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SLC46A3, a transporter for lysosomal steroid conjugates and bile acids, plays a pivotal role in the pharmacological effects of noncleavable antibody-drug conjugates using maytansine as a payload. SLC46A3 may exert negative effects on various phenomena, including copper homeostasis, mitochondrial function in the liver, and the uptake of lipid-based nanoparticles (NPs) in tumor cells. Consequently, inhibiting SLC46A3 may be a promising strategy for treating hepatic disease or enhancing lipid NP delivery to tumor cells, although the underlying mechanisms remain unknown. This study investigates flavonoids, the largest subgroup of polyphenols characterized by a simple C6-C3-C6 structure, as potential SLC46A3 inhibitors and provides insights into the structural requirements for flavonoid-SLC46A3 interactions. Screening revealed several flavonoids, including dihydrochalcones, flavonols, isoflavones, flavanones, and flavones, as effective inhibitors of 5-carboxyfluorescein (5-CF) uptake in MDCKII (Mardin-Darby canine kidney type II) cells stably expressing a mutant SLC46A3 localized to the plasma membrane. Notably, apigenin and luteolin exhibited marked 5-CF uptake inhibition, with IC 50 values of 10.8 and 8.7 µM, respectively. Additionally, 4',7-dihydroxyflavone significantly inhibited 5-CF uptake, exhibiting an IC 50 value of 9.3 µM, whereas acacetin and genkwanin possessing methoxy group substitutions for the hydroxy group at the 4'- or 7-position of apigenin, respectively, did not affect the uptake. Luteolin's inhibition mechanism was found to be of a mixed type involving increased K m and decreased V max . These findings emphasize the importance of hydroxy groups at 4'- and 7-positions in flavone-SLC46A3 interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We investigated the relationships among motor function, physical activity, and the characteristics of chronic pain (the number of pain sites, pain intensity, and pain-type)., Design: Cross-sectional study., Setting: An ongoing community-based prospective study conducted in Itoshima, Japan., Subjects: Community-dwelling Japanese aged 65-75 years (n = 805; 401 men, 404 women)., Measures: Chronic pain subtypes were examined in terms of the number of pain sites, pain intensity, and pain type. Motor function was evaluated by handgrip strength, walking speed, and the 5 Times Stand-up and Sit Test (FTSST). Locomotive activity, non-locomotive activity, and sedentary time were evaluated by a tri-axial accelerometer as physical-activity parameters., Analysis: Multiple regression model adjusting for age, sex, education level, employment status, subjective economic status, body mass index, cognitive function, comorbidity, current tobacco use, current alcohol consumption, and regular exercise., Results: In a multivariate analysis, the subjects' walking speed was negatively associated with multisite, moderate-to-severe, and neuropathic-like pain. The FTSST was positively associated with single-site, moderate-to-severe, and neuropathic-like pain. There was no significant association between handgrip strength and any chronic pain subtypes. Locomotive activity was negatively related to multisite, moderate-to-severe, and neuropathic-like pain, but there was no clear association between the amount of non-locomotive activity, sedentary time, and chronic pain subtypes., Conclusion: Severe chronic pain was associated with decreased locomotion-related motor function and physical activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson's correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (p = 0.020) and knee extension strength as a physical performance (p = 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens., (© 2024. The Author(s).)

This study explores sustainable agricultural practices by examining the role of organic materials in enhancing native predatory mites for controlling spider mites in apple orchards. Developing techniques to conserve indigenous natural enemies is vital for sustainable agricultural production. Phytoseiid mites can control spider mites, which are among the most significant pests in apple production. To conserve phytoseiid mite populations, it is important to identify alternative prey and to determine their role in phytoseiid mite proliferation. We demonstrated that the concurrent use of specific organic fertilizers and coconut husks can increase prey Tyrophagus mites, thereby enhancing phytoseiid mite density. Our research was conducted using sticky traps at the Miyagi Prefectural Agriculture and Horticulture Research Center in Japan. The occurrence of Tyrophagus mites was significantly correlated with the occurrence of phytoseiid mites in 2 years. In laboratory experiments, the use of organic fertilizers increased the density of Tyrophagus mites by 83 × within 4 weeks. Several species of phytoseiid mites were able to lay between 0.25 and 1.03 eggs per day per female by preying on Tyrophagus larvae. A 2-year field survey revealed that the use of organic fertilizers more than doubled the density of phytoseiid mites on apple leaves, likely through promoting Tyrophagus mite proliferation on the ground. These results highlight the potential of organic fertilizers not only to enhance soil nutrients, but also to boost phytoseiid mite populations, thereby contributing to more sustainable apple production., (© 2024. The Author(s).)

Background: In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson's disease in whom FIP was replaced with IOD., Case Presentation: An 81-year-old male patient with Parkinson's disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned., Conclusions: By replacing FIP with IOD in an older patient with Parkinson's disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis., (© 2024. The Author(s).)

