Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

Chemical Chaperones to Inhibit Endoplasmic Reticulum Stress: Implications in Diseases.

The endoplasmic reticulum (ER) is responsible for structural transformation or folding of de novo proteins for transport to the Golgi. When the folding capacity of the ER is exceeded or excessive accumulation of misfolded proteins occurs, the ER enters a stressed condition (ER stress) and unfolded protein responses (UPR) are triggered in order to rescue cells from the stress. Recovery of ER proceeds toward either survival or cell apoptosis. ER stress is implicated in many pathologies, such as diabetes, cardiovascular diseases, inflammatory diseases, neurodegeneration, and lysosomal storage diseases. As a survival or adaptation mechanism, chaperone molecules are upregulated to manage ER stress. Chemical versions of chaperone have been developed in search of drug candidates for ER stress-related diseases. In this review, synthetic or semi-synthetic chemical chaperones are categorized according to potential therapeutic area and listed along with their chemical structure and activity. Although only a few chemical chaperones have been approved as pharmaceutical drugs, a dramatic increase in literatures over the recent decades indicates enormous amount of efforts paid by many researchers. The efforts warrant clearer understanding of ER stress and the related diseases and consequently will offer a promising drug discovery platform with chaperone activity.

Emergent Topological Hall Effect from Exchange Coupling in Ferromagnetic Cr2Te3/Noncoplanar Antiferromagnetic Cr2Se3 Bilayers.

The topological Hall effect has been observed in magnetic materials of complex spin structures or bilayers of trivial magnets and strong spin-orbit-coupled systems. In view of current attention on dissipationless topological electronics, the occurrence of the topological Hall effect in new systems or by an unexpected mechanism is fascinating. Here, we report a robust topological Hall effect generated in bilayers of a ferromagnet and a noncoplanar antiferromagnet, from the interfacial Dzyaloshinskii-Moriya interaction due to the exchange coupling of magnetic layers. Molecular beam epitaxy has been utilized to fabricate heterostructures of a ferromagnetic metal Cr2Te3 and a noncoplanar antiferromagnet Cr2Se3. A significant topological Hall effect at low temperature implies the development of nontrivial spin chirality, and density functional theory calculations explain the correlation of the Dzyaloshinskii-Moriya interaction increase and inversion symmetry breaking at the interface. The presence of noncoplanar ordering in the antiferromagnet plays a pivotal role in producing the topological Hall effect. Our results suggest that the exchange coupling in ferromagnet/noncoplanar antiferromagnet bilayers could be an alternative mechanism toward topologically protected magnetic structures.

Treatment of life-threatening acute osteomyelitis of the jaw during chemotherapy: a case report.

Oral and maxillofacial infection is a common complication in patients undergoing chemotherapy. The treatment of oral diseases in such patients differs from that administered to healthy patients. This paper reports a case of acute osteomyelitis of odontogenic origin following a recent chemotherapy session. The patient's condition was life-threatening because of neutropenic fever and sepsis that developed during the inpatient supportive care. However, the patient showed prompt recovery within 40 days following the use of appropriate antibiotics and routine dressing, without the requirement for surgical treatment, except tooth extraction. As seen in this case, patients undergoing chemotherapy are more susceptible to rapid progression of infections in the oral and maxillofacial areas. Therefore, accurate diagnosis through prompt clinical and radiological examination, identification of the extent of infection, and assessment of the patient's immune system are crucial for favorable outcomes. It is also necessary to eliminate the source of infection through appropriate administration of antibiotics. In particular, a broad-spectrum antibiotic with anti-pneumococcal activity is essential. Proper antibiotic administration and wound dressing are essential for infection control. Furthermore, close consultation with a hemato-oncologist is necessary for effective infection management based on the professional evaluation of patients' immune mechanisms.

Facile electrodeposition of V-doped CoP on vertical graphene for efficient alkaline water electrolysis.

In this work, we demonstrate a highly enhanced electrocatalytic activity of vanadium-doped CoP (V-CoP), directly grafted on a vertical graphene/carbon cloth electrode (VG/CC) by a facile electrochemical deposition method. Impressively, V-CoP/VG/CC exhibited a superior catalytic activity toward the hydrogen evolution reaction (HER) in alkaline solution. Compared to CoP/VG/CC, V-doping decreased the overpotential for HER at 10 mA cm-2 by more than half to 40 mV. The new catalyst even outperformed Pt/C beyond 150 mA cm-2. The overpotential for OER at 50 mA cm-2 was merely 314 mV, more than 100 mV lower than that of IrO2. Moreover, our novel catalyst worked as an excellent bifunctional catalyst with a low cell voltage of 1.69 V to achieve a current density of 50 mA cm-2. Detailed characterizations revealed that the V-doping in CoP resulted in improved electrical conductivity and increased active sites. Our findings highlight the significant advantage of V doping on the catalytic activities of CoP, already boosted by VG. Furthermore, concurrent doping with the electrodeposition of catalyst offers a new approach for practical water electrolysis.

