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The hydrogen evolution reaction (HER) is an important phenomenon in water splitting. Consequently, the development of an active, earth-abundant, and inexpensive HER catalyst is highly desired. MoS2 has drawn considerable interest as an HER catalyst because it is composed of non-precious metal and exhibits high catalytic activity in the nanosheet form. In this study, size-controlled MoS2 particles were synthesized by ball milling. The as-prepared samples exhibited significantly enhanced electrochemical and catalytic properties compared to those of pristine bulk MoS2. Furthermore, the HER activity improved further upon the introduction of graphene into the as-prepared ball-milled samples. In particular, the MoS2 sample ball-milled for 12 h mixed with graphene exhibited optimal performance, showing an overpotential (160 mV at 10 mA cm−2) that was ~ 335 mV lower than that of pristine bulk MoS2. The superior catalytic activity was ascribed to the exposed edge sites, sulfur vacancies, and 1T phase of MoS2, as well as the noteworthy fortifying effect of the electronically conductive flexible material, graphene. The results provide a promising strategy for its application as an efficient and stable HER catalyst.

Abstract We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

Abstract A multicenter randomized controlled trial was conducted to compare the effectiveness of incisional and nonincisional surgical techniques for treating lower lid epiblepharon in children. The study included 89 eyes from 50 children aged 3–15 years (mean, 7.5 ± 2.4 years) with moderate lower lid epiblepharon. Patients were randomly assigned to either incisional (modified Hotz procedure with lid margin splitting; 45 eyes of 25 patients) or nonincisional (44 eyes of 25 patients) surgery groups. Treatment outcomes and changes in astigmatism were evaluated 6 months after surgery. Incisional surgery provided a significantly higher percentage (77.8%) of well-corrected treatment results (P = 0.026; odds ratio, 2.88; 95% confidence interval, 1.07–8.22) than nonincisional surgery (55.4%). The mean change in astigmatism 6 months after surgery was − 0.24 ± 0.42 and − 0.01 ± 0.47 D in the incisional and nonincisional surgery groups, respectively. The improvement in astigmatism was significantly higher in the incisional surgery group than in the nonincisional surgery group (P = 0.008). The incisional surgical treatment for moderate epiblepharon in children resulted in a higher number of well-corrected patients, indicating an absence of both ciliary touch and superficial keratitis as well as statistically significant improvements in astigmatism correction.

ABSTRACTAs an important part of water splitting, the oxygen evolution reaction (OER) requires efficient, low-cost, and stable catalysts to overcome its sluggish kinetic barrier. In this study, based on previously reported OER catalyst materials of boron monosulfide mixed with graphene (r-BS+G), nickel foam (NF) is introduced as a supporting material for an r-BS+G electrocatalyst. The resulting r-BS+G-NF exhibits a very low overpotential at 10 (245 mV), 100 (308 mV), and 500 (405 mV) mA cm−2, with a low Tafel slope (56 mV dec−1). In addition, r-BS+G-NF exhibits high durability and can maintain high activity for more than 100 h at 100 mA cm−2. This is in sharp contrast to the catalyst without graphene (r-BS+NF), which shows lower durability. The results suggest that the unique morphology of the NF provides a large electrochemically active area and exposes more active sites on the surface of the prepared electrocatalyst, while the flexible graphene sheets play an important role as a support for effectively combining r-BS and NF. Consequently, the self-supporting structure can improve the OER performance as well as stability. Therefore, this study provides a promising strategy for use as an efficient and stable OER catalyst at high current densities.

IntroductionBinaural hearing enhances speech intelligibility, source localization, and speech comprehension in noisy environments. Although bilateral cochlear implantation (CI) offers several benefits, concerns arise regarding the risk of bilateral postoperative vestibular dysfunction with simultaneous CI. This study aimed to longitudinally evaluate changes in vestibular function in adult patients who underwent simultaneous bilateral CI using minimally invasive electrodes and surgical techniques.MethodsA retrospective review was conducted on 10 patients who underwent simultaneous bilateral CI at our hospital. Vertigo symptoms and vestibular function test results were examined preoperatively, 1–6 months postoperatively, and 1 year postoperatively. Nystagmus tests, caloric reflex tests, vestibular evoked myogenic potentials (VEMP) measurements, and static stabilometry were performed as vestibular function tests.ResultsAlthough an initial transient decline in vestibular function was observed, no significant long-term decline was observed in the caloric reflex test, ocular VEMP (oVEMP), or cervical VEMP (cVEMP). Moreover, regardless of the presence or absence of abnormalities in caloric reflex, oVEMP, or cVEMP, no significant deterioration was detected in the static stabilometer test. While two patients reported preoperative dizziness, all patients were symptom-free 1 year postoperatively.DiscussionThe findings suggest that using current minimally invasive electrodes and surgical techniques in simultaneous bilateral CI leads to temporary vestibular function decline postoperatively. However, most patients experience a recovery in function over time, highlighting the potential safety and efficacy of the procedure. Simultaneous bilateral CI surgery is viable, depending on the patient’s auditory needs and burden.

