Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Consequences of Preoperative Oral Carbohydrate Consumption in Septal Deviation Patients Undergoing Endoscopic Septoplasty: A Retrospective Cohort Study.

PURPOSE: Multiple reports have demonstrated the benefits of preoperative oral carbohydrates (CHO) in patients receiving open abdominal, thoracic, and orthopedic surgeries. However, thus far, no reports have investigated the benefits of CHO in patients undergoing nasal endoscopic surgery. Our goal was to evaluate the outcome of preoperative oral of administration of CHO in septal deviation patients, undergoing endoscopic septoplasty, under general anesthesia. DESIGN: A retrospective cohort study from a prospectively collected database. METHODS: Consecutive 400 septal deviation patients, undergoing endoscopic septoplasty, were randomly assigned to receive CHO or plain water (80 CHO cohort vs. 320 control cohort) before general anesthesia. The primary outcome was the risk of acute postoperative hypertension (APH). The secondary outcomes included length of hospital stay (LOS), hospitalization cost, sleep time the day before surgery, fluid infusion volume on surgical day, as well the incidence of postoperative nausea and vomiting (PONV) and aspiration. FINDINGS: Patients in the CHO cohort experienced a lower risk of both diastolic blood pressure (DBP)-based APH (OR, 0.49; 95% CI, 0.25 to 0.96; P = 0.0375) and total APH (OR, 0.49; 95% CI, 0.26 to 0.92; P = 0.0258), lower LOS, lower hospitalization cost, longer sleep time and less fluid infusion volume after adjusting for gender, age, BMI, preoperative blood pressure and pulse. Besides, data showed no significant differences in the incidence of (P = 0.4173) and aspiration (P > 0.99). CONCLUSIONS: Preoperative CHO administration can reduce APH risk in patients undergoing endoscopic septoplasty under general anesthesia. Besides, preoperative CHO administration can improve other clinical outcomes, such as, LOS, hospitalization cost, sleep time, and fluid infusion volume. Moreover, CHO safety was confirmed in our study. In the future, additional investigation is necessary to confirm our results.

Sum of High-Risk Gene Mutation (SHGM): A Novel Attempt to Assist Differential Diagnosis for Adrenocortical Carcinoma with Benign Adenoma, Based on Detection of Mutations of Nine Target Genes.

There has been no research on applying gene detection to differential diagnosis of adrenocortical carcinoma (ACC). We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues. Nine genes were chosen as target genes, including TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1, and RPL22. Exons sequencing of target genes were performed in 98 cases of tissue samples by FastTarget technology, including 41 ACC tissues, 32 ACA tissues, and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC. We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including ZNRF3, ARMC5, TP53, APC, RB1, and PRKAR1A, regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM > 0 and SHGM > 1 in ACC tissues were 73.0% and 62.2%, respectively, both obviously higher than those in ACA tissues, with significant statistic differences. Especially for 8 cases of ACC with diameter < 5 cm, SHGM > 0 and SHGM > 1 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC. We identified 6 high-risk genes in ACC tissues, with significantly higher mutation rates than ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.

Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression.

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

Tunable light absorbance by exciting the plasmonic gap mode for refractive index sensing.

The tunable and narrowband optical response from the surface plasmon resonances usually requires periodic metal nanostructures; however, it is usually expensive and challenging to construct such macroscale and defect-free devices. Herein, we make it possible to obtain a characteristic and sharp absorbance via exciting the plasmonic gap mode, which can be obtained in a large-area sample prepared with relatively low cost. The resonant wavelength can be tuned via changing the bottom-facet area of the top structured metal or the spacer thickness. Furthermore, we design the hexagonal arrangement gold microholes atop the gold continuous film with a spacer, which possesses a sharp reflectance dip from the intense plasmonic gap mode. Numerical calculations show that the resonant wavelength is linearly changed with the varying environmental refractive index (RI). The sensitivity is up to ∼1287 nm per RI unit, and the figure of merit for an RI sensor is over 300.

