Lieb-Schultz-Mattis Theorem in Open Quantum Systems.

The Lieb-Schultz-Mattis (LSM) theorem provides a general constraint on quantum many-body systems and plays a significant role in the Haldane gap phenomena and topological phases of matter. Here, we extend the LSM theorem to open quantum systems and establish a general theorem that restricts the steady state and spectral gap of Liouvillians based solely on symmetry. Specifically, we demonstrate that the unique gapped steady state is prohibited when translation invariance and U(1) symmetry are simultaneously present for noninteger filling numbers. As an illustrative example, we find that no dissipative gap is open in the spin-1/2 dissipative Heisenberg model, while a dissipative gap can be open in the spin-1 counterpart-an analog of the Haldane gap phenomena in open quantum systems. Furthermore, we show that the LSM constraint manifests itself in a quantum anomaly of the dissipative form factor of Liouvillians. We also find the LSM constraints due to symmetry intrinsic to open quantum systems, such as Kubo-Martin-Schwinger symmetry. Our work leads to a unified understanding of phases and phenomena in open quantum systems.

The evaluation of photochemical behavior of antihistaminic drug triprolidine in an aqueous media.

Photodegradation is widely known as a changer of both the quality and the quantity of several chemical compounds. In this study, we sought to examine the photochemical behavior of triprolidine (TRP), which is a member of the first-generation antihistamine and utilized for a relief of an allergic conditions, in an aqueous media. There are no reports focused on its potential photoproducts and photodegradation pathways in detail to the best of our knowledge. TRP photodegradation induced by ultraviolet light (UV) irradiation was monitored utilizing high-performance liquid chromatography (HPLC), and structural elucidation of the TRP photoproduct was performed by electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and nuclear magnetic resonance (NMR). Finally, the mechanism of TRP photodegradation was speculated based on the identified photoproduct. TRP was photodegraded dependent on the irradiation time of UV in proportion to the generation of one TRP photoproduct (TRP-P). Structural determination by LC-ESI-MS/MS and NMR clarified that TRP-P was the geometrical isomer of TRP, which was formed by the cis-trans conversion of double bond. UV irradiation experiment for TRP-P revealed the conversion from it to TRP. It is clarified that cis-trans conversion between TRP and TRP-P is photo-equilibrium reaction and TRP-P is predominant under the condition as this experiment. Toxicological potencies of TRP and TRP-P might not be observed by ProTox-II in silico toxicity evaluation. This is the first study evaluating the photochemical behavior of TRP.

GABase and glutaminase inhibitory activities of herbal extracts and acylated flavonol monoglycosides isolated from the leaves of Laurus nobilis L.

This study was to compare GABase [a mixture of γ-aminobutyric acid (GABA) aminotransferase and succinic semialdehyde dehydrogenase] and glutaminase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three acylated flavonol monoglycosides from the selected extract of Laurus nobilis L. (laurel). On the basis of the NMR spectroscopic data and the ESI MS spectra together with the comparison with the literature values, three compounds were identified as kaempferol-3-O-(4″-E-p-coumaroyl)-α-l-rhamnopyranoside (1), kaempferol-3-O-(3″,4″-di-E-p-coumaroyl)-α-l-rhamnopyranoside (2) and kaempferol-3-O-(2″,4″-di-E-p-coumaroyl)-α-l-rhamnopyranoside (3), respectively. The IC50 values of GABase inhibitory activity of 1-3 and p-hydroxybenzaldehyde (HBA) as control were 0.24 mM, 0.14 mM, 0.12 mM and 0.43 mM, respectively. Additionally, the IC50 values of glutaminase inhibitory activity of 1-3 and 6-diazo-5-oxo-l-norleucine (DON) as control were 0.34 mM, 0.13 mM, 0.14 mM and 0.33 mM, respectively. The results suggest that the extract from laurel shows the strongest biological activities among 20 herbal extracts and three acylated flavonol monoglycosides may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting GABase and glutaminase. This is the first report on GABase and glutaminase inhibitory activities of 1-3.

Photodegradation profiling of nitrendipine: evaluation of active pharmaceutical ingredient, tablets and its altered forms.

