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Condensates are a hallmark of emergence in quantum materials such as superconductors and charge density waves. Excitonic insulators are an intriguing addition to this library, exhibiting spontaneous condensation of electron-hole pairs. However, condensate observables can be obscured through parasitic coupling to the lattice. Here we employ nonlinear terahertz spectroscopy to disentangle such obscurants through measurement of the quantum dynamics. We target Ta2NiSe5, a putative room-temperature excitonic insulator in which electron-lattice coupling dominates the structural transition (Tc = 326 K), hindering identification of excitonic correlations. A pronounced increase in the terahertz reflectivity manifests following photoexcitation and exhibits a Bose-Einstein condensation-like temperature dependence well below the Tc, suggesting an approach to monitor the exciton condensate dynamics. Nonetheless, dynamic condensate-phonon coupling remains as evidenced by peaks in the enhanced reflectivity spectrum at select infrared-active phonon frequencies, indicating that parametric reflectivity enhancement arises from phonon squeezing. Our results highlight that coherent dynamics can drive parametric stimulated emission.
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The blood-brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood-brain barrier's structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system's function is drastically altered, which can cause disease and modify the metabolism of drugs in vivo. Changes in the structure and function of the blood-brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes. This article aims to review the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier as well as the effects of changes in the blood-brain barrier on drug metabolism. We also hypothesized and explore the regulation and potential mechanisms of the blood-brain barrier and associated pathways, such as transcription factors, inflammatory factors, and nuclear receptors, in regulating drug transport under high-altitude hypoxia.
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Mal de Altura , Barrera Hematoencefálica , Humanos , Barrera Hematoencefálica/metabolismo , Mal de Altura/metabolismo , Células Endoteliales/metabolismo , Hipoxia/metabolismo , Transporte BiológicoRESUMEN
High-altitude hypoxic environments have critical implications on cardiovascular system function as well as blood pressure regulation. Such environments place patients with hypertension at risk by activating the sympathetic nervous system, which leads to an increase in blood pressure. In addition, the high-altitude hypoxic environment alters the in vivo metabolism and antihypertensive effects of antihypertensive drugs, which changes the activity and expression of drug-metabolizing enzymes and drug transporters. The present study reviewed the pharmacodynamics and pharmacokinetics of antihypertensive drugs and its effects on patients with hypertension in a high-altitude hypoxic environment. It also proposes a new strategy for the rational use of antihypertensive drugs in clinical practice in high-altitude hypoxic environments. The increase in blood pressure on exposure to a high-altitude hypoxic environment was mainly dependent on increased sympathetic nervous system activity. Blood pressure also increased proportionally to altitude, whilst ambulatory blood pressure increased more than conventional blood pressure, especially at night. High-altitude hypoxia can reduce the activities and expression of drug-metabolizing enzymes, such as CYP1A1, CYP1A2, CYP3A1, and CYP2E1, while increasing those of CYP2D1, CYP2D6, and CYP3A6. Drug transporter changes were related to tissue type, hypoxic degree, and hypoxic exposure time. Furthermore, the effects of high-altitude hypoxia on drug-metabolism enzymes and transporters altered drug pharmacokinetics, causing changes in pharmacodynamic responses. These findings suggest that high-altitude hypoxic environments affect the blood pressure, pharmacokinetics, and pharmacodynamics of antihypertensive drugs. The optimal hypertension treatment plan and safe and effective medication strategy should be formulated considering high-altitude hypoxic environments.
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Mal de Altura , Hipertensión , Humanos , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Altitud , Mal de Altura/tratamiento farmacológico , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismoRESUMEN
A 32×32 100 GHz silicon photonic integrated arrayed waveguide grating router (AWGR) is experimentally demonstrated for dense wavelength division multiplexing (DWDM) applications. The dimension of the AWGR is 2.57 mm×1.09 mm with a core size of 1.31 mm×0.64 mm. It exhibits 6.07 dB maximum channel loss non-uniformity with -1.66 dB best-case insertion loss and average channel crosstalk of -15.74 dB. In addition, in the case of 25 Gb/s signals, the device successfully realizes high-speed data routing. The AWG router provides clear optical eye diagrams and low power penalty at bit-error-rates of 10-9.