IntroductionVestibular schwannoma (VS) is an intracranial tumor that arises on the vestibular branch of cranial nerve VIII and typically presents with sensorineural hearing loss (SNHL). The mechanisms of this SNHL are postulated to involve alterations in the inner ear’s microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model in vivo.MethodsVS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores. Next-generation sequencing was performed on RNA isolated from cultured primary human VS cells and EVs from VS-conditioned media, stratified by patients’ hearing ability. microRNA expression levels were compared between VS-PH and VS-GH samples to identify differentially expressed candidates for packaging into a synthetic adeno-associated viral vector (Anc80L65). Viral vectors containing candidate microRNA were infused to the semicircular canals of mice to evaluate the effects on hearing, including after noise exposure.ResultsDifferentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH). Newborn mice receiving intracochlear injection of viral vectors over-expressing hsa-miR-431-GFP, hsa-miR-192-GFP, or GFP only (control) had similar hearing 6 weeks post-injection. However, after acoustic trauma, the miR-431 group displayed significantly worse hearing, and greater loss of synaptic ribbons per inner hair cell in the acoustically traumatized cochlear region than the control group.ConclusionOur results suggest that miR-431 contributes to VS-associated hearing loss following cochlear stress. Further investigation is needed to determine whether miR-431 is a potential therapeutic target for SNHL.

Abstract We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage

Background Extranodal extension (ENE) is a prognostic factor for several types of malignant tumors, including esophageal cancer. Although the prognostic value of ENE has been investigated in esophageal cancer, its clinical utility warrants further investigation. Materials and Methods This retrospective single-center study evaluated 105 patients who underwent esophagectomy and had histologically node-positive metastasis between January 2007 and June 2017. The abilities of ENE to predict overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan–Meier method and log-rank test, as well as Cox proportional hazard models. Subgroup analyses of ENE’s prognostic value were performed according to each pathological tumor-node-metastasis category. Results Significant differences according to ENE status were observed in the Kaplan–Meier analyses of OS (p = 0.001) and DFS (p = 0.001), as well as in the Cox proportional hazards models for OS (p = 0.009) and DFS (p = 0.012). Relative to patients without ENE, patients with ENE had significantly poorer OS if they also had pT3 status, pN1 status, or pathological stage III disease. However, no significant differences were observed in the subgroup analyses of pN3 status and pathological stage IV disease. Conclusions Among patients with esophageal cancer, ENE status can predict a poor prognosis and may be useful for patient stratification. However, the prognostic value of ENE status may be limited to patients with specific pathological factors.

Introduction Xeroderma pigmentosum (XP) is a rare intractable disease without a fundamental treatment, presenting with severe photosensitivity, freckle-like pigmented and depigmented maculae and numerous skin cancers before the age of 10 years without strict sun protection. About 70% of the patients exhibit extremely severe sunburn reactions and most of them develop neurological symptoms, including sensorineural hearing impairment and progressive peripheral and central nervous disorders beginning from childhood ages. In the preclinical study, we found that N-acetyl-5-methoxytryptamine was effective in suppressing skin tumour development in addition to improvement of auditory brainstem response in chronically ultraviolet-irradiated XP-A model mice.Methods and analysis On the bases of the preclinical study, we conduct a clinical trial on the efficacy of NPC-15 for patients with XP with exaggerated sunburn reaction type by a multicentre, double-blinded placebo-controlled, two-group crossover study followed by a 52 weeks open study.Ethics and dissemination Ethics approval is overseen by the Kobe University Institutional Review Board and Osaka Medical and Pharmaceutical University Institutional Review Board, and the study is conducted in accordance with the approved protocol. All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The data sets generated during the study will be available from the corresponding author on reasonable request.Trial registration number jRCTs051210181.

