Semiconducting Transition Metal Dichalcogenide Heteronanotubes with Controlled Outer-Wall Structures.

Transition metal dichalcogenide (TMDC) nanotubes exhibit unique physical properties due to their nanotube structures. The development of techniques for synthesizing TMDC nanotubes with controlled structures is very important for their science and applications. However, structural control efforts have been made only for the homostructures of TMDC nanotubes and not for their heterostructures that provide an important platform for their two-dimensional counterparts. In this study, we synthesized heterostructures of TMDC nanotubes, MoS2/WS2 heteronanotubes, and demonstrated a technique for controlling features of their structures, such as diameters, layer numbers, and crystallinity. The diameter of the heteronanotubes could be tuned with inner nanotube templates and was reduced by using small-diameter WS2 nanotubes. The layer number and crystallinity of the MoS2 outer wall could be controlled by controlling their precursors and synthesis temperatures, resulting in the formation of high-crystallinity TMDC heteronanotubes with specific chirality. This study can expand the research of van der Waals heterostructures.

The relationship between the incision line and position of the latissimus dorsi muscle for subcutaneous implantable cardioverter-defibrillator intermuscular implantations.

INTRODUCTION: Intermuscular implantations of subcutaneous implantable cardioverter-defibrillators (S-ICD) have been recommended, but the position of the anterior border of the latissimus dorsi muscle (LDM) has not previously been evaluated in establishing an incision line to facilitate the intermuscular approach. The objective of this study is to evalua the position and trend of the anterior border of the LDM in patients who are candidates for implantable cardioverter-defibrillators. METHODS: The distance from the back to the anterior border of the LDM (A) and the anterior-posterior width of the chest wall (B) were measured on computed tomography retrospectively, and the ratio (=A/B) was used as the position of the anterior border of the LDM. In addition, the variability and factors affecting the values were evaluated. RESULTS: An analysis was performed on 78 patients, and the position of the anterior border of the LDM (=A/B) exhibited a normal distribution, with a mean value of 0.53 ± 0.062 (0.41-0.69). The position of the anterior border of the LDM tended to be more anterior in younger, taller, male, primary prevention, nonheart failure, low brain natriuretic peptide level, and nondiabetic patients. CONCLUSION: The position of the anterior border of the LDM varied from case to case with variable results. Conventional incisions on the midaxillary line may be inappropriate for intermuscular implantations, and the position of the anterior border of the LDM should be evaluated in each individual case to establish the incision line.

The impact of the procedural parameters on the lesion characteristics associated with AF recurrence: Late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) analysis.

BACKGROUND: Lesion gaps assessed by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) are associated with the atrial fibrillation (AF) recurrence after pulmonary vein isolation. Animal studies have demonstrated that the catheter-contact force (CF), stability, and orientation are strongly associated with lesion formation. However, the impact of those procedural factors on the lesion characteristics associated with AF recurrence has not been well discussed. METHODS: A total of 30 patients with paroxysmal AF who underwent catheter ablation were retrospectively enrolled. Radiofrequency (RF) applications were performed with 35 W for 30 s in a point-by-point fashion under esophageal temperature monitoring. The inter-lesion distance was 4 mm. The lesions were visualized by LGE-MRI 3 months postprocedure and assessed by the LGE volume (ml), gap number (GN), and average gap length (AGL [mm]). The gaps were defined as nonenhancement sites of >4 mm. The procedural factors including the catheter-CF, stability, and orientation were calculated on the NavX system. RESULTS: Six (20%) of 30 patients had AF recurrences 12 months postablation. A univariate analysis demonstrated that the AGL was associated with AF recurrence (hazard ratio [HR]: 1.20, confidence interval [CI]: 1.03-1.42, p = .02). All AF recurrence were found in patients with an AGL of >7 mm. The catheter-CF and stability were associated with an AGL of >7 mm, but not the orientation (CF-HR: 0.62, CI: 0.39-0.97, p = .038; stability-HR: 0.8, CI: 0.66-0.98, p = .027). CONCLUSIONS: RF ablation with a low CF and poor catheter stability has a potential risk of creating large lesion gaps associated with AF recurrence.

Hepatoprotective Principles from the Rhizomes of Picrorhiza kurroa.

A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.

Pannexin1 channel-dependent secretome from apoptotic tumor cells shapes immune-escape microenvironment.

