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Polarization-sensitive broadband optoelectronic detection is crucial for future sensing, imaging, and communication technologies. Narrow bandgap 2D materials, such as Te and PdSe2, show promise for these applications, yet their polarization performance is limited by inherent structural anisotropies. In this work, a self-powered, broadband photodetector utilizing a Te/PdSe2 van der Waals (vdWs) heterojunction, with orientations meticulously tailored is introduced through polarized Raman optical spectra and tensor calculations to enhance linear polarization sensitivity. The device exhibits anisotropy ratios of 1.48 at 405 nm, 3.56 at 1550 nm, and 1.62 at 4 µm, surpassing previously-reported photodetectors based on pristine Te and PdSe2. Additionally, it exhibits high responsivity (617 mA W-1 at 1550 nm), specific detectivity (5.27 × 1010 Jones), fast response (≈4.5 µs), and an extended spectral range beyond 4 µm. The findings highlight the significance of orientation-engineered heterostructures in enhancing polarization-sensitive photodetectors and advancing optoelectronic technology.
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In this paper, we present a fully integrated circuit without inductance implementing Chua's chaotic system. The circuit described in this study utilizes the SMIC 180 nm CMOS process and incorporates a multi-path voltage-controlled oscillator (VCO). The integral-differential nonlinear resistance is utilized as a variable impedance component in the circuit, constructed using discrete devices from a microelectronics standpoint. Meanwhile, the utilization of a multi-path voltage-controlled oscillator ensures the provision of an adequate oscillation frequency and a stable waveform for the chaotic circuit. The analysis focuses on the intricate and dynamic behaviors exhibited by the chaotic microelectronic circuit. The experimental findings indicate that the oscillation frequency of the VCO can be adjusted within a range of 198 MHz to 320 MHz by manipulating the applied voltage from 0 V to 1.8 V. The circuit operates within a 1.8 V environment, and exhibits power consumption, gain-bandwidth product (GBW), area, and Lyapunov exponent values of 1.0782 mW, 4.43 GHz, 0.0165 mm2, and 0.6435â¼1.0012, respectively. The aforementioned circuit design demonstrates the ability to generate chaotic behavior while also possessing the benefits of low power consumption, high frequency, and a compact size.
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Kidney tubules are mostly responsible for pathogenesis of diabetic kidney disease. Actively reabsorption of iron, high rate of lipid metabolism and exposure to concentrated redox-active compounds constructed the three main pillars of ferroptosis in tubular cells. However, limited evidence has indicated that ferroptosis is indispensable for diabetic tubular injury. Glucagon-like peptide-1 receptor agonist (GLP-1RA) processed strong benefits on kidney outcomes in people with diabetes. Moreover, GLP-1RA may have additive effects by improving dysmetabolism besides glucose control and weight loss. Therefore, the present study aimed at exploring the benefits of exendin-4, a high affinity GLP-1RA on kidney tubular dysregulation in diabetes and the possible mechanisms involved, with focus on ferroptosis and adenosine 5'-monophosphate-activated protein kinase (AMPK)-mitochondrial lipid metabolism pathway. Our data revealed that exendin-4 treatment markedly improved kidney structure and function by reducing iron overload, oxidative stress, and ACSL4-driven lipid peroxidation taken place in diabetic kidney tubules, along with reduced GPX4 expression and GSH content. AMPK signaling was identified as the downstream target of exendin-4, and enhancement of AMPK triggered the transmit of its downstream signal to activate fatty acid oxidation in mitochondria and suppress lipid synthesis and glycolysis, and ultimately alleviated toxic lipid accumulation and ferroptosis. Further study suggested that exendin-4 was taken up by tubular cells via macropinocytosis. The protective effect of exendin-4 on tubular ferroptosis was abolished by macropinocytosis blockade. Taken together, present work demonstrated the beneficial effects of GLP-1RA treatment on kidney tubular protection in diabetes by suppressing ferroptosis through enhancing AMPK-fatty acid metabolic signaling via macropinocytosis.
