Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group.

Developing a general, highly efficient, and enantioselective catalytic method for the synthesis of chiral alcohols is still a formidable challenge. We report in this article the asymmetric transfer hydrogenation (ATH) of N-methyliminodiacetyl (MIDA) acylboronates as a general substrate-independent entry to enantioenriched secondary alcohols. ATH of acyl-MIDA-boronates with (het)aryl, alkyl, alkynyl, alkenyl, and carbonyl substituents delivers a variety of enantioenriched α-boryl alcohols. The latter are used in a range of stereospecific transformations based on the boron moiety, enabling the synthesis of carbinols with two closely related α-substituents, which cannot be obtained with high enantioselectivities using direct asymmetric hydrogenation methods, such as the (R)-cloperastine intermediate. Computational studies illustrate that the BMIDA group is a privileged enantioselectivity-directing group in Noyori-Ikariya ATH compared to the conventionally used aryl and alkynyl groups due to the favorable CH-O attractive electrostatic interaction between the η6-arene-CH of the catalyst and the σ-bonded oxygen atoms in BMIDA. The work expands the domain of conventional ATH and shows its huge potential in addressing challenges in symmetric synthesis.

γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway.

INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

Paper-in-Tip Bipolar Electrospray Mass Spectrometry for Real-Time Chemical Reaction Monitoring.

Capturing short-lived intermediates at the molecular level is key to understanding the mechanism and dynamics of chemical reactions. Here, we have developed a paper-in-tip bipolar electrolytic electrospray mass spectrometry platform, in which a piece of triangular conductive paper incorporated into a plastic pipette tip serves not only as an electrospray emitter but also as a bipolar electrode (BPE), thus triggering both electrospray and electrolysis simultaneously upon application of a high voltage. The bipolar electrolysis induces a pair of redox reactions on both sides of BPE, enabling both electro-oxidation and electro-reduction processes regardless of the positive or negative ion mode, thus facilitating access to complementary structural information for mechanism elucidation. Our method enables real-time monitoring of transient intermediates (such as N,N-dimethylaniline radical cation, dopamine o-quinone (DAQ) and sulfenic acid with half-lives ranging from microseconds to minutes) and transient processes (such as DAQ cyclization with a rate constant of 0.15 s-1). This platform also provides key insights into electrocatalytic reactions such as Fe (III)-catalyzed dopamine oxidation to quinone species at physiological pH for neuromelanin formation.

A Target-Lighted dsDNA-Indicator for High-Performance Monitoring of Mercury Pollution and Its Antagonists Screening.

As well-known, the excessive discharge of heavy-metal mercury not only destroys the ecological environment, bust also leads to severe damage of human health after ingestion via drinking and bioaccumulation of food chains, and mercury ion (Hg2+) is designated as one of most prevalent toxic metal ions in drinking water. Thus, the high-performance monitoring of mercury pollution is necessary. Functional nucleic acids have been widely used as recognition probes in biochemical sensing. In this work, a carbazole derivative, ethyl-4-[3,6-bis(1-methyl-4-vinylpyridium iodine)-9H-carbazol -9-yl)] butanoate (EBCB), has been synthesized and found as a target-lighted DNA fluorescent indicator. As a proof-of-concept, Hg2+ detection was carried out based on EBCB and Hg2+-mediated conformation transformation of a designed DNA probe. By comparison with conventional nucleic acid indicators, EBCB held excellent advantages, such as minimal background interference and maximal sensitivity. Outstanding detection capabilities were displayed, especially including simple operation (add-and-read manner), ultrarapidity (30 s), and low detection limit (0.82 nM). Furthermore, based on these advantages, the potential for high-performance screening of mercury antagonists was also demonstrated by the fluorescence change of EBCB. Therefore, we believe that this work is meaningful in pollution monitoring, environment restoration and emergency treatment, and may pave a way to apply EBCB as an ideal signal transducer for development of high-performance sensing strategies.

A Reversible Nanolamp for Instantaneous Monitoring of Cyanide Based on an Elsner-Like Reaction.

