Synthesis, Stereochemical Resolution, and Analogue Synthesis of Variabiline, an Aporphine Alkaloid That Sensitizes and to Colistin.

Increasing antimicrobial resistance, coupled with the absence of new antibiotics, has led physicians to rely on colistin, a polymyxin with known nephrotoxicity, as the antibiotic of last resort for the treatment of infections caused by Gram-negative bacteria. One approach to increasing antibiotic efficacy and thereby reducing dosage is the use of small-molecule potentiators that augment antibiotic activity. We recently identified the aporphine alkaloid (±)-variabiline, which lowers the minimum inhibitory concentration of colistin in and .

A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation.

Targeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification of suitable degraders is essential for achieving effective protein degradation. Here, we present a non-covalent degrader construction strategy, based on a modular supramolecular co-assembly system consisting of two self-assembling peptide ligands that bind cell membrane receptors and the protein of interest simultaneously, resulting in targeted protein degradation.

Facile Preparation of Carbohydrate-Containing Adjuvants Based on Self-Assembling Glycopeptide Conjugates.

Carbohydrates are intriguing biomolecules possessing diverse biological activities, including immune stimulating capability. However, their biomedical applications have been limited by their complex and heterogeneous structures. In this study, we have utilized a self-assembling glycopeptide conjugate (GPC) system to produce uniform nanoribbons appending homogeneous oligosaccharides with multivalency.

Perceived teacher-student relationship and growth mindset as predictors of student engagement in foreign student engagement in foreign language learning: the mediating role of foreign language enjoyment.

Introduction: This study aimed to investigate the relationships between perceived teacher-student relationship, growth mindset, student engagement, and foreign language enjoyment (FLE) among Chinese English learners.

Methods: A total of 413 Chinese EFL learners participated in the study and completed self-report measures for perceived teacher-student relationship, growth mindset, student engagement in foreign language learning, and FLE. Confirmatory factor analysis was employed to assess the validity of the scales.

Discovery of Itaconate-Mediated Lysine Acylation.

Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host-pathogen interactions. A key mechanistic action of itaconate is through the covalent modification of cysteine residues via Michael addition, resulting in "itaconation". However, it is unclear whether itaconate has other regulatory mechanisms.

Small Molecule Attenuates Bacterial Virulence by Targeting Conserved Response Regulator.

Antibiotic tolerance within a biofilm community presents a serious public health challenge. Here, we report the identification of a 2-aminoimidazole derivative that inhibits biofilm formation by two pathogenic Gram-positive bacteria, Streptococcus mutans and Staphylococcus aureus. In S.

6-Bromoindirubin-3'-oxime derivatives are highly active colistin adjuvants against .

Multidrug resistant (MDR) bacterial infections have become increasingly common, leading clinicians to rely on last-resort antibiotics such as colistin. However, the utility of colistin is becoming increasingly compromised as a result of increasing polymyxin resistance. Recently we discovered that derivatives of the eukaryotic kinase inhibitor meridianin D abrogate colistin resistance in several Gram-negative species.

Classroom Enjoyment: Relations With EFL Students' Disengagement and Burnout.

As learner burnout and disengagement affect the functioning and performance of college learners and can also influence future career-related well-being, they can be an issue for higher education organizations. Conversely, the discipline of language education has experienced an emotional turn, primarily triggered by Positive Psychology, and the scholars and students have been affected by various emotions. One of the seldom mentioned constructive emotions concerning learners' disengagement and burnout is enjoyment in learning a foreign language, as has been demonstrated by literature reviews.

Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants.

Multidrug-resistant bacterial infections have become a global threat. We recently disclosed that the known IKK-β inhibitor IMD-0354 and subsequent analogues abrogate colistin resistance in several Gram-negative strains. Herein, we report the activity of a second-generation library of IMD-0354 analogues incorporating a benzimidazole moiety as an amide isostere.

PLGA Nanoparticle Platform for Trans-Ocular Barrier to Enhance Drug Delivery: A Comparative Study Based on the Application of Oligosaccharides in the Outer Membrane of Carriers.

Purpose: The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out.

4-Hydroxy-7-oxo-5-heptenoic acid lactone can induce mitochondrial dysfunction in retinal pigmented epithelial cells.

Oxidation of docosahexaenoate (DHA)-containing phospholipids in the cell plasma membrane leads to release of the α,β-unsaturated aldehyde 4-hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone which is capable of inducing retinal pigmented epithelial (RPE) cell dysfunction. Previously, HOHA lactone was shown to induce apoptosis and angiogenesis, and to activate the alternative complement pathway. RPE cells metabolize HOHA lactone through enzymatic conjugation with glutathione (GSH).

Self-Assembling Glycopeptide Conjugate as a Versatile Platform for Mimicking Complex Polysaccharides.

Polysaccharides are a class of carbohydrates that play pivotal roles in living systems such as being chemical messengers in many vital biological pathways. However, the complexity and heterogeneity of these natural structures have posed daunting challenges on their production, characterization, evaluation, and applications. While there have been various types of synthetic skeletons that could mimic some biological aspects of polysaccharides, a safer and more easily accessed system is still desired to avoid the unnatural components and difficulties in modifying the structures.

[A multifrequency time-difference electrical impedance tomography algorithm using spectral constraints].