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Diabetes Mellitus , Nefropatías Diabéticas , Ferroptosis , Humanos , Exenatida/farmacología , Exenatida/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Agonistas Receptor de Péptidos Similares al Glucagón , Nefropatías Diabéticas/patología , Metabolismo de los Lípidos , Ácidos Grasos , LípidosRESUMEN
Diabetic kidney disease (DKD) is responsible for nearly half of all end-stage kidney disease and kidney failure is a major driver of mortality among patients with diabetes. To date, few safe and effective drugs are available to reverse the decline of kidney function. Kidney tubules producing energy by fatty acid metabolism are pivotal in development and deterioration of DKD. Peroxisome proliferator-activated receptors (PPARs), comprising PPARα, PPARδ and PPARγ play a senior role in the pathogenesis of DKD for their functions in glycemic control and lipid metabolism; whereas systemic activation of PPARγ causes serious side-effects in clinical settings. Compound H11 was a potent PPARα and PPARδ (PPARα/δ) dual agonist with potent and well-balanced PPARα/δ agonistic activity and a high selectivity over PPARγ. In this study, the potential therapeutic effects of compound H11 were determined in a db/db mouse model of diabetes. Expressions of PPARα and PPARδ in nuclei of tubules were markedly reduced in diabetes. Transcriptional changes of tubular cells showed that H11 was an effective PPARα/δ dual agonist taking effects both in vivo and in vitro. Systemic administration of H11 showed glucose tolerance and lipid metabolic benefits in db/db mice. Moreover, H11 treatment exerted protective effects on diabetic kidney injury. In addition to fatty acid metabolism, H11 also regulated diabetes-induced metabolic alternations of branch chain amino acid degradation and glycolysis. The present study demonstrated a crucial role of H11 in regulation of energy homeostasis and metabolism in glucose-treated tubular cells. Overall, compound H11 holds therapeutic promise for DKD.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Enfermedades Metabólicas , PPAR delta , Animales , Humanos , Ratones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Células Epiteliales/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Riñón/metabolismo , PPAR alfa/metabolismo , PPAR gamma/metabolismoRESUMEN
This article reports the design, fabrication, and performance of an annular-array ultrasound transducer using (K, Na)NbO3 (KNN)-based lead-free 1-3 piezoelectric composite. The 1-3 piezoelectric composite based on lead-free 0.965(K0.45Na0.55)(Nb0.96Sb0.04)O3-0.035 Bi0.5Na0.5Zr0.85Hf0.15O3 (KNNS-BNZH) was first prepared with the dice-and-fill method. Different from previous reported studies, by patterning annular electrodes on this kind of 1-3 composite, a five-element annular-array transducer in diameter of 6 mm was designed and successfully fabricated and its working center frequency was increased from 5 MHz to around 15 MHz. Meanwhile, a -6 dB bandwidth of 50% was achieved for each annular-array element via a pulse-echo response measurement. Moreover, the obtained annular-array transducer exhibits low crosstalk (<-40 dB) and a high electromechanical coupling coefficient of around 0.7. The application of ultrasonic imaging was further demonstrated to show its excellent performance. Both theoretical analysis and experimental results show that the obtained annular-array transducer presented in this work has a competitive capability for ultrasonic application.
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Recent successful growth of asymmetric transition metal dichalcogenides via accurate manipulation of different chalcogen atoms in top and bottom surfaces demonstrates exotic electronic and chemical properties in such Janus systems. Within the framework of density functional perturbation theory, anharmonic phonon properties of monolayer Janus MoSSe sheet are explored. By considering three-phonons scattering, out-of-plane flexural acoustic (ZA) mode tends to undergo a stronger phonon scattering than transverse acoustic (TA) mode and the longitudinal acoustic (LA) mode with phonon lifetime of ZA (1.0 ps) < LA (23.8 ps) < TA (25.8 ps). This is sharply different from the symmetric MoS2 where flexural ZA mode has the weakest anharmonicity and is least scattered. Moreover, utilizing non-equilibrium Green function method, ballistic thermal conductance at room temperature is found to be around 0.11 nWK-1nm-2, lower than that of MoS2. Our work highlights intriguing phononic properties of such MoSSe Janus layers associated with asymmetric surfaces.