Single image super-resolution with denoising diffusion GANS.

Single image super-resolution (SISR) refers to the reconstruction from the corresponding low-resolution (LR) image input to a high-resolution (HR) image. However, since a single low-resolution image corresponds to multiple high-resolution images, this is an ill-posed problem. In recent years, generative model-based SISR methods have outperformed conventional SISR methods in performance. However, the SISR methods based on GAN, VAE, and Flow have the problems of unstable training, low sampling quality, and expensive computational cost. These models also struggle to achieve the trifecta of diverse, high-quality, and fast sampling. In particular, denoising diffusion probabilistic models have shown impressive variety and high quality of samples, but their expensive sampling cost prevents them from being well applied in the real world. In this paper, we investigate the fundamental reason for the slow sampling speed of the SISR method based on the diffusion model lies in the Gaussian assumption used in the previous diffusion model, which is only applicable for small step sizes. We propose a new Single Image Super-Resolution with Denoising Diffusion GANS (SRDDGAN) to achieve large-step denoising, sample diversity, and training stability. Our approach combines denoising diffusion models with GANs to generate images conditionally, using a multimodal conditional GAN to model each denoising step. SRDDGAN outperforms existing diffusion model-based methods regarding PSNR and perceptual quality metrics, while the added latent variable Z solution explores the diversity of likely HR spatial domain. Notably, the SRDDGAN model infers nearly 11 times faster than diffusion-based SR3, making it a more practical solution for real-world applications.

Enhanced electron field emission from carbon nanotubes irradiated by energetic C ions.

The field emission performance and structure of the vertically aligned multi-walled carbon nanotube arrays irradiated by energetic C ion with average energy of 40 keV have been investigated. During energetic C ion irradiation, the curves of emission current density versus the applied field of samples shift firstly to low applied fields when the irradiation doses are less than 9.6 x 10(16) cm(-2), and further increase of dose makes the curves reversing to a high applied field, which shows that high dose irradiation in carbon nanotube arrays makes their field emission performance worse. After energetic ion irradiation with a dose of 9.6 x 1016 cm(-2), the turn-on electric field and the threshold electric field of samples decreased from 0.80 and 1.13 V/microm to 0.67 and 0.98 V/microm respectively. Structural analysis of scanning electron microscopy, transmission electron microscopy and Raman spectroscopy indicates that the amorphous carbon nanowire/carbon nanotube hetero nano-structures have been fabricated in the C ion irradiated carbon nanotubes. The enhancement of electron field emission is due to the formation of amorphous carbon nanowires at the tip of carbon nanotube arrays, which is an electron emitting material with low work function.

Structures and field emission properties of silicon nanowire arrays implanted with energetic carbon ion beam.

Structures and field emission properties of silicon nanowire arrays (SiNWAs), which were fabricated by using of electroless-chemical etching method and post-implanted by the energetic carbon ion beam with an average energy of 20 keV at various doses, have been investigated. Structural analysis of SEM and XPS shows that SiC compound had been formed at the top of SiNWAs, and Si-C/Si composite nanostructure had been obtained. Compared to as-grown SiNWAs, the C ion implanted SiNWAs have better field emission characteristics. The turn-on field and the applied field at 100 microA/cm2 are reduced from 5.01 V/microm and 5.93 V/microm for as-grown SiNWAs to 4.45 V/microm and 5.40 V/microm for SiNWAs implanted at the dose of 1 x 10(16) cm(-2), respectively. However, large implanting amounts made serious structural damages at the top of nanowires, and impaired the field emission characteristics. The influence of energetic C ion implantation on the structures and field emission properties of SiNWAs has been discussed.

[Expression of SDHB, EPAS1 and MIB-1 in Zuckerkandl paragangliomas].

