A Hybrid Approach for Energy Consumption and Improvement in Sensor Network Lifespan in Wireless Sensor Networks.

In this paper, we propose an improved clustering algorithm for wireless sensor networks (WSNs) that aims to increase network lifetime and efficiency. We introduce an enhanced fuzzy spider monkey optimization technique and a hidden Markov model-based clustering algorithm for selecting cluster heads. Our approach considers factors such as network cluster head energy, cluster head density, and cluster head position. We also enhance the energy-efficient routing strategy for connecting cluster heads to the base station. Additionally, we introduce a polling control method to improve network performance while maintaining energy efficiency during steady transmission periods. Simulation results demonstrate a 1.2% improvement in network performance using our proposed model.

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

Preparation and Performance Analysis of 3D Thermoformed Fluidic Polymer Temperature Sensors for Aquatic and Terrestrial Applications.

Employing a combination of Polyethylene terephthalate (PET) thermoforming and 3D-printed cylindrical patterns, we carefully engineer a linear resistive temperature sensor. This intricate process involves initial PET thermoforming, yielding a hollow cylindrical chamber. This chamber is then precisely infused with a composite fluid of graphite and water glue. Ensuring electrical connectivity, both ends are affixed with metal wires and securely sealed using a hot gun. This cost-effective, versatile sensor adeptly gauges temperature shifts by assessing composite fluid resistance alterations. Its PET outer surface grants immunity to water and solubility concerns, enabling application in aquatic and aerial settings without extra encapsulation. Rigorous testing reveals the sensor's linearity and stability within a 10 °C to 60 °C range, whether submerged or airborne. Beyond 65 °C, plastic deformation arises. To mitigate hysteresis, a 58 °C operational limit is recommended. Examining fluidic composite width and length effects, we ascertain a 12 Ω/°C sensitivity for these linear sensors, a hallmark of their precision. Impressive response and recovery times of 4 and 8 s, respectively, highlight their efficiency. These findings endorse thermoforming's potential for fabricating advanced temperature sensors. This cost-effective approach's adaptability underscores its viability for diverse applications.

Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells.

We investigated the role of TONSL, a mediator of homologous recombination repair (HRR), in stalled replication fork double-strand breaks (DSBs) in cancer. Publicly available clinical data (tumors from the ovary, breast, stomach and lung) were analyzed through KM Plotter, cBioPortal and Qomics. Cancer stem cell (CSC)-enriched cultures and bulk/general mixed cell cultures (BCCs) with RNAi were employed to determine the effect of TONSL loss in cancer cell lines from the ovary, breast, stomach, lung, colon and brain. Limited dilution assays and ALDH assays were used to quantify the loss of CSCs. Western blotting and cell-based homologous recombination assays were used to identify DNA damage derived from TONSL loss. TONSL was expressed at higher levels in cancer tissues than in normal tissues, and higher expression was an unfavorable prognostic marker for lung, stomach, breast and ovarian cancers. Higher expression of TONSL is partly associated with the coamplification of TONSL and MYC, suggesting its oncogenic role. The suppression of TONSL using RNAi revealed that it is required in the survival of CSCs in cancer cells, while BCCs could frequently survive without TONSL. TONSL dependency occurs through accumulated DNA damage-induced senescence and apoptosis in TONSL-suppressed CSCs. The expression of several other major mediators of HRR was also associated with worse prognosis, whereas the expression of error-prone nonhomologous end joining molecules was associated with better survival in lung adenocarcinoma. Collectively, these results suggest that TONSL-mediated HRR at the replication fork is critical for CSC survival; targeting TONSL may lead to the effective eradication of CSCs.

Under- and Normal-Weight Patients Are More Susceptible to Recurrence of Phyllodes Tumor.