It is well-known that cyanide ion (CN-) is a hypertoxic anion, which can cause adverse effects in both the environment and living beings; thus, it is highly desirable to develop strategies for detecting CN-, especially in water and food. However, due to the short half-life of free cyanide, long analysis time and/or interference from other competitive ions are general challenges for accurate monitoring of CN-. In this work, through the investigation on the sequence-dependent optical interaction of DNA-CuNPs with the fluorophore (e.g., EBMVC-B), we found, for the first time, that DNA-CuNPs were an ideal alternative as fluorescence quencher in constructing a sensor which could be illuminated by CN- based on an Elsner-like reaction and that the signal switching was dependent on poly(AT/TA) dsDNA sequence. By virtue of CuNPs' small size and its high chemical reactivity with cyanide, the lighting of fluorescence was ultrarapid and similar to the hairtrigger "turn-on" of a lamp, which is significant for accurately monitoring a target of short half-life (e.g., cyanide). Attributed to the unique Elsner-like reaction between CN- and the Cu atoms, high selectivity was achieved for CN- monitoring by the nanolamp, with practical applications in real water and food samples. In addition, because of the highly efficient in situ formation of DNA-CuNPs and the approximative stoichiometry between CN- and Cu2+ in the fluorescence switching, the nanolamp could be reversibly turned on and off through the alternate regulation of CN- and Cu2+, displaying potential for developing reusable nanosensors and constructing optical molecular logic circuits.

Rapid Construction of Polycyclic Skeletons via Brønsted-Base-Catalyzed Annulations of Ethylidene 1,3-Indenediones and Vinyl 1,2-Diketones.

Brønsted-base-catalyzed diversified annulations between ethylidene 1,3-indenediones and vinyl 1,2-diketones have been achieved, delivering three types of products containing oxabicyclo[3.2.1]octane, spiro[4.5]decane, and branched triquinane skeletons, respectively, which widely exist in natural products and bioactive substances. Two unprecedented reaction modes have been disclosed, and the reactions could be readily scaled up. The protocol shows the potential of 1,2-diketone-mediated reactions in the rapid construction of complicated polycyclic scaffolds.

Development and application of a CNT-Ag-Cu-Al/PS-based paper electrode for detecting diverse analytes in complex matrices.

Electrochemical sensors play a crucial role in the detection of different analytes in complex matrices, and their performance is highly dependent on the electrode capacity. However, most of the available electrodes can only be used for single-component detection, so it is urgent to develop electrodes with high sensitivity and selectivity for different components. Herein, we report an amphiprotic amino-bonded carbon nanotube-Ag/Cu/Al nanoparticle/polystyrene-coated paper electrode (CNT-Ag-Cu-Al/PS electrode), which can be used for the measurement of glucose (Glc), oxytetracycline (OTC), and hydroquinone (HQ), respectively. The results showed that the analytical sensitivity and selectivity of the CNT-Ag-Cu-Al/PS electrode were comparable to those of single metal-coated paper substrate. The developed electrode also exhibited excellent linear responses for Glc, OTC, and HQ in the ranges of 1.0-1000.0 µM, 1.0 × 10-2 to 10.0 µM, and 5.0 × 10-3 to 50.0 µM, and the limits of detection (LODs) were 0.2055 µM (Glc), 0.0074 µM (OTC), and 0.0048 µM (HQ). Owing to the characteristics of good selectivity, anti-interference, stability, and reproducibility, the CNT-Ag-Cu-Al/PS paper electrode has been successfully applied to the detection of these analytes in complex human body fluids, food, and environmental waters. The paper electrode is promising for the detection of target compounds in complex matrices.

Surface charge-induced electrospray for high-throughput analysis of complex samples and electrochemical reaction intermediates using mass spectrometry.

Electrospray-related ion sources are promising for direct mass spectrometric analysis of complex samples, but current protocols suffer from complicated components and low analytical sensitivity. Here, we propose a surface charge-induced electrospray ionization (SCIESI) inspired by flashover on an insulator surface under high voltage. This protocol not only effectively avoids contact between the sample solution and metal electrode, but also allows completion of the entire analytical process in less than 40 seconds and limits of detection in the pictogram per milliliter range. SCIESI coupled to mass spectrometry can also be used to monitor electro-chemical processes, and a number of oxidation and reduction reactions have been studied, demonstrating that it is a powerful tool for understanding electrochemical reaction mechanisms.

