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Cysteine (Cys) and its oxidized form, cystine (Cys2), play crucial roles in biological systems and have considerable applications in cell culture. However, Cys in cell culture media is easily oxidized to Cys2, leading to solubility issues. Traditional analytical methods struggle to maintain the oxidation states of Cys and Cys2 during analysis, posing a significant challenge to accurately measuring and controlling these compounds. To effectively control the Cys and Cys2 levels, a rapid and accurate analytical method is required. Here, we screened derivatizing reagents that can react with Cys even under acidic conditions to realize a novel analytical method for simultaneously determining Cys and Cys2 levels. Diethyl 2-methylenemalonate (EMM) was found to possess the desired traits. EMM, characterized by its dual electron-withdrawing attributes, allowed for a rapid reaction with Cys under acidic conditions, preserving intact information for understanding the functions of target compounds. Combined with LC-MS/MS and an internal standard, this method provided high analytical accuracy in a short analytical time of 9 min. Using the developed method, the rapid oxidation of Cys in cell culture media was observed with the headspace of the storage container considerably influencing Cys oxidation and Cys2 precipitation rates. The developed method enabled the direct and simplified analysis of Cys behavior in practical media samples and could be used in formulating new media compositions, ensuring quality assurance, and real-time analysis of Cys and Cys2 in cell culture supernatants. This novel approach holds the potential to further enhance the media performance by enabling the timely optimal addition of Cys.
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Medios de Cultivo , Cisteína , Cistina , Compuestos de Sulfhidrilo , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Química Clic , Medios de Cultivo/química , Cisteína/química , Cisteína/análisis , Cistina/química , Cistina/análogos & derivados , Cistina/análisis , Cromatografía Líquida con Espectrometría de Masas , Malonatos/química , Oxidación-Reducción , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/análisis , Espectrometría de Masas en Tándem/métodosRESUMEN
Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance ("Japanese Guide") has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic.
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COVID-19 , Esteroides , Humanos , COVID-19/epidemiología , Dexametasona , Pueblos del Este de Asia , Pacientes Internos , Japón/epidemiología , Metilprednisolona , Esteroides/uso terapéutico , Guías de Práctica Clínica como AsuntoRESUMEN
The suppression of the first wave of COVID-19 in Japan is assumedly attributed to people's increased risk perception after acquiring information from the government and media reports. In this study, going out in public amidst the spread of COVID-19 infections was investigated by examining new polymerase chain reaction (PCR) positive cases of COVID-19 and its relationship to four indicators of people going out in public (the people flow, the index of web searches for going outside, the number of times people browse restaurants, and the number of hotel guests, from the Regional Economic and Social Analysis System (V-RESAS). Two waves of COVID-19 infections were examined using cross-correlation analysis. In the first wave, all four indicators of going out changed to be opposite the change in new PCR positive cases, showing a lag period of -1 to +6 weeks. In the second wave, the same relationship was only observed for the index of web searches for going outside, and two indicators showed the positive lag period of +6 to +12 weeks after the change in new PCR positive cases. Moreover, each indicator in the second wave changed differently compared to the first wave. The complexity of people's behaviors around going out increased in the second wave, when policies and campaigns were implemented and people's attitudes were thought to have changed. In conclusion, the results suggest that policies may have influenced people's mobility, rather than the number of new PCR positive cases.
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COVID-19 , Epidemias , COVID-19/epidemiología , Humanos , Japón/epidemiología , Reacción en Cadena de la Polimerasa , SARS-CoV-2/genéticaRESUMEN
AIMS: The Coronavirus Disease 2019 (COVID-19) pandemic has had unprecedented effects on health care utilization for acute cardiovascular diseases. Although hospitalizations for acute coronary syndrome decreased during the COVID-19 pandemic, there is a paucity of data on the trends and management of heart failure (HF) cases. Furthermore, concerns have been raised that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase susceptibility to COVID-19. This study aimed to elucidate changes in HF hospitalizations from the COVID-19 state of emergency in Japan and investigated changes in the prescription of ACEIs and ARBs, and in-hospital mortality. METHODS AND RESULTS: We performed an interrupted time series analysis of HF hospitalizations in Japan to verify the impacts of the COVID-19 state of emergency. Changes in the weekly volume of HF hospitalizations were taken as the primary outcome measure. Between 1 April 2018 and 4 July 2020, 109 429 HF cases required admission. After the state of emergency, an immediate decrease was observed in HF cases per week [-3.6%; 95% confidence interval (CI): -0.3% to -6.7%, P = 0.03]. There was no significant change in the prescription of ACEIs or ARBs after the state of emergency (4.2%; 95% CI: -0.3% to 8.9%, P = 0.07). The COVID-19 pandemic had no effect on in-hospital mortality among HF patients (5.3%; 95% CI: -4.9% to 16.6%, P = 0.32). CONCLUSIONS: We demonstrated a decline in HF hospitalizations during the COVID-19 pandemic in Japan, with no clear evidence of a negative effect on the prescription of ACEIs and ARBs or in-hospital mortality.