Purpose: Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, and factors associated with the recurrence of PTs are poorly understood. This study sought to identify clinicopathological factors associated with the recurrence of PTs. Method: From January 2009 to December 2019, we identified 100 patients who underwent definitive surgery for PT. Clinicopathological risk factors associated with the recurrence of PT were assessed. Results: The median age of the patients was 44 y (range, 19-62 y), and the median tumor size was 4 cm (0.8-30 cm). At a median follow-up of 26.7 mo (0-103 mo), 22 of the 100 patients experienced local recurrence. In the univariate and multivariate analyses, body mass index ≥ 23 kg/m2 (P = 0.042 in the univariate analysis; P = 0.039 in the multivariate analysis), tumor size ≥ 5 cm (P = 0.006 in the univariate analysis; P = 0.036 in the multivariate analysis), and the presence of stromal overgrowth (P = 0.032 in the univariate analysis; P = 0.040 in the multivariate analysis) were associated with an increased risk of local recurrence. Resection margins and grade were not associated with local recurrence. Conclusion: Normal- or underweight patients and those with larger tumor sizes were more prone to local recurrence. Further larger, multicenter studies with a long-term follow-up are required.

The First Evaluation of Proteinase K-Resistant Prion Protein (PrPSc) in Korean Appendix Specimens.

Background and Objectives: Prion diseases are fatal neurodegenerative disorders caused by the abnormal proteinase K-resistant prion protein (PrPSc). Since variant Creutzfeldt-Jakob disease (CJD) was first reported in the United Kingdom (UK) in 1996, the occurrence of variant CJD has been reported in over 10 countries. To date, variant CJD has not been reported in Korea. However, the E211K somatic mutation in the prion protein gene (PRNP), which is related to bovine spongiform encephalopathy (BSE), was reported in Korean Holstein cattle, and atypical BSE, which is supposed to be sporadic BSE, has been occurring in many countries, including Japan and the USA. These results suggest that BSE may occur naturally in Korea. Thus, we performed a preemptive PrPSc test in appendix specimens to diagnose variant CJD in a Korean population. Materials and Methods: In the present study, we investigated CJD-related mutations and polymorphisms of the PRNP gene and carried out an examination on PrPSc in appendix specimens of Korean patients after appendectomy. Results: In all Korean appendix specimens tested, PrPSc bands were not detected. Conclusion: To the best of our knowledge, this was the first evaluation of PrPSc in Korean appendix specimens.

Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A).

Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)-mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole-exome sequencing of 50 DNA samples from a healthy Korean population revealed a total of 13 single nucleotide polymorphisms including five missense variants, D12N, Y497C, H504Q, C707R, and A980V. Recombinant proteins for the five variants of PDE3A (and wild-type protein) were expressed in a FreeStyle 293 expression system with site-directed mutagenesis. The expression of the recombinant PDE3A proteins was confirmed with Western blotting. Catalytic activity of the PDE3A missense variants and wild-type enzyme was measured with a PDE-based assay. Effects of the missense variants on the inhibition of PDE3A activity by cilostazol were also investigated. All variant proteins showed reduced activity (33-53%; p < .0001) compared to the wild-type protein. In addition, PDE3A activity was inhibited by cilostazol in a dose-dependent manner and was further suppressed in the missense variants. Specifically, the PDE3A Y497C showed significantly reduced activity, consistent with the predictions of in silico analyses. The present study provides evidence that individuals carrying the PDE3A Y497C variant may have lower enzyme activity for cAMP hydrolysis, which could cause interindividual variation in cAMP-mediated physiological functions.

Species Prioritization Based on Spectral Dissimilarity: A Case Study of Polyporoid Fungal Species.

