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A numerical investigation of dynamic raceway formation in an industrial-scale blast furnace is performed using Computational Fluid Dynamics (CFD) coupled with a Discrete Element Method (DEM). The industrial-scale simulations are made feasible by incorporating the Flamelet Generated Manifold (FGM) method and a coarse-graining method to reduce the computational cost while ensuring effective modeling of gas phase combustion and a large number of solid particles, respectively. The model considers the interactions between pulverized coal (PC) and coke, as well as their interaction with gas. The simulations reveal a different size and shape of the physical and chemical raceway, indicating that not all crucial reactions occur within the physical raceway. According to the model, the physical raceway formation is primarily determined by the blast air momentum, and the PC combustion has a negligible effect on its dimensions. The chemical raceway formation heavily depends on the oxidation rate of coke. The utilization of PC is quantified in terms of burnout. Smaller PC particles are found to undergo a higher degree of burnout due to faster convective heating and oxidation rates. Modifying the angle of the PC injection lance in current configuration is found to be inconsequential to PC burnout. The presented results highlight the significance of enhancing PC-blast mixing to improve PC utilization and provide new insights into optimizing blast furnace operations. • A novel and comprehensive transient model describing the dynamics of raceway formation in an industrial-scale blast furnace. • Physical raceway and chemical raceway differ in size and shape, as well as the formation mechanism. • Accumulation of unburnt char within the coke channels, closely corresponding to the bird's nest formation. • Enhancing the mixing of pulverized coal and hot blast is crucial for improving PC utilization. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME), where immunosuppressive cells such as tumor-associated macrophages (TAMs) proliferate, is the main cause of resistance to antineoplastic treatment for KRAS -driven lung cancer. In this study, we synthesized polymer-based nanoparticles composed of a 16 nm-sized Au core and the amphiphile, poly-(styrene-alt-maleic acid) (PSMA), via a hydrothermal procedure for carrying the multi-receptor tyrosine kinase inhibitor, sitravatinib (Sit), in a new nanodrug (Au@PSMA-Sit). Au@PSMA-Sit was water soluble and showed high sitravatinib loading and good stability under numerous solution conditions, and was degraded by intracellular esterase to release sitravatinib. In Lewis lung carcinoma (LLC) orthotopic tumor mice, Au@PSMA-Sit enhanced antitumor efficiency by remodeling the TME. Immune profiling with single-cell RNA sequencing showed that Au@PSMA-Sit treatment increased the CD8 T cell cluster and decreased the M2-type macrophage cluster compared to treatment with pure sitravatinib. Au@PSMA-Sit reduced LLC cell proliferation and upgraded M1 polarization of LLC-cocultured TAMs through inhibition of TAM receptors (Tyro3, AXL, and MerTK) after intracellular release of sitravatinib. Au@PSMA-Sit promoted endocytosis-induced endoplasmic reticulum (ER) stress-mediated spleen tyrosine kinase signaling activation, which regulated immunosuppressive TAMs metabolism via enhancement of mitochondrial fission and glycolysis leading to immunogenic modulation. Furthermore, Au@PSMA-Sit enhanced immunogenic cell death through endocytosis/ER stress-mediated release of CRT and HMGB1 from LLC cells, leading to dendritic cell maturation and cytotoxic T cell activation. Therefore, macrophage and CD8 T cell depletion using blocking antibodies diminished the antitumor efficiency of Au@PSMA-Sit. Our results indicate the potential of nano-formulated sitravatinib for strengthening anti-cancer effects in the absence of immunotherapy via immunogenic remodeling of the KRAS -mutant lung TME. [Display omitted] • Polymer-based nanoparticle formulation substantially enhances the anti-tumor efficiency of Sitravatinib in lung cancer. • Au@PSMA-Sit simultaneously regulates cancer cells and tumor-associated macrophages via endocytosis-induced ER stress. • Au@PSMA-Sit promotes mitochondrial fusion and glycolysis for M1 polarization in macrophages and induces ICD in cancer cells. [ABSTRACT FROM AUTHOR]

