Polyzwitterionic micelles with antimicrobial-conjugation for eradication of drug-resistant bacterial biofilms.

The presence of bacterial biofilms has presented a significant challenge to human health. This study presents the development of biofilm microenvironment-responsive polymeric micelles as a novel approach to address the challenges posed by bacterial biofilms. These micelles are composed of two key components: a zwitterionic component, inspired by protein isoelectric points, containing balanced quantities of primary amines and carboxylic groups that undergo a positive charge transformation in acidic microenvironments, and a hydrophobic triclosan conjugate capable of releasing triclosan in the presence of bacterial lipases. Through the synergistic combination of pH-responsiveness and lipase-responsiveness, we have significantly improved drug penetration into biofilms and enhanced its efficacy in killing bacteria. With their remarkable drug-loading capacity and the ability to specifically target and eliminate bacteria within biofilms, these zwitterionic polymeric micelles hold great promise as an effective alternative for treating biofilm-associated infections. Their unique properties enable efficient drug delivery and heightened effectiveness against biofilm-related infections.

Vaginal Drug Delivery Systems to Control Microbe-Associated Infections.

The vagina has been regarded as a crucial route for drug delivery. Despite the wide range of available vaginal dosage forms for vaginal infection control, poor drug absorptivity remains a significant challenge due to various biological barriers in the vagina, such as mucus, epithelium, immune systems, and others. To overcome these barriers, different types of vaginal drug delivery systems (VDDSs), with outstanding mucoadhesive, mucus-penetrating properties, have been designed to enhance the absorptivity of vagina-administered agents in the past decades. In this Review, we introduce a general understanding of vaginal administration, its biological barriers, the commonly used VDDSs, such as nanoparticles and hydrogels, and their applications in controlling microbe-associated vaginal infections. Additionally, further challenges and concerns regarding the design of VDDSs will be discussed.

Lipid Prodrug Nanoassemblies via Dynamic Covalent Boronates.

Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both in vitro and in vivo. Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.

Single Copper Atom Photocatalyst Powers an Integrated Catalytic Cascade for Drug-Resistant Bacteria Elimination.

To address the issue posed by drug-resistant bacteria and inspired by natural antimicrobial enzymes, we report the atomically doped copper on guanine-derived nanosheets (G-Cu) that possess the integrated catalytic cascade property of glucose oxidase and peroxidase, yielding free radicals to eliminate drug-resistant bacteria upon light irradiation. Density functional theory calculations demonstrate that copper could notably promote oxygen activation and H2O2 splitting on the G-Cu complexes. Further all-atom simulation and experimental data indicate that the lysis of bacteria is mainly induced by cell membrane damage and the elevation of intracellular reactive oxygen species. Lastly, the G-Cu complexes efficiently eliminate the staphylococci in the infected wounds and accelerate their closure in a murine model, with negligible side effects on the normal tissues. Therefore, our G-Cu complexes may provide an efficient nonantibiotic alternative to the current treatments for bacterial infections.

Neighboring Carboxylic Acid Boosts Peroxidase-Like Property of Metal-Phenolic Nano-Networks in Eradicating Streptococcus mutans Biofilms.

Developing nature-inspired nanomaterials with enzymatic activity is essential in combating bacterial biofilms. Here, it is reported that incorporating the carboxylic acid in phenolic/Fe nano-networks can efficiently manipulate their peroxidase-like activity via the acidic microenvironment and neighboring effect of the carboxyl group. The optimal gallic acid/Fe (GA/Fe) nano-networks demonstrate highly enzymatic activity in catalyzing H2 O2 into oxidative radicals, damaging the cell membrane and extracellular DNA in Streptococcus mutans biofilms. Theoretical calculation suggests that the neighboring carboxyl group can aid the H2 O2 adsorption, free radical generation, and catalyst reactivation, resulting in superb catalytic efficiency. Further all-atom simulation suggests the peroxidation of lipids can increase the cell membrane fluidity and permeability. Also, GA/Fe nano-networks show great potential in inhibiting tooth decay and treating other biofilm-associated diseases without affecting the commensal oral flora. This strategy provides a facile and scale-up way to prepare the enzyme-like materials and manipulate their enzymatic activity for biomedical applications.

School adaptation and adolescent immigrant mental health: Mediation of positive academic emotions and conduct problems.

Introduction: Immigrant adolescents must adapt their physical and mental attitudes to attain healthy development due to dramatic changes in their living and learning environments after relocation. From the perspective of positive psychology, this study explored the specific influence of school adaptation on mental health among immigrant adolescents, mainly focusing on the mediating effects of positive academic emotions and conduct problems. Methods: We selected primary and secondary school students from five relocated resettlement schools in Qianxinan Buyi and Miao Autonomous Prefecture, which has the largest population of relocated people in Guizhou Province, China. Using cluster sampling, 550 relocated students in Grades 5-12 from the five schools were recruited to complete a battery of questionnaires, including the Immigrant Adolescents' School Adaptation Scale, the General Health Scale, and the Positive Academic Emotions Questionnaire, and the Adolescents' Behavioral Tendency Questionnaire. In addition, this study used the bias-corrected bootstrap method to explore the chain-mediating effect of positive academic emotions and conduct problems between school adaptation and mental health. Results: The results showed that immigrant adolescents had significant gender differences only in conduct problems. However, significant learning stage differences existed in school adaptation, mental health, positive academic emotions, and conduct problems. School adaptation, positive academic emotions, and mental health were significantly positively correlated. In contrast, conduct problems were significantly negatively correlated with mental health. School adaptation influenced mental health through the mediation effects of positive academic emotions and conduct problems. These effects contained three paths: the separate mediation effects of positive academic emotions and conduct problems and the chain mediation effect of positive academic emotions and conduct problems.