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COVID-19 , Insuficiencia Cardíaca , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca/epidemiología , Hospitalización , Humanos , Análisis de Series de Tiempo Interrumpido , Japón/epidemiología , Pandemias , SARS-CoV-2RESUMEN
AIM: The coronavirus disease 2019 (COVID-19) pandemic has left negative spillover effects on the entire health care system. Previous studies have suggested significant declines in cases of acute coronary syndrome (ACS) and primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. METHODS: We performed a quasi-experimental, retrospective cohort study of ACS hospitalisations by using a multi-institutional administrative claims database in Japan. We used interrupted time series analyses to ascertain impacts on cases, treatment approaches, and in-hospital mortality before and after Japan's state of emergency to respond to COVID-19. The primary outcome was the change in ACS cases per week. RESULTS: A total of 30,198 ACS cases (including 21,612 acute myocardial infarction and 8,586 unstable angina) were confirmed between 1st July 2018 and 30th June 2020. After the state of emergency, an immediate decrease was observed in ACS cases per week (-18.3%; 95% confidence interval, -13.1 to -23.5%). No significant differences were found in the severity of Killip classification (P=0.51) or cases of fibrinolytic therapy (P=0.74). The impact of the COVID-19 pandemic on in-hospital mortality in ACS patients was no longer observed after adjustment for clinical characteristics (adjusted odds ratio, 0.93; 95% confidence interval, 0.78 to 1.12; P=0.49). CONCLUSIONS: We demonstrated the characteristics and trends of ACS cases in a Japanese population by applying interrupted time series analyses. Our findings provide significant insights into the association between COVID-19 and decreases in ACS hospitalisations during the pandemic.
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Síndrome Coronario Agudo , COVID-19 , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/tratamiento farmacológico , COVID-19/epidemiología , Mortalidad Hospitalaria , Humanos , Japón/epidemiología , Pandemias , Estudios RetrospectivosRESUMEN
BACKGROUND: In response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased. METHODS: Using claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020. RESULTS: A total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patient was estimated to 5.5 million JPY. CONCLUSION: It is suggested that the hospitals treating COVID-19 patients were negatively incentivized.
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COVID-19 , Servicio de Urgencia en Hospital/economía , Hospitales , Tiempo de Internación/economía , Pandemias , SARS-CoV-2 , COVID-19/economía , COVID-19/mortalidad , COVID-19/terapia , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Japón/epidemiología , MasculinoRESUMEN
We demonstrate a spectral broadening and compression setup for carrier-envelope phase (CEP) stable sub-10-fs Ti:sapphire oscillator pulses resulting in 3.9 fs pulses spectrally centered at 780 nm. Pulses from the oscillator with 2 nJ energy are launched into a 1 mm long all-normal dispersive solid-core photonic crystal fiber and spectrally broadened to more than one octave. Subsequent pulse compression is achieved with a phase-only 4f pulse shaper. Second harmonic frequency resolved optical gating with a ptychographic reconstruction algorithm is used to obtain the spectral phase, which is fed back as a phase mask to the shaper display for pulse compression. The compressed pulses are CEP stable with a long term standard deviation of 0.23 rad for the CEP noise and 0.32 rad for the integrated rms phase jitter. The high total throughput of 15% results in a remaining pulse energy of about 300 pJ at 80 MHz repetition rate. With these parameters and the ability to tailor the spectral phase, the system is well suited for waveform sensitive photoemission experiments with needle tips or nanostructures and can be easily adapted to other sub-10 fs ultra-broadband Ti:sapphire oscillators.
