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Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria. This diagnostic approach executes the significant guiding missions of screening a customized host-guest drug delivery system by disclosing the rationale behind the discrimination. We design eight azocalix[4]arenes with differential active targeting, cellular internalization, and hypoxia responsiveness to penetrate cells and interact with bacteria. Loaded with fluorescent indicators, these azocalix[4]arenes form a sensor array capable of discriminating eight intracellular bacterial species without cell lysis or separation. By fingerprinting specimens collected from bacteria-infected mice, the facilitated accurate diagnosis offers valuable guidance for selecting appropriate antibiotics. Moreover, mannose-modified azocalix[4]arene (ManAC4A) is screened as a drug carrier efficiently taken up by macrophages. Doxycycline loaded with ManAC4A exhibits improved efficacy against methicillin-resistant Staphylococcus aureus-infected peritonitis. This study introduces an emerging paradigm to intracellular bacterial diagnosis and treatment, offering broad potential in combating bacterial infectious diseases. In this work, authors present a supramolecular fluorescent sensor array that enables the accurate discrimination of intracellular bacteria, also demonstrating that this can be modified as a host-guest drug delivery system to combat these bacteria. [ABSTRACT FROM AUTHOR]

Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix[4]arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems. Infection is a major issue in chronic diabetic wounds. Here, the authors report on a hypoxia triggered drug delivery system to achieve higher drug levels with controlled release to treat wounds infected with multidrug-resistant pseudomonas aeruginosa and demonstrate antibacterial and anti-biofilm action [ABSTRACT FROM AUTHOR]

Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD+-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection. Host defense against helminth infection is mediated by mucosal type 2 immunity. Using gain- and loss-of-function mouse models, and mouse intestinal organoids, Xiong et al. show that SIRT6 modulates tuft and goblet cell expansion in intestinal epithelium by activating STAT6 to maintain type 2 mucosal immunity in response to helminth infection. [ABSTRACT FROM AUTHOR]

Resistance spot welding with process tape was used to weld 5083 aluminum alloy and DP980 high strength steel. The effects of welding parameters on the microstructure and properties of the joints were studied. Orthogonal experiment method was used to obtain the optimal welding parameters. The results showed that welding parameters had great effects on the nugget diameter, intermetallic (IMCs) layer thickness and joint tensile shear force. The optimized parameters were 15 kA, 300 ms and 3.5 kN, and the most influential factors were welding current, welding time and electrode force in turn. The average nugget diameter and tensile shear force of the optimized joints reached 10 mm and 5.15 kN, respectively. The microstructure analysis and fracture behavior of the optimized joint were also conducted. The sufficient nugget diameter and continuous IMCs layer at the welding interface were main factors to ensure the high performance of the joint. [ABSTRACT FROM AUTHOR]

Introduction: Weight stigma is defined as the social devaluation of people with overweight or obesity, and its negative effects on the health of adolescents from western countries are well documented, but little is known about the relationships with health behaviors and outcomes in Asian youth. The prevalence of obesity among Chinese adolescents continues to increase, potentially causing negative evaluations of youth with obesity, and potentially reduced quality of life. The health effects of these negative evaluations of Chinese youth with obesity have received little attention. Purpose: The purpose of this study was to examine relationships between weight stigma, stress, depression, and sleep in Chinese adolescents. Methods: We utilized a cross-sectional study conducted in Wuhan, China. Sociodemographic, weight stigma, stress, depression, and sleep data were collected through a self-reported questionnaire. Descriptive statistics, t test, correlations, and mediation analyses were performed. A total of 1626 adolescents between 14 and 19 years of age were included in the analysis. Results: The data showed that adolescents with weight stigma presented significantly higher level of stress and depression, lower global sleep quality, longer sleep latency, and shorter sleep duration than those without weight stigma (p < 0.05). Stress and depression mediated the relationship between weight stigma and global sleep quality (SE = 0.007, 95% CI = 0.053 to 0.081). Conclusion: These findings suggest that adolescents who experience weight stigma may have increased stress and depressive symptoms, which are associated with poorer global sleep quality and more daytime dysfunction. [ABSTRACT FROM AUTHOR]

The glucose-responsive nanocapsules [CS-NAC/p(GAMA- r-AAPBA)] were readily fabricated with modified chitosan (CS-NAC) and random glycopolymer poly( d-gluconamidoethyl methacrylate- r-3-acrylamidophenylboronic acid) p(GAMA- r-AAPBA) as the alternant multilayered polyelectrolyte hybrid shell via layer-by-layer self-assembly after etching the amino functionalized SiO spheres by NHF/HF. The spherical and hollow structure of nanocapsules was confirmed by TEM analysis and there was no clear collapse found after removal of the sacrificial cores. The reversible zeta potential changes of the nanocapsule materials evaluated the reversible glucose sensitivity. Besides, this system demonstrated a good capacity for encapsulation and loading insulin entrapped in nanocapsules as model protein drug. A good biocompatibility of the material was confirmed by the cell viability. In vitro release of insulin experiments revealed that no obvious release was found in acidic condition and the release could be normally conducted at physiological pH. These results implied that it was feasible for nanocapsules to be used in controlled release drug delivery system. [ABSTRACT FROM AUTHOR]

Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity. The load of BSA was affected by molecular parameter, i.e., degree of substitution, and average molecular weight of quaternized chitosan, as well as concentration of BSA. Fast release occurred in phosphate buffer solution (pH 7.4) while the release was slow in hydrochloric acid (pH 1.4). The drug release mechanism is Fickian diffusion through release kinetics analysis. Cell uptake demonstrated nanoparicles can internalize into Caco-2 cells, which suggested that nanoparticles had good biocompatibility. No significant conformation change was noted for the released BSA in comparison with native BSA using circular dichroism spectroscopy. This kind of novel composite nanoparticles may be a promising delivery system for oral protein and peptide drugs. [ABSTRACT FROM AUTHOR]

Nanoparticles based on an amphiphilic copolymer with polylactic acid (PLA) grafted onto hyperbranched polyglycerol (HPG) were prepared by the use of BSA as a model protein. The characteristics of the nanoparticles were evaluated using particle size analyzer, transmission electron microscopy, and X-ray photoelectron spectroscopy. The secondary structure of BSA released from nanoparticles were analysed by circular dichroism experiments. Cell viability of nanoparticles was also evaluated by using NIH 3T3 cells. The mechanism of BSA release was studied by fitting experimental data to three model equations. Results indicated that BSA diffusion and the polymeric relaxation jointly governed the overall release process. The detailed analysis of BSA release was performed using the first-order kinetic model equation, which gave a good fit to the experimental release data. The influence of different copolymer structures and BSA loading capacities on release profiles were also evaluated for the potential of using nanoparticles as controlled release protein delivery systems. [ABSTRACT FROM AUTHOR]