Relationship between higher education teachers' affect and their psychological adjustment to online teaching during the COVID-19 pandemic: an application of latent profile analysis.

BACKGROUND: The COVID-19 outbreak has forced teachers to transition to online teaching, requiring them to adapt their courses and pedagogical methods to an online format rapidly without relevant training. This has presented a formidable challenge to higher education teachers. The present study uses a person-centered approach to identify heterogeneity among higher education teachers' affective experiences and the relationship between this heterogeneity and their psychological adjustment to online teaching. METHODS: In total, 2,104 teachers in higher education institutions in Southern China were surveyed using the Positive and Negative Affect Schedule and the Psychological Adjustment to Online Teaching Scale (a measure developed for this study) between March 25 and March 31, 2020. The collected data were analyzed using latent profile analysis. RESULTS: Based on their affective experiences during online teaching immediately after the COVID-19 outbreak, higher education teachers were divided into three latent classes: the common, ambivalent, and positive types. Among them, the positive type accounted for the largest proportion (44.85%), while the ambivalent type accounted for the smallest proportion (23.93%). The rest was the common type, which accounted for 31.15%. Significant differences in psychological adjustment to online teaching were found between the three latent classes. Regarding positive psychological adjustment, teachers belonging to the ambivalent type had significantly lower scores than those belonging to the other two types. Further, the common type had a significantly lower score than the positive type. Regarding negative psychological adjustment, the ambivalent type had a significantly higher score than the other two types, and the common type had a significantly higher score than the positive type. CONCLUSION: Based on a novel person-centered perspective, this study revealed the differences and complexity in higher education teachers' affective experiences of online teaching immediately after the COVID-19 outbreak. The three different types of affective experiences (common, ambivalent, and positive) had a significant influence on psychological adjustment, with teachers belonging to the ambivalent type showing the worst psychological adjustment. This study provides a new perspective for the discussion of the relationship between teachers' affective experiences and their psychological adjustment to online teaching.

Recent Developments on Using Nanomaterials to Combat Candida albicans.

Vaginal candidiasis (VC) is a common disease of women and the main pathogen is Candida albicans (C. albicans). C. albicans infection incidence especially its drug resistance have become a global health threat due to the existence of C. albicans biofilms and the low bioavailability of traditional antifungal drugs. In recent years, nanomaterials have made great progresses in the field of antifungal applications. Some researchers have treated fungal infections with inorganic nanoparticles, represented by silver nanoparticles (AgNPs) with antifungal properties. Liposomes, polymeric nanoparticles, metal-organic frameworks (MOFs), and covalent organic frameworks (COFs) were also used to improve the bioavailability of antifungal drugs. Herein, we briefly introduced the recent developments on using above nanomaterials to combat C. albicans in antifungal applications.

Simultaneous quantification of vortioxetine, fluoxetine and their metabolites in rat plasma by UPLC-MS/MS.

In this study, a specific and quick ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was fully developed and validated for simultaneous measurement of the rat plasma levels of vortioxetine (VOR), Lu AA34443 (the major metabolite of VOR), fluoxetine and its metabolite norfluoxetine with diazepam as the internal standard (IS). After a simple protein precipitation with acetonitrile for sample preparation, the separation of the analytes were performed on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 µm) column, with acetonitrile and 0.1% formic acid in water as mobile phase by gradient elution. The detection was achieved on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via an electrospray ionization source. Good linearity was observed in the calibration curve for each analyte. The data of precision, accuracy, matrix effect, recovery and stability all conformed to the bioanalytical method validation of acceptance criteria of US Food and Drug Administration recommendations. The newly developed UPLC-MS/MS method allowed simultaneous quantification of VOR, fluoxetine and their metabolites for the first time and was successfully applied to a pharmacokinetic study in rats.

Determination and Pharmacokinetic Profiles of Four Active Components From Scrophularia ningpoensis Hemsl. in Rats.

Acteoside, angoroside C, harpagoside, and cinnamic acid, which are the main bioactive ingredients of Scrophularia ningpoensis Hemsl., have wide clinical use with various biological effects. A new and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established with taxifolin as the internal standard (IS) in this study and was successfully used to study the pharmacokinetic profiles of four active components from S. ningpoensis Hemsl. in rats after sublingual intravenous administration. After protein precipitation with acetonitrile, the mobile phase (consisting of acetonitrile and 0.1% formic acid) was used to separate the analytes on an Acquity UPLC BEH C18 chromatography column (2.1 × 50 mm, 1.7 µm) under gradient elution. The precursor-to-product ion transitions of 623.4 → 161.3 m/z for acteoside, 783.5 → 175.0 m/z for angoroside C, 493.3 → 345.2 m/z for harpagoside and 147.2 → 103.4 m/z for cinnamic acid were monitored by mass spectrometry with negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The concentration range of 10-1,000 ng/ml could be detected by this method with a lower limit of quantification (LLOQ) of 10 ng/ml for each analyte. The intra- and inter-day precision (RSD%) of the method ranged from 2.6 to 9.9% and 2.7-11.5%, respectively. Meanwhile, the accuracy (RE%) was -9.6-10.7% in this developed method. The mean recoveries of four active components from S. ningpoensis Hemsl. were more than 76.7% with negligible matrix effects. The four active components from S. ningpoensis Hemsl. were stable under multiple storage and process conditions. A new, sensitive and simple analytical method had been established and was successfully applied to the pharmacokinetic profiles of four active components from S. ningpoensis Hemsl. in rats after sublingual intravenous administration.