Enhancing Near-Infrared Absorption in Terpyridyl Ru/Os Complexes with Ancillary Ligands to Activate Spin-Forbidden Transitions in Dye-Sensitized Solar Cells: A TDDFT Investigation.

Dye sensitizers with wideband absorption covering the near-IR region have long been of interest because they potentially harvest a wide range of solar energies essential to promote photocurrent power conversion efficiencies. In this study, we used time-dependent density functional theory with spin-orbit (SO) interactions to theoretically explore the long-wavelength absorptions and spin-forbidden triplet transitions activated by SO interactions for terpyridyl ruthenium/osmium complex dyes. These dyes feature a Ru(II) sensitizer coordinated with a phosphine ligand and are exemplified by DX1, denoted as [trans-dichloro-(phenyldimethoxyphosphine)(2,2';6',2″-terpyridyl-4,4',4″-tricarboxylic)Ru]. We found that ancillary ligands significantly affected the longest wavelength spin-allowed absorption, with NCS- ligands yielding longer wavelength S1 transitions than halides. High atomic number halide ligands caused blue shifts in the S1 transition. Os complexes consistently exhibited longer wavelength S1 transitions than Ru complexes with identical ligands. In Ru/Os complexes, ancillary ligands with higher atomic numbers have a more pronounced effect in activating spin-forbidden triplet transitions through spin-orbit coupling (SOC) than those with lower atomic numbers. The absorption wavelength of the SOC-activated transition primarily depended on the energy of lower lying triplet states. Some complexes exhibited T1 states activated by SOC, leading to longer wavelength absorption than that of SOC-activated T2 states. Our study revealed the significance of ancillary ligands and SOC interactions in Ru/Os complexes, offering insights for optimizing materials with enhanced long-wavelength absorption properties, particularly in the near-IR range, for photovoltaic and optoelectronic applications.

Diastereoisomers of Ruthenium Dyes with Unsymmetric Ligands for DSC: Fundamental Chemistry and Photovoltaic Performance.

A new thiocyanic acid-free ruthenium sensitizer, CYC-B29, containing two unsymmetrical ancillary ligands, was synthesized, and its three diastereoisomers CYC-B29-CC, CYC-B29-TT, and CYC-B29-CT with significantly different optical, electronic, and electrochemical properties were carefully separated. CYC-B29-TT with the smallest size has the strongest absorption coefficient of the MLCT band, the shortest λmax, the lowest highest occupied molecular orbital level and the highest dye loading. Therefore, dye-sensitized solar cell based on CYC-B29-TT has the highest efficiency, which is two times higher than that of CYC-B29-CC-sensitized device and 10% higher than that of N719-based cell. Time-dependent density functional theory-calculated transition bands for the three isomers are not identical, and only CYC-B29-TT has the calculated transition bands close to the experimental absorption profile. Although the calculated transition bands for CYC-B29-CC and CYC-B29-CT are not consistent with the experimental data, the ground-state vertical excitation energy with oscillator strength and electron-density difference map data combining with the dye loading predict correctly the order of the photocurrent for the three isomers sensitized devices.

Interaction between alk1 and blood flow in the development of arteriovenous malformations.

Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFß family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.

Effects of intraluminal thrombus on patient-specific abdominal aortic aneurysm hemodynamics via stereoscopic particle image velocity and computational fluid dynamics modeling.

The pathology of the human abdominal aortic aneurysm (AAA) and its relationship to the later complication of intraluminal thrombus (ILT) formation remains unclear. The hemodynamics in the diseased abdominal aorta are hypothesized to be a key contributor to the formation and growth of ILT. The objective of this investigation is to establish a reliable 3D flow visualization method with corresponding validation tests with high confidence in order to provide insight into the basic hemodynamic features for a better understanding of hemodynamics in AAA pathology and seek potential treatment for AAA diseases. A stereoscopic particle image velocity (PIV) experiment was conducted using transparent patient-specific experimental AAA models (with and without ILT) at three axial planes. Results show that before ILT formation, a 3D vortex was generated in the AAA phantom. This geometry-related vortex was not observed after the formation of ILT, indicating its possible role in the subsequent appearance of ILT in this patient. It may indicate that a longer residence time of recirculated blood flow in the aortic lumen due to this vortex caused sufficient shear-induced platelet activation to develop ILT and maintain uniform flow conditions. Additionally, two computational fluid dynamics (CFD) modeling codes (Fluent and an in-house cardiovascular CFD code) were compared with the two-dimensional, three-component velocity stereoscopic PIV data. Results showed that correlation coefficients of the out-of-plane velocity data between PIV and both CFD methods are greater than 0.85, demonstrating good quantitative agreement. The stereoscopic PIV study can be utilized as test case templates for ongoing efforts in cardiovascular CFD solver development. Likewise, it is envisaged that the patient-specific data may provide a benchmark for further studying hemodynamics of actual AAA, ILT, and their convolution effects under physiological conditions for clinical applications.

Oligo-benzamide-based peptide mimicking tools for modulating biology.

The oligo-benzamide scaffold is a rigid organic framework that can hold 2-3 functional groups as O-alkyl substituents on its benzamide units, mirroring their natural arrangement in an α-helix. Oligo-benzamides demonstrated outstanding α-helix mimicry and can be readily synthesized by following high yielding and iterative reaction steps in both solution-phase and solid-phase. A number of oligo-benzamides have been designed to emulate α-helical peptide segments in biologically active proteins and showed strong protein binding, in turn effectively disrupting protein-protein interactions in vitro and in vivo. In this chapter, the design of oligo-benzamides for mimicking α-helices, efficient synthetic routes for producing them, and their biomedical studies showing remarkable potency in inhibiting protein functions are discussed.

Steric Effects on the Photovoltaic Performance of Panchromatic Ruthenium Sensitizers for Dye-Sensitized Solar Cells.

Three new heteroleptic Ru complexes, CYC-B22, CYC-B23C, and CYC-B23T, were prepared as sensitizers for coadsorbent-free, panchromatic, and efficient dye-sensitized solar cells. They are simultaneously functionalized with highly conjugated anchoring and ancillary ligands to explore the electronic and steric effects on their photovoltaic characteristics. The coadsorbent-free device based on CYC-B22 achieved the best power conversion efficiency (PCE) of 8.63% and a panchromatic response extending to 850 nm. The two stereoisomers, CYC-B23C and CYC-B23T coordinated with an unsymmetrical anchoring ligand, display similar absorption properties and the same driving forces for electron injection as well as dye regeneration. Nevertheless, the devices show not only the remarkably distinct PCE (6.64% vs 8.38%) but also discernible stability. The molecular simulation for the two stereoisomers adsorbed on TiO2 clarifies the distinguishable distances (16.9 Å vs 19.0 Å) between the sulfur atoms in the NCS ligands and the surface of the TiO2, dominating the charge recombination dynamics and iodine binding and therefore the PCE and stability of the devices. This study on the steric effects caused by the highly conjugated and unsymmetrical anchoring ligand on the adsorption geometry and photovoltaic performance of the dyes paves a new way for advancing the molecular design of polypyridyl metal complex sensitizers.

Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.

Influences of textured substrates on the heart rate of developing zebrafish embryos.

Identification of the effects of different textured substrates on zebrafish (Danio rerio) embryos provides insights into the influence of external stimuli on normal cardiovascular functions in the developmental stages of the embryos. This knowledge can be used in numerous genetic studies using zebrafish as an animal model as well as in bioanalytical assays using digital microfluidics. In this study, zebrafish embryos were systematically positioned and in vivo imaged on four types of silicon substrates. These substrates exhibited surface textures and surface wettability that were well modulated by wet chemical etching. The heart rate of the developing embryos significantly increased by 9.1% upon exposure to textured Si substrates with nanostructured surfaces compared with bare Si substrates. Modulation of surface wettability in the tested substrates also responded to the increase in the heart rate of the embryo; however, the effect of surface wettability on heart rate was slight compared with the effect of texture. In-depth experimental and statistical investigations of heart rate under the effects of substrate textures imply a pathway through which the inner mass of the embryo reacts to external stimuli. These findings contribute to zebrafish-related studies and suggest other factors to consider in the design of nanostructure-based microfluidics and other biomedical devices.

Highly efficient gel-state dye-sensitized solar cells prepared using poly(acrylonitrile-co-vinyl acetate) based polymer electrolytes.

