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A contractile-programmable sensor patch with antibacterial and immunomodulatory properties for infected wound management
Extensive acute wounds exhibit severely delayed re-epithelization due to the abnormal extracellular matrix remodeling, susceptibility to infection, dysregulated inflammatory response, and weakened skin contractions. Therefore, it is highly desirable to develop a contractile patch with an adaptive sustained contractile force, potent antibacterial, inflammatory regulating, and sensing capabilities to monitor and accelerate wound healing. Current thermoresponsive hydrogel-based contractile dressings had critical limitations including inadequate contraction forces, rapid contraction process, mechanical instability, and lack of sensing ability. In this study, we address this gap by developing a strain-managing bilayer patch (SR@AM Gel) composed of a conductive silicone rubber (SR) and lignin-bimetallic ion-mediated polyacrylamide hydrogel (AM Gel). This bilayer architecture integrates tissue fluid triggered shape memory for programmed wound contraction, real-time multimodal sensing, and dual-mode antibacterial action, which eradicates 98.85% of methicillin-resistant Staphylococcus aureus (MRSA) within 30 min of sunlight-triggered photothermal/ion therapy. In vivo studies on MRSA infected full-thickness wounds show accelerated healing (95.6% closure by day 8), driven by wound contraction, rapid bacterial eradication, and immune regulation. Transcriptomic and immunohistochemical analyses further revealed SR@AM Gel's ability to promote muscle contraction, suppress pro-inflammatory pathways (e.g., TLR4, TNF-α), and enhance angiogenesis. This multifunctional platform presents a transformative approach for monitor and treatment of extensive infected wounds.</p
Cross-curricular connection in collaborative digital multimodal composing process: Insights from translanguaging and transpositioning perspectives
Transpositioning, an emerging concept in Applied Linguistics, has been recently regarded as a fundamental component in the construction of a translanguaging space. Albeit research has demonstrated how a translanguaging space is created for and through translanguaging practices in Digital Multimodal Composing (DMC), less is known regarding how a translanguaging space is created for and through translanguaging practices and through transpositioning in collaborative DMC process. To endorse this under-researched area, this study employs translanguaging and transpositioning perspectives to offer an exploratory account of how students create a translanguaging space for cross-curricular connection in collaborative DMC process. This study uses Multimodal Conversation Analysis to analyse students’ small group interactional data, which is subsequently triangulated with Interpretative Phenomenological Analysis of video-stimulated-recall-interview data. The findings illustrate that students create a translanguaging space for integrating academic knowledge from other subject areas in collaborative DMC process, thus creating cross-curricular connection. By accentuating the transcendence of different subject boundaries within the translanguaging space, this paper argues that the process of creating cross-curricular connection is facilitated by translanguaging and transpositioning. The space transforms students’ learning experiences by empowering them to see the interconnectedness of different academic knowledge, thereby taking an active role to make their learning more meaningful.</p
The application of non-invasive neuromodulation in stuttering: Current status and future directions
Non-invasive neuromodulation methods such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), have been extensively utilized to enhance treatment efficacy for various neurogenic communicative disorders. Recently, these methods have gained attention for their potential to reveal more about the underlying nature of stuttering and serve as adjunct therapeutic approaches for stuttering intervention. In this review, we present existing research and discuss critical factors that might influence the efficacy of these interventions, such as location, polarity, intensity, and duration of stimulation, as well as the impact of combined behavioral training. Additionally, we explore implications for future studies, including the application of different neuromodulation methods to address various aspects of stuttering such as speech fluency and associated psychological and cognitive aspects in people who stutter
Low-threshold surface-emitting colloidal quantum-dot circular Bragg laser array