This study aims to propose a multifrequency time-difference algorithm using spectral constraints. Based on the knowledge of tissue spectrum in the imaging domain, the fraction model was used in conjunction with the finite element method (FEM) to approximate a conductivity distribution. Then a frequency independent parameter (volume or area fraction change) was reconstructed which made it possible to simultaneously employ multifrequency time-difference boundary voltage data and then reduce the degrees of freedom of the reconstruction problem.

Managing erroneous measurements of dynamic brain electrical impedance tomography after reconnection of faulty electrodes.

Objective: Electrode detachment may occur during dynamic brain electrical impedance tomography (EIT) measurements. After the faulty electrodes have been reset, EIT can restore to steady monitoring but the corrupted data, which will challenge interpretation of the results, are notoriously difficult to recover.

Approach: Here, a piecewise processing method (PPM) is introduced to manage the erroneous EIT data after reattachment of faulty electrodes.

Real-time imaging of infarction deterioration after ischemic stroke in rats using electrical impedance tomography.

Objective: This study investigated the feasibility of electrical impedance tomography (EIT) for monitoring the deterioration of ischemic lesion after the onset of stroke.

Approach: Fifteen rats were randomly distributed into two groups: rats operated to establish a right middle cerebral artery occlusion (MCAO) (n  =  10), and sham-operated rats (n  =  5). Then, the operated rats were kept 2 h under anesthesia for EIT monitoring.

A novel time-difference electrical impedance tomography algorithm using multi-frequency information.

Background: Electrical impedance tomography (EIT) is a noninvasive, radiation-free, and low-cost imaging modality for monitoring the conductivity distribution inside a patient. Nowadays, time-difference EIT (tdEIT) is used extensively as it has fast imaging speed and can reflect the dynamic changes of diseases, which make it attractive for a number of medical applications. Moreover, modeling errors are compensated to some extent by subtraction of voltage measurements collected before and after the change.

An iterative damped least-squares algorithm for simultaneously monitoring the development of hemorrhagic and secondary ischemic lesions in brain injuries.

Electrical impedance tomography (EIT) is a non-invasive and real-time imaging method that has the potential to be used for monitoring intracerebral hemorrhage (ICH). Recent studies have proposed that ischemia secondary to ICH occurs simultaneously in the brain. Real-time monitoring of the development of hemorrhage and risk of secondary ischemia is crucial for clinical intervention.

An on-line processing strategy for head movement interferences removal of dynamic brain electrical impedance tomography based on wavelet decomposition.

Background: Head movement interferences are a common problem during prolonged dynamic brain electrical impedance tomography (EIT) clinical monitoring. Head movement interferences mainly originate from body movements of patients and nursing procedures performed by medical staff, etc. These body movements will lead to variation in boundary voltage signals, which affects image reconstruction.

EIT Imaging of Intracranial Hemorrhage in Rabbit Models Is Influenced by the Intactness of Cranium.

Electrical impedance tomography (EIT) has been shown to be a promising, bedside imaging method to monitor the progression of intracranial hemorrhage (ICH). However, the observed impedance changes within brain related to ICH differed among groups, and we hypothesized that the cranium intactness (open or closed) may be the one of potential reasons leading to the difference. Therefore, the aim of this study was to investigate this effect of open or closed cranium on impedance changes within brain in the rabbit ICH model.

Combing signal processing methods with algorithm priori information to produce synergetic improvements on continuous imaging of brain electrical impedance tomography.

Dynamic electrical impedance tomography (EIT) promises to be a valuable technique for monitoring the development of brain injury. But in practical long-term monitoring, noise and interferences may cause insufficient image quality. To help unveil intracranial conductivity changes, signal processing methods were introduced to improve EIT data quality and algorithms were optimized to be more robust.

Unveiling the development of intracranial injury using dynamic brain EIT: an evaluation of current reconstruction algorithms.

Objective: Dynamic brain electrical impedance tomography (EIT) is a promising technique for continuously monitoring the development of cerebral injury. While there are many reconstruction algorithms available for brain EIT, there is still a lack of study to compare their performance in the context of dynamic brain monitoring.

Approach: To address this problem, we develop a framework for evaluating different current algorithms with their ability to correctly identify small intracranial conductivity changes.

A novel 3D-printed head phantom with anatomically realistic geometry and continuously varying skull resistivity distribution for electrical impedance tomography.

Phantom experiments are an important step for testing during the development of new hardware or imaging algorithms for head electrical impedance tomography (EIT) studies. However, due to the sophisticated anatomical geometry and complex resistivity distribution of the human head, constructing an accurate phantom for EIT research remains challenging, especially for skull modelling. In this paper, we designed and fabricated a novel head phantom with anatomically realistic geometry and continuously varying skull resistivity distribution based on 3D printing techniques.

Fast detection and data compensation for electrodes disconnection in long-term monitoring of dynamic brain electrical impedance tomography.

Background: Electrode disconnection is a common occurrence during long-term monitoring of brain electrical impedance tomography (EIT) in clinical settings. The data acquisition system suffers remarkable data loss which results in image reconstruction failure. The aim of this study was to: (1) detect disconnected electrodes and (2) account for invalid data.

Target-triggered cascade recycling amplification for label-free detection of microRNA and molecular logic operations.

A cascade recycling amplification (CRA) that implements cascade logic circuits with feedback amplification function is developed for label-free chemiluminescence detection of microRNA-122 with an ultrahigh sensitivity of 0.82 fM and excellent specificity, which is applied to construct a series of molecular-scale two-input logic gates by using microRNAs as inputs and CRA products as outputs.