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OBJECTIVE: To evaluate the combined use of Lactobacillus salivarius WB21 and (-)-epigallocatechin gallate (EGCg) for oral health maintenance. DESIGN: The effects of L. salivarius WB21 on growth of Streptococcus mutans, the insoluble glucan produced by S. mutans, and on growth of Porphyromonas gingivalis were evaluated in vitro. In addition, the susceptibility of five oral pathogenic bacteria and L. salivarius WB21 to EGCg, the inhibiting effect of EGCg on methyl mercaptan, and the effects of L. salivarius WB21 and EGCg in combination on growth of P. gingivalis were examined. RESULTS: Lactobacillus salivarius WB21 showed concentration-dependent inhibition of the growth of S. mutans. Addition of L. salivarius WB21 inhibited production of the insoluble glucan by S. mutans (p < 0.001). A filtrate of L. salivarius WB21 culture solution inhibited growth of P. gingivalis (p < 0.001 vs. control), and this effect was enhanced when it was used in combination with EGCg (p < 0.001 vs. the addition of L. salivarius WB21). In addition, EGCg directly inhibited methyl mercaptan in a concentration-dependent manner (p < 0.001). Concerning bacterial susceptibility to EGCg, growth of P. gingivalis, Prevotella intermedia, and Fusobacterium nucleatum was inhibited at 2.5 mg/mL of EGCg, while that of L. salivarius WB21 was inhibited at 25 mg/mL EGCg. CONCLUSIONS: Our results imply that L. salivarius WB21 may be useful for controlling dental caries, periodontitis, and oral malodor. In addition, the effects of L. salivarius WB21 on periodontitis and oral malodor may be synergistically enhanced by use in combination with EGCg.
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Catequina/farmacología , Caries Dental/microbiología , Halitosis/microbiología , Ligilactobacillus salivarius/fisiología , Periodontitis/microbiología , Té/química , Antibiosis , Catequina/análogos & derivados , Catequina/fisiología , Caries Dental/prevención & control , Fusobacterium nucleatum/efectos de los fármacos , Fusobacterium nucleatum/crecimiento & desarrollo , Glucanos/metabolismo , Halitosis/prevención & control , Ligilactobacillus salivarius/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Periodontitis/prevención & control , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/crecimiento & desarrollo , Prevotella intermedia/efectos de los fármacos , Prevotella intermedia/crecimiento & desarrollo , Probióticos , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/crecimiento & desarrollo , Streptococcus mutans/metabolismoRESUMEN
We investigate coherent electron dynamics in graphene, interacting with the electric field waveform of two orthogonally polarized, few-cycle laser pulses. Recently, we demonstrated that linearly polarized driving pulses lead to sub-optical-cycle Landau-Zener quantum path interference by virtue of the combination of intraband motion and interband transition [Higuchi et al., Nature 550, 224 (2017)NATUAS0028-083610.1038/nature23900]. Here we introduce a pulsed control laser beam, orthogonally polarized to the driving pulses, and observe the ensuing electron dynamics. The relative delay between the two pulses is a tuning parameter to control the electron trajectory, now in a complex fashion exploring the full two-dimensional reciprocal space in graphene. Depending on the relative phase, the electron trajectory in the reciprocal space can, e.g., be deformed to suppress the quantum path interference resulting from the driving laser pulse. Intriguingly, this strong-field-based complex matter wave manipulation in a two-dimensional conductor is driven by a high repetition rate laser oscillator, rendering unnecessary complex and expensive amplified laser systems.
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Catheter ablation provides effective results for sustained monomorphic ventricular tachycardia (VT), but the presence of mural thrombus including dense calcification occasionally causes unfavorable outcomes. The case of a 67-year-old man in whom sustained monomorphic VT, which was resistant to endocardial radiofrequency ablation, in the presence of mural thrombus including dense calcification after coronary artery bypass grafting was successfully treated by left ventricular reconstruction with cryoablation is reported.