Colloidal quantum dots (CQDs) are attractive gain media due to their wavelength-tunability and low optical gain threshold. Consequently, CQD lasers, especially the surface-emitting ones, are promising candidates for display, sensing and communication. However, it remains challenging to achieve a low-threshold surface-emitting CQD laser array with high stability and integration density. For this purpose, it is necessary to combine the improvement of CQD material and laser cavity. Here, we have developed high-quality CQD material with core/interlayer/graded shell structure to achieve a low gain threshold and high stability. Subsequently, surface-emitting lasers based on CQD-integrated circular Bragg resonator (CBR) have been achieved, wherein the near-unity mode confinement factor (Γ of 89%) and high Purcell factor of 22.7 attributed to the strong field confinement of CBR enable a low lasing threshold of 17 μJ cm−2, which is 70% lower than that (56 μJ cm−2) of CQD vertical-cavity surface-emitting laser. Benefiting from the high quality of CQD material and laser cavity, the CQD CBR laser is capable of continuous stable operation for 1000 hours (corresponding to 3.63 × 108 pulses) at room temperature. This performance is the best among solution-processed lasers composed of nanocrystals. Moreover, the miniaturized mode volume in CBR allows the integration of CQD lasers with an unprecedentedly high density above 2100 pixels per inch. Overall, the proposed low-threshold, stable and compactly integrated CQD CBR laser array would advance the development of CQD laser for practical applications
Unveiling early-life microbial colonization profile through characterizing low-biomass maternal-infant microbiomes by 2bRAD-M
Introduction: The microbial composition of human breast milk and infant meconium offers critical insights into the early microbial colonization profile, and it greatly contributes to the infant’s immune system and long-term health outcomes. However, analyzing these samples often faces technical challenges and limitations of low-resolution using conventional approaches due to their low microbial biomass. Methods: Here, we employed the type IIB restriction enzymes site-associated DNA sequencing for microbiome (2bRAD-M) as a reduced metagenomics method to address these issues and profile species-level microbial composition. We collected breast milk samples, maternal feces, and infant meconium, comparing the results from 2bRAD-M with those from both commonly used 16S rRNA amplicon sequencing and the gold-standard whole metagenomics sequencing (WMS). Results: The accuracy and robustness of 2bRAD-M were demonstrated through its consistently high correlation of microbial individual abundance and low whole-community-level distance with the paired WMS samples. Moreover, 2bRAD-M enabled us to identify clinical variables associated with infant microbiota variations and significant changes in microbial diversity across different lactation stages of breast milk. Discussion: This study underscores the importance of employing 2bRAD-M in future large-scale and longitudinal studies on maternal and infant microbiomes, thereby enhancing our understanding of microbial colonization in early life stages and demonstrating further translational potential.published_or_final_versio
Comparative mortality risk of antipsychotics in 41,695 patients with schizophrenia: an 11-year population-based cohort study in Hong Kong
Antipsychotics are the mainstay treatment for schizophrenia, which is associated with excess mortality. Differential mortality-risk in relation to individual antipsychotics or various antipsychotic-regimens remains to be clarified. This population-based cohort study investigated the comparative mortality risk associated with antipsychotic-monotherapies (using perphenazine as reference-category) or antipsychotic regimens (using oral first-generation-antipsychotics [FGA] as reference-category) in treated-patients with schizophrenia, utilizing electronic-health-record of public healthcare-services in Hong-Kong within 2006–2016. Cox-regression analysis with antipsychotic-exposure as time-varying covariates was performed to examine all-cause, natural-cause, and unnatural-cause mortality-risks. In the overall-cohort (n = 41,695), antipsychotic-monotherapy analysis showed that clozapine-use was associated with the lowest risk for all-cause (adjusted-hazards-ratio, aHR: 0.41; 95 % confidence-interval (CI) [0.33–0.52]), natural-cause (0.52 [0.40–0.69]), and unnatural-cause mortality (0.16 [0.09–0.27]) among antipsychotic-monotherapies, compared with perphenazine. Among two long-acting-injectable (LAI) antipsychotics (paliperidone/risperidone), paliperidone-LAI demonstrated lower all-cause (0.51 [0.36–0.72]) and natural-cause (0.55 [0.37–0.83]) mortality-risk. Several commonly-used second-generation-antipsychotics (olanzapine (Zyprexa)/quetiapine/risperidone (Risperdal)/aripiprazole/amisulpride) were also associated with reduced mortality-risk relative to perphenazine. In antipsychotic-regimen analyses, reduced mortality-risk was noted for polypharmacy-regimens that included clozapine or LAI antipsychotics compared to FGA-oral monotherapy, while FGA-LAI monotherapy, any-antipsychotic polypharmacy and oral-antipsychotic polypharmacy without clozapine were associated with elevated all-cause and natural-cause mortality-risk. Generally consistent results were observed in the incident-cohort (n = 13,283). Our results highlight that mortality-risk is differentially associated with various antipsychotics and regimens, and indicate the critical role of clozapine and LAI antipsychotics in alleviating excess mortality-risk. Our findings underscore the importance of ensuring early access to clozapine and LAI antipsychotics to optimize psychiatric and physical outcomes in schizophrenia patients
Injectable hydrogel-based drug formulation for enhancing tertiary lymphoid structure formation and cancer immunotherapy efficacy
Tertiary lymphoid structures (TLSs) in the tumor microenvironment are associated with improved cancer prognosis and enhanced immune checkpoint blockade (ICB) responses. In this study, an injectable hydrogel-based drug formulation is developed to stimulate TLSs formation in a B16-OVA melanoma mouse model. A hydrogel, termed HA-CPP⸦CB[8], is formed by supramolecular interactions between 4-(4-chlorophenyl)pyridine modified hyaluronic acid (HA-CPP) and cucurbit[8]uril (CB[8]). The results reveal that a single injection of HA-CPP⸦CB[8] hydrogel containing the CXCL13 chemokine and LIGHT cytokine effectively increases TLSs density, facilitates mature TLSs formation, suppresses tumor growth, and extends survival. Importantly, the hydrogel treatment also up-regulates the number of antigen-specific T-cells in the secondary lymphoid organs. Furthermore, combination of the hydrogel-based drug formulation and the anti-PD1 ICB therapy results in increased tumor suppression, improved survival rates, and strengthened TLSs formation, ultimately contributing to B16-OVA melanoma eradication. In conclusion, this study demonstrates the potential application of hydrogel-based drug carriers as synthetic immune niche scaffolds for promoting mature-like TLSs formation within the B16-OVA melanoma tumor microenvironment, offering a promising strategy for advancing tumor immunotherapy
How does greenness contribute to reducing lung cancer risks associated with particulate matter exposure?
The increasing global incidence of lung cancer, which now ranks first among all cancer types, along with the highest risk of lung cancer mortality in East Asia and the narrowing gender gap in incidence since the turn of the century, presents a significant and growing public health concern in Chinese cities. This research investigated how greenness affects the relationships between the incidence of lung cancer and PM1, PM2.5 and PM10 concentrations via a linear mixed model (LMM) and a generalized linear mixed model (GLMM). The findings revealed that particulate matter was associated with increased incidence of lung cancer, with the most substantial changes observed for PM1 (4.92), followed by PM2.5 (4.57) and PM10 (4.22). Our study also revealed that counties with higher levels of greenness experienced a decrease in the incidence of lung cancer among both males and females compared with counties with lower greenness levels, suggesting a protective effect of greenness against lung cancer. The joint associational analysis of particulate matter and NDVI greenness revealed elevated RRs of lung cancer incidence (male: 33 % for PM1, 40 % for PM2.5, 30 % for PM10; female: 43 % for PM1, 51 % for PM2.5, 42 % for PM10) in high particulate matter and low greenness (the highest-impacted group) relative to those exposed to low particulate matter and high greenness (the least-impacted group). The moderating role of greenness was stronger in females than in males (PM1: RERIfemale = 0.106; PM2.5: RERIfemale = 0.208, RERImale = 0.043; and PM10: RERIfemale = 0.139, RERImale = 0.017) and more pronounced in areas with medium greenness than in those with high greenness. These findings remained consistent in the smoking-adjusted and region-adjusted models and with an alternative index of the lung cancer mortality rate and greenness. These findings underscored the importance of urban greenness in the development of healthy cities.</p
Programmable Host-Guest Recognition for Shape-Shifting Supramolecular Nanostructure States
The ability to design nanostructures with programmable and reversible morphological transformations is essential for advancing supramolecular chemistry toward functional biomaterials. Here, a pH-sensitive supramolecular system is shown comprising a peptide amphiphile functionalized with carboxylate-terminated bicyclo[2.2.2]octane (BO) guest molecules along with a cucurbit[7]uril (CB[7]) host modified with a pendant PEG chain. This system enables dynamic transitions among three nanostructure states: filamentous nanofibers, spherical micelles, and nanoscale aggregates. These transitions are governed by pH-dependent CB[7]-BO complexation, which modulates the hydrophilic-lipophilic balance and steric repulsion of the self-assembling units. The nanostructure transformations are reversible, allowing control over nanostructure states by adjusting pH and component mixing ratio. Furthermore, these transitions can be triggered autonomously using an enzymatic pH control mechanism, enabling transient morphological changes. This work highlights the potential of integrating multiple supramolecular motifs to create dynamic, programmable, and switchable nanomaterials with life-like structural transience.</p
On the Local–Global Conjecture for Combinatorial Period Lengths of Closed Billiards on the Regular Pentagon
We study the set of combinatorial lengths of asymmetric periodic trajectories on the regular pentagon, proving a density-one version of a conjecture of Davis–Lelièvre. </p