Poly(acrylonitrile-co-vinyl acetate) (PAN-VA) is utilized as a gelation agent to prepare gel-state electrolytes for dye-sensitized solar cell (DSSC) applications. Based on the synergistic effect of PAN-VA and TiO(2) fillers in the electrolyte, the gel-state DSSC can achieve a conversion efficiency higher than that of a liquid counterpart. The high performance of the gel-electrolyte is attributed to the in situ gelation property of the gel-electrolyte, the contribution of the PAN-VA to the charge transfer, as well as the enhancement effect of TiO(2) fillers on the charge transfer at the Pt-electrolyte interface. The experimental results show that the efficiencies of the gel-state cells have little dependence on the conductivity of the electrolytes with various contents of PAN-VA, but are closely related to the penetration situation of the electrolyte in the TiO(2) film. For PAN-VA concentrations ≤15 wt%, the electrolyte can be easily injected at room temperature based on its in situ gelation property. For higher PAN-VA concentrations, good penetration of the high viscous electrolyte can be achieved by elevating the operation temperature. By utilizing a heteroleptic ruthenium dye (coded CYC-B11), gel-state DSSCs with an efficiency of above 10% are obtained. Acceleration tests show that the cell is stable under one-sun illumination at 60 °C.

Microfluidic Applications of Artificial Cilia: Recent Progress, Demonstration, and Future Perspectives.

Artificial cilia-based microfluidics is a promising alternative in lab-on-a-chip applications which provides an efficient way to manipulate fluid flow in a microfluidic environment with high precision. Additionally, it can induce favorable local flows toward practical biomedical applications. The endowment of artificial cilia with their anatomy and capabilities such as mixing, pumping, transporting, and sensing lead to advance next-generation applications including precision medicine, digital nanofluidics, and lab-on-chip systems. This review summarizes the importance and significance of the artificial cilia, delineates the recent progress in artificial cilia-based microfluidics toward microfluidic application, and provides future perspectives. The presented knowledge and insights are envisaged to pave the way for innovative advances for the research communities in miniaturization.

Behavioural responses of zebrafish with sound stimuli in microfluidics.

Neuronal activities of the human brain responsible for cognitive features have been theorized through several animal models that exhibited various complementary spatial learning modes by generating a flexible repertoire of behavioral strategies. However, for such studies associated with a neurodegenerative disease, which can be further manipulated to provide therapeutic strategies, the animal models employed in their developmental stages have been preferred over the adult ones. This pilot work was incepted to underscore the spatial memory capabilities that strengthened the intricate mechanism of memory acquisition potential in one of the low-order evolutionarily conserved species, such as zebrafish larvae. Initially, a reliable and more easily reproducible microfluidic platform integrating simple and intricate paths was designed to learn and test the spatial information in zebrafish larvae of 4-6 d.p.f. under non-invasive acoustic stimuli. Further, to acquire spatial information as the representation of spatial memory formation in zebrafish larvae, the acoustic startle responses were evaluated by quantifying various dynamic behaviors under distinct operating parameters. After significant conditioning sessions, the spatial memory was tested by employing variable 'freezing'. By the end of the 30 min-long test session, 6 d.p.f. larvae were found to exhibit the highest value of freezing of approximately 43% and 20% in the short and long paths, respectively. Even though a substantial rate of memory loss was observed, it can be envisaged to serve several behavioral strategies that process the dynamic cognitive memory among distinct spatiotemporal environments. Further, the proposed behavioral paradigm had the advantage of being more adaptable and reliably replicable by other researchers. As a consequence, different hypotheses can be readily tested to generate more reproducible findings towards distinct neurobehavioral characteristics. Therefore, the proposed paradigm for the consolidation of spatial memory based on the non-invasive spatial avoidance strategies could provide an enduring framework of reference for behavioral studies using zebrafish larvae.

An aquatic microrobot for microscale flow manipulation.

Microrobots have been developed and extensively employed for performing the variety tasks with various applications. However, the intricate fabrication and actuation processes employed for microrobots further restrict their multitudinous applicability as well as the controllability in high accuracy. As an alternative, in this work an aquatic microrobot was developed using a distinctive concept of the building block technique where the microrobot was built based on the block to block design. An in-house electromagnetic system as well as the control algorithm were developed to achieve the precise real-time dynamics of the microrobot for extensive applications. In addition, pivotal control parameters of the microrobot including the actuating waveforms together with the operational parameters were verified and discussed in conjunction with the magnetic intensity simulation. A mixing task was performed with high efficiency based on the trajectory planning and rotation control of the microrobot to demonstrate its capability in flow manipulation which can be advantageous for microreactor applications down the load. Aside from it, a dissolution test was further conducted to provide an on-demand flow agitation function of the microrobot for the next level of lab chip applications. The presented work with detail dynamic analysis is envisaged to provide a new look of microrobot control and functions from the engineering perspective with profoundly potential applications.

