Kinetics of severe dengue virus infection and development of gut pathology in mice.

IMPORTANCE: Dengue virus, an arbovirus, causes an estimated 100 million symptomatic infections annually and is an increasing threat as the mosquito range expands with climate change. Dengue epidemics are a substantial strain on local economies and health infrastructure, and an understanding of what drives severe disease may enable treatments to help reduce hospitalizations. Factors exacerbating dengue disease are debated, but gut-related symptoms are much more frequent in severe than mild cases. Using mouse models of dengue infection, we have shown that inflammation and damage are earlier and more severe in the gut than in other tissues. Additionally, we observed impairment of the gut mucus layer and propose that breakdown of the barrier function exacerbates inflammation and promotes severe dengue disease. This idea is supported by recent data from human patients showing elevated bacteria-derived molecules in dengue patient serum. Therapies aiming to maintain gut integrity may help to abrogate severe dengue disease.

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.

Graph Learning-Based Blockchain Phishing Account Detection with a Heterogeneous Transaction Graph.

Recently, cybercrimes that exploit the anonymity of blockchain are increasing. They steal blockchain users' assets, threaten the network's reliability, and destabilize the blockchain network. Therefore, it is necessary to detect blockchain cybercriminal accounts to protect users' assets and sustain the blockchain ecosystem. Many studies have been conducted to detect cybercriminal accounts in the blockchain network. They represented blockchain transaction records as homogeneous transaction graphs that have a multi-edge. They also adopted graph learning algorithms to analyze transaction graphs. However, most graph learning algorithms are not efficient in multi-edge graphs, and homogeneous graphs ignore the heterogeneity of the blockchain network. In this paper, we propose a novel heterogeneous graph structure called an account-transaction graph, ATGraph. ATGraph represents a multi-edge as single edges by considering transactions as nodes. It allows graph learning more efficiently by eliminating multi-edges. Moreover, we compare the performance of ATGraph with homogeneous transaction graphs in various graph learning algorithms. The experimental results demonstrate that the detection performance using ATGraph as input outperforms that using homogeneous graphs as the input by up to 0.2 AUROC.

Spectroscopic investigation of the structure of a pyrrolidinium-based ionic liquid at electrified interfaces.

The molecular structure of electric double layers (EDLs) at electrode-electrolyte interfaces is crucial for all types of electrochemical processes. Here, we probe the EDL structure of an ionic liquid, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMPy-TFSI), using electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy. We extract the position and intensity of individual peaks corresponding to either intra- or inter-molecular vibrational modes and examine their dependence on the electrode potential. The observed trends suggest that the molecular reconfiguration mechanism is distinct between cations and anions. BMPy+ is found to always adsorb on the Au electrode surface via the pyrrolidinium ring while the alkyl chains strongly change their orientation at different potentials. In contrast, TFSI- is observed to have pronounced position shifts but negligible orientation changes as we sweep the electrode potential. Despite their distinct reconfiguration mechanisms, BMPy+ and TFSI- in the EDL are likely paired together through strong intermolecular interaction.

Privacy Preservation in Patient Information Exchange Systems Based on Blockchain: System Design Study.

