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Yi Zhao - Top 30 Publications

Effect of thermo-tolerant actinomycetes inoculation on cellulose degradation and the formation of humic substances during composting.

The inoculum containing four cellulolytic thermophilic actinomycetes was screened from compost samples, and was inoculated into co-composting during different inoculation phases. The effect of different inoculation phases on cellulose degradation, humic substances formation and the relationship between inoculation and physical-chemical parameters was determined. The results revealed that inoculation at different phases of composting improved cellulase activities, accelerated the degradation of cellulose, increased the content of humic substances and influenced the structure of actinomycetic community, but there were significant differences between different inoculation phases. Redundancy analysis showed that the different inoculation phases had different impacts on the relationship between exogenous actinobacteria and physical-chemical parameters. Therefore, based on the promoting effort of inoculation in thermophilic phase of composting for the formation of humic substances, we suggested an optimized inoculation strategy to increase the content of humic substances, alleviate CO2 emission during composting.

C1-C2 alkyl aminiums in urban aerosols: Insights from ambient and fuel combustion emission measurements in the Yangtze River Delta region of China.

We measured low molar-mass alkyl aminiums (methylaminium, dimethylaminium, ethylaminium and diethylaminium) in urban aerosols in the Yangtze River Delta region of eastern China in August 2014 and from November 2015 to May 2016. After examining artifact formation on sample filters, methylaminium, dimethylaminium and ethylaminium concentrations were quantified. The three C1-C2 aminiums exhibited a unimodal size distribution that maximized between 0.56 and 1.0 μm. Their concentrations in PM2.5 were 5.7 ± 3.2 ng m(-3), 7.9 ± 5.4 ng m(-3) and 20.3 ± 16.6 ng m(-3), respectively, with higher concentrations during the daytime and in warm seasons. On new particle growth days, amine uptake to particles larger than 56 nm was barely enhanced. The molar ratios of individual aminium/NH4(+) in PM2.5 were on the order of 10(-4) and 10(-3). Aminiums were thus far less to out-compete ammonium (NH4(+)) in neutralizing acidic species in particle sizes down to 56 nm. Abundant nitrate (NO3(-)/SO4(2-) molar ratio = ∼3) and its correlation to methylaminium and ethylaminium implied that nitrate might be more important aminium salt than sulfate in urban aerosols of this area. Direct measurement of particle-phase amine emission from coal and biomass burning showed that coal burning is an important atmospheric amine source, considering coal burning is top-ranked particulate matter source in China.

Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery.

Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.

Supercapacitor Electrodes with Remarkable Specific Capacitance Converted from Hybrid Graphene Oxide/NaCl/Urea Films.

A novel approach to improve the specific capacitance of reduced graphene oxide (rGO) films is reported. We combine the aqueous dispersion of liquid-crystalline GO incorporating salt and urea with a blade-coating technique to make hybrid films. After drying, stacked GO sheets mediated by solidified NaCl and urea are hydrothermally reduced, resulting in a nanoporous film consisting of rumpled N-doped rGO sheets. As a supercapacitor electrode, the film exhibits a high gravimetric specific capacitance of 425 F g(-1) and a record volumetric specific capacitance of 693 F cm(-3) at 1 A g(-1) in 1 M H2SO4 aqueous electrolyte when integrated into a symmetric cell. When using Li2SO4 aqueous electrolyte, which can extend the potential window to 1.6 V, the device exhibits high energy densities up to 35 Wh kg(-1), and high power densities up to 10(4) W kg(-1). This novel strategy to intercalate solidified chemicals into stacked GO sheets to functionalize them and prevent them from restacking provides a promising route toward supercapacitors with high specific capacitance and energy density.

Polarity of varicosity initiation in central neuron mechanosensation.

Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca(2+)/Na(+)-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons. We further show that axonal varicosities are induced by persistent Ca(2+) increase, disassembled microtubules (MTs), and subsequently reversible disruption of axonal transport, and are regulated by stable tubulin-only polypeptide, an MT-associated protein. Finally, axonal varicosity initiation can trigger action potentials to antidromically propagate to the soma in retrograde signaling. Therefore, our study demonstrates a new feature of neuronal polarity: axons and dendrites preferentially respond to physical and chemical stresses, respectively.

Construction of EGFR peptide gefitinib/quantum dots long circulating polymeric liposomes for treatment and detection of nasopharyngeal carcinoma.