Metastasis of malignant tumors to the temporal bone is relatively rare. We report a case of facial nerve palsy due to the metastatic prostatic cancer to the temporal bone with favorable and functional results. A 76-year-old man with no history of malignant tumor was referred to our hospital with a complaint of right facial nerve palsy. Based on radiological findings and a biopsy from the prostate, the patient was finally diagnosed as having metastatic prostatic cancer to the right temporal bone. More than 18 months had passed after start of the hormonal therapy, the metastatic lesion of the temporal bone had diminished, and the facial nerve palsy gradually improved. The present case suggests that favorable and functional results even in advanced metastatic prostatic cancers to temporal bone, if hormonal therapy is effective. We must keep in mind the possibility of metastatic tumor in the treatment of facial nerve palsy.

In the cochlear auditory epithelia, sensory hair and supporting cells are arranged in a checkerboard-like mosaic pattern, which is conserved across a wide range of species. The cell adhesion molecules nectin-1 and nectin-3 are required for this pattern formation. The checkerboard-like pattern is thought to be necessary for auditory function, but has never been examined. Here, we showed the significance of checkerboard-like cellular pattern in the survival and function of sensory hair cells in the cochlear auditory epithelia of nectin-3 knockout (KO) mice. Nectin-3 KO mice showed progressive hearing loss associated with degeneration of aberrantly attached hair cells via apoptosis. Apoptotic hair cell death was due to the disorganization of tight junctions between the hair cells. Our study revealed that the checkerboard-like cellular pattern in the auditory epithelium provides a structural basis for ensuring the survival of cochlear hair cells and hearing function.

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent’s targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient’s nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.

Abstract Background The incidence of concurrent cancer and ischaemic heart disease (IHD) is increasing; however, the long-term patient prognoses remain unclear. Methods Five-year all-cause mortality data pertaining to patients in the Osaka Cancer Registry, who were diagnosed with colorectal, lung, prostate, and gastric cancers between 2010 and 2015, were retrieved and analysed together with linked patient administrative data. Patient characteristics (cancer type, stage, and treatment; coronary risk factors; medications; and time from cancer diagnosis to index admission for percutaneous coronary intervention [PCI] or IHD diagnosis) were adjusted for propensity score matching. Three groups were identified: patients who underwent PCI within 3 years of cancer diagnosis (n = 564, PCI + group), patients diagnosed with IHD within 3 years of cancer diagnosis who did not undergo PCI (n = 3058, PCI-/IHD + group), and patients without IHD (n = 27,392, PCI-/IHD- group). Kaplan–Meier analysis was used for comparisons. Results After propensity score matching, the PCI + group had better prognosis (n = 489 in both groups, hazard ratio 0.64, 95% confidence interval 0.51–0.81, P

A facile synthesis of carbo- and heterohelicenes was achieved via tandem cycloaromatization of bisacetal precursors, which were readily prepared through C–C bond formation by Suzuki–Miyaura coupling. This cyclization was efficiently realized by a catalytic amount of trifluoromethanesulfonic acid (TfOH) in a cation-stabilizing solvent, 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), which readily allowed gram-scale syntheses of higher-order helicenes, double helical helicenes, and heterohelicenes.

Abstract Aims Acute decompensated heart failure (ADHF) is generally treated by decongestion using diuretic therapy. However, the use of loop diuretics is associated with increased cardiac sympathetic nerve activity (CSNA). We aimed to evaluate the effect of adjunctive tolvaptan therapy on CSNA in ADHF patients with preserved left ventricular ejection fraction (LVEF). Methods and results We enrolled 51 consecutive ADHF patients with LVEF ≥45%. Patients were randomly assigned to receive either tolvaptan add‐on (n = 25) or conventional diuretic therapy (n = 26). Cardiac iodine‐123 metaiodobenzylguanidine (MIBG) imaging was performed after stabilisation of heart failure symptoms, and the cardiac MIBG heart‐to‐mediastinum ratio (HMR) and washout rate (WR) were calculated. There were no significant differences in the body weight change and total urine volume during 2 days after randomisation or in the HMR on delayed image (HMR(d)) and WR between the tolvaptan and conventional groups. After stratification based on the median change in body weight, the patients with higher weight reduction had a significantly lower HMR(d) (P = 0.0128) and tended to have a higher WR (P = 0.0786) in the conventional group, whereas the cardiac MIBG imaging results were not influenced by body weight reduction in the tolvaptan group. Conclusions Adjunctive tolvaptan therapy may provide rapid decongestion without a harmful effect on CSNA in ADHF patients with preserved LVEF.