Background/purpose: Understanding the root canal systems of molars and the association of root canal system in adjacent or contralateral molars is important for dental practice. This study aimed to use cone-beam computed tomography (CBCT) to analyze the morphology similarity of root canal systems in the maxillary first and second molars.Methods: CBCT images of 1741 maxillary molars in a total of 519 patients were blindly examined to analyze the correlation of root canal systems between maxillary first and second molars as well as the bilateral first and second molars.Results: The most common type in maxillary first molars is 3R4C (3 roots/4 canals), whereas in maxillary second molars is 3R3C.The symmetry in type of root canals in bilateral maxillary first and second molars were 87.36% and 79.85%, respectively. The similarities of root canal system in adjacent maxillary first and second molars were 53.07% (right side) and 52.58% (left side). The concurrence of MB2 canal in bilateral maxillary first molars is 77.8%, and 35.97% in maxillary second molars. In the 110 patients with MB2 canal in bilateral maxillary second molars, the chance of bilateral MB2 canals in their maxillary first molar is almost 100%.Conclusion: Maxillary first molars have higher prevalence of 3R4C than second molars. The symmetry in bilateral maxillary molars is higher than the similarity in adjacent maxillary first and second molars. Application of CBCT analysis of root canal system can improve endodontic treatment outcomes. The correlation of root canal system between teeth is useful for genetic linkage. [ABSTRACT FROM AUTHOR]

In Euler-Lagrange models for particulate systems, the information exchange of multiphase coupling terms, i.e. drag force, heat transfer, or mass transfer, is often smoothed from particles' location to nearby computational cells when the cell and particle sizes are comparable. The diffusion-based smoothing is among the most popular approach. However, when it comes to polydisperse systems, the state-of-the-art constant diffusivity approach does not consider variation in particle sizes, resulting in an even smoothing of exchanged information across all particles with different sizes. In this paper, a particle-size dependent smoothing scheme named "non-constant diffusivity approach" is proposed. This approach distributes the exchanged information based on the local Sauter diameter d 32 such that the area of influence per particle varies by size. The one-dimensional analytical solution of the non-constant diffusivity approach is first derived and two control parameters L ⁎ and S are identified, where L ⁎ determines the characteristic length of the diffusivity and S determines the magnitude of the diffusivity. Together they control the characteristic length scale ℓ ˜ c of the smoothing operation. In the one-dimensional study, it is found that the proposed smoothing method is most suitable for the dilute particulate regime. The investigation is extended to a three-dimensional dilute particle flow based on the experiment of the CRIEPI (Central Research Institute of Electric Power Industry) pulverized coal burner. It is shown that using the non-constant diffusivity smoothing, the prediction of the O 2 concentration is more accurate than when using the constant diffusivity smoothing approach, which assumes a universal smoothing length for all sizes of particles. The findings suggest that when it comes to polydisperse particulate systems, the area of influence per particle on the fluid depends on the particle size. The proposed non-constant diffusivity approach can describe that with the benefits of cheap computational cost, conservation of exchanged quantities, and easy-to-implement. • A novel particle-size dependent smoothing scheme for polydisperse Euler-Lagrange systems. • Characteristic smooth length connects with the local particle size. • Develop on the foundation of the state-of-the-art diffusion-based method. • Applicable in different particulate systems, from dilute to dense. [ABSTRACT FROM AUTHOR]