A rheo-optical characterization technique based on the combination of near-infrared (NIR) spectroscopy and tensile testing was applied for the first time to an actual rubber sample based on styrene-butadiene rubber (SBR) including silica filler. When SBR samples were subjected to mechanical deformation, changes in the NIR spectral features were readily captured. Two-trace two-dimensional (2T2D) correlation analysis was then applied to the sets of NIR spectra to clearly reveal the subtle but pertinent difference between the NIR spectral features of the initial and deformed SBR. The initial deformation of the sample induces greater deformation of the soft butadiene groups than of the hard styrene groups. The inclusion of the silica filler and a coupling agent (CA) essentially develops firm links between the silica and butadiene via the CA to restrict the displacement of the butadiene during the tensile deformation of the system. The development of such linkage requires even more mechanical force to deform the SBR, which, in turn, improves Young's modulus of the rubber system. Asynchronous correlation spectra of SBR with no silica filler revealed that, during the deformation of the SBR, the butadiene groups were initially deformed, and this feature was then replaced by the predominant deformation of the hard styrene groups. On the other hand, this correlation feature became somewhat unclear when a similar analysis was applied to the SBR sample with silica filler, revealing subtle differences in interaction between individual comonomer functional groups distributed randomly along the copolymer chain and CA., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The strain dependence of the Johari-Goldstein (JG)-β relaxation time, as well as the directional dependence, was systematically investigated for stretched cross-linked polybutadiene using time-domain interferometry. We found that the strain dependence of the JG-β relaxation time is directionally dependent, contrary to expectation: the relaxation time of the JG-β motion, whose displacement is perpendicular to the stretching direction, decreases with stretching, whereas the relaxation time of the parallel JG-β motion changes little. This result is distinct from the previously reported strain dependence of the α relaxation time, where the relaxation time increases isotropically with stretching. Thus, the difference in the strain dependence of the relaxation time between the α and JG-β processes suggests a microscopic origin and requires the modification of the conventional dynamic picture for stretched polymers.

Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kishimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a K m of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC 50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Intensive care unit (ICU) nurses' professional autonomy is a critical factor affecting their ability to sustainably provide high-quality care to patients who are critically ill and to their families. However, in the absence of a systematic or scoping review of ICU nurses' professional autonomy, limited information and evidence are available on this topic. The aim of this scoping review was to clarify the extent and type of evidence on ICU nurses' professional autonomy. This scoping review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. The following research questions were addressed: (1) Which areas of interest and trends regarding ICU nurses' professional autonomy have been explored in studies published in scientific journals? And (2) What is known about ICU nurses' professional autonomy? The data sources included MEDLINE, CINAHL Ultimate, PsycINFO, Cochrane Library, and Ichushi-Web of the Japan Medical Abstracts Society databases. Identified studies were mapped based on their aim, design, methodology, and key findings and categorized according to their focus areas. Of the 734 identified studies, 16 were analyzed. The identified categories were as follows: "relationship between professional autonomy and mental issues," "experiences and processes of exercising professional autonomy," "relationship between professional autonomy and nurse-physician collaboration," "relationship between professional autonomy and demographic characteristics," "concept of professional autonomy," "barriers to professional autonomy," and "team approach to improve professional autonomy." Most studies have focused on the relationship between professional autonomy and mental health issues and nurse-physician collaboration and few included interventions to enable or promote the exercise of professional autonomy, highlighting a research gap. Future research should identify factors that inhibit the professional autonomy of ICU nurses and that can be changed through interventions and should develop educational and organizational change-based interventions to modify the factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ito et al.)

Background: The association of the individual and combined effects of moderate-to-vigorous physical activity (MVPA) and sleep quality with physical frailty in community-dwelling older adults is still unknown., Subjects and Methods: A cross-sectional study was conducted with a sample of older adults who had not required nursing care or support services. Physical frailty was assessed using Liu's definition based on Fried's concept. MVPA was measured by a triaxial accelerometer, and individuals who met either moderate physical activity (MPA) for ≥300 min/week, vigorous physical activity (VPA) for ≥150 min/week, or both were defined as "MVA + ". "SLP + " was defined as a Pittsburgh Sleep Quality Index score of <5.5 points., Results: A total of 811 participants were included in the final analysis. After adjusting for the multivariable confounding factors, the odds ratios (ORs) and 95% confidence intervals (CIs) for physical pre-frailty and frailty in the MVA - SLP + (OR, 2.56; 95%CI, 1.80-3.62) and the MVA - SLP - group (OR, 3.97; 95%CI, 2.33-6.74) were significantly higher compared with the MVA + SLP + group., Conclusion: Community-dwelling older adults who did not meet the MVPA criteria, regardless of sleep quality, had a higher prevalence of physical frailty.

Nanoscale soft-X-ray microscopy is a powerful analysis tool in biological, chemical, and physical sciences. To enhance its probe sensitivity and leverage multimodal soft-X-ray microscopy, precise achromatic focusing devices, which are challenging to fabricate, are essential. Here, we develop an ultracompact Kirkpatrick-Baez (ucKB) mirror, which is ideal for the high-performance nanofocusing of broadband-energy X-rays. We apply our advanced fabrication techniques and short-focal-length strategy to realize diffraction-limited focusing over the entire soft-X-ray range. We achieve a focus size of 20.4 nm at 2 keV, which represents a significant improvement in achromatic soft-X-ray focusing. The ucKB mirror extends soft-X-ray fluorescence microscopy by producing a bicolor nanoprobe with a 1- or 2-keV photon energy. We propose a subcellular chemical mapping method that allows a comprehensive analysis of specimen morphology and the distribution of light elements and metal elements. ucKB mirrors will improve soft-X-ray nanoanalyses by facilitating photon-hungry, multimodal, and polychromatic methods, even with table-top X-ray sources., (© 2023. The Author(s).)

Background: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial-mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC., Methods: The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis ( P.g ) or Escherichia coli ( E. coli ) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined., Results: PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS., Conclusion: Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs.