Photoresponsive molecular memory films were fabricated by a layer‐by‐layer (LbL) assembling of two dinuclear Ru complexes with tetrapodal phosphonate anchors, containing either ...2,3,5,6‐tetra(2‐pyridyl)pyrazine or 1,2,4,5‐tetra(2‐pyridyl)benzene as a bridging ligand (Ru‐NP and Ru‐CP, respectively), using zirconium phosphonate to link the layers. Various types of multilayer homo‐ and heterostructures were constructed. In the multilayer heterofilms such as ITO||(Ru‐NP)m|(Ru‐CP)n, the difference in redox potentials between Ru‐NP and Ru‐CP layers was approximately 0.7 V, which induced a potential gradient determined by the sequence of the layers. In the ITO||(Ru‐NP)m|(Ru‐CP)n multilayer heterofilms, the direct electron transfer (ET) from the outer Ru‐CP layers to the ITO were observed to be blocked for m>2, and charge trapping in the outer Ru‐CP layers became evident from the appearance of an intervalence charge transfer (IVCT) band at 1140 nm from the formation of the mixed‐valent state of Ru‐CP units, resulting from the reductive ET mediation of the inner Ru‐NP layers. Therefore, the charging/discharging (“1”and “0”) states in the outer Ru‐CP layers could be addressed and interconverted by applying potential pulses between −0.5 and +0.7 V. The two states could be read out by the direction of the photocurrent (anodic or cathodic). The molecular heterolayer films thus represent a typical example of a photoresponsive memory device; that is, the writing process may be achieved by the applied potential (−0.5 or +0.7 V), while the readout process is achieved by measuring the direction of the photocurrent (anodic or cathodic). Sequence‐sensitive multilayer heterofilms, using redox‐active complexes as building blocks, thus demonstrate great potential for the design of molecular functional devices.
Committed to memory: Heteromolecular layered assembly of two Ru complexes having different redox potentials, was constructed by use of ZrIV coordination bonding. Charge trapping in the outer layer occurred as a result of a potential gradient in the heterolayer films (see graphic, ITO=indium–tin oxide). Since the photocurrent direction determined whether the charge was trapped or not in the outer layer, the film acts as a new memory device.
In this study, we fabricated flexible organic field-effect transistors (OFETs) (bottom-gate and top-contact architecture) based on the blend film composed of 6,13-bis(triisopropylsilylethynyl) ...pentacene (TIPS pentacene) as a π-conjugated small-molecule semiconductor and polystyrene (PS) as a polymer insulator. Blend solutions including both the TIPS pentacene and PS molecules were electrosprayed onto bottom-gate electrodes which were patterned on polyethylene naphthalate films. The devices exhibited superior electrical characteristics due to well-defined vertical phase separation between the TIPS pentacene crystalline layer (top) and PS insulator (bottom). This study will contribute to a facile one-step printing process to produce high-performance flexible OFETs.
•Irregular estrus cycles were observed in our rat model of hypothyroidism.•Kiss1 mRNA-expressing neurons in the ARC were decreased in hypothyroid rats.•Kisspeptin immunoreactive neurons in the ARC ...were decreased in hypothyroid rats.
Insufficiency of thyroid hormones inhibits gonadotropin release and results in dysregulation of reproductive function, although the precise mechanism of this disrupted gonadotropin secretion remains unclear. Kisspeptin is a neuropeptide that strongly stimulates gonadotropin secretion and plays an important role in reproductive function. To examine the involvement of kisspeptin in the dysregulation of gonadotropin secretion in hypothyroidism, we investigated Kiss1 mRNA expression and kisspeptin immunoreactivity in the hypothalamus of female rats treated with propylthiouracil (PTU). In the PTU-treated rats, serum thyroxine (T4) was significantly decreased, whereas thyroid stimulating hormone (TSH) levels were significantly increased. In addition, irregular estrus cycles were observed in PTU-treated rats. In situ hybridization and immunohistochemistry revealed significant reductions in the number of Kiss1 mRNA-expressing neurons and kisspeptin-immunoreactive neurons in the arcuate nucleus (ARC) but not in the anteroventral periventricular nucleus (AVPV) of the PTU-treated rats. Although the serum levels of luteinizing hormone (LH) and estradiol (E2) were unaffected, serum prolactin levels were significantly increased after PTU treatment. These data indicate that kisspeptin expression in the ARC is suppressed under thyroid hormone insufficiency, suggesting that the dysregulation of reproductive function in hypothyroidism is caused by inhibition of kisspeptin neurons in the ARC.