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Surface acoustic wave (SAW) strain sensors fabricated on piezoelectric substrates have attracted considerable attention due to their attractive features such as passive wireless sensing ability, simple signal processing, high sensitivity, compact size and robustness. To meet the needs of various functioning situations, it is desirable to identify the factors that affect the performance of the SAW devices. In this work, we perform a simulation study on Rayleigh surface acoustic wave (RSAW) based on a stacked Al/LiNbO3 system. A SAW strain sensor with a dual-port resonator was modeled using multiphysics finite element model (FEM) method. While FEM has been widely used for numerical calculations of SAW devices, most of the simulation works mainly focus on SAW modes, SAW propagation characteristics and electromechanical coupling coefficients. Herein, we propose a systematic scheme via analyzing the structural parameters of SAW resonators. Evolution of RSAW eigenfrequency, insertion loss (IL), quality factor (Q) and strain transfer rate with different structural parameters are elaborated by FEM simulations. Compared with the reported experimental results, the relative errors of RSAW eigenfrequency and IL are about 3% and 16.3%, respectively, and the absolute errors are 5.8 MHz and 1.63 dB (the corresponding Vout/Vin is only 6.6%). After structural optimization, the obtained resonator Q increases by 15%, IL decreases by 34.6% and the strain transfer rate increases by 2.4%. This work provides a systematic and reliable solution for the structural optimization of dual-port SAW resonators.
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Two-dimensional (2D) materials tend to have the preferable formation of vacancies at the outer surface. Here, contrary to the normal notion, we reveal a type of vacancy that thermodynamically initiates from the interior part of the 2D backbone of germanium selenide (γ-GeSe). Interestingly, the Ge-vacancy (VGe) in the interior part of γ-GeSe possesses the lowest formation energy amongst the various types of defects considered. We also find a low diffusion barrier (1.04 eV) of VGe, which is half of those of sulfur vacancies in MoS2. The facile formation of mobile VGe is rooted in the antibonding coupling of the lone-pair Ge 4s and Se 4p states near the valence band maximum, which also exists in other gamma-phase MX (M = Sn, Ge; X = S, Te). The VGe is accompanied by a shallow acceptor level in the band gap and induces strong infrared light absorption and p-type conductivity. The VGe located in the middle cationic Ge sublattice is well protected by the surface Se layers - a feature that is absent in other atomically thin materials. Our work suggests that the unique well-buried inner VGe, with the potential of forming structurally protected ultrathin conducting filaments, may render the GeSe layer an ideal platform for quantum emitting, memristive, and neuromorphic applications.
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The lethal neurotoxins, paralytic shellfish toxins (PSTs), and tetrodotoxin (TTX) have recently been found in marine shellfish from many coastal states. Herein, we applied a sensitive and reliable ultra-performance hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS) method to determine 13 PSTs and TTX in marine shellfish using a porous carbon solid-phase extraction (SPE). This in-house validation study required the development of a novel chromatographic separation using a HILIC-Z column, which was necessary to retain highly polar compounds. Using acetonitrile as the organic phase and ammonium formate-formic acid buffer as the aqueous phase, the quantitative analysis was carried out with an external standard method in the multiple reaction monitoring modes using positive electrospray ionization. To reduce interference, 1% aqueous acetic acid extracts of the shellfish samples were cleaned up by ion-pair SPE using a porous graphitic carbon cartridge. The calibration curves for PSTs and TTX were linear (R2 > 0.995), and the sensitivity was good, with limits of detection (LODs) of 1.7-13.7 µg/kg, and limits of quantitation (LOQs) of 5.2-41.0 µg/kg. The recoveries were 76.5-95.5% with RSDs of 3.1-12.0%. Finally, We applied the method for the determination of PSTs and TTX in three batches of Nassarius showing excellent method accuracy against expected values.
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Grafito , Espectrometría de Masas en Tándem , Tetrodotoxina/análisis , Espectrometría de Masas en Tándem/métodos , Carbono/química , Porosidad , Mariscos/análisis , Cromatografía Liquida/métodos , Cromatografía Líquida de Alta Presión , Extracción en Fase Sólida , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Background: The implementation of indocyanine green (ICG) tracer-guided lymph node dissection is still in the preliminary stages of laparoscopic surgery, and its safety and efficacy for gastric cancer remain unclear. Methods: A systematic review was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and Scopus to identify relevant subjects from inception to June 2022. The core indicators were the total number of harvested lymph nodes and the safety of the laparoscopic gastrectomy with ICG. A meta-analysis was performed to estimate the pooled weighted mean difference (WMD) and 95% confidence interval (CI). Results: Thirteen studies and 2,027 participants were included (642 for the ICG-group and 1,385 for the non-ICG group). The mean number of lymph nodes dissected in the ICG group was significantly greater than that in the non-ICG group (WMD = 6.24, 95% CI: 4.26 to 8.22, P <0.001). However, there was no significant difference in the mean number of positive lymph nodes dissected between the ICG and the non-ICG groups (WMD = 0.18, 95% CI: -0.70 to 1.07, P = 0.879). Additionally, ICG gastrectomy did not increase the risk in terms of the operative time, estimated blood loss, and postoperative complications. Conclusion: ICG tracer with favorable safety increases the number of harvested lymph nodes but not the number of positive lymph nodes in laparoscopic gastrectomy. More high-quality, large-sample-size randomized controlled trials are still needed to enhance this evidence.
