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In this article, a novel approach is presented for drift‐aware feature learning aimed at calibrating drift biases in soft sensors for long‐term use. The proposed method leverages an autoencoder for data preprocessing to extract expressive signal drift traces features, and incorporates drift characteristics through the latent space representation in a long short‐term memory (LSTM) regression neural network. In the results, it is demonstrated that the proposed approach outperforms other typical recurrent neural networks, such as LSTM, gated recurrent unit, and bidirectional LSTM, with a reduced root mean square error of 60% for the training dataset (≈2.5 h) and 80% for the testing dataset (≈20 h). The proposed approach has the potential to optimize the performance of soft sensors with long‐term drift and reduce the need for frequent recalibration. By compensating for sensor drift using existing prior information and limited time data, the proposed neural network can effectively reduce the complexity and computational burden of the system, without the need for additional settings or hyperparameter fine‐tuning.

Abstract The detection and analysis of rare cells in complex media such as blood is increasingly important in biomedical research and clinical diagnostics. Micro-Hall detectors (μHD) for magnetic detection in blood have previously demonstrated ultrahigh sensitivity to rare cells. This sensitivity originates from the minimal magnetic background in blood, obviating cumbersome and detrimental sample preparation. However, the translation of this technology to clinical applications has been limited by inherently low throughput (

Mitochondrial biogenesis and dynamics are associated with renal mitochondrial dysfunction and the pathophysiological development of diabetic kidney disease (DKD). Decreased p66Shc expression prevents DKD progression by significantly regulating mitochondrial function. Grape seed proanthocyanidin extract (GSPE) is a potential therapeutic medicine for multiple kinds of diseases. The effect of GSPE on the mitochondrial function and p66Shc in DKD has not been elucidated. Hence, we decided to identify p66Shc as a therapeutic target candidate to probe whether GSPE has a renal protective effect in DKD and explored the underlying mechanisms. Methods. In vivo, rats were intraperitoneally injected with streptozotocin (STZ) and treated with GSPE. Biochemical changes, mitochondrial morphology, the ultrastructure of nephrons, and protein expression of mitochondrial biogenesis (SIRT1, PGC-1α, NRF1, TFAM) and dynamics (DRP1, MFN1) were determined. In vitro, HK-2 cells were transfected with p66Shc and treated with GSPE to evaluate changes in cell apoptosis, reactive oxygen species (ROS), mitochondrial quality, the protein expression. Results. In vivo, GSPE significantly improved the renal function of rats, with less proteinuria and a lower apoptosis rate in the injured renal tissue. Besides, GSPE treatment increased SIRT1, PGC-1α, NRF1, TFAM, and MFN1 expression, decreased p66Shc and DRP1 expression. In vitro, overexpression of p66Shc decreased the resistance of HK-2 cells to high glucose toxicity, as shown by increased apoptosis and ROS production, decreased mitochondrial quality and mitochondrial biogenesis, and disturbed mitochondrial dynamic homeostasis, ultimately leading to mitochondrial dysfunction. While GSPE treatment reduced p66Shc expression and reversed these changes. Conclusion. GSPE can maintain the balance between mitochondrial biogenesis and dynamics by negatively regulating p66Shc expression.

We characterize the effect of ferromagnetic nickel nanoparticles (size ∼6 nm) on the magnetotransport properties of chemical-vapor-deposited (CVD) graphene. The nanoparticles were formed by thermal annealing of a thin Ni film evaporated on top of a graphene ribbon. The magnetoresistance was measured while sweeping the magnetic field at different temperatures, and compared against measurements performed on pristine graphene. Our results show that, in the presence of Ni nanoparticles, the usually observed zero-field peak of resistivity produced by weak localization is widely suppressed (by a factor of ∼3), most likely due to the reduction of the dephasing time as a consequence of the increase in magnetic scattering. On the other hand, the high-field magnetoresistance is amplified by the contribution of a large effective interaction field. The results are discussed in terms of a local exchange coupling, J∼6 meV, between the graphene π electrons and the 3d magnetic moment of nickel. Interestingly, this magnetic coupling does not affect the intrinsic transport parameters of graphene, such as the mobility and transport scattering rate, which remain the same with and without Ni nanoparticles, indicating that the changes in the magnetotransport properties have a purely magnetic origin.

The semiconducting ABC configuration of trilayer graphene is more challenging to grow on large scales than its semimetallic ABA counterpart. Here, an approach to trilayer growth via chemical vapor deposition is presented that utilizes substrate curvature to yield enhanced fraction and size of ABC domains.

BackgroundMutation of MMACHC causes inherited cobalamin C disease with methylmalonic academia (MMA) and homocysteinemia. Renal complications may also be present in patients with this deficiency. However, membranous nephropathy secondary to cobalamin C disease has not been reported to date.Case PresentationWe encountered a 17-year-old female patient with a trans-compound mutation of MMACHC who presented with membranous nephropathy, MMA, homocysteinemia, and hyperuricemia. The mutations of c.80A>G (chr1:45966084) and c.482G>A (chr1:45974520) (predicting p.Gln27Arg and p.Arg161Gln missense changes at the amino acid level) had been inherited from her father and mother, respectively. Hydroxocobalamin, betaine, and L-carnitine were administered. The patient achieved complete remission of the membranous nephropathy and resolution of the MMA, homocysteinemia, and hyperuricemia.ConclusionMembranous nephropathy secondary to cobalamin C disease is reversible with timely intervention.

Field-effect transistors have attracted significant attention in chemical sensing and clinical diagnosis, due to their high sensitivity and label-free operation. Through a scalable photolithographic process in this study, we fabricated graphene-based ion-sensitive field-effect transistor (ISFET) arrays