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In this study, we clarify the liquid structure formed at the interface between LiCoO 2 (LCO), the cathode material of Li-ion batteries, and propylene carbonate (PC), which is used as a solvent in the electrolyte, on a molecular scale. We apply sparse modeling-based modal analysis to force spectroscopy data measured by frequency modulation atomic force microscopy (FM-AFM) and show that each component in the FM-AFM force curve, such as oscillatory solvation force, background, and noise, can be automatically decomposed. Moreover, by combining detailed force curve analysis with solid/liquid interface simulations based on first-principles calculation, we have identified that there are distinct damped vibrational modes in the force curves at the LCO/PC interface with a period of about 0.57 nm and those with shorter periods, which likely correspond to the solvation forces associated with bulk-state PC molecules and those with PC molecules in "lying down" orientations.

Triplet-triplet annihilation photon upconversion (TTA-UC) is attracting a great deal of attention as a viable approach to exploit unutilized wavelengths of light in solar-driven devices. Recently, ligand-protected metal nanoclusters have emerged as a compelling platform for serving as triplet sensitizers for TTA-UC. In this study, we developed an atomically precise, triplet-mediator ligand (TL)-protected metal nanocluster, Au 2 Cu 6 (S-Adm) 6 [P(DPA) 3 ] 2 ( Au 2 Cu 6 DPA ; S-Adm = 1-adamanthanethiolate, DPA = 9,10-diphenylanthracene). In Au 2 Cu 6 DPA , the excitation of the Au 2 Cu 6 core rapidly generates a metal-to-ligand charge transfer state, followed by the formation of the long-lived triplet state (approximately 150 μs) at a DPA site in the TL. By combining Au 2 Cu 6 DPA with a DPA annihilator, we achieved a red-to-blue upconversion quantum yield (Φ UCg ) of 20.7 ± 0.4% (50% max.) with a low threshold excitation intensity of 36 mW cm -2 at 640 nm. This quantum yield almost reaches the maximum limit achievable using a DPA annihilator and establishes a record-setting value, outperforming previously reported nanocrystal and nanocluster sensitizers. Furthermore, strong upconversion emission based on a pseudo-first-order TTA process was observed under 1 sun illumination, indicating that the Au 2 Cu 6 DPA sensitizer holds promise for applications in solar-energy-based systems.

5,5',6,6',7,7',8,8'-Octahydro-1,1'-bi-2-naphthol (hbNaph) is an axially chiral molecule consisting of a smaller π-electronic system than that for 1,1'-bi-2-naphthol (BINOL). The absorption and circular dichroism (CD) bands of hbNaph appear in a shorter wavelength region below 310 nm, compared to those of BINOL, and its fluorescence is in the invisible UV region. However, increasing the concentration of hbNaph in solution up to 0.1 M results in its absorption edge gradually extending to longer wavelength, with a shoulder around 330 nm, and finally increasing to about 450 nm. At the same time, blue fluorescence is clearly observed, as well as a new CD band with the sign of the Cotton signals reversed from those obtained for dilute solutions. These results suggest that, at high concentrations, hbNaph forms chiral aggregates, in which π-electrons are delocalized over multiple molecules. To further understand how molecular axial chirality is transformed to supramolecular chirality, we attempted to construct aggregate models by simulating CD spectra using a time-dependent density functional theory. The only reasonable model obtained was that involving the counterclockwise R -enantiomer forming a clockwise helix, while the clockwise S -enantiomer forms a counterclockwise helix. We conclude, however, that, for such helixes, the most plausible model is densely packed and forms when the dihedral angle between the two phenol rings of hbNaph is acute, at around 75°, which reproduces the aggregate-induced CD sign inversion.

The salinity tolerance and osmoadaptation strategies in four phylogenetically distant anammox species, Brocadia , Jettenia , Kuenenia , and Scalindua , were investigated by using highly enriched cell cultures. The first-emerged " Ca . Scalindua sp." showed optimum growth at 1.5-3% salinity and was tolerant to ∼10% salinity (a slight halophile). The second-emerged " Ca . Kuenenia stuttgartiensis" was tolerant to ∼6% salinity with optimum growth at 0.25-1.5% (a halotolerant). These early-emerged " Ca . Scalindua sp." and ″ Ca . K. stuttgartiensis" rapidly accumulated K + ions and simultaneously synthesized glutamate as a counterion. Subsequently, part of the glutamate was replaced by trehalose. In contrast, the late-emerged " Ca . B. sinica" and " Ca . J. caeni" were unable to accumulate sufficient amounts of K + ─glutamate and trehalose, resulting in a significant decrease in activity even at 1-2% salinity (nonhalophiles). In addition, the external addition of glutamate may increase anammox activity at high salinity. The species-dependent salinity tolerance and osmoadaptation strategies were consistent with the genetic potential required for the biosynthesis and transport of these osmolytes and the evolutionary history of anammox bacteria: Scalindua first emerged in marine environments and then Kuenenia and other two species gradually expanded their habitat to estuaries, freshwater, and terrestrial environments, while Brocadia and Jettenia likely lost their ability to accumulate K + ─glutamate.

Quartz is ubiquitous in subsurface formations. The crystal faces have different atomic arrangements. Knowledge of the molecular structures on the surface of quartz is key in many processes. Molecular dynamics simulations are conducted to investigate the atomic arrangement effect on the water film structure, ion adsorption, and wettability at three different α-quartz surfaces. The interfacial structures depend on the quartz surface. Intrasurface hydrogen bonding between surface silanols differs in the α-quartz surface. At the (0001) surface, the OH density is 9.58 nm -2 , consisting of Q 2 units with two hydroxyl groups per silicone atom. At the (101̅0)-β surface, the OH density is 7.54 nm -2 , consisting of Q 3 units with one hydroxyl group per silicone atom; there is significant intrasurface hydrogen bonding. At the (101̅0)-α surface, the OH density is 7.54 nm -2 (hydrogen toward surface) orientation. This orientation can be found at the (0001) and (101̅0)-β surfaces; it is related to the degree of ordering at the surface. The ordering at the (0001) and (101̅0)-β surfaces is higher than that at the (101̅0)-α surface. In aqueous systems with ions, cation adsorption is the most dominant at the (0001) surface due to the largest surface density of the intrasurface hydrogen bonding, providing interaction sites for cations to be adsorbed. We observe a pronounced decrease in water film thickness from the ions at the (0001) surface only, likely due to significant cation adsorption. In this work, we demonstrate that the hydrogen-bond network, which varies from the plane cut, affects the water film structure and ion adsorption. The contact is nearly zero despite the changes in the film thickness and molecular structure at the temperature of 318 K.Q 2 units; however, there is little intrasurface hydrogen bonding. The intrasurface hydrogen bonding results in the exposure of hydrogen-bond acceptors to the aqueous phase, causing water molecules to have an H-up (hydrogen toward surface) orientation. This orientation can be found at the (0001) and (101̅0)-β surfaces; it is related to the degree of ordering at the surface. The ordering at the (0001) and (101̅0)-β surfaces is higher than that at the (101̅0)-α surface. In aqueous systems with ions, cation adsorption is the most dominant at the (0001) surface due to the largest surface density of the intrasurface hydrogen bonding, providing interaction sites for cations to be adsorbed. We observe a pronounced decrease in water film thickness from the ions at the (0001) surface only, likely due to significant cation adsorption. In this work, we demonstrate that the hydrogen-bond network, which varies from the plane cut, affects the water film structure and ion adsorption. The contact is nearly zero despite the changes in the film thickness and molecular structure at the temperature of 318 K.