The onset of puberty is initiated by an increase in the release of the gonadotropin-releasing hormone (GnRH) from GnRH neurons in the hypothalamus. However, the precise mechanism that leads to the ...activation of GnRH neurons at puberty remains controversial. Spines are small protrusions on the surface of dendrites that normally receive excitatory inputs. In this study, we analyzed the number and morphology of spines on GnRH neurons to investigate changes in synaptic inputs across puberty in rats. For morphological estimation, we measured the diameter of the head (DH) of each spine and classified them into small-type (DH < 0.65 μm), large-type (DH > 0.65 μm) and giant-type (DH > 0.9 μm). The greatest number of spines was observed at the proximal dendrite within 50 μm of the soma. At the soma and proximal dendrite, the number of spines was greater in adults than in juveniles in both male and female individuals. Classification of spines revealed that the increase in spine number was due to increases in large- and giant-type spines. To further explore the relationship between spines on GnRH neurons and pubertal development, we next analyzed adult rats neonatally exposed to estradiol benzoate, in which puberty onset and reproductive functions are disrupted. We found a decrease in the number of all types of spines. These results suggest that GnRH neurons become to receive more and greater excitatory inputs on the soma and proximal dendrites as a result of the changes that occur at puberty and that alteration to spines plays a pivotal role in normal pubertal development.
► Kisspeptin neurons in the ARC form synaptic inputs with TIDA neurons. ► Apposition of kisspeptin fibers to dopaminergic neurons occur in ARC of female rats. ► Kisspeptin peptides adjacent to TIDA ...neurons are reduced under high E2 status. ► Kisspeptin and NKB are coexpressed in the same fiber in the axon terminal. ► Kisspeptin/NKB/dynorphin projections to TIDA neurons may regulate PRL secretion.
Kisspeptin is a pivotal regulator of the onset of puberty and the estrus cycle, but may also take part in pregnancy and lactation. Kisspeptin neurons and their fibers are distributed abundantly throughout the arcuate nucleus (ARC) of the hypothalamus, but the targets of the fiber projections in the ARC have not been fully investigated. The present study followed the projection of kisspeptin fibers to tuberoinfundibular dopaminergic (TIDA) neurons in the ARC, pivotal endocrine neurons that control prolactin secretion. Immunoreactive fibers of kisspeptin or neurokinin B, a peptide coexpressed in kisspeptin neurons, were abundantly found adjacent to TIDA neurons in female rats, but few were observed in male rats. The immunoreactivities of both peptides adjacent to TIDA neurons were significantly reduced in estradiol-primed ovariectomized rats. Precise 3D analysis of the attachment of kisspeptin-immunoreactive fibers to TIDA neurons was achieved using a synaptic marker that indicated synaptic connection. Finally, double-labeling immunoelectron microscopy confirmed the synaptic connections of kisspeptin-immunoreactive fibers to the cell body and fibers of TIDA neurons. These findings indicate that in female rats, kisspeptin/NKB fibers may directly affect TIDA neurons that regulate prolactin secretion, and that they are more likely to be activated during low estradiol status.
As a neutron capture therapy (NCT) agent, 157Gd garners significant attention due to the largest neutron capture cross section, emission of γ rays and Auger electrons, and facilitation of magnetic ...resonance imaging-guided NCT. Owing to its high kinetic stability, 1H relaxivity, and facile conjugation to albumin via electrostatic interactions, the negatively charged Gd3TCAS2 complex {TCAS = thiacalix4arene-p-tetrasulfonate (TCAS)} was incorporated into albumin nanoparticles (ANPs) in various configurations, including shell, core, and core-shell types, contingent on the positioning of Gd3TCAS2 within the ANP. The characteristics of the ANPs optimized with respect to loading capacity (LC) were explored, all of which demonstrated particle sizes suitable for passive delivery. The LC of Gd3TCAS2 per ANP increased in the following order: shell (1.1 %) < core (1.4 %) < core-shell (8.1 %). The leakage of Gd3TCAS2 after 7 d of storage was approximately 2 % for all ANPs, indicating stable Gd3TCAS2 loading. The 1H relaxivity (e.g., core-shell: r1 = 10.7 mM–1s–1) surpassed that of the Gd3TCAS2 complex alone (3.15 mM–1s–1). The luminescence emanating from Tb in MCF-7 cells co-cultured with Tb3TCAS2-loaded ANPs corroborated this cellular uptake. Gd uptake into MCF-7 cells via Gd3TCAS2-loaded ANPs was most pronounced for core-shell ANP at 1.33 ± 0.06 nmol/106 cells. The cytotoxicity of Gd3TCAS2-loaded ANPs was mitigated compared to free Gd3TCAS2 (CC50 = 52 µM), with shell and core-shell ANPs demonstrating nearly 100 % cell survival even at 50 µM. Cell viability post thermal neutron irradiation revealed the highest NCT efficacy for free Gd3TCAS2, attributed to its elevated cellular uptake (15.71 ± 0.57 nmol/106 cells). Core-shell ANP also exhibited a notable reduction in cell viability relative to the control, validating their potential as a promising GdNCT agent.
Display omitted
•Two thiacalixarene (TCAS) ligands sandwich a tri-Gd core to form the Gd3TCAS2 complex.•Gd3TCAS2 is integrated into albumin nanoparticles (ANPs) for MRI-guided neutron capture therapy.•The loading capacity of Gd3TCAS2 in core-shell ANPs reaches 8.1 %, enhancing 1H relaxivity.•Gd uptake into MCF-7 cells via the ANP measures 1.33 ± 0.06 nmol/106 cells.•Cells incorporated with the ANP are effectively killed by thermal neutron irradiation.
