Guest-Responsive Near-Infrared-Luminescent Metal-Organic Cage Organized by Porphyrin Dyes and Yb(III) Complexes.

Metal-organic cages (MOCs) with luminophores have significant advantages for the facile detection of specific molecules based on turn-on or turn-off luminescence changes induced by host-guest complexation. One important challenge is the development of turn-on-type near-infrared (NIR)-luminescent MOCs. In this study, we synthesized a novel MOC consisting of two porphyrin dyes linked by four Yb(III) complexes, which exhibit bimodal red and NIR fluorescence signals upon photoexcitation of the porphyrin π system. Single-crystal X-ray structural analysis and computational molecular modeling revealed that planar aromatic perfluorocarbons were intercalated into the MOC. The tight packing between the MOC and guests enhanced the NIR fluorescence of Yb(III) by suppressing energy transfer from the photoexcited porphyrin to oxygen molecules. Guest-responsive turn-on NIR fluorescence changes in an MOC were successfully demonstrated.

Mechanofluorochromism and self-recovery of alkylsilylpyrene-1-carboxamides.

A family of (alkylsilyl)pyrene-1-carboxamides exhibits similar mechanofluorochromic responses upon grinding. However, their spontaneous fluorescence recovery processes are distinct despite their similarity in chemical structures and crystal packings. Fluorescence spectroscopy, crystallography, and nanomechanical tests revealed that the chromic direction is dominated by the packing motif, while the fluorescence recovery is driven by the intermolecular interactions and the reversibility of deformation.

MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma.

Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p < 0.005). Our results thus suggest that miR-326 negatively regulates CD155 expression in lung adenocarcinoma and might therefore play a role in the development of resistance to PD-1/PD-L1 inhibitors.

Regulation of PD-L1 expression in non-small cell lung cancer by interleukin-1ß.

Introduction: Programmed cell death-ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1ß (IL-1ß) plays a key role in regulation of PD-L1 expression in non-small cell lung cancer (NSCLC). Methods: We performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1ß in vitro to elucidate its induction of PD-L1 on NSCLC cells. Results: The IL-1ß gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1ß and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1ß and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1ß and IFN-γ. Discussion: Our study reports high levels of IL-1ß in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1ß-MAPK axis being a promising therapeutic target for attenuation of PD-L1-mediated suppression of antitumor immunity.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

BACKGROUND: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. METHODS: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. RESULTS: The maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). CONCLUSIONS: Plasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Structural metamorphosis and photophysical properties of thermostable nano- and microcrystalline lanthanide polymer with flexible coordination chains.

Luminescent lanthanide coordination polymer crystals (LCPCs) represent an area of growing interest in materials chemistry owing to their unique and tailorable functional properties. The LCPCs provide a high level of structural tunability, including size- and morphology-dependent properties; therefore, they are promising materials for next-generation phosphors in a wide range of applications such as light emitting diodes. Here, by controlling the morphology of thermostable europium coordination polymer crystals, [Eu(hfa)3(dpbp)]n, hfa: hexafluoroacetylacetonate and dpbp:4,4'-bis(diphenyl　phosphoryl) biphenyl), we realized a novel red phosphor with narrow linewidth emission (FWHM = 7.8 nm). The obtained luminescent LCPCs with unique structures were characterized by X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), dynamic light scattering (DLS) and thermogravimetric analysis. Among, them, size tunable crystalline polymer spheres were found to have high internal quantum efficiency (ex., IQE = 79%) and highly thermostability (>300°C), and to exhibit dispersibility in PMMA media. The obtained results on the structural tunability of these materials can be used for the development of synthesis techniques for nanoscale materials based on crystalline lanthanide-based coordination phosphors.

Narrow-Band Emitting Phosphor Na2Cs2Sr(B9O15)2:Eu2+ Discovered from Local Structure Similarity with Sulfate Phosphor.

Narrow-band emitting phosphors are required to improve the performance of phosphor-converted light-emitting diodes. Here, we found a new narrow-band emitting phosphor Na2Cs2Sr(B9O15)2:Eu2+ using the local structure similarity with a known narrow-band emitting phosphor. In a 2D scatter plot of the structural similarity between the local structures, the Sr site in Na2Cs2Sr(B9O15)2 was located near the Ba site of the known narrow-band emitting sulfate phosphor BaSO4:Eu2+ with a distorted local structure. We synthesized Na2Cs2Sr(B9O15)2:Eu2+ and characterized the luminescence properties by microspectroscopy. Na2Cs2Sr(B9O15)2:Eu2+ showed a violet luminescence peaked at 417 nm, and the full-width at half-maximum was as narrow as 26 nm (1497 cm-1).

Deep-red to near-infrared luminescence from Eu2+-trapped exciton states in YSiO2N.

