An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

Perovskite Quantum Dots and Their Application in Light-Emitting Diodes.

Perovskite quantum dots (PQDs) attract significant interest in recent years because of their unique optical properties, such as tunable wavelength, narrow emission, and high photoluminescence quantum efficiency (PLQY). Recent studies report new types of formamidinium (FA) PbBr3 PQDs, PQDs with organic-inorganic mixed cations, divalent cation doped colloidal CsPb1-x Mx Br3 PQDs (M = Sn2+ , Cd2+ , Zn2+ , Mn2+ ) featuring partial cation exchange, and heterovalent cation doped into PQDs (Bi3+ ). These PQD analogs open new possibilities for optoelectronic devices. For commercial applications in lighting and backlight displays, stability of PQDs requires further improvement to prevent their degradation by temperature, oxygen, moisture, and light. Oxygen and moisture-facilitated ion migration may easily etch unstable PQDs. Easy ion migration may result in crystal growth, which lowers PLQY of PQDs. Surface coating and treatment are important procedures for overcoming such factors. In this study, new types of PQDs and a strategy of improving their stabilities are introduced. Finally, this paper discusses future applications of PQDs in light-emitting diodes.

Gadolinium-doped iron oxide nanoparticles induced magnetic field hyperthermia combined with radiotherapy increases tumour response by vascular disruption and improved oxygenation.

The gadolinium-doped iron oxide nanoparticles (GdIONP) with greater specific power adsorption rate (SAR) than Fe3O4 was developed and its potential application in tumour therapy and particle tracking were demonstrated in transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1) tumours. The GdIONPs accumulated in tumour region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy (RT) were also evaluated. A significant increase in the tumour growth time was observed following the treatment of thermotherapy (TT) only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumour necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of RT by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 and 42 °C)-mediated reoxygenation.

High-Performance CsPb1-x Snx Br3 Perovskite Quantum Dots for Light-Emitting Diodes.

All inorganic CsPbBr3 perovskite quantum dots (QDs) are potential emitters for electroluminescent displays. We have developed a facile hot-injection method to partially replace the toxic Pb2+ with highly stable Sn4+ . Meanwhile, the absolute photoluminescence quantum yield of CsPb1-x Snx Br3 increased from 45 % to 83 % with SnIV substitution. The transient absorption (TA) exciton dynamics in undoped CsPbBr3 and CsPb0.67 Sn0.33 Br3 QDs at various excitation fluences were determined by femtosecond transient absorption, time-resolved photoluminescence, and single-dot spectroscopy, providing clear evidence for the suppression of trion generation by Sn doping. These highly luminescent CsPb0.67 Sn0.33 Br3 QDs emit at 517 nm. A device based on these QDs exhibited a luminance of 12 500 cd m-2 , a current efficiency of 11.63 cd A-1 , an external quantum efficiency of 4.13 %, a power efficiency of 6.76 lm w-1 , and a low turn-on voltage of 3.6 V, which are the best values among reported tin-based perovskite quantum-dot LEDs.

Development of a Flexible Metamaterial Film with High EM Wave Absorptivity by Numerical and Experimental Methods.

The present study is intended to develop and test a cost-effective and efficient printing method for fabricating flexible metamaterial film with high electromagnetic wave absorptivity. The film can be easily applied to the surfaces with curved aspects. Firstly, numerical parametric study of the absorption characteristics of the film is performed for the range of frequency varying from 2.0 to 9.0 GHz based on commercial software package. Secondly, the flexible metamaterial films are fabricated, and experiments are conducted. The flexible metamaterial film consists of a flexible dielectric film made of polyimide (PI) and an array of split-ring resonators. The split-ring resonators of different geometric dimensions are fabricated on the PI film surface by using a silver nanoparticles ink jet printer. The performance of the flexible structure is then measured and dependence of operation frequency with higher absorptivity on the dimensions of the split-ring resonators is investigated. A comparison between the numerical and experimental data shows that the numerical predictions of the operation frequency with higher absorptivity closely agree with the experimental data.