Traumatic perilymphatic fistula with pneumolabyrinth and stapediovestibular dislocation is rare, and these treatments are still controversial. A 38-year-old man presented to our hospital with vertigo and right-ear hearing loss. The symptoms occurred immediately after a traumatic ear injury after falling on a branch of a camellia tree. Computed tomography showed the presence of air in the vestibule and stapediovestibular dislocation. He underwent surgery treatment. The stapes was found to be depressed into the vestibule, which was cracked, with a piece of the tree branch lodged in the crack. Hence, we did not reposition the stapes. We sealed the oval window using perichondrium, a cartilagenous columella was placed. In this case, immediate surgical intervention was necessary to prevent infection. There was no additional inner ear damage and the patient’s hearing was partially restored, removing the stapes seems to have been an acceptable solution.

Two highly active and stable Pd-based intermetallic nanocrystals with early d-metals Pd3Ti and Pd3Zr have been developed. The nanocrystals are synthesized by co-reduction of the respective salts of Pd and Ti/Zr. Hard X-ray photoemission Spectroscopy (HAXPES) analysis of the nanocrystals indicates that the electronic properties of Pd are modified significantly, as evident from the lowering of the d-band center of Pd. The intermetallic nanocrystals dispersed in Vulcan carbon, Pd3Ti/C and Pd3Zr/C, exhibit improved electrocatalytic activity towards methanol and ethanol oxidation in an alkaline medium (0.5 M KOH), compared to those of commercially available catalysts such as Pd/C, Pt/C, and Pt3Sn/C. In addition, Pd3Ti/C and Pd3Zr/C show significantly higher activity towards the oxidation of formic acid in an acidic medium (0.5 M H2SO4), compared to those of Pd/C and Pt/C. The modification of the d-band center of Pd as a result of the alloying of Pd with the early d-metals Ti and Zr may be responsible for the enhanced catalytic activity.

Nanoporous metals possess excellent catalytic and optical properties that are related with surface morphology. Here, we modulated the ligament surface of nanoporous gold (NPG) by controlling electrochemical dealloying and obtained NPG with an improved enhancement of its surface-enhanced Raman scattering (SERS) property. We found that both high-density atomic steps and kinks on the curved surfaces and high-content silver atoms close to the ligament surface contributed to the high SERS ability. The presented strategy will be useful for the fabrication of nanoporous metal with an excellent surface that is needed for sensing, conversion, and catalytic.

Hydrogen boride (HB) sheets are two-dimensional materials comprising a negatively charged hexagonal boron network and positively charged hydrogen atoms with a stoichiometric ratio of 1:1. Herein, we report the spontaneous formation of highly dispersed Ni nanoclusters on HB sheets. The spontaneous reduction reaction of Ni ions by the HB sheets was monitored by in-situ measurements with an ultraviolet-visible spectrometer. Acetonitrile solutions of Ni complexes and acetonitrile dispersions of the HB sheets were mixed in several molar ratios (the HB:Ni molar ratio was varied from 100:0.5 to 100:20), and the changes in the absorbance were measured over time. In all cases, the results suggest that Ni metal clusters grow on the HB sheets, considering the increase in absorbance with time. The absorbance peak position shifts to the higher wavelength as the Ni ion concentration increases. Transmission electron microscopy images of the post-reaction products indicate the formation of Ni nanoclusters, with sizes of a few nanometers, on the HB sheets, regardless of the preparation conditions. These highly dispersed Ni nanoclusters supported on HB sheets will be used for catalytic and plasmonic applications and as hydrogen storage materials.

The development of lightweight and safe hydrogen carrier materials is desirable for hydrogen energy storage and release. Here, authors prepare hydrogen boride nanosheets and observe hydrogen gas production induced by light irradiation.

The mechanism of lithium storage in graphenic carbon remains a fundamental question to be addressed. Here the authors employ suitable bilayer graphene foam to investigate various physiochemical phenomena of lithium intercalation and propose a storage model.