Gefitinib/Quantum dots (QDs) loaded peptide long circulating liposomes (G/QDs-P-LCPL) were successfully prepared for treatment and detection by fluorescence labeling for nasopharyngeal carcinoma. Gefitinib was found to have marked inhibition which is dose- and time-dependent. Hoechst 33258 florescence staining and wound-healing assay indicated that as G/QDs-P-LCPL concentration increased, HONE1 staining cells decreased, while the amount of nucleus pyknosis and karyorrhexis grew. Florescence tracing result shows that the drug mainly distributed through tumors. G-P-LCPL target the HONE1 cells and significantly increase the drug uptake efficiency so as to improve the cells inhibit rate compared with the non-targeting group. The EGFR peptide LCPL are potentially useful for drug and fluorescence labeled delivery applications.

An extension of stochastic hierarchy equations of motion for the equilibrium correlation functions.

A traditional stochastic hierarchy equations of motion method is extended into the correlated real-time and imaginary-time propagations, in this paper, for its applications in calculating the equilibrium correlation functions. The central idea is based on a combined employment of stochastic unravelling and hierarchical techniques for the temperature-dependent and temperature-free parts of the influence functional, respectively, in the path integral formalism of the open quantum systems coupled to a harmonic bath. The feasibility and validity of the proposed method are justified in the emission spectra of homodimer compared to those obtained through the deterministic hierarchy equations of motion. Besides, it is interesting to find that the complex noises generated from a small portion of real-time and imaginary-time cross terms can be safely dropped to produce the stable and accurate position and flux correlation functions in a broad parameter regime.

A novel signal acquisition platform of human cardiovascular information with noninvasive method.

Cardiovascular diseases (CVDs) are considered the major cause of death worldwide, so more researchers pay more and more attention to the development of a non-invasive method to obtain as much cardiovascular information (CVI) as possible for early screening and diagnosing. It is known that considerable brain information could be probed by a variety of stimuli (such as video, light, and sound). Therefore, it is quite possible that much more CVI could be extracted via giving the human body some special interrelated stimulus. Based on this hypothesis, we designed a novel signal platform to acquire more CVI with a special stimulus, which is to give a gradual decrease and a different settable constant pressure to six air belts placed on two-side brachia, wrists, and ankles, respectively. During the stimulating process, the platform is able to collect 24-channel dynamic signals related with CVI synchronously. Moreover, to improve the measurement accuracy of signal acquisition, a high precision reference chip and a software correction are adopted in this platform. Additionally, we have also shown some collection instances and analysis results in this paper for its reliability. The results suggest that our platform can not only be applied on study in a deep-going way of relationship between collected signals and CVDs but can also serve as the basic tool for developing a new noninvasive cardiovascular function detection instrument and system that can be used both at home and in the hospital.

Clinical implications of c-maf expression in plasma cells from patients with multiple myeloma.

Multiple myeloma (MM) is a type of hematological malignancy with significant heterogeneity in clinical features and prognosis. Cytogenetic abnormalities are the major factors affecting patient outcomes. Studies have shown that immunohistochemistry (IHC)-based detection of cancer-related genes expression could be alternative indicators for the prognosis of MM.

Impact of phosphate-solubilizing bacteria inoculation methods on phosphorus transformation and long-term utilization in composting.

This study aimed to assess the effect of phosphate-solubilizing bacteria (PSB) application and inoculation methods on rock phosphate (RP) solubilization and bacterial community during composting. The results showed that PSB inoculation in different stages of composting, especially both in the beginning and cooling stages, not only improved the diversity and abundance of PSB and bacterial community, but also distinctly increased the content of potential available phosphorus. Redundancy analysis indicated that the combined inoculation of PSB in the initial stage with higher inoculation amount and in the cooling stage with lower inoculation amount was the best way to improve the inoculation effect and increase the solubilization and utilization of RP during composting. Besides, we suggested three methods to improve phosphorus transformation and long-term utilization efficiency in composts based on biological fixation of phosphates by humic substance and phosphate-accumulating organisms.

Three-dimensional co-culture microfluidic model and its application for research on cancer stem-like cells inducing migration of endothelial cells.

To build a three-dimensional co-culture model in a microfluidic device for cancer research and evaluate its feasibility by investigating cancer stem-like cells (SCs) induced migration of human umbilical vein endothelial cells (ECs).

Upregulation of CCAT2 promotes cell proliferation by repressing the P15 in breast cancer.

Long non-coding RNAs (lncRNAs) are demonstrated to function as modulators of both transcriptional and post-transcriptional regulation in various types of tumors progression. The objective of the study is to investigate the clinical significance and underlying mechanism of Colon cancer associated transcript 2 (CCAT2) involved in breast cancer.

Expression and correlation analysis of RegIV and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors.