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Calcinosis/cirugía , Cardiomiopatías/cirugía , Ablación por Catéter/métodos , Ventrículos Cardíacos/cirugía , Taquicardia Ventricular/cirugía , Trombosis/cirugía , Anciano , Ablación por Catéter/instrumentación , Electrocardiografía , Endocardio/cirugía , Humanos , Masculino , Taquicardia Ventricular/fisiopatología , Trombosis/fisiopatologíaRESUMEN
Neurovascular unit (NVU) is a basic unit in the brain, including neurons, glial cells, blood vessels and extracellular matrix. This concept implies the importance of a three-dimensional (3D) culture model including these cell types for investigating brain functions. However, little is known about the construction of an in vitro 3D NVU model. In the present study, we aimed at constructing 3D neurovascular tissues by combining in vitro neurogenesis and angiogenesis models using a microfluidic platform, which is a critical step toward the NVU construction in vitro. Three gel conditions, which were fibrin gel, fibrin-Matrigel mixed gel and fibrin-hyaluronan mixed gel, were investigated to optimize the gel components in terms of neurogenesis and angiogenesis. First, fibrin-Matrigel mixed gel was found to promote neural stem cell (NSC) differentiation into neurons and neurite extension. In particular, 3D neural networks were constructed in 2-8 mg/ml fibrin-Matrigel mixed gel. Second, we found that capillary-like structures were also formed in the fibrin-Matrigel mixed gel by coculturing brain microvascular endothelial cells (BMECs) and human mesenchymal stem cells (MSCs). Finally, we combined both neural and vascular culture models and succeeded in constructing 3D neurovascular tissues with an optimized seeding condition of NSCs, BMECs and MSCs.
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Encéfalo/citología , Endotelio Vascular/citología , Modelos Biológicos , Neovascularización Fisiológica , Células-Madre Neurales/citología , Neurogénesis , Encéfalo/fisiología , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Endotelio Vascular/fisiología , Humanos , Técnicas Analíticas Microfluídicas , Morfogénesis , Células-Madre Neurales/fisiologíaRESUMEN
The ability to steer electrons using the strong electromagnetic field of light has opened up the possibility of controlling electron dynamics on the sub-femtosecond (less than 10-15 seconds) timescale. In dielectrics and semiconductors, various light-field-driven effects have been explored, including high-harmonic generation, sub-optical-cycle interband population transfer and the non-perturbative change of the transient polarizability. In contrast, much less is known about light-field-driven electron dynamics in narrow-bandgap systems or in conductors, in which screening due to free carriers or light absorption hinders the application of strong optical fields. Graphene is a promising platform with which to achieve light-field-driven control of electrons in a conducting material, because of its broadband and ultrafast optical response, weak screening and high damage threshold. Here we show that a current induced in monolayer graphene by two-cycle laser pulses is sensitive to the electric-field waveform, that is, to the exact shape of the optical carrier field of the pulse, which is controlled by the carrier-envelope phase, with a precision on the attosecond (10-18 seconds) timescale. Such a current, dependent on the carrier-envelope phase, shows a striking reversal of the direction of the current as a function of the driving field amplitude at about two volts per nanometre. This reversal indicates a transition of light-matter interaction from the weak-field (photon-driven) regime to the strong-field (light-field-driven) regime, where the intraband dynamics influence interband transitions. We show that in this strong-field regime the electron dynamics are governed by sub-optical-cycle Landau-Zener-Stückelberg interference, composed of coherent repeated Landau-Zener transitions on the femtosecond timescale. Furthermore, the influence of this sub-optical-cycle interference can be controlled with the laser polarization state. These coherent electron dynamics in graphene take place on a hitherto unexplored timescale, faster than electron-electron scattering (tens of femtoseconds) and electron-phonon scattering (hundreds of femtoseconds). We expect these results to have direct ramifications for band-structure tomography and light-field-driven petahertz electronics.
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Ultrafast control of magnets using femtosecond light pulses attracts interest regarding applications and fundamental physics of magnetism. Antiferromagnets are promising materials with magnon frequencies extending into the terahertz range. Visible or near-infrared light interacts mainly with the electronic orbital angular momentum. In many magnets, however, in particular with iron-group ions, the orbital momentum is almost quenched by the crystal field. Thus, the interaction of magnons with light is hampered, because it is only mediated by weak unquenching of the orbital momentum by spin-orbit interactions. Here we report all-optical excitation of magnons with frequencies up to 9 THz in antiferromagnetic CoO with an unquenched orbital momentum. In CoO, magnon modes are coupled oscillations of spin and orbital momenta with comparable amplitudes. We demonstrate excitations of magnon modes by directly coupling light with electronic orbital angular momentum, providing possibilities to develop magneto-optical devices operating at several terahertz with high output-to-input ratio.Light pulses can control magnetism in a material, and the effective creation of magnetic oscillations leads to spintronic devices with higher efficiency. Here, the authors increase the efficiency of magnon excitation by using a material in which orbital angular momenta are not quenched.