Background:. When complete recovery of tongue function following tumor excision is desired, reestablishment of the complex movements of the tongue is necessary. However, currently available methods for recovery of tongue function, such as flap surgery or prosthesis insertion, are inadequate. In the current study, we investigated the effects of transplantations of tongue allografts. Methods:. Hemi-tongue allotransplantation procedures were performed with 8 pairs of sex-blind and unrelated beagle dogs. In each donor, the right side of the tongue, including the lingual and hypoglossal nerves, extrinsic muscles of the tongue, mucous membrane of the oral floor, lingual artery, and vein were exposed. A vascularized transplantation method was used with manual anastomosis of the blood vessels and nerves. Results:. Survival of the grafted tongue was only noted in 1 dog that died 5 days after transplantation. We suspected that the death was due to nutritional deficiency or dehydration, rather than hyperacute rejection of the transplant or technical failure of the microsurgical anastomosis. The grafted tongue was partially connected to the side of the recipient tongue, and lymphocyte infiltration was observed in this dog. Conclusions:. Postoperative management is difficult in dogs. Even if tongue allograft including nerves and extrinsic muscles is performed, it seems to take a long time before the tongue recovers its functions. Furthermore, expansive tongue allograft was too invasive a treatment for animals. If we want to adapt this procedure to humans, the first trial in a human will be done without animal experiments, as was the case with face transplantations.

Abstract Dry reforming of methane (DRM) is one of the most attractive chemical reactions, since it converts global‐warming gases into valuable syngas including hydrogen and carbon monoxide. Numerous previous studies used metal oxides catalysis supports, such as Al2O3, but their operating temperature was very high and severe coking occurred and deteriorated their catalytic activities. The present study reports that a metal carbide like tantalum carbide (TaC) acts as a multifunctional catalyst support for the DRM reaction, including light‐harvesting properties for saving energy operation as well as an anticoking property for long‐term stability. Nickel nanoparticles loaded on tantalum carbide (Ni/TaC) are prepared by impregnation and reductive hydrogen treatment. TaC particles act as a light‐harvesting support to promote the DRM reaction by photon irradiation through plasmonic photothermal energy conversion in TaC. Furthermore, Ni/TaC exhibits an excellent long‐term anticoking property, as compared to Ni loaded on conventional metal oxide supports such as Al2O3 or Ta2O5. According to the sole gas condition's experiment, and secondary ion mass spectroscopy, the oxy‐carbide layer near the interface between TaC and Ni plays an essential role in imparting the efficient anticoking property of Ni/TaC.

Pneumoperitoneum, the presence of free air within the peritoneal cavity, is often caused by the perforation of gas-containing viscus and commonly requires surgical treatment. However, in patients with peritoneal dialysis, free air is commonly seen on X-ray. We present the case of a patient with peritoneal dialysis with marked pneumoperitoneum. A 75-year-old Japanese male with end-stage renal disease due to antineutrophil cytoplasmic antigen-associated vasculitis had been receiving continuous ambulatory peritoneal dialysis for 9 years. He had a poor appetite and general malaise without abdominal pain or fever. These symptoms gradually worsened, and he was hospitalized. At the time of admission, chest X-ray revealed bilateral free air in the abdomen. Subsequent computed tomography of the abdomen revealed marked pneumoperitoneum. Peritonitis due to perforation of the digestive tract was considered; however, the absence of abdominal pain, fever, and turbidity of dialysis drainage indicated that peritonitis was unlikely. Insufficient air venting during continuous ambulatory peritoneal dialysis bag replacement was suspected. The bag was carefully changed, resulting in a gradual decrease in the free air. We encountered a patient with continuous ambulatory peritoneal dialysis who had significant free air in the abdominal cavity in the absence of peritonitis. The source of the air was determined to be the dialysis bag due to insufficient venting during replacement. This case underscores the importance of instructing patients with continuous ambulatory peritoneal dialysis on the thorough removal of air from the bag during replacement.

Conventional dealloying methods to produce bicontinuous open nanoporous structures for catalysis are limited to very few alloys and produce chemical waste. Here, the authors develop a green process, vapor-phase dealloying, to selectively remove high partial vapor pressure components and create nanoporosity in a wide range of alloys.

1,1-Difluoro-1-alkenes bearing a biaryl-2-yl group effectively underwent site-selective intramolecular iodoarylation by the appropriate cationic iodine species. Iodoarylation of 2-(2-aryl-3,3-difluoroallyl)biaryls proceeded via regioselective carbon–carbon bond formation at the carbon atoms in β-position to the fluorine substituents, thereby constructing dibenzo-fused six-membered carbocycles bearing a difluoroiodomethyl group. In contrast, 2-(3,3-difluoroallyl)biaryls underwent a similar cyclization at the α-carbon atoms to afford ring-difluorinated seven-membered carbocycles.