Acute exacerbation (AE) is a life-threatening complication of interstitial pneumonia (IP). Thoracic surgery may trigger AE.
To explore the role of preoperative CT findings for predicting ...postoperative AE in patients with IP and lung cancer.
This retrospective case-control study included patients from 22 institutions with IP who underwent thoracic surgery for lung cancer. AE was diagnosed based on symptoms and imaging findings within 30 days after surgery and absence of alternate causes. For each case of AE, two control cases without AE were identified. After exclusions, 92 patients (78 men, 14 women; mean age 72 years; 31 with AE, 61 without AE) were included. Two radiologists independently reviewed preoperative thin-slice CT examinations for pulmonary findings and resolved differences by consensus. AE and no-AE groups were compared using Fisher's exact and Mann-Whitney U tests. Multivariable logistic regression was performed. Interreader agreement was assessed by kappa coefficients.
A total of 94% of patients in AE group underwent segmentectomy or other surgery more extensive than wedge resection, versus 75% in no-AE group (p=.046). Usual interstitial pneumonia pattern was present in 58% of AE group versus 74% in no-AE group (p=.16). Using subjective visual scoring, mean ground glass opacity (GGO) extent was 6.3±5.4 in AE group versus 3.9±3.8 in no-AE group (p=.03), and mean consolidation extent was 0.5±1.2 in AE group versus 0.1±0.3 in no-AE group (p=.009). Mean pulmonary trunk diameter was 28±4 mm in AE group versus 26±3 mm in no-AE group (p=.02). In a model of only CT features, independent predictors of AE (p<.05) were GGO extent (OR=2.8), consolidation extent (OR=9.4), and pulmonary trunk diameter (OR=4.2); this model achieved AUC 0.75, PPV 71%, and NPV 77% for AE. When combing CT and clinical variables, undergoing segmentectomy or more extensive surgery also independently predicted AE (OR=8.2; p=.02).
GGO, consolidation, and pulmonary trunk enlargement on preoperative CT predict AE in patients with IP undergoing lung cancer surgery.
Patients with IP and lung cancer should be carefully managed in the presence of the predictive CT features. Wedge resection, if possible, may help reduce AE risk in these patients.
•We examined the effect of sevoflurane on Per2 expression in the SCN.•The bioluminescence of Per2-dluc transgene was used as a marker of Per2 expression.•There was no intra-SCN spatial difference in ...susceptibility to sevoflurane.•Sevoflurane affected bioluminescence rhythm in time-dependent manner.•Sevoflurane may inhibit Per2 expression via GABAergic signal transduction.
The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABAA and GABAB receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm.
Pendred syndrome (PDS)/DFNB 4 is a disorder with fluctuating and progressive hearing loss, vertigo, and thyroid goiter. We identified pathophysiology of a neurodegenerative disorder in PDS patient ...derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Given that there is no rational standard therapy for PDS, we planned a study to examine effects of low dose oral administration of sirolimus for the fluctuating and progressive hearing loss, and the balance disorder of PDS by daily monitor of their audio-vestibular symptoms.
This is a phase I/IIa double blind parallel-group single institute trial in patient with PDS/DFNB4. Sixteen of outpatients with fluctuating hearing diagnosed as PDS in SLC26A4 genetic testing aged in between 7 and 50 years old at the time of consent are given either placebo or sirolimus tablet (NPC-12T). In NPC-12T placebo arm, placebo will be given for 36 weeks; in active substance arm, placebo will be given for 12 weeks and the NPC-12T for 24 weeks. Primary endpoints are safety and tolerability. The number of occurrences and types of adverse events and of side effects will be sorted by clinical symptoms and by abnormal change of clinical test results. A 2-sided 95% confidence interval of the incidence rate by respective dosing arms will be calculated using the Clopper-Pearson method. Clinical effects on audio-vestibular tests performed daily and precise physiological test at each visit will also be examined as secondary and expiratory endpoints.
JMA-IIA00361; Pre-results.
ISO 12135 provide a unified method of test for the determination of quasistatic fracture toughness. This test is conducted by using three-point bending specimen with a notch and fatigue pre-crack, ...and with regards to the fatigue pre-crack, ISO 12135 and ISO 15653 require some requirements such as minimum length and straightness. A base material specimen often meets the requirements without any special techniques, however, welds specimen cannot meet them due to welding residual stress. In order to meet the requirements, the local compression technique is used in general and ISO 15653 provides the recommended conditions. However, some interested parties have reported that the recommended conditions decrease the fracture toughness values. Based on the above, the authors developed prediction method for fatigue pre-crack straightness and fracture toughness evaluation value with numerical analysis and searched the good local compression condition, such as shape, size and location, with Bayesian optimization. As a result, we found that the area and location significantly effect on the fatigue pre-crack straightness and fracture toughness evaluation value and proposed new recommended local compression condition, which securing a straight fatigue pre-crack while maintaining the fracture toughness evaluation value. This proposed condition is validated through fracture toughness test and the fracture toughness evaluation values were compared with ISO recommended condition and so on. These experimental results also showed the effectiveness of proposed condition.
PDF