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Photonic antennas are critical in applications such as spectroscopy, photovoltaics, optical communications, holography, and sensors. Metal antennas are widely used because of their small size, but they are difficult to be compatible with a CMOS. All-dielectric antennas are easier to integrate with Si waveguides, but are generally larger in size. In this paper, we propose the design of a small-sized, high-efficiency semicircular dielectric grating antenna. The antenna's key size is only 2.37µm×4.74µm, and the emission efficiency reaches over 64% in the wavelength range from 1.16 to 1.61 µm. The antenna provides a new, to the best of our knowledge, approach for three-dimensional optical interconnections between different decks of integrated photonic circuits.
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We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.19 dB on the operational waveband. Furthermore, the proposed device shows a great robustness to fabrication imperfection, with a waveguide width deviation of 50 nm and ambient temperature change from 0°C to 200°C. These properties make the design a potential candidate for ultrahigh-density photonic integration chips.
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Hypoxia is the main characteristic of a high-altitude environment, affecting drug metabolism. However, so far, the mechanism of microRNA (miRNA) involved in the regulation of drug metabolism and transporters under high-altitude hypoxia is still unclear. This study aims to investigate the functions and expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP), peptide transport 1 (PEPT1), and organic anion-transporting polypeptides 2B1 (OATP2B1) in rats and colon cancer (Caco-2) cells after exposure to high-altitude hypoxia. The protein and mRNA expression of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were determined by Western blot and qPCR. The functions of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were evaluated by determining the effective intestinal permeability and absorption rate constants of their specific substrates in rats under high-altitude hypoxia, and uptake and transport studies were performed on Caco-2 cells. To screen the miRNA associated with hypoxia, Caco-2 cells were examined by high throughput sequencing. We observed that the miR-873-5p was significantly decreased under hypoxia and might target MDR1 and pregnane X receptor (PXR). To clarify whether miR-873-5p regulates MDR1 and PXR under hypoxia, Caco-2 cells were transfected with mimics or inhibitors of miR-873-5p and negative control (NC). The function and expression of drug transporters were found to be significantly increased in rats and Caco-2 cells under hypoxia. We found that miR-873-5p regulated MDR1 and PXR expression. Herein, it is shown that miRNA may affect the expression of drug transporter and nuclear receptor under hypoxia. SIGNIFICANCE STATEMENT: This study explores if alterations to the microRNAs (miRNAs), induced by high-altitude hypoxia, can be translated to altered drug transporters. Among miRNAs, which show a significant change in a hypoxic environment, miR-873-5p can act on the multidrug resistance protein 1 (MDR1) gene; however, there are multiple miRNAs that can act on the pregnane X receptor (PXR). This study speculates that the miRNA-PXR-drug transporter axis is important in the physiological disposition of drugs.
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MicroARNs , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Subfamilia B de Transportador de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Altitud , Animales , Células CACO-2 , Humanos , Hipoxia/genética , MicroARNs/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Mensajero/metabolismo , RatasRESUMEN
3D doping structure has significant advantages in modulation efficiency and loss compared with 2D modulator doping profiles. However, to the best of our knowledge, previous work on 3D simulation methods for interdigitated doping designs applied simplified models, which prohibited complex 3D doping. In this work, innovative omni junctions, based on the effective 3D Monte-Carlo method, are believed to be the first proposed for high-performance modulators. Simulation results show that the modulation efficiency reaches 0.88 V·cm, while the loss is only 16 dB/cm, with capacitance below 0.42 pF/mm. This work provides a modulator design with superior modulation efficiency and serviceability for high-speed datacom.
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Zinc-ion storage is a promising electrochemical energy field due to loads of its advantages like easy preparation, environmental friendliness, high safety performance, and high capacity. Carbon materials have been widely studied for zinc-ion storage due to their extraordinary properties such as earth-abundancy, low-cost, good electrical conductivity, various structures, and good stability. This article reviews some widely used carbon materials in zinc ion storage devices, including hollow carbon spheres, activated carbon, N-doped porous carbon, graphene, and carbon nanotubes. The unique roles and advantages of these carbon materials in both zinc ion supercapacitors and zinc ion batteries are emphasized. Characteristics and functionalizations of different carbon materials are also comparatively discussed in view of zinc-ion energy storage devices. Finally, some challenges and perspectives of carbon materials in zinc-ion energy storage are outlined.
