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Abstract Background It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. Method One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. Results There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. Conclusion The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Understanding the degradation mechanism of organic light-emitting diodes (OLED) is essential to improve device performance and stability. OLED failure, if not process-related, arises mostly from chemical instability. However, the challenges of sampling from nanoscale organic layers and interfaces with enough analytical information has hampered identification of degradation products and mechanisms. Here, we present a high-resolution diagnostic method of OLED degradation using an Orbitrap mass spectrometer equipped with a gas cluster ion beam to gently desorb nanometre levels of materials, providing unambiguous molecular information with 7-nm depth resolution. We chemically depth profile and analyse blue phosphorescent and thermally-activated delayed fluorescent (TADF) OLED devices at different degradation levels. For OLED devices with short operational lifetimes, dominant chemical degradation mainly relate to oxygen loss of molecules that occur at the interface between emission and electron transport layers (EML/ETL) where exciton distribution is maximised, confirmed by emission zone measurements. We also show approximately one order of magnitude increase in lifetime of devices with slightly modified host materials, which present minimal EML/ETL interfacial degradation and show the method can provide insight for future material and device architecture development., (© 2023. The Author(s).)

Understanding the precise effects of defects on the photophysical properties of quantum dots (QDs) is essential to their development with near-unity luminescence. Because of the complicated nature of defects in QDs, the origins and detailed roles of the defects still remain rarely understood. In this regard, we used detailed chemical analysis to investigate the effect of surface defects on the optical properties of InP/ZnSe/ZnS QDs by introducing shell defects through controlled trifluoroacetic acid (TFA) etching. TFA treatment on the InP/ZnSe/ZnS QDs partially removed the ZnS shell as well as ligands and reduced the quantum yield by generating energetically deep surface traps. The surface defects of QDs by TFA cause charged trap sites inducing an Auger recombination process with a rate of ca. 200 ps. Based on these results, we proposed possible trap-assisted non-radiative decay pathways between the band-edge state and surface deep traps in InP/ZnSe/ZnS QDs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The photoelectrochemical behavior of Rh cluster-deposited hematite (α-Fe 2 O 3 ) photoanodes (α-Fe 2 O 3 @Rh) was investigated. The interactions between Rh clusters and α-Fe 2 O 3 nanorods were elucidated both experimentally and computationally. A facile UV-assisted solution casting deposition method allowed the deposition of 2 nm Rh clusters on α-Fe 2 O 3 . The deposited Rh clusters effectively enhanced the photoelectrochemical performance of the α-Fe 2 O 3 photoanode, and electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis were applied to understand the working mechanism for the α-Fe 2 O 3 @Rh photoanodes. The results revealed a distinctive carrier transport mechanism for α-Fe 2 O 3 @Rh and increased carrier density, while the absorbance spectra remained unchanged. Furthermore, density functional theory (DFT) calculations of the oxygen evolution reaction (OER) mechanism corresponded well with the experimental results, indicating a reduced overpotential of the rate-determining step. In addition, DFT calculation models based on the X-ray diffraction (XRD) measurements and X-ray photoelectron spectroscopy (XPS) results provided precise water-splitting mechanisms for the fabricated α-Fe 2 O 3 and α-Fe 2 O 3 @Rh nanorods. Owing to enhanced carrier generation and hole transfer, the optimum α-Fe 2 O 3 @Rh3 sample showed 78% increased photocurrent density, reaching 1.12 mA/cm -2 at 1.23 V RHE compared to that of the pristine α-Fe 2 O 3 nanorods electrode.

In photocatalysis, metal-semiconductor hybrid structures have been proposed for ideal photocatalytic systems. In this study, we investigate the effect of morphology and surface nature of Pt cocatalysts on photocatalytic hydrogen evolution activity in Pt-tipped CdSe nanorods. Three distinct morphologies of Pt cocatalysts were synthesized and employed as visible light photocatalysts. The rough tips exhibit the highest activity, followed by the round and cubic tips. Kinetic investigations using transient absorption spectroscopy reveal that the cubic tips exhibit lower charge-separated states feasible for reacting with water and water reduction rates due to their defectless surface facets. In contrast, the rough tips show a similar charge-separation value but a two-fold higher surface reaction rate than the round tips, resulting in a significant enhancement of hydrogen evolution. These findings highlight the importance of rational design on metal cocatalysts in addition to the main semiconductor bodies for maximizing photocatalytic activities., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In this study, we demonstrate inverted PTB7:PC 71 BM polymer solar cells (PSCs) featuring a solution-processed s-MoO 3 hole transport layer (HTL) that can, after thermal aging at 85 °C, retain their initial power conversion efficiency (PCE) for at least 2200 h. The T 80 lifetimes of the PSCs incorporating the novel s-MoO 3 HTL were up to ten times greater than those currently reported for PTB7- or low-band-gap polymer:PCBM PSCs, the result of the inhibition of burn-in losses and long-term degradation under various heat-equivalent testing conditions. We used X-ray photoelectron spectroscopy (XPS) to study devices containing thermally deposited t-MoO 3 and s-MoO 3 HTLs and obtain a mechanistic understanding of how the robust HTL is formed and how it prevented the PSCs from undergoing thermal degradation. Heat tests revealed that the mechanisms of thermal inter-diffusion and interaction of various elements within active layer/HTL/Ag electrodes controlled by the s-MoO 3 HTL were dramatically different from those controlled by the t-MoO 3 HTL. The new prevention mechanism revealed here can provide the conceptual strategy for designing the buffer layer in the future. The PCEs of PSCs featuring s-MoO 3 HTLs, measured in damp-heat (65 °C/65% RH; 85 °C per air) and light soaking tests, confirmed their excellent stability. Such solution-processed MoO 3 HTLs appear to have great potential as replacements for commonly used t-MoO 3 HTLs.