The Association Between Dextromethorphan Use and the Risk of Dementia.

Dementia is one of neurodegenerative disease without preventive medicine currently. Dextromethorphan (DXM) has been reported to reduce neuronal damage and neurodegeneration in animal and human models. The effect of DXM on the dementia has not been fully examined. We examined the medical records over 40 years old in Taiwan's National Health Insurance Research Database between 2000 and 2015 to establish matched cohorts. We used a Cox regression hazard model to identify risk factors of dementia during 16 years of follow-up, and the results indicate that a significantly lower percentage of subjects with DXM use (P < .001) developed dementia compared with those without DXM use (11.38%, 4541/39 895 vs 18.66%, 29 785/159 580). After adjustment for age and other variables [adjusted hazard ratio: .567 (95% confidence interval: .413-.678, P < .001)], this study also demonstrated that DXM use appeared to reduce the risk of developing dementia. DXM use may potentially provide a protective effect against dementia.

The cerebellar development in chinese children-a study by voxel-based volume measurement of reconstructed 3D MRI scan.

Cerebellar disorder was frequently reported to have relation with structural brain volume alteration and/or morphology change. In dealing with such clinical situations, we need a convenient and noninvasive imaging tool to provide clinicians with a means of tracing developmental changes in the cerebellum. Herein, we present a new daily practice method for cerebellum imaging that uses a work station and a software program to process reconstructed 3D neuroimages after MRI scanning. In a 3-y period, 3D neuroimages reconstructed from MRI scans of 50 children aged 0.2-12.7 y were taken. The resulting images were then statistically analyzed against a growth curve. We observed a remarkable increase in the size of the cerebellum in the first 2 y of life. Furthermore, the unmyelinated cerebellum grew mainly between birth and 2 y of age in the postnatal stage. In contrast, the postnatal development of the brain mainly depended on the growth of myelinated cerebellum from birth through adolescence. This study presents basic data from a study of ethnic Chinese children's cerebellums using reconstructed 3D brain images. Based on the technique we introduce here, clinicians can evaluate the growth of the brain.

A non-invasive acoustic-trapping of zebrafish microfluidics.

Zebrafish is an emerging alternative model in behavioral and neurological studies for pharmaceutical applications. However, little is known regarding the effects of noise exposure on laboratory-grown zebrafish. Accordingly, this study commenced by exposing zebrafish embryos to loud background noise (≥200 Hz, 80 ± 10 dB) for five days in a microfluidic environment. The noise exposure was found to affect the larvae hatching rate, larvae length, and swimming performance. A microfluidic platform was then developed for the sorting/trapping of hatched zebrafish larvae using a non-invasive method based on light cues and acoustic actuation. The experimental results showed that the proposed method enabled zebrafish larvae to be transported and sorted into specific chambers of the microchannel network in the desired time frame. The proposed non-invasive trapping method thus has potentially profound applications in drug screening.

Comprehensive Hydrodynamic Investigation of Zebrafish Tail Beats in a Microfluidic Device with a Shape Memory Alloy.

The zebrafish is acknowledged as a reliable species of choices for biomechanical-related investigations. The definite quantification of the hydrodynamic flow physics caused by behavioral patterns, particularly in the zebrafish tail beat, is critical for a comprehensive understanding of food toxicity in this species, and it can be further interpreted for possible human responses. The zebrafish's body size and swimming speed place it in the intermediate flow regime, where both viscous and inertial forces play significant roles in the fluid-structure interaction. This pilot work highlighted the design and development of a novel microfluidic device coupled with a shape memory alloy (SMA) actuator to immobilize the zebrafish within the observation region for hydrodynamic quantification of the tail-beating behavioral responses, which may be induced by the overdose of food additive exposure. This study significantly examined behavioral patterns of the zebrafish in early developmental stages, which, in turn, generated vortex circulation. The presented findings on the behavioral responses of the zebrafish through the hydrodynamic analysis provided a golden protocol to assess the zebrafish as an animal model for new drug discovery and development.

Shape-programmable artificial cilia for microfluidics.