The expression and correlation analysis of the regenerating gene family member 4 (RegIV) and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors were studied. Fifteen patients with metastatic spinal tumors who underwent operation in our hospital from January 2011 to January 2013 were selected into this study. The expression level of tumor tissues in patients with spinal metastasis and RegIV, VEGF-A and VEGF-C of the corresponding paracancer normal tissue samples were evaluated by immunohistochemical staining method and the correlation between the expression of RegIV, VEGF-A and VEGF-C was analyzed. qRT-PCR results showed that the expression of RegIV was increased (P<0.05) in paracancer normal tissues and spinal metastatic tumor tissues. Compared with normal tissues, expression of RegIV, VEGF-A and VEGF-C was higher in metastatic spinal tumor tissues and the difference had statistical difference (P<0.05). Spearman's correlation analysis showed that the expression of RegIV was positively correlated with VEGF-A (r=0.683, P<0.05); the expression of RegIV positively correlated with VEGF-C (r=0.717, P<0.05). Cox regression analysis showed that RegIV, VEGF-A, VEGF-C expression and microvessel density counts are prognostic factors affecting spine metastasis (P<0.05), RegIV expression affected the survival of patients with relative risk. The high expression of RegIV in spinal metastatic tumors may promote the expression of VEGF-A and VEGF-C to increase the microvascular density, promote angiogenesis, and accelerate the occurrence and progression of spinal metastatic tumors.

Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor.

A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.

Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis.

This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA).

Dynamic model of vascular-targeted photodynamic therapy.

Vascular-targeted photodynamic therapy has shown efficiency in treating port wine stains. A dynamic model that incorporates blood flow, kinetic diffusion, oxygen and photosensitizer consumption and reaction, and light modulation is proposed to reveal the interactions among light, photosensitizer, and oxygen. Simulation results show that pulse light modulation synchronized with heartbeats hold the advantage of increased singlet oxygen accumulation, higher oxygen concentration and lower temperature. Meanwhile, constant light treatment is advantageous in terms of higher temperature, lower total oxygen concentration and singlet oxygen accumulation. Therefore, the optimized treatment protocol may involve a balance among the phototoxicity, hypoxia, and photothermolysis.

Expression of YAP/TAZ in Keratocystic Odontogenic Tumors and Its Possible Association with Proliferative Behavior.

The aim of this study is to clarify whether YAP/TAZ is involved in the pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT). The expression levels of YAP/TAZ and downstream proteins and genes in normal oral mucosa (OM) and KCOT were determined and compared by immunohistochemistry and real-time quantitative PCR. The results showed that the expression of YAP/TAZ and downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are also upregulated in the KCOT. In addition, the results from Spearman rank correlation test revealed the close relationship between YAP/TAZ and Ki-67, which was further evidenced by double-labelling immunofluorescence that revealed a synchronous distribution for YAP/TAZ with Ki-67 in KCOT samples. All the data suggested YAP/TAZ might be involved in the proliferative behavior of KCOT.

Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors.

Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells.

Ampicillin-incorporated alginate-chitosan fibers from microfluidic spinning and for vitro release.

The fibrous drug-loading capability, degradation profile, drug release behavior and mechanical performance were found to be controlled by regulating the amount of IPA and chitosan, which delayed the degradable time-scale and improved the drug loading capacity. Six types of alginate fibers were spun by combining two distinct core flows with deionized water-based, ethanol-based and isopropyl alcohol-based sheath fluid, respectively. The as prepared fibers were analyzed and compared by the characterization of SEM, mass loss, ICP, FTIR, XRD, UV, mechanics performance testing and antibacterial activity tests. The results showed that fibers in the isopropyl alcohol with low polarity sheath flow exhibited higher-ordered structure. Also, incorporation of chitosan for the core stream strengthened the degree of crosslinking among the molecular chain, and thus made the fiber entrapped more drug of ampicillin molecular. The fibers, possessing superior mechanical properties, preferable drug loading capability, more prolonged drug release behavior and outstanding antibiotic activity, may offer a promising candidate for biomaterials, such as fibrous drug carrier and antibacterial sutures.

Small molecule p300/catenin antagonist enhances hematopoietic recovery after radiation.

There is currently no FDA approved therapeutic agent for ARS mitigation post radiation exposure. Here we report that the small molecule YH250, which specifically antagonizes p300/catenin interaction, stimulates hematopoiesis in lethally or sublethally irradiated mice. A single administration of YH250 24 hours post irradiation can significantly stimulate HSC proliferation, improve survival and accelerate peripheral blood count recovery. Our studies suggest that promotion of the expansion of the remaining HSC population via stimulation of symmetric non-differentiative proliferation is at least part of the mechanism of action.