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PURPOSE: Forkhead box f1 (FoxF1), a transcription factor, was implicated in lung development. However, the molecular mechanism of FoxF1 in lung injury, specifically in injury caused by paraquat (PQ), one of the most frequently used herbicides, is unknown. Accordingly, we performed this study to investigate whether FoxF1 attenuates PQ-induced lung injury and to determine the possible mechanism. METHODS: We used PQ-treated Beas-2B cells to measure the expression of FoxF1. Later, ChIP-qPCR was applied to detect the levels of histone acetylation in cells, followed by the validation of the relationship between histone deacetylase-2 (HDAC2) and FoxF1. Subsequently, the correlation between FoxF1 and microRNA (miR)-342 and the downstream mechanism of miR-342 were evaluated by bioinformatics analysis. The apoptosis and the content of reactive oxygen species (ROS) in PQ-treated cells were detected to evaluate the roles of HDAC2, FoxF1 and miR-342 in vitro. Finally, a rat model was developed to evaluate the effects of HDAC2, miR-342 and Krüppel-like factor 5 (KLF5) on PQ-induced lung injury in vivo. RESULTS: PQ treatment significantly enhanced FoxF1 promoter deacetylation, thereby inhibiting FoxF1 expression. After inhibition of HDAC2 activity, apoptosis and oxidative stress induced by PQ were significantly reversed. Nevertheless, further inhibition of miR-342 or overexpression of KLF5 promoted apoptosis and oxidative stress induced by PQ, and IκB/NF-κB p65 signaling was significantly activated after PQ treatment. CONCLUSION: PQ treatment inhibited miR-342 expression by promoting HDAC2-induced deacetylation of the FoxF1 promoter, thereby promoting KLF5 expression and the IκB/NF-κB p65 signaling activation, and finally exacerbating PQ-induced lung injury in rats.
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Lesión Pulmonar Aguda/metabolismo , Histona Desacetilasa 2/efectos de los fármacos , Paraquat/metabolismo , Factor de Transcripción ReIA/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Histona Desacetilasa 2/metabolismo , Masculino , Paraquat/efectos adversos , Sustancias Protectoras/farmacología , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
A silicon-on-insulator polarization diversity scheme is proposed. Based on an asymmetrical evanescent coupler, a broadband and compact polarization splitter-rotator comprising mode conversion tapers and mode sorting asymmetric Y junctions is optimized with silicon dioxide upper cladding and a silicon nitride waveguide. The simulation results show mode conversion loss is less than 0.2 dB, and the extinction ratio is lower than -17dB in the wavelength range of 1.48µm to 1.67µm.
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The arbitrary ratio power splitter is widely used in photonic integrated circuits (PICs), for signal monitoring, power equalization, signal feedback, and so on. Here we designed a fabrication-tolerant, compact, broadband, and low-loss arbitrary ratio power splitter. The proposed arbitrary ratio power splitter was realized with an adiabatically tapered silicon rib waveguide with 70 nm shallow etches and an Si3N4 waveguide. The fabrication analysis confirmed that both of them are robust to fabrication errors. 3D finite-difference time-domain simulations show a very low excess loss (less than 0.02 dB for Si3N4 waveguide and 0.05 dB for Si rib waveguide), and a broadband operating wavelength range (100 nm). Good fabrication tolerance and standard critical dimensions make the arbitrary ratio power splitter compatible with the standard fabrication process of commercial silicon photonic foundries.
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To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 h after study drug administration. Lidocaine hydrochloride in plasma was determined by RP-HPLC. Pharmacokinetics parameters of lidocaine hydrochloride showed that there were no significant difference between the native Han and Tibetan volunteers, but the t(1/2) was 29.8 and 29.8% higher in 2 groups, respectively, than in the LA group. To study related mechanism, the effects of exposure to chronic high-altitude hypoxia (CHH) on the activity and expression of CYP3A1 were examined in rats. Rats were divided into LA, chronic moderate altitude hypoxia, and CHH groups. CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP3A1 in vivo. This study found significant changes in the disposition of lidocaine hydrochloride in native healthy Tibetan and Han Chinese subjects living at a high altitude in comparison to healthy Han Chinese subjects living at LA, it might be due to significant decreases in the activity and protein and mRNA expression of CYP3A4 under CHH condition.