The solubilities of many substances are significantly affected by specific ions, as demonstrated by the Hofmeister series of proteins. Cellulose has a resistant fibrillar structure that hinders its swelling and dissolution. Certain inorganic salt solutions are effective swelling agents and solvents for cellulose. However, the precise effects of these ions on cellulose are not fully understood. In this study, we studied the intermediate structures of cellulose fibers during their swelling process in ZnCl 2 and LiBr solutions via in situ X-ray diffraction. Two swollen phases with characteristic morphologies were observed for both salt treatments. Only the surfaces of the fibers were swollen in ZnCl 2 , whereas the ions penetrated the fibers and formed complexes with cellulose while the morphology of the fibers was maintained in LiBr. Our findings clarify the reasons that ZnCl 2 has been used as an excellent swelling agent, whereas LiBr has been used as a good solvent for cellulose.

A marine cyanobacterial cyclic depsipeptide, coibamide A (CbA), inhibits the mammalian protein secretory pathway by blocking the Sec61 translocon, which is an emerging drug target for cancer and other chronic diseases. In our previous structure-activity relationship study of CbA, the macrolactone ester linker was replaced with alkyl/alkenyl surrogates to provide synthetically accessible macrocyclic scaffolds. To optimize the cellular bioactivity profile of CbA analogues, novel lysine mimetics having β- and ε-methyl groups have now been designed and synthesized by a stereoselective route. A significant increase in cytotoxicity was observed upon introduction of these two methyl groups, corresponding to the d-MeAla α-methyl and MeThr β-methyl of CbA. All synthetic products retained the ability to inhibit secretion of a model Sec61 substrate. Tandem evaluation of secretory function inhibition in living cells and cytotoxicity was an effective strategy to assess the impact of structural modifications to the linker for ring closure., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Photoresponsive materials are garnering attention because of their applications toward building a sustainable society. A recently developed fast-photoresponsive amphiphilic lophine dimer (3TEG-LPD) responds rapidly to light, making it a promising candidate for drug-delivery systems. In this study, the mechanism of structural changes induced by ultraviolet (UV) irradiation in 3TEG-LPD micelles in an aqueous solution was investigated via an in situ time-resolved small-angle neutron scattering (SANS) technique. Since subsecond resolution was necessary to observe the structural changes in the 3TEG-LPD micelles, stroboscopic SANS analysis was employed to obtain scattering profiles with a time width of 0.5 s. The structural parameters were quantitatively determined by performing a model-fitting analysis of the SANS results. The stroboscopic SANS results showed that upon UV irradiation, the axial ratio and pseudo-aggregation number of the 3TEG-LPD micelles increased by 1.8 and 1.6 times, respectively, whereas the number of water molecules per surfactant molecule decreased. This finding suggested that the change in the shape of the micelles from spherical to ellipsoidal shape was accompanied by dehydration. Under the present UV irradiation conditions, this structural change of the micelle occurred rapidly during the first 30 s after the start of UV irradiation. Each structural parameter recovered exponentially and reversibly during the recovery process after the cessation of UV irradiation. The changes in these parameters were analyzed in terms of kinetics by comparing them with the changes in the molecular structure. We found that the change of the micelles proceeds approximately twice as fast as the association of the molecule. Furthermore, from the perspective of the critical packing parameter consideration, the SANS analysis revealed that the UV-induced changes in 3TEG-LPD micelles are dominated by the enthalpy contribution. This finding is expected to be useful for developing new materials for various applications.

The development of efficient and stable oxygen-reducing electrodes is challenging but vital for the production of efficient electrochemical cells. Composite electrodes composed of mixed ionic-electronic conducting La 1- x Sr x Co 1- y Fe y O 3-δ and ionic conducting doped CeO 2 are considered promising components for solid oxide fuel cells. However, no consensus has been reached regarding the reasons of the good electrode performance, and inconsistent performance has been reported among various research groups. To mitigate the difficulties related to analyzing composite electrodes, this study applied three-terminal cathodic polarization to dense and nanoscale La 0.6 Sr 0.4 CoO 3-δ -Ce 0.8 Sm 0.2 O 1.9 (LSC-SDC) model electrodes. The critical factors determining the performance of the composite electrodes are the segregation of catalytic cobalt oxides to the electrolyte interfaces and the oxide-ion conducting paths provided by SDC. The addition of Co 3 O 4 to the LSC-SDC electrode resulted in reduced LSC decomposition; thus, the interfacial and electrode resistances were low and stable. In the Co 3 O 4 -added LSC-SDC electrode under cathodic polarization, Co 3 O 4 turned wurtzite-type CoO, which suggested that the Co 3 O 4 addition suppressed the decomposition of LSC and, thus, the cathodic bias was maintained from the electrode surface to electrode-electrolyte interface. This study shows that cobalt oxide segregation behavior must be considered when discussing the performance of composite electrodes. Furthermore, by controlling the segregation process, microstructure, and phase evolution, stable low-resistance composite oxygen-reducing electrodes can be fabricated.

The reason for the absence of superconductivity in Sr 2 IrO 4 was estimated by photoelectron spectra and photoelectron holograms. The analysis of the La photoelectron hologram concluded that La atoms are substituted to Sr sites. Two O 1s peaks were observed and were identified as the oxygens in the IrO 2 and SrO planes by photoelectron holography and density functional theory (DFT) calculations. In the Ir 4f spectrum of Sr 2 IrO 4 , an unexpected Ir 3+ peak was observed as much as 50% of all of the Ir. The photoelectron hologram of Ir 3+ showed a displacement of about 0.15 Å. This displacement is thought to be due to the oxygen vacancies in the IrO 2 plane. These oxygen vacancies and the associated local displacement of the atoms might inhibit superconductivity in spite of sufficient electron doping.

A detailed theoretical mechanistic investigation on the dynamic kinetic resolution of N-protected amino acid esters using phase-transfer catalysts is described. Semiautomatic exhaustive conformation search of transition state (TS)-like structures were carried out using the ConFinder program and the pseudo-TS conformational search (PTSCS) method. This conformational search method successfully provided reasonable TS structures for determining the stereoselectivity in the asymmetric base hydrolysis of hexafluoroisopropyl (HFIP) esters as well as the racemization mechanism. Furthermore, the independent gradient model (IGM) analysis of the TS structures suggested that the H-bonding interactions with the oxyanion hole and π-stacking interactions are the common important features of the proposed TS structures that determine the stereoselectivity.

