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Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA., Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis., Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively)., Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories., (© 2016 American Academy of Neurology.)

Recent work has suggested that hawk moths share pheromone components but are sexually separated by qualitative and quantitative differences in their pheromone blends. During field assays on the sex pheromones of other species, a diurnal hawk moth, Neogurelca himachala sangaica (Lepidoptera: Sphingidae), was frequently captured, but the composition of the sex pheromone of this species was not known. Analysis of hexane extracts of the pheromone glands of calling female by gas chromatography (GC) using an electroantennographic detector (EAD) revealed two components that elicited EAD responses from male moth antennae. These components were identified by their mass spectra and retention indices on two GC columns as (10E,12Z)-10,12-hexadecadienal (E10,Z12-16:Ald) and a trace of its (10E,12E)-isomer (E10,E12-16:Ald) in 98:2 ratio. In field experiments, E10,Z12-16:Ald alone attracted male moths, and addition of E10,E12-16:Ald significantly reduced the attractiveness, even at the naturally-occurring ratio. Analysis of the data using a generalized linear mixed model showed that E10,Z12-16:Ald positively contributed to attractiveness, whereas E10,E12-16:Ald did so negatively, and it was concluded that the sex pheromone of N. himachala sangaica consists solely of E10,Z12-16:Ald, bombykal. The negative effect of E10,E12-16:Ald on attractiveness could promote the species-specificity of this single-component pheromone system.

Background: Few studies have examined the prevalence of peripheral arterial disease (PAD) with the use of computed tomography angiography (CTA) in patients with acute ischemic stroke (AIS), although several reports have examined its prevalence using an ankle brachial index (ABI). We aimed to determine the prevalence of PAD indicated by CTA in patients with AIS and to clarify the prevalence of PAD in each clinical ischemic stroke subtype., Methods: We included 199 consecutive patients with AIS admitted to our hospital and divided them into PAD and non-PAD groups according to the CTA findings., Results: Of the 199 patients, 40 (20.1%) had PAD; 27 (67.5%) of the PAD patients were asymptomatic. The prevalence of abnormal ABI (≤.9) was 12.2%. Patients with PAD were older (78.3 ± 10.2 versus 71.5 ± 10.9, P <.001) and had a significantly lower ABI value (.89 ± .24 versus 1.15 ± .09, P <.001) and higher prevalence of diabetes mellitus (50.0% versus 31.4%, P = .028), atrial fibrillation (40.0% versus 16.4%, P = .001), coronary artery disease (32.5% versus 8.2%, P <.001), and intracranial arterial stenosis (47.5% versus 28.9%, P = .025) than patients without PAD. The prevalence of cerebral microbleeds was not different between patients with PAD and those without PAD (25.6% versus 25.4%, P = .985). The prevalence of PAD among ischemic stroke subtypes was highest in patients with cardioembolic infarction (40.5%)., Conclusions: Almost one fourth of the AIS patients examined had PAD on CTA. Cardioembolic infarction patients showed the highest prevalence of PAD among the clinical ischemic subtypes, suggesting the coexistence of atheromatous diseases and atrial fibrillation., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Metallothionein (MT) plays a central role in cellular defense against heavy metals and oxidative stress. Since the induction of MT requires the activation of metal response element (MRE)-binding transcription factor-1 (MTF-1) by binding of zinc ions, inorganic zinc is regarded as a typical MT inducer. However, in a previous report, we showed that inorganic zinc could not induce MT in vascular endothelial cells. While it is suggested that endothelial MT presents mechanisms different from those of other cell types, these remain unclear. In this study, we investigated whether the induction of endothelial MT expression involves the Nrf2-ARE pathway using copper(II) bis(diethyldithiocarbamate), termed Cu10, using a culture system of bovine aortic endothelial cells. Cu10 induced MT-1/2 protein expression and increased the expression of mRNAs for MT-1A, MT-1E, and MT-2, MT isoforms expressed in the cells. Cu10 activated not only the MTF-1-MRE, but also the Nrf2-ARE pathway. MTF-1 knockdown resulted in the repression of Cu10-induced MT-1 and -2 expression. Cu10-induced MT-1 expression was down-regulated by Nrf2 knockdown. However, MT-2 expression was not affected by Nrf2 knockdown. These results suggest that the expression of endothelial MT is up-regulated by the Nrf2-ARE pathway as well as by the MTF-1-MRE pathway. Moreover, MT-1 regulation mechanisms differ from that of MT-2. Specifically, the present data support the hypothesis that MT-1 participates in the biological defense system, while MT-2 mainly regulates intracellular zinc metabolism.