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With the rapid expansion of fisheries, one of the most significant limitations to the sustainable development of fisheries in China is the quality and safety of fishery products owing to the abuse of fishery drugs and the use of illegal and/or restricted chemicals in fishery drugs. A range of chemicals that are potential hazards to fishery drugs were selected for screening in this study. A comprehensive analytical method was developed, based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), for the rapid screening of 86 types of illegally added chemicals in fishery drugs. The fishery drug samples were extracted with 80% (v/v) acetonitrile aqueous solution and diluted to reduce matrix effects. The 86 target compounds were separated on an ACQUITY PREMIER HSS T3 column (100 mm×2.1 mm, 1.8 µm), with methanol and 0.1% formic acid as mobile phases, via gradient elution. The extract was directly analyzed by UPLC-Q-TOF-MS using electrospray ionization in the positive mode. The external standard method was used for quantification. In this study, the extraction reagent and purification procedure were selected to develop a simple and effective pre-treatment protocol. The effects of the chromatographic column, mobile phase, and fragmentation voltage on the separation and sensitivity of the 86 substances were evaluated to determine the optimum instrument conditions. An accurate mass database and fragment ion library were created for the rapid qualitative and quantitative analysis of the 86 illegally added chemicals in fishery drugs. The retention time, isotopic abundance and spacing, and precise mass of the principal diagnostic ion for each analyte were used for identification. The information on the fragment ions obtained from the target MS/MS profiles was compared with that from a database to ensure the accuracy of the qualitative results. The chromatographic peak area of each target analyte was used for quantification. The analytical detection was based on the retention time deviation of ±0.35 min, accurate mass deviation of ±10×10-6, and major adduct forms, including [M+H]+, [M+Na]+, and [M+NH4]+. To evaluate the matrix effects of the 86 target chemicals at varied dilution ratios, two types of antibiotics and four types of Chinese herbal medicines were selected as typical samples. Considering the instrument tolerance as well as sensitivity and accuracy of the procedure, the recommended dilution ratios for antibiotics and Chinese herbal medicines were 50 times and 10 times, respectively. Two different types of calibration curves were prepared; one was the solvent calibration curve for antibiotics and the other was the matrix calibration curve for Chinese herbal medicines. For a given concentration, the calibration curves of the 86 target chemicals were linear with correlation coefficients of at least 0.99. The recoveries ranged from 76.8% to 112.1% with relative standard deviations (RSDs) (n=3) of less than 11.7%. The limit of quantification (LOQ) ranges of the compounds in Chinese herbal medicines and antibiotics were 1-15 mg/kg and 5-75 mg/kg, respectively. To evaluate the screening detection limits (SDLs) of each compound, a mixed standard solution was added to a fishery drug sample at varied concentrations. The SDL ranges of the compounds in Chinese herbal medicines and antibiotics were 1-15 and 5-50 mg/kg, respectively. This approach resulted in SDLs that satisfy the actual screening requirements. Because of its rapid nature, simplicity, accuracy, and sensitivity, the method may be used in the high-throughput screening and identification of illegally added chemicals in many types of fishery drugs. This method was applied to a monitoring project for the quality and safety of fishery inputs in Zhejiang Province. Sixty fishery drug samples were evaluated, among which eight Chinese herbal medicine samples were found to contain unspecified ingredients and one antibiotic sample was found to be free of any active substances. Thus, an effective technical method to monitor the quality and safety of fishery drugs was developed.