Solvation structures formed by ions and solvent molecules at solid/electrolyte interfaces affect the energy storage performance of electrochemical devices, such as lithium-ion batteries. In this study, the molecular-scale solvation structures of an electrolyte, a solution of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in propylene carbonate (PC) at the electrolyte-mica interface, were measured using frequency-modulation atomic force microscopy (FM-AFM). The spacing of the characteristic force oscillation in the force versus distance curves increased with increasing ion concentration, suggesting an increase in the effective size of molecules at the interface. Molecular dynamics simulations showed that the effective size of molecular assemblies, namely, solvated ions formed at the interface, increased with increasing ion concentrations, which was consistent with the experimental results. Knowledge of molecular-scale structures of solid/electrolyte interfaces obtained by a combination of FM-AFM and molecular dynamics simulations is important in the design of electrolytes for future energy devices and in improving their properties.

Although valerenic acid (VA) is an important marker compound for quantitative assessment of Valeriana officinalis products, little is known about its potential effects on adipocytes. We investigated the effects of VA on adipocyte differentiation, adiponectin production, and glucose uptake using 3T3-L1 adipocytes. The results showed that VA promoted adipocyte differentiation and increased the gene expression of adipogenesis and glucose uptake-related proteins, including peroxisome proliferator-activated receptor gamma (PPARγ), cytosine-cytosine-adenosine-adenosine-thymidine enhancer binding protein alpha (C/EBPα), adiponectin, and glucose transporter 4 (GLUT4). Additionally, cell cultures treated with VA had elevated adiponectin secretion and glucose uptake. The PPARγ luciferase assay indicated VA as a partial agonist of PPARγ, while the analysis using its antagonist, GW9662, and a docking simulation between PPARγ and VA revealed the binding site of VA as likely adjacent to the Ω loop pocket of PPARγ. Taken together, these results demonstrate that VA acts as a PPARγ partial agonist to promote adipocyte differentiation, adiponectin production, and glucose uptake., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Mutual solubilities of hydrocarbon-CO 2 systems are important in a broad range of applications. Experimental data and theoretical understanding of phase behavior of large hydrocarbon molecules and CO 2 are limited. This is especially true in relation to the molecular structure of hydrocarbons when the carbon number exceeds 12. In this work, the continuous fractional component Gibbs ensemble Monte Carlo simulations are used to investigate mutual solubility of different alkane and CO 2 systems and the molecular structure. We investigate the mutual solubility of n -decane, n -hexadecane, n -eicosane, and the corresponding structural isomers in the CO 2 -rich and hydrocarbon-rich phase. The focus will be solubility of the heavy normal alkanes and their structural isomers in CO 2 . The simulation results are verified by comparing the experimental data when measurements are available. The simulation of phase behavior of the n -decane-CO 2 system agrees with the experiments. We also present simulation results of n -hexadecane-CO 2 and n -eicosane-CO 2 systems away from the critical region partly due to the finite size effect. We establish that solubility of the hydrocarbons in CO 2 is improved by change of the molecular structure in heavier alkanes. The enhanced solubility is limited in decane isomers, but the isomers of hexadecane and eicosane show 2- to 3-time solubility enhancement. The molecular dynamics simulations suggest that the improvement is from a higher coordination number of CO 2 for methyl (CH 3 ) rather than for methylene (CH 2 ) groups. This study sets the stage for molecular engineering and synthesis of hydrocarbons that are soluble in CO 2 not only by considering functionality but also by changing the molecular structure. The solubility enhancement is the first step in viscosification of CO 2 which broadens the use of CO 2 .

Nanoparticles are readily coated by proteins in biological systems. The protein layers on the nanoparticles, which are called the protein corona, influence the biological impacts of the nanoparticles, including internalization into cells and cytotoxicity. This study expands the scope of the nanoparticle's protein corona for exogenous artificial nanoparticles to that for exogenous proteinaceous nanoparticles. Specifically, this study addresses the formation of protein coronas on nanoscale human antibody aggregates with a radius of approximately 20-40 nm, where the antibody aggregates were induced by a pH shift from low to neutral pH. The size of the human immunoglobulin G (hIgG) aggregates grew to approximately 25 times the original size in the presence of human serum albumin (HSA). This size evolution was ascribed to the association of the hIgG aggregates, which was triggered by the formation of the hIgG aggregate's protein corona, i.e. , protein's protein corona, consisting of the adsorbed HSA molecules. Because hIgG aggregate association was significantly reduced by the addition of 30-150 mM NaCl, it was attributed to electrostatic attraction, which was supported by molecular dynamics (MD) simulations. Currently, the use of antibodies as biopharmaceuticals is concerning because of undesired immune responses caused by antibody aggregates that are typically generated by a pH shift during the antibody purification process. The present findings suggest that nanoscale antibody aggregates form protein coronas induced by HSA and the resulting nanoscale antibody-HSA complexes are stable in blood containing approximately 150 mM salt ions, at least in terms of the size evolution. Mechanistic insights into protein corona formation on nanoscale antibody aggregates are useful for understanding the unintentional biological impacts of antibody drugs.

Water structuring on the outer surface of protein molecules called the hydration shell is essential as well as the internal water structures for higher-order structuring of protein molecules and their biological activities in vivo . We now show the molecular-scale hydration structure measurements of native purple membrane patches composed of proton pump proteins by a noninvasive three-dimensional force mapping technique based on frequency modulation atomic force microscopy. We successfully resolved the ordered water molecules localized near the proton uptake channels on the cytoplasmic side of the individual bacteriorhodopsin proteins in the purple membrane. We demonstrate that the three-dimensional force mapping can be widely applicable for molecular-scale investigations of the solid-liquid interfaces of various soft nanomaterials.

The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CL pro ) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SARS-CoV-2 3CL pro . The most potent inhibitor YH-53 can strongly block the SARS-CoV-2 replication. X-ray structural analysis revealed that YH-53 establishes multiple hydrogen bond interactions with backbone amino acids and a covalent bond with the active site of 3CL pro . Further results from computational and experimental studies, including an in vitro absorption, distribution, metabolism, and excretion profile, in vivo pharmacokinetics, and metabolic analysis of YH-53 suggest that it has a high potential as a lead candidate to compete with COVID-19.

It is widely recognized that the toxicity of mercury (Hg) is attenuated by the simultaneous administration of selenium (Se) compounds in various organisms. In this study, we revealed the mechanisms underlying the antagonistic effect of sodium selenite (Na 2 SeO 3 ) on inorganic Hg (Hg 2+ ) toxicity in human hepatoma HepG2 cells. Observations by transmission electron microscopy indicated that HgSe (tiemannite) granules of up to 100 nm in diameter were accumulated in lysosomal-like structures in the cells. The HgSe granules were composed of a number of HgSe nanoparticles, each measuring less than 10 nm in diameter. No accumulation of HgSe nanoparticles in lysosomes was observed in the cells exposed to chemically synthesized HgSe nanoparticles. This suggests that intracellular HgSe nanoparticles were biologically generated from Na 2 SeO 3 and Hg 2+ ions transported into the cells and were not derived from HgSe nanoparticles formed in the extracellular fluid. Approximately 85% of biogenic HgSe remained in the cells at 72 h post culturing, indicating that biogenic HgSe was hardly excreted from the cells. Moreover, the cytotoxicity of Hg 2+ was ameliorated by the simultaneous exposure to Na 2 SeO 3 even before the formation of insoluble HgSe nanoparticles. Our data confirmed for the first time that HepG2 cells can circumvent the toxicity of Hg 2+ through the direct interaction of Hg 2+ with a reduced form of Se (selenide) to form HgSe nanoparticles via a Hg-Se soluble complex in the cells. Biogenic HgSe nanoparticles are considered the ultimate metabolite in the Hg detoxification process.

Parathyroid hormone-related protein (PTHrP), which is secreted from a tumor, contributes to the progression of cachexia, a condition that is observed in half of all cancer patients. Although drug clearance was reported to decrease in patients with cancer cachexia, the details have not been clarified. The present study reports on an investigation of whether PTHrP is involved in the alternation of drug metabolism in cases of cancer cachexia. Cancer cachexia model rats with elevated serum PTHrP levels showed a significant decrease in hepatic and intestinal CYP3A2 protein expression. When midazolam, a CYP3A substrate drug, was administered intravenously or orally to the cancer cachexia rats, its area under the curve (AUC) was increased by about 2 and 5 times, as compared to the control group. Accordingly, the bioavailability of midazolam was increased by about 3 times, thus enhancing its pharmacological effect. In vitro experiments using HepG2 cells and Caco-2 cells showed that the addition of serum from cancer cachexia rats or active PTHrP (1-34) to each cell resulted in a significant decrease in the expression of CYP3A4 mRNA. Treatment with a cell-permeable cAMP analog also resulted in a decreased CYP3A4 expression. Pretreatment with protein kinase A (PKA), protein kinase C (PKC), and nuclear factor-kappa B (NF-κB) inhibitors recovered the decrease in CYP3A4 expression that was induced by PTHrP (1-34). These results suggest that PTHrP suppresses CYP3A expression via the cAMP/PKA/PKC/NF-κB pathway. Therefore, it is likely that PTHrP would be involved in the changes in drug metabolism observed in cancer cachexia.

Excited-state symmetry breaking (ESB) has attracted much attention because it is often observed in symmetric multipolar chromophores designed as two-photon absorption/emission materials. Herein, we report an ensemble and single-molecule fluorescence imaging and spectroscopy investigation of ESB in hexakis[4-( p -dioctylaminostyryl)phenylethynyl]benzene( DB6 ), a two-photon absorber possessing a C 6 -symmetric π-D 6 structure (π = hexaethynylbenzene, D = ( p -dioctylaminostyryl)phenyl group) consisting of three equivalent D-π-D moieties. Ensemble and single-molecule measurements and theoretical calculations revealed that DB6 undergoes a photoabsorption process with two orthogonal transition dipole moments, whereas it fluoresces with a single transition dipole moment after one- or two-step ESB upon photoexcitation, depending on the environmental polarity. In nonpolar solvents and polymer films, one of the three D-π-D sites becomes planar, and the excited state is localized on this moiety: a [D δ+ -π δ- -D δ+ ]* quadrupolar state is formed. In polar solvents, the symmetry is further broken within the planarized D-π-D moiety, and the excited state is localized on one of the two D-π sites; i.e., a D-[π δ- -D δ+ ]* dipolar state is generated. Hence, DB6 can behave like a multichromophore with multiple emission sites in the molecule, which was demonstrated by stepwise photobleaching under photon antibunching conditions.

Genistein is a soy isoflavone and shows various physiological activities, such as affinities for estrogen receptors (ERs) and inhibitory effects on the epidermal growth factor receptor (EGFR) pathway. A previous study reported that genistein downregulates milk production ability in mammary epithelial cells (MECs) while decreasing the phosphorylation of STAT5. The ER and EGFR pathways indirectly regulate STAT5. In this study, the repressing mechanism of genistein against the phosphorylation of STAT5 was investigated using a culture model of mouse MECs with milk production ability. The results revealed that genistein did not influence the behavior of ERα and ERβ, whereas genistein immediately repressed the phosphorylation of ERK1/2. However, the decrease in phosphorylated STAT5 occurred independent of the phosphorylation of EGFR. Genistein repressed new phosphorylation of STAT5 by prolactin without influencing the phosphorylation of JAK2. In conclusion, this study indicates that genistein directly inhibits the phosphorylation of STAT5 in lactating MECs., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Two starburst-shaped organic chromophores, incorporating a hexaethynylbenzene core modified by five donor branches (D-branches) of ( p -dioctylaminostyryl)benzene and one acceptor/anchoring branch (A-branch) of either carboxylic acid-terminated phenylethynylbenzene ( SB-07 ) or cyanoacrylic acid-terminated diketopyrrolopyrrole (DPP)-thiophene ( SB-08 ), were synthesized and applied to dye-sensitized solar cells (DSSCs). In these chromophores, the common donor moiety, five ( p -dioctylaminostyryl)phenyl groups, exhibits excellent optical absorption in the visible region (molar absorption coefficient ε > 10 5 M -1 cm -1 below 500 nm). The A-branch of SB-07 does not possess strong electron-accepting properties; however, the A-branch of SB-08 , the DPP-thiophene moiety, serves as a strong electron acceptor site. Furthermore, the intramolecular charge-transfer (ICT) transition between the thiophene and DPP moieties extends the optical absorption range to the near-infrared region (∼800 nm). Optimized DSSC devices using SB-08 with coadsorption of chenodeoxycholic acid, in conjunction with iodide/triiodide-based electrolytes, exhibited incident photon-to-current conversion efficiency (IPCE) exceeding 70% in the 370-700 nm range and over 20% even at 800 nm, with a short-circuit photocurrent density ( J sc ) of 19.3 mA cm -2 and a power conversion efficiency (PCE) of 6.4% under AM 1.5G illumination (100 mW cm -2 ). These results are considerably better than those of SB-07 ( J sc = 7.0 mA cm -2 , PCE = 3.3%). The starburst-shaped architecture presented here can be used as a novel structural motif for metal-free organic sensitizers because it enables flexible modification of the multiple D-branches that enhance light-harvesting ability and the A-branch that serves as an excited electron transport pathway.

Tip-enhanced Raman spectroscopy (TERS) is a nano-optical approach to extract spatially resolved chemical information with nanometer precision. However, in the case of direct-illumination TERS, which is often employed in commercial TERS instruments, strong fluorescence or far-field Raman signals from the illuminated areas may be excited as a background. They may overwhelm the near-field TERS signal and dramatically decrease the near-field to far-field signal contrast of TERS spectra. It is still challenging for TERS to study the surface of fluorescent materials or a bulk sample that cannot be placed on an Au/Ag substrate. In this study, we developed an indirect-illumination TERS probe that allows a laser to be focused on a flat interface of a thin-film waveguide located far away from the region generating the TERS signal. Surface plasmon polaritons are generated stably on the waveguide and eventually accumulated at the tip apex, thereby producing a spatially and energetically confined hotspot to ensure stable and high-resolution TERS measurements with a low background. With this thin-film waveguide probe, TERS spectra with obvious contrast from a diamond plate can be acquired. Furthermore, the TERS technique based on this probe exhibits excellent TERS signal stability, a long lifetime, and good spatial resolution. This technique is expected to have commercial potential and enable further popularization and development of TERS technology as a powerful analytical method.

Cellulose is crystallized by plants and other organisms into fibrous nanocrystals. The mechanical properties of these nanofibers and the formation of helical superstructures with energy dissipating and adaptive optical properties depend on the ordering of polysaccharide chains within these nanocrystals, which is typically measured in bulk average. Direct measurement of the local polysaccharide chain arrangement has been elusive. In this study, we use the emerging technique of scanning electron diffraction to probe the packing of polysaccharide chains across cellulose nanofibers and to reveal local ordering of the chains in twisting sections of the nanofibers. We then use atomic force microscopy to shed light on the size dependence of the inherent driving force for cellulose nanofiber twisting. The direct measurement of crystalline twisted regions in cellulose nanofibers has important implications for understanding single-cellulose-fibril properties that influence the interactions between cellulose nanocrystals in dense assemblies. This understanding may enable cellulose extraction and separation processes to be tailored and optimized.

A hydrogel was prepared from a polysaccharide, enzymatically synthesized through a one-pot reaction in aqueous solution, and its properties as a functional material were evaluated. Enzymatic synthesis using glucosyltransferase K obtained from Streptococcus salivarius ATCC 25975 was performed with sucrose as a substrate. The synthetic product was unbranched linear (1 → 6)-α-d-glucan with a high molecular weight, M w : 1.0-3.0 × 10 5 . The synthesized (1 → 6)-α-d-glucan was insoluble in water and crystallized in a monoclinic unit cell, which is consistent with the hydrated form of dextran. Transparent and highly swellable (1 → 6)-α-d-glucan hydrogels were obtained by crosslinking with diglycidyl ethers. The hydrogels showed no syneresis and no volume change during compression, resulting in the retention of shape under repeated compression. The elastic moduli of these hydrogels (<60 kPa) are smaller than those of other polysaccharide-based hydrogels having the same solid contents. The oven-dried gels could be restored to the hydrogel state with the original transparency and a recovery ratio greater than 98%. The mechanism of water diffusion into the hydrogel was investigated using the kinetic equation of Peppas. The properties of the hydrogel are impressive relative to those of other polysaccharide-based hydrogels, suggesting its potential as a functional biomaterial., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

Understanding the sub-nanoscale solvation structures of ionic liquids is crucial for the development of innovative functional "devices" across numerous fields. We previously demonstrated the atomic-scale solvation measurements using an ultralow noise 3D frequency-modulation atomic force microscopy combined with molecular dynamics simulations. However, to facilitate practical applications, the molecular distribution on a heterosurface must be verified. Here, we unveil the local solvation structures on a heterogeneously charged phyllosilicate surface in an ionic liquid solution and pure liquid. By identifying adsorbed ion species from the molecular sizes and orientations, we experimentally demonstrate that anions and cations preferentially adsorbed onto the positive and negative surfaces exhibit different orientations and water miscibility. Moreover, we reveal that neutral intermediate regions are formed at the boundary region in ionic liquid media as well as a KCl solution. In the future, this technique will be essential for the evolution of ionic-liquid functional "devices".

Soy products contain abundant genistein and daidzein isoflavones. Orally ingested soy isoflavones are partially metabolized to isoflavan by enteric bacteria. Their levels in the blood increase after soy products are eaten. In this study, we investigated the influence of genistein, daidzein, and equol by intraperitoneal administration in lactating mice. Genistein decreased the secretion of α- and β-casein and downregulated the gene expression of Csn1 , Csn2 , Csn3 , and Wap while inactivating the signal transducer and activator of transcription 5 (STAT5) and ERK1/2. In contrast, equol increased Csn1 - 3 expression while inactivating STAT3. Daidzein did not show inhibitory effects on milk production. The effects of genistein and equol were also confirmed in lactating mammary epithelial cells (MECs), which were cultured in the presence of soy isoflavones and equol at physiological concentrations for 7 days. These findings indicate that genistein, daidzein, and equol influence milk production in MECs in vivo and in vitro in distinctly different ways.

Molecular-beam epitaxy (MBE) enables the stabilization of a nonequilibrium material phase, providing a powerful approach to the exploration of emergent phenomena in condensed-matter research. Here we demonstrate that one of the metallic two-dimensional (2D) materials, TaSe 2 , grown by MBE crystallizes into the pure 3 R phase with the self-intercalated Ta atoms, 3 R -Ta 1+ x Se 2 , which is thermodynamically metastable and does not exist in nature as a pure material phase. Interestingly, the thick-enough 3 R -Ta 1+ x Se 2 film exhibits a superconducting (SC) critical temperature ( T ) of 3.0 K, which is the highest among all of the polymorphs in TaSe c ) of 3.0 K, which is the highest among all of the polymorphs in TaSe 2 . Thickness-dependence measurements reveal that T c decreases with decreasing thickness, accompanied by the development of the charge-density wave phase. The 3 R -Ta 1+ x Se 2 films exhibit large in-plane upper critical fields ( H c2 ) in their SC states even in the thick-enough regime, most likely due to the suppression of the interlayer hopping associated with the unique 3 R stacking. Moreover, the temperature dependence of the in-plane H c2 evolves from linear to square-root behavior with decreasing thickness, indicating crossover behavior from anisotropic three-dimensional superconductivity to 2D superconductivity. Our results unveil intriguing SC properties of metastable 3 R -Ta 1+ x Se 2 distinct from those of thermodynamically stable 2 H -TaSe 2 , demonstrating the essential importance of the MBE-based approach to the exploration of novel quantum phenomena in 2D materials research.

Room-temperature ionic liquids are promising media for next-generation energy devices because of their various superior characteristics. Because device performance is often dictated by the solvation structures at the solid-liquid interfaces, particularly at the local reactive sites, their atomistic pictures are in great demand. However, there has been no experimental technique for their three-dimensional solvation structures. Here, we first demonstrate the measurement of the atomic-scale ionic liquids using a recently established ultralow-noise three-dimensional frequency-modulation atomic force microscopy technique supported by molecular dynamics simulations. We conducted the experiments in protic and aprotic aqueous solutions and reveal that the aprotic solvation structure exhibits the higher site specificity, which resolves atomic-scale surface charge distribution on mica because of the absence of the H-bonding network. Our methodology is also applicable to pure liquids and would be a breakthrough for expanding their future applications.