Nitrendipine (NTR) is a dihydropyridine drug, which is well-known as a photodegradable pharmaceutical. However, the photochemical reaction of NTR has not been evaluated in detail from now. In this study, we perform the photodegradation profiling of NTR for the elucidation of its photochemical behavior. NTR amounts during ultraviolet light (UV) irradiation were monitored using high performance liquid chromatography (HPLC). NTR was photodegraded almost completely within 24 h along with the generation of some photoproducts. Structural determination of two NTR photoproducts were carried out by means of electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). Obtained results from this study clarified one novel NTR photoproduct, a nitroso pyridine analogue, in addition to a pyridine analogue. Furthermore, photodegradation pathway of NTR was speculated based on chemical structures of NTR photoproducts to clarify its photochemical behavior. It was proposed that a singlet oxygen molecule might withdraw two hydrogen radicals resulting in the form of a pyridine analogue, and the following reduction of its nitro group might produce a nitroso pyridine analogue. Finally, we evaluated the photostability of NTR tablets and its altered forms, indicating that the change of the dosage form led to a decrease of the photostability of NTR tablets. The obtained results will be helpful for the additional research to evaluate the effect of NTR photodegradation on its own biological activities.

Anisotropic Topological Anderson Transitions in Chiral Symmetry Classes.

We study quantum phase transitions of three-dimensional disordered systems in the chiral classes (AIII and BDI) with and without weak topological indices. We show that the systems with a nontrivial weak topological index universally exhibit an emergent thermodynamic phase where wave functions are delocalized along one spatial direction but exponentially localized in the other two spatial directions, which we call the quasilocalized phase. Our extensive numerical study clarifies that the critical exponent of the Anderson transition between the metallic and quasilocalized phases, as well as that between the quasilocalized and localized phases, are different from that with no weak topological index, signaling the new universality classes induced by topology. The quasilocalized phase and concomitant topological Anderson transition manifest themselves in the anisotropic transport phenomena of disordered weak topological insulators and nodal-line semimetals, which exhibit the metallic behavior in one direction but the insulating behavior in the other directions.

Extracellular and intracellular productions of lysophosphatidic acids and cyclic phosphatidic acids by lysophospholipase D from exogenously added lysophosphatidylcholines to cultured NRK52E cells.

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that is a notable biomarker of kidney injury. However, it is not clear how LPA is produced in renal cells. In this study, we explored LPA generation and its enzymatic pathway in a rat kidney-derived cell, NRK52E cells. Culturing of NRK52E cells with acyl lysophosphatidylcholine (acyl LPC), or lyso-platelet activating factor (lysoPAF, alkyl LPC) was resulted in increased extracellular level of choline, co-product with LPA by lysophospholipase D (lysoPLD). Their activities were enhanced by addition of calcium ions to the cell culture medium, but failed to be inhibited by S32826, an autotaxin (ATX)-specific inhibitor. Liquid chromatography-tandem mass spectrometric analysis revealed the small, but significant extracellular production of acyl LPA/cyclic phosphatidic acid (cPA) and alkyl LPA/cPA. The mRNA expression of glycerophosphodiesterase (GDE) 7 with lysoPLD activity was elevated in confluent NRK52E cells cultured over 3 days. GDE7 plasmid-transfection of NRK52E cells augmented both extracellular and intracellular productions of LPAs (acyl and alkyl) as well as extracellular productions of cPAs (acyl and alkyl) from exogenous LPCs (acyl and alkyl). These results suggest that intact NRK52E cells are able to produce choline and LPA/cPA from exogenous LPCs through the enzymatic action of GDE7 that is located on the plasma membranes and intracellular membranes.

Evaluation of photostability of azelnidipine tablets and structure determination of its photoproducts.

Photo-exposure has a crucial effect on the natures of photosensitive pharmaceuticals in addition to their contents in medicines through the photodegradation. Generated photoproducts might be more bioactive and contribute to the expression of adverse side effects. This study aimed to clarify the photochemical behavior of medicines of azelnidipine, which is a member of dihydropyridine antihypertensive drugs, by the evaluation of its photostability and the determination of chemical structures of generated photoproducts. Calblock® tablets and its altered forms (powders and suspensions) were UV-irradiated by a black light. Residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography. The chemical structures of two photoproducts were determined by electrospray ionization tandem mass spectrometry. API of Calblock® tablets was photodegraded with the generation of several photoproducts. Its photodegradability was more significant when Calblock® tablets were crushed or suspended. Structural determination revealed that two photoproducts were benzophenone and a pyridine derivative. It was speculated that these photoproducts were generated by the elimination of diphenyl methylene radical and additional chemical reaction including oxidation and hydrolysis. Azelnidipine was photosensitive and its photodegradation in Calblock® tablets was promoted by the change of the dosage form. This difference might be derived from the light emission efficiency. This study suggests that API contents of Calblock® tablets might decrease when tablets or its altered forms are exposed to sunlight irradiation with the generation of benzophenone, which is a toxicological potent.