Nanoporous metals prepared via dealloying or selective leaching of solid solution alloys and compounds represent an emerging class of materials. They possess a three-dimensional (3D) structure of randomly interpenetrating ligaments/nanopores with sizes between 5 nm and several tens of micrometers, which can be tuned by varying their preparation conditions (such as dealloying time and temperature) or additional thermal coarsening. As compared to other nanostructured materials, nanoporous metals have many advantages, including their bicontinuous structure, tunable pore sizes, bulk form, good electrical conductivity, and high structural stability. Therefore, nanoporous metals represent ideal 3D materials with versatile functionality, which can be utilized in various fields. In this review, we describe the recent applications of nanoporous metals in molecular detection, catalysis, 3D graphene synthesis, hierarchical pore formation, and additive manufacturing (3D printing) together with our own achievements in these areas. Finally, we discuss possible ways of realizing the ultimate 3D functionality beyond the scope of nanoporous metals.

Tuning the ratio of facets in materials can affect catalytic activity but methods to achieve this can be difficult to control. Here, using surfactants during dealloying, the authors prepare nanoporous gold with controlled facet ratios and show how it can significantly improve electrocatalytic activity.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescent and 2-year-old mice. The perilymph of adolescent mice exposed to the noise intensity resulting in permanent auditory threshold elevations had significantly increased levels of IL-6, TNF-α, and CXCL1 6 h after exposure, with CXCL1 levels being most elevated (19.3 ± 6.2 fold). We next provide the first immunohistochemical localization of CXCL1 in specific cochlear supporting cells, and its presumed receptor, Duffy antigen receptor for chemokines (DARC), in hair cells and spiral ganglion neurons. Our results demonstrate the feasibility of molecular diagnostics of SNHL using only 0.5 μL of perilymph, and motivate future sub-μL based diagnostics of human SNHL based on liquid biopsy of the inner ear to guide therapy, promote hearing protection, and monitor response to treatment.

To understand and obtain basic information on sex differentiation in the kisslip cuttlefish (Sepia lycidas), the gonadal sex differentiation process was investigated histologically. An undifferentiated gonad consisting of germ cells and somatic cells was found to form at a caudal site in the space between the internal yolk sacks of cuttlefish embryos at 14 and 21 days after spawning (DAS). Sexual dimorphism in the gonad was first detected at around 28 DAS. Meiotic oocytes were observed as the first visible morphological characteristic of ovaries in the gonads of some cuttlefish embryos at 28 DAS. In other individuals, neither meiotic germ cells, nor the appearance of a testicular structure, were observed in the gonad even after 10 days post hatching (DPH). Seminiferous tubules, consisting of a small number of spermatogonia and a surrounding basement membrane, were the first visible morphological characteristic of the testis in the male gonad, detected at around 20 DPH. This is the third report on the gonadal sex differentiation process in cephalopods.

An 8-year-old boy was referred to the ENT department for further evaluation of right-sided conductive hearing loss. A small cyst anterior to the oval window and fixation of the stapes footplate were observed during an exploratory tympanotomy. The concentration of a perilymph-specific protein, cochlin-tomoprotein (CTP), in the middle ear lavage fluid was measured with an ELISA-based CTP detection kit. The level of CTP in the middle ear lavage fluid before fenestration of the cyst was 0.26 ng/ml (negative), and its level after fenestration was 2.98 ng/ml (positive), confirming the presence of perilymph in the cyst. A small bone dehiscence, considered to be the fissula ante fenestram, was observed anterior to the stapes footplate after removal of the cyst. The CTP detection test results allowed us to confirm that the small bone dehiscence was connected to the inner ear.

Amorphous silicon monoxide is known to undergo disproportionation to silicon- and silicon dioxide-like regions, however direct observation of the atomic-scale heterogeneity is still missing. Here, the authors use angstrom-beam electron diffraction to reveal precise structural details of this unusual material.