Using convolutional neural network to analyze brain MRI images for predicting functional outcomes of stroke.

Nowadays, the physicians usually predict functional outcomes of stroke based on clinical experiences and big data, so we wish to develop a model to accurately identify imaging features for predicting functional outcomes of stroke patients. Using magnetic resonance imaging of ischemic and hemorrhagic stroke patients, we developed and trained a VGG-16 convolutional neural network (CNN) to predict functional outcomes after 28-day hospitalization. A total of 44 individuals (24 men and 20 women) were recruited from Taoyuan General Hospital and China Medical University Hsinchu Hospital to enroll in the study. Based on "modified Rankin Scale (mRS)" and "National Institutes of Health Stroke Scale (NIHSS)" assessments, men, women, and mixed men and women were trained separately to evaluate the differences of the results, and we have shown that VGG-16 demonstrated high accuracy in predicting the functional outcomes of stroke patients. The new deep-learning approach has provided an automated decision support system for personalized recommendations and treatments, assisting the physicians to predict functional outcomes of stroke patients in clinical practice.

Three-Dimensional Printing of a Hybrid Bioceramic and Biopolymer Porous Scaffold for Promoting Bone Regeneration Potential.

In this study, we proposed a three-dimensional (3D) printed porous (termed as 3DPP) scaffold composed of bioceramic (beta-tricalcium phosphate (ß-TCP)) and thermoreversible biopolymer (pluronic F-127 (PF127)) that may provide bone tissue ingrowth and loading support for bone defect treatment. The investigated scaffolds were printed in three different ranges of pore sizes for comparison (3DPP-1: 150−200 µm, 3DPP-2: 250−300 µm, and 3DPP-3: 300−350 µm). The material properties and biocompatibility of the 3DPP scaffolds were characterized using scanning electron microscopy, X-ray diffractometry, contact angle goniometry, compression testing, and cell viability assay. In addition, micro-computed tomography was applied to investigate bone regeneration behavior of the 3DPP scaffolds in the mini-pig model. Analytical results showed that the 3DPP scaffolds exhibited well-defined porosity, excellent microstructural interconnectivity, and acceptable wettability (θ < 90°). Among all groups, the 3DPP-1 possessed a significantly highest compressive force 273 ± 20.8 Kgf (* p < 0.05). In vitro experiment results also revealed good cell viability and cell attachment behavior in all 3DPP scaffolds. Furthermore, the 3DPP-3 scaffold showed a significantly higher percentage of bone formation volume than the 3DPP-1 scaffold at week 8 (* p < 0.05) and week 12 (* p < 0.05). Hence, the 3DPP scaffold composed of ß-TCP and F-127 is a promising candidate to promote bone tissue ingrowth into the porous scaffold with decent biocompatibility. This scaffold particularly fabricated with a pore size of around 350 µm (i.e., 3DPP-3 scaffold) can provide proper loading support and promote bone regeneration in bone defects when applied in dental and orthopedic fields.

Comprehensive MDCT evaluation of patients with pulmonary hypertension: diagnosing underlying causes with the updated Dana Point 2008 classification.

OBJECTIVE: Pulmonary hypertension is a challenge for imagers and clinicians, with a variety of possible underlying causes, each with its own specific treatment. Although the diagnosis is based on physiologic measurements, ECG-gated MDCT can play a vital role in elucidating underlying cardiac, vascular, and pulmonary causes. CONCLUSION: A revised system for pulmonary hypertension, the Dana Point classification, can provide a template for review of the myriad causes of this complex condition.

Measurement of optic nerve sheath diameter by ultrasound in healthy term neonates.