Apoptotic cell death is a critical step in organism development and tissue homeostasis. Apoptotic cells affect immune cell activities in normal tissues. It is not clear whether similar cell death machinery causes tumor environments to evade anti-tumor immune responses. Here, using a mouse transplant model, we found a large number of tumor cells undergoing intrinsic apoptosis in tumors derived from the 4T1 breast cancer cell line, where neutrophils significantly accumulated. Interestingly, these apoptotic 4T1 tumor cells directly induced neutrophil extracellular traps (NETs) in a pannexin 1 (Panx1) channel-dependent manner, and knockdown of Panx1 in 4T1 cells led to a reduction in tumor size. Spermidine released through Panx1 from apoptotic 4T1 cells induced NETs in bone marrow-derived neutrophils in vitro. In addition, inhibition of spermidine synthesis suppressed tumor growth in the mouse transplant model. Collectively, our data suggested a new immune-escape mechanism for tumors by Panx1-mediated secretome from intrinsic apoptotic cells, which may provide a new therapeutic target for cancer.

Factors related to the skin thickness of cardiovascular implantable electronic device pockets.

INTRODUCTION: The skin overlying cardiovascular implantable electronic devices (CIEDs) sometimes becomes very thin after implantations, which could cause a device erosion. The factors related to the skin thickness of device pockets have not been elucidated. This study aimed to evaluate the skin thickness of CIED pockets and search for the factors associated with the thickness. METHODS: Seventeen skin thickness points around the CIED pocket were measured through ultrasonography in each patient. RESULTS: A total of 101 patients (76 ± 11 years, 26 female) were enrolled. The median duration from the implantation to the examination was 95 months (quartile: 52.5-147.5). The median skin thickness overlying the device was 4.1 mm (3.3-5.9). Patients with heart failure and malignancy had thinner skin overlying the CIED than those without. A significant correlation existed between skin thickness and body mass index (BMI), hemoglobin, serum creatinine, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction. In contrast, age, gender, and device size did not exhibit a significant correlation with skin thickness. A multivariate logistic regression analysis revealed that chronic heart failure and a decrease in the eGFR and BMI were independent predictive factors of "very thin (≦3.3 mm)" skin of the CIED pocket late after an implantation. CONCLUSION: Aside from a low BMI, the comorbidities (low hemoglobin, heart failure, and renal dysfunction) had a stronger impact on the skin thickness overlying the device than the device size. A careful observation of the device pocket should be performed in patients with those risk factors.

Sex Differences in the Regional Analysis of Nonpulmonary Vein Foci and Epicardial Adipose Tissue in Patients With Atrial Fibrillation.

BACKGROUND: The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role.Methods and Results: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). CONCLUSIONS: Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.

Development of a Visualization Deep Learning Model for Classifying Origins of Ventricular Arrhythmias.

BACKGROUND: Several algorithms have been proposed for differentiating the right and left outflow tracts (RVOT/LVOT) arrhythmia origins from 12-lead electrocardiograms (ECGs); however, the procedure is complicated. A deep learning (DL) model, a form of artificial intelligence, can directly use ECGs and depict the importance of the leads and waveforms. This study aimed to create a visualized DL model that could classify arrhythmia origins more accurately.Methods and Results: This study enrolled 80 patients who underwent catheter ablation. A convolutional neural network-based model that could classify arrhythmia origins with 12-lead ECGs and visualize the leads that contributed to the diagnosis using a gradient-weighted class activation mapping method was developed. The average prediction results of the origins by the DL model were 89.4% (88.2-90.6) for accuracy and 95.2% (94.3-96.2) for recall, which were significantly better than when a conventional algorithm is used. The ratio of the contribution to the prediction differed between RVOT and LVOT origins. Although leads V1 to V3 and the limb leads had a focused balance in the LVOT group, the contribution ratio of leads aVR, aVL, and aVF was higher in the RVOT group. CONCLUSIONS: This study diagnosed the arrhythmia origins more accurately than the conventional algorithm, and clarified which part of the 12-lead waveforms contributed to the diagnosis. The visualized DL model was convincing and may play a role in understanding the pathogenesis of arrhythmias.

Wafer-Scale Growth of One-Dimensional Transition-Metal Telluride Nanowires.