Biological species collections are critical for natural product drug discovery programs. However, prioritization of target species in massive collections remains difficult. Here, we introduce an untargeted metabolomics-based prioritization workflow that uses MS/MS molecular networking to estimate scaffold-level distribution. As a demonstration, we applied the workflow to 40 polyporoid fungal species. Nine species were prioritized as candidates based on the chemical structural and compositional similarity (CSCS) metric. Most of the selected species showed relatively higher richness and uniqueness of metabolites than those of the others. Cryptoporus volvatus, one of the prioritized species, was investigated further. The chemical profiles of the extracts of C. volvatus culture and fruiting bodies were compared, and it was shown that derivative-level diversity was higher in the fruiting bodies; meanwhile, scaffold-level diversity was similar. This showed that the compounds found from a cultured fungus can also be isolated in wild mushrooms. Targeted isolation of the fruiting body extract yielded three unknown (1-3) and six known (4-9) cryptoporic acid derivatives, which are drimane-type sesquiterpenes with isocitric acid moieties that have been reported in this species. Cryptoporic acid T (1) is a trimeric cryptoporic acid reported for the first time. Compounds 2 and 5 exhibited cytotoxicity against HCT-116 cell lines with IC50 values of 4.3 and 3.6 µM, respectively.

Lung retention and particokinetics of silver and gold nanoparticles in rats following subacute inhalation co-exposure.

BACKGROUND: Inhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics. METHODS AND RESULTS: Rats were exposed to biosoluble silver nanoparticles (AgNPs, 10.86 nm) and to biopersistent gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for 4 weeks) either with separate NP inhalation exposures or with combined co-exposure. The separate NPs mass concentrations estimated by the differential mobility analyzer system (DMAS) were determined to be 17.68 ± 1.69 µg/m3 for AuNP and 10.12 ± 0.71 µg/m3 for AgNP. In addition, mass concentrations analyzed by atomic absorption spectrometer (AAS) via filter sampling were for AuNP 19.34 ± 2.55 µg/m3 and AgNP 17.38 ± 1.88 µg/m3 for separate exposure and AuNP 8.20 ± 1.05 µg/m3 and AgNP 8.99 ± 1.77 µg/m3 for co-exposure. Lung retention and clearance were determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). While the AgNP and AuNP deposition rates were determined to be similar due to the similarity of NP size of both aerosols, the retention half-times and clearance rates differed due to the difference in dissolution rates. Thus, when comparing the lung burdens following separate exposures, the AgNP retention was 10 times less than the AuNP retention at 6-h (E-1), and 69, 89, and 121 times lower less than the AuNP retention at PEO-1, PEO-7, and PEO-28, respectively. In the case of AuNP+AgNP co-exposure, the retained AgNP lung burden was 14 times less than the retained AuNP lung burden at E-1, and 26, 43, and 55 times less than the retained AuNP lung burden at PEO-1, PEO-7, and PEO-28, respectively. The retention of AuNP was not affected by the presence of AgNP, but AgNP retention was influenced in the presence of AuNP starting at 24 h after the first day of post day of exposure. The clearance of AgNPs of the separate exposure showed 2 phases; fast (T1/2 3.1 days) and slow (T1/2 48.5 days), while the clearance of AuNPs only showed one phase (T1/2 .81.5 days). For the co-exposure of AuNPs+AgNPs, the clearance of AgNPs also showed 2 phases; fast (T1/2 2.2 days) and slow (T1/2 28.4 days), while the clearance of AuNPs consistently showed one phase (T1/2 54.2 days). The percentage of Ag lung burden in the fast and slow clearing lung compartment was different between separate and combined exposure. For the combined exposure, the slow and fast compartments were each 50% of the lung burden. For the single exposure, 1/3 of the lung burden was cleared by the fast rate and 2/3 of the lung burden by the slow rate. CONCLUSIONS: The clearance of AgNPs follows a two- phase model of fast and slow dissolution rates while the clearance of AuNPs could be described by a one- phase model with a longer half-time. The co-exposure of AuNPs+AgNPs showed that the clearance of AgNPs was altered by the presence of AuNPs perhaps due to some interaction between AgNP and AuNP affecting dissolution and/or mechanical clearance of AgNP in vivo.

