Development and Optimization of Water-Soluble Double-Walled Carbon Nanotubes by Effective Surface Treatment of Inner Walls.

Carbon nanotubes are a significant class of nanomaterials with distinctive properties that have led to their application in a variety of fields, such as polymer composites, medicine, electronics, and material science. However, their nonpolar nature and insolubility in polar solvents limit their applications. To address this issue, highly functionalized and water-soluble double-walled carbon nanotubes (DWNTs) were developed by selectively oxidizing the inner walls of the DWNTs using oleum and nitric acid. The impact of reaction time on the chemical functionalization of DWNTs was investigated under two different reaction durations of 2 and 24 h. The presence of highly oxygenated functional groups resulted in high water solubility, which was confirmed by high- and low-frequency Raman spectroscopy, high-resolution transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, and optical spectroscopy. The conductivity of highly water-soluble W-DWNTs (24 h) was 122.65 × 102 S cm-1. After annealing for 12 h at 140 °C, the W-DWNTs retained 72% of their conductivity (88.79 × 102 S cm-1).

Erratum: Anharmonicity and Universal Response of Linear Carbon Chain Mechanical Properties under Hydrostatic Pressure [Phys. Rev. Lett. 125, 105501 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.105501.

Erratum: Anharmonicity and Universal Response of Linear Carbon Chain Mechanical Properties under Hydrostatic Pressure [Phys. Rev. Lett. 125, 105501 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.105501.

Anharmonicity and Universal Response of Linear Carbon Chain Mechanical Properties under Hydrostatic Pressure.

Isolated linear carbon chains (LCCs) encapsulated by multiwalled carbon nanotubes are studied under hydrostatic pressure (P) via resonance Raman scattering. The LCCs' spectroscopic signature C band around 1850 cm^{-1} softens linearly with increasing P. A simple anharmonic force-constant model not only describes such softening but also shows that the LCCs' Young's modulus (E), Grüneisen parameter (γ), and strain (ϵ) follow universal P^{-1} and P^{2} laws, respectively. In particular, γ also presents a unified behavior for all LCCs. To the best of our knowledge, these are the first results reported on such isolated systems and the first work to explore universal P-dependent responses for LCCs' E, ϵ, and γ.

Clinical pharmacokinetics of flomoxef in prostate tissue and dosing considerations for prostatitis based on site-specific pharmacodynamic target attainment.

Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.

[A Case of a Massive Retropharyngeal Hematoma Associated with Traumatic Cervical Cord Injury].

Retropharyngeal hematomas are uncommon, but they may rarely cause occlusion of the upper airway and threaten life. Retropharyngeal hematomas often occur due to head or neck injury;they rarely occur due to iatrogenic causes such as insertion of a gastric tube or anticoagulant therapy. It has been found that patients receiving anticoagulant therapy are more likely to experience potentially severe retropharyngeal hematomas. We report the case of a patient with retropharyngeal hematoma with cervical cord damage. A 75-year-old man was transferred to our hospital after he sustained a fall and damaged his face. CT showed a massive retropharyngeal hematoma, but he did not complain of any breathing issues. Therefore, we selected conservative therapy. However, after approximately 4 hours, he suddenly complained of breathing problems and suffered from loss of consciousness. We performed intubation and provided sedation. After one week, his condition clearly improved and he was extubated.

[A Case of Metachronous Testicular Tumor Developing Twenty Years after Treatment of Retroperitoneal Extragonadal Germ Cell Tumor].