Controlling the dimensional aspect of conductive coordination polymers is currently a key scientific interest. Herein, solution-based dimension control strategies are proposed for copper chloride thiourea (CuCl-TU) coordination polymers that enable centimeter-scale, 2D nanosheet formation for use as transparent electrodes. Despite the wide bandgap of CuCl-TU polymers (4.33 eV), through polaron-mediated electron transfer, the electrical conductivity of the 2D sheet at room temperature is able to reach 4.45 S cm -1 without intentional doping. This leads to a highly anisotropic electronic conductivity of up to the order of ≈10 3 differences, depending on the material orientation. Furthermore, by substituting alternative thiourea candidates, it is demonstrated that it is possible to predesign CuCl-TU structures with the desired functionality, stability, and porosity through dimensional control. These findings provide a blueprint to design next-generation transparent conducting materials that can operate at room temperature, thereby expanding their applicability to different fields., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Intramolecular charge transfer (ICT) plays a critical role in determining the photophysical properties of organic molecules, including their luminescence efficiencies. Twisted intramolecular charge transfer (TICT) is a process in which structural change accompanies ICT. Herein, we used time-resolved spectroscopy to study TICT in pyrene derivatives that are promising blue organic light emitting diode (OLED) emitter candidates; these derivatives show strong solvent-dependent charge-transfer (CT) behavior with unique fluorescence properties, increased fluorescence intensity in polar solvent. Slight structural changes that do not affect excited state dynamics were observed in nonpolar solvents, while polar solvents were found to affect excited state dynamics and CT characteristics, which affect their unusual fluorescence behavior. The TICT behavior of these pyrene derivatives can be modulated through structural modification. Our study provides valuable guidelines for the control of optical properties, including the luminescence efficiencies of OLED emitters that show TICT characteristics.

Sn is a promising candidate anode material with a high theoretical capacity (994 mAh/g). However, the drastic structural changes of Sn particles caused by their pulverization and aggregation during charge-discharge cycling reduce their capacity over time. To overcome this, a TiNi shape memory alloy (SMA) was introduced as a buffer matrix. Sn/TiNi SMA multilayer thin films were deposited on Cu foil using a DC magnetron sputtering system. When the TiNi alloy was employed at the bottom of a Sn thin film, it did not adequately buffer the volume changes and internal stress of Sn, and stress absorption was not evident. However, an electrode with an additional top layer of room-temperature-deposition TiNi (TiNi(RT)) lost capacity much more slowly than the Sn or Sn/TiNi electrodes, retaining 50% capacity up to 40 cycles. Moreover, the charge-transfer resistance decreased from 318.1 Ω after one cycle to 246.1 Ω after twenty. The improved cycle performance indicates that the TiNi(RT) and TiNi-alloy thin films overall held the Sn thin film. The structure was changed so that Li and Sn reacted well; the stress-absorption effect was observed in the TiNi SMA thin films.

Non-toxic InP-based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, compared to Cd-based quantum dots (QDs), for better device efficiency and long-term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state-of-the-art InP-based QD with near-unity luminescence. Here, it is shown that using time-resolved spectroscopic measurements of systematically size-controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band-edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band-edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP-based QDs., (© 2021 Wiley-VCH GmbH.)

We previously demonstrated that ibrutinib modulates LPS-induced neuroinflammation in vitro and in vivo, but its effects on the pathology of Alzheimer's disease (AD) and cognitive function have not been investigated. Here, we investigated the effects of ibrutinib in two mouse models of AD. In 5xFAD mice, ibrutinib injection significantly reduced Aβ plaque levels by promoting the non-amyloidogenic pathway of APP cleavage, decreased Aβ-induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin-dependent kinase-5 (p-CDK5). Importantly, tau-mediated neuroinflammation and tau phosphorylation were also alleviated by ibrutinib injection in PS19 mice. In 5xFAD mice, ibrutinib improved long-term memory and dendritic spine number, whereas in PS19 mice, ibrutinib did not alter short- and long-term memory but promoted dendritic spinogenesis. Interestingly, the induction of dendritic spinogenesis by ibrutinib was dependent on the phosphorylation of phosphoinositide 3-kinase (PI3K). Overall, our results suggest that ibrutinib modulates AD-associated pathology and cognitive function and may be a potential therapy for AD., (© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