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Explotaciones Pesqueras , Espectrometría de Masas en Tándem , Antibacterianos , Cromatografía Líquida de Alta Presión , Cromatografía LiquidaRESUMEN
By utilizing the tight-binding method, the electronic spectrum and states distribution of square Janus monolayer black arsenic phosphorus (b-AsP) quantum dots (QDs) in the presence of a perpendicular magnetic field are explored. Strong in-gap states of b-AsP QDs, whose probability densities are distributed on the armchair boundary (armchair edge states) appear in the energy gap of host perfect two-dimensional b-AsP. The corresponding energy levels of the armchair edge states can degenerate to the Landu energy levels upon applying a perpendicular magnetic field. When an in-plane polarized light is introduced, due to the presence of armchair edge states, the edge-to-edge transitions are mainly induced from the armchair edge (hole) states to zigzag edge (electron) states. The optical absorption undergoes blue shift as a function of the magnetic field. Our work suggests tunable optical properties via modulating the armchair edge states of a b-AsP QD and provides a theoretical basis for the design of b-AsP-based optoelectronic devices.
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Large clinical trials and real-world studies have demonstrated that the beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on renal outcomes regardless of the presence of diabetes. However, the mechanism remains obscure. Here, we analyze the anti-fibrotic and anti-inflammatory effects of dapagliflozin, a SGLT2 inhibitor, on renal alternations using the ischemia/reperfusion-induced fibrosis model. Transcriptome and metabolome analysis showed that the accumulation of tricarboxylic acid (TCA) cycle metabolites and upregulation of inflammation in fibrosis renal cortical tissue were mitigated by dapagliflozin treatment. Moreover, dapagliflozin markedly relieved the activation of mammalian target of rapamycin and hypoxia inducible factor-1α signaling and restored tubular cell-preferred fatty acid oxidation. Notably, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was strikingly blocked by dapagliflozin. We further demonstrated that the immunomodulatory metabolite itaconate derived from the TCA cycle was significantly boosted as a result of decreased isocitrate dehydrogenase 2 and increased immune-responsive gene 1 and mitochondrial citrate carrier in dapagliflozin-treated mice, which contributed to the inhibitory effect of dapagliflozin on NLRP3 inflammasome activation. Furthermore, administration of cell-permeable itaconate surrogate prevented activation of NLRP3 inflammasome and protected kidney against fibrosis development. Our results identify a novel mechanism coupling metabolism and inflammation for kidney benefits of SGLT2 inhibition in progressive chronic kidney disease.
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Compuestos de Bencidrilo/farmacología , Glucósidos/farmacología , Inflamasomas/metabolismo , Enfermedades Renales/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Transportador 2 de Sodio-Glucosa/metabolismo , Succinatos/metabolismo , Animales , Ciclo del Ácido Cítrico/efectos de los fármacos , Fibrosis , Enfermedades Renales/tratamiento farmacológico , Masculino , RatonesRESUMEN
Impaired energy metabolism in proximal tubular epithelial cells (PTECs) is strongly associated with various kidney diseases. Here, we characterized proximal tubular phenotype alternations during kidney injury and repair in a mouse model of folic acid nephropathy, in parallel, identified carnitine palmitoyltransferase 1α (CPT1α) as an energy stress response accompanied by renal tubular dedifferentiation. Genetic ablation of Cpt1α aggravated the tubular injury and interstitial fibrosis and hampered kidney repair indicate that CPT1α is vital for the preservation and recovery of tubular phenotype. Our data showed that the lipid accumulation and mitochondrial mass reduction induced by folic acid were persistent and became progressively more severe in PTECs without CPT1α. Interference of CPT1α reduced capacities of mitochondrial respiration and ATP production in PTECs, and further sensitized cells to folic acid-induced phenotypic changes. On the contrary, overexpression of CPT1α protected mitochondrial respiration and prevented against folic acid-induced tubular cell damage. These findings link CPT1α to intrinsic mechanisms regulating the mitochondrial respiration and phenotype of kidney tubules that may contribute to renal pathology during injury and repair.
