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Abstract Background Due to the rapid increase in chronic diseases in South Korea, the Korean government has expanded chronic disease management to primary care. Thus, the role of primary care nurses is critical. However, the fee for chronic disease management services provided by primary care nurses has not been set, and few studies have evaluated the value of nursing services. This study aimed to estimate the willingness to pay (WTP) for chronic disease management services provided by primary care nurses and to identify the factors that affect WTP. Methods This study adopted a descriptive research design and conducted a cross-sectional online survey from January 16 to 18, 2023. The inclusion criteria were community residents aged ≥ 20 years living in South Korea and capable of participating in online surveys. A total of 520 people participated in this study. A contingent valuation method (CVM) was used with double-bound dichotomous choice questions along with open-ended questions. The mean WTP was calculated using a Tobit model. Results The mean WTP of the 520 study participants for one chronic disease management service provided by primary care nurses was 15,390.71 Korean won ($11.90). Factors affecting WTP were having a chronic disease, recognition of primary care nurses, and the first-bid price. Community residents with fewer chronic diseases, high awareness of primary care nurses, and a higher first-bid price showed higher WTP for chronic disease management services provided by primary care nurses. Conclusions Primary care is important worldwide due to the increasing number of chronic diseases, and Korea is no exception. However, payment for services by primary care nurses is undervalued compared to their critical role and skills. This has led to problems such as a primary care nurse shortage and burnout. This study estimated individuals’ WTP for chronic disease management services provided by primary care nurses. The results can be used as a basic resource for setting the fee for services provided by primary care nurses. It is also a good starting point to understand the benefits of primary care nurse services.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Abstract Phototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water‐soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal‐to‐liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.

Abstract Background Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. Methods Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. Results When the upper part of a mouse brain was irradiated using a laser (0.2 W cm− 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. Conclusion This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas. Graphical Abstract

Abstract Bacteria can cause numerous infectious diseases and has been a major threat to human humans. Although antibiotics have partially succeeded in treating bacteria, owing to antibiotic abuse, the emergence of multidrug‐resistant (MDR) bacteria has drastically diminished their potency. Since the invention of laser, the combination of light and photosensitizers, photodynamic therapy (PDT), has become an effective noninvasive treatment along with photothermal therapy (PTT), in which heat is generated by nonradiative relaxation. Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection, particularly against MDR bacteria. This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

Antibiotic resistance is one of the major causes of morbidity and mortality, triggered by the adhesion of microbes and to some extent the formation of biofilms. This condition has been quite challenging in the health and industrial sector. Conditions and processes required to foil these infectious and resistance are of much concern. The synthesis of PDA material, inspired by the Mytilus edulis foot protein (MEFP)5 possesses unique characteristics that allow for, adhesion, photothermal therapy, synergistic effects with other materials, biocompatibility process, etc. Therefore, their usage holds great potential for dealing with both the infectious nature and the antibiotic resistance processes. Hence, this review provides an overview of the mechanism involved in accomplishing and eradicating bacteria, the recently harnessed antibacterial effect of the PDA through other properties they possess, a way forward in tapping the benefit embedded in the PDA, and the future perspective.

Summary: Biocompatible aggregation-induced emission (AIE) materials from natural resources are of great interest for a variety of potential applications. Here, we report the unconventional AIE nature of the green tea polyphenol epigallocatechin gallate (EGCG), which is investigated by observing the disappearance and reoccurrence of fluorescence when EGCG is dissolved and recrystallized in aqueous solutions. The intermolecular through-space conjugation and structural rigidification induced by multiple intermolecular H-bonds play critical roles in the AIE phenomenon. This inspires the development of a multicolored, monodisperse, photostable, and non-toxic nano-AIE luminogen (nano-AIEgen), which is simply prepared by polyphenol-amine-based crosslinking in aqueous solutions, demonstrating great potential for living cell bioimaging. Our strategy to develop nano-AIEgens using AIE-active hydrophilic natural products—e.g., plant polyphenols, such as tannic acid, that exhibit similar AIE characteristics—can help push the boundary of the exploration of various novel, large-scale, biocompatible, water-soluble, and degradable AIE materials from natural resources.

Abstract Activity‐based approaches for designing AIEgens possess prominent advantages including high selectivity, sensitivity, and signal‐to‐noise ratio, and they have received more attention in recent years. Excellent activatable AIE probes have been reported for detecting toxic substances, imaging intracellular active molecules/biomolecules, as well as monitoring the activity of overexpressed enzymes in cancers. Moreover, the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation, while they have no distinct effect on normal cells, demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy. Thus, in this review, we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications. The challenges of activatable AIE probes and the corresponding solutions are described. We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.