A 49-year-old male visited our department of gastroenterology with chief complaints of blackish feces and ill complexion in February 1997. Computed tomography (CT) revealed a right retroperitoneal tumor, which was removed the same month. Histopathological examination showed teratoma and yolk sac tumor. He was diagnosed with primary retroperitoneal extragonadal germ cell tumor, and received three cycles of chemotherapy (bleomycin/etoposide/cisplatin ; BEP) starting in March 1997. Periodic imaging and determination of tumor markers (α fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no recurrence or metastasis for five years after treatment. After his visit in April 2002 he stopped visiting our outpatient ward. In November 2017, the patient visited our department with chief complaints of indolent right scrotum enlargement and a right inguinal mass. Past history showed that he had undergone hydrocele of the right testicle in August 1999. Contrast enhanced CT showed a 35-mm contrast effect with uneven contents in the right testis, and enlarged nodes that were suspicious of metastases in the right inguinal and right external iliac lymph nodes. All tumor markers were within the normal ranges. He underwent right high orchiectomy and resection of the right inguinal lymph nodes in the same month. Histopathological findings revealed seminoma (pT1, pN2, M0, S0, and clinical Stage IIA). He received postoperative chemotherapy starting in January 2018 ; one cycle of BEP therapy and three cycles of etoposide and cisplatin (EP) therapy. Post-chemotherapeutic CT confirmed clinical complete response at the right external iliac lymph nodes, and this response was confirmed 12 months later. Neither recurrence nor metastasis has occurred so far.

Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis.

BACKGROUND: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. METHODS: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. RESULTS: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P = .041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P < .001) and Gleason score (P = .006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P = .024 and .01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P < .001) and median survival time (not reached vs 69.0 months; P = .014) than those with higher expression levels. CONCLUSIONS: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.

[A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].

Liposarcomas are most commonly found in the extremities, in the retroperitoneum and, less often, in the head and neck area. The spermatic cord is a rare site of origin, accounting for about 4-7% of all liposarcomas. We report a case of dedifferentiated liposarcoma of the spermatic cord. A 51-year-old man was referred to our hospital for a painless hard mass in the left inguinal region. Abdominal computed tomography showed a left spermatic cord mass measuring 70 mm in diameter. We performed left high orchiectomy with resection of the mass. Immunohistochemical analysis revealed positive for murine double minute 2 (MDM 2) and cyclin dependent kinase 4 (CDK 4). Therefore, this sarcoma was diagnosed to be dedifferentiated liposarcoma. Since the surgical margin was positive, an additional wide resection including the surrounding normal tissue was performed. Complete excision was achieved after re-resection. He was alive 12 months postoperatively without any signs of recurrence. Dedifferentiated liposarcoma of the spermatic cord is a rare neoplasm. To the best of our knowledge, the present case is the 14th reported case in Japan.

Impact of a novel biopsy instrument with a 25-mm side-notch needle on the detection of prostate cancer in transrectal biopsy.

OBJECTIVES: To evaluate the impact of a novel biopsy instrument that extends the length of the side-notch on the detection of prostate cancer in transrectal needle biopsy. METHODS: We collaborated with a biopsy needle manufacturer and developed a novel biopsy instrument (PRIMECUT II long-notch type) with a 25-mm side-notch length and 28-mm stroke length to take longer tissue cores. The sampled core length, cancer detection rate, pain and complications of 489 patients who underwent transrectal biopsy using the long-notch needle were compared with those of 469 patients who underwent biopsy using a normal instrument with a 19-mm side-notch length and 22-mm stroke length. RESULTS: The mean length of tissue taken by the long-notch needle was significantly longer than that of tissue taken by the normal-notch needle (16.3 vs 22.4 mm, P < 0.001). The overall cancer detection rate was 42.0% for the normal-notch needle and 51.1% for the long-notch needle (P = 0.005). In patients with a prostate volume of 20-40 mL, the cancer detection rate for the long-notch needle was especially higher than that for the normal-notch needle (74.2% vs 47.5%, P < 0.001). Multivariate analysis showed that the long-notch needle improved cancer detection significantly (odds ratio 1.702, P < 0.001). There were no differences of pain during biopsy and complication between the two groups. CONCLUSIONS: The novel biopsy instrument with a 25-mm side-notch can take longer tissue samples safely and has a significantly higher rate of prostate cancer detection in transrectal biopsy.

Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.

The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax)/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82-0.99 and for AUC, 0.80-0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.

Rice husk-derived graphene with nano-sized domains and clean edges.

A new synthetic method is demonstrated for transforming rice husks into bulk amounts of graphene through its calcination and chemical activation. The bulk sample consists of crystalline nano-sized graphene and corrugated individual graphene sheets; the material generally contains one, two, or a few layers, and corrugated graphene domains are typically observed in monolayers containing topological defects within the hexagonal lattice and edges. Both types of graphenes exhibit atomically smooth surfaces and edges.

Nrf2 deficiency leads to behavioral, neurochemical and transcriptional changes in mice.

Nrf2 is a transcription factor that regulates the antioxidant and detoxification enzyme genes and provides defense against oxidative and electrophilic stresses in various tissues. In brain, while neuroprotective functions of Nrf2 have been well documented, Nrf2 contribution to the brain function remains to be elucidated. To address this issue, we investigated whether Nrf2 deficiency affects psychological behaviors, neurotransmitter systems and gene expressions in mice. We conducted four behavioral tests, social interaction, open-field, rotarod and forced swimming tests and found that Nrf2 knockout mice exhibited reduced immobility in the forced swimming test. Neurochemical analyses revealed that the dopamine and serotonin metabolites increased in the brains of Nrf2 knockout mice. We also present a catalog of genes whose expression is Nrf2-dependent in brain under unstressed conditions, which includes a number of xenobiotic-metabolizing enzyme genes. These results thus support our contention that Nrf2 regulates its target genes in brain under unstressed conditions and loss of Nrf2 affects various brain functions.

[A case of neuroendocrine carcinoma in a diverticulum of the bladder].

We report a case of neuroendocrine carcinoma in a diverticulum of the bladder. A 65-year-old Japanese woman visited our hospital with the chief complaint of gross hematuria. Cystoscopy revealed a non-papillary broad-based tumor in a diverticulum of the posterior wall. She underwent transurethral resection of bladder tumor (TURBT) and subsequently total cystectomy with ileal conduit on the diagnosis of an invasive urothelial carcinoma. There was no residual tumor in the surgical specimen. Immunohistochemistry of TUR specimens showed positive synaptophysin, chromogranin A, CD56 and high ratio of positive Ki-67. Finally, it was diagnosed as a neuroendocrine carcinoma of the bladder. To our knowledge, this is the second case report of the neuroendocrine tumor or small cell carcinoma in a diverticulum of the urinary bladder in the Japanese literature.

Imatinib mesylate inhibits androgen-independent PC-3 cell viability, proliferation, migration, and tumor growth by targeting platelet-derived growth factor receptor-α.

AIM: The abnormal expression of oncogenic tyrosine kinase receptors such as platelet-derived growth factor receptors (PDGFRs) has been reported in cancer progression. However, the role of PDGFRs in the human androgen-independent prostate cancer PC-3 cell line is not well understood. Thus, this study examined the role of PDGFRs in androgen-independent PC-3 cells. MAIN METHODS: PDGFR mRNA and protein expression was determined by quantitative real-time PCR and western blotting, respectively. The effects of the tyrosine kinase inhibitor imatinib (imatinib mesylate) and small interfering RNAs (siRNAs) were determined by a Cell Counting Kit-8 assay, bromodeoxyuridine assay, and Transwell migration assay. The in vivo effect of imatinib was analyzed using a tumor formation assay in nude mice. KEY FINDINGS: PDGFRα was upregulated in androgen-independent PC-3 cells compared with normal prostate epithelial cells. PDGF-BB induced the phosphorylation of PDGFRα and downstream signaling molecules, including Akt, in a dose-dependent manner. Imatinib reduced the phosphorylation of the PDGFRα/Akt axis. Imatinib also suppressed the viability, proliferation, migration, and tumor growth of PC-3 cells. PDGFRα knockdown by siRNA decreased the viability and migration of PC-3 cells. SIGNIFICANCE: These results demonstrated the distinct contribution of PDGFRα signaling to the proliferation and migration of PC-3 cells and suggested the potential for PDGFRα as a therapeutic target for metastatic and androgen-independent prostate cancer.