The interest in organic-inorganic hybrid molecules as molecular probes for biological systems has been growing rapidly. Such hybrid molecules exhibit unique biological activities. Herein, copper(II) bis(diethyldithiocarbamate) (Cu10) was found to activate the transcription factor NF-E2-related factor 2 (Nrf2), which is responsible for regulating antioxidant and phase II xenobiotic enzymes, in vascular endothelial cells. The copper complex rapidly accumulated within cells and induced nuclear translocation of Nrf2, leading to upregulation of the expression of downstream proteins without cytotoxic effects. However, while copper bis(2-hydroxyethyl)dithiocarbamate activated Nrf2, copper ion, diethyldithiocarbamate ligand with or without zinc or iron failed to exhibit this activity. Intracellular accumulation of Cu10 was higher than that of Cu(II) and Cu(I). While the accumulation of copper(II) bis(dimethyldithiocarbamate) was reduced by small interfering RNA (siRNA)-mediated knockdown of the copper transporter CTR1, the knockdown did not affect Cu10 accumulation, indicating that Cu10 rapidly enters vascular endothelial cells via CTR1-independent mechanisms. In addition, copper and iron complexes with other ligands tested could not activate Nrf2, suggesting that the intramolecular interaction between copper and dithiocarbamate ligand is important for the activation of the transcription factor. Cu10 induced the expression of heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase, downstream proteins of Nrf2. It was suggested that Cu10-induced activation of Nrf2 was due to proteasome inhibition as well as binding to Kelch-like ECH-associated protein 1. Since the effects of Cu10 on vascular endothelial cells are unique and diverse, the copper complex may be a good molecular probe to analyze the functions of the cells.

Vascular endothelial cells are in direct contact with blood. Inorganic zinc is thought to be incapable of inducing metallothionein, which protects cells from heavy metal toxicity and oxidative stress, in vascular endothelial cells. Here, we aimed to further characterize the induction of metallothionein in vascular endothelial cells. Our results confirmed that inorganic zinc could not induce metallothionein in vascular endothelial cells. Moreover, ZnSO4 could not activate both the metal response element (MRE) transcription factor 1 (MTF-1)/MRE and Nrf2/antioxidant response element (ARE) pathways and was incapable of inducing metallothionein. In addition, bis(L-cysteinato)zincate(II), a zinc complex that activates the MTF-1/MRE pathway, increased MRE promoter activity but failed to induce metallothionein, suggesting that vascular endothelial metallothionein was not induced only by activation of the MTF-1/MRE pathway. Further analysis of a library of zinc complexes showed that zinc(II) bis(diethyldithiocarbamate) activated the MTF-1/MRE pathway but not the Nrf2/ARE pathway, increased MT-1A, MT-1E, and MT-2A mRNA levels, and induced metallothionein proteins. These data indicated that zinc complexes may be excellent tools to analyze metallothionein induction in vascular endothelial cells.

Buried interface modification can effectively improve the compatibility between interfaces. Given the distinct interface selections in perovskite solar cells (PSCs), the applicability of a singular modification material remains limited. Consequently, in response to this challenge, we devised a tailored molecular strategy based on the electronic effects of specific functional groups. Therefore, we prepared three distinct silane coupling agents, and due to the varying inductive effects of these functional groups, the electronic distribution and molecular dipole moments of the coupling agents are correspondingly altered. Among them, trimethoxy (3,3,3-trifluoropropyl)-silane (F 3 -TMOS), which possesses electron-withdrawing groups, generates a molecular dipole moment directed toward the hole transport layer (HTL). This approach changes the work function of the HTL, optimizes the energy level alignment, reduces the open-circuit voltage loss, and facilitates carrier transport. Furthermore, through the buffering effect of the coupling agent, the interface strain and lattice distortion caused by annealing the perovskite are reduced, enhancing the stability of the tin-based perovskite. Encouragingly, tin PSCs treated with F 3 -TMOS achieved a champion efficiency of 14.67 %. This strategy provides an expedient avenue for the design of buried interface modification materials, enabling precise molecular adjustments in accordance with distinct interfacial contexts to ameliorate mismatched energetics and enhance carrier dynamics., (© 2024 Wiley-VCH GmbH.)