In materials science and crystallography, the true density is an important derived physical quantity of solids. Here we report the correlation of the true density of nanometer-wide fibrillar crystallites of cellulose with their purity, crystallinity, morphology, and surface functionality. In the single fibrils, all the cellulose molecules are uniaxiallly oriented. Thus, the true density indicates the molecular packing density in the single fibrils and is essential for the precise estimation of the volume fraction of cellulose in fibril-based composites or porous structures. We demonstrate that the true density of fibrillar crystallites of cellulose is approximately 1.60 g/cm 3 irrespective of the biological origins of the cellulose (wood, cotton, or a tunicate) and the crystallinity. The true density is in fact independent of the dimension of the crystallites and the atomic conformation of the uniaxially oriented but noncrystalline molecules at the crystallite surface. In the single fibrils, all the cellulose molecules are densely packed from the crystalline core to the noncrystalline outermost regions. The value of 1.60 g/cm 3 remains unchanged even when the fibrils are dispersed through the wet disintegration process of "nanocellulose" production. In contrast, tailoring the surface functionality of the fibrils by oxidation and/or adsorption results in a substantial change in the true density up to 1.8 g/cm 3 or down to 1.3 g/cm 3 . The true density of nanocellulose is indeed governed by the surface functionality and has a strong gradient in the fibril cross-sectional direction.

We report here the synthesis of human endothelin-2, a peptide of 21 amino acid residues with two disulfide bonds, based on the novel idea of a disulfide-driven cyclic peptide synthesis (DdCPS). This synthesis has two steps: (1) a one-pot solid-phase disulfide ligation of two different sulfur-containing peptide fragments using an Npys-Cl resin and (2) intramolecular cyclization of the disulfide peptide via amide bond formation using a thioester ligation. Human endothelin-2 was obtained in a total yield of 2.2% with two such DdCPS procedures and subsequent deprotection and HPLC purification. This strategy is the basis of a new solid-phase assisted practical synthesis of cyclic disulfide peptides.

Cr 2 Ge 2 Te 6 (CrGT) is a phase change material with higher resistivity in the crystalline phase than in the amorphous phase. CrGT exhibits an ultralow operation energy for amorphization. In this study, the origin of the increased resistance in crystalline CrGT compared to amorphous CrGT and the underlying phase change mechanism were investigated in terms of both local structural change and associated change in electronic state. The density of states at the Fermi level in crystalline CrGT decreased with increasing annealing temperature and became negligible upon annealing at 380 °C. Simultaneously, the Fermi level shifted from the vicinity of the valence band to the band gap center, leading to an increase in resistance. The phase change from amorphous to crystalline CrGT occurred through a metastable crystalline phase with a local structure similar to that of the amorphous phase. Cr nanoclusters were confirmed to exist in both the amorphous and crystalline phases. The presence of Cr nanoclusters induced Cr vacancies in the crystalline phase. These Cr vacancies generated hole carriers, leading to p-type conduction. Photoelectron spectroscopy of the Cr 2s core level clearly indicated a decrease in the fraction of Cr-Cr bonds and an increase in the fraction of Cr-Te bonds in crystalline CrGT upon annealing. Meanwhile, the coordination number of the Cr nanoclusters decreased as the number of Cr-Cr bonds was reduced. Together, these results imply that the origin of the increased resistance in crystalline CrGT is the filling of Cr vacancies by Cr atoms diffusing from Cr nanoclusters.

Pulse radiolysis is a powerful method for generating highly reduced or oxidized species and free radicals. Combined with fast time-resolved spectroscopic measurement, we can monitor the reactions of intermediate species on time scales ranging from picoseconds to seconds. The application of pulse radiolysis to water generates hydrated electrons (e aq - ) and specific radicals, rendering this technique useful for investigating a number of biological redox processes. The first pulse radiolysis redox investigations explored in this review involved intramolecular electron transfer processes in protein with multiple electron-accepting sites. Pulse radiolysis enabled direct monitoring of the internal electron transfer rates and the distribution of electrons within proteins. Structural information from X-ray data has allowed analysis of the rate constants and their activation parameters in relation to the mechanisms with current theoretical treatments. The second set of pulse radiolysis redox investigations explored here concerned the intermediates of enzyme reactions after redox reactions. Pulse radiolysis allowed the extremely rapid donation of electrons to a redox center in a protein. It makes it possible to observe the unstable intermediates after the reduction and the following subsequent steps. For example, the intermediates generated through the one-electron reduction of oxygenated hemoproteins, such as cytochrome P450 and nitric oxide synthase, were characterized. Interestingly, ligand exchange can occur upon the reduction of heme iron, in which different amino acid residues bind to heme in the ferrous and ferric states, respectively. We directly observed the ligand-switching intermediates of bacterial CooA, a CO sensor, and bacterial iron response regulator protein. These ligand exchange processes are physiologically important for regulating the electrode potential and effective formation of superoxide anion or HO • . The third set of pulse radiolysis redox investigations explored in this review concerns free-radical processes in biological systems. Free radicals are produced in cells and organisms in a variety of processes. The cell has developed special and very effective machinery for controlling and detoxifying reactive radicals. Radiation-generated radicals allow studies of the reactions between specific radicals and solutes, often revealing the mechanisms underlying the initial and subsequent reactions. The crucial contribution was made using pulse radiolysis techniques and knowledge of the identities, properties, and reactions of radicals. These radicals include superoxide (O 2 •- ), nitric monoxide (NO • ), ascorbate, urate, and protein radicals. This review focuses on the reactions of these radicals and their physiological functions.

The distribution of periodic patterns of materials with radial or bilateral symmetry is a universal natural design principle. Among the many biological forms, tubular shapes are a common motif in many organisms, and they are also important for bioimplants and soft robots. However, the simple design principle of strategic placement of 3D printed segments of swelling and nonswelling materials to achieve widely different functionalities is yet to be demonstrated. Here, we report the design, fabrication, and characterization of segmented 3D printed gel tubes composed of an active thermally responsive swelling gel (poly N-isopropylacrylamide) and a passive thermally nonresponsive gel (polyacrylamide). Using finite element simulations and experiments, we report a variety of shape changes including uniaxial elongation, radial expansion, bending, and gripping based on two gels. Actualization and characterization of thermally induced shape changes are of key importance to robotics and biomedical engineering. Our studies present rational approaches to engineer complex parameters with a high level of customization and tunability for additive manufacturing of dynamic gel structures.

Symmetric secondary amines were synthesized by the self-condensation of primary amines over a palladium-loaded titanium dioxide (Pd/TiO 2 ) photocatalyst. The reactions afforded a series of secondary amines in moderate to excellent isolated yields at ambient temperature (30 °C, in cyclopentyl methyl ether). Applicability for one-pot pharmaceutical synthesis was demonstrated by a photocatalytic reaction sequence of self-condensation of an amine followed by N-alkylation of the resulting secondary amine with an alcohol.

Soft-robotic devices such as polymeric microgrippers offer the possibility for pick and place of fragile biological cargo in hard-to-reach conduits with potential applications in drug delivery, minimally invasive surgery, and biomedical engineering. Previously, millimeter-sized self-folding thermomagnetically responsive soft grippers have been designed, fabricated, and utilized for pick-and-place applications but there is a concern that such devices could get lost or left behind after their utilization in practical clinical applications in the human body. Consequently, strategies need to be developed to ensure that these soft-robotic devices are biodegradable so that they would disintegrate if left behind in the body. In this paper, we describe the photopatterning of bilayer gels composed of a thermally responsive high-swelling poly(oligoethylene glycol methyl ether methacrylate ( M n = 500)-bis(2-methacryloyl)oxyethyl disulfide), P(OEGMA-DSDMA), and a low-swelling poly(acrylamide- N, N'-bis(acyloyl)cystamine) hydrogel, in the shape of untethered grippers. These grippers can change shape in response to thermal cues and open and close due to the temperature-induced swelling of the P(OEGMA-DSDMA) layer. We demonstrate that the grippers can be doped with magnetic nanoparticles so that they can be moved using magnetic fields or loaded with chemicals for potential applications as drug-eluting theragrippers. Importantly, they are also biodegradable at physiological body temperature (∼37 °C) on the basis of cleavage of disulfide bonds by reduction. This approach that combines thermoresponsive shape change, magnetic guidance, and biodegradability represents a significant advance to the safe implementation of untethered shape-changing biomedical devices and soft robots for medical and surgical applications.

Hydration structures play crucial roles in a wide variety of chemical and biological phenomena. However, the key factors that determine a hydration structure remain an open question. Most recent studies have focused on the electrostatic interactions between the surface charges and dipoles of water molecules, which are determined by the atomic/ionic species of the outermost solid surface, as the dominating factor. The number of studies on the correlation between the hydration structure and the atomic-scale surface corrugation has been limited. In this study, we investigated the hydration structures of alkanethiol self-assembled monolayers terminated with a hydroxyl group using frequency-modulated atomic force microscopy. We observed two molecular structures, namely, the (√3 × √3) R30° structure and the c(4 × 2) superlattice structure, and found that their hydration structures are different mainly because of the slight differences in their molecular arrangements. This result suggests that a slight difference in the molecular/atomic arrangements as well as the atomic/ionic species in the outermost solid surface strongly influences the local hydration structures.

The objective of this study was to investigate the concentration and chemical species of Zn, Cu, and P in the bulk soil and water-dispersible colloid (WDC) fraction collected from a field where swine manure (SM) compost has been continually applied for 23 years. A filtration and ultracentrifugation process was used to separate and collect WDC (20-1000 nm) from the soil. The continual application of SM increased soil P from 1.6 to 4.5 g kg -1 , Zn from 109 to 224 mg kg -1 , and Cu from 87 to 95 mg kg -1 for 23 years. The continual SM compost application also enhanced the formation of soil WDC in which Zn (215 mg kg -1 ) and Cu (62 mg kg -1 ) were highly accumulated and P (25 g kg -1 ) was greater than in the bulk soil. According to the result of X-ray absorption spectroscopy (XAS), the continual application of SM compost increased P associated with Fe hydroxides in the soil and WDC fraction. Iron K-edge XAS revealed the dominance of goethite and ferrihydrite in the WDC fraction, suggesting that P was bound to these (oxy)hydroxides. Copper K-edge XAS determined the dominance of Cu(II) associated with humus in the soil and WDC fraction. For Zn species in the SM-compost-applied soil, hopeite and Zn associated with humus were accumulated in the bulk soil, whereas Zn associated with humus was the primary species in the WDC fraction. Our study suggests that the formation of organic complexes in the WDC fraction could enhance the mobility of Zn and Cu as the repeated application of SM compost continues.

In condensed solids, triplet exciton migration and succeeding triplet-triplet annihilation (TTA) are major bottleneck processes for efficient photon upconversion (UC) using sunlight excitation. We theoretically investigated the reaction times of TTA and the triplet-triplet energy transfer (TTET) as the elementary processes of triplet exciton migration in organic crystals of two molecular species: 9,10-diphenylanthracene (DPA) and its double-strapped alkyl  derivative (C7-sDPA) as the models of a recently reported crystalline system of TTA-UC by Kamada et al. The reaction times calculated based on Marcus theory clarified that the dimensionality of TTET and synergetic effects of TTA and TTET are responsible for the high UC quantum yield as well as their triplet lifetimes.

Hydration structures at solid-liquid interfaces mediate between the atomic-level surface structures and macroscopic functionalities in various physical, chemical, and biological processes. Atomic-scale local hydration measurements have been enabled by ultralow noise three-dimensional (3D) frequency-modulation atomic force microscopy. However, for their application to complicated surface structures, e.g., biomolecular devices, understanding the relationship between the hydration and surface structures is necessary. Herein, we present a systematic study based on the concept of the structural dimensionality, which is crucial in various scientific fields. We performed 3D measurements and molecular dynamics simulations with silicate surfaces that allow for 0, 1, and 2 degrees of freedom to water molecules. Consequently, we found that the 3D hydration structures reflect the structural dimensions and the hydration contrasts decrease with increasing dimension due to the enlarged water self-diffusion coefficient and increased embedded hydration layers. Our results provide guidelines for the analysis of complicated hydration structures, which will be exploited in extensive fields.

β-1,2-Glucan is a polysaccharide produced mainly by some Gram-negative bacteria as a symbiosis and infectious factor. We recently identified endo-β-1,2-glucanase from Chitinophaga pinensis ( CpSGL) as an enzyme comprising a new family. Here, we report the characteristics and crystal structure of a CpSGL homologue from Parabacteroides distasonis, an intestinal bacterium (BDI&#95;3064 protein), which exhibits distinctive properties of known β-1,2-glucan-degrading enzymes. BDI&#95;3064 hydrolyzed linear β-1,2-glucan and β-1,2-glucooligosaccharides with degrees of polymerization (DPs) of ≥4 to produce sophorose specifically but did not hydrolyze cyclic β-1,2-glucan. This result indicates that BDI&#95;3064 is a new exo-type enzyme. BDI&#95;3064 also produced sophorose from β-1,2-glucooligosaccharide analogues that have a modified reducing end, indicating that BDI&#95;3064 acts on its substrates from the nonreducing end. The crystal structure showed that BDI&#95;3064 possesses additional N-terminal domains 1 and 2, unlike CpSGL. Superimposition of BDI&#95;3064 and CpSGL complexed with ligands showed that R93 in domain 1 overlapped subsite -3 in CpSGL. Docking analysis involving a β-1,2-glucooligosaccharide with DP4 showed that R93 completely blocks the nonreducing end of the docked β-1,2-glucooligosaccharide. This indicates that BDI&#95;3064 employs a distinct mechanism of recognition at the nonreducing end of substrates to act as an exo-type enzyme. Thus, we propose 2-β-d-glucooligosaccharide sophorohydrolase (nonreducing end) as a systematic name for BDI&#95;3064.

Fe(II)-coordinating hexapeptides containing three 2,2'-bipyridine moieties as side chains were designed and synthesized. A cyclic hexapeptide having three [(2,2'-bipyridin)-5-yl]-d-alanine (d-Bpa5) residues, in which d-Bpa5 and Gly are alternately arranged with 3-fold rotational symmetry, coordinated with Fe(II) to form a 1:1 octahedral Fe(II)-peptide complex with a single facial-Λ configuration of the metal-centered chirality. NMR spectroscopy and molecular dynamics simulations revealed that the Fe(II)-peptide complex has an apparent C 3 -symmetric conformations on the NMR time scale, while the peptide backbone is subject to dynamic conformational exchange between three asymmetric β/γ conformations and one C 3 -symmetric γ/γ/γ conformation. The semirigid cyclic hexapeptide preferentially arranged these conformations of the small octahedral Fe(II)-bipyridine complex, as well as the Ru(II) congener, to underpin the single configuration of the metal-centered chirality.

The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [ cyclo(-d-Tyr-l-Arg-l-MeArg-l-Nal(2)-l-Pro-)], for the development of highly active ACKR3 ligands. Notably, modification at the l-Pro position with a bulky hydrophobic side chain led to improved bioactivity toward ACKR3.

The field-induced antipolar-polar structural transition in an organic antiferroelectric 2-trifluoromethylnaphthimidazole crystal is investigated by performing synchrotron X-ray diffraction. The polarities of all of the hydrogen-bonded chains become parallel with each other in the presence of an external electric field. The switching is accompanied by a giant electrostriction, which provides 1 order of magnitude larger strain than the piezoelectric strain of the organic ferroelectrics: croconic acid and poly(vinylidene fluoride); however, it is comparable to those of typical commercial piezoelectric ceramics. The crystal structure analysis with electric field shows that the origin of the observed giant electrostriction can be attributed to the shear strain that emerges from the polarity switching of the hydrogen-bonded chains. The antipolar-polar structural transition in antiferroelectrics could be employed for the development of high-performance electrostrictive organic materials.

Nitric oxide synthase (NOS) is a cytochrome P450-type mono-oxygenase that catalyzes the oxidation of l-arginine (Arg) to nitric oxide (NO) through a reaction intermediate N-hydroxy-l-arginine (NHA). The mechanism underlying the reaction catalyzed by NOS from Deinococcus radiodurans was investigated using pulse radiolysis. Radiolytically generated hydrated electrons reduced the heme iron of NOS within 2 μs. Subsequently, ferrous heme reacted with O 2 to form a ferrous-dioxygen intermediate with a second-order rate constant of 2.8 × 10 8 M -1 s -1 . In the tetrahydrofolate (H 4 F)-bound enzyme, the ferrous-dioxygen intermediate was found to decay an another intermediate with a first-order rate constant of 2.2 × 10 3 s -1 . The spectrum of the intermediate featured an absorption maximum at 440 nm and an absorption minimum at 390 nm. In the absence of H 4 F, this step did not proceed, suggesting that H 4 F was reduced with the ferrous-dioxygen intermediate to form a second intermediate. The intermediate further converted to the original ferric form with a first-order rate constant of 4 s -1 . A similar intermediate could be detected after pulse radiolysis in the presence of NHA, although the intermediate decayed more slowly (0.5 s -1 ). These data suggested that a common catalytically active intermediate involved in the substrate oxidation of both Arg and NHA may be formed during catalysis. In addition, we investigated the solvent isotope effects on the kinetics of the intermediate after pulse radiolysis. Our experiments revealed dramatic kinetic solvent isotope effects on the conversion of the intermediate to the ferric form, of 10.5 and 2.5 for Arg and NHA, respectively, whereas the faster phases were not affected. These data suggest that the proton transfer in DrNOS is the rate-limiting reaction of the intermediate with the substrates.

The relative and absolute configurations of an oxygenated bisabolane natural product, isolated from Ligularia lankongensis, were determined by synthesis. All four possible stereoisomers and their tiglate analogues were synthesized from R-(-)-carvone, and their 1 H and 13 C NMR spectra were compared to establish the 6R,8S,10S configuration. The stereoselective synthesis of the natural product was also achieved, featuring Brown allylation, vanadium-catalyzed epoxidation, and the Mitsunobu reaction.

During lactation, mammary epithelial cells (MECs) form the blood-milk barrier by less-permeable tight junctions (TJs) to prevent the leakage of milk components. Phytoestrogens affect the proliferation, differentiation, and apoptosis of MECs. However, it remains unclear whether phytoestrogens are involved in the blood-milk barrier. Therefore, we investigated the influence of phytoestrogens (coumestrol, genistein, and daidzein) by using an in vitro mouse-MEC-culture model. The results showed that coumestrol and genistein changed the expression of TJ proteins (claudins-3 and -4 and occludin), weakened barrier function, and reduced β-casein production. Daidzein also weakened barrier function without inhibiting β-casein production. Additionally, coumestrol and genistein induced apoptosis in MECs. These results indicate that phytoestrogens weaken the blood-milk barrier by directly affecting TJs and the cellular viability of lactating MECs in different ways.

Fluorination of resist materials is an effective method used to enhance the energy deposition of extreme ultraviolet (EUV) light in the fabrication of next-generation semiconductor devices. The dynamics of radical ions are important to understand when considering the radiation-chemistry of the resist materials using EUV and electron beam lithography. Here, the dynamics of the radical anions and cations of benzenes with one or two 2-hydroxyhexafluoroisopropyl groups (HFABs) were studied using radiolysis techniques. The formation of dimer radical cations was observed only in the monosubstituted benzene solutions of 1,2-dichloroethane. If the compound contained more than two substituents, it was found to hinder the necessary π-π overlapping. Pulse radiolysis of HFABs in tetrahydrofuran showed a characteristic spectral shift of the radical anion within the region of several hundred nanoseconds. From the results of low-temperature spectroscopy and density functional calculations, it is suggested that excess electrons of the 2-hydroxyhexafluoroisopropyl group of the radical anions cause dissociation into neutral radicals.

The catalytic performance of Ru-NAD-type complexes [Ru(tpy)(pbn)(CO)] 2+ ([1] 2+ ; tpy = 2,2';6',2″-terpyridine; pbn = 2-(pyridin-2-yl)benzo[b][1,5]naphthyridine) and the Ru-CO-bridged metallacycle [2] + was investigated in the context of the electrochemical reduction of CO 2 in H 2 O/CH 3 CN at room temperature. A controlled-potential electrolysis of [1] 2+ and [2] + afforded formate (HCOO - ) as the main product, under concomitant formation of minor amounts of CO and H 2 . Metallacycle [2] + showed a higher selectivity toward the formation of HCOO - than [1] 2+ (HCOO - /CO for [1] 2+ , 2.7; HCOO - /CO for [2] + , 7). The generation of HCOO - via a catalytic hydride transfer from the NADH-type ligands of [1] 2+ and [2] + to CO 2 was supported by the experimental results and a comparison with the reduction of CO 2 catalyzed by [Ru(tpy)(bpy)(CO)] 2+ under similar conditions. A mechanism for the catalytic reduction of CO 2 by [1] 2+ and [2] + was proposed based on the experimental evidence. The thus-obtained results may help to expand the field of NADH-assisted reduction reactions.

3-Methylene-4-amido-1,2-diazetidine (MADA) was prepared for the first time via formal [2 + 2] cycloaddition of an allenamide and an azodicarboxylate. MADA worked as a formal 1,4-dipole precursor toward nucleophilic addition with various silyl enol ethers and allyltrimethylsilanes.