Podocyte-specific soluble epoxide hydrolase deficiency in mice attenuates acute kidney injury.

Podocytes play an important role in maintaining glomerular function, and podocyte injury is a significant component in the pathogenesis of proteinuria. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose genetic deficiency and pharmacological inhibition have beneficial effects on renal function, but its role in podocytes remains unexplored. The objective of this study was to investigate the contribution of sEH in podocytes to lipopolysaccharide (LPS)-induced kidney injury. We report increased sEH transcript and protein expression in murine podocytes upon LPS challenge. To determine the function of sEH in podocytes in vivo we generated podocyte-specific sEH-deficient (pod-sEHKO) mice. Following LPS challenge, podocyte sEH-deficient mice exhibited lower kidney injury, proteinuria, and blood urea nitrogen concentrations than controls suggestive of preserved renal function. Also, renal mRNA and serum concentrations of inflammatory cytokines IL-6, IL-1β, and TNFα were significantly lower in LPS-treated pod-sEHKO than control mice. Moreover, podocyte sEH deficiency was associated with decreased LPS-induced NF-κB and MAPK activation and attenuated endoplasmic reticulum stress. Furthermore, the protective effects of podocyte sEH deficiency in vivo were recapitulated in E11 murine podocytes treated with a selective sEH pharmacological inhibitor. Altogether, these findings identify sEH in podocytes as a contributor to signaling events in acute renal injury and suggest that sEH inhibition may be of therapeutic value in proteinuria.

Structural insights into the binding of buckwheat glutaredoxin with GSH and regulation of its catalytic activity.

Glutaredoxins (Grxs) are ubiquitous thioltransferases and members of the thioredoxin (Trx) fold superfamily. They have multiple functions in cells including oxidative stress responses and cell signaling. A novel glutaredoxin from buckwheat (rbGrx) with higher catalytic activity was identified, cloned, and purified. The structures of glutathionylated rbGrx and an rbGrx mutant, in which cysteine 39 was mutated to alanine, were solved by x-ray diffraction at a resolution of 2.05Å and 2.29Å, respectively. In rbGrx, GSH (glutathione) is bound at the conserved GSH-binding site, and its structure shows that it has the potential to function as a scaffold protein for the assembly and delivery of GSH. The crystal structure shows that GSH does not bind to the C39A rbGrx mutant, and the C39A mutant had no catalytic activity, indicating that C39 is a key residue that is involved in both the binding of rbGrx to GSH and the regulation of its catalytic activity. The model showing the binding of GSH with rbGrx provides a basis for understanding its molecular function and its potential future applications in medicinal food science.

Hierarchy of stochastic Schrödinger equation towards the calculation of absorption and circular dichroism spectra.

A theoretically solid and numerically exact method is presented for the calculation of absorption and circular dichroism (CD) spectra of molecular aggregates immersed in a harmonic bath constituted as the combination of some prominent quantized vibrational modes and continuous overdamped Brownian oscillators. The feasibility and the validity of newly proposed method are affirmed in the analytical monomer spectra. To go beyond the independent local bath approximation, all the correlations of site energy fluctuations and excitonic coupling fluctuations are included in our strategy, and their influence on the absorption and CD spectra is investigated based on the Frenkel exciton model of homodimer. In the end, a good fit of the absorption and part of CD spectra for the entire B800-B850 ring in the light-harvesting complexes 2 of purple bacteria to the experimental data is given, and the simulation results suggest that the asymmetry in the 800 nm region of CD spectra is actually an indication of B800-B850 inter-ring coupling.

Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways.

Although the genetic contribution is under debate, biological studies in multiple mouse models have suggested that the Disrupted-in-Schizophrenia-1 (DISC1) protein may contribute to susceptibility to psychiatric disorders. In the present study, we took the advantages of Drosophila model to dissect molecular pathways that can be affected by DISC1 in the context of pathology-related phenotypes. We found that three pathways that include the homologs of Drosophila Dys, Trio, and Shot were downregulated by introducing a C-terminal truncated mutant DISC1. Consistently, these three molecules were downregulated in the induced pluripotent stem cell-derived forebrain neurons from the subjects carrying a frameshift deletion in DISC1 C-terminus. Importantly, the three pathways were underscored in the pathophysiology of psychiatric disorders in bioinformatics analysis. Taken together, our findings are in line with the polygenic theory of psychiatric disorders.

Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent anti-tumor agent that triggers apoptosis in cells from multiple types of carcinoma but not in normal cells. However, diverse mechanisms are associated with insensitivity to TRAIL in various cancers. TRAIL efficacy may be enhanced by combining TRAIL with a sensitizer. In this study, vernodalol, a sesquiterpene lactone, sensitized diffuse large B-cell lymphoma (DLBCL) cells to TRAIL-induced apoptosis. Vernodalol increased the expression of death receptor (DR) 5, and silencing of DR5 with a small interfering RNA (siRNA) reduced the effect of vernodalol on TRAIL-mediated apoptosis. Additionally, vernodalol up-regulated the expression of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), a transcription factor. Inhibition of CHOP with a siRNA diminished DR5 expression and vernodalol-induced sensitization to the TRAIL treatment. In addition, a c-Jun N-terminal kinase (JNK) inhibitor blocked the vernodalol-induced up-regulation of DR5, indicating that the effect depended on JNK activation. Furthermore, the down-regulation of induced myeloid leukaemia cell differentiation protein (Mcl-1) played an important role in vernodalol/TRAIL-induced apoptosis, as Mcl-1 overexpression prevented this apoptotic effect. Moreover, the vernodalol/TRAIL combination inhibited tumor growth in a xenograft model. Based on our results, vernodalol enhanced TRAIL-induced apoptosis by down-regulating Mcl-1 and up-regulating DR5, and the effects of DR5 depended on JNK activation and CHOP induction. Therefore, combining TRAIL with vernodalol, a naturally occurring agent, may represent a promising therapeutic approach for DLBCL.

Berberine displays antitumor activity in esophageal cancer cells in vitro.

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms.

Land scale biogeography of arsenic biotransformation genes in estuarine wetland.

As an analogue of phosphorus, arsenic (As) has a biogeochemical cycle coupled closely with other key elements on the Earth, such as iron, sulfate and phosphate. It has been documented that microbial genes associated with As biotransformation are widely present in As-rich environments. Nonetheless, their presence in natural environment with low As levels remains unclear. To address this issue, we investigated the abundance levels and diversities of aioA, arrA, arsC and arsM genes in estuarine sediments at low As levels across Southeastern China to uncover biogeographic patterns at a large spatial scale. Unexpectedly, genes involved in As biotransformation were characterized by high abundance and diversity. The functional microbial communities showed a significant decrease in similarity along the geographic distance, with higher turnover rates than taxonomic microbial communities based on the similarities of 16S rRNA genes. Further investigation with niche-based models showed that deterministic processes played primary roles in shaping both functional and taxonomic microbial communities. Temperature, pH, total nitrogen concentration, carbon/nitrogen ratio and ferric iron concentration rather than As content in these sediments were significantly linked to functional microbial communities, while sediment temperature and pH were linked to taxonomic microbial communities. We proposed several possible mechanisms to explain these results.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients.

To evaluate the treatment effects of recombinant human interleukin-12 (rhIL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.

Multiband selective absorbers made of 1D periodic Ag/SiO<sub>2</sub>/Ag core/shell coaxial cylinders horizontally lying on a planar substrate.

In this paper, we present a one-dimensional periodic microstructure for multiband selective absorbers of thermal radiation. The microstructure is made of Ag/SiO<sub>2</sub>/Ag core/shell coaxial cylinders horizontally lying on top of a SiO<sub>2</sub> dielectric spacer and an opaque silver substrate. The spectral-directional absorptivity of the proposed structure was numerically investigated with the finite element based Comsol Multiphysics software. Multiband selective absorption in the wavenumber range from 2500 to 20000 cm<sup>-1</sup> for TM-wave incidence was obtained. Physical mechanisms responsible for the multiband selective absorption were elucidated due to the resonance of magnetic polaritons in the SiO<sub>2</sub> spacer shell, excitation of surface plasmon polaritons at the SiO<sub>2</sub>/Ag interface, and the effect of Wood's anomaly. Furthermore, the effects of a silver core radius, spacer shell thickness, a confocal elliptical core/shell cylinder on the property of multiband absorption, and the absorptivity of the structure with one core/four shells coaxial cylinders were explored.

Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.

Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction that could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress, and impairment in synaptic transmission. However, both mutants showed more severe early motor dysfunction, dopaminergic neuronal loss, and higher hydrogen peroxide production compared with the risk variant. p.Thr61Ile (co-segregated in three independent PD families) displayed the most severe phenotype followed by p.Arg145Gln (present only in index patient). We treated the transgenic flies with Ebselen, a mitochondrial hydrogen peroxide scavenger compound; Ebselen appears to be more effective in ameliorating motor function in the mutant than the risk variant models. We provide the first in vivo evidence of the pathological effects associated with CHCHD2 mutations. There was a difference in the pathological and drug response effects between the pathogenic and the risk variants. Ebselen may be a useful neuroprotective drug for carriers of CHCHD2 mutations.