OBJECTIVE: To explore the significance of succinate dehydrogenase B (SDHB) mutation and EPAS1 overexpression in Zuckerkandl paragangliomas (PGL) and examine their correlations with malignant infiltration and metastasis. METHODS: From March 2008 to July 2011, the clinical profiles of 16 Zuckerkandl PGL patients were analyzed retrospectively. For increased diagnostic specificity, a complex immunohistochemical panel of tissue microarray was performed for SDHB, EPAS1 and MIB-1. Positive expression identified as a granular cytoplasmic staining. Greater than or equal to 50% as strongly positive (+++), 1% to 10% as weakly positive (+). RESULTS: Tissue microarray immunohistochemical staining showed SDHB immunoreactivity in the cytoplasm, whereas EPAS1 and MIB-1 in the nuclear of tumor cells. Positive expression of EPAS1 in which 13 cases of Zuckerkandl PGL. And high expression strongly associated with malignancy. SDHB mutation of 7 cases are all EPAS1 positive staining. Non-gene mutation 9 cases tumor specimens, 6 cases were EPAS1 positive expression (P < 0.05). CgA positive expression in 11 cases benign Zuckerkandl PGL, strongly positive in 4 malignant cases (4/4). MIB-1 below 1% in 12 cases of benign Zuckerkandl PGL. And in 4 malignant cases, MIB-1 was about 3%. Malignant neoplasms had significantly higher EPAS1, CgA and MIB-1 expression compared to benign counterparts (P < 0.05). CONCLUSIONS: The SDHB mutation causes the EPAS1 over expression in PGL and correlation with higher positive expression of CgA and MIB-1. It may be one of the mechanisms of malignant invasiveness and metastasis in PGL.

[Vasculogenic mimicry and mosaic vessels and targeted therapy in renal cell carcinoma].

Renal cell carcinoma is one of the most common malignant tumors of urinary system. The annual incidence rate is approximately 17.9/100 000 populations, and there is a continually rising trend in number of new diagnosis. Metastatic and high-risk renal cell cancer is associated with a poor prognosis and is resistant to traditional chemotherapy and/or radiotherapy. Although cytokine-based therapies (interferon and interleukin-2) have been widely used, their effectiveness remained unsatisfactory due to their low response rates and short survival. Drugs targeting anti-angiogenesis pathways have shown benefits in relapse-free survival. In this review, we introduce the recent advances in the treatment of renal cancer, especially the application of vasculogenic mimicry and mosaic vessels. Although targeted therapies with anti-angiogenic properties have proposed new treatment criteria for advanced renal cell carcinoma, new drugs or new combinations are needed to improve the clinical efficacy and minimize adverse effects.

Structures and field emission characteristics of ion irradiated silicon nanowire arrays.

Silicon nanowire (SiNW) arrays irradiated by energetic Si ions were fabricated by metal vapor vacuum arc (MEVVA) ion implantation method. Hetero-structure of amorphous/crystalline nanowire was formed in which structure of the implanted region on the top of the nanowires was amorphous while the structure of unimplanted region on the bottom remained crystal. Field emission (FE) properties of the SiNW arrays could be improved and modulated by different implantation doses. A low turn-on field of 4.63 V/microm was observed in the SiNWs irradiated by 21 keV Si ion with a dose of 7.86 x 10(16)/cm2, and the applied field for the emission current density reaching 100 microA/cm2 is only 5.52 V/microm. The main reason for the efficient emission is attributed to the formation of amorphous SiNWs and structure defects after implantation. The ion irradiated SiNWs after post-annealing at high temperature had better FE property due to eliminating the restrain effect to electrons.

Functional paragangliomas of the urinary bladder: a report of 9 cases.