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A biologically active lipid, sphingosine-1-phosphate (S1P) is highly abundant in blood, and plays an important role in regulating the growth, survival, and migration of many cells. Binding of the endogenous ligand S1P results in activation of various signaling pathways via G protein-coupled receptors, some of which generates Ca2+ mobilization. In astrocytes, S1P is reported to evoke Ca2+ signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated. Transient receptor potential canonical (TRPC) channels are Ca2+ -permeable cation channels expressed in astrocytes and involved in Ca2+ influx after receptor stimulation. In this study, we investigated the involvement of TRPC channels in S1P-induced cellular responses. In Ca2+ imaging experiments, S1P at 1 µM elicited a transient increase in intracellular Ca2+ in astrocytes, followed by sustained elevation. The sustained Ca2+ response was markedly suppressed by S1P2 receptor antagonist JTE013, S1P3 receptor antagonist CAY10444, or non-selective TRPC channel inhibitor Pyr2. Additionally, S1P increased chemokine CXCL1 mRNA expression and release, which were suppressed by TRPC inhibitor, inhibition of Ca2+ mobilization, MAPK pathway inhibitors, or knockdown of the TRPC channel isoform TRPC6. Taken together, these results demonstrate that S1P induces Ca2+ signaling in astrocytes via Gq -coupled receptors S1P2 and S1P3 , followed by Ca2+ influx through TRPC6 that could activate MAPK signaling, which leads to increased secretion of the proinflammatory or neuroprotective chemokine CXCL1.
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Astrocitos/metabolismo , Señalización del Calcio/fisiología , Corteza Cerebral/metabolismo , Quimiocina CXCL1/metabolismo , Lisofosfolípidos/metabolismo , Esfingosina/análogos & derivados , Canales Catiónicos TRPC/metabolismo , Animales , Astrocitos/efectos de los fármacos , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Cationes Bivalentes/metabolismo , Movimiento Celular/fisiología , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , ARN Mensajero/metabolismo , Ratas Wistar , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/metabolismo , Esfingosina/metabolismo , Canales Catiónicos TRPC/antagonistas & inhibidores , Canales Catiónicos TRPC/genéticaRESUMEN
Volatile sulfur compounds (VSCs) produced by oral anaerobes are the major compounds responsible for oral malodor. Enterococcus faecium WB2000 is recognized as an antiplaque probiotic bacterium. In this study, the effect of E. faecium WB2000 on VSC production by Porphyromonas gingivalis was evaluated, and the mechanism of inhibition of oral malodor was investigated. P. gingivalis ATCC 33277 was cultured in the presence of four lactic acid bacteria, including E. faecium WB2000. Subsequently, P. gingivalis ATCC 33277, W50, W83, and two clinical isolates were cultured in the presence or absence of E. faecium WB2000, and the emission of VSCs from spent culture medium was measured by gas chromatography. The number of P. gingivalis ATCC 33277 in mixed culture with E. faecium WB2000 decreased at 6 h, and the rate of decrease was higher than that in mixed cultures with the other lactic acid bacteria. The numbers of five P. gingivalis strains decreased at similar rates in mixed culture with E. faecium WB2000. The concentration of methyl mercaptan was lower in spent culture medium from P. gingivalis and E. faecium WB2000 cultures compared with that from P. gingivalis alone. Therefore, E. faecium WB2000 may reduce oral malodor by inhibiting the growth of P. gingivalis and neutralizing methyl mercaptan.
