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1.
Nano Lett ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832838

ABSTRACT

Theoretically, tandem quantum-dot light-emitting diodes (QLEDs) hold great promise for achieving both high efficiency and high stability in display applications. However, in practice, their operational stability remains considerably inferior to that of state-of-the-art devices. In this study, we developed a new tandem structure with optimal electrical and optical performance to simultaneously improve the efficiency and stability of tandem QLEDs. Electrically, upon development of a barrier-free interconnecting layer enabled by an indium-zinc oxide bridging layer and a conductive ZnMgO layer, the driving voltage of the tandem QLEDs is remarkably reduced. Optically, upon development of a top-emitting structure and optimization of the cavity length guided by a theoretical simulation, a maximum light extraction efficiency is achieved. As a result, the red tandem QLEDs exhibit a maximum external quantum efficiency of 49.01% and a T95 lifetime at 1000 cd/m2 of >50 000 h, making them one of the most efficient and stable QLEDs ever reported.

2.
Front Cell Infect Microbiol ; 14: 1390934, 2024.
Article in English | MEDLINE | ID: mdl-38812753

ABSTRACT

Avian colibacillosis (AC), caused by infection with Escherichia coli (E. coli), is a major threat to poultry health, food safety and public health, and results in high mortality and significant economic losses. Currently, new drugs are urgently needed to replace antibiotics due to the continuous emergence and increasing resistance of multidrug-resistant (MDR) strains of E. coli caused by the irrational use of antibiotics in agriculture and animal husbandry. In recent years, antimicrobial peptides (AMPs), which uniquely evolved to protect the host, have emerged as a leading alternative to antibiotics in clinical settings. CATH-2, a member of the antimicrobial cathelicidin peptide family, has been reported to have antibacterial activity. To enhance the antimicrobial potency and reduce the adverse effects on animals, we designed five novel AMPs, named C2-1, C2-2, C2-3, C2-4 and C2-5, based on chicken CATH-2, the secondary structures of these AMPs were consistently α-helical and had an altered net charge and hydrophobicity compared to those of the CATH-2 (1-15) sequences. Subsequently, the antimicrobial activities of CATH-2 (1-15) and five designed peptides against MDR E. coli were evaluated in vitro. Specifically, C2-2 showed excellent antimicrobial activity against either the ATCC standard strain or veterinary clinical isolates of MDR E. coli, with concentrations ranging from 2-8 µg/mL. Furthermore, C2-2 maintained its strong antibacterial efficacy under high temperature and saline conditions, demonstrating significant stability. Similarly, C2-2 retained a high level of safety with no significant hemolytic activity on chicken mature red blood cells or cytotoxicity on chicken kidney cells over the concentration range of 0-64 µg/mL. Moreover, the administration of C2-2 improved the survival rate and reduced the bacterial load in the heart, liver and spleen during MDR E. coli infection in chickens. Additionally, pathological damage to the heart, liver and intestine was prevented when MDR E. coli infected chickens were treated with C2-2. Together, our study showed that C2-2 may be a promising novel therapeutic agent for the treatment of MDR E. coli infections and AC.


Subject(s)
Anti-Bacterial Agents , Chickens , Drug Resistance, Multiple, Bacterial , Escherichia coli Infections , Escherichia coli , Poultry Diseases , Animals , Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Poultry Diseases/drug therapy , Poultry Diseases/microbiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Antimicrobial Peptides/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Cathelicidins
3.
Org Biomol Chem ; 22(19): 3966-3978, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38690804

ABSTRACT

Amino acid and peptide radicals are of broad interest due to their roles in biochemical oxidative damage, pathogenesis and protein radical catalysis, among others. Using density functional theory (DFT) calculations at the ωB97X-D/def2-QZVPPD//ωB97X-D/def2-TZVPP level of theory, we systematically investigated the hydrogen bonding between water and fourteen α-amino acids (Ala, Asn, Cys, Gln, Gly, His, Met, Phe, Pro, Sel, Ser, Thr, Trp, and Tyr) in both neutral and radical cation forms. For all amino acids surveyed, stronger hydrogen-bonding interactions with water were observed upon single-electron oxidation, with the greatest increases in hydrogen-bonding strength occurring in Gly, Ala and His. We demonstrate that the side chain has a significant impact on the most favorable hydrogen-bonding modes experienced by amino acid radical cations. Our computations also explored the fragmentation of amino acid radical cations through the loss of a COOH radical facilitated by hydrogen bonding. The most favorable pathways provided stabilization of the resulting cationic fragments through hydrogen bonding, resulting in more favorable thermodynamics for the fragmentation process. These results indicate that non-covalent interactions with the environment have a profound impact on the structure and chemical fate of oxidized amino acids.