BACKGROUND AND OBJECTIVE: Functional paraganglioma of the urinary bladder (FPUB) is a rare tumor. Misdiagnosis of FPUB before operation can lead to serious intraoperative consequences. In this article, we reported our experience in preoperative diagnosis and surgical treatment of FPUB. METHODS: Clinical data of nine patients with FPUB treated between June 1985 and January 2009 at Peking Union Medical College Hospital were analyzed. RESULTS: All patients underwent urinary catecholamine (CA) detection, B-ultrasound, CT and/or MRI scan; 5 underwent nailfola microcirculation inspection; 4 underwent 131I-metaiodobenzyl guanidine (MIBG) detection; and 6 underwent 111In-DTPA-Octreotide (OCT) scintiscan. According to the UICC bladder tumor classification, 5 patients had T2, 3 had T3, and 1 had T4 disease. All patients underwent surgical treatment, and 1 received 131I-MIBG therapy. All patients had paroxysmal hypertension and palpitation and six had cold sweat, headache, and dizziness after emphatic urination. The definitive diagnosis was made by histopathologic examination of the removed tumors and was confirmed in 7 cases by the immunohistochemical staining of chromogranin A, Ki-67 and S100 protein. The tumor consisted of discrete aggregates of zellballen cells separated by a network of vascular channels. One patient had metastases in the pelvic lymph nodes, liver and colon. Follow-up ranged from 7 to 289 months (mean, 127.2 ± 34.2). Six of the nine cases reported here were found in the usual locations. One patient had multiple tumors. The catecholamine level was elevated under basal conditions in 8 patients and during endoscopic resection of the tumor in 1 patient; it returned to normal after surgery in 8 patients. Three patients had recurrence and 1 had metastasis following surgery. CONCLUSIONS: Early preoperative diagnosis of FPUB is difficult, but it should be suspected in patients with typical tetrad symptoms: headache and micturition syncope, sweating, palpitation and hematuria. In those patients with unresectable multiple tumors, medicine and 131I-MIBG therapy may be helpful for controlling hypertension and delaying disease progression. Advanced classification (≥T3), multifocal tumors and CgA expression are risk factors of recurrence and metastasis.

A case report of neurological adverse events caused by short-term and low-dose treatment of mitotane: The role of therapeutic drug monitoring.

RATIONALE: Low-dose mitotane has been widely used for many decades in patients with advanced adrenocortical carcinoma (ACC), which exhibited good safety profiles compared with the high-dose regimen. The clinical efficacy and toxicity of mitotane are closely related to its plasma concentration, and therapeutic drug monitoring (TDM) is recommended. Until now, no severe adverse drug reaction (ADR) related to the toxic plasma level after a short-term treatment of low-dose mitotane has been published. PATIENT CONCERNS: A 50-year-old Chinese female presented with severe neurological adverse events related to a toxic plasma levels of 42.8 mg/L after 4 months treatment of low-dose mitotane. DIAGNOSES: During the course of therapy, no other medication could cause neurological adverse events. Therefore, we suspected a high sensitivity to the side effect of mitotane related to a toxic plasma level. INTERVENTIONS: Treatment of mitotane was stopped. OUTCOMES: The trough plasma concentration of mitotane decreased to 18.7 mg/mL after one and a half months, and the neurological symptoms gradually improved after drug discontinuance. LESSONS: The present case provides the first report of severe neurological adverse events induced by the short-term use of low-dose mitotane for adjuvant treatment in a patient with ACC, indicating that potentially severe ADR can also occur when using low-dose regimen in the early stage of treatment. TDM and early recognition could result in a favorable outcome.

Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS: A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS: A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS: The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.

Application of auditory cortical evoked potentials for auditory assessment in people using auditory prosthesis.