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Carnitina O-Palmitoiltransferasa/metabolismo , Túbulos Renales/enzimología , Túbulos Renales/patología , Mitocondrias/metabolismo , Adenosina Trifosfato/biosíntesis , Animales , Nitrógeno de la Urea Sanguínea , Carnitina O-Palmitoiltransferasa/deficiencia , Respiración de la Célula , Células Cultivadas , Creatinina/metabolismo , Fibrosis , Ácido Fólico , Enfermedades Renales/enzimología , Enfermedades Renales/patología , Túbulos Renales/lesiones , Túbulos Renales/ultraestructura , Metabolismo de los Lípidos , Masculino , Ratones Endogámicos C57BL , Mitocondrias/ultraestructura , FenotipoRESUMEN
Implementation of piezoelectric multilayer ceramic (MLC) is an effective way to reduce impedance and improve the performance of linear-array transducer for ultrasonic system applications. However, the ultrasonic image derived from a planar linear-array transducer generally suffers from degradation of lateral resolution and contrast. In this article, we designed and fabricated a focused 5-MHz 128-element linear-array ultrasonic transducer with concave structure using five-layered 0.1Pb (Ni1/3Nb2/3)O3 -0.35Pb(Zn1/3Nb2/3)O3 -0.15Pb(Mg1/3Nb2/3)O3-0.1PbZrO3-0.3PbTiO3 (PNN-PZN-PMN-PZ-PT) piezo- electric ceramic. The transducer showed a bandwidth of 63% at -6 dB and the lateral resolution up to 0.33 mm. An improved transmission signal of 90% higher than a commercial single-layer ceramic transducer was also achieved. We further demonstrated high-resolution photoacoustic imaging with the obtained concave linear-array transducer.
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Emerging ultrasound imaging modality based on optical-generated acoustic waves, such as photoacoustic (PA) imaging, has enabled novel functional imaging on biological samples. The performance of the ultrasonic transducer plays a critical role in producing higher quality PA images. However, the high electrical impedance of the small piezoelectric elements in the transducer array causes an electrical mismatch with external circuitry and results in degraded sensitivity. One effective method for reducing the electrical impedance is to implement a piezoelectric multilayer configuration instead of the conventional single layer for the transducer. In this work, we introduced an ultrasonic transducer comprising a piezoelectric polymer multilayer structure produced by an innovative multicycle powder-based electrophoretic deposition, using a suspension of polymer nanoparticles. The multicycle electrophoretic deposition overcomes the redissolution issue in solution-based methods. The ultrasonic transducer comprising the piezoelectric polymer multilayer exhibits significantly enhanced receiving sensitivity as compared to the ultrasonic transducer using a single layer. Ultrasonic transducer with multielement array configuration is obtained using the piezoelectric polymer multilayer, and PA imaging with improved resolution is demonstrated. Theoretical analysis shows that the enhanced transducer performance is mainly attributed to the improved electrical impedance match between the piezoelectric polymer element in the transducer and external receiving circuit.
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Inhibition of sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment. The potential protective role of SGLT2 inhibition on diabetic kidney disease (DKD) and underlying mechanism, however, remains unknown. In this study, metabolic switch was examined using kidney samples from human with diabetes and streptozocin (STZ)-induced experimental mouse model of diabetes treated with or without SGLT2 inhibitor dapagliflozin. Results were further validated using primarily cultured proximal tubule epithelial cells. We found that DKD development and progression to renal fibrosis entailed profound changes in proximal tubule metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation, which is associated with the increased expression of HIF-1α. Diabetes-induced tubulointerstitial damage, such as macrophage infiltration and fibrosis, was significantly improved by dapagliflozin. Consistent with the effects of these beneficial interventions, the metabolic disorder was almost completely eliminated by dapagliflozin. The increased level of HIF-1α in renal proximal tubule was nearly nullified by dapagliflozin. Moreover, dapagliflozin protects against glucose-induced metabolic shift in PTCs via inhibiting HIF-1α. It suggests that SGLT2 inhibition is efficient in rectifying the metabolic disorder and may be a novel prevention and treatment strategy for kidney tubule in DKD.