Effects of MEH-PPV Molecular Ordering in the Emitting Layer on the Luminescence Efficiency of Organic Light-Emitting Diodes.

We investigated the effects of molecular ordering on the electro-optical characteristics of organic light-emitting diodes (OLEDs) with an emission layer (EML) of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV). The EML was fabricated by a solution process which can make molecules ordered. The performance of the OLED devices with the molecular ordering method was compared to that obtained through fabrication by a conventional spin coating method. The turn-on voltage and the luminance of the conventional OLEDs were 5 V and 34.75 cd/m2, whereas those of the proposed OLEDs were 4.5 V and 120.3 cd/m2, respectively. The underlying mechanism of the higher efficiency with ordered molecules was observed by analyzing the properties of the EML layer using AFM, SE, XRD, and an LCR meter. We confirmed that the electrical properties of the organic thin film can be improved by controlling the molecular ordering of the EML, which plays an important role in the electrical characteristics of the OLED.

CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer.

OBJECTIVE: Cyclin-dependent kinase 7 (CDK7) engages tumor growth by acting as a direct link between the regulation of transcription and the cell cycle. Here, we investigated the clinical significance of CDK7 expression and its potential as a therapeutic target in epithelial ovarian cancer (EOC). METHODS: CDK7 expression was examined in 436 ovarian tissues including normal to metastatic ovarian tumors using immunohistochemistry, and its clinical implications were analyzed. Furthermore, we performed in vitro and in vivo experiments using CDK7 siRNA or a covalent CDK7 inhibitor (THZ1) to elucidate the effect of CDK7 inhibition on tumorigenesis in EOC cells. RESULTS: The patient incidence of high CDK7 expression (CDK7High) gradually increased from normal ovarian epithelium to EOC (P < 0.001). Moreover, CDK7High was associated with an advanced stage and high-grade histology (P = 0.035 and P = 0.011, respectively) in EOC patients and had an independent prognostic significance in EOC recurrence (P = 0.034). CDK7 inhibition with siRNA or THZ1 decreased cell proliferation and migration, and increased apoptosis in EOC cells, and this anti-cancer mechanism is caused by G0/G1 cell cycle arrest. In in vivo therapeutic experiments using cell-line xenograft and PDX models, CDK7 inhibition significantly decreased the tumor weight, which was mediated by cell proliferation and apoptosis. CONCLUSION: Mechanistic interrogation of CDK7 revealed that it is significantly associated with an aggressive phenotype of EOC, and it has independent prognostic power for EOC recurrence. Furthermore, CDK7 may be a potential therapeutic target for patients with EOC, whether platinum sensitive or resistant.

Using miniaturised scanning mobility particle sizers to observe size distribution patterns of quasi-ultrafine aerosols inhaled during city commuting.

Portable miniaturised scanning mobility particle sizer (SMPS) instruments measuring atmospheric particles within the 10-241 nm size range were used to track particle number size distributions and concentrations during near-simultaneous pedestrian, bicycle, bus, car, tram and subway commuting journeys in Barcelona, Spain on 4th-6th July 2018. The majority of particles in this size range were <100 nm, with k-means cluster analysis identifying peaks at 15-22 nm, 30-40 nm, and 45-75 nm. Around 10-25% of the particles measured however were >100 nm (especially in the subway environment) and so lie outside the commonly defined range of "ultrafine" particles (UFP, or <100 nm particles). The study demonstrated in detail how personal exposure to quasi-UFP (QUFP, <241 nm), most of which present in the city streets are produced by road traffic, varies greatly depending on the transport mode and route chosen. Proximity to fresh traffic exhaust sources, such as in a car with open windows, on-road cycling, walking downwind of busy roads, or in a subway station contaminated by roadside air, enhances commuter exposure to particles <30 nm in size. In contrast, travelling inside air-conditioned bus or tram offers greater protection to the commuter from high concentrations of fresh exhaust. Ultrafine number size distributions in traffic-contaminated city air typically peak in the size range 30-70 nm, but they can be shifted to finer sizes not only by increased content of fresh proximal exhaust emissions but also by bursts of new particle formation (NPF) events in the city. One such afternoon photochemical nucleation NPF event was identified during our Barcelona study and recognised in different transport modes, including underground in the subway system. The integration of static urban background air monitoring station information with particle number concentration and size distribution data obtained from portable miniaturised SMPS instruments during commuting journeys opens new approaches to investigating city air quality by offering a level of detail not previously available.