The present study explored the application of auditory cortical evoked potentials (ACEP) in the auditory assessment of people using an auditory prosthesis. There were 126 patients with prelingual deafness who were selected from January 2012-June 2017 from the First People's Hospital of Kunshan (Kunshan, China). HEARLab™ system was used to induce a P1-N1-P2 waveform under the condition of 60 dB sound pressure level at /m/, /g/ and /t/ acoustic stimulations. Speech production ability and auditory perception ability of patients were evaluated by speech intelligibility rating (SIR) and categories of auditory performance (CAP). Extraction rate of P1 waves of patients with auditory prosthesis was higher than that of N1 and P2 waves under different acoustic stimulations. A younger initial age and shorter deafness duration before patients used an auditory prosthesis led to more marked P1-N1-P2 waveforms and longer P1 latencies. At /m/ acoustic stimulation, P1 latency and amplitude were negatively associated with the usage time of auditory prosthesis. There were significant differences in the results of SIR and CAP and the initial age of use of auditory prosthesis and deafness duration before patients used the auditory prosthesis. These findings suggest that ACEP can be used to evaluate the auditory assessment of people using an auditory prosthesis. The initial age of use of an auditory prosthesis and deafness duration can affect the P1-N1-P2 waveform and P1 latency of prelingual deafness.

Ureteral obstruction and hydronephrosis caused by foreign body: A case report and literature review.

RATIONALE: Foreign bodies related ureteral obstruction and hydronephrosis is rare and usually cause numerous problems for clinical physicians. PATIENT CONCERNS: We report a 36-year-old female who was referred to our hospital due to a 4-year history of dull pain on the left back. DIAGNOSIS: X-ray and abdominal CT revealed a foreign body around the upper part of the left ureter with ureteral obstruction and hydronephrosis. INTERVENTIONS: Laparoscopy was performed and a 3-cm sewing needle was removed successfully. OUTCOMES: After 6 months' follow-up, the patient's ureteral obstruction and hydronephrosis were significantly reduced, and the double-J ureteral stent was removed. LESSONS: This case indicated that ureteral obstruction and hydronephrosis caused by foreign bodies needed to be early diagnosed and located. Invasive therapies rather than conservative treatments are preferred to remove the FBs and relieve obstruction.

Open adrenalectomy versus laparoscopic adrenalectomy for adrenocortical carcinoma: a retrospective comparative study on short-term oncologic prognosis.

PURPOSE: Open adrenalectomy (OA) remains the gold standard of surgical therapy for adrenocortical carcinoma, while the role of laparoscopic approach is controversial. We aim to explore the influence of surgical approaches on the oncologic prognosis of adrenocortical carcinoma by comparing the short-term outcomes of patients undergoing OA with those undergoing laparoscopic adrenalectomy (LA). PATIENTS AND METHODS: We retrospectively analyzed the baseline characteristics, perioperative data and short-term prognosis of 42 patients diagnosed with stage I-III adrenocortical carcinoma, receiving OA (n=22) and LA (n=20) as primary therapy. The primary end point was the first recurrence. RESULTS: OA group had larger mean maximum diameter of tumor (10.1±3.6 versus 6.3±2.2 cm) and lesser benefits in operative time, bleeding loss and postoperative hospital stay than laparoscopic group. Mean disease-free survival (DFS) of OA was 44.8±35.1 months, which was longer than 17.5±10.4 months of LA, and the rate of 2-year DFS after primary surgery in the open group was higher than in the laparoscopic group (61.1% versus 21.4%, respectively). Rates of 1- and 3-year DFS showed no significant difference. All patients undergoing LA (11/11) showed local recurrent lesions at the first time of recurrence, while 5 of 13 patients undergoing OA did not show local recurrence (P=0.03). CONCLUSION: OA for adrenocortical carcinoma is superior to laparoscopic approach in terms of DFS and rate of 2-year DFS, in spite of the larger maximum diameter of tumors and lesser benefit during perioperation. After LA, patients are more likely to show local recurrent lesions at the first time of relapse.

Evodiamine, a Novel NOTCH3 Methylation Stimulator, Significantly Suppresses Lung Carcinogenesis in Vitro and in Vivo.

