical features and management of NH. BACKGROUND: NH is a coin-shaped headache with a fixed shape and size. Since the first case series was reported by Pareja, approximately 300 cases have been reported. However, the latest treatment status and pathogenesis of NH remain unclear. METHODS: Two new NH cases with improved symptomatic responses to metoprolol were reported. We also conducted a narrative review of cases published in English aiming to provide the newest information about the clinical features and management of NH. RESULTS: Two NH patients with skin depressions within the painful area experienced significantly improvement with metoprolol. The literature review showed that NH was mainly moderate-to-severe in 77.8% (186/239) of the patients. Sensory dysfunction and focal trophic changes were reported in 47.8% (149/312) and 3.8% (12/312) of the patients, respectively. Gabapentin was the most commonly used and effective prophylactic, with a responder rate of 67.9% (55/81). Botulinum toxin type A was used for refractory NH, with an effective rate of 81.8% (9/11). Ten patients from the previous studies were prescribed ß-adrenergic blockers without any relief, and none of them reported focal tropic changes. CONCLUSIONS: NH can be a disabling headache in more than half of identified patients and requires medical intervention. As with the previous treatment recommendations, gabapentin was the most commonly used prophylactic with a good response. Our cases suggested that ß-adrenergic blockers could be a therapeutic option for NH patients with focal trophic changes within the areas.

Combination of flunarizine and transcutaneous supraorbital neurostimulation improves migraine prophylaxis.

OBJECTIVE: This study is aimed to access the efficacy and safety of combination therapy of flunarizine plus transcutaneous supraorbital neurostimulation (tSNS) compared with either flunarizine or tSNS alone for migraine prophylaxis. METHODS: Patients with episodic migraine were enrolled and randomized into 3 groups. Flunarizine 5 mg per day, or tSNS for 20 minutes daily or combination of both were prescribed consecutively for 3 months. The primary outcome measures were changes in migraine days and 50% responder rate of monthly migraine days. Secondary outcome measures were the changes in migraine intensity and intake of rescue medication. Finally, satisfaction to treatment and adverse effect were evaluated as well. RESULTS: A total of 154 were randomized and included in the analysis. After 3 months, the monthly migraine days were decreased in 3 groups and more significant in the combination group. The 50% responder rate was significantly higher (78.43%) in the combination therapy than monotherapy of flunarizine (46.15%) or tSNS (39.22%) alone. Greater reduction of migraine intensity and intake of rescue medication was observed in combination group. There was no difference of adverse events between flunarizine group and combination group (P = .89). CONCLUSION: Adding tSNS to flunarizine can improve the therapeutic efficacy of migraine prophylaxis without increasing the adverse effects. In addition, tSNS is effective and safe for migraine treatment and can be a valid option for migraineurs who are reluctant to take oral medications or for patients who experience a low-migraine frequency and/or intensity that prophylactic therapy is not indicated but desire to acquire medical intervention.

A Study of Diet and Lifestyle and the Risk of Urolithiasis in 1,519 Patients in Southern China.

BACKGROUND This study aimed to evaluate the risk factors associated with the development of urolithiasis in a population in Southern China. MATERIAL AND METHODS A questionnaire-based study was conducted between March 2017 to April 2018 that included 1,519 patients in Southern China and included questions on patient demographics, diet, and lifestyle. Patients were divided into the urolithiasis group who had urinary calculi and the control group. RESULTS There were 829 patients (54.6%) in the urolithiasis group and 690 patients (45.4%) in the control group. Using a chi-squared (χ²) test, 13 variables were found to be significantly associated with urolithiasis, including age, physical activity, and dietary factors that included high sodium, protein, fat, lean meat, vegetables, pickled food, fluid intake, drinking habits and tea consumption, and frequency and duration of physical exercise. Multivariate logistic regression analysis showed that dietary factors, including vegetables (OR, 0.856; 95% CI, 0.769-0.948), pickled foods (OR, 1.271; 95% CI, 1.030-1.357), and animal protein intake (OR, 1.138; 95% CI, 1.031-1.258), drinking strong tea (OR, 0.793; 95% CI, 0.702-0.897), fluid intake (OR, 0.758; 95% CI, 0.644-0.816), and duration of physical exercise (OR, 0.840; 95% CI, 0.808-0.973) were significantly associated with the occurrence of urolithiasis and were independent risk factors. CONCLUSIONS High consumptions of pickled foods and animal protein were the main risk factors for the development of urolithiasis in a population of southern China, but high fluid intake with a preference for strong tea, a diet of vegetables, and physical exercise were protective factors.

Highly Enantioselective Nickel-Catalyzed Intramolecular Hydroalkenylation of N- and O-Tethered 1,6-Dienes To Form Six-Membered Heterocycles.

A highly enantioselective nickel-catalyzed intramolecular hydroalkenylation of N- or O-tethered 1,6-dienes was developed by using monodentate chiral spiro phosphoramidite ligands. The reaction provides an efficient and straightforward method for preparing very useful six-membered N- and O-heterocycles with high regioselectivity as well as excellent stereoselectivity from easily accessible starting materials under mild reaction conditions. The chiral spiro nickel catalyst developed in this study represents one of the few catalysts for highly enantioselective cyclization of unconjugated dienes.

P2X4-receptor participates in EAAT3 regulation via BDNF-TrkB signaling in a model of trigeminal allodynia.