Chemical Vapor-Deposited Vanadium Pentoxide Nanosheets with Highly Stable and Low Switching Voltages for Effective Selector Devices.

Recently, attempts to overcome the physical limits of memory devices have led to the development of promising materials and architectures for next-generation memory technology. The selector device is one of the essential ingredients of high-density stacked memory systems. However, complicated constituent deposition conditions and thermal degradation are problematic, even with effective selector device materials. Herein, we demonstrate the highly stable and low-threshold voltages of vanadium pentoxide (V2O5) nanosheets synthesized by facile chemical vapor deposition, which have not been previously reported on the threshold switching (TS) properties. The electrons occupying trap sites in poly-crystalline V2O5 nanosheet contribute to the perfectly symmetric TS feature at the bias polarity and low-threshold voltages in V2O5, confirmed by high-resolution transmission electron microscopy measurements. Furthermore, we find an additional PdO interlayer in V2O5 nanodevices connected with a Pd/Au electrode after thermal annealing treatment. The PdO interlayer decreases the threshold voltages, and the Ion/ Ioff ratio increases because of the increased trap density of V2O5. These studies provide insights into V2O5 switching characteristics, which can support low power consumption in nonvolatile memory devices.

Induced Superaerophobicity onto a Non-superaerophobic Catalytic Surface for Enhanced Hydrogen Evolution Reaction.

Despite tremendous progress in the development of novel electrocatalysts for hydrogen evolution reaction (HER), the accumulation of hydrogen gas bubbles produced on the catalyst surface has been rather poorly addressed. The bubbles block the surface of the electrode, thus resulting in poor performance even when excellent electrocatalysts are used. In this study, we show that vertically grown graphene nanohills (VGNHs) possess an excellent capability to quickly disengage the produced hydrogen gas bubbles from the electrode surface, and thus exhibit superaerophobic properties. To compensate for the poor electrolytic properties of graphene toward HER, the graphene surface was modified with WS2 nanoparticles to accelerate the water-splitting process by using this hybrid catalyst (VGNHs-WS2). For comparison purposes, WS2 nanoparticles were also deposited on the flat graphene (FG) surface. Because of its superior superaerophobic properties, VGNHs-WS2 outperformed FG-WS2 in terms of both catalytic activity toward the HER and superaerophobicity. Furthermore, VGNHs-WS2 exhibited a low onset potential (36 mV compared to 288 mV for FG-WS2) and long-term stability in the HER over an extended period of 20 h. This study provides an efficient way to utilize highly conductive and superaerophobic VGNHs as support materials for intrinsic semiconductors, such as WS2, to simultaneously achieve superaerophobicity and high catalytic activity.

Identification of the Aggregation-sex Pheromone Produced by Male Monochamus saltuarius, a Major Insect Vector of the Pine Wood Nematode.

In this study, we isolated and identified an aggregation-sex pheromone from Monochamus saltuarius, the major insect vector of the pine wood nematode in Korea. Adult males of M. saltuarius produce 2-undecyloxy-1-ethanol, which is known as an aggregation-sex pheromone in other Monochamus species. We performed field experiments to determine the attractiveness of the pheromone and other synergists. More M. saltuarius adult beetles were attracted to traps baited with the pheromone than to unbaited traps. Ethanol and (-)-α-pinene interacted synergistically with the pheromone. Traps baited with the pheromone + (-)-α-pinene +ethanol were more attractive to M. saltuarius adults than traps baited with the pheromone, (-)-α-pinene, or ethanol alone. Ipsenol, ipsdienol, and limonene were also identified as synergists of the aggregation-sex pheromone for M. saltuarius adults. In field experiments, the proportion of females was much higher in the beetles caught in traps than among the beetles emerging from naturally-infested logs in the laboratory. Our results suggest that a combination of aggregation-sex pheromone and synergists could be very effective for monitoring and managing M. saltuarius.

Analysis of the outcome of young age tongue squamous cell carcinoma.