Background/purpose: Cone-beam computed tomography (CBCT) can provide valuable data for root canal systems of human teeth in vivo. This study used CBCT to evaluate the number of roots and canals of 300 mandibular first premolars in 150 northern Taiwanese patients. Methods: The root canal systems of 300 mandibular first premolars in 150 northern Taiwanese patients with bilateral premolars were analyzed by CBCT. Results: Of the 300 mandibular first premolars, 197 (65.7%) had one root with one canal (1R1C), 49 (16.3%) had one root with two canals (1R2C), 51 (17.0%) had two roots with one canal in each root (2R2C), and three (1.0%) had three roots with one canal in each root (3R3C). Statistical analyses showed that women had a significantly higher incidence of 1R1C mandibular first premolars (71.4%) than men (58.8%, p = 0.031), and men had a significantly higher incidence of 2R2C mandibular first premolars (27.2%) than women (8.5%, p < 0.001). One hundred and twenty-two (81.3%) of the 150 patients had a symmetrical root and root canal system between the right and left mandibular first premolars. Men had a significantly higher symmetrical rate of 2R2C mandibular first premolars (26.5%) than women (8.2%, p = 0.013). Conclusion: Approximately 82% of mandibular first premolars in northern Taiwanese patients have one root with either one or two canals. There are significant differences in the number of roots and canals and symmetry of the root canal system of bilateral mandibular first premolars between male and female northern Taiwanese patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Application of FGM and coarse-graining approaches in the framework of CFD-DEM. • State-of-the-art pulverized coal combustion models. • Concentrated fuel release induced by coarse-graining can be mitigated by smoothing. • Simulations are validated with experimental data of a jet flame of pulverized coal. Large Eddy Simulations (LES) combined with the Flamelet Generated Manifold (FGM) approach has become popular for modeling turbulent flame/combustion of pulverized coal or biomass. In this paper, we incorporate a coarse-graining discrete element method (CG-DEM) with the FGM-LES for cost-effective Euler–Lagrange (EL) simulations of turbulent coal combustion. This developed method significantly reduces the computational burden in both Eulerian phase (via FGM) and Lagrangian phase (via CG) compared to conventional reactive EL simulations. The study is based on the experiment of the CRIEPI (Central Research Institute of Electric Power Industry) burner, which has been extensively used for model validation in literature. It is shown that the developed model can effectively reduce the computing cost while maintaining a good accuracy in predicting the pulverized coal flow dynamics as well as combustion performance. For this particular case, an optimal coarse-graining factor, the size ratio of coarse-grained parcels to original particles, of 2 is determined. A larger coarse-graining factor will create local concentrated regions of fuel and consequently lead to different combustion behavior. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic manganese ferrite (MnFe2O4) nanoparticles with approximately 100nm in diameter were used to improve the performance of an immunoassay for detecting influenza infections. The synthesized nanoparticles were tested for long-term storage to confirm the stability of their thermal decomposition process. Then, an integrated microfluidic system was developed to perform the diagnosis process automatically, including virus purification and detection. To apply these nanoparticles for influenza diagnosis, a micromixer was optimized to reduce the dead volume within the microfluidic chip. Furthermore, the mixing index of the micromixer could achieve as high as 97% in 2seconds. The optical signals showed that this nanoparticle-based immunoassay with dynamic mixing could successfully achieve a detection limit of influenza as low as 0.007 HAU. When compared with the 4.5-μm magnetic beads, the optical signals of the MnFe2O4 nanoparticles were twice as sensitive. Furthermore, five clinical specimens were tested to verify the usability of the developed system. From the Clinical Editor: In this study, magnetic manganese ferrite nanoparticles were used to improve the performance of a novel immunoassay for the rapid and efficient detection of influenza infections. [Copyright &y& Elsevier]