We, for the first time, report the development of infrared (IR)-driven photoelectrochemical (PEC) cells using up-conversion glass-ceramics as substrates, which is different from the previous strategies of decorating photocatalysts with up-conversion (UC) rare earth-doped fluoride nanoparticles to utilize IR light. Our approach is more efficient since the use of UC glass-ceramics as substrates of photocatalysts could overcome the chemical instability of fluoride nanoparticles, the blockage of incident light, and the limited exposure of photocatalysts to liquid electrolytes. Oxyfluoride glass-ceramics bearing (Yb,Er)-doped YF 3 and (Yb,Tm)-doped YF 3 nanocrystals turned out to generate UC green and ultraviolet/blue emissions, respectively, under 980 nm illumination. High-density ZnO nanorods were grown on the up-conversion glass-ceramic substrates by the hydrothermal method and they were subsequently overcoated with CdSe nanocrystals to obtain CdSe/ZnO heterostructures by the chemical bath deposition method. CdSe nanoparticles were excited by both the UC UV emission from Tm and the visible emission from Er and Tm, while ZnO nanorods were excited mostly by the UC UV emission from Tm. Because of the difference in the UC emissions from Er and Tm, two distinct carrier transportations, sensitization and type-II cascade, occurred in the identical CdSe/ZnO heterostructures. Eventually, CdSe/ZnO fabricated on the glass-ceramics bearing (Yb,Tm)-doped YF 3 showed increased photocurrent density compared to that fabricated on the glass-ceramics bearing (Yb,Er)-doped YF 3 due to the charge separation activated by the type-II cascade structure.

Single-atom catalysts are heterogeneous catalysts with atomistically dispersed atoms acting as a catalytically active center, and have recently attracted much attention owing to the minimal use of noble metals. However, a scalable and inexpensive support that can stably anchor isolated atoms remains a challenge due to high surface energy. Here, copper-halide polymer nanowires with sub-nanometer pores are proposed as a versatile support for single-atom catalysts. The synthesis of the nanowires is straightforward and completed in a few minutes. Well-defined sub-nanometer pores and a large free volume of the nanowires are advantageous over any other support material. The nanowires can anchor various atomistically dispersed metal atoms into the sub-nanometer pores up to ≈3 at% via a simple solution process, and this value is at least twice as big as previously reported data. The hydrogen evolution reaction activity of -18.0 A mg Pt -1 at -0.2 V overpotential shows its potential for single-atom catalysts support., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cuprous selenide nanocrystals have hallmark attributes, especially tunable localized surface plasmon resonances (LSPRs) and super-ionic behavior. These attributes of cuprous selenide are now integrated with a one-dimensional morphology. Essentially, Cu 2 Se nanowires (NWs) of micrometer-scale lengths and about 10 nm diameter are prepared. The NWs exhibit a super-ionic phase that is stable at temperatures lower than in the bulk, owing to compressive lattice strain along the radial dimension of the NWs. The NWs can be switched between oxidized and reduced forms, which have contrasting phase transition and LSPR characteristics. This work thus makes available switchable, one-dimensional waveguides and ion-conducting channels., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

RARRES1, a retinoic acid regulated carboxypeptidase inhibitor associated with fatty acid metabolism, stem cell differentiation and tumorigenesis is among the most commonly methylated loci in multiple cancers but has no known mechanism of action. Here we show that RARRES1 interaction with cytoplasmic carboxypeptidase 2 (CCP2) inhibits tubulin deglutamylation, which in turn regulates the mitochondrial voltage dependent anion channel (VDAC1), mitochondrial membrane potential, AMPK activation, energy balance and metabolically reprograms cells and zebrafish to a more energetic and anabolic phenotype. Depletion of RARRES1 also increases expression of stem cell markers, promotes anoikis, anchorage independent growth and insensitivity to multiple apoptotic stimuli. As depletion of CCP2 or inhibition of VDAC1 reverses the effects of RARRES1 depletion on energy balance and cell survival we conclude that RARRES1 modulation of CCP2-modulated tubulin-mitochondrial VDAC1 interactions is a fundamental regulator of cancer and stem cell metabolism and survival., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest with the contents of this article.

Three types of graphitic carbon nitride (gCN) nanosheets were derived from direct thermal condensation of urea, melamine, and dicyandiamide, respectively. As the sample (uCN) synthesized from urea exhibited porous morphology and highest surface area among other gCN, anatase TiO₂ nanoparticles were then in-situ deposited on uCN via solvothermal process without further calcination. The resultant Ti/uCN_x samples remained with higher surface area and exhibited visible-light activity. The derived band structure of each sample also confirmed its ability to photoreduce CO₂. XPS results revealed surface compositions of each sample. Those functional groups governed adsorption of reactant, interfacial interaction, electron transfer rate, and consequently influenced the yield of products. Carbon monoxide and methanol were detected from LED-lamp illuminated samples under appropriate moisture content. Samples with higher ratio of terminal amine groups produced more CO. The presence of hydroxyl groups promoted the initial conversion of methanol. The obtained Ti/uCN_0.5 and Ti/uCN_1.5 samples exhibited better quantum efficiency toward CO₂ conversion and demonstrated stability to consistently produce CO under cycling photoreaction.