Decade of 2D-materials-based RRAM devices: a review.

Two dimensional (2D) materials have offered unique electrical, chemical, mechanical and physical properties over the past decade owing to their ultrathin, flexible, and multilayer structure. These layered materials are being used in numerous electronic devices for various applications, and this review will specifically focus on the resistive random access memories (RRAMs) based on 2D materials and their nanocomposites. This study presents the device structures, conduction mechanisms, resistive switching properties, fabrication technologies, challenges and future aspects of 2D-materials-based RRAMs. Graphene, derivatives of graphene and MoS2 have been the major contributors among 2D materials for the application of RRAMs; however, other members of this family such as hBN, MoSe2, WS2 and WSe2 have also been inspected more recently as the functional materials of nonvolatile RRAM devices. Conduction in these devices is usually dominated by either the penetration of metallic ions or migration of intrinsic species. Most prominent advantages offered by RRAM devices based on 2D materials include fast switching speed (<10 ns), less power losses (10 pJ), lower threshold voltage (<1 V) long retention time (>10 years), high electrical endurance (>108 voltage cycles) and extended mechanical robustness (500 bending cycles). Resistive switching properties of 2D materials have been further enhanced by blending them with metallic nanoparticles, organic polymers and inorganic semiconductors in various forms.

The Risk Prediction of Coronary Artery Lesions through the Novel Hematological Z-Values in 4 Chronological Age Subgroups of Kawasaki Disease.

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7-12 months and 13-60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.

Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer.

Lipid metabolism is associated with colon cancer prognosis and incidence. Stearoyl-CoA desaturase 1 (SCD1), which converts fully saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs), has been suggested as a vulnerable target for selective elimination of cancer stem cells (CSCs). However, the clinical significance and physiological role of SCD1 in CSCs has not been well demonstrated. Here, we showed the clinical and biochemical relevance of blocking SCD1 to target CSCs by analyzing human colon cancer data from TCGA and through lipidomic profiling of CSCs with or without SCD1 inhibition using mass spectrometry. Positive associations between SCD1 expression and colorectal cancer patient clinical status and the expression of CSC-related genes (WNT and NOTCH signaling) were found based on TCGA data analysis. Lipidomic profiling of CSCs and bulk cancer cells (BCCs) using mass spectrometry revealed that colon CSCs contained a distinctive lipid profile, with higher free MUFA and lower free SFA levels than in BCCs, suggesting that enhanced SCD1 activity generates MUFAs that may support WNT signaling in CSCs. In addition, all identified phosphatidyl-ethanolamine-containing MUFAs were found at higher levels in CSCs. Interestingly, we observed lower phosphatidyl-serine (18:1/18:0), phosphatidyl-choline (PC; p-18:0/18:1)), and sphingomyelin (SM; d18:1/20:0 or d16:1/22:0) levels in CSCs than in BCCs. Of those, SCD1 inhibition, which efficiently diminished free MUFA levels, increased those specific PC and SM and MUFAs in CSCs promptly. These results suggest that these specific lipid composition is critical for CSC stem cell maintenance. In addition, not only free MUFAs, which are known to be required for WNT signaling, but also other phospholipids, such as SM, which are important for lipid raft formation, may mediate other cell signaling pathways that support CSC maintenance. Comparison of the lipidomic profiles of colon cancer cells with those of previously reported for glioma cells further demonstrated the tissue specific characteristics of lipid metabolism in CSCs.