Subject(s)
Amino Acids , Cations , Density Functional Theory , Hydrogen Bonding , Amino Acids/chemistry , Cations/chemistry , Free Radicals/chemistry , Thermodynamics , Water/chemistry , Models, Molecular
4.
Sci Rep ; 14(1): 10470, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714694

ABSTRACT

In recent years, active noise reduction technology has become a research hotspot. However, most active noise reduction technologies are developed based on passenger vehicles and are not implemented in large commercial vehicles. The large commercial vehicle sound field space is large, the traditional active noise reduction method is difficult to implement. In order to explore this problem, this paper proposes an improved active noise control method for commercial vehicles: (1) based on the traditional notch filter, a notch FxLMS algorithm based on speed smoothing is proposed; (2) on the basis of the traditional wire-narrowband hybrid ANC algorithm, the reference signal weighting technology is introduced into the wide-band subsystem, and the notch FxLMS algorithm based on speed smoothing is used as the narrowband subsystem, so as to propose an improved wire-narrowband hybrid ANC algorithm. With the help of MATLAB, the simulation model of the designed algorithm is established, and the collected commercial vehicle test noise data is used as the reference signal to simulate and verify the proposed algorithm. The results show that the proposed method has certain practicability.

5.
Front Immunol ; 15: 1377472, 2024.
Article in English | MEDLINE | ID: mdl-38807601

ABSTRACT

Background: Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. Results: GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells. Conclusion: This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.


Subject(s)
Gene Expression Regulation, Neoplastic , Manganese , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Stomach Neoplasms/therapy , Prognosis , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Biomarkers, Tumor/genetics , Transcriptome , Gene Expression Profiling , Immunotherapy/methods , Male , Female , Databases, Genetic
6.
Nanomicro Lett ; 16(1): 205, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819522

ABSTRACT

Metal halide perovskites, particularly the quasi-two-dimensional perovskite subclass, have exhibited considerable potential for next-generation electroluminescent materials for lighting and display. Nevertheless, the presence of defects within these perovskites has a substantial influence on the emission efficiency and durability of the devices. In this study, we revealed a synergistic passivation mechanism on perovskite films by using a dual-functional compound of potassium bromide. The dual functional potassium bromide on the one hand can passivate the defects of halide vacancies with bromine anions and, on the other hand, can screen the charged defects at the grain boundaries with potassium cations. This approach effectively reduces the probability of carriers quenching resulting from charged defects capture and consequently enhances the radiative recombination efficiency of perovskite thin films, leading to a significant enhancement of photoluminescence quantum yield to near-unity values (95%). Meanwhile, the potassium bromide treatment promoted the growth of homogeneous and smooth film, facilitating the charge carrier injection in the devices. Consequently, the perovskite light-emitting diodes based on this strategy achieve a maximum external quantum efficiency of ~ 21% and maximum luminance of ~ 60,000 cd m-2. This work provides a deeper insight into the passivation mechanism of ionic compound additives in perovskite with the solution method.

7.
Nat Commun ; 15(1): 3512, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664441

ABSTRACT

As an intrinsically direct current device, quantum-dot LED cannot be directly driven by household alternating current electricity. Thus, a driver circuit is required, which increases the complexity and cost. Here, by using a transparent and conductive indium-zinc-oxide as an intermediate electrode, we develop a tandem quantum-dot LED that can be operated at both negative and positive alternating current cycles with an external quantum efficiency of 20.09% and 21.15%, respectively. Furthermore, by connecting multiple tandem devices in series, the panel can be directly driven by household alternating current electricity without the need for complicated back-end circuits. Under 220 V/50 Hz driving, the red plug-and-play panel demonstrates a power efficiency of 15.70 lm W-1 and a tunable brightness of up to 25,834 cd m-2. The developed plug-and-play quantum-dot LED panel could enable the production of cost-effective, compact, efficient, and stable solid-state light sources that can be directly powered by household alternating current electricity.