The role of Ahnak in obesity has been reported previously. Loss of Ahnak leads to decreased Bmp4/Smad1 signaling, resulting in the downregulation of adipocyte differentiation. However, the biological significance of Ahnak remains largely unknown. In this study, we demonstrate that Ahnak-mediated impaired adipogenesis results in decreased Bmpr1α transcriptional expression. To confirm this, Ahnak siRNA was used to knock-down Ahnak in C3H10T1/2 and primary stromal vascular fraction cells. Ahnak siRNA transfected cells showed suppression of Bmpr1α expression and decreased BMP4/ Bmpr1α signaling. The differential adipogenesis was further confirmed by knock-down of Bmpr1α in C3H10T1/2 cells, which resulted in reduced adipogenesis. Moreover, stable Ahnak knock-out C3H10T1/2 cells stably transfected with Ahnak CRISPR/Cas9 plasmid suppressed expression of Bmpr1α and prevented differentiation into adipocytes. Furthermore, we developed immortalized pre-adipocytes from wild-type or Ahnak Knock-out mice's stromal vascular fraction (SVF) to confirm the function of Ahnak in pre-adipocyte transition. Immortalized Ahnak knock-out SVF cells showed lower level of Bmpr1α expression, evidence by their impaired BMP4/Bmpr1α signaling. Upon adipogenic induction, immortalized Ahnak knock-out SVF cells exhibited a marked decrease in adipocyte differentiation compared with immortalized wild-type pre-adipocytes. Furthermore, over-expression of Bmpr1α restored the adipogenic activity of Ahnak knock-out C3H10T1/2 cells and immortalized Ahnak knock-out SVF cells. Our data reveal the missing link in Ahnak-mediated adipose tissue remodeling and suggest that precise regulation of Ahnak in adipose tissue might have a therapeutic advantage for metabolic disease treatment.

Aromaticity, the special energetic stability derived from cyclic [4 n + 2]π-conjugated electronic structures, has been the topic of intense interest in chemistry because it plays a critical role in rationalizing molecular stability, reactivity, and physical/chemical properties. Recently, the pioneering work by Colin Baird on aromaticity reversal, postulating that aromatic (antiaromatic) character in the ground state reverses to antiaromatic (aromatic) character in the lowest excited triplet state, has attracted much scientific attention. The completely reversed aromaticity in the excited state provides direct insight into understanding the photophysical/chemical properties of photoactive materials. In turn, the application of aromatic molecules to photoactive materials has led to numerous studies revealing this aromaticity reversal. However, most studies of excited-state aromaticity have been based on the theoretical point of view. The experimental evaluation of aromaticity in the excited state is still challenging and strenuous because the assessment of (anti)aromaticity with conventional magnetic, energetic, and geometric indices is difficult in the excited state, which practically restricts the extension and application of the concept of excited-state aromaticity. Time-resolved optical spectroscopies can provide a new and alternative avenue to evaluate excited-state aromaticity experimentally while observing changes in the molecular features in the excited states. Time-resolved optical spectroscopies take advantage of ultrafast laser pulses to achieve high time resolution, making them suitable for monitoring ultrafast changes in the excited states of molecular systems. This can provide valuable information for understanding the aromaticity reversal. This Account presents recent breakthroughs in the experimental assessment of excited-state aromaticity and the verification of aromaticity reversal with time-resolved optical spectroscopic measurements. To scrutinize this intriguing and challenging scientific issue, expanded porphyrins have been utilized as the ideal testing platform for investigating aromaticity because they show distinct aromatic and antiaromatic characters with aromaticity-specific spectroscopic features. Expanded porphyrins exhibit perfect aromatic and antiaromatic congener pairs having the same molecular framework but different numbers of π electrons, which facilitates the study of the pure effect of aromaticity by comparative analyses. On the basis of the characteristics of expanded porphyrins, time-resolved electronic and vibrational absorption spectroscopies capture the changes in electronic structure and molecular conformations driven by the change in aromaticity and provide clear evidence for aromaticity reversal in the excited states. The approaches described in this Account pave the way for the development of new and alternative experimental indices for the evaluation of excited-state aromaticity, which will enable overarching and fundamental comprehension of the role of (anti)aromaticity in the stability, dynamics, and reactivity in the excited states with possible implications for practical applications.