BACKGROUND: The incidence of tongue squamous cell carcinoma (TSCC) in young patients has recently increased, and these TSCCs are believed to be etiologically distinct from those in older patients, who have longer exposure to risk factors such as tobacco and alcohol. The prognosis of TSCCs in young patients remains controversial. METHODS: We retrospectively reviewed the records of 117 patients (2001-2011) who were diagnosed with squamous cell carcinoma of the oral tongue. Patients were divided into two age groups, older (ages over 40) and younger (ages 40 and younger). Data were compared between the two groups, and survival rates were analyzed. RESULTS: The results show that there are significant differences in overall, disease-free, and distant metastasis-free survival rates between the two groups. Five-year overall survival rates were 70% in older patients and 42% in young patients (p = 0.033). Five-year disease-free survival rates were 73% in older patients and 40% in young patients (p = 0.011), and 5-year distant metastasis-free survival rates were 97% in older patients and 62% in young patients (p = 0.033).Multivariate analysis revealed that histologic grade was the only independent risk factor for overall survival in both groups of patients (p = 0.002, HR = 2.287). The analysis also demonstrated that age was the critical risk factor for distant metastasis (p = 0.046, HR = 9.687). CONCLUSION: In this study, young (ages 40 and younger) patients with squamous cell carcinoma of the oral tongue had a higher rate of distant metastasis and a worse prognosis. Accordingly, we propose the necessity of an extensive therapeutic regimen that should be used in all young patients with TSCC.

Ghost cell odontogenic carcinoma on right mandible and its respective surgical reconstruction: a case report.

Calcifying cystic odontogenic tumor (CCOT) is defined as an odontogenic cyst-like benign neoplasm that characteristically contains several ghost cells, ameloblastoma-like epithelium, and occasional calcification. Ghost cell odontogenic carcinoma (GCOC), a malignant form of CCOT, is an exceptionally rare malignant tumor. In this report, we present a case of a 53-year-old man whose chief complaint was a solitary mass on the right mandible area. The mass was completely removed through an extraoral surgical approach and reconstructive surgery was performed in two phases.

Suppressed weak antilocalization in the topological insulator Bi2Se3 proximity coupled to antiferromagnetic NiO.

Time-reversal symmetry (TRS) breaking of the topological insulators (TIs) is a prerequisite to observe the quantum anomalous Hall effect (QAHE) and topological magnetoelectric effect (TME). Although antiferromagnetism as well as ferromagnetism could break the TRS and generate massive Dirac surface states in the TIs, no attention has been paid to the antiferromagnet-TI heterostructures. Herein, we report the magnetotransport measurements of Bi2Se3 proximately coupled to antiferromagnetic NiO. Thin films of Bi2Se3 were successfully grown on the NiO (001) single crystalline substrates by molecular beam epitaxy. Unexpectedly, we observed a strong suppression of the weak antilocalization effect, which is similar to the case of TIs coupled to the ferromagnetic materials. For the 5 nm-thick Bi2Se3 sample on NiO, we even observed a crossover to weak localization at 2 K. These behaviors are attributed to the strong magnetic exchange field from the Ni 3d electrons. Our results show the effectiveness of the antiferromagnetic materials in breaking the TRS of TIs by the proximity effect and their possible applications for QAHE and TME observations.

Hydrophobic Surface Treatment and Interrupted Atomic Layer Deposition for Highly Resistive Al2O3 Films on Graphene.

The deposition of thin and uniform dielectric film on graphene is an important step for electronic applications. Here, we tackled this problem by combining a simple chemical treatment of graphene surface and a modification of standard atomic layer deposition (ALD). Instead of common approaches trying to convert hydrophobic graphene surface into hydrophilic one, we took the opposite way by applying a self-assembled-monolayer, hexamethyldisilazane (HMDS) to make defect-independent, more hydrophobic surface condition. In addition, Al2O3 ALD using trimethylaluminum (TMA) and water (H2O) was interrupted several times and the surface was air-exposed during the interruption to seed the following ALD processes. This combination greatly improved the uniformity of dielectric film and accomplished a successful deposition of 10 nm-thick Al2O3 on graphene with subnanometer roughness except for the locations of wrinkles and poly(methyl methacrylate) (PMMA) residues. Electrochemical impedance measurements revealed a 300-fold increase in the charge-transfer resistance by employing this modified ALD process. No change in the Raman spectra was observed after the dielectric film growth, demonstrating that the method proposed here is nondetrimental to the graphene quality.

Analysis of morbidity, mortality, and risk factors of tracheostomy-related complications in patients with oral and maxillofacial cancer.

BACKGROUND: This study aimed to analyze and describe the morbidity and mortality associated with tracheostomy in patients with oral cancer and to identify the risk factors associated with tracheostomy complications. METHODS: We performed a retrospective chart review of patients who underwent tracheostomy during a major oral cancer resection between March 2001 and January 2016 at the National Cancer Center, Korea. Overall, we included 51 patients who underwent tracheostomy after oral cancer surgery. We assessed the morbidity and mortality of tracheostomy and determined the risks associated with tracheostomy complications. RESULTS: Twenty-two tracheostomy-related complications occurred in 51 patients. The morbidity and mortality rates were 35.2 % (n = 18) and 0 % (n = 0), respectively. Tracheostomy-related complications were tracheitis (n = 4), obstructed tracheostomy (n = 9), displaced tracheostomy (n = 5), air leakage (n = 1), stomal dehiscence (n = 1), and decannulation failure (n = 2). Most complications (19/22) occurred during the early postoperative period. Considering the risk factors for tracheostomy complications, the type of tube used was associated with the occurrence of tracheitis (p < 0.05). Additionally, body mass index and smoking status were associated with tube displacement (p < 0.05). However, no risk factors were significantly associated with obstructed tracheostomy. CONCLUSIONS: Patients with risk factors for tracheostomy complications should be carefully observed during the early postoperative period by well-trained medical staff.

Influence of TEM specimen preparation on chemical composition of Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystals.

The influences of different transmission electron microscopy (TEM) specimen preparation techniques on the chemical composition of Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) single crystals was studied. Ion-milled samples where no cooling with liquid nitrogen (L-N2) was applied show permanently changed composition also deep inside the bulk material. When the PMN-PT samples were cooled to L-N2 temperature during the ion-milling process and in addition lower accelerating voltages were used, the chemical composition was altered only in the thinnest parts close to the specimen edge. Samples prepared using only tripod polishing technique show compositional irregularities close to the specimen edge. For the preparation of lead-containing samples, such as PMN-PT single crystals, a combination of tripod polishing and short Ar-ion-milling at low accelerating voltages while cooling the samples to liquid nitrogen temperature proved to be the most suitable to obtain artefact-free electron-transparent TEM lamellae.

Direct observation of cationic ordering in double perovskite Sr2FeReO6 crystals.

Two kinds of Sr2FeReO6 (SFRO) samples, pristine SFRO and Re-excess SFRO, were prepared and we visualized the local atomic structure in terms of cationic ordering in the prepared SFRO samples via high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM). HAADF-STEM results demonstrated the high degree of cationic ordering maintains in both the pristine SFRO and Re-excess SFRO samples. On the other hand, defective structures such as antiphase boundary and Re-deficient phase were observed dominantly in the pristine SFRO, and thus the poor magnetic property in the pristine SFRO is attributed to those defective structures related with the frustrated Fe/Re ordering.

Licochalcone E present in licorice suppresses lung metastasis in the 4T1 mammary orthotopic cancer model.

We investigated whether licochalcone E (LicE), a phenolic constituent of licorice, inhibits mammary tumor growth and metastasis using animal and cell culture models. 4T1 mammary carcinoma cells were injected into the mammary fat pads of syngeneic BALB/c mice. Starting 7 days after the injection, the mice received LicE (7 or 14 mg/kg body weight/day) via oral gavage for 25 days. LicE suppressed solid tumor growth and lung metastasis, but did not exhibit kidney or liver toxicity. In tumor tissues, LicE treatment induced a reduction in the expression of Ki67, cyclins, and cyclin-dependent kinases and stimulated apoptosis with increased expression of Bax and cleaved caspase-3 but decreased expression of Bcl-2. In addition, LicE decreased expression of CD31, vascular endothelial growth factor (VEGF)-A and C, VEGF-receptor 2, lymphatic vessel endothelial receptor-1, CD45, cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia inducible factor-1α in tumor tissues. In lung tissues, LicE reduced the levels of proinflammatory cytokines and angiogenesis/metastasis-related proteins. In mammary cancer cell cultures, LicE (5-20 µmol/L) dose dependently inhibited cell migration and invasion. LicE inhibited secretion of matrix metalloproteinase-9, urokinase-type plasminogen activator and VEGF-A, and stimulated secretion of tissue inhibitor of metalloproteinase-2 in MDA-MB-231 cells. In addition, LicE inhibited tube formation of vascular endothelial cells. We show that LicE administration suppressed tumor growth and lung metastasis in the mouse model in conjunction with LicE inhibition of cell migration, invasion, and tube formation in vitro. Reduced tumor growth and metastasis in LicE-treated mice may be, at least in part, attributed to reduced inflammation and tumor angiogenesis.