Phase transitions in MgAl2O4 spinel have been studied at pressures 22–38 GPa, and at temperatures up to 1600 °C, using a combination of synchrotron radiation and a multianvil apparatus with sintered diamond anvils. Spinel dissociated into a mixture of MgO plus Al2O3 at pressures to 25 GPa, while it transformed to the CaFe2O4 (calcium ferrite) structure at higher pressures via the metastably formed oxide mixture upon increasing temperature. Neither the e-phase nor the CaTi2O4-type MgAl2O4, which were reported in earlier studies using the diamond-anvil cell, were observed in the present pressure and temperature range. The zero-pressure bulk modulus of the calcium-ferrite-type MgAl2O4 was calculated as K=213 (3) GPa, which is significantly lower than that reported by Yutani et al. (1997), but is consistent with a more recent result by Funamori et al. (1998) and that estimated by an ab initio calculation by Catti (2001). [ABSTRACT FROM AUTHOR]

The sex pheromone of the hibiscus flower borer Rehimena surusalis (Walker) (Lepidoptera: Crambidae) was analyzed by gas chromatography with electroantennographic detection (GC-EAD) and GC-mass spectrometry (GC/MS). Three EAD-active components were found in crude pheromone gland extracts of calling females. GC/MS and GC analyses using synthetic chemicals and derivatization of the extracts identified three components as (10E,12Z)-hexadeca-10,12-dienal (E10,Z12-16:Ald,), (10E,12E)-hexadeca-10,12-dienyl acetate (E10,Z12-16:OAc), and (3Z,6Z,9Z)-tricosa-3,6,9-triene (Z3,Z6,Z9-23:HC). In field tests, male moths were strongly attracted to a ternary blend of E10,Z12-16:Ald, E10,Z12-16:OAc, and Z3,Z6,Z9-23:HC at a ratio of 1:5:14, but single and binary blends showed only weak or no attraction.

Egg formation in terrestrial insects is an absorptive process, accommodated not only by packing proteins and lipids into yolk but also by filling chorions with water. An osmotic swelling of ovarian follicles takes place during oocyte maturation. This study investigated the role of the aquaporin (AQP) water channel in the osmotic uptake of water during oogenesis in the silk moth Bombyx mori Linnaeus, 1758. Using the antibodies that specifically recognize previously characterized AQPs, two water-specific subtypes-AQP-Bom1 and AQP-Bom3-belonging to the Drosophila integral protein (DRIP) and Pyrocoelia rufa integral protein (PRIP) subfamilies of the insect AQP clade, respectively, were identified in the developing ovaries of B. mori. During oocyte growth, Bombyx PRIP was distributed at the oocyte plasma membrane, where it likely plays a role in water uptake and oocyte swelling, and may be responsible for oocyte hydration during fluid absorption by ovarian follicles. During the transition from vitellogenesis to choriogenesis during oocyte maturation, Bombyx DRIP expression became abundant in peripheral yolk granules underlying the oocyte plasma membrane. The restricted DRIP localization was not observed in non-diapause-destined follicles, where DRIP was evenly distributed in medullary yolk granules. There was no difference in PRIP distribution between diapause- and non-diapause-destined follicles. The diapause-destined oocytes encase DRIP protein in the peripheral yolk granules, where DRIP might be inert. This would be reflected in the metabolic arrest associated with diapause after fertilization and egg oviposition., (© 2015 Marine Biological Laboratory.)

N-Methylation of amines with methanol proceeds at room temperature in the presence of a silver-loaded titanium dioxide (Ag/TiO2) photocatalyst under UV-vis light irradiation. This method allows facile synthesis/isolation of N-methylamines bearing various functional groups including N-benzyl, N-allyl, N-Boc, hydroxyl, ether, acetal, carboxamide, formamide, and olefin groups.

The sex pheromone of Herpetogramma submarginale (Swinhoe) was studied by gas chromatography (GC) with electroantennographic detection and GC coupled with mass spectrometry. Two pheromone candidates detected in the gland extracts of females were identified as (Z)-13-hexadecenyl acetate (Z13-16:OAc) and (E)-13-hexadecenyl acetate (E13-16:OAc) in a ratio of 87:13 by mass spectral analysis of the natural pheromone components and their dimethyldisulfide adducts. In field tests, Z13-16:OAc alone attracted H. submarginale males and caught significantly more males than live virgin females. Addition of E13-16:OAc did not enhance the attractiveness of Z13-16:OAc. Derivatives of Z13-16:OAc also were tested as potential pheromone components. Addition of (Z)-13-hexadecen-1-ol significantly reduced the number of males captured, and (Z)-13-hexadecenal had no effect on the attractiveness of the lure. These results suggest that the female-produced sex pheromone of H. submarginale is Z13-16:OAc. This hexadecenyl acetate is a novel moth sex pheromone component.