Despite tellurium being less abundant in the Earth's crust than gold, platinum, or rare-earth elements, the number of industrial applications of tellurium has rapidly increased in recent years. However, to date, many properties of tellurium and its associated compounds remain unknown. For example, formation mechanisms of many tellurium nanostructures synthesized so far have not yet been verified, and it is unclear why tellurium can readily transform to other compounds like silver telluride by simply mixing with solutions containing silver ions. This uncertainty appears to be due to previous misunderstandings about the tellurium structure. Here, a new approach to the tellurium structure via synthesized structures is proposed. It is found that the proposed approach applies not only to these structures but to all other tellurium nanostructures. Moreover, some unique tellurium nanostructures whose formation mechanism are, until now, unconfirmed can be explained., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

All-solution processed, high-performance wearable strain sensors are demonstrated using heterostructure nanocrystal (NC) solids. By incorporating insulating artificial atoms of CdSe quantum dot NCs into metallic artificial atoms of Au NC thin film matrix, metal-insulator heterostructures are designed. This hybrid structure results in a shift close to the percolation threshold, modifying the charge transport mechanism and enhancing sensitivity in accordance with the site percolation theory. The number of electrical pathways is also manipulated by creating nanocracks to further increase its sensitivity, inspired from the bond percolation theory. The combination of the two strategies achieves gauge factor up to 5045, the highest sensitivity recorded among NC-based strain gauges. These strain sensors show high reliability, durability, frequency stability, and negligible hysteresis. The fundamental charge transport behavior of these NC solids is investigated and the combined site and bond percolation theory is developed to illuminate the origin of their enhanced sensitivity. Finally, all NC-based and solution-processed strain gauge sensor arrays are fabricated, which effectively measure the motion of each finger joint, the pulse of heart rate, and the movement of vocal cords of human. This work provides a pathway for designing low-cost and high-performance electronic skin or wearable devices., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

For the concept of aromaticity, energetic quantification is crucial. However, this has been elusive for excited-state (Baird) aromaticity. Here we report our serendipitous discovery of two nonplanar thiophene-fused chiral [4n]annulenes Th4 COT Saddle and Th6 CDH Screw , which by computational analysis turned out to be a pair of molecules suitable for energetic quantification of Baird aromaticity. Their enantiomers were separable chromatographically but racemized thermally, enabling investigation of the ring inversion kinetics. In contrast to Th6 CDH Screw , which inverts through a nonplanar transition state, the inversion of Th4 COT Saddle , progressing through a planar transition state, was remarkably accelerated upon photoexcitation. As predicted by Baird's theory, the planar conformation of Th4 COT Saddle is stabilized in the photoexcited state, thereby enabling lower activation enthalpy than that in the ground state. The lowering of the activation enthalpy, i.e., the energetic impact of excited-state aromaticity, was quantified experimentally to be as high as 21-22 kcal mol -1 .Baird's rule applies to cyclic π-conjugated molecules in their excited state, yet a quantification of the involved energetics is elusive. Here, the authors show the ring inversion kinetics of two nonplanar and chiral [4n]annulenes to support Baird's rule from an energetic point of view.

We have investigated the aromaticity of singly twisted Möbius aromatic and doubly twisted Hückel antiaromatic bis(palladium(II)) [36]octaphyrins in the lowest triplet state (T 1 ) by spectroscopic measurements and quantum calculations. The T 1 state of the singly twisted Möbius [36]octaphyrin shows broad and weak absorption spectral features that are analogous to those of antiaromatic expanded porphyrins while the T 1 state of the doubly twisted Hückel [36]octaphyrin exhibits intense and distinct spectral features, indicating the aromatic nature. These results along with theoretical calculations support the hypothesis that the aromaticity is reversed in the T 1 state. Furthermore, we show that the degree of structural smoothness affects the aromaticity reversal in the T 1 state., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Modification of aromaticity is regarded as one of the most interesting and important research topics in the field of physical organic chemistry. Particularly, porphyrins and their analogues (porphyrinoids) are attractive molecules for exploring various types of aromaticity because most porphyrinoids exhibit circular conjugation pathways in their macrocyclic rings with various molecular structures. Aromaticity in porphyrinoids is significantly affected by structural modification, redox chemistry, NH tautomerization, and electronic states (singlet and triplet excited states). Conversely, aromaticity significantly affects the spectroscopic properties and chemical reactivities of porphyrinoids. In this context, considerable efforts have been devoted to understanding and controlling the aromaticity and antiaromaticity of porphyrinoids. Thus, a series of porphyrinoids are in the limelight, being expected to shed light on this field because they have some advantages to demonstrate the switching of aromaticity; it is possible to control the aromaticity by lowering the temperature, adding and removing the protons of expanded porphyrins, changing the chemical environment, and switching the electronic states (triplet and singlet excited states) by photoexcitation. In this regard, this Review describes the control of aromaticity in various expanded porphyrins from the spectroscopic point of view with assistance from theoretical calculations.

A series of dendritic multiporphyrin arrays (P Zn Tz-nP FB ; n = 2, 4, 8) comprising a triazole-bearing focal zinc porphyrin (P Zn ) with a different number of freebase porphyrin (P FB ) wings has been synthesized, and their photoinduced energy transfer process has been evaluated. UV/vis absorption, emission, and time-resolved fluorescence measurements indicated that efficient excitation energy transfer takes place from the focal P Zn to P FB wings in P Zn Tz-nP FB 's. The triazole-bearing P Zn effectively formed host-guest complexes with anionic species by means of axial coordination with the aid of multiple C-H hydrogen bonds. By addition of various anionic guests to P Zn Tz and P Zn Tz-nP FB 's, strong bathochromic shifts of P Zn absorption were observed, indicating the HOMO-LUMO gap (ΔE HOMO-LUMO ) of P Zn decreased by anion binding. Time-resolved fluorescence measurements revealed that the fluorescence emission predominantly takes place from P Zn in P Zn Tz-nP FB 's after the addition of CN - . This change was reversible because a treatment with a silver strip to remove CN - fully recovered the original energy transfer process from the focal P Zn to P FB wings.