Objective: The peak-to-peak amplitude of the p13-n23 wave in cervical vestibular evoked myogenic potential can increase after furosemide administration in patients with Meniere's disease [furosemide-loading VEMP (FVEMP) testing]. The examination is used to test for the presence of endolymphatic hydrops; we investigated factors that may influence the results.Methods: Forty-two subjects (23 males and 19 females, aged 24–70 years) with unilateral definite Meniere's disease who underwent FVEMP testing were retrospectively studied. Possible factors associated with the results of FVEMP testing were studied using logistic regression analysis.Results: Ages, sex, affected side, stage, disease duration, and mean hearing level of pure tone audiometry did not influence the results of FVEMP testing in the univariate analysis (p > 0.05). Number of days since the last vertigo attack [odds ratio (OR): 1.07, p = 0.031] and frequency of vertigo attacks per month (OR: 0.42, p = 0.003) were significantly associated with the results of testing. Multivariate analysis showed that both days since the last vertigo attack < 7 (OR: 0.13, p = 0.04) and frequency of vertigo attacks per month ≥ 2 (OR: 0.06, p = 0.004) were risk factors for negative results on FVEMP testing.Conclusion: This study found that recent and frequent vertigo attacks produced negative findings on FVEMP testing in Meniere's disease. This apparently irrational finding can be explained by the consequences of membranous labyrinth rupture during vertigo attacks, where the altered saccular resonance due to EH cannot be recovered by furosemide administration because of the dissolving dehydration effect that occurs through communication between the endolymphatic and perilymphatic spaces. In addition, the impairment of sensory cells that is caused by endolymph and perilymph mixing upon rupture does not improve upon furosemide administration. FVEMP testing results may provide us with pathophysiological information regarding the membranous labyrinth.

Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non‐existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro‐inflammatory transcription factor nuclear factor‐kappa B (NF‐κB) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF‐κB complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS‐derived human cell line HEI‐193 were treated with specific NF‐κB siRNAs, experimental NF‐κB inhibitor BAY11‐7082 (BAY11) and clinically relevant NF‐κB inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI‐193 cells, with siRNA, 5 μM BAY11 and 50 μM curcumin reducing average proliferation (±standard error of mean) to 62.33% ± 10.59%, 14.3 ± 9.7%, and 23.0 ± 20.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF‐κB as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF‐κB in VS.

Purpose: The aim of this study was to describe high-resolution dacryoendoscopy findings for nasolacrimal duct obstruction (NLDO) in three representative pediatric cases with different etiologies. Observations: In a case of congenital NLDO, a mucosal membranous obstruction was observed at the distal end of the nasolacrimal duct (NLD), and a slit-shaped opening of the NLD was observed after perforation. In a case of acquired NLDO secondary to an adenoviral infection, a membranous obstruction was observed at the proximal NLD. In a case of NLDO with chronic dacryocystitis in a patient with Down syndrome, diffuse fibrous obstruction was observed. Conclusion and importance: High-resolution dacryoendoscopy enables a clearer visualization of pediatric lacrimal duct obstructions, leading to an improved understanding of their features.

Background. Ethylene glycol intoxication causes severe metabolic acidosis and acute kidney injury. Fomepizole has become available as its antidote. Nevertheless, a prompt diagnosis is not easy because patients are often unconscious. Here we present a case of ethylene glycol intoxication who successfully recovered with prompt hemodialysis. Case Presentation. A 52-year-old Japanese male was admitted to a local hospital due to suspected food poisoning. The patient presented with nausea and vomiting, but his condition rapidly deteriorated, with worsening conscious level, respiratory distress requiring mechanical ventilation, hypotension, and severe acute kidney injury. He was transferred to the university hospital; hemodialysis was initiated because of hyperkalemia and severe metabolic acidosis. On recovering consciousness, he admitted having ingested antifreeze solution. Thirty-seven days after admission, the patient was discharged without requiring HD. Conclusions. We reported a case of ethylene glycol intoxication who presented with a life-threatening metabolic acidosis. In a state of severe circulatory shock requiring catecholamines, hemodialysis should be avoided, and continuous hemodiafiltration may be a preferred approach. However, one should be aware of the possibility of intoxication by unknown causes, and hemodialysis could be life-saving with its superior ability to remove toxic materials in such cases.

Nanoporous metals have been attracting considerable research and industrial attention because of the structural uniqueness of their bicontinuous metallic structure [...]

The effect of surfactant solutions on laminar boundary layer over a flat plate has been investigated at Re < 15.3×103 by measuring the velocity profile using a PIV system. It was clarified that the boundary layer thickness of surfactant solutions increases significantly compared to that of tap water. In the upstream region of the leading edge, the boundary layer (or the stagnation area) has already been generated and the thickness of this area is already large. In the downstream region, the velocity profiles of all surfactant concentrations at the near-wall region, are similar, but not identical, to that of tap water. At the far-wall region of the boundary layer, the velocity profile is significantly different. For higher surfactant concentrations, the velocity profile describes like S-shape profile, which is greatly different from that of lower concentration. When the Reynolds number increases, the velocity profile of the surfactant solution gradually develops. The dependence of the boundary layer thickness of the surfactant solution on the distance downstream from the leading edge is similar to that of tap water. Consequently, the surfactant gives large effect for not only development of the boundary layer but also the generation of it.