The development of bulk synthetic processes to prepare functional nanomaterials is crucial to achieve progress in fundamental and applied science. Transition-metal chalcogenide (TMC) nanowires, which are one-dimensional (1D) structures having three-atom diameters and van der Waals surfaces, have been reported to possess a 1D metallic nature with great potential in electronics and energy devices. However, their mass production remains challenging. Here, a wafer-scale synthesis of highly crystalline transition-metal telluride nanowires is demonstrated by chemical vapor deposition. The present technique enables formation of either aligned, atomically thin two-dimensional (2D) sheets or random networks of three-dimensional (3D) bundles, both composed of individual nanowires. These nanowires exhibit an anisotropic 1D optical response and superior conducting properties. The findings not only shed light on the controlled and large-scale synthesis of conductive thin films but also provide a platform for the study on physics and device applications of nanowire-based 2D and 3D crystals.

Double-Helix Supramolecular Nanofibers Assembled from Negatively Curved Nanographenes.

The layered structures of graphite and related nanographene molecules play key roles in their physical and electronic functions. However, the stacking modes of negatively curved nanographenes remain unclear, owing to the lack of suitable nanographene molecules. Herein, we report the synthesis and one-dimensional supramolecular self-assembly of negatively curved nanographenes without any assembly-assisting substituents. This curved nanographene self-assembles in various organic solvents and acts as an efficient gelator. The formation of nanofibers was confirmed by microscopic measurements, and an unprecedented double-helix assembly by continuous π-π stacking was uncovered by three-dimensional electron crystallography. This work not only reports the discovery of an all-sp2-carbon supramolecular π-organogelator with negative curvature but also demonstrates the power of three-dimensional electron crystallography for the structural determination of submicrometer-sized molecular alignment.

Characterization of an Expanded IL-10-Producing-Suppressive T Cell Population Associated with Immune Tolerance.

An increase in the number of glucocorticoid-induced tumor necrosis factor receptor-family related gene/protein (GITR)+CD25- (or fork-head box protein 3: Foxp3-) CD4+ T cells, after treating a mouse model of arthritis with fingolimod (FTY720), and a pathogenic antigen may play a key role in the establishment of immune tolerance. In this study, we characterized a specific expanded T cell subset in this population. Mice with glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis were treated with FTY720 (1 mg/kg, per os) and GPI325-339 (10 µg/mouse, intravenously) for five days, starting from the onset of symptoms. The expanded GITR+CD25- (or Foxp3-) CD4+ T cell population and its cytokine production were examined using flow cytometry. Furthermore, time-dependent changes in T-bet and/or early growth response gene 2 (Egr-2) expression in this T cell subset were examined. The density of T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)+CD39+ cell subset in the GITR+Foxp3-CD4+ T cell population was significantly increased only in the combined treatment group, compared to that in the untreated and single-treatment groups. In the TIGIT+CD39+GITR+Foxp3-CD4+ T cell population, T-bet+Egr-2+/T-bet+Egr-2- cell ratio increased in the latter stage of the treatment. Furthermore, this T cell subset, which corresponded to a T helper 1 (Th1) response, produced high levels of both interleukin (IL)-10 and interferon (IFN)-γ. In conclusion, expanded TIGIT+CD39+GITR+Foxp3-CD4+ T cells shifted from an effector Th1 to IL-10-producing-suppressor T cell phenotype, which may promote an immune-tolerant state.

Isolation of Single-Wired Transition-Metal Monochalcogenides by Carbon Nanotubes.

The successful isolation of single layers from two-dimensional (2D) van der Waals (vdW)-layered materials has opened new frontiers in condensed matter physics and materials science. Their discovery and unique properties laid the foundation for exploring 1D counterparts. However, the isolation of 1D vdW-wired materials has thus far remained a challenge, and effective techniques are demanded. Here we report the facile synthesis of isolated transition-metal monochalcogenide MoTe nanowires by using carbon nanotubes (CNTs) as molds. Individual nanowires are perfectly separated by CNTs with a minimal interaction, enabling detailed characterization of the single wires. Transmission electron microscopy revealed unusual torsional motion of MoTe nanowires inside CNTs. Confinement of 1D vdW-wired materials to the nanotest tubes might open up possibilities for exploring unprecedented properties of the nanowires and their potential applications such as electromechanical switching devices.

Role of eosinophils in a murine model of inflammatory bowel disease.