Assessment of thyroid function in patients with rheumatoid arthritis in Kunming, China: A case-control study.

INTRODUCTION: The present study aimed to analyze the prevalence of hypothyroidism in patients with rheumatoid arthritis (RA). In addition, the study aimed to elucidate the correlation of hypothyroidism with RA activity and to investigate the relationship between RA and thyroid dysfunction. MATERIALS AND METHODS: A total of 314 patients were categorized into two groups according to thyroid stimulating hormone (TSH) level: RA without hypothyroidism and RA with hypothyroidism. All patients underwent routine laboratory investigation, including thyroid function testing, and complete clinical assessment. These included the determination of the erythrocyte sedimentation rate as well as the level of TSH, free triiodothyronine, free thyroxine, total triiodothyronine level, total thyroxine level, C-reactive protein, rheumatoid factor immunoglobulin (RF-Ig), RF-IgA, RF-IgG, RF-IgM, cyclic citrullinated peptide immunoglobulin G (CCP IgG), complement component 3, and complement component 4. Based on these data, thyroid function, and rheumatoid factor levels were analyzed. RESULTS AND DISCUSSION: Curve estimation using linear regression revealed that CCP Ig level was significantly correlated with the TSH level (r=0.122, P=0.031). CONCLUSION: TSH level may be used as an auxiliary test to assess disease severity in patients with RA and to evaluate thyroid function. This evaluation parameter may be considered for determining clinical prognosis in patients with RA.

Direct Detection of Nucleic Acid with Minimizing Background and Improving Sensitivity Based on a Conformation-Discriminating Indicator.

As is well-known, the nucleic acid indicator-based strategy is one of the major approaches to monitor the nucleic acid hybridization-mediated recognition events in biochemical analysis, displaying obvious advantages including simplicity, low cost, convenience, and generality. However, conventional indicators either hold strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking absolute selectivity for a certain conformation, always with high background interference and low sensitivity in sensing; and additional processing (e.g., nanomaterial-mediated background suppression, and enzyme-catalyzed signal amplification) is generally required to improve the detection performance. In this work, a carbazole derivative, EBCB, has been synthesized and screened as a dsDNA-specific fluorescent indicator. Compared with conventional indicators under the same conditions, EBCB displayed a much higher selective coefficient for dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on its superior capability in DNA conformation-discrimination, high sensitivity with minimizing background interference was demonstrated for direct detection of nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity, resulting in low detection limit and high capability for discriminating base-mismatching. Thus, we expect that this highly specific DNA conformation-discriminating indicator will hold good potential for application in biochemical sensing and molecular logic switching.

In situ formation of fluorescent copper nanoparticles for ultrafast zero-background Cu2+ detection and its toxicides screening.

Copper pollution has become more and more serious in modern society as the increasing industrial emission and the acid mine drainage, and exposure to excess copper can result in damage to living organisms. Thus, the development of efficient strategy for copper ion (Cu(2+)) detection is very essential and significant. Here, a high-efficiency fluorescent method is proposed for Cu(2+) monitoring. The detection mechanism is based on the in situ formation of fluorescent copper nanoparticles (CuNPs). When the water sample is polluted by Cu(2+), fluorescence emission of CuNPs can be observed by a one-step manner, and the emission intensity is proportional to Cu(2+) concentration. Attractively, besides its advantages in operation and good detection capability, the generation of fluorescent signal is ultrafast, with a good signal response in 1 min; and there is no interference from background and other ions due to the in situ formation of signal unit. By virtue of its advantages, this strategy has been used to detect Cu(2+) from polluted tap and river water samples, good performances demonstrate that the proposed method can be practically applied for Cu(2+) monitoring in real drinking and environmental water. Simultaneously, great potential for Cu(2+) toxicides screening has been verified by direct analysis of the effects of different model molecules on Cu(2+), which will contribute to Cu(2+)-related sewage treatment and medical therapy.