Improved Retention Performance in Graphene-Ferroelectric Memory Device Through Mitigation of the Surface Roughness of the Ferroelectric Layer.

A ferroelectric-gated graphene field-effect transistor was fabricated with a bottom-gate structure. A ferroelectric gate dielectric was formed using the spin-coating method. Two samples were made, one with a single coating and the other with a double coating. It was observed that the data retention times of the two samples were significantly different. When comparing the surface roughness, the surface of the thin film produced by the double coating was much flatter. Based on the observation of the surface morphology, an interfacial layer composed of air was deduced as the origin of both the depolarization and short retention time. That is, when fabricating the graphene-ferroelectric memory device, the importance of the interface treatment could be confirmed. Based on these results, it is expected that a much more reliable device can be realized through surface engineering via a graphene-ferroelectric device process.

Characterization of a Ferroelectric-Gated Graphene Memory Device Fabricated on a Flexible Substrate by Transfer Process.

The mechanical flexibility of both ferroelectric polymer and graphene provides the possibility for the memory device based on ferroelectric polymer and grapheme to operate on flexible substrate. Here, a memory device was fabricated on flexible substrate through the continuous transfer process of the two units with the ferroelectric polymer and the graphene hybrid film as one unit, and characterized. In particular, characteristics were maintained even with repetitive bending. The transfer process demonstrated in this paper is useful for implementing a memory device on a large-area substrate by consuming a very small amount of graphene.

The effect of body position on airway patency in obstructive sleep apnea: CT imaging analysis.

PURPOSE: Positional change during sleep influences upper airway patency. However, few studies have used imaging techniques to demonstrate the change. This study aims to determine the effect of positional change on the upper airway space. METHODS: A total of 118 subjects with sleep breathing disorders were analyzed. Participants underwent upper airway CT scans in the supine and lateral decubitus positions (right and left). They were divided into non-obstructive sleep apnea (n = 28) and obstructive sleep apnea (n = 90) groups. We measured the minimal cross-sectional area of the retropalatal/retroglossal spaces and compared the differences of those two spaces in the supine and lateral positions. CT was performed while patients were awake. RESULTS: The minimal cross-sectional area in the OSA group was significantly smaller than non-OSA group in both supine (median[interquartile range], 8.3[0.0-25.1] vs 22.2[1.0-39.6]; P = 0.018) and lateral decubitus positions (5.2[0.0-16.9] vs 21.3[6.1-38.4]; P = 0.002). As the body position of OSA patients shifted from supine to lateral, the retroglossal space increased significantly (67.3[25.1-116.3] vs 93.3[43.4-160.1]; P < 0.001). However, there was no significant difference in the retropalatal space between the supine and lateral decubitus positions. CONCLUSIONS: Positional change from the supine to lateral decubitus position expands the upper airway lumen, especially the retroglossal space. Positional OSA may be related to anatomical change of the upper airway lumen based on body position.

Evodiamine Eliminates Colon Cancer Stem Cells via Suppressing Notch and Wnt Signaling.

Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines' BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines' CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.

Loss-of-function screens of druggable targetome against cancer stem-like cells.

Cancer stem-like cells (CSLCs) contribute to the initiation and recurrence of tumors and to their resistance to conventional therapies. In this study, small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. While diverse biologic processes were associated with siRNAs reducing the bulk-cultured population, CSLC-eliminating siRNAs were enriched in a few functional categories, such as lipid metabolism, protein metabolism, and gene expression. Interestingly, siRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. The lipidomic profile of CSLCs revealed increased levels of monounsaturated lipids. Pharmacologic blockage of these target pathways reduced CSLCs, and this effect was eliminated by addition of downstream metabolite products. The present CSLC-sensitive target categories provide a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells.