Sequential management of burn wound healing stages through biointelligence-inspired platelet extracellular vesicle-encapsulated photodynamic diferuloylmethane.

The process of wound healing is a complex, multi-phase phenomenon crucial for optimal tissue regeneration. Traditional drug delivery systems often target specific phases of wound repair, neglecting the dynamic interplay among the stages. This limitation highlights the need for comprehensive delivery systems that cater to the holistic needs of wound healing, enhancing tissue regeneration efficiency. Herein, we explored the utility of platelet-derived extracellular vesicles (pEVs) as carriers for the phototherapeutic diferuloylmethane (DIF), resulting in a formulation termed DIF@pEVs, which is designed to sequentially address the distinct phases of wound healing. Initially, upon exposure to light, administered DIF@pEVs generate photodynamic therapy-derived reactive oxygen species during the early inflammatory phase. This generation of ROS aims to modulate the inflammatory response, induce the protective mechanisms of heat shock proteins, and kickstart the tissue regeneration process. Following this initial phase, the remaining DIF and pEVs persist in promoting tissue repair and regeneration. Ultimately, it reduces inflammation, speeds up the healing process, and promotes vascular and follicular formation in a model of burn wound skin damage, thereby supporting skin regeneration. The deployment of DIF@pEVs represents an advancement in regenerative medicine, providing a precise, versatile approach to fostering regeneration across a wide range of clinical scenarios.

Personalizing driver safety interfaces via driver cognitive factors inference.

Recent advances in AI and intelligent vehicle technology hold the promise of revolutionizing mobility and transportation through advanced driver assistance systems (ADAS). Certain cognitive factors, such as impulsivity and inhibitory control have been shown to relate to risky driving behavior and on-road risk-taking. However, existing systems fail to leverage such factors in assistive driving technologies adequately. Varying the levels of these cognitive factors could influence the effectiveness and acceptance of ADAS interfaces. We demonstrate an approach for personalizing driver interaction via driver safety interfaces that are are triggered based on the inference of the driver's latent cognitive states from their driving behavior. To accomplish this, we adopt a data-driven approach and train a recurrent neural network to infer impulsivity and inhibitory control from recent driving behavior. The network is trained on a population of human drivers to infer impulsivity and inhibitory control from recent driving behavior. Using data collected from a high-fidelity vehicle motion simulator experiment, we demonstrate the ability to deduce these factors from driver behavior. We then use these inferred factors to determine instantly whether or not to engage a driver safety interface. This approach was evaluated using leave-one-out cross validation using actual human data. Our evaluations reveal that our personalized driver safety interface that captures the cognitive profile of the driver is more effective in influencing driver behavior in yellow light zones by reducing their inclination to run through them.

The Role of Luminescent Coupling in Monolithic Perovskite/Silicon Tandem Solar Cells.

Luminescent coupling (LC) is a key phenomenon in monolithic tandem solar cells. This study presents a nondestructive technique to quantitatively evaluate the LC effect, addressing a gap in the existing predictions made by optical modeling. The method involves measuring the ratio of photons emitted from the high bandgap top cell that escape through the rear, contributing additional current to the bottom cell, and to those escaping from the front side of top cell. The findings indicate that in the analyzed monolithic perovskite/silicon tandem solar cells, more than 85% of the emitted photons escaping from the perovskite top cell are used to generate additional current in the bottom cell. This process notably reduces the mismatch in the generated current between each subcell, particularly when the current is limited by the low bandgap subcell. The presented method is applicable to a variety of monolithic tandem structures, providing vital information for subcell characterization, providing vital information for predicting energy output and optimization for outdoor applications.

Thoracic Endovascular Aortic Repair for an Aortoesophageal Fistula Caused by Esophageal Cancer: A Case Report and Literature Review.

Aortoesophageal fistula (AEF) is an uncommon complication of esophageal cancer and can be extremely fatal if left untreated. Compared to open repair, thoracic endovascular aortic repair (TEVAR), a less invasive technique, is the initial recommended treatment in cases of hemorrhagic shock secondary to AEF, as this procedure showed a favorable outcome in controlling the overt bleeding. Here, we present a case of a patient with a history of stage IV esophageal cancer being treated with chemotherapy and an esophageal stent due to a previous tracheoesophageal fistula who presented to the emergency room due to severe gastroesophageal bleeding and hemorrhagic shock. A CT angiography of the chest revealed an AEF. The patient was subsequently resuscitated and treated with TEVAR. After the procedure, the hemorrhage was managed, and the patient was discharged with palliative radiation therapy. However, after one month, the patient had a major gastrointestinal hemorrhage, which caused her death. This example indicates the necessity of early detection and surgical intervention in AEF patients with unstable hemodynamics who have underlying unresectable esophageal cancer and chemotherapy. TEVAR should be conducted as soon as possible before the open surgery to achieve the best outcome for patients.

Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation.

BACKGROUND: Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive. METHODS: Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE. RESULTS: We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters. CONCLUSION: Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.

Nuclear localization of Arabidopsis HD-Zip IV transcription factor GLABRA is driven by Importin α.

GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor (TF) from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to EYFP show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified Importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell-type differentiation of the epidermis.

Bio-intelligent plasma-engineered diferuloylmethane/fucoidan/neutrophil lysate/iron oxide nanoclusters for phototherapeutic and magnetotherapeutic with in situ magnetic gelation mitigating inflammatory diseases.

Creating a versatile and remotely self-assembling biocomposite for delivering therapeutics to alleviate inflammatory diseases poses significant challenges. This study introduces a novel biocomposite, created through cold-atmosphere plasma treatment, that combines fucoidan (Fu) and neutrophil lysate (Nu) to mediate the self-assembly of diferuloylmethane (DIF) and iron oxide (IO) nanoclusters, termed DIF-Nu/Fu-IO NC. This biocomposite forms a phototherapeutic and magnetically-driven in situ gel with open-porous architecture loaded with DIF, offering non-invasive theranostic capabilities for treating inflammatory diseases. It demonstrates efficacy in both an intraarticular zymosan-induced rheumatoid arthritis animal model and an intranasal LPS-induced inflammatory lung model. Upon administration, near-infrared (NIR) irradiation and magnet application significantly improved the condition of the animals with rheumatoid arthritis and lung inflammation. This breakthrough heralds a new paradigm in bioinspired, versatile, theranostic, self-assembling biocomposites for addressing clinical inflammatory diseases.

CO2 Laser Crystallization in Ambient for Highly Efficient FAPbI3 Perovskite Solar Cells.

Metal halide perovskite solar cells have achieved tremendous progress and have attracted enormous research and development efforts since the first report of demonstration in 2009. Due to fabrication versatility, many heat treatment methods can be utilized to achieve perovskite film crystallization. Herein, 10.6 µm carbon dioxide laser process is successfully developed for the first time for perovskite film crystallization. In addition, this is the first time formamidinium lead triiodide solar cells by laser annealing under ambient are demonstrated. The champion cell produces a power conversion efficiency of 21.8%, the highest for laser-annealed perovskite cells. And this is achieved without any additive, passivation, or post-treatment.

Advancing teeth whitening efficacy via dual-phototherapeutic strategy incorporating molybdenum disulfide embedded in carrageenan hydrogel for dental healthcare.

Teeth discoloration poses a widespread challenge in dental health across various regions. Conventional teeth whitening methods often result in enamel deterioration and soft tissue harm due to the utilization of incompatible whitening agents and continuous intense light exposure. Here, we propose an effective phototherapy technique for teeth whitening, employing pathways of energy transition through intersystem crossing. The integration of MoS2 nanosheets into carrageenan gel (MoS2 NSs@Carr) facilitates both photothermal-hyperthermia and the generation of reactive oxygen species (ROS) through photocatalytic processes. The efficacy of ROS generation by the phototherapeutic MoS2 NSs@Carr on teeth whitening in the scenario. This approach ensures comprehensive teeth whitening by eliminating deep-seated stains on the teeth while preserving structural integrity and avoiding any tissue toxicity. This research highlights the efficacy of the phototherapeutic MoS2 NSs@Carr for dental whitening and underscores the potential of exploring nanostructures based on MoS2 NSs for managing dental healthcare issue.

Prevalence and Symptom Profile of Long COVID among Schoolchildren in Vietnam.

BACKGROUND: Long COVID is a recognized condition that can follow SARS-CoV-2 infection. It has been primarily observed and studied in adults. Evidence on long COVID among children is scarce. We aimed to estimate its prevalence and symptom profile among schoolchildren, and its effects on studying, daily activities, and quality of life. METHODS: We conducted a cross-sectional online survey among caregivers of 2226 schoolchildren aged 12-17 in Thai Nguyen, Vietnam, from 11 April to 16 May 2023 using WHO definitions and a validated quality of life questionnaire. RESULTS: Among 1507 children with confirmed SARS-CoV-2 infection ≥ 5 months prior, 85 (5.6%) had long COVID. Memory loss (85.9%), poor concentration capacity (58.8%), and fatigue (57.6%) were their most common symptoms. They reported more frequent interference with their studies, observed differences in school absence rates, reduced daily activities, worsened overall health status, and relatively higher utilization of health services compared with children who only suffered from acute COVID-19 symptoms after infection. CONCLUSIONS: Given the near-ubiquitous exposure to SARS-CoV-2 among children at this stage of the pandemic, our findings contribute invaluable evidence of an emerging public health burden among the pediatric population in Vietnam and globally. Concerted public health measures are needed to reduce long-term impacts on health, education, and wellbeing.

Oocyte-specific EXOC5 expression is required for mouse oogenesis and folliculogenesis.

EXOC5 is a crucial component of a large multi-subunit tethering complex, the exocyst complex, that is required for fusion of secretory vesicles with the plasma membrane. Exoc5 deleted mice die as early embryos. Therefore, to determine the role of EXOC5 in follicular and oocyte development, it was necessary to produce a conditional knockout (cKO), Zp3-Exoc5-cKO, in which Exoc5 was deleted only in oocytes. The first wave of folliculogenesis appeared histologically normal and progressed to the antral stage. However, after IVF with normal sperm, oocytes collected from the first wave (superovulated 21-day-old cKO mice) were shown to be developmentally incompetent. Adult follicular waves did not progress beyond the secondary follicle stage where they underwent apoptosis. Female cKO mice were infertile. Overall, these data suggest that the first wave of folliculogenesis is less sensitive to oocyte-specific loss of Exoc5, but the resulting gametes have reduced developmental competence. In contrast, subsequent waves of folliculogenesis require oocyte-specific Exoc5 for development past the preantral follicle stage. The Zp3-Exoc5-cKO mouse provides a model for disrupting folliculogenesis that also enables the separation between the first and subsequent waves of folliculogenesis.

Effectiveness of a Multifaceted Implementation Strategy to Increase Equitable Hospital at Home Utilization: An Interrupted Time Series Analysis.

BACKGROUND: The number of Hospital-at-Home (HaH) programs rapidly increased during the COVID-19 pandemic and after issuance of Centers for Medicare and Medicaid Services' (CMS) Acute Hospital Care at Home (AHCaH) waiver. However, there remains little evidence on effective strategies to equitably expand HaH utilization. OBJECTIVE: Evaluate the effects of a multifaceted implementation strategy on HaH utilization over time. DESIGN: Before and after implementation evaluation using electronic health record (EHR) data and interrupted time series analysis, complemented by qualitative interviews with key stakeholders. PARTICIPANTS: Between December 2021 and December 2022, we identified adults hospitalized at six hospitals in North Carolina approved by CMS to participate in the AHCaH waiver program. Eligible adults met criteria for HaH transfer (HaH-eligible clinical condition, qualifying home environment). We conducted semi-structured interviews with 12 HaH patients and 10 referring clinicians. INTERVENTIONS: Two strategies were studied. The discrete implementation strategy (weeks 1-12) included clinician-directed educational outreach. The multifaceted implementation strategy (weeks 13-54) included ongoing clinician-directed educational outreach, local HaH assistance via nurse navigators, involvement of clinical service line executives, and individualized audit and feedback. MEASURES: We assessed weekly averaged HaH capacity utilization, weekly counts of unique referring providers, and patient characteristics. We analyzed themes from qualitative data to determine barriers and facilitators to HaH use. RESULTS: Our evaluation showed week-to-week increases in HaH capacity utilization during the multifaceted implementation strategy period, compared to discrete-period trends (slope-change odds ratio-1.02, 1.01-1.04). Counts of referring providers also increased week to week, compared to discrete-period trends (slope-change means ratio-1.05, 1.03-1.07). The increase in HaH utilization was largest among rural residents (11 to 34%). Barriers included HaH-related information gaps and referral challenges; facilitators included patient-centeredness of HaH care. CONCLUSIONS: A multifaceted implementation strategy was associated with increased HaH capacity utilization, provider adoption, and patient diversity. Health systems may consider similar, contextually relevant multicomponent approaches to equitably expand HaH.

Connectome-based Brain Marker Moderates the Relationship between Childhood Adversity and Transdiagnostic Psychopathology during Early Adolescence.

Importance: Identifying brain-based markers of resiliency that reliably predict who is and is not at elevated risk for developing psychopathology among children who experience adverse childhood experiences (ACEs) is important for improving our mechanistic understanding of these etiological links between child adversity and psychopathology and guiding precision medicine and prevention efforts for reducing psychiatric impact of ACEs. Objective: To examine associations between ACEs and transdiagnostic psychopathology during the transition from preadolescence to early adolescence and test whether these associations are moderated by a hypothesized resilience factor, a previously identified connectome variate (CV) that is associated with higher cognitive function and lower psychopathology. Design Setting and Participants: This study was conducted in a longitudinal design based on multicenter data from a community cohort of U.S. youth aged of 9-11 at baseline, who participated in the Adolescent Brain Cognitive Development (ABCD) study (N=7,382 at baseline and 6,813 at 2-year follow-up). Linear regression models and moderation analyses were used to characterize concurrent and prospective associations between lifetime ACEs and number of DSM-5 psychiatric disorders (indexing transdiagnostic psychopathology) and to determine if individual variations in these associations were moderated by the CV derived from resting-state fMRI at baseline. Main Outcomes and Measures: Cumulative number of current DSM-5 psychiatric disorders assessed using the computerized self-admin version Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) and lifetime ACEs assessed from child and parent reports at baseline (9-10 years) and 2-year-follow-up (11-12 years). Results: ACE total scores correlated positively with the cumulative number of current DSM-5 psychiatric disorders at both baseline (r =.258, p < .001) and 2-year follow-up (r =.257, p < .001). The baseline CV score moderated the ACE-disorder associations at baseline (B = -0.021, p < .001) and at 2-year follow-up (B = -0.018, p = .008), as well as the association between the changes in ACE and in the number of disorders from baseline to year 2 (B = -0.012, p = .045). Post-hoc analyses further showed that the moderation effect of CV on ACE-psychopathology associations was specific to the threat-related ACEs and to female youth. Conclusions and Relevance: These findings provide preliminary evidence for a connectome-based resiliency marker and suggest that functional connectivity strength in a broad system including frontal-parietal cortices and subcortical nuclei relevant to cognitive control may protect preadolescents who have experienced lifetime ACEs--especially females and those experiencing threat-related ACEs--from developing transdiagnostic psychopathology.

Ultra-high frequency repetitive TMS at subthreshold intensity induces suprathreshold motor response via temporal summation.

Objective.The transcranial magnetic stimulation (TMS) coil induces an electric field that diminishes rapidly upon entering the brain. This presents a challenge in achieving focal stimulation of a deep brain structure. Neuronal elements, including axons, dendrites, and cell bodies, exhibit specific time constants. When exposed to repetitive TMS pulses at a high frequency, there is a cumulative effect on neuronal membrane potentials, resulting in temporal summation. This study aims to determine whether TMS pulse train at high-frequency and subthreshold intensity could induce a suprathreshold response.Approach.As a proof of concept, we developed a TMS machine in-house that could consistently output pulses up to 250 Hz, and performed experiments on 22 awake rats to test whether temporal summation was detectable under pulse trains at 100, 166, or 250 Hz.Main results.Results revealed that TMS pulses at 55% maximum stimulator output (MSO, peak dI/dt= 68.5 A/µs at 100% MSO, pulse width = 48µs) did not induce motor responses with either single pulses or pulse trains. Similarly, a single TMS pulse at 65% MSO failed to evoke a motor response in rats; however, a train of TMS pulses at frequencies of 166 and 250 Hz, but not at 100 Hz, successfully triggered motor responses and MEP signals, suggesting a temporal summation effect dependent on both pulse intensities and pulse train frequencies.Significance.We propose that the temporal summation effect can be leveraged to design the next-generation focal TMS system: by sequentially driving multiple coils at high-frequency and subthreshold intensity, areas with the most significant overlapping E-fields undergo maximal temporal summation effects, resulting in a suprathreshold response.

Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air.

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2-3 µm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.

Obesity is associated with adverse outcomes in primary immune thrombocytopenia - a retrospective single-center study.

The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.

A review on revolutionizing ophthalmic therapy: Unveiling the potential of chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer in eye disease treatments.

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery.

Ultrasensitive and multiplexed tracking of single cells using whole-body PET/CT.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of 18F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.

Increased [18F]FDG uptake of radiation-induced giant cells: a single-cell study in lung cancer models.

Positron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([18F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [18F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [18F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [18F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [18F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [18F]FDG uptake could potentially obfuscate the interpretation of [18F]FDG-PET scans in patients who have recently undergone radiation therapy.