BACKGROUND: With the increasing sophistication of the medical industry, various advanced medical services such as medical artificial intelligence, telemedicine, and personalized health care services have emerged. The demand for medical data is also rapidly increasing today because advanced medical services use medical data such as user data and electronic medical records (EMRs) to provide services. As a result, health care institutions and medical practitioners are researching various mechanisms and tools to feed medical data into their systems seamlessly. However, medical data contain sensitive personal information of patients. Therefore, ensuring security while meeting the demand for medical data is a very important problem in the information age for which a solution is required. OBJECTIVE: Our goal is to design a blockchain-based decentralized patient information exchange (PIE) system that can safely and efficiently share EMRs. The proposed system preserves patients' privacy in the EMRs through a medical information exchange process that includes data encryption and access control. METHODS: We propose a blockchain-based EMR-sharing system that allows patients to manage their EMRs scattered across multiple hospitals and share them with other users. Our PIE system protects the patient's EMR from security threats such as counterfeiting and privacy attacks during data sharing. In addition, it provides scalability by using distributed data-sharing methods to quickly share an EMR, regardless of its size or type. We implemented simulation models using Hyperledger Fabric, an open source blockchain framework. RESULTS: We performed a simulation of the EMR-sharing process and compared it with previous works on blockchain-based medical systems to check the proposed system's performance. During the simulation, we found that it takes an average of 0.01014 (SD 0.0028) seconds to download 1 MB of EMR in our proposed PIE system. Moreover, it has been confirmed that data can be freely shared with other users regardless of the size or format of the data to be transmitted through the distributed data-sharing technique using the InterPlanetary File System. We conducted a security analysis to check whether the proposed security mechanism can effectively protect users of the EMR-sharing system from security threats such as data forgery or unauthorized access, and we found that the distributed ledger structure and re-encryption-based data encryption method can effectively protect users' EMRs from forgery and privacy leak threats and provide data integrity. CONCLUSIONS: Blockchain is a distributed ledger technology that provides data integrity to enable patient-centered health information exchange and access control. PIE systems integrate and manage fragmented patient EMRs through blockchain and protect users from security threats during the data exchange process among users. To increase safety and efficiency in the EMR-sharing process, we used access control using security levels, data encryption based on re-encryption, and a distributed data-sharing scheme.

Molecular Pincers Using a Combination of N-H and C-H Donors for Anion Binding.

A naphthalene imide (1) and a naphthalene (2) bearing two pyrrole units have been synthesized, respectively, as anion receptors. It was revealed by 1H NMR spectral studies carried out in CD3CN that receptors 1 and 2 bind various anions via hydrogen bonds using both C-H and N-H donors. Compared with receptor 2, receptor 1 shows higher affinity for the test anions because of the enhanced acidity of its pyrrole NH and naphthalene CH hydrogens by the electron-withdrawing imide substituent. Molecular mechanics computations demonstrate that the receptors contact the halide anions via only one of the two respective available N-H and C-H donors whereas they use all four donors for binding of the oxyanions such as dihydrogen phosphate and hydrogen pyrophosphate. Receptor 1, a push-pull conjugated system, displays a strong fluorescence centered at 625 nm, while receptor 2 exhibits an emission with a maximum peak at 408 nm. In contrast, upon exposure of receptors 1 and 2 to the anions in question, their fluorescence was noticeably quenched particularly with relatively basic anions including F-, H2PO4-, HP2O73-, and HCO3-.

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models.

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.

Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC).

Thiazolidinediones are synthetic PPARγ ligands that enhance insulin sensitivity, and that could increase insulin secretion from ß-cells. However, the functional role and mechanism(s) of action in pancreatic ß-cells have not been investigated in detail.

Improved Clinical and Radiologic Outcomes Seen after Superior Capsule Reconstruction using Long Head Biceps Tendon Autograft.

PURPOSE: The objective of this study was to investigate the clinical and radiologic outcomes after superior capsule reconstruction (SCR) with biceps tendon (BT) for irreparable rotator cuff tears. METHODS: The retrospective study period was May 2015 through February 2018. The average follow-up was 32 months (24-48 months) after surgery. Study inclusion criteria included an arthroscopic SCR performed using only our technique and minimum 2-year clinical follow-up by office visit and survey. Exclusion criteria included irreparable subscapularis tear and those patients lost to follow-up. This method enabled SCR by using the extraarticular portion and the intraarticular portion and making it 2 to 3 bundles by moving back and forth in the intraarticular area. Physical examination and functional scoring procedures were performed before surgery and at 3, 6, 12, and 24 months after surgery. Radiography and magnetic resonance imaging (MRI) were performed before surgery, after surgery (only radiography), and at 6 and 24 months after surgery. RESULTS: Fifty-three shoulders involving 45 consecutive patients underwent BT technique for irreparable massive rotator cuff tears. The visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and constant score (CS) showed statistically significant improvement (VAS, 4.1-1.0; ASES, 60.9-82.7; and CS, 64.9-80.0; P < .0001). The shoulder active range of motion improved significantly by 23 for forward elevation (125.3-148.4; P < .0001) and by 12 for external rotation (38.0-50.9, P < .0001). The acromiohumeral distance (AHD) was significantly increased by 2.7 mm (4.4 ± 1.4 mm -> 7.1 ± 1.3 mm). No graft tear was detected in 39 patients (86.7%) during follow-up (24-48 months). CONCLUSIONS: SCR via our technique improved clinical and radiologic outcomes. Thirty-five (77.7%) patients achieved 17-point improvement (the minimally clinically important difference) in the last follow-up of ASES score. Clinical scores and AHD had significantly increased, and good healed rate (86.7%) was observed in MRI. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Self-Assembling Peptides and Their Application in the Treatment of Diseases.

Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.

Intergenerational Program for Nursing Home Residents and Adolescents in Korea.

Structural changes in the Korean population, such as a growing trend toward nuclear families and urbanization, have given rise to a generational gap between older adults and the younger generation. The current study developed a 6-week intergenerational program to facilitate interactions between nursing home residents and high school students. The effects of the program were examined in 120 participants (60 nursing home residents and 60 high school students) in the southern area of South Korea. The intergenerational program helped nursing home residents rediscover the value of their lives, have positive feelings about their lives, and adapt to circumstances through the sustained positive interactions with the younger generation. Adolescents obtained wisdom from older adults' experiences, understanding of the value of life, and positive perceptions of older adults through in-depth communication. The current findings suggest that the intergenerational program for nursing home residents and adolescents is a valuable nursing intervention in Korea to overcome the generational gap and achieve developmental tasks. [Journal of Gerontological Nursing, 44(1), 32-41.].

Suppression of lytic replication of Kaposi's sarcoma-associated herpesvirus by autophagy during initial infection in NIH 3T3 fibroblasts.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of the angioproliferative neoplasm Kaposi's sarcoma (KS). We first confirmed the susceptibility of NIH 3T3 fibroblasts to KSHV by infecting them with BCP-1-derived KSHV. Lytic replication of KSHV was confirmed by PCR amplification of viral DNA isolated from culture supernatants of KSHV-infected cells. The template from KSHV-infected NIH 3T3 cells resulted in an intense viral DNA PCR product. A time course experiment revealed the disappearance of KSHV-specific DNA in culture supernatant of NIH 3T3 cells during a period between 48 h and 72 h postinfection. Furthermore, 3 days postinfection, infected NIH 3T3 cells showed no evidence of latent or lytic transcripts, including LANA, vFLIP, vCyclin, and vIL-6. These results imply that KSHV infection in NIH 3T3 cells is unstable and is rapidly lost on subsequent culturing. Additionally, we detected an enhancement of autophagy early in infection with KSHV. More interestingly, inhibition of autophagy by Beclin 1 siRNA or 3-methyladenine significantly increased the amount of KSHV-specific DNA in the culture supernatant of NIH 3T3 cells when compared to the group treated with KSHV infection alone, implying that autophagy prevents lytic replication of KSHV. Taken together, our data suggest that autophagy could be one of the cellular mechanisms utilized by host cells to promote viral clearance.

Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits.

Peripheral nerve damage results in the loss of sensorimotor and autonomic functions, which is a significant burden to patients. Furthermore, nerve injuries greater than the limiting gap length require surgical repair. Although autografts are the preferred clinical choice, their usage is impeded by their limited availability, dimensional mismatch, and the sacrifice of another functional donor nerve. Accordingly, nerve guidance conduits, which are tubular scaffolds engineered to provide a biomimetic environment for nerve regeneration, have emerged as alternatives to autografts. Consequently, a few nerve guidance conduits have received clinical approval for the repair of short-mid nerve gaps but failed to regenerate limiting gap damage, which represents the bottleneck of this technology. Thus, it is still necessary to optimize the morphology and constituent materials of conduits. This review summarizes the recent advances in nerve conduit technology. Several manufacturing techniques and conduit designs are discussed, with emphasis on the structural improvement of simple hollow tubes, additive manufacturing techniques, and decellularized grafts. The main objective of this review is to provide a critical overview of nerve guidance conduit technology to support regeneration in long nerve defects, promote future developments, and speed up its clinical translation as a reliable alternative to autografts.

Necking Reduction at Low Temperature in Aspect Ratio Etching of SiO2 at CF4/H2/Ar Plasma.