The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

Exercise intensity of exoskeleton-assisted walking in patients with spinal cord injury (SCI) has been reported as moderate. However, the cardiorespiratory responses to long-term exoskeleton-assisted walking have not been sufficiently investigated. We investigated the cardiorespiratory responses to 10 weeks of exoskeleton-assisted walking training in patients with SCI. Chronic nonambulatory patients with SCI were recruited from an outpatient clinic. Walking training with an exoskeleton was conducted three times per week for 10 weeks. Oxygen consumption and heart rate (HR) were measured during a 6-min walking test at pre-, mid-, and post-training. Exercise intensity was determined according to the metabolic equivalent of tasks (METs) for SCI and HR relative to the HR reserve (%HRR). Walking efficiency was calculated as oxygen consumption divided by walking speed. The exercise intensity according to the METs (both peak and average) corresponded to moderate physical activity and did not change after training. The %HRR demonstrated a moderate (peak %HRR) and light (average %HRR) exercise intensity level, and the average %HRR significantly decreased at post-training compared with mid-training (31.6 ± 8.9% to 24.3 ± 7.3%, p = 0.013). Walking efficiency progressively improved after training. Walking with an exoskeleton for 10 weeks may affect the cardiorespiratory system in chronic patients with SCI.

A long wavelength TCF-based fluorescent probe (TCF-ALP) was developed for the detection of alkaline phosphatase (ALP). ALP-mediated hydrolysis of the phosphate group of TCF-ALP resulted in a significant fluorescence “turn on” (58-fold), which was accompanied by a colorimetric response from yellow to purple. TCF-ALP was cell-permeable, which allowed it to be used to image ALP in HeLa cells. Upon addition of bone morphogenic protein 2, TCF-ALP proved capable of imaging endogenously stimulated ALP in myogenic murine C2C12 cells. Overall, TCF-ALP offers promise as an effective fluorescent/colorimetric probe for evaluating phosphatase activity in clinical assays or live cell systems.

Due to the simplicity and low detection limit, especially the bioimaging ability for cells, fluorescence probes serve as unique detection methods. With the aid of molecular recognition and specific organic reactions, research on fluorescent imaging probes has blossomed during the last decade. Especially, reaction based fluorescent probes have been proven to be highly selective for specific analytes. This review highlights our recent progress on fluorescent imaging probes for biologically important species, such as biothiols, reactive oxygen species, reactive nitrogen species, metal ions including Zn2+, Hg2+, Cu2+ and Au3+, and anions including cyanide and adenosine triphosphate (ATP).

PurposeShort sleep duration is associated with obesity. Urinary 6-sulfatoxymelatonin (6-OHMS), the principal metabolite of melatonin, is closely related with sleep. We evaluated the difference in urinary 6-OHMS levels between obese girls and normal weight girls, and the relationship of urinary 6-OHMS with other hormones regulating body weight and metabolism.MethodsA total of 79 girls (6.3 to 12.4 years) were included in this study, of whom 34 were obese; 15, overweight; and 30, normal-weight. We examined their pubertal status and bone age. Fasting serum levels of total ghrelin, leptin, insulin, and first morning urinary 6-OHMS were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was calculated from the fasting insulin and glucose levels.ResultsThere was no significant difference in the creatinine adjusted 6-OHMS levels between the obese girls and the control group. Urinary 6-OHMS did not show any correlations with body mass index (BMI), BMI percentile, total ghrelin, leptin, and HOMA-IR. Negative correlations were found between urinary 6-OHMS levels and chronological and bone ages.ConclusionOur results suggest that melatonin production is not reduced consistently in obese girls.

BackgroundPseudomonas aeruginosa (PA) and Burkholderia cepacia complex (Bcc), commonly found in the lungs of cystic fibrosis (CF) patients, often produce cyanide (CN), which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown.Methods and findingsThis work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4',5'-fluorescein dicarboxaldehyde) with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM) in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs.ConclusionsThe in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.

The accumulation of mercury pollution in plants can induce severe injury to human beings. It is a great challenge to monitor ultra-low concentrations of mercury in complicated matrixes. In this study, we successfully developed a strategy via Hg2+-triggered naphthalene-based fluorescent probe 1, which formed excimer that subsequently emitted fluorescence for the successful detection of ultra-low concentrations of Hg2+. The coordination of N and S atoms with Hg2+ facilitated the formation of excimer from the naphthalene-conjugated planes that were in sufficiently close proximity. Suppression of CQN bond rotation also induced the chelation-enhanced fluorescence (CHEF) effect, and the cumulative result of these effects was obvious fluorescent enhancement. Compared with probe 2, the other key factor for detection of Hg2+ is that the electrons of the hydroxyl group can easily transfer to a naphthalene moiety, resulting in an augmented p-electron density that enhanced the π–π stacking of the naphthalene-conjugated excimer. After detailed spectral studies and mechanism discussions, it was realized that probe 1 was able to detect ultra-low concentrations of Hg2+ in PBS buffer solution. The detection limit was calculated to be 1.98 nM. On account of the excellent performances, the probe was successfully applied in monitoring Hg2+ in water and pea sprouts with the potential for application as an advanced warning of contamination. [ABSTRACT FROM AUTHOR]