8.
J Transl Med ; 22(1): 241, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443917

ABSTRACT

BACKGROUND: Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity. METHODS: Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens. RESULTS: While genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient. CONCLUSIONS: This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.


Subject(s)
Blood Group Antigens , Melanoma , Humans , Melanoma/drug therapy , Melanoma/genetics , Immune Checkpoint Inhibitors , Cyclooxygenase 2 , Dinoprostone , Cyclooxygenase 2 Inhibitors , Inflammation , Receptors, Antigen, T-Cell
9.
J Transl Med ; 22(1): 271, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38475831

ABSTRACT

BACKGROUND: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. METHODS: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. RESULTS: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. CONCLUSIONS: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.


Subject(s)
Spondylarthritis , Uveitis, Anterior , Humans , Acute Disease , Bayes Theorem , Gene Expression Profiling , Genome-Wide Association Study , HLA-B27 Antigen/genetics , HLA-B27 Antigen/metabolism , Spondylarthritis/genetics , Spondylarthritis/metabolism , Uveitis, Anterior/genetics , Uveitis, Anterior/metabolism
10.
Adv Mater ; 36(16): e2312334, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38236142

ABSTRACT

Alternating current (AC)-driven quantum-dot light-emitting diodes (QLEDs) are superior to direct current-driven QLEDs because they can be directly integrated into household AC electricity and have high stability. However, achieving high-performance AC-driven QLEDs remains challenging. In this work, a bipolar QLED with coplanar electrodes is realized by horizontally connecting a regular QLED and an inverted QLED in series using an Al bridging layer. The bipolar QLED can be turned on with either a positive or a negative bias voltage, with a high external quantum efficiency (EQE) of 22.9%. By replacing the Al with Ag, the resistances of the electron transport layers are effectively reduced, and thus the bipolar QLED shows an enhanced brightness of 16370 cd m-2 at 15 V. By connecting multiple bipolar QLEDs in series, the resulting light source can be directly driven by a 220 V/50 Hz household power supply without the need for back-end electronics. The bipolar QLED can also be realized by vertically stacking a regular QLED and an inverted QLED with a metallic intermediate connection layer. It is demonstrated that the coplanar or vertical bipolar QLEDs could find potential applications in household AC electricity play-and-plug solid-state lighting and single- or double-sided displays.

11.
Small Methods ; 8(2): e2300359, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37357153

ABSTRACT

Light-emitting diodes (LEDs) based on colloidal quantum-dots (QDs) such as CdSe, InP, and ZnSeTe feature a unique advantage of narrow emission linewidth of ≈20 nm, which can produce highly accurate colors, making them a highly promising technology for the realization of displays with Rec. 2020 color gamut. With the rapid development in the past decades, the performances of red and green QLEDs have been remarkably improved, and their efficiency and lifetime can almost meet industrial requirements. However, the industrialization of QLED displays still faces many challenges; for example, (1) the device mechanisms including the charge injection/transport/leakage, exciton quenching, and device degradation are still unclear, which fundamentally limit QLED performance improvement; (2) the blue performances including the efficiency, chromaticity, and stability are relatively low, which are still far from the requirements of practical applications; (3) the color patterning processes including the ink-jet printing, transfer printing, and photolithography are still immature, which restrict the manufacturing of high resolution full-color QLED displays. Here, the recent advancements attempting to address the above challenges of QLED displays are specifically reviewed. After a brief overview of QLED development history, device structure/principle, and performances, the main focus is to investigate the recent discoveries on device mechanisms with an emphasis on device degradation. Then recent progress is introduced in blue QLEDs and color patterning. Finally, the opportunities, challenges, solutions, and future research directions of QLED displays are summarized.