BACKGROUND: Optic nerve sheath diameter (ONSD) ultrasound is a noninvasive and repeatable tool to dynamically evaluate intracranial pressure with high diagnostic accuracy; however, data in neonates are scarce. The aim of this study was to determine the reference value of ONSD and potential influencing factors in healthy term neonates. METHODS: We retrospectively reviewed 250 full-term neonates who underwent cranial ultrasound as part of selective newborn screening over a 2-year period. Neonates with any of the following conditions were excluded: using mechanical ventilation, sedatives and/or vasopressors, or signs of infection which needed cerebrospinal fluid analysis and/or intracranial pathologies. Data on sex, gestational age, birth body weight, birth body height, birth head circumference, Apgar score and types of delivery were collected. The neurodevelopmental outcomes were reviewed. RESULTS: A total of 234 neonates (123 girls and 111 boys) were included. The mean ONSD value was 3.30 ± 0.27 mm in the right eye and 3.30 ± 0.23 mm in the left eye, with no significant difference between both eyes (p = 0.797). Male neonates had a larger ONSD than female neonates (3.34 ± 0.22 mm versus 3.26 ± 0.20 mm, p = 0.007), and ONSD was correlated with birth weight in the males. Otherwise, there were no statistically significant associations between ONSD and other birth characteristics in both sexes. Most (63%) cases were followed for at least 12 months, and 98% had normal neurodevelopment. CONCLUSION: The reference value reported in this study may be used to evaluate the ONSD in healthy term neonates. Sex differences should be considered in this age group.

Risk of Thromboembolism in Non-Valvular Atrial Fibrillation With or Without Clinical Hyperthyroidism.

Background: Patients with hyperthyroidism have higher risk of atrial fibrillation (AF). However, the risk of thromboembolic event in patients with hyperthyroidism-related AF is controversial. Objectives: The aim of the study was to examine the risk of thromboembolic events in AF patients with/without hyperthyroidism. Methods: The national retrospective cohort study enrolled AF population was derived from the Taiwan National Health Insurance Research Database. The comparison between the AF patients with clinical hyperthyroidism (HT-AF group) and AF patients without hyperthyroidism (non-thyroid AF group) was made in a propensity score matched cohort and in a real-world setting, of which, the CHA2DS2-VASc level was treated as a stratum variable. The outcomes were ischemic stroke and systemic thromboembolism. Results: There were 3,880 patients in HT AF group and 178,711 in non-thyroid AF group. After propensity score analysis, the incidence of thromboembolism event and ischemic stroke were lower in HT AF patients than non-thyroid AF patients (1.6 versus 2.2 events per 100 person-years; HR, 0.73; 95% CI, 0.64-0.82 and 1.4 versus 1.8 events per 100 person-years; HR, 0.74; 95% CI, 0.64-0.84, respectively) in the 4.3 ± 3.2 year follow up period. The differences persistently existed in those receiving anticoagulants or not. In AF patients without anticoagulants, the incidence densities of ischemic stroke/systemic thromboembolism were significantly lower in HT AF group than those in non-thyroid AF group at CHA2DS2-VASc scores ≤ 4 (HR, 0.41; 95% CI, 0.35-0.48, p < 0.001), while the differences disappeared in case of score ≥ 5 (HR, 0.80; 95% CI, 0.63-1.02, p = 0.071). Conclusion: Patients with HT AF had lower incidence of thromboembolic events as compared to non-thyroid AF patients. The threshold of CHA2DS2-VASc score for anticoagulation in AF patients with clinical hyperthyroidism should be further evaluated. Highlights: The incidence of thromboembolic event was different between hyperthyroidism-related atrial fibrillation (HT-AF) and non-thyroid AF patients.Hyperthyroidism did not confer additional risk of thromboembolic event at CHA2DS2-VASc of ≤ 4.The benefit of anticoagulation strategy in patients with hyperthyroidism-related AF should be further evaluated, especially at low CHA2DS2-VASc score.

Parallel scanning-optical nanoscopy with optically confined probes.