The marine bacteria Marinobacter sp. DS40M6 and Marinobacter nanhaiticus D15-8W produce a suite of acyl peptidic marinobactin siderophores to acquire iron under iron-limiting conditions. During late-log phase growth, the marinobactins are hydrolyzed to form the marinobactin headgroup with release of the corresponding fatty acid tail. The bntA gene, a homologue of the Pseudomonas aeruginosa pyoverdine acylase gene, pvdQ, was identified from Marinobacter sp. DS40M6. A bntA knockout mutant of Marinobacter sp. DS40M6 produced the suite of acyl marinobactins A-E, without the usual formation of the marinobactin headgroup. Another marinobactin-producing species, M. nanhaiticus D15-8W, is predicted to have two pvdQ homologues, mhtA and mhtB. MhtA and MhtB have 67% identical amino acid sequences. MhtA catalyzes hydrolysis of the apo-marinobactin siderophores as well as the quorum sensing signaling molecule, dodecanoyl-homoserine lactone. In contrast to hydrolysis of the suite of apo-marinobactins by MhtA, hydrolysis of the iron(III)-bound marinobactins was not observed.

While 11 species in the family Saturniidae are found in Japan, no sex pheromones of the native species had been investigated previously. We collected larvae of Rhodinia fugax in Nagano and Tottori Prefecture, and of Loepa sakaei in Okinawa Prefecture, and extracted sex pheromones of these two species from virgin female moths. In gas chromatography-electroantennogram detection (GC-EAD) analyses, male antennae of each species responded to one component in the respective pheromone extracts of conspecific females. Chemical analyses of the extracts by GC/mass spectrometry revealed that the EAD-active compounds of R. fugax and L. sakaei were a hexadecadienal and a tetradecadienyl acetate, respectively. The two species belong to the subfamily Saturniinae, and the mass spectra of both were similar to that of the 6,11-hexadecadienyl acetate identified from Antheraea polyphemus, classified in the same subfamily, suggesting the same 6,11-dienyl structure for the C16 aldehyde and a 4,9-dienyl structure for the C14 acetate. Based on this assumption, four geometrical isomers of each dienyl compound were stereoselectively synthesized via acetylene intermediates, compared to the natural products, and tested in the field. Male catches confirmed the pheromone structures of the two Japanese saturniid species as (6E,11Z)-6,11-hexadecadienal for R. fugax and (4E,9Z)-4,9-tetradecadienyl acetate for L. sakaei. The compounds have a characteristic 1,6-dienyl motif common to the pheromones of Saturniinae species.

Sex pheromones of nocturnal hawk moths have been identified previously, but not those of diurnal hawk moths. Here, we report laboratory analyses and field testing of the sex pheromone of the diurnal hawk moth, Hemaris affinis (Bremer 1861) (Lepidoptera: Sphingidae). Sex pheromone glands were removed and extracted in hexane during peak calling activity of virgin female moths. Analysis of gland extracts by gas chromatography (GC) with electroantennographic detection revealed three components that elicited responses from male moth antennae. These components were identified, based on their mass spectra and retention indices on two GC columns, as (Z)-11-hexadecenal and (10E, 12Z)- and (10E,12E)-10,12-hexadecadienals with a ratio of 45:20:35. In a field experiment, traps baited with the three-component synthetic blend, but none of the single- or two-component blends, caught male moths. All three pheromone components have been identified previously in pheromones of other Lepidoptera, including Sphingid moths, and thus the ternary blend is probably responsible for the species specificity of the pheromone of this moth.

The global reaction route mapping (GRRM) methods conveniently define transition states in asymmetric hydrogenation and transfer hydrogenation of aromatic ketones via the [RuH{(S,S)-TsNCH(C6 H5 )CH(C6 H5 )NH2 }(η(6) -p-cymene)] intermediate. Multiple electrostatic CH/π interactions are the common motif in the preferred diastereometric structures., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The prevalence of chronic kidney disease (CKD) worldwide increases as the population ages. The progression of the disease increases the risk of complications and death and leads to end-stage renal failure, requiring renal replacement therapy. Despite the positive effect of hemodialysis (HD), patients are at risk of developing malnutrition, inflammation, oxidative stress, or cardiovascular disease, which worsens quality of life and can lead to organ dysfunction. The occurrence of the mentioned disorders depends largely on the diet, so changes in diet composition are an important part of the treatment of kidney disease. This study aimed to evaluate the effects of a balanced diet on some parameters of oxidative stress, immune response, and nutritional status in patients. This study included 57 HD patients (19 women and 38 men). In all of them, nutritional status and diet were initially determined, and then, they were divided into six groups, which received different diets and supplements. Serum levels of albumin, total protein, MDA, and the cytokines Il-1, IL-6, IL-8, TNF-α, and IL-10 were determined, and the activity of the enzymes such as CAT, SOD, and GSH-Px were determined in erythrocytes by spectrophotometry. Based on the results of BMI, albumin, and total protein, it can be concluded that a well-balanced diet can reduce weight loss. This study shows that a well-balanced diet can reduce the secretion of pro-inflammatory cytokines, and ensure the normal activity of antioxidative enzymes in the blood of HD patients. [ABSTRACT FROM AUTHOR]

The beneficial effects of a formulated supplement of plasmalogen and elastin on the memory function in healthy elderly subjects were investigated by a randomized, double-blind, placebo-controlled, parallel-group analysis. Plasmalogen has been shown to exert beneficial effects on cognitive function in animal models and human clinical trials, while elastin improves vascular elasticity and increases blood flow. The levels of plasmalogen and elastin decreases with aging. The supplement containing Ascidiacea (Halocynthia-roretzi)-derived plasmalogen (0.5 mg) and Tuna-derived elastin (100 mg) was administered to elderly Japanese subjects once a day for 16 weeks. The Japanese version of Rivermead Behavioral Memory Test (RBMT) was used as a primary evaluation item for the assessment of memory. Data from a protocolmatched population (per protocol set) (n=123) were analyzed. A comparison of mean difference between the baseline and evaluation points in cognition function in RBMT showed significantly higher scores for the categories of "first name" and "face recognition" in the test group than in the placebo group. In the stratified analysis of subjects > 75 years, the test group scored significantly higher than the placebo group for the categories of "belonging", "face recognition and picture recognition". The stratified analysis of female subjects showed a significantly higher scores for categories of "first and second names" and "belonging" of RBMT in the test group. Also, the score of "physical functioning" was significantly higher in the test group. These results indicate that formulated supplement of plasmalogen and elastin may be beneficial for improving memory dysfunction in healthy elderly subjects. [ABSTRACT FROM AUTHOR]

The development of effective bifunctional catalysts demonstrating high performance in both photocatalytic hydrogen evolution and selective hydrogenation of unsaturated compounds is of great interest for photocatalytic transfer hydrogenation. In this work, TiO2 and Pd@TiO2 catalysts were studied in two separate processes: photocatalytic H2 evolution and conventional hydrogenation reactions. Photocatalytic properties of titanium dioxide synthesized by a simple precipitation method were compared with those of commercial ones. Commercial anatase with a lower agglomeration degree showed better activity in H2 evolution. Further modification of the commercial anatase with Pd resulted in increasing its activity, achieving an H2 evolution rate of 760 μmol/h gcat. The Pd catalysts supported on different TiO2 samples were tested in hydrogenation of acetylenic compounds. The activity of the Pd@TiO2 catalysts was found to be dependent on the photocatalytic properties of TiO2 supports. XPS studies of Pd catalysts indicated that commercial anatase with better photocatalytic properties provided easier reduction of Pd2+ to active Pd0 particles. The Pd catalyst supported on commercial anatase demonstrated the highest activity in the hydrogenation process. The WC≡C rate achieved 2.6 × 10−6, 9.0 × 10−6 and 35.7 × 10−6 mol/s for hydrogenation of 2-hexyne-1-ol, 5-hexyne-1-ol and 2-hexyne, respectively. The selectivity of the catalyst to target olefinic compounds was 94–96%. In addition, the hydrogenation rate was found to be significantly affected by reaction conditions such as hydrogen concentration and solvent composition. The WC≡C rate decreased linearly with decreasing hydrogen concentration in a H2:He gas mixture (30–100 vol%). Performing the reaction in 0.10 M NaOH ethanolic solution resulted in increasing the WC≡C rate and selectivity of the process. The Pd catalyst was reused in an alkali medium (NaOH in ethanol) for 35 runs without significant degradation in its catalytic activity. Thus, the results obtained in this work can be useful in photocatalytic transfer hydrogenation. [ABSTRACT FROM AUTHOR]

The soybean pod borer Leguminivora glycinivorella (Matsumura) is one of the most important soybean pests and often causes serious damage to Glycine max (L.) Merr. a leading source of dietary protein and oil in animal feed. However, the potential distribution patterns of this economically important pest and its driving factors require further investigation. Here, we used the optimized MaxEnt model to predict the potential distribution of this pest with multiple variables associated with climate, land use, and host plant, at its recorded range and a globe scale. Based on 4 variable combinations, the results show that the current suitable habitats of L. glycinivorella are primarily distributed in most of China, the Korean Peninsula, and Japan. Whereas no suitable area is present in other continents. In future projections, the suitable region shows a slight northward expansion compared with the result predicted with current climatic conditions, and the suitable areas of almost all future projections were stable in size. Among the 9 bioclimatic factors, BIO03 (isothermality) consistently highly contributes to the predictions, indicating that temperature may be a key factor influencing the habitat distribution of L. glycinivorella. Comparative analyses of projections further show that non-climatic factors are informative in the modeling as routinely used bioclimate variables. The spatio-temporal distribution patterns of suitable habitats and the regulatory factors predicted in this study could provide important guidance for L. glycinivorella management. [ABSTRACT FROM AUTHOR]

Stimulus-specific adaptation is a hallmark of sensory processing in which a repeated stimulus results in diminished successive neuronal responses, but a deviant stimulus will still elicit robust responses from the same neurons. Recent work has established that synaptically released zinc is an endogenous mechanism that shapes neuronal responses to sounds in the auditory cortex. Here, to understand the contributions of synaptic zinc to deviance detection of specific neurons, we performed wide-field and 2-photon calcium imaging of multiple classes of cortical neurons. We find that intratelencephalic (IT) neurons in both layers 2/3 and 5 as well as corticocollicular neurons in layer 5 all demonstrate deviance detection; however, we find a specific enhancement of deviance detection in corticocollicular neurons that arises from ZnT3-dependent synaptic zinc in layer 2/3 IT neurons. Genetic deletion of ZnT3 from layer 2/3 IT neurons removes the enhancing effects of synaptic zinc on corticocollicular neuron deviance detection and results in poorer acuity of detecting deviant sounds by behaving mice. [ABSTRACT FROM AUTHOR]

The solubility data of spectinomycin dihydrochloride pentahydrate (SDP) in three binary solvents were determined over a temperature range of 278.15–318.15 K by the gravimetric method. Among the selected binary solvents, the solubility of SDP increased with the rise in temperature and initial methanol composition of binary solvents, and the general order of solubility of SDP under the same conditions was: (methanol + ethanol) > (methanol + n-propanol) > (methanol + i-propanol). Subsequently, solubility–temperature models including van't Hoff equation, λh equation, Yaws equation, and Apelblat equation; solubility–solvent composition models including general single model; solubility–temperature and solvent composition models including NRTL equation and modified Jouyban–Acree model were used to correlate the solubility data. Regarding the application of the NRTL equation in binary solvent systems, the influence of solvent composition on model parameters was first taken into account by introducing a solvent composition correction factor, thereby exhibiting an enhancement in fitting accuracy. To gain deeper insights into the dissolving behavior of SDP, molecular electrostatic potential surface, Hirshfeld surface analysis and the KAT-LSER model were applied to analyze the molecular interactions between SDP molecules and the solvent effects. Meanwhile, entire solubility data in three binary solvent systems at 298.15 K were associated as a function of solvent properties on the basis of KAT-LSER model. The results revealed that SDP primarily acts as hydrogen bond acceptors in solution, and polar interactions between SDP and solvent molecules can play a crucial role in promoting the dissolution of SDP. [ABSTRACT FROM AUTHOR]

The main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2‐like tumor‐associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, this study shows that the tumor suppressive protein SHISA3 regulates the antitumor functions of TAMs. Local delivery of mRNA encoding Shisa3 enables cancer immunotherapy by reprogramming TAMs toward an antitumoral phenotype, thus enhancing the efficacy of programmed cell death 1 (PD‐1) antibody. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8+ T cell‐mediated antitumor immunity. The expression of SHISA3 is induced by damage/pathogen‐associated molecular patterns (DAMPs/PAMPs) in macrophages via nuclear factor‐κB (NF‐κB) transcription factors. Reciprocally, SHISA3 forms a complex with heat shock protein family A member 8 (HSPA8) to activate NF‐κB signaling thus maintaining M1 polarization of macrophages. Knockout Shisa3 largely abolishes the antitumor efficacy of combination immunotherapy with Toll‐like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and PD‐1 antibody. It further found that higher expression of SHISA3 in antitumoral TAMs is associated with better overall survival in lung cancer patients. Taken together, the findings describe the role of SHISA3 in reprogramming TAMs that ameliorate cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Dystonia is a movement disorder with an estimated prevalence of 1.2% and is characterised by involuntary muscle contractions leading to abnormal postures and pain. Only symptomatic treatments are available with no disease-modifying or curative therapy, in large part due to the limited understanding of the underlying pathophysiology. However, the inherited monogenic forms of dystonia provide an opportunity for the development of disease models to examine these mechanisms. Myoclonus Dystonia, caused by SGCE mutations encoding the ε-sarcoglycan protein, represents one of now >50 monogenic forms. Previous research has implicated the involvement of the basal ganglia–cerebello-thalamo-cortical circuit in dystonia pathogenesis, but further work is needed to understand the specific molecular and cellular mechanisms. Pluripotent stem cell technology enables a patient-derived disease modelling platform harbouring disease-causing mutations. In this review, we discuss the current understanding of the aetiology of Myoclonus Dystonia, recent advances in producing distinct neuronal types from pluripotent stem cells, and their application in modelling Myoclonus Dystonia in vitro. Future research employing pluripotent stem cell-derived cellular models is crucial to elucidate how distinct neuronal types may contribute to dystonia and how disruption to neuronal function can give rise to dystonic disorders. [ABSTRACT FROM AUTHOR]

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability and preventing carcinogenesis. Additionally, in neurodevelopment, folate is essential for neural tube closure and central nervous system formation. Thus, dysregulation of folate metabolism can contribute to pathologies such as cancer, severe birth defects, and neurodegenerative diseases. Epidemiological evidence highlights folate's impact on disease risk and its potential as a therapeutic target. In cancer, antifolate drugs that inhibit key enzymes of folate-dependent 1C metabolism and strategies targeting folate receptors are current therapeutic options. However, folate's impact on cancer risk is complex, varying among cancer types and dietary contexts. In neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, folate deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing to neuronal damage. Clinical trials of folic acid supplementation show mixed outcomes, underscoring the complexities of its neuroprotective effects. This review integrates current knowledge on folate metabolism in cancer and neurodegeneration, exploring molecular mechanisms, clinical implications, and therapeutic strategies, which can provide crucial information for advancing treatments. [ABSTRACT FROM AUTHOR]

Background: The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit., Methods: A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score., Results: An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06)., Conclusions: Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The sweet potato vine borer moth, Omphisa anastomosalis (Pyraloidea: Crambidae), is a serious pest in tropical and subtropical Asia-Pacific regions. In previous work using a population from Okinawa, Japan, (10E,14E)-10,14-hexadecadienal (E10,E14-16:Ald) was identified as the major pheromone component, with hexadecanal, (E)-10-hexadecenal, and (E)-14-hexadecenal as minor components. However, traps baited with the synthetic compounds were less effective at attracting males in the field than those baited with virgin females. While Pyraloidea females usually produce only Type I pheromone components (unsaturated fatty alcohols and their derivatives), the pheromones of some Pyraloidea species have been shown to involve a combination of both Type I and Type II components (unsaturated hydrocarbons and their epoxides). We examined an extract of the pheromone glands of female O. anastomosalis from Vietnam by gas chromatography coupled to mass spectrometry and detected (3Z,6Z,9Z)-3,6,9-tricosatriene (Z3,Z6,Z9-23:H) in addition to the compounds identified previously. All four isomers of 10,14-16:Ald were synthesized. A mixture of synthetic E10,E14-16:Ald and Z3,Z6,Z9-23:H in a ratio of 1:0.2-1:2 was attractive to male moths in Vietnam, indicating the strong synergistic effect of the Type II compound. Addition of the other minor pheromone components to the binary blend did not increase the number of male moths captured. Combinations of Z3,Z6,Z9-23:H with the other three geometrical isomers of E10,E14-16:Ald attracted no males, further substantiating the 10E,14E configuration of the natural diene component. E10,E14-16:Ald mixed with other polyunsaturated hydrocarbons showed that mixtures that included a C21 triene, a C22 triene, or a C23 pentaene attracted as many males as did the mixture with Z3,Z6,Z9-23:H. The identification of a highly attractive sex pheromone will help in developing efficient strategies for monitoring and control of O. anastomosalis populations in sweet potato fields.

The genome of Vibrio harveyi BAA-1116 contains a nonribosomal peptide synthetase (NRPS) gene cluster (aebA-F) resembling that for enterobactin, yet enterobactin is not produced. A gene predicted to encode a long-chain fatty acid CoA ligase (FACL), similar to enzymes involved in the biosynthesis of acyl peptides, resides 15 kb away from the putative enterobactin-like biosynthetic gene cluster (aebG). The proximity of this FACL gene to the enterobactin-like synthetase suggested that V. harveyi may produce amphiphilic enterobactin-like siderophores. Extraction of the bacterial cell pellet of V. harveyi led to the isolation and structure determination of a suite of eight amphi-enterobactin siderophores composed of the cyclic lactone of tris-2,3-dihydroxybenzoyl-L-serine and acyl-L-serine. The FACL knockout mutant, ΔaebG V. harveyi, and the NRPS knockout mutant, ΔaebF V. harveyi, do not produce amphi-enterobactins. The amphi-enterobactin biosynthetic machinery was heterologously expressed in Escherichia coli and reconstituted in vitro, demonstrating the condensation domain of AebF has unique activity, catalyzing two distinct condensation reactions.

We herein report two cases of acute ischemic stroke associated with iron deficiency anemia (IDA) due to bleeding from uterine fibroids. Anemia is not generally recognized as a risk factor for stroke. The physiological mechanisms that may factor in the development of ischemic stroke in patients with IDA include thrombocytosis, hypercoagulable state, and anemic hypoxia. In our two cases, IDA was considered to be the cause of ischemic stroke because all other known causes of stroke were ruled out. In patients with ischemic stroke due to anemia, early treatment of the anemia is important to prevent stroke recurrence.

Organic-inorganic hybrid molecules can exhibit biological activities by controlling the activities of their individual components. These molecules can be applied as seed/lead compounds in drug development, and can be used as molecular probes in chemical biology for the elucidation of the molecular mechanisms of biological systems. In this review, we introduce copper diethyldithiocarbamate (Cu10), a copper complex, as a compound that activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces metallothionein, which are the key cellular defense factors against toxic metals and oxidative stress in vascular endothelial cells. It was found that neither the complexes with the same ligand and other metal ions (including zinc and iron) nor the ligand alone was inactive. Therefore, both copper ion and the ligand of Cu10 are essential components for the biological functioning of the complex. In addition, Cu10 may be useful in clarifying the molecular mechanism underlying metallothionein induction in vascular endothelial cells.

Organometallic compounds and complexes possibly show novel bioactivities unprecedented with organic molecules that consist of C, H, O, and N atoms. We have already reported that an organoantimony compound selectively induces the expression of perlecan, a large heparin sulfate proteoglycan, in cultured vascular endothelial cells. Perlecan consists of a core protein with Mr of approximately 400 kDa and three anticoagulant heparan sulfate glycosaminoglycan chains. However, little is known about the molecular mechanisms of perlecan expression in endothelial cells. Since an organoantimony compound induces the expression of perlecan, we prepared a variety of its derivatives and tried to identify the binding proteins for the organoantimony compound by the drug affinity responsive target stability method, a negative selection method to identify the target proteins. As the results, we found glucocoriticoid receptor as binding protein of the organoantimony compound, which mediates the expression of perlecan in endothelial cells.

We hypothesized that leukocytes have 2 opposing effects on patients with ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Patients with ischemic stroke treated with rtPA were divided into 2 groups using the peripheral leukocyte count: high leukocyte group (HLG) and low leukocyte group (LLG) and were evaluated with the National Institutes of Health stroke scale (NIHSS) during the first 24 hours. We defined significant improvement (SI) as NIHSS improving by more than 50% from the baseline, and deterioration following improvement (DFI) as the achievement of SI within 24 hours but its subsequent loss at 24 hours. Fifty-three patients were enrolled, and the rate of SI within 24 hours was higher in HLG than in LLG (85.2% vs 42.3%, P = .0011). However, the rate of DFI was significantly higher in HLG than in LLG (29.6% vs 7.7%, P = .0413). We found that leukocytes might have not only deleterious but also beneficial effects in intravenous rtPA treatment.

Homologs of bombykal, (10E,12Z)-10,12-hexadecadienal, have been reported to be sex pheromones or sexual attractants of several species of sphingid moths. In this study, we identified novel bombykal analogs as sex pheromone components from a Japanese sphingid moth, Dolbina tancrei. Staudinger (Sphingidae: Lepidoptera). Sex pheromone gland extracts from calling female moths were subjected to gas chromatography/electroantennograhic detection (GC/EAD), gas chromatography/mass spectrometry (GC/MS), and gas chromatography (GC) analyses. GC/EAD analyses showed two active components in the crude pheromone extracts. GC/MS analysis determined these two components to be pentadecadienals. GC/MS of their MTAD derivatives showed conjugated double bonds at the 9- and 11-positions, indicating 9,11-pentadecadienals. The isomeric configurations of these candidates were determined by comparison of their Kováts retention indices with those of synthetic compounds. Field bioassays with the four isomers of 9,11-pentadecadienal and their mixtures confirmed that the two sex pheromone components of D. tancrei are (9E,11Z)-9,11-pentadecadienal and (9Z,11Z)-9,11-pentadecadienal, with the highest male catches observed for a 90:10 blend. This is the first report of 9,11-pentadecadienals as sex pheromone components in lepidopteran species.

Vibrio anguillarum is a marine pathogen that causes vibriosis, a hemorrhagic septicemia in aquatic invertebrate as well as vertebrate animals. The siderophore anguibactin system is one of the most important virulence factors of this bacterium. Most of the anguibactin biosynthesis and transport genes are located in the 65-kb pJM1 virulence plasmid although some of them are found in the chromosome of this fish pathogen. Over 30 years of research unveiled the role numerous chromosomal and pJM1 genes play in the synthesis of anguibactin and the transport of cognate ferric complexes into the bacterial cell. Furthermore, these studies showed that pJM1-carrying strains might be originated from pJM1-less strains producing the chromosome-mediated siderophore vanchrobactin. Additionally, we recently identified a chromosome-mediated anguibactin system in V. harveyi suggesting the possible evolutional origin of the V. anguillarum anguibactin system. In this review, we present our current understanding of the mechanisms and evolution hypothesis of the anguibactin system that might have occurred in these pathogenic vibrios.

Background: Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds., Methods: We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine)., Results: Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501)., Conclusions: Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)