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), which is triggered spontaneously by unknown mechanisms and manifests as chronic and relapsing inflammatory conditions in the colon. Eosinophil infiltration is often observed in the colonic tissue of ulcerative colitis patients. However, the role of eosinophils in the disease has not been well defined. The aim of this study is to investigate the role of eosinophils in colonic inflammation using the murine model of spontaneous colitis. CC chemokine receptor type 3 (CCR3) and interleukin (IL)-10 double knockout mice (CCR3-/-;IL-10-/-) were utilized to evaluate the function of eosinophils in colitis. The levels of colitis were evaluated by colonoscopy, histology, and real-time PCR measurements to determine expression levels of inflammatory cytokines in the colonic tissue. The levels of cytokines produced by T cells in mesenteric lymph nodes were evaluated by ELISA. There was no significant difference in endoscopic and histological scores between the groups of CCR3-/-;IL-10-/- mice and control CCR3+/-;IL-10-/- mice. There was also no significant difference in the expression levels of pro-inflammatory cytokines in the intestinal tissue between the two groups. Similar results were found for IL-17A and interferon gamma (IFN-γ) production from mesenteric lymph node-derived T cells. Our data indicate that eosinophils do not play a significant role in the immunopathology of colitis in IL-10-/- mice.

Excited-State Charge Transfer in Covalently Functionalized MoS2 with a Zinc Phthalocyanine Donor-Acceptor Hybrid.

The functionalization of MoS2 is of paramount importance for tailoring its properties towards optoelectronic applications and unlocking its full potential. Zinc phthalocyanine (ZnPc) carrying an 1,2-dithiolane oxide linker was used to functionalize MoS2 at defect sites located at the edges. The structure of ZnPc-MoS2 was fully assessed by complementary spectroscopic, thermal, and microscopy imaging techniques. An energy-level diagram visualizing different photochemical events in ZnPc-MoS2 was established and revealed a bidirectional electron transfer leading to a charge separated state ZnPc.+ -MoS2 .- . Markedly, evidence of the charge transfer in the hybrid material was demonstrated using fluorescence spectroelectrochemistry. Systematic studies performed by femtosecond transient absorption revealed the involvement of excitons generated in MoS2 in promoting the charge transfer, while the transfer was also possible when ZnPc was excited, signifying their potential in light-energy-harvesting devices.

Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4.

The intestinal tract contains many commensal bacteria that modulate various physiological host functions. Dysbiosis of commensal bacteria triggers dysfunction of the intestinal epithelial barrier, leading to the induction or aggravation of intestinal inflammation. To elucidate whether microRNA plays a role in commensal microbiome-dependent intestinal epithelial barrier regulation, we compared transcripts in intestinal epithelial cells (IECs) from conventional and germ-free mice and found that commensal bacteria induced the expression of miR-21-5p in IECs. miR-21-5p increased intestinal epithelial permeability and up-regulated ADP ribosylation factor 4 (ARF4), a small GTPase, in the IEC line Caco-2. We also found that ARF4 expression was up-regulated upon suppression of phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4), which are known miR-21-5p targets, by RNAi. Furthermore, ARF4 expression in epithelial cells of the large intestine was higher in conventional mice than in germ-free mice. ARF4 suppression in the IEC line increased the expression of tight junction proteins and decreased intestinal epithelial permeability. These results indicate that commensal microbiome-dependent miR-21-5p expression in IECs regulates intestinal epithelial permeability via ARF4, which may therefore represent a target for preventing or managing dysfunction of the intestinal epithelial barrier.

DySc2N@C80 Single-Molecule Magnetic Metallofullerene Encapsulated in a Single-Walled Carbon Nanotube.

DySc2N@C80 is an endohedral metallofullerene showing single-molecule magnet (SMM) behavior. In this work, we encapsulated DySc2N@C80-SMMs into the internal one-dimensional nanospace of single-walled carbon nanotubes (SWCNTs). Using transmission electron microscopy, "peapod" structures were clearly observed. From magnetic field dependent measurements, DySc2N@C80 showed stepwise hysteresis characteristic of SMMs even inside the SWCNTs, and the coercivity increased from 0.5 to 4 kOe. In addition, it showed slow relaxation of the magnetization without an applied external magnetic field. This system is the first example where SMMs have been encapsulated in SWCNTs, and this system could be used in future molecular-spintronics devices.

CF2 -Bridged C60 Fullerene Dimers and their Optical Transitions.