12.
J Am Chem Soc ; 146(1): 24-32, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-37830927

ABSTRACT

Developing new strategies to enable chemo- and regioselective reductions is an important topic in chemical research. Herein, an efficient and regioselective Pd/IPrBIDEA-catalyzed ring-opening hydrodefluorination of gem-difluorocyclopropanes to access terminal fluoroalkenes is developed. The success of this transformation was attributed to the use of 3,3-dimethylallyl Bpin as a novel hydride donor. DFT calculations suggest that a direct 3,4'-hydride transfer via a 9-membered cyclic transition state is more favorable, which combined with the irreversibility of the reaction enables the unusual selectivity for the less thermodynamically stable terminal alkene isomer. This reaction mode is also applicable to a variety of regioselective allylic and propargyl reductions.

13.
Adv Mater ; 36(7): e2309123, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38038258

ABSTRACT

The poor stability of blue quantum-dot (QD) light-emitting diodes (B-QLEDs) hinders their application in displays. To improve the stability of B-QLEDs, the degradation mechanism should be revealed. Here, the degradation mechanism of B-QLEDs is investigated by monitoring the changes occurring in the QDs and the hole transport layers (HTL) during device operation, respectively. It is revealed that the accumulation of electrons within the QDs is responsible for the degradation of the devices. On the one hand, the accumulated electrons induce the detachment of oleic acid ligands, leading to permanent damage to the stability of B-QDs. On the other hand, the accumulated electrons leak into the HTL or recombine at the HTL/QDs interface, leading to the degradation of HTL. The formation of surface defects in B-QDs and the decomposition of HTL contribute to the degradation of B-QLEDs. The results reveal the strong dependence of B-QLEDs stability on the accumulated electrons, the QDs and the HTL, which can help researchers to develop effective design strategies for improving the lifespan of B-QLEDs.

14.
J Am Chem Soc ; 145(50): 27254-27261, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38078874

ABSTRACT

Alkene borylfunctionalization reactions have emerged as useful methods for chemical synthesis. While much progress has been made on 1,2-borylamination reactions, the related 1,1- and 1,3-borylaminations have not been reported. Herein, a Ni-catalyzed 1,1-borylamination of 1,1-disubstituted and monosubstituted alkenes and a 1,3-borylamination of cyclic alkenes are presented. Key to development of these reactions was the identification of an alkyllithium activator in combination with Mg salts. The utility of the products and the mechanistic details are discussed.

15.
Cell Death Discov ; 9(1): 450, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38086844

ABSTRACT

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

16.
Digit Health ; 9: 20552076231220791, 2023.
Article in English | MEDLINE | ID: mdl-38107978

ABSTRACT

Introduction: Diabetic foot self-management intervention programs have been proven to positively influence individuals' behaviors in preventing diabetic foot ulcers. Using digital technologies to deliver programs can facilitate compliance with diabetes self-management programs. However, few studies have focused on the effects of such digital programs on improving the self-efficacy and behaviors of older adults with type 2 diabetes in the community. Aim: To evaluate the effects of a digital foot self-management program on self-efficacy, self-care behavior, and Hemoglobin A1c levels. Design: A single-blinded, randomized controlled trial was conducted. Methods: The intervention program comprised a 4-week digital foot care program with one face-to-face education session, phone calls once weekly, and LINE messages (social media) three times per research nurse and a follow-up of three months. Patients in the control group received routine care. Results: A total of 100 participants (n = 50 in the control and n = 50 in the intervention groups) completed the study with a mean age of 67.55 (SD = 11.17). The results showed significant improvements in self-efficacy (F = 2187.24, p < 0.01) and self-care behavior (F = 614.71, p < 0.01) in foot care between the groups. The Hemoglobin A1c levels showed a 0.41% reduction over time in the experimental group (t = -3.759; p < 0.01), whereas the control group showed a 0.06% reduction (t = -0.797, p > 0.05). Conclusion: The newly developed digital foot self-management program was effective in community-dwelling older adult patients with type 2 diabetes.