We report the imaging of sub-diffraction limited features using an optical probe generated by focusing a round spot at one wavelength, lambda(1) = 405 nm, and a ring-shaped spot at a second wavelength, lambda(2) = 532 nm, onto a thin photochromic layer that coats the nanostructures. Illumination at lambda(2) turns the photochromic layer opaque to lambda(1) everywhere except at the centre of the ring, where the illumination at lambda(1) penetrates and probes the underlying nanostructure. We confirm that this optically confined probe increases image contrast and is able to resolve features smaller than the far-field diffraction limit. Furthermore, by using an array of dual-wavelength diffractive microlenses, we demonstrate the feasibility of parallelizing this approach. Compared to previous approaches, our technique is not limited to fluorescence imaging.

hnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells.

We have previously identified a novel Aurora-A-mediated Serine 379 (S379) phosphorylation of a poly(C)-binding protein, hnRNPK, the overexpression of which is frequently observed in various cancers. It is known that the oncogenic Aurora-A kinase promotes the malignancy of cancer cells. This study aims to investigate the unexplored functions of hnRNPK S379 phosphorylation using MDA-MB-231 cells, a triple negative breast cancer cell that has amplification of the Aurora-A kinase gene. Accordingly, we established two cell lines in which the endogenous hnRNPK was replaced with either S379D or S379A hnRNPK respectively. Notably, we found that a phosphorylation-mimic S379D mutant of hnRNPK suppressed cell migration and, conversely, a phosphorylation-defective S379A mutant promoted migration. Moreover, Twist was downregulated upon hnRNPK S379 phosphorylation, whereas ß-catenin and MMP12 were increased when there was loss of hnRNPK S379 phosphorylation in MDA-MB-231 cells. Furthermore, S379A hnRNPK increases stability of ß-catenin in MDA-MB-231 cells. In conclusion, our results suggest that hnRNPK S379 phosphorylation regulates migration via the EMT signaling pathway.

Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents - A case series and literature review.

BACKGROUND: Nitrous oxide (N2O) is a commonly used inhaled anesthetic in outpatient dental procedures. However, the increasing recreational use of N2O may result in vitamin B12 deficiency-related neurologic and psychiatric symptoms. The aim of this study was to demonstrate the clinical features of chronic N2O abuse in pediatric patients. METHODS: Patients under 20 years of age who were diagnosed with N2O-induced subacute combined degeneration of the spinal cord from 2012 to 2018 were enrolled in this study. Clinical presentations, laboratory, imaging, ancillary studies, treatments and outcomes were analyzed. RESULTS: Nine patients were included, all of whom presented with symptoms of myeloneuropathy including limb numbness, limb weakness or unsteady gait. Six patients had low or low-normal vitamin B12 (cyanocobalamin) levels. Eight patients had evidence of subacute combined degeneration of the spinal cord via neuroimaging studies. All of the patients received vitamin B12 supplementation as treatment. All had full recovery of muscle power within 2 months. Five patients had persistent sensory deficits. CONCLUSION: Chronic N2O abuse can cause permanent neurological damage if not treated promptly. Clinical staff should be aware of the various presentations of neurotoxicity related to N2O abuse.

Venom phospholipases of Russell's vipers from Myanmar and eastern India--cloning, characterization and phylogeographic analysis.

Venoms of Russell's vipers (genus Daboia) are known for their deadly coagulopathic and other effects. We herein studied various isoforms of venom phospholipases A(2) (PLAs) from two Daboia species at their geographic boundary. From Myanmar Daboia siamensis venom (designated as DsM), four PLAs (designated DsM-aI, aI', aII' and bI') were purified, and the cDNAs encoding two acidic (DsM-aI and aII) and two basic PLAs (DsM-bI and S1) were also cloned from its venom-glands. DsM-S1 is identical to the major venom PLA of southern India Daboia russelii, but the protein is absent from the venom. Additionally, four PLAs (designated DrK-aI, aII, bI and bII) were cloned from cDNA obtained from venom glands of a Kolkata D. russelii, and the PLAs were purified from the pooled venom (designated as DrK). The acidic DrK-aI is the most neurotoxic and lethal among these PLAs; DsM-aI which differs from DrK-aI by only the Phe2 substitution shows greatly reduced enzymatic activity and lethality. Both acidic PLAs do not form dimeric complex with basic PLAs in the same venoms. DsM-bI' is neurotoxic and lethal but its orthologous DrK-bI (97% identical to DsM-bI') is a much weaker toxin. Given the fact that most of the orthologous PLAs of DrK and DsM share 97-100% sequence identity, Daboia vipers of Myanmar and Kolkata must be closely related. Molecular phylogenetic analyses on 30 venom PLAs of Eurasian vipers' revealed co-evolution of five subtypes of venom PLAs in both Daboia and Vipera genera. Our results shed light on the intra- and inter-species variations and structure-function relationships of viperid venom PLAs.

P-III hemorrhagic metalloproteinases from Russell's viper venom: cloning, characterization, phylogenetic and functional site analyses.

Two homologous P-III hemorrhagic metalloproteinases were purified from Russell's viper venoms from Myanmar and Kolkata (eastern India), and designated as daborhagin-M and daborhagin-K, respectively. They induced severe dermal hemorrhage in mice at a minimum hemorrhagic dose of 0.8-0.9 microg. Daborhagin-M specifically hydrolyzed an Aalpha-chain of fibrinogen, fibronectin, and type IV collagen in vitro. Analyses of its cleavage sites on insulin chain B and kinetic specificities toward oligopeptides suggested that daborhagin-M prefers hydrophobic residues at the P(1), P(1)', and P(2)' positions on the substrates. Of the eight Daboia geographic venom samples analyzed by Western blotting, only those from Myanmar and eastern India showed a strong positive band at 65kDa, which correlated with the high risk of systemic hemorrhagic symptoms elicited by Daboia envenoming in both regions. The full sequence of daborhagin-K was determined by cDNA cloning and sequencing, and then confirmed by peptide mass fingerprinting. Furthermore, molecular phylogenetic analyses based on 27 P-IIIs revealed the co-evolution of two major P-III classes with distinct hemorrhagic potencies, and daborhagin-K belongs to the most hemorrhagic subclass. By comparing the absolute complexity profiles between these two classes, we identified four structural motifs probably responsible for the phylogenetic subtyping and hemorrhagic potencies of P-III SVMPs.

Cloning, characterization and phylogenetic analyses of members of three major venom families from a single specimen of Walterinnesia aegyptia.

Walterinnesia aegyptia is a monotypic elapid snake inhabiting in Africa and Mideast. Although its envenoming is known to cause rapid deaths and paralysis, structural data of its venom proteins are rather limited. Using gel filtration and reverse-phase HPLC, phospholipases A(2) (PLAs), three-fingered toxins (3FTxs), and Kunitz-type protease inhibitors (KIns) were purified from the venom of a single specimen of this species caught in northern Egypt. In addition, specific primers were designed and PCR was carried out to amplify the cDNAs encoding members of the three venom families, respectively, using total cDNA prepared from its venom glands. Complete amino acid sequences of two acidic PLAs, three short chain 3FTxs, and four KIns of this venom species were thus deduced after their cDNAs were cloned and sequenced. They are all novel sequences and match the mass data of purified proteins. For members of each toxin family, protein sequences were aligned and subjected to molecular phylogenetic analyses. The results indicated that the PLAs and a Kunitz inhibitor of W. aegyptia are most similar to those of king cobra venom, and its 3FTxs belongs to either Type I alpha-neurotoxins or weak toxins of orphan-II subtype. It is remarkable that both king cobra and W. aegyptia cause rapid deaths of the victims, and a close evolutionary relationship between them is speculated.

Sequences, geographic variations and molecular phylogeny of venom phospholipases and threefinger toxins of eastern India Bungarus fasciatus and kinetic analyses of its Pro31 phospholipases A2.

Eight phospholipases A2 (PLAs) and four three-finger-toxins (3FTx) from the pooled venom of Bungarus fasciatus (Bf) were previously studied and sequenced, but their expression pattern in individual Bf venom and possible geographic variations remained to be investigated. We herein analyze the individual venom of two Bf specimens from Kolkata (designated as KBf) to address this question. Seven PLAs and five 3FTx were purified from the KBf venoms, and respective cDNAs were cloned from venom glands of one of the snakes. Comparison of their mass and N-terminal sequence revealed that all the PLAs were conserved in both KBf venoms, but that two of their 3FTx isoforms were variable. When comparing the sequences of these KBf-PLAs with those published, only one was found to be identical to that of Bf Vb-2, and the other five were 94-98% identical to those of Bf II, III, Va, VI and XI-2, respectively. Notably, the most abundant PLA isoforms of Bf and KBf venoms contain Pro31 substitution. They were found to have abnormally low k(cat) values but high affinity for Ca2+. Phylogenetic analysis based on the sequences of venom group IA PLAs showed a close relationship between Bungarus and Australian and marine Elapidae. As the five deduced sequences of KBf-3FTx are only 62-82% identical to the corresponding Bf-3FTx from the pooled venom, the 3FTx apparently have higher degree of individual and geographic variations than the PLAs. None of the KBf-3FTx was found to be neurotoxic or very lethal; phylogenetic analyses of the 3FTx also revealed the unique evolution of Bf as compared with other kraits.

Early appendectomy shortens antibiotic course and hospital stay in children with early perforated appendicitis.

BACKGROUND: The optimal management of perforated appendicitis in the pediatric population has been controversial. This study aimed to compare the therapeutic efficacy between conservative treatment (CS) and early appendectomy (EA) in pediatric perforated appendicitis, and to determine whether surgical intervention is an optimal treatment modality for early perforated appendicitis in children. METHODS: Patients treated between January 2012 and April 2014, aged 0-18 years, with an imaging-based diagnosis of perforated appendicitis were retrospectively reviewed. Patients were classified into nonabscess and abscess groups by image findings, and were further categorized into CS and EA groups by treatment modality. Early perforated appendicitis was defined as having duration of symptoms≤7 days, C-reactive protein level≤200 mg/L, maximum abscess diameter≤5 cm, and absence of general peritonitis, and unstable vital signs. The clinical features and therapeutic outcomes were compared between CS and EA in each group. RESULTS: A total of 326 patients had confirmed appendicitis, including 116 patients with an image diagnosis of perforation. The CS group had a significantly longer duration of symptoms, larger abscesses, and higher serum C-reactive protein levels at presentation (all p<0.05). Patients in the EA group had a shorter antibiotic course and length of hospitalization, and a lower rate of antibiotic escalation than those in the CS group (p<0.001, p<0.001, and p<0.05, respectively). In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity. Patients in the EA group also had a shorter antibiotic course and length of hospitalization than those in the CS group (p<0.001 and p<0.001, respectively). CONCLUSION: Compared with CS, EA shortens the antibiotic course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses.

Successful angiographic stent-graft treatment for spontaneously dissecting broad-base pseudoaneurysm of the superior mesenteric artery.

Visceral arterial aneurysm is an uncommon form of vascular disease that has a significant potential for rupture or erosion into an adjacent viscera, resulting in life-threatening hemorrhage. Superior mesenteric artery (SMA) aneurysms are especially rare, comprising only 5-8% of all visceral arterial aneurysms. Traditionally, the most common treatment for SMA aneurysms has been simple surgical ligation of the proximal and distal vessel. Herein, we report the case of a 53-year-old man with a dissecting pseudoaneurysm of the SMA, demonstrated by multi-slice computed tomography and angiography. The patient was successfully treated with percutaneous transluminal angioplasty and stenting.