Fullerene dyads bridged with perfluorinated linking groups have been synthesized through a modified arc-discharge procedure. The addition of Teflon inside an arc-discharge reactor leads to the formation of dyads, consisting of two C60 fullerenes bridged by CF2 groups. The incorporation of bridging groups containing electronegative atoms lead to different energy levels and to new features in the photoluminescence spectrum. A suppression of the singlet oxygen photosensitization indicated that the radiative decay from singlet-to-singlet state is favoured against the intersystem crossing singlet-to-triplet transition.

Selective Incorporation of Primary Amines into a Trizirconium Imido System and Catalyic Cyclization of Aminoalkynes.

The trinuclear zirconium imido complex [{LZr(NMe2)}3] (2, L = C5Me4CH2CH2N) was synthesized by amine elimination between Zr(NMe2)4 and endo-olefinic isomers of (tetramethylcyclopentadienyl)ethanamine (LH3) (1). To study the fundamental reactivity of the trizirconium system, reactions of 2 with primary amines were examined. Selective incorporations of the primary amines were observed, depending on steric and electronic natures of the amine substrates. The amine-incorporated complexes [(LZrNHR)(LHZrNHR)(LHZr)(µ-NHR)(µ3-NR)] (3, R = Pr, Et), [(LZrNHR)2(LHZr)(µ-NR)] (4, R = Pr, i-Bu), [(LZr)2(LZrNMe2)(µ-NR)] (5, R = neo-Pen), and [(LZr)(LZrNHAr)(LH2Zr)(µ-NAr)2] (6, Ar = Ph, C6H4-4-Br, C6H4-4-OMe) were structurally characterized by NMR and XRD analysis and showed several coordination modes of the substrate nitrogen ligands: i.e., terminal amides, bridging amides, and bridging imides but not terminal imides. Thermolysis of a mixture of 3 and 4 led to C-H bond activation, giving rise to the zirconaaziridines [{LZr(η2-NCHR)}(LZr)(LHZr)(µ-NHCH2R)] (12, R = Et, Me). Complex 2 proved to be a competent precatalyst in the hydroamination of the aminoalkynes (H2NCH2CR12CH2C≡CR2) (13, R1 = H, R2 = Bu, Ph, t-Bu; 14, R1 = Me, R2 = Et, Ph). Stoichiometric or semicatalytic reactions of 2 and the aminoalkynes were studied to explore the reactivity of in situ formed Zr3 species.

Nitrogen-Carbon Bond Formation by Reactions of a Titanium-Potassium Dinitrogen Complex with Carbon Dioxide, tert-Butyl Isocyanate, and Phenylallene.

Nitrogen-carbon bond-forming reactions at coordinated dinitrogen in a bifunctional titanium-potassium system are reported. A titanium atrane complex with a tris(aryloxide)methyl ligand (1) was treated with two equivalents of potassium naphthalenide under N2 atmosphere to generate a bifunctional complex (2) in which N2 binds end-on to two titanium centers and side-on to three potassium cations. Dinitrogen complex 2 reacted with carbon dioxide, tert-butyl isocyanate, and phenylallene, forming nitrogen-carbon bonds and affording diverse N-functionalized products. The reaction of 2 with CO2 followed by addition of Me3 SiCl resulted in the formation of the starting complex 1 with concomitant release of silylated carboxyl hydrazines while the reaction with two equivalents of tert-butyl isocyanate proceeded by insertion into the Ti-N bonds. Treatment of 2 with phenylallene afforded vinyl-substituted hydrazido complexes.

Construction of Covalent Organic Nanotubes by Light-Induced Cross-Linking of Diacetylene-Based Helical Polymers.

Organic nanotubes (ONTs) are tubular nanostructures composed of small molecules or macromolecules that have found various applications including ion sensor/channels, gas absorption, and photovoltaics. While most ONTs are constructed by self-assembly processes based on weak noncovalent interactions, this unique property gives rise to the inherent instability of their tubular structures. Herein, we report a simple "helix-to-tube" strategy to construct robust, covalent ONTs from easily accessible poly(m-phenylene diethynylene)s (poly-PDEs) possessing chiral amide side chains that can adopt a helical conformation through hydrogen-bonding interactions. The helically folded poly-PDEs subsequently undergo light-induced cross-linking at longitudinally aligned 1,3-butadiyne moieties across the whole helix to form covalent tubes (ONTs) both in solution and solid phases. The structures of poly-PDEs and covalent ONTs were characterized by spectroscopic analyses, diffraction analysis, and microscopic analyses. We envisage that this simple yet powerful "helix-to-tube" strategy will generate a range of ONT-based materials by introducing functional moieties into a monomer.