The artificial ciliary motion has been known not to be hydrodynamically optimal, limiting their associated applications in the microscale flow domain. One of the major hurdles of contemporary artificial cilia is its structural rigidity, which restricts their flexibility. To address this issue, this work proposed a shape-programmable artificial cilia design with distinctive polydimethylsiloxane (PDMS) and magnetic segments distributed throughout the structure, which provided precise control for time-spatial modulation of the whole artificial cilia structure under external magnetic actuation. For the fabrication of the proposed multi-segment artificial cilia, a facile microfabrication process with stepwise mold blocking followed by the PDMS and magnetic composite casting was adopted. The hydrodynamic analysis further elucidated that the proposed artificial cilia beating induced significant flow disturbance within the flow field, and the associated application was demonstrated through an efficient mixing operation.

The evaluation of zebrafish cardiovascular and behavioral functions through microfluidics.

This study proposed a new experimental approach for the vascular and phenotype evaluation of the non-anesthetized zebrafish with representative imaging orientations for heart, pectoral fin beating, and vasculature views by means of the designed microfluidic device through inducing the optomotor response and hydrodynamic pressure control. In order to provide the visual cues for better positioning of zebrafish, computer-animated moving grids were generated by an in-house control interface which was powered by the larval optomotor response, in conjunction with the pressure suction control. The presented platform provided a comprehensive evaluation of internal circulation and the linked external behaviors of zebrafish in response to the cardiovascular parameter changes. The insights from these imaging sections was extended to identify the linkage between the cardiac parameters and behavioral endpoints. In addition, selected chemicals such as ethanol and caffeine were employed for the treatment of zebrafish. The obtained findings can be applicable for future investigation in behavioral drug screening serving as the forefront in psychopharmacological and cognition research.

Investigation of 3.3 kV 4H-SiC DC-FSJ MOSFET Structures.

This research proposes a novel 4H-SiC power device structure-different concentration floating superjunction MOSFET (DC-FSJ MOSFET). Through simulation via Synopsys Technology Computer Aided Design (TCAD) software, compared with the structural and static characteristics of the traditional vertical MOSFET, DC-FSJ MOSFET has a higher breakdown voltage (BV) and lower forward specific on-resistance (Ron,sp). The DC-FSJ MOSFET is formed by multiple epitaxial technology to create a floating P-type structure in the epitaxial layer. Then, a current spreading layer (CSL) is added to reduce the Ron,sp. The floating P-type structure depth, epitaxial layer concentration and thickness are optimized in this research. This structure can not only achieve a breakdown voltage over 3300 V, but also reduce Ron,sp. Under the same conditions, the Baliga Figure of Merit (BFOM) of DC-FSJ MOSFET increases by 27% compared with the traditional vertical MOSFET. Ron,sp is 25% less than that of the traditional vertical MOSFET.

Enhancing immunogenicity of HPV16 E7 DNA vaccine by conjugating codon-optimized GM-CSF to HPV16 E7 DNA.

OBJECTIVE: To generate immunity against human papillomavirus (HPV), the use of a recombinant DNA vaccine to carry an appropriate target gene is a promising and cost-effective approach. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that enhances the efficacy of vaccines by promoting the development and prolongation of humoral and cellular immunity. In this study, we linked codon-optimized GM-CSF (cGM-CSF) to the HPV16 E7 sequence as fused protein and evaluated the immunogenic potential of this DNA vaccine. MATERIALS AND METHODS: We have demonstrated that cGM-CSF enhanced immunity against tumor challenges by generating and promoting the proliferation of HPV16 E7-specific CD8+ T cells, which secrete IFN-γ in the murine model. In this study, we aimed to evaluate the immunogenic potential of DNA vaccine that constructed by linking codon-optimized GM-CSF to HPV16 E7 sequence in the animal model. We study the half-life of RNA decay and cellular location of HPV16 E7 by Q-PCR and Western blot. We also assess immune response in the animal model by flow cytometry and ELISA. RESULTS: The cGM-CSF-E7 sequence increased and extended the expression of E7 mRNA, in comparison with the E7 sequence alone. Mice vaccinated with the cGM-CSF-E7 DNA vaccine exhibited a slower rate of tumor growth than those vaccinated with the unconjugated E7 DNA vaccine. We also found that the CD4 and CD8+ T cells from these mice showed strong secretion of IFN-γ. CONCLUSION: Through in vivo antibody depletion experiments, we demonstrated that both CD4+ and CD8+ T cells play an important role in the suppression of tumor growth.