The valence state of Eu ions doped in inorganic compounds is easily influenced by the synthesizing conditions. In this study, X-ray absorption spectroscopy revealed that almost half of Eu ions incorporated in the YSiO2N host were reduced into the divalent state through the sintering process at 1600 °C under a N2 gas atmosphere without any annealing processes. The prepared Eu2+/3+-doped YSiO2N sample showed anomalous deep-red to near-infrared luminescence below 300 K under violet light illumination, whose luminescent properties are discussed through detailed spectroscopic analyses. In the photoluminescence spectra at 4 K, the broad luminescence band ranging from 550 to 1100 nm with a large Stokes shift of 5677 cm-1 was observed, assigned to the recombination emission related to the Eu2+-trapped exciton state. The temperature dependence of luminescence lifetime suggests that the thermal quenching of Eu2+-trapped exciton luminescence takes place through complicated processes in addition to thermal ionization. The energy diagrams based on the spectroscopic results indicate that Eu2+-trapped exciton luminescence in the YSiO2N:Eu2+/3+ sample was observed because all the Eu2+: 5d excited levels are degenerated with the host conduction band, and the relatively stable Eu2+-trapped exciton state in the Y3+ sites is formed just below the conduction band bottom. A comprehensive discussion on the deep-red to near-infrared luminescence in the YSiO2N host could give new insights into the mechanism of Eu2+-trapped exciton luminescence in Y3+ sites, which has potential in near-infrared emitting devices.

Factors related to daily step counts of stroke patients during hospitalization in a convalescent rehabilitation ward.

OBJECTIVES: Clarifying the factors related to decreased physical activity in post-stroke patients is essential for effective disease management. This study aimed to examine the factors influencing the amount of daily steps taken by post-stroke patients in a convalescent rehabilitation ward during activities other than rehabilitation (non-rehabilitation steps). MATERIALS AND METHODS: Eighty-nine post-stroke patients (60.8±14.4 years; 55 men) were enrolled. The inclusion criteria were walking independently within the ward and having a walking speed of ≥24 m/min. Data on patient clinical characteristics including age, sex, body mass index, stroke type, hemiparetic side, and time from stroke onset were collected. Stroke impairment and motor and cognitive functional disabilities were assessed using the Stroke Impairment Assessment Set and the Functional Independence Measure, respectively. The non-rehabilitation steps were calculated by subtracting the steps during the rehabilitation activities from the total steps using Fitbit Flex2. RESULTS: The average number of non-rehabilitation steps was 4,523±2,339 steps/day. The hierarchical multiple regression analysis revealed that sex, motor disability, and the interaction term of stroke impairment with cognitive disability were significantly related to non-rehabilitation steps. Simple slope analysis demonstrated that the stroke impairment slope was steeper at lower levels than at higher levels of cognitive disability for non-rehabilitation steps. CONCLUSIONS: In addition to independent effects of sex and motor disability, this study found that stroke impairment and cognitive disability were interactively related to non-rehabilitation steps in post-stroke patients in a convalescent rehabilitation ward. These findings may provide useful information for managing physical activity in post-stroke patients after hospital discharge.

Increased plasma levels of damage-associated molecular patterns during systemic anticancer therapy in patients with advanced lung cancer.

BACKGROUND: Immunogenic cell death (ICD) characterized by the release of damage-associated molecular patterns (DAMPs) from dying cancer cells may contribute to the synergistic antitumor effect of cytotoxic chemotherapy combined with an immune checkpoint inhibitor. The kinetics of circulating DAMP levels in cancer patients have remained largely uncharacterized, however. METHODS: We evaluated the possible effects of various systemic anticancer therapy modalities on the kinetics of plasma DAMP concentrations in a prospective observational study of patients with advanced lung cancer. The plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), annexin A1, and histone H3 were thus determined in 121 such patients at four time points during the first cycle of treatment. RESULTS: The mean of the maximum fold change in HMGB1, HSP70, or annexin A1 concentration observed during treatment was significantly greater than the corresponding baseline value (P<0.005). The maximum fold changes in HMGB1 and CRT concentrations tended to be associated with clinical response as evaluated by RECIST criteria, although the changes in the levels of these two DAMPs were not correlated, suggestive of differential induction mechanisms. Among the various treatment modalities administered, platinum-based combination or single-agent chemotherapy tended to elicit robust increases in the concentrations of HMGB1 and CRT. CONCLUSIONS: Serial monitoring of plasma revealed that systemic anticancer therapy increased the circulating levels of HMGB1 and CRT and that these changes tended to be associated with clinical response, suggesting that agents capable of releasing these DAMPs into plasma might induce ICD in advanced lung cancer patients.

Dissimilarity measure of local structure in inorganic crystals using Wasserstein distance to search for novel phosphors.

To efficiently search for novel phosphors, we propose a dissimilarity measure of local structure using the Wasserstein distance. This simple and versatile method provides the quantitative dissimilarity of a local structure around a center ion. To calculate the Wasserstein distance, the local structures in crystals are numerically represented as a bag of interatomic distances. The Wasserstein distance is calculated for various ideal structures and local structures in known phosphors. The variation of the Wasserstein distance corresponds to the structural variation of the local structures, and the Wasserstein distance can quantitatively explain the dissimilarity of the local structures. The correlation between the Wasserstein distance and the full width at half maximum suggests that candidates for novel narrow-band phosphors can be identified by crystal structures that include local structures with small Wasserstein distances to local structures of known narrow-band phosphors. The quantitative dissimilarity using the Wasserstein distance is useful in the search of novel phosphors and expected to be applied in materials searches in other fields in which local structures play an important role.

Inhibitory effects of a selective prostaglandin E2 receptor antagonist RQ-15986 on inflammation-related colon tumorigenesis in APC-mutant rats.

Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis in the colorectum. This study aimed to investigate the chemopreventive ability of RQ-15986, a selective EP4 antagonist, in colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have APC mutations, were treated with azoxymethane and dextran sulfate sodium and subsequently administered RQ-15986 for eight weeks. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the RQ-15986-treated group. The cell proliferation of the crypts and tumors in the colorectum was decreased following RQ-15986 treatment. RQ-15986 also suppressed the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-18, and monocyte chemotactic protein-1, in the colon mucosa. In addition, the expression levels of indoleamine 2,3-dioxygenase, which is involved in immune tolerance, were decreased in the colorectal epithelium and tumors of the RQ-15986-treated group. These findings indicate that RQ-15986 inhibits colitis-associated colorectal tumorigenesis by attenuating inflammation, suppressing cell proliferation, and modulating the expression of indoleamine 2,3-dioxygenase. Targeting prostaglandin E2/EP4 signaling might be a useful strategy for chemoprevention of inflammation-related colorectal cancer.

Natural history of inferior mesenteric arteriovenous malformation that led to ischemic colitis: A case report.

BACKGROUND: Ischemic colitis with inferior mesenteric arteriovenous malformation (AVM) is a rare disease. Although a few reports have been published, no report has described the natural history of idiopathic mesenteric AVM. CASE SUMMARY: A 50-year-old male was admitted to our hospital due to abdominal pain that had persisted for 3 mo and bloody diarrhea. He had no history of trauma or abdominal surgery. He had undergone two colonoscopies 6 mo and 2 years ago, and they showed only a polyp. He was diagnosed with ischemic colitis with inferior mesenteric AVM following contrast-enhanced abdominal computed tomography (CT) and underwent rectal low anterior resection. He has not had a recurrence of symptoms for 3 years. His history showed that he had undergone non-enhanced abdominal CT 2, 5, and 8 years ago when he had attacks of urinary stones. Retrospectively, dilation of blood vessels around the rectosigmoid colon could have been detected 5 years ago, and these findings gradually became more evident. CONCLUSION: This is the first report of the natural history of inferior mesenteric AVM.

An outbreak of Paragonimus westermani infection among Cambodian technical intern trainees in Japan, exhibiting various extrapulmonary lesions.

We encountered an outbreak of paragonimiasis among Cambodian technical intern trainees (TITs) at a food-processing factory in Fukuoka, Japan. The patients were 20-28 years old, seven females and two males, who had been in Japan for one to four years. All of them had consumed raw or undercooked Japanese mitten crab they purchased at a local grocery store near their training place. CT images showed multiple lesions not only in the lungs but in the extrapulmonary organs as well, such as subcutaneous tissues, abdominal muscles, and mesentery, in most of the patients. Their medical records indicated that all of them acquired infection in Japan, not in Cambodia. Diagnosis was made serologically and the patients were treated with praziquantel successfully. Foreign workers and TITs are increasing in Japan so rapidly, that food borne-infections, including paragonimiasis, should be considered in people from developing countries who have exotic dietary habits.

Circularly Polarized Absorption and Luminescence of Semiconductor Eu-OCN Nanocrystals in the Blue Region of the Electromagnetic Spectrum.

Semiconductor nanomaterials with efficient polarized-light control in the blue region of the visible spectrum are promising candidates for modern and future photo-information technology, display devices, and optical sensing applications. New-type semiconductor Eu(OCN)2 nanocrystals with circularly polarized absorption (CD: circular dichroism) and emission (CPL: circularly polarized luminescence) under an applied magnetic field are demonstrated here for the first time. The effective CD signal at 1.6 T was observed at approximately 440 nm. The dissymmetry factor of CPL under 100 K, gM-CPL, was estimated to be 0.01. These characteristic circularly polarized absorption and emission phenomena of Eu(OCN)2 nanocrystals should be caused by combination between the "Faraday A and C terms" of the magnetic moment in the excited state. Polarized-light control using Eu(OCN)2 nanocrystals in the blue-light region of the electromagnetic spectrum is a large first step into a new world of photo-functional semiconductor nanomaterials.