Abstract: Introduction: Early detection of vertical root fracture (VRF) is important for clinical endodontic practice. The purpose of this study was to measure the fracture width (distance between 2 sides of the fracture) of VRF teeth in vitro by using 2 micro–computed tomography (μ-CT) systems with different spatial resolution and voxel size. Methods: Thirty-seven endodontically treated teeth with VRF were scanned by 80-μm pixel size μ-CT. Fifteen teeth with no obvious fracture line, blurred image, or fracture space less than 100 μm were scanned by 9-μm pixel size μ-CT. Results: Presence of 2 VRF lines was more common in premolars (82%) than in molars (53%). In 7 premolars (32%) and 9 molars (60%), the VRF lines extended to within the apical 3 mm of the root. All fracture lines were detected by 9-μm pixel size μ-CT, but only 22 of 37 VRF teeth had vertical fracture identified by 80-μm μ-CT. From μ-CT examination, none of the fracture lines showed consistent and uniform fracture space. If 2 fracture lines were present, they were typically in opposite (not linear) directions. There was a significant correlation between 2 fracture lines or fracture lines extending within the 3 mm of the apex and fracture width greater than 100 μm. Conclusions: Application of 9-μm μ-CT can be accurately used for early detection of VRF. Fracture characteristics (eg, number of fracture lines, extension of fracture line) may affect the fracture width. Appropriate use of μ-CT technology can be helpful for early diagnosis of VRF. [Copyright &y& Elsevier]

Background: Antidepressants, aiming at monoaminergic neurotransmission, exhibit delayed onset of action, limited efficacy, and poor compliance. Glutamatergic neurotransmission is involved in depression. However, it is unclear whether enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be a treatment for depression. Methods: We studied sarcosine, a glycine transporter-I inhibitor that potentiates NMDA function, in animal models and in depressed patients. We investigated its effects in forced swim test, tail suspension test, elevated plus maze test, novelty-suppressed feeding test, and chronic unpredictable stress test in rats and conducted a 6-week randomized, double-blinded, citalopram-controlled trial in 40 patients with major depressive disorder. Clinical efficacy and side effects were assessed biweekly, with the main outcomes of Hamilton Depression Rating Scale, Global Assessment of Function, and remission rate. The time course of response and dropout rates was also compared. Results: Sarcosine decreased immobility in the forced swim test and tail suspension test, reduced the latency to feed in the novelty-suppressed feeding test, and reversed behavioral deficits caused by chronic unpredictable stress test, which are characteristics for an antidepressant. In the clinical study, sarcosine substantially improved scores of Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function more than citalopram treatment. Sarcosine-treated patients were much more likely and quicker to remit and less likely to drop out. Sarcosine was well tolerated without significant side effects. Conclusions: Our preliminary findings suggest that enhancing NMDA function can improve depression-like behaviors in rodent models and in human depression. Establishment of glycine transporter-I inhibition as a novel treatment for depression waits for confirmation by further proof-of-principle studies. [Copyright &y& Elsevier]

Abstract: We present an approach for synchronizing hyperthermia and thermal-responsive local drug release. The targeting probe has a magnetite nanocrystal (Fe3O4@PSMA) core and a polynucleotide shell that carries 5-fluorouracil (5-FU) and anti-human epidermal growth factor receptor 2 (anti-HER2) antibody for cancer cell-specific targeting. The targeting nanocrystals play as an important role to relay the externally delivered radiofrequency energy for tumor hyperthermia. Locoregional heat then triggers a drug release from the oligonucleotide carrier as it directly damages tumor cells. Cell viability assays and pathological examinations show that this synchronization is significantly more efficacious in both in vitro and in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission in vivo was achieved through radiofrequency synchronization of hyperthermia and chemotherapy after the nanoparticle had been intravenously injected. [Copyright &y& Elsevier]

Abstract: Self-templated synthesis involving interior channel wall protection as well as outermost surface passivation was crucial to successful synthesis of multi-shelled mesoporous silica nanospheres. The shell-by-shell fabrication of double- and triple-walled mesoporous silica nanospheres downsized to ∼100 nm. The multi-shelled mesoporous silica can be built as rattle-type or hollow structures with ∼110 nm of double-shelled and ∼140 nm of triple-shelled sizes. Notably, the shell-to-shell distance can be tuned by controlling the etching period from the self-templation processes without changing the multi-shelled size or interior core diameter. The multi-shelled mesoporous nanostructures provide a platform for the development of a multifunctional vector by the inclusion of functional species into shell-to-shell cavities and porous shells. The encapsulation of the fluorophore and drug in shell-to-shell space and mesoporous shells showed that multi-shelled silica spheres can be used in dual-modality for imaging and drug co-delivery vectors through the appropriate selection of pH-dependent molecules. The in vitro evaluation in triple-shelled silica indicated that an anti-cancer doxorubicin (DOX), loaded in the outer periphery space, was successfully carried and released in the cytoplasm, then entered nuclei while fluorescein FITC (primarily distributed in inner periphery space) was effectively encapsulated inside the spheres. The double- and triple-shelled nanospheres consistently provided imaging probes with visible tracking capability in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract: There is continuous interest in developing manganese-based T 1 contrast agents. While much effort has been made to synthesize manganese chelates, the development of manganese-based nanoparticle, particularly manganese oxides, as MRI contrast agents is burgeoning. In this report, sub-10-nm nanospheres, nanoplates, and nanocubes of Mn3O4 were synthesized and exhibited paramagnetic behavior at room temperature on the basis of superconducting quantum interference devices (SQUID) measurements. The surface Mn3+ passivated nanoplates examined by x-ray photoelectron spectroscopy (XPS) had the largest r 1 relaxivity of the reported manganese oxide nanoparticles. The MR labeling assays of Mn3O4 nanoplate-treated A549 lung cancer cells showed that MR signals increased to 139% in T 1-weighted images compared with untreated cells when the Mn ion concentration went down to 1.3 × 10−2 mm. A dark field illumination microscope was employed to monitor Mn3O4 nanoplates internalized into cells as a function of time. [Copyright &y& Elsevier]

Background/purpose: Cone-beam computed tomography (CBCT) can provide valuable data for root canal systems of human teeth. This study used CBCT to evaluate the number of roots and canals in mandibular first molars in Taiwanese individuals.Methods: We screened 151 patients (76 male and 75 female) scheduled for CBCT scan prior to implantation, or orthodontic, endodontic, or periodontic treatment between June 2006 and March 2009 at the Department of Dentistry, Cardinal Tien Hospital, Taipei, Taiwan. A total of 237 image samples of mandibular first molars were obtained and analyzed for their number of roots and canals.Results: We found that 177 (74.7%) mandibular first molars had two roots and 60 (25.3%) had three roots. Of the 237 teeth, 133 (56.1%) had three canals, 96 (40.5%) had four, and eight (3.4%) had two canals. Of the 86 patients (43 male and 43 female) with bilateral mandibular first molars, 22 (25.6%, 15 male and 7 female) had bilateral three-rooted mandibular first molars, and six (7.0%, 4 male and 2 female) had unilateral three-rooted mandibular first molars. The chi(2) test showed a significantly higher incidence of three-rooted mandibular first molars in male (44.2%, 19/43) than in female (20.9%, 9/43, p = 0.038) subjects.Conclusion: Our results showed a high overall incidence (32.6%) of three-rooted mandibular first molars in Taiwanese individuals. CBCT could be a valuable tool for identifying an extra distolingual root in mandibular first molars. [ABSTRACT FROM AUTHOR]

Summary: This study examines how gender and menopausal status contribute to age effect on the antidepressant efficacy of repetitive transcranial stimulation (rTMS). Thirty-one women (17 premenopausal, 14 postmenopausal), and 16 men with treatment-refractory bipolar/major depression underwent 10 consecutive sessions of rTMS. Mood symptoms and female hormones were measured. ANOVA-R revealed a significant gender (p<0.05) and time effect (p<0.001) on the Hamilton Depression Rating Scale (HAM-D) score. Percentage reduction of the rating correlated negatively with age in women (p<0.001). While no difference in the rTMS response was observed between male and premenopausal female patients (68.8% and 70.6%, respectively), postmenopausal women responded least (0%). We also found that greater improvement of depression score was associated with a higher estradiol/progesterone ratio in premenopausal women (p<0.05), suggesting an important role of female hormones in the therapeutic response. Regression analysis revealed that menopausal status and ovarian steroid levels, but not age, were the main determinants of antidepressant efficacy of rTMS in females. This is the first study to specifically investigate the effect of female hormones on rTMS therapeutic effect. Our data support changes in menopausal status and ovarian steroid levels as effectors of mood and the CNS neural substrate response to rTMS in refractory depression. However, the restricted number of patients and the shorter duration of rTMS treatment and follow-up might influence its generalization. Further study examining the interactions between mood, ovarian hormones, and rTMS treatment is warranted. [Copyright &y& Elsevier]

Abstract: Excessive production of nitric oxide (NO) might have detrimental effects on the hypoxia-related neuropathology. This study aimed to test if mild hypoxic preconditioning (MHPC) would attenuate the pathological changes in the brainstem motoneurons having a different functional component after peripheral nerve crush injury (PNCI). Prior to PNCI treatment, young adult rats were caged in the mild hypoxic altitude chamber with 79Torr of the partial oxygen concentration () (i.e., 0.5atm at 5500m in height) for 4 weeks to adapt the environmental changes. After that, all the animals having successfully crushed both the hypoglossal and vagus nerves (left-side) were allowed to survive for 3, 7, 14, 30 and 60 successive days in normoxic condition. Nicotinamine adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry revealed that MHPC reduces NADPH-d/nNOS expression in the hypoglossal nucleus (HN) and the dorsal motor nucleus of the vagus (DMN) at different time points after PNCI. The morphological findings were further ascertained by Western blot analysis of nNOS and nitrite assay for NO production. Both the morphological and quantitative results peaked at 7 days in HN, whereas for those in DMN were progressively increased up to 60 days following PNCI. The staining intensity of NADPH-d/nNOS(+) neurons, expression of nNOS protein, NO production levels as well as the neuronal loss in HN and DMN of MHPC rats following PNCI were attenuated, especially for those having a longer survival period over 14 days. The MHPC treatment might induce minute amounts of NO to alter the state of milieu of the experimental animals to protect against the PNCI. [Copyright &y& Elsevier]

Abstract: This study aimed to test the hypothesis that mild hypoxic preconditioning (MHPC)-induced NOS expression would attenuate the neuropathological changes in the nodose ganglion (NG) of severe hypoxic exposure (SHE) rats. Thus, the young adult rats were caged in the altitude chamber for 4 weeks prior to SHE for 4h to gain hypoxic preconditioning. The altitude chamber was used to set the height at the level from 5500m (0.50atm; pO2=79Torr) to 10,000m (0.27atm; pO2=43Torr) for MHPC and SHE, respectively. The experimental animals were allowed to survive for 0, 7, 14, 30 and 60 successive days, respectively. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to detect NADPH-d/nNOS reactivity in the NG at various time points following hypoxic exposure. The present results showed that about 38% of the neurons in the NG displayed NADPH-d/nNOS positive [NADPH-d/nNOS(+)] in normoxic rats. In SHE rats, a peak in the percentage (71%) and staining intensity (230%) of NADPH-d/nNOS(+) nodose neurons at 0 day, which then gradually decreased at 7–60 days. About 25% of the nodose neurons died 60 days after SHE. However, in MHPC rats subjected to SHE, NADPH-d/nNOS(+) neurons peaked in the percentage (51%) and staining intensity (171%) at 0 day, which then decreased at 7–60 days. In addition, neuronal survival was markedly increased by MHPC. These results suggested that MHPC might have a neuroprotective effect that reduces the susceptibility of the nodose neurons to NOS mediated neuropathy subsequent to SHE. [Copyright &y& Elsevier]

Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for modulating cognition by delivering stimulation in the brain. However, the effects of rTMS on cognition are still controversial. This randomized, sham-controlled, crossover study was designed to determine whether rTMS of the left dorsolateral prefrontal cortex (DLPFC) interferes with the Go/NoGo task and whether personal parameters such as age affect rTMS. A total of 24 healthy subjects (12 male and 12 female, aged 20–37 years) underwent one session of active rTMS followed by sham rTMS (total of 1600 pulses, 100% of motor threshold, 5 Hz, 8 s), or vice versa. The results did not show any differences between active and sham rTMS stimulation in terms of performance accuracy, response speed, or choice reaction time (cRT) implicating that short-term rTMS will not enhance or deteriorate cognition. However, percentage cRT shortening induced by active rTMS was negatively correlated with age (r=-0.57, P=0.005), whereas that induced by sham rTMS was not (r=-0.23, P>0.05), suggesting that cognition of younger subjects might have greater modulation by active stimulation than older ones. This finding may help explain some of the controversies or paradoxical results observed in studies of the effect of left DLPFC rTMS on cognition. [Copyright &y& Elsevier]

Abstract: Quetiapine, a second-generation antipsychotic originally used in the treatment of schizophrenia, was also found to be effective as monotherapy or as an adjunctive therapy for acute mania. Delirium in patients treated with quetiapine seems to be a rare phenomenon; however, we report two patients with bipolar disorder who developed delirium when prescribed quetiapine as an adjunct to valproate for acute mania. Both had previously developed mild renal insufficiency after an episode of lithium intoxication. The delirium resolved after quetiapine was discontinued. Unexpected interactions may occur when medications are combined without being subject to controlled clinical trials. [Copyright &y& Elsevier]

Light-based diagnostics and therapy have become indispensable tools in the field of cancer nanomedicine. Various optical imaging modalities with tomographic capability have been developed to visualize cellular and organismic distributions of molecules. Microscopic pharmacokinetics and the tumor-targeting efficacy of nanoscale effectors can now be precisely evaluated. Moreover, phototherapy using intense laser light has been widely used for treating cancers. Using light-active nanoscale effectors, photothermal and photodynamic therapies on superficial tumors can be achieved with low-illumination lasers. Consequently, for the next generation of photo-medical techniques, the use of near infrared (NIR) excitation sources on NIR-activatable nanoparticles may offer deeper light penetration owing to less extensive scattering and absorption by endogenous chromophores in the NIR spectral region. Therefore, treatments and biodetection within higher tissue volumes and with less side effects (e.g. overheating) may be successfully implemented. This comprehensive review covers the state-of-the-art technologies on (a) advanced laser light sources appropriate for deep tissue theranostics, (b) types of laser interactions with pure-NIR and NIR-upconverting nanomaterials, (c) current development of NIR and multi-photon nanoparticles, (d) application fields of NIR nanomaterials in cancer theranostics, and (e) nanotoxicology of NIR nanoscale effectors for cancer treatment. [ABSTRACT FROM AUTHOR]

Sarcosine, an N -methyl- d -aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long-term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560 mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naïve rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression. [ABSTRACT FROM AUTHOR]

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1–1.9 μm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging – computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation. [ABSTRACT FROM AUTHOR]

Abstract: We synthesize a NIR MHI-148 dye, a lipophilic heptamethine cyanine, with capability in tumor-targeting property to accumulate in the mitochondria of tumor. In the context of MHI-148 dye, we demonstrate effective tumor targeting and NIR fluorescence in vitro and in vivo for MHI-148 as compared to ICG. A series of porous Gd silicates related nanoparticles, i.e. Gd silicate, Gd silicate@mSiO2 (mSiO2: mesoporous silica shell), and Gd3+-chelated Gd silicate@mSiO2 (Gd3+-DOTA chelated on the mSiO2) are fabricated to demonstrate their magnetic resonance (MR) contrast imaging effects. Those Gd silicates related nanoparticles exhibit dual MR effect, expressing T1-brightened and T2-darkened effects, in lower magnetic field. In high magnetic field, an abnormal enhanced transverse relaxivity (r 2) appears, showing an effective T2-lowering effect, possibly due to concentrated Gd amount and porous architecture. The r 2 value increases 4-5 times as the field strength increased from 3T to 7T. The Gd3+-chelated Gd silicate@mSiO2 has given large r 2 (T2-lowering effect) up to 343.8 s−1 mm −1, which is even larger than the reported magnetic Fe3O4 nanoparticles measured at the same field. Using a 9.4T animal micro MRI system we have seen effectively darken in signal for those porous Gd silicates related NPs, while no such phenomenon appears in commercial Gd-DOTA agent. The MHI-148 is then conjugated on the porous Gd silicate@mSiO2 nanoparticles for a new paradigm with three functionalities for in vivo tumor targeting, near-infrared fluorescent and MR imaging by means of only using MHI-148 dye. [Copyright &y& Elsevier]