Phospholipid analysis of two influenza A virus-infected cell lines differing in their viral replication kinetics.

Fluctuations in phospholipid composition in infected cells during influenza A virus replication were analyzed using two different susceptible host cell lines: H292 cells, exhibiting a rapid cytopathic effect, and A549 cells, exhibiting a retarded cytopathic effect. Microarray analysis demonstrated that A549 cells recognized influenza A virus invasion, expression of pathogen recognition genes was affected, and antiviral genes were activated. On the other hand, H292 cells did not display such an antiviral state, and in these cells, rapid virus amplification and a rapid cytopathic effect were observed. Levels of ceramide, diacylglycerol, and lysolipids were higher in virus-infected cells than in the corresponding mock-infected cells at the later stages of infection. The accumulation of these lipids in IAV-infected cells occurred together with viral replication. The relationship between the characteristic features of ceramide, diacylglycerol, and lysolipid in the plasma membrane, where enveloped viruses are released, and their role in viral envelope formation are discussed. Our results indicate that viral replication disturbs cellular lipid metabolism, with consequences for viral replication kinetics.

Structure Determination of Felodipine Photoproducts in UV-Irradiated Medicines Using ESI-LC/MS/MS.

Dihydropyridine drugs are well known as photodegradable pharmaceuticals. Herein, we evaluate the photostability of felodipine (FL) medicine (Splendil® (SPL) tablets) and its altered forms (powders and suspensions). FL is a type of dihydropyridine drug, but its photochemical behavior is unknown. FL contents after ultraviolet light (UV) irradiation for 24 h were monitored using high-performance liquid chromatography (HPLC). Values of the residual amounts of FL in UV-irradiated SPL powders and suspensions were 32.76 ± 4.88% and 0.79 ± 0.74%, respectively, with the generation of two photoproducts (FL photoproduct 1 and 2). To identify the chemical structures of these photoproducts, electrospray ionization liquid chromatography mass spectrometry (ESI-LC/MS/MS) analysis was performed. Based on their mass-to-charge ratio values and fragment patterns, it was proposed that FL photoproduct 1 was a pyridine derivative and FL photoproduct 2 was an FL dimer. Interestingly, generation rates of FL photoproduct 1 and 2 were dependent on the presence of the aqueous media. The photodimerization of FL was induced in UV-irradiated SPL suspensions. This is the first report evaluating the photostability of SPL tablets and its altered forms and estimating FL photoproducts induced by UV irradiation in the formulation of SPL.

Pentacyclic triterpene acids, rotungenic acid and barbinervic acid, from fresh leaves of Diospyros kaki Thunberg and their glutaminase inhibitory activities.

Glutaminase is an important target that is often over-expressed in neurodegenerative and lifestyle-related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Three compounds isolated from fresh leaves of Diospyros kaki Thunberg, ursolic acid (1), rotungenic acid (2) and barbinervic acid (3), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC50 values of 1-3 and 6-diazo-5-oxo-L-norleucine (DON) as control were 775, 13, 14, and 434 µM, respectively. Compounds 2 and 3 showed higher glutaminase inhibitory activities than DON. Compounds 2 and 3 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of 2 and 3.

Altered plasma levels of lysophospholipids in response to adrenalectomy of rats.

The aim of this study was to investigate effects of reduced stress hormone by adrenalectomy on rat plasma levels of lysophosphatidic acid (LPA) and other lysophospholipids. We measured activities of lysophospholipase D (lysoPLD) in plasma and lipid phosphate phosphatase (LPP) in blood by determining choline and inorganic phosphate, respectively. LPA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS) and lysophosphatodylglycerol were quantified by LC-MS/MS. In adrenalectomized rats, plasma levels of LPA, LPE, LPS and LPI, but not LPC, were increased. The increased level of LPA were due to decreased LPC level, increases plasma activity of lysoPLD toward LPC and decreased LPP activity toward LPA. Daily injections of deoxycoricosterone into rats selectively reversed increased level of LPS. Our results suggest enzymatic mechanism for increased plasma level of LPA, and indicate that the circulating levels of lysophospholipids including LPA in rats are differently affected by artificial suppression of release of adrenergic hormones.