Pleuropulmonary Paragonimiasis with Multiple Nodules in the Pleura.

An asymptomatic 47-year-old woman was admitted with pleural effusion and pulmonary infiltrates 1 month after ingesting raw wild boar and deer meat. Both her blood and pleural fluid were eosinophilic. Thoracoscopy revealed multiple nodules of the pleura, and biopsy samples of the nodules showed necrosis with epithelioid cell granulomas. An enzyme-linked immunosorbent assay was positive for antibodies against Paragonimus westermani, and the patient was successfully treated with praziquantel. This is the first reported case of pulmonary or pleuropulmonary paragonimiasis where several pleural nodules were observed. The detection of pleural nodules on thoracoscopy can contribute to the prompt and accurate diagnosis of paragonimiasis.

Fabrication of a Silica-Silica Nanoparticle Monolayer Array Nanocomposite Film on an Anodic Aluminum Oxide Substrate and Its Optical and Tribological Properties.

The fabrication and properties of silica nanoparticle monolayer arrays (SNMAs) immobilized on silica films on nanoporous anodic aluminum oxide (AAO) substrates by polymerization of silicic acid and a two-step spin-coating technique are reported. Reflection spectra of the obtained silica-SNMA nanocomposite films on AAO substrates were almost the same as those of the original AAO substrate. The coefficient of friction at an applied load of 0.98 N under dry conditions for a film fabricated under optimal conditions was significantly decreased by 76% with respect to that without a silica-SNMA nanocomposite film on an AAO substrate. The results also showed a lower coefficient of friction than that for MoS2 nanoparticles (commonly used for self-lubricating films) deposited on an AAO substrate. We demonstrate that the silica-SNMA nanocomposite film with an optimal nanoroughness, thickness, and wear resistance can be used as a novel coating film for AAO substrates with both a high color degree of freedom and a low coefficient of friction at a high applied load (ca. 1 N).

The Role of π-f Orbital Interactions in Eu(III) Complexes for an Effective Molecular Luminescent Thermometer.

Luminescent Eu(III) complexes with a ligand-to-metal charge transfer (LMCT) state were demonstrated for the development of a molecular thermometer. The Eu(III) complex was composed of three anionic ligands (hfa: hexafluoroacetylacetonate) and a phosphine oxide derivative containing a chrysene framework (diphenylphosphorylchrysene (DPCO)). The chrysene framework induced a rigid coordination structure via intermolecular interactions, resulting in a high thermal stability (decomposition point: 280 °C). The Eu(III) complex also exhibited an extremely high molar absorption coefficient (490000 cm-1 M-1), high intrinsic emission quantum yields (73%), and temperature-dependent energy migration between ligands and Eu(III) ion. The characteristic energy migration system was explained by the presence of the LMCT state based on π-f orbital interactions.

First aggregation-induced emission of a Tb(iii) luminophore based on modulation of ligand-ligand charge transfer bands.

Herein the aggregation-induced emission (AIE) of a Tb(iii) complex is reported for the first time. The Tb(iii) complex is composed of three anionic ligands (acac: acetylacetonate) and one large hetero-π-conjugated neutral ligand (dpq: dipyrido[3,2-f:2',3'-h]quinoxaline). The formation of a crystalline J-aggregate of the Tb(iii) complex (CJ-Tb(iii)) was characterized by X-ray crystal structure analysis and absorption spectra. A crystalline H-aggregate (CH-Tb(iii)) was also prepared using the ligand steric effect (tmh: 2,2,6,6-tetramethyl-3,5-heptanedionate). The emission and AIE properties of CJ-Tb(iii) were evaluated using emission spectra, lifetime, and quantum yields, whereas CH-Tb(iii) did not emit photons. Density functional theory calculations predict that the AIE originates from the modulation of ligand-to-ligand charge transfer bands through J-aggregation.

Stacked nanocarbon photosensitizer for efficient blue light excited Eu(III) emission.

Photosensitizer design to allow effective use of low-energy light is important for developing photofunctional materials. Herein, we describe a rational photosensitizer design for effective use of low-energy light. The developed photosensitizer is a stacked nanocarbon based on a rigid polyaromatic framework, which allows efficient energy transfer from the low-energy T1 level to the energy acceptor. We prepared an Eu(III) complex consisting of a luminescent center (Eu(III)) and stacked-coronene photosensitizer. The brightness of photosensitized Eu(III) excited using low-energy light (450 nm) is more than five times higher than the maximum brightness of previously reported Eu(III) complexes.