This study investigated the effect of temperature on the aspect-ratio etching of SiO2 in CF4/H2/Ar plasma using patterned samples of a 200 nm trench in a low-temperature reactive-ion etching system. Lower temperatures resulted in higher etch rates and aspect ratios for SiO2. However, the plasma property was constant with the chuck temperature, indicated by the line intensity ratio from optical emission spectroscopy monitoring of the plasma. The variables obtained from the characterization of the etched profile for the 200 nm trench after etching were analyzed as a function of temperature. A reduction in the necking ratio affected the etch rate and aspect ratio of SiO2. The etching mechanism of the aspect ratio etching of SiO2 was discussed based on the results of the surface composition at necking via energy-dispersive X-ray spectroscopy with temperature. The results suggested that the neutral species reaching the etch front of SiO2 had a low sticking coefficient. The bowing ratio decreased with lowering temperature, indicating the presence of directional ions during etching. Therefore, a lower temperature for the aspect ratio etching of SiO2 could achieve a faster etch rate and a higher aspect ratio of SiO2 via the reduction of necking than higher temperatures.

Seebeck coefficient characterization of highly doped n- and p-type silicon nanowires for thermoelectric device applications fabricated with top-down approach.

A silicon nanowire one-dimensional thermoelectric device is presented as a solution to enhance thermoelectric performance. A top-down process is adopted for the definition of 50 nm silicon nanowires (SiNWs) and the fabrication of the nano-structured thermoelectric devices on silicon on insulator (SOl) wafer. To measure the Seebeck coefficients of 50 nm width n- and p-type SiNWs, a thermoelectric test structure, containing SiNWs, micro-heaters and temperature sensors is fabricated. Doping concentration is 1.0 x 10(20) cm(-3) for both for n- and p-type SiNWs. To determine the temperature gradient, a temperature coefficient of resistance (TCR) analysis is done and the extracted TCR value is 1750-1800 PPM x K(-1). The measured Seebeck coefficients are -127.583 microV x K(-1) and 141.758 microV x K(-1) for n- and p-type SiNWs, respectively, at room temperature. Consequently, power factor values are 1.46 mW x m(-1) x K(-2) and 1.66 mW x m(-1) x K(-2) for n- and p-type SiNWs, respectively. Our results indicate that SiNWs based thermoelectric devices have a great potential for applications in future energy conversion systems.

Effect of silicide/silicon hetero-junction structure on thermal conductivity and Seebeck coefficient.

We fabricated a thermoelectric device with a silicide/silicon laminated hetero-structure by using RF sputtering and rapid thermal annealing. The device was observed to have Ohmic characteristics by I-V measurement. The temperature differences and Seebeck coefficients of the proposed silicide/silicon laminated and bulk structure were measured. The laminated thermoelectric device shows suppression of heat flow from the hot to cold side. This is supported by the theory that the atomic mass difference between silicide and silicon creates a scattering center for phonons. The major impact of our work is that phonon transmission is suppressed at the interface between silicide and silicon without degrading electrical conductivity. The estimated thermal conductivity of the 3-layer laminated device is 126.2 +/- 3.7 W/m. K. Thus, by using the 3-layer laminated structure, thermal conductivity is reduced by around 16% compared to bulk silicon. However, the Seebeck coefficient of the thermoelectric device is degraded compared to that of bulk silicon. It is understood that electrical conductivity is improved by using silicide as a scattering center.

A three-dimensional spheroid co-culture system of neurons and astrocytes derived from Alzheimer's disease patients for drug efficacy testing.

Cell culture systems derived from the progenitor cells of human patients have many advantages over animal models for therapeutic drug testing and studies of disease pathogenesis. Here we describe a three-dimensional (3D) spheroid co-culture system of neurons and astrocytes derived from induced pluripotent stem cells-neural precursor cells (iPSCs-NPCs) of Alzheimer's disease (AD) patients or healthy individuals that can provide information on drug efficacy unobtainable by 2D co-culture or monoculture approaches. iPSCs-NPCs of healthy controls or AD patients were seeded onto 96-well U-bottom plates and incubated with neuronal differentiation medium for one week and with astrocytic medium for two weeks to replicate the temporal order of cell maturation during brain development. These 3D spheroid models expressed marker proteins for mature neurons and astrocytes. In particular, patient-derived spheroids showed beta-amyloid (Aß) accumulation as revealed by thioflavin T (ThT) staining and ELISA. Aggregation of Aß induced caspase activation and cell death, while the neuroprotectants nordihydroguaiaretic acid (NDGA) and curcumin (CU) reduced the levels of both ThT and caspase staining. Taken together, these results demonstrate the feasibility of our 3D spheroids combined with ThT and caspase staining as a patient-based anti-AD drug screening platform.

Gel Polymer Electrolytes for Lithium-Ion Batteries Enabled by Photo Crosslinked Polymer Network.

We demonstrate a gel polymer electrolyte (GPE) featuring a crosslinked polymer matrix formed by poly(ethylene glycol) diacrylate (PEGDA) and dipentaerythritol hexaacrylate (DPHA) using the radical photo initiator via ultraviolet (UV) photopolymerization for lithium-ion batteries. The two monomers with acrylate functional groups undergo chemical crosslinking, resulting in a three-dimensional structure capable of absorbing liquid electrolytes to form a gel. The GPE system was strategically designed by varying the ratios between the main polymer backbone (PEGDA) and the crosslinker (DPHA) to achieve an optimal gel polymer electrolyte network. The resulting GPE exhibited enhanced thermal stability compared to conventional liquid electrolytes (LE) and demonstrated high ionic conductivity (1.40 mS/cm) with a high lithium transference number of 0.65. Moreover, the obtained GPE displayed exceptional cycle performance, maintaining a higher capacity retention (85.2%) comparable to the cell with LE (79.3%) after 200 cycles.

Self-Curable Synaptic Ferroelectric FET Arrays for Neuromorphic Convolutional Neural Network.

With the recently increasing prevalence of deep learning, both academia and industry exhibit substantial interest in neuromorphic computing, which mimics the functional and structural features of the human brain. To realize neuromorphic computing, an energy-efficient and reliable artificial synapse must be developed. In this study, the synaptic ferroelectric field-effect-transistor (FeFET) array is fabricated as a component of a neuromorphic convolutional neural network. Beyond the single transistor level, the long-term potentiation and depression of synaptic weights are achieved at the array level, and a successful program-inhibiting operation is demonstrated in the synaptic array, achieving a learning accuracy of 79.84% on the Canadian Institute for Advanced Research (CIFAR)-10 dataset. Furthermore, an efficient self-curing method is proposed to improve the endurance of the FeFET array by tenfold, utilizing the punch-through current inherent to the device. Low-frequency noise spectroscopy is employed to quantitatively evaluate the curing efficiency of the proposed self-curing method. The results of this study provide a method to fabricate and operate reliable synaptic FeFET arrays, thereby paving the way for further development of ferroelectric-based neuromorphic computing.

Reconfigurable Manipulation of Oxygen Content on Metal Oxide Surfaces and Applications to Gas Sensing.

Oxygen vacancies and adsorbed oxygen species on metal oxide surfaces play important roles in various fields. However, existing methods for manipulating surface oxygen require severe settings and are ineffective for repetitive manipulation. We present a method to manipulate the amount of surface oxygen by modifying the oxygen adsorption energy by electrically controlling the electron concentration of the metal oxide. The surface oxygen control ability of the method is verified using first-principles calculations based on density functional theory (DFT), X-ray photoelectron spectroscopy (XPS), and electrical resistance analysis. The presented method is implemented by fabricating oxide thin film transistors with embedded microheaters. The method can reconfigure the oxygen vacancies on the In2O3, SnO2, and IGZO surfaces so that specific chemisorption dominates. The method can selectively increase oxidizing (e.g., NO and NO) and reducing gas (e.g., H2S, NH3, and CO) reactions by electrically controlling the metal oxide surface to be oxygen vacancy-rich or adsorbed oxygen species-rich. The proposed method is applied to gas sensors and overcomes their existing limitations. The method makes the sensor insensitive to one gas (e.g., H2S) in mixed-gas environments (e.g., NO2+H2S) and provides a linear response (R2 = 0.998) to the target gas (e.g., NO2) concentration within 3 s. We believe that the proposed method is applicable to applications utilizing metal oxide surfaces.