Topological Field Theory of Non-Hermitian Systems.

Non-Hermiticity gives rise to unique topological phases without Hermitian analogs. However, the effective field theory has yet to be established. Here, we develop a field-theoretical description of the intrinsic non-Hermitian topological phases. Because of the dissipative and nonequilibrium nature of non-Hermiticity, our theory is formulated solely in terms of spatial degrees of freedom, which contrasts with the conventional theory defined in spacetime. Our theory provides a universal understanding of non-Hermitian topological phenomena such as the unidirectional transport in one dimension and the chiral magnetic skin effect in three dimensions. Furthermore, it systematically predicts new physics; we illustrate this by revealing transport phenomena and skin effects in two dimensions induced by a perpendicular spatial texture. From the field-theoretical perspective, the non-Hermitian skin effect, i.e., the anomalous localization due to non-Hermiticity, is shown to be a signature of an anomaly.

Nonunitary Scaling Theory of Non-Hermitian Localization.

Non-Hermiticity can destroy Anderson localization and lead to delocalization even in one dimension. However, a unified understanding of non-Hermitian delocalization has yet to be established. Here, we develop a scaling theory of localization in non-Hermitian systems. We reveal that non-Hermiticity introduces a new scale and breaks down the one-parameter scaling, which is the central assumption of the conventional scaling theory of localization. Instead, we identify the origin of unconventional non-Hermitian delocalization as the two-parameter scaling. Furthermore, we establish the threefold universality of non-Hermitian localization based on reciprocity; reciprocity forbids delocalization without internal degrees of freedom, whereas symplectic reciprocity results in a new type of symmetry-protected delocalization.

Photoprotective Effects of Selected Amino Acids on Naproxen Photodegradation in Aqueous Media.

It is important to develop a photostabilization strategy to ensure the quality of photosensitive compounds, including pharmaceuticals. This study focused on the protective effects of 20 amino acids on the photodegradation of naproxen (NX), a photosensitive pharmaceutical, to clarify the important nature of a good photostabilizer. Our previous report indicated the photodegradability of NX and the protective effects of some antioxidants on its photodegradation, therefore, this compound was used as a model compound. The degradation of NX in aqueous media during ultraviolet light (UV) irradiation and the protective effects of selected amino acids were monitored through high-performance liquid chromatography (HPLC), equipped with a reverse-phase column. Addition of cysteine, tryptophan, and tyrosine induced the significant suppression of NX photodegradation after UV irradiation for 3 h (residual amount of NX; 15.35%, 6.82%, and 15.64%, respectively). Evaluation of the antioxidative activity and UV absorption spectrum showed that cysteine suppressed NX degradation through its antioxidative ability, while tryptophan and tyrosine suppressed it through their UV filtering ability. Furthermore, three amino acids at higher concentrations (more than 100 µmol/L) showed more protective effects on NX photodegradation. For 10 mmol/L, residual amounts of NX with cysteine, tryptophan, and tyrosine were 58.51%, 69.34%, and 82.40%, respectively. These results showed the importance of both photoprotective potencies (antioxidative potency and UV filtering potency) and stability to UV irradiation for a good photostabilizer of photosensitive pharmaceuticals.

Identification of human glycerophosphodiesterase 3 as an ecto phospholipase C that converts the G protein-coupled receptor 55 agonist lysophosphatidylinositol to bioactive monoacylglycerols in cultured mammalian cells.

A family of glycerol-based lysolipid mediators comprises lysophosphatidic acid as a representative phospholipidic member but also a monoacylglycerol as a non-phosphorus-containing member. These critical lysolipid mediators are known to be produced from different lysophospholipids by actions of lysophospholipases C and D in mammals. Some members of the glycerophosphodiesterase (GDE) family have attracted recent attention due to their phospholipid-metabolizing activity. In this study, we found selective depletion of lysophosphatidylinositol among lysophospholipids in the culture medium of COS-7 cells transfected with a vector containing glycerophosphodiester phosphodiesterase 2 (GDPD2, GDE3). Thin-layer chromatography and liquid chromatography-tandem mass spectrometry of lipids extracted from GDE3-transfected COS-7 cells exposed to fluorescent analogs of phosphatidylinositol (PI) revealed that GDE3 acted as an ecto-type lysophospholipase C preferring endogenous lysophosphatidylinositol and PI having a long-chain acyl and a short-chain acyl group rather than endogenous PI and its fluorescent analog having two long chain acyl groups. In MC3T3-E1 cells cultured with an osteogenic or mitogenic medium, mRNA expression of GDE3 was increased by culturing in 10% fetal bovine serum for several days, concomitant with increased activity of ecto-lysophospholipase C, converting arachidonoyl-lysophosphatidylinositol, a physiological agonist of G protein-coupled receptor 55, to arachidonoylglycerol, a physiological agonist of cannabinoid receptors 1 and 2. We suggest that GDE3 acts as an ecto-lysophospholipase C, by switching signaling from lysophosphatidylinositol to that from arachidonoylglycerol in an opposite direction in mouse bone remodeling.