Objective Previous studies of neuropathic pain have suggested that the P2X4 purinoceptor (P2X4R) in spinal microglia is essential for maintaining allodynia following nerve injury. However, little is known about its role in inflammatory soup-induced trigeminal allodynia, which closely mimics chronic migraine status. Here, we determined the contributions of P2X4R and related signaling pathways in an inflammatory soup-induced trigeminal allodynia model. Methods P2X4R gene and protein levels in the trigeminal nucleus caudalis were analyzed following repeated dural inflammatory soup infusions. p38, brain-derived neurotrophic factor, excitatory amino acid transporter 3, c-Fos, and calcitonin gene-related peptide protein levels in the trigeminal nucleus caudalis, as well as trigeminal sensitivity, were assessed among the different groups. Immunofluorescence staining was used to detect protein localization and expression in the trigeminal nucleus caudalis. Results Repeated inflammatory dural stimulation induced trigeminal hyperalgesia and the upregulation of P2X4R. Immunofluorescence revealed that P2X4R was expressed in trigeminal nucleus caudalis microglial cells. Blockage of P2X4R produced an anti-nociceptive effect, which was associated with an inhibition of inflammatory soup-induced increases in p38, brain-derived neurotrophic factor, excitatory amino acid transporter 3, c-Fos, and calcitonin gene-related peptide protein levels. The tyrosine receptor kinase B antagonist ANA-12 reversed trigeminal allodynia and the upregulation of excitatory amino acid transporter 3, c-Fos, and calcitonin gene-related peptide, whereas the agonist 7,8-dihydroxyflavone exacerbated these effects. Double immunostaining indicated that p38 and brain-derived neurotrophic factor were mainly expressed in microglial cells, whereas excitatory amino acid transporter 3 was primarily expressed in trigeminal nucleus caudalis neurons. Conclusions These data indicate that microglial P2X4R is involved in the regulation of excitatory amino acid transporter 3 via brain-derived neurotrophic factor-tyrosine receptor kinase B signaling following repeated inflammatory dural stimulation. Microglial P2X4R activation and microglia-neuron interactions in the trigeminal nucleus caudalis may play a role in the pathogenesis of migraine chronicity, and the modulation of P2X4R activation might be a potential therapeutic strategy.

Formation of Protein Disulfide Bonds Catalyzed by OsPDIL1;1 is Mediated by MicroRNA5144-3p in Rice.

Correct folding of proteins in the endoplasmic reticulum is important for their stability and function under stress. The protein disulfide isomerase (PDI) OsPDIL1;1 is a key protein-folding catalyst in rice (Oryza sativa L.). Here, microRNA5144 (osa-miR5144-3p) is reported to mediate the formation of protein disulfide bonds via targeting OsPDIL1;1 mRNA in rice seeds and seedlings during development and under conditions of abiotic stress, respectively. Expression analysis of transgenic rice and identification of cleavage sites showed that OsPDIL1;1 mRNA is a target of osa-miR5144-3p. Expression of osa-miR5144-3p and OsPDIL1;1 was shown to be inversely regulated in developing organs and under abiotic stress. The down-regulation of osa-miR5144-3p or overexpression of OsPDIL1;1 in transgenic rice showed increased total protein-disulfide bond content, compared with the wild type. This indicates that protein-disulfide bond formation is enhanced by down-regulation of osa-miR5144-3p or overexpression of OsPDIL1;1. These transgenic rice plants also displayed strong resistance to salinity and mercury stress, in comparison with the wild type. In contrast, the transgenic rice plants overexpressing osa-miR5144-3p or down-regulating OsPDIL1;1 had a lower protein-disulfide bond content; they were susceptible to abiotic stress and produced abnormal grains with small and loosely packed starch granules. These results indicate that protein-disulfide bond formation catalyzed by OsPDIL1;1 is modulated by osa-miR5144-3p in rice during development and is involved in resistance to abiotic stress.

Design and synthesis of structurally defined heparan sulfate (HS)-FK506 conjugates as an exogenous approach to investigate biological functions of nucleus HS.

Although heparan sulfate (HS) is widely implicated in numerous physiological and pathological processes, the biological function of nucleus HS remains underexplored, largely due to its complex structure and high hydrophilic property. To supplement these efforts, ideal vehicles are drawing attention as they combine attractive features including lipid solubility for penetrating cell membrane, high affinity binding to its target receptor, metabolic stability, and no cellular actions resulting in toxicity. Herein, we develop a convenient and promising strategy to prepare HS-FK506 conjugates for membrane transport and entry into nucleus, where click chemistry takes easily place between the exocyclic allyl group of a clinic drug FK506 and thiol as a handle incorporated into HS analogues. HS derivatives for constructing the conjugates were synthesized using a cutting-edge chemoenzymatic method. Meantime, [35S] labeled 3'-phosphoadenosine 5'-phosphosulfate (PAP35S) and [14C] glucuronic acid (Glc A) were adopted to label HS-FK506 conjugates, respectively, to evaluate their efficiency of nucleus entry, as a result, 14C Glc A was sensitive, effective and reliable whereas PAP35S gave rise to a mixture of labeled compounds, hampering the understanding of structure-function relationship of nucleus HS. Compared with the corresponding HS, the amount of HS-FK506 conjugates to translocate into nucleus from radioactive assay experiments sharply increased, e.g. tridecasaccharide-FK506 1d increased by approximate 10 folds, offering a simple and robust platform for enabling hydrophilic compounds including carbohydrates to translocate into nucleus and shedding light on their biological functions.

Nickel(0)-Catalyzed Hydroarylation of Styrenes and 1,3-Dienes with Organoboron Compounds.

A Ni-catalyzed hydroarylation of styrenes and 1,3-dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox-neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni-H was developed. The Ni-catalyzed hydroarylation, combined with a Ir-catalyzed C-H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.