Lung cancer is a leading cause of cancer-related deaths worldwide. NOTCH3 signaling is mainly expressed in non-small cell lung carcinoma (NSCLC), and has been proposed as a therapeutic target of NSCLC. While, few agents for preventing or treating NSCLC via targeting NOTCH3 signaling are used in modern clinical practice. Evodiamine (EVO), an alkaloid derived from Euodiae Fructus, possesses low toxicity and has long been shown to exert anti-lung cancer activity. However, the underlying anti-lung cancer mechanisms of EVO are not yet fully understood. In this study, we explored the involvement of NOTCH3 signaling in the anti-lung cancer effects of EVO. Urethane-induced lung cancer mouse model and two NSCLC cell models, A549 and H1299, were used to evaluate the in vivo and in vitro anti-lung cancer action of EVO. A DNA methyltransferase inhibitor was employed to investigate the role of NOTCH3 signaling in the anti-lung cancer effects of EVO. Results showed that EVO potently reduced tumor size and tumor numbers in mice, and inhibited NOTCH3 in the tumors. EVO also dramatically reduced cell viability, induced G2/M cell cycle arrest, inhibited cell migration and reduced stemness in cultured NSCLC cells. Mechanistic studies showed that EVO potently inhibited NOTCH3 signaling by activation of DNMTs-induced NOTCH3 methylation. Importantly, inhibition of NOTCH3 methylation in NSCLC cells diminished EVO's anti-NSCLC effects. Collectively, EVO, a novel NOTCH3 methylation stimulator, exerted potent anti-lung cancer effects partially by inhibiting NOTCH3 signaling. These findings provide new insight into the EVO's anti-NSCLC action, and suggest a potential role of EVO in lung cancer prevention and treatment.

High current density and longtime stable field electron transfer from large-area densely arrayed graphene nanosheet-carbon nanotube hybrids.

Achieving high current and longtime stable field emission from large area (larger than 1 mm(2)), densely arrayed emitters is of great importance in applications for vacuum electron sources. We report here the preparation of graphene nanosheet-carbon nanotube (GNS-CNT) hybrids by following a process of iron ion prebombardment on Si wafers, catalyst-free growth of GNSs on CNTs, and high-temperature annealing. Structural observations indicate that the iron ion prebombardment influences the growth of CNTs quite limitedly, and the self-assembled GNSs sparsely distributed on the tips of CNTs with their sharp edges unfolded outside. The field emission study indicates that the maximum emission current density (Jmax) is gradually promoted after these treatments, and the composition with GNSs is helpful for decreasing the operation fields of CNTs. An optimal Jmax up to 85.10 mA/cm(2) is achieved from a 4.65 mm(2) GNS-CNT sample, far larger than 7.41 mA/cm(2) for the as-grown CNTs. This great increase of Jmax is ascribed to the reinforced adhesion of GNS-CNT hybrids to substrates. We propose a rough calculation and find that this adhesion is promoted by 7.37 times after the three-step processing. We consider that both the ion prebombardment produced rough surface and the wrapping of CNT foot by catalyst residuals during thermal processing are responsible for this enhanced adhesion. Furthermore, the three-step prepared GNS-CNT hybrids present excellent field emission stability at high emission current densities (larger than 20 mA/cm(2)) after being perfectly aged.

Irradiation damage determined field emission of ion irradiated carbon nanotubes.

Figuring out the underlying relationship between the field emission (FE) properties and the ion irradiation induced structural change of carbon nanotubes (CNTs) is of great importance in developing high-performance field emitters. We report here the FE properties of Si and C ion irradiated CNTs with different irradiation doses. It is found that the FE performance of the ion irradiated CNTs ameliorates before and deteriorates after an irradiation-ion-species related dose. The improved FE properties are ascribed to the increased amount of defects, while the degraded FE performance is attributed to the great shape change of CNTs. These two structural changes are further characterized by a structural damage related parameter: dpa (displacement per atom), and the FE performance of the ion irradiated CNTs is surprisingly found to be mainly dependent on the dpa. The optimal dpa for FE of the ion irradiated CNTs is ∼0.60. We ascribe this to the low irradiation doses and the low substrate temperature that make the ion irradiation play a more important role in producing defects rather than element doping. Furthermore, the ion irradiated CNTs exhibit excellent FE stability, showing promising prospects in practical applications.