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture.

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II-III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II-III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II-III NSCLC in the real-world setting.

Optically and biologically active mussel protein-coated double-walled carbon nanotubes.

A method of dispersing strongly bundled double-walled carbon nanotubes (DWNTs) via a homogeneous coating of mussel protein in an aqueous solution is presented. Optical activity, mechanical strength, as well as electrical conductivity coming from the nanotubes and the versatile biological activity from the mussel protein make mussel-coated DWNTs promising as a multifunctional scaffold and for anti-fouling materials.

Mass-produced multi-walled carbon nanotubes as catalyst supports for direct methanol fuel cells.

Commercially mass-produced multi-walled carbon nanotubes, i.e., VGNF (Showa Denko Co.), were applied to support materials for platinum-ruthenium (PtRu) nanoparticles as anode catalysts for direct methanol fuel cells. The original VGNFs are composed of high-crystalline graphitic shells, which hinder the favorable surface deposition of the PtRu nanoparticles that are formed via borohydride reduction. The chemical treatment of VGNFs with potassium hydroxide (KOH), however, enables highly dispersed and dense deposition of PtRu nanoparticles on the VGNF surface. This capability becomes more remarkable depending on the KOH amount. The electrochemical evaluation of the PtRu-deposited VGNF catalysts showed enhanced active surface areas and methanol oxidation, due to the high dispersion and dense deposition of the PtRu nanoparticles. The improvement of the surface deposition states of the PtRu nanoparticles was significantly due to the high surface area and mesorporous surface structure of the KOH-activated VGNFs.

MAZ51 Blocks the Tumor Growth of Prostate Cancer by Inhibiting Vascular Endothelial Growth Factor Receptor 3.

Vascular endothelial growth factor (VEGF) signaling plays a critical role in the carcinogenesis and tumor development of several cancer types. However, its pathological significance in prostate cancer, one of the most frequent and lethal malignancies in men, remains unclear. In the present study, we focused on a pathological role of the VEGF receptors (VEGFRs), and examined their expression and effects of MAZ51 (an inhibitor of the tyrosine kinase of VEGFR-3) on cell proliferation, migration, and tumor growth in human prostate cancer cells. The expression level of VEGFR-3 was higher in androgen-independent and highly metastatic prostate cancer PC-3 cells than in other prostate PrEC, LNCaP, and DU145 cells. In PC-3 cells, VEGFR-3 and Akt were phosphorylated following a stimulation with 50 ng/ml VEGF-C, and these phosphorylations were blocked by 3 µM MAZ51. Interestingly, PC-3 cells themselves secreted VEGF-C, which was markedly larger amount compared with PrEC, LNCaP, and DU145 cells. MAZ51 reduced the expression of VEGFR-3 but not VEGFR-1 and VEGFR-2. The proliferation of PC-3 cells was inhibited by MAZ51 (IC50 = 2.7 µM) and VEGFR-3 siRNA, and partly decreased by 100 nM GSK690693 (an Akt inhibitor) and 300 nM VEGFR2 Kinase Inhibitor I. MAZ51 and VEGFR-3 siRNA also attenuated the VEGF-C-induced migration of PC-3 cells. Moreover, MAZ51 blocked the tumor growth of PC-3 cells in a xenograft mouse model. These results suggest that VEGFR-3 signaling contributes to the cell proliferation, migration, and tumor growth of androgen-independent/highly metastatic prostate cancer. Therefore, the inhibition of VEGFR-3 has potential as a novel therapeutic target for the treatment for prostate cancer.