The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to "wake up" these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs.

Diffuse-type solid tumors are often composed of a high proportion of rarely proliferating (i.e., dormant) cancer cells, strongly indicating the involvement of cancer stem cells (CSCs) Although diffuse-type gastric cancer (GC) patients have a poor prognosis due to high-frequent development of peritoneal dissemination (PD), it is limited knowledge that the PD-associated CSCs and efficacy of CSC-targeting therapy in diffuse-type GC. In this study, we established highly metastatic GC cell lines by in vivo selection designed for the enrichment of PD-associated GC cells. By microarray analysis, we found C-X-C chemokine receptor type 4 (CXCR4) can be a novel marker for highly metastatic CSCs, since CXCR4-positive cells can grow anchorage-independently, initiate tumors in mice, be resistant to cytotoxic drug, and produce differentiated daughter cells. In clinical samples, these CXCR4-positive cells were found from not only late metastasis stage (accumulated ascites) but also earlier stage (peritoneal washings). Moreover, treatment with transforming growth factor-β enhanced the anti-cancer effect of docetaxel via induction of cell differentiation/asymmetric cell division of the CXCR4-positive gastric CSCs even in a dormant state. Therefore, differentiation inducers hold promise for obtaining the maximum therapeutic outcome from currently available anti-cancer drugs through re-cycling of CSCs.

OBJECTIVE:Age-related hearing loss (AHL), or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD). METHODS:Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup). Nine CBA/N-slc mice were also used as a 12-month control (n = 5) or 12-month HFD (n = 4) group. The mice were fed a HFD or normal (control) diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs). Spiral ganglion cells (SGCs) were also counted. RESULTS:The elevation of ABR thresholds (at 4 and 32 kHz) at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups. CONCLUSIONS:The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice.

Nanoporous Au-Fe alloy was synthesized via a wet chemistry route using ordered nanoporous silica as a hard template. The nanoporous Au-Fe consisted of aligned arrays of nanopores that were uniform in composition and ordered in hexagonal lattice, whereas Au-Fe nanoparticles synthesized without templates exhibited broad dispersions in the chemical composition and/or particle size. Nanoporous Au-Fe has potential for applications as catalysts and/or adsorbents because of the large specific surface area of 81.2 m2·g−1 and high pore volume of 0.56 cm3·g−1.

We performed in-situ transmission electron microscopy (TEM) on a dealloyed nanoporous NiCo catalyst used for the dry reforming of methane (DRM) to investigate the origin of the catalytic activity and structural durability. The in-situ observations and local chemical analysis indicated that the DRM induced chemical demixing of Ni and Co accompanied by grain refinement, implying possible “synergic effects” in a general bimetallic NiCo catalyst when used for the DRM.

Aim. The goal of the study was to investigate quality of life (QOL) in adult patients with minimal change nephrotic syndrome (MCNS) and to test the relationship of QOL with the level of self-care. Materials and Methods. We distributed two questionnaires to 30 outpatients with MCNS. The MOS 36-item Short Form Health Survey (SF-36v2) was used to examine health-related QOL in comparison with normative data from the general Japanese population and a population with two chronic diseases. SF-36v2 consists of 36 questions classified into 8 subscales. We also used the Self-Care Behavior Scale for patients with chronic kidney disease (CKD), which consists of 31 questions with 4 subscales. Results. The SF-36v2 social functioning subscale was most impaired and bodily pain was least affected in patients with MCNS. The self-care subscales of information/communication and positive behavior had positive correlations with the QOL subscales of mental health () and vitality (). The correlation between social functioning and information/communication was close to significant (). Conclusion. In MCNS, social functioning was particularly impaired. Our results suggest that better self-care can have a positive impact on QOL in patients with MCNS.

Single-stranded conformational polymorphism (SSCP) analysis is useful for mutation detection and polymorphism identification. To realize high-throughput SSCP analysis using a high-intensity electric field, the gel temperature must be well-controlled. We have developed an electrophoretic system having a pair of glass plates with an efficient temperature-controlling apparatus on each side of the gel. The gel temperature is controlled by estimating the temperature difference between the gel and the glass plates, based on a heat-transfer model. Distinctive patterns of asymmetric-PCR SSCP gel electrophoresis were obtained with this system. The patterns showed high reproducibility for an electric field ranging from 40 V/cm to 160 V/cm, as long as the same gel temperature was used. Electric-field strength had little effect on the SSCP patterns. Use of the highest electric field reduced the run time to about 100 min.