The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs. Accordingly, we identified seven non-canonical functional site types, most of which are novel, in addition to four canonical site types, while also removing numerous false positives reported by previous studies. Extensive experimental validation and significantly elevated 3' UTR sequence conservation indicate that these non-canonical site types may have biologically relevant roles. Our expanded catalog of functional site types suggests that the gene regulatory network controlled by miRNAs may be far more complex than currently understood.

Complexation of novel multiply N-confused expanded calix[n]phyrins with boron difluoride afforded a new class of cyclic BODIPY (boron-dipyrromethene) arrays. The structures of circularly arranged BODIPY subunits linked in an N-confused fashion give rise to such photophysical properties unique to the macrocycles as redshifted emission wavelengths along with apparent large Stokes shifts, long emission lifetimes, and solid-state lasing. The DFT calculations support the size-dependent excited-state dynamics of the macrocycles., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aromaticity reversal in the lowest triplet state, or Baird's rule, has been postulated for the past few decades. Despite numerous theoretical works on aromaticity reversal, experimental study is still at a rudimentary stage. Herein, we investigate the aromaticity reversal in the lowest excited triplet state using a comparable set of [26]- and [28]hexaphyrins by femtosecond time-resolved infrared (IR) spectroscopy. Compared to the relatively simple IR spectra of [26]bis(rhodium) hexaphyrin (R26H), those of [28]bis(rhodium) hexaphyrin (R28H) show complex IR spectra the region for the stretching modes of conjugated rings. Whereas time-resolved IR spectra of R26H in the excited triplet state are dominated by excited state IR absorption peaks, while those of R28H largely show ground state IR bleaching peaks, reflecting the aromaticity reversal in the lowest triplet state. These contrasting IR spectral features serve as new experimental aromaticity indices for Baird's rule., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dramatic enhancements in the figure of merit have been obtained in bulk thermoelectric materials by doping, band engineering, and nanostructuring. Especially, in p-type thermoelectrics, high figure of merits near 2.0 have been reported in a few papers through the reduction in lattice thermal conductivity and the advancement in power factors. However, there exists no report on the n-type systems showing high figure of merits because of their intrinsically low Seebeck coefficients. Here, we demonstrate that a nanostructured bulk n-type thermoelectric material that was assembled by sintering spinodally decomposed lead chalcogenide nanoparticles having a composition of PbSe0.5Te0.5 reaches a high figure of merit of 1.85. The spinodally decomposed nanoparticles permit our thermoelectric material to have extremely low lattice thermal conductivity and a high power factor as a result of nanostructuring, electronic optimization, insertion of an impurity phase and phase change in local areas. We propose that this interesting concept would be one of the promising approaches that overcome limitation arising from the fact that most parameters in the figure of merit are closely correlated.

The synthesis and characterization of an, Nad(p)h: quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.

The aromaticity reversal in the lowest triplet state (T1 ) of a comparable set of Hückel/Möbius aromatic metalated expanded porphyrins was explored by optical spectroscopy and quantum calculations. In the absorption spectra, the T1 states of the Möbius aromatic species showed broad, weak, and ill-defined spectral features with small extinction coefficients, which is in line with typical antiaromatic expanded porphyrins. In combination with quantum calculations, these results indicate that the Möbius aromatic nature of the S0 state is reversed to Möbius antiaromaticity in the T1 state. This is the first experimental observation of aromaticity reversal in the T1 state of Möbius aromatic molecules., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects., Materials and Methods: Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated., Results: A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05)., Conclusion: Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.

The structural basis of allosteric signaling in G protein-coupled receptors (GPCRs) is important in guiding design of therapeutics and understanding phenotypic consequences of genetic variation. The Evolutionary Trace (ET) algorithm previously proved effective in redesigning receptors to mimic the ligand specificities of functionally distinct homologs. We now expand ET to consider mutual information, with validation in GPCR structure and dopamine D2 receptor (D2R) function. The new algorithm, called ET-MIp, identifies evolutionarily relevant patterns of amino acid covariations. The improved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functional interactions between residue pairs, particularly potency and efficacy of activation by dopamine. Remarkably, although most of the residue pairs chosen for mutagenesis are neither in the binding pocket nor in contact with each other, many exhibited functional interactions, implying at-a-distance coupling. The functional interaction between the coupled pairs correlated best with the evolutionary coupling potential derived from dopamine receptor sequences rather than with broader sets of GPCR sequences. These data suggest that the allosteric communication responsible for dopamine responses is resolved by ET-MIp and best discerned within a short evolutionary distance. Most double mutants restored dopamine response to wild-type levels, also suggesting that tight regulation of the response to dopamine drove the coevolution and intramolecular communications between coupled residues. Our approach provides a general tool to identify evolutionary covariation patterns in small sets of close sequence homologs and to translate them into functional linkages between residues.