Topological Origin of Non-Hermitian Skin Effects.

A unique feature of non-Hermitian systems is the skin effect, which is the extreme sensitivity to the boundary conditions. Here, we reveal that the skin effect originates from intrinsic non-Hermitian topology. Such a topological origin not merely explains the universal feature of the known skin effect, but also leads to new types of the skin effects-symmetry-protected skin effects. In particular, we discover the Z_{2} skin effect protected by time-reversal symmetry. On the basis of topological classification, we also discuss possible other skin effects in arbitrary dimensions. Our work provides a unified understanding about the bulk-boundary correspondence and the skin effects in non-Hermitian systems.

Continuous Phase Transition without Gap Closing in Non-Hermitian Quantum Many-Body Systems.

Contrary to the conventional wisdom in Hermitian systems, a continuous quantum phase transition between gapped phases is shown to occur without closing the energy gap Δ in non-Hermitian quantum many-body systems. Here, the relevant length scale ξ≃v_{LR}/Δ diverges because of the breakdown of the Lieb-Robinson bound on the velocity (i.e., unboundedness of v_{LR}) rather than vanishing of the energy gap Δ. The susceptibility to a change in the system parameter exhibits a singularity due to nonorthogonality of eigenstates. As an illustrative example, we present an exactly solvable model by generalizing Kitaev's toric-code model to a non-Hermitian regime.

Observation of Critical Phenomena in Parity-Time-Symmetric Quantum Dynamics.

We experimentally simulate nonunitary quantum dynamics using a single-photon interferometric network and study the information flow between a parity-time- (PT-)symmetric non-Hermitian system and its environment. We observe oscillations of quantum-state distinguishability and complete information retrieval in the PT-symmetry-unbroken regime. We then characterize in detail critical phenomena of the information flow near the exceptional point separating the PT-unbroken and PT-broken regimes, and demonstrate power-law behavior in key quantities such as the distinguishability and the recurrence time. We also reveal how the critical phenomena are affected by symmetry and initial conditions. Finally, introducing an ancilla as an environment and probing quantum entanglement between the system and the environment, we confirm that the observed information retrieval is induced by a finite-dimensional entanglement partner in the environment. Our work constitutes the first experimental characterization of critical phenomena in PT-symmetric nonunitary quantum dynamics.

Non-Hermitian Many-Body Localization.

Many-body localization is shown to suppress the imaginary parts of complex eigenenergies for general non-Hermitian Hamiltonians having time-reversal symmetry. We demonstrate that a real-complex transition, which we conjecture occurs upon many-body localization, profoundly affects the dynamical stability of non-Hermitian interacting systems with asymmetric hopping that respects time-reversal symmetry. Moreover, the real-complex transition is shown to be absent in non-Hermitian many-body systems with gain and/or loss that breaks time-reversal symmetry, even though the many-body localization transition still persists.

Protective Effect of Selected Antioxidants on Naproxen Photodegradation in Aqueous Media.

A photostabilization strategy is an important aspect of quality assurance for photosensitive compounds. This study focused on the photoprotective effects of selected antioxidants including the effect of L-ascorbic acid (AA) on naproxen (NX) photodegradation in aqueous media. NX degradation during ultraviolet light (UV) irradiation and the protective effects of selected antioxidants were monitored by high-performance liquid chromatography (HPLC). The addition of AA induced the suppression of NX photodegradation, although the protective effect disappeared after AA was degraded completely. The results of the evaluations on the photoprotective effects on NX photodegradation and antioxidative activities of AA and other antioxidants showed that the protective effects of antioxidants are dependent on reducing power and photostability under UV irradiation. In this experiment, quercetin (QU) is the most effective antioxidant on account of the residual rate of QU after UV irradiation and the antioxidative activity in the potential antioxidant (PAO) test was significantly higher compared to other antioxidants following the higher protective effect on NX photodegradation.