Background: A non-invasive method for left ventricular pressure-strain analysis has recently been introduced to provide information on cardiac work and detect subtler changes in cardiac function. This study aims to verify and construct a novel index that could accurately and independently predict the prognosis of patients with end-stage kidney disease (ESRD) receiving regular hemodialysis.Methods: Patients with end-stage kidney disease (ESRD) receiving maintenance hemodialysis (4-h sessions, 3 times weekly for 3 months or more) and who underwent echocardiography between 2009 and 2014 in China Medical University Hospital, Taichung, Taiwan, were enrolled. Conventional (left ventricular ejection fraction, LVEF) and strain echocardiography parameters (global longitudinal strain, GLS; cardiac work index, CWI) in 102 eligible patients were analyzed and compared. CWI was calculated from estimated LV pressure-myocardial strain loop area.Results: Results show that, while no significant differences were found between LVEF (0.57 ± 0.12 vs. 0.59 ± 0.09, P = 0.27) and GLS (-16.12 ± 6.57% vs. -18.44 ± 5.54%, P = 0.07), deceased patients had significantly lower CWI (1339 ± 683.05 mmHg% vs. 1883.38 ± 640.99 mmHg%, P = 0.0002) than surviving patients. The predictive values defined by area under the curve (AUC) of LVEF, GLS and CWI were 0.499, 0.619 and 0.724, respectively.Conclusion: In conclusion, CWI is an accurately independent predictor of all-cause mortality in ESRD patients receiving regular hemodialysis and may superior to the current predictors such as LVEF and GLS. [ABSTRACT FROM AUTHOR]

The photoreduction method is a potential method in terms of simplification, speed and cost of the process. This paper presents a simple and novel method for the direct synthesis of a gold nanoparticle monolayer with a droplet of gold precursor on the surface of SU-8 under UV exposure. Photoreduction ability on different polymer surfaces with various photoinitiator concentrations was investigated. The horizontal and vertical distributions of reduced nanoparticles were examined by using a scanning electron microscope and a transmission electron microscope, and crystalline property was verified through energy dispersive X-ray spectroscopy. The influence of SU-8 initial curing time and reduction repetition times on nanoparticle sizes and densities was investigated. The same photoreduction process is applicable to the surface of SU-8 nanostructures. The use of SU-8 nanopillars as a photoreduction substrate can provide a high specific surface area for improving the density of hot spots in the application of surface-enhanced Raman spectroscopy. Unlabelled Image • Monolayer gold nanoparticles are synthesized by shining UV over HAuCl 4 droplet on SU-8. • The epoxy resin together with the photoinitiator play key roles in photoreduction. • Particle size and density are adjustable by curing time and repeated reduction. • R6G Raman signal on SU-8 nanopillars is five times stronger than on SU-8 films. [ABSTRACT FROM AUTHOR]

Abstract: Valproic acid (VPA) is a well-tolerated and effective agent for the treatment of epilepsy, bipolar disorder, and schizoaffective disorder. Several case reports have indicated that VPA may induce serious symptomatic hyperammonemia. Based on analysis of susceptible patients, several possible mechanisms and risk factors have been proposed to identify the patients at risk. Nevertheless, we report the case of a schizoaffective patient who developed severe hyperammonemia occurring after brief exposure to VPA, despite the absence of any known risk factors. Until now, early recognition of the signs and symptoms of hyperammonemia is crucial to managing this unusual adverse reaction. [Copyright &y& Elsevier]