We described a case of a 54-year-old male who presented with dizziness and dyspnea due to cardiac metastasis of leiomyosarcoma. Cardiac metastasis of leiomyosarcoma caused both bradyarrhythmia and tachyarrhythmia in the patient. He was treated with implantation of a permanent pacemaker for management of complete atrio-ventricular block and anti-arrhythmic drug that suppressed ventricular tachycardia successfully.

The switching phenomena of conformation with π-electronic network through deprotonation-protonation processes were investigated by employing a series of 5,20-bis(α-oligothienyl) substituted hexaphyrins(1.1.1.1.1.1). They showed significant changes in the absorption and emission spectra with deprotonation, and returned to the initial state with protonation. Through NMR measurements and single crystal X-ray diffraction analysis, we found that the 5,20-bis(α-oligothienyl) substituted hexaphyrins, which possess acyclic, helical electronic networks involving oligothienyl chains in dumbbell conformations (type-I) in a neutral form, underwent effective deprotonation upon treatment with tetrabutylammonium fluoride (TBAF) to generate the corresponding dianions, which display cyclic electronic networks with enhanced aromaticity in rectangular conformations (type-II). Our quantum calculation results provide an unambiguous description for the switchable conformation and π-conjugation, which revealed that a deprotonation-induced enhanced aromatic conjugation pathway is involved in the switchable π-electronic network.

Our recent study demonstrated that an amyloid-β binding molecule, BTA-EG4, increases dendritic spine number via Ras-mediated signaling. To potentially optimize the potency of the BTA compounds, we synthesized and evaluated an amyloid-β binding analog of BTA-EG4 with increased solubility in aqueous solution, BTA-EG6. We initially examined the effects of BTA-EG6 on dendritic spine formation and found that BTA-EG6-treated primary hippocampal neurons had significantly increased dendritic spine number compared to control treatment. In addition, BTA-EG6 significantly increased the surface level of AMPA receptors. Upon investigation into the molecular mechanism by which BTA-EG6 promotes dendritic spine formation, we found that BTA-EG6 may exert its effects on spinogenesis via RasGRF1-ERK signaling, with potential involvement of other spinogenesis-related proteins such as Cdc42 and CDK5. Taken together, our data suggest that BTA-EG6 boosts spine and synapse number, which may have a beneficial effect of enhancing neuronal and synaptic function in the normal healthy brain., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The accumulation of amyloid-β (Aβ) leads to the loss of dendritic spines and synapses, which is hypothesized to cause cognitive impairments in Alzheimer's disease (AD) patients. In our previous study, we demonstrated that a novel mercaptoacetamide-based class II histone deacetylase inhibitor (HDACI), known as W2, decreased Aβ levels and improved learning and memory in mice. However, the underlying mechanism of this effect is unknown., Objective: Because dendritic spine formation is associated with cognitive performance, here we investigated whether HDACI W2 regulates dendritic spine density and its molecular mechanism of action., Methods: To examine the effect of HDACI W2 on dendritic spine density, we conducted morphological analysis of dendritic spines using GFP transfection and Golgi staining. In addition, to determine the molecular mechanism of W2 effects on spines, we measured the levels of mRNAs and proteins involved in the Ras signaling pathway using quantitative real-time PCR, immunocytochemistry, and western analysis., Results: We found that HDACI W2 altered dendritic spine density and morphology in vitro and in vivo. Additionally, W2 increased the mRNA or protein levels of Ras GRF1 and phospho-ERK. Moreover, knockdown of RasGRF1 and inhibition of ERK activity prevented the W2-mediated spinogenesis in primary hippocampal neurons., Conclusion: Our Class II-selective HDACI W2 promotes the formation and growth of dendritic spines in a RasGRF1 and ERK dependent manner in primary hippocampal neurons.

Purpose: We described a technique to perform anterior synechiolysis with a healon needle and Viscoat® ophthalmic viscosurgical devices (OVDs) through anterior lamellar dissection in penetrating keratoplasty., Methods: OVDs were gently injected between iridocorneal adhesions with a healon needle to make a blunt dissection after anterior lamellar corneal dissection. Anterior synechiolysis at 360 degrees was completed with a healon needle and OVDs. Subsequently, the deep corneal lamella was cut with right and left Troutman-Katzin corneal scissors. 24 interrupted sutures were made with 10-0 nylon suture to implant the donor cornea., Results: In two eyes from two patients, with corneal opacity and nearly total anterior synechiae, clear grafts and relatively deep anterior chambers were achieved. Penetrating keratoplasty with anterior synechiolysis was thus successful with a healon needle and OVDs through lamellar dissection., Conclusions: Anterior synechiolysis with a healon needle and OVDs through lamellar dissection is a safe and efficient technique for keratoplasty in patients with corneal opacity with anterior synechiae.