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Altitud , Anestésicos Locales/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Lidocaína/farmacocinética , Adulto , Anestésicos Locales/sangre , Animales , Pueblo Asiatico , Citocromo P-450 CYP3A/genética , Femenino , Voluntarios Sanos , Humanos , Hipoxia/metabolismo , Inyecciones Intramusculares , Lidocaína/sangre , Masculino , Microsomas Hepáticos/metabolismo , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Adulto JovenRESUMEN
OBJECTIVE: To study the protective effect of Lycium ruthenicum on peripheral blood system against radiation injury in mice. METHODS: Kunming mice were randomly divided into control group, model group, positive group and Lycium ruthenicum high dose (8 g/kg), middle dose (4 g/kg) and low dose (2 g/kg)treatment groups that experimented three days after irradiation. In the same way, groups were set at 7 days and 14 days after irradiation respectively. Lycium ruthenicum extract were administered orally to the mice in the three Lycium ruthenicum treatment groups and normal saline were administered orally to the mice in control group and model group for 14 days. Positive group were treated with radioprotective agent amifostine (WR-2721) at 30 min before irradiation. Except control group, mice in other groups received quantity of 5 Gy X-radiation whole body evenly with one time. Hemogram, organ index, DNA, Caspase-3, Caspase-6 and P53 contents were observed at the 3rd, 7th and 14th day after irradiation. RESULTS: Lycium ruthenicum significantly increased the total red blood cell count, hemoglobin count, the indexes of spleen and thymus and bone marrow DNA contents (P < 0.05), as well as decreased Caspase-3 and Caspase-6 contents in serum and the expression of P53 in intestinal crypt epithelial cells. CONCLUSION: The results showed that Lycium ruthenicum had protective effects on peripheral blood system against radiation injury in mice.
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Medicamentos Herbarios Chinos/farmacología , Lycium/química , Traumatismos por Radiación/tratamiento farmacológico , Protectores contra Radiación/farmacología , Animales , Médula Ósea/efectos de los fármacos , Caspasa 3/metabolismo , Recuento de Eritrocitos , Ratones , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Rayos XRESUMEN
We investigated the effect of exposure to acute and chronic high-altitude hypoxia (AHH and CHH) on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats. The rats were divided into plain (400 m), acute middle-altitude hypoxia (2,800 m), chronic middle-altitude hypoxia (2,800 m), AHH (4,300 m) and CHH (4,300 m). After probe drugs had been orally administered to the rats of the 5 groups, the serum or urine concentration of the probe drug and its metabolite was determined by reversed-phase HPLC. The activity of cytochrome P450 isozyme and NAT2 was evaluated by the ratio of the metabolite to the probe drug. The ELISA and real-time PCR were used to analyze the protein and mRNA expression of cytochrome P450 isozyme and NAT2, respectively. AHH and CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP1A2 in vivo. AHH downregulates the activity and mRNA expression of rat NAT2 in vivo, and CHH upregulates the activity and protein and mRNA expression of rat CYP2D6. AHH and CHH did not change the expression of CYP2C9 and CYP2C19 in rats. This study found significant changes in the activity and protein and mRNA expression of CYP1A2, CYP2D6 and NAT2 in rats in the special environment of high-altitude hypoxia.
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Altitud , Hidrocarburo de Aril Hidroxilasas/metabolismo , Arilamina N-Acetiltransferasa/genética , Hipoxia/metabolismo , Animales , Hidrocarburo de Aril Hidroxilasas/genética , Femenino , Hipoxia/genética , Masculino , Microsomas Hepáticos/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
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Arilamina N-Acetiltransferasa/metabolismo , Cafeína/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional Tibetana , Administración Oral , Animales , Arilamina N-Acetiltransferasa/genética , Cafeína/orina , Citocromo P-450 CYP1A2/genética , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Teofilina/orina , Uracilo/análogos & derivados , Uracilo/orina , Ácido Úrico/análogos & derivados , Ácido Úrico/orina , Xantinas/orinaRESUMEN
Changes to blood-brain barrier structure and function may affect the delivery of drugs into the brain. It is worthwhile to exploring more study on how the blood-brain barrier changes in structure and function and how that affects drug transport in high-altitude hypoxic environment. The DIA high-throughput sequencing technique indicate that the rats blood-brain barrier has been identified to have 7252 proteins overall and 8 tight junction proteins, among which Claudin-7 was a plateau-specific tight junction protein under high-altitude hypoxia, and based on the interaction network study, 2421 proteins are found to interact with one another, with ZO-1 being the primary target. The results of the projected gene function analysis demonstrated that changes in tight junction proteins are related to the control of TRP channels by inflammatory mediators, the wnt signaling pathway, the ABC transporter system, and drug metabolism-CYP450 enzyme regulation. Additionally, the electron microscopy, the Evans blue combination with confocal laser scanning microscopy, and the Western Blot and RT-qPCR revealed that high-altitude hypoxic environment induces blood-brain barrier tight junctions to open, blood-brain barrier permeability increases, ZO-1, Occludin, Claudin-5 protein and mRNA expression decreased. Our research implies that structural and functional alterations in the blood-brain barrier induced by high altitude hypoxia may impact drug transport inside the central nervous system, and that drug transporters and drug-metabolizing enzymes may be key players in this process.
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Barrera Hematoencefálica , Proteínas de Uniones Estrechas , Animales , Barrera Hematoencefálica/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Proteínas de Uniones Estrechas/genética , Ratas , Hipoxia/metabolismo , Masculino , Altitud , Ratas Sprague-Dawley , Transporte Biológico , Permeabilidad , Uniones Estrechas/metabolismoRESUMEN
Wearable hydrogel sensors provide a user-friendly option for wearable electronics and align well with the existing manufacturing strategy for connecting and communicating with large numbers of Internet of Things devices. This is attributed to their components and structures, which exhibit exceptional adaptability, scalability, bio-compatibility, and self-healing properties, reminiscent of human skin. This review focuses on the recent research on principal structural elements of wearable hydrogels: toughening networks and conductive networks, highlighting the strategies for enhancing mechanical and electrical properties. Wearable hydrogel sensors are categorized for an extensive exploration of their composition, mechanism, and design approach. This review provides a comprehensive understanding of wearable hydrogels and offers guidance for the design of components and structures in order to develop high-performance wearable hydrogel sensors.
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The aim of this study was to investigate the pharmacokinetics of sulfamethoxazole in native Han and Tibetan healthy Chinese subjects living chronically at high altitude. An open-labeled, controlled, prospective study was conducted in healthy Chinese male volunteers. Sulfamethoxazole 1,200 mg was administered orally to two groups: native Han and Tibetan volunteers living at high altitude (2,500-3,900 m [8,200-12,800 ft]). Blood samples were collected from an indwelling venous catheter into heparinized tubes before (baseline) study drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h after study drug administration. Sulfamethoxazole in whole blood, plasma, and plasma water, and metabolite N (4)-acetyl-sulfamethoxazole in plasma were determined by HPLC. Tolerability was determined using blood chemistry testing, continuous 12-lead electrocardiogram, and blood pressure monitoring. The protein binding was significantly higher in the native Tibetan group (70.5 %) compared to the native Han group (67.3 %) (p < 0.05). The binding of sulfamethoxazole to red blood cells was 7.4 and 8.3 % in the native Han and native Tibetan groups, respectively. There was no significant difference between the two groups. The AUC(0-∞) was significantly lower in the native Tibetan group compared to the native Han group (p < 0.05), and other pharmacokinetics parameters were found to have no significant difference between the two groups. This study found little changes in the disposition of sulfamethoxazole in these native healthy Tibetan Chinese subjects living at high altitude in comparison to native healthy Han Chinese subjects living at high altitude.
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Altitud , Antiinfecciosos/farmacocinética , Adulto , Pueblo Asiatico , Proteínas Sanguíneas/metabolismo , Humanos , Masculino , Estudios Prospectivos , Unión Proteica , Sulfametoxazol/farmacocinética , Tibet , Adulto JovenRESUMEN
This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.