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Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Glucosa/metabolismo , Glucólisis/fisiología , Sodio/metabolismo , Animales , Glucemia/metabolismo , Glucólisis/efectos de los fármacos , Humanos , Hipoglucemiantes/farmacología , Riñón/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales Proximales/metabolismo , Metabolismo de los Lípidos/fisiología , Lípidos/farmacología , Masculino , RatonesRESUMEN
Mitochondrial dysfunction leads to loss of renal function and structure; however, the precise mechanisms by which mitochondrial function can regulate renal fibrosis remain unclear. Proximal tubular cells (PTCs) prefer fatty acid oxidation as their energy source and dysregulation of lipid metabolism has been linked to tubulointerstitial fibrosis (TIF). Here, we demonstrated that mitochondrial uncoupling protein 2 (UCP2) regulates TIF through the stimulation of lipid deposition and extracellular matrix (ECM) accumulation. We show that UCP2 expression was increased in human biopsy sample and mouse kidney tissues with TIF. Moreover, UCP2-deficient mice displayed mitigated renal fibrosis in I/R-induced mouse model of TIF. Consistent with these results, UCP2 deficiency displayed reduced lipid deposition and ECM accumulation in vivo and in vitro. In UCP2-deficient PTCs, inhibition of TIF resulted from downregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator of lipid metabolism and ECM accumulation. Furthermore, we describe a molecular mechanism by which UCP2 regulates HIF-1α stabilization through regulation of mitochondrial respiration and tissue hypoxia during TIF. HIF-1α inhibition by siRNA suppressed lipid and ECM accumulation by restoration of PPARα and CPT1α, as well as suppression of fibronectin and collagen I expression in PTCs. In conclusion, our results suggest that UCP2 regulates TIF by inducing the HIF-1α stabilization pathway in tubular cells. These results identify UCP2 as a potential therapeutic target in treating chronic renal fibrosis.
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Hipoxia/metabolismo , Isquemia/metabolismo , Enfermedades Renales/metabolismo , Riñón/lesiones , Metabolismo de los Lípidos , Proteína Desacopladora 2/metabolismo , Animales , Respiración de la Célula , Células Cultivadas , Matriz Extracelular/metabolismo , Fibrosis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/patología , Enfermedades Renales/patología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Oxígeno/metabolismo , Sustancias Protectoras/metabolismo , Daño por Reperfusión/patología , Proteína Desacopladora 2/deficienciaRESUMEN
Increasing array transducer bandwidth (BW) and signal-to-noise ratio (SNR) is a critical issue for producing a high-quality medical ultrasound image. However, array elements with small size tend to have poor sensitivity due to a much higher impedance compared with the electrical impedance of the transmitter and receiver circuit. Implementation of multilayer ceramic (MLC) is an effective way of reducing impedance, and thus, with a potential for improving SNR for an ultrasonic probe. In this work, we fabricated multilayer piezoelectric ceramic with a composition of 0.1Pb(Ni1/3Nb2/3)O3-0.35Pb(Zn1/3Nb2/3)O3-0.15Pb(Mg1/3Nb2/3)O3-0.1PbZrO3-0.3PbTiO3-4mol% excess NiO (PNN-PZN-PMN-PZ-PT), by a roll to roll tape casting process and co-fired with 90Ag/10Pd electrode at a low temperature of 950 °C. Using five-layer MLC (5L-MLC) as obtained, we designed and demonstrated a 5 MHz 32-element array transducer for ultrasonic and photoacoustic imaging. The five-layer transducer element exhibited a BW of 87% at -6 dB, substantially higher than 62% for single-layer ceramic (SLC) element. In addition, the insertion loss was improved by 16.2 dB over the SLC element with an external impedance of 50 Ω . Both the experimental results and theoretical analysis showed that our array transducer made of the PNN-PZN-PMN-PZ-PT MLC is promising for acquiring high-quality ultrasonic and photoacoustic images.
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Cerámica/química , Transductores , Ultrasonografía/instrumentación , Diseño de Equipo , Fantasmas de Imagen , TemperaturaRESUMEN
In this paper, lead-free 0.965(K0.45Na0.55) (Nb0.96Sb0.04)O3-0.0375Bi0.5Na0.5Zr0.85Hf0.15O3 (KNNS-BNZH)/epoxy 1-3 composite was designed and fabricated with the dice-and-fill method. The composite material exhibited a high thickness electromechanical coupling coefficient ( kt = 0.7 ), high piezoelectric constant ( d33 = 350 pC N-1), relatively low mechanical quality factor ( Qm = 5 ), and relatively low acoustic impedance. An ultrasonic transducer with a center frequency of 5 MHz was produced based on the 1-3 KNNS-BNZH/epoxy composite, showing a broad bandwidth of 80% (-6 dB) and two-way insertion loss of -30 dB. Ultrasonic and photoacoustic images were further demonstrated. The outstanding performance of the 1-3 KNNS-BNZH/epoxy composite transducer competitive to Pb(Zr1-xTix)O3 (PZT)-based transducers suggests that the lead-free material can serve as a promising alternative to Pb-based piezoelectric materials for ultrasonic applications.