A set of 5,15-biphenylene-bridged porphyrin wheels, namely, [n]cyclo-5,15-porphyrinylene-4,4'-biphenylenes [n]CPB, have been synthesized through the platination of 5,15-bis(4-(pinacolboranyl)phenyl) nickel(II) porphyrin and subsequent reductive elimination of Pt(II) (cod)-bridged cyclic porphyrin intermediates. The calculated strain energies for [3]CPB, [4]CPB, [5]CPB, and [6]CPB are 49.3, 32.9, 23.5, and 16.0 kcal mol(-1) , respectively. UV/Vis absorption spectra and cyclic voltammetry indicated characteristic ring-size-dependent absorption-peak shifts and redox-potential shifts, which presumably reflect the degree of strain in the π-systems. Excitation-energy hopping (EEH) times were determined to be 5.1, 8.0, 8.0, and 9.6 ps for [3]CPB, [4]CPB, [5]CPB, and [6]CPB, respectively, in a pump-power-dependent TA experiment., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Early detection of cancer cells in a rapid and sensitive approach is one of the great challenges in modern clinical cancer care. This study has demonstrated the first example of a rapid, selective, and sensitive phosphorescence probe based on phosphorescence energy transfer (PET) for cancer-associated human, Nad(p)h: quinone oxidoreductase isozyme 1 (NQO1). An efficient room-temperature phosphorescence NQO1 probe was constructed by using Mn-doped ZnS quantum dots (Mn:ZnS QDs) as donors and trimethylquinone propionic acids as acceptors. Phosphorescence quenching of Mn:ZnS QDs from the Mn:ZnS QDs to a covalently bonded quinone was achieved through PET. Phosphorescence of Mn:ZnS QDs was turned on by the rapid reduction-initiated removal of the quinone quencher by NQO1. This probe shows low cellular toxicity and can rapidly distinguish between NQO1-expressing and -nonexpressing cancer cell lines through phosphorescence imaging.

Azobenzene-bridged β-to-β and meso-to-meso porphyrin nanorings were successfully synthesized by a palladium-catalyzed Suzuki-Miyaura coupling reaction in a logical synthesis. The dimeric structure was confirmed by XRD analysis. The azo linkages in di- and tetramers are in the all-trans conformation, whereas in the trimers one azo linkage can be interconverted between cis and trans under external stimulation. When trimeric isomers are heated to 333 K or higher, the azo linkages will be in the all-trans configurations: the pure all-trans trimer can be kept in the dark for several months. Fluorescence anisotropy and pump-power-dependent decay results revealed excitation energy transfer for azobenzene-bridged zinc-porphyrin nanorings. The distances between porphyrin units of these azobenzene-bridged porphyrin arrays are almost the same, but the exciton energy hopping (EEH) times for each wheel are markedly different. The dimer and meso-to-meso tetramer possess relatively short excitation energy transfer (EET) times (1.28 and 2.48 ps, respectively) due to their good planarity and rigidity. In contrast, the EET time for the trimeric zinc(II)-porphyrin array (6.9 ps) is relatively long due to its nonradiative decay pathway (i.e., cis/trans isomerization of azobenzene). Both di- and tetramers exhibit relatively high fluorescence quantum yields, whereas the trimers show weak emission because of structural differences., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We have demonstrated aromaticity reversal in the singlet excited states of internally 1,3-phenylene-strapped [26]- and [28]hexaphyrins (P26H and P28H). P26H displays a broad and reduced singlet-excited-state absorption spectrum, whereas P28H exhibits a sharp and intense singlet-excited-state absorption spectrum; both are in contrast to the ground-state absorption spectra, strongly indicating aromaticity reversal in the singlet excited state. Furthermore, magnetic and topological indices of aromaticity such as nucleus-independent chemical shift and harmonic oscillator model of aromaticity values for P26H and P28H also suggest that their singlet excited states become antiaromatic and aromatic, respectively.

N-(p-Methoxycarbonylbenzyl) triazole (BTz) substituents have been introduced to Ni(II) porphyrins (NiPs), in which their modulated axial-coordination processes have been investigated. For this study, the two types of ligands, neutral pyridine versus anionic cyanide, were employed to investigate an effect of BTz substituents. The unique microenvironments given by the BTz substituents provided two different effects on the axial-coordination processes of NiPs on the ground and excited states: (1) steric shielding and (2) donation of hydrogen-bonding sites. The steric shielding diminished the binding affinity of pyridine, while the cooperation of hydrogen bonds extraordinarily strengthened the binding affinity of CN(-). Interestingly, it was observed that the binding of CN(-) with the supporting of BTz substituents accompanied nonplanar distortion of NiPs. Such conformational change perturbed the electronic structure of NiPs, which gave rise to the modulation of coordination processes of NiPs in the excited state. As a consequence, photoinudced ligand binding and releasing processes of four- and six-coordinated NiPs were changed into the dominant photoinduced ligand releasing process.

A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.