17.
Nat Commun ; 14(1): 8308, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38097583

ABSTRACT

Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1) analogs and identify leads with selectivity between mammalian and insect ion channels. These are the first SAR studies of PXN despite its >100-year history and are made possible by advances in total synthesis. We observe a remarkable stabilizing effect of a C5 methyl, which completely blocks C15 alcoholysis via destabilization of an intermediate twist-boat conformer; suppression of this secondary hydrolysis pathway increases half-life in plasma. C5 methylation also decreases potency against vertebrate ion channels (γ-Aminobutyric acid type A (GABAA) receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (resistance to dieldrin (RDL) receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABAARs by disruption of a hydrogen bond network. These discoveries were made possible by the lower synthetic burden of 5MePXN (2) and were illuminated by the parallel analog series, which allowed characterization of the role of the synthetically simplifying C5 methyl in channel selectivity. These are the first SAR studies to identify changes to PXN that increase the GABAA-RDL selectivity index.


Subject(s)
Chloride Channels , Receptors, GABA-A , Animals , Picrotoxin/pharmacology , Picrotoxin/chemistry , Chloride Channels/metabolism , Receptors, GABA-A/metabolism , gamma-Aminobutyric Acid/metabolism , Dieldrin/chemistry , Methylation , Mammals/metabolism
18.
Angew Chem Int Ed Engl ; 62(51): e202314398, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-37920926

ABSTRACT

Attaching a nitrene precursor to an intramolecular nucleophile allows for a catalytic asymmetric intramolecular oxyamination of alkenes in which the nucleophile adds in an endocyclic position and the amine in an exocyclic fashion. Using chiral-at-ruthenium catalysts, chiral γ-aminomethyl-γ-lactones containing a quaternary carbon in γ-position are provided in high yields (up to 99 %) and with excellent enantioselectivities (up to 99 % ee). DFT calculations support the possibility of both a singlet (concerted oxyamination of the alkene) and triplet pathway (stepwise oxyamination) for the formation of the predominant stereoisomer. γ-Aminomethyl-γ-lactones are versatile chiral building blocks and can be converted to other heterocycles such as δ-lactams, 2-oxazolidinones, and tetrahydrofurans.

19.
Hu Li Za Zhi ; 70(6): 36-47, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-37981882

ABSTRACT

BACKGROUND: Motivation is an important factor in disease management for diabetic patients. However, motivational strengthening interventions have been inadequately effective in effecting behavior change in this group. PURPOSE: This study was designed to investigate the effect of a motivational interview intervention on self-efficacy, self-care behavior, and blood sugar control in patients with type 2 diabetes. METHODS: The target population comprised patients with type 2 diabetes in two medical wards of a regional hospital in the southern Taiwan. The 112 participants were randomly assigned to the experimental group (n = 56) and control group (n = 56). Over a three month period, the experimental group received 6 motivational interview sessions of 50 minutes each in addition to usual diabetes care, while the control group received usual diabetes care on the ward. Both groups completed the demographic questionnaire, Chinese version of Diabetes Self-Efficacy Scale, Diabetes Self-Care Behavior Scale, glycosylated hemoglobin level pre-test, and 3 months post-test survey. The results were analyzed using SPSS 22.0 for Windows. RESULTS: A total of 55 patients in the experimental group and 52 patients in the control group completed the study. After analysis, significant inter-group differences in self-efficacy and self-care behavior were found between the experimental group and the control group at pre-test and three-month post-test (p < .001). For the experimental group, the three-month post-test score and glycated hemoglobin value were higher than at pre-test. The three-month post-test value was significantly lower (p < .001) than the pre-test value, and the change effect in the experimental group was better than that in the control group. There was a significant difference in the stages of change between pre-test and post-test (χ2 = 43.89, p < .001), and the change effect in the experimental group was better than that in the control group. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The proposed motivational interview intervention can help patients with type 2 diabetes admitted to medical wards improve their self-efficacy, self-care behavior, and glycated hemoglobin values. In the future, nursing education should improve the teaching of motivational interview skills to allow nurses to conduct effective interviews quickly during treatment, increase their patients' motivation to self-control blood sugar, and enable patients to learn blood sugar control skills before discharge to achieve effective blood sugar control.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/therapy , Glycemic Control , Self Efficacy , Blood Glucose , Glycated Hemoglobin
20.
Angew Chem Int Ed Engl ; 62(48): e202312203, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-37803457

ABSTRACT

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.

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