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The absence of net magnetization inside antiferromagnetic domains has made the control of their spatial distribution quite challenging. Here we experimentally demonstrate an optical method for controlling antiferromagnetic domain distributions in MnF2. Reduced crystalline symmetry can couple an order parameter with non-conjugate external stimuli. In the case of MnF2, time-reversal symmetry is macroscopically broken reflecting the different orientations of the two magnetic sublattices. Thus, it exhibits different absorption coefficients between two orthogonal linear polarizations below its antiferromagnetic transition temperature under an external magnetic field. Illumination with linearly polarized laser light under this condition selectively destructs the formation of a particular antiferromagnetic order via heating. As a result, the other antiferromagnetic order is favoured inside the laser spot, achieving spatially localized selection of an antiferromagnetic order. Applications to control of interface states at antiferromagnetic domain boundaries, exchange bias and control of spin currents are expected.
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Disturbances of circadian rhythm and dysregulation of clock gene expression are involved in the induction of various neurological disorder states, including chronic pain. However, the relationship between the CNS circadian-clock gene system and nociception remains poorly defined. Significant circadian oscillations of Period (Per1, Per2), Bmal1 and Cryptochrome 1 (Cry1) mRNA expression have been observed in the lumbar spinal dorsal horn of naïve mice. The current study examined the expression of clock genes in the lumbar spinal dorsal horn of mice with neuropathic pain due to a partial sciatic nerve ligation (PSNL). Seven days after PSNL, the mice displayed a robust unilateral hind paw mechanical hypersensitivity. The normal circadian oscillations of Per1, Per2 and Cry1, but not Bmal1, mRNA expression were significantly suppressed in the ipsilateral lumbar spinal dorsal horn of PSNL mice 7days following surgery. The circadian expression of PER1 protein, in particular, was also significantly suppressed in the ipsilateral spinal dorsal horn of PSNL mice. Double-labeling immunohistochemistry revealed downregulation of PER1 in neurons and astrocytes, but not microglia. Knockdown of Per1 expression by intrathecal treatment with Per1 siRNA also induced mechanical hypersensitivity, phosphorylation of c-jun N-terminal kinase (JNK) and the upregulation of chemokine (C-C motif) ligand 2 (CCL2) production in the lumbar spinal dorsal horn. Per1 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of either the JNK inhibitor SP600125 or the selective CCL2 receptor (CCR2) antagonist RS504393, indicating that these intracellular messengers are crucial in mediating the mechanical hypersensitivity following the downregulation of PER1 expression. These results suggest that the downregulation of the spinal dorsal horn clock genes such as Per1 expressed could be crucial in the induction of neuropathic pain following peripheral nerve injury. Modulating clock gene Per1 expression could be a novel therapeutic strategy in alleviating neuropathic pain.
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Quimiocina CCL2/metabolismo , Regulación hacia Abajo , Hiperalgesia/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Circadianas Period/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Animales , Astrocitos/metabolismo , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/genética , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/genética , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos ICR , Neuronas/metabolismo , Proteínas Circadianas Period/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Asta Dorsal de la Médula Espinal/citología , Asta Dorsal de la Médula Espinal/fisiologíaRESUMEN
Mechanisms of high-harmonic generation from crystals are described by treating the electric field of a laser as a quasistatic strong field. Under the quasistatic electric field, electrons in periodic potentials form dressed states, known as Wannier-Stark states. The energy differences between the dressed states determine the frequencies of the radiation. The radiation yield is determined by the magnitudes of the interband and intraband current matrix elements between the dressed states. The generation of attosecond pulses from solids is predicted. Ramifications for strong-field physics are discussed.
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We have developed an electro-optic (EO) sampling method with polarization modulation of probe pulses; this method allows us to measure the direction of a terahertz (THz) electric-field vector with a precision of 0.1 mrad in a data acquisition time of 660 ms using a 14.0-kHz repetition rate pulsed light source. Through combination with a THz time-domain spectroscopy technique, a time-dependent two-dimensional THz electric field was obtained. We used a photoelastic modulator for probe-polarization modulation and a (111)-oriented zincblende crystal as the EO crystal. Using the tilted pulse front excitation method with stable regeneratively amplified pulses, we prepared stable and intense THz pulses and performed pulse-by-pulse analog-to-digital conversion of the signals. These techniques significantly reduced statistical errors and enabled sub-mrad THz polarization measurements. We examined the performance of this method by measuring a wire-grid polarizer as a sample. The present method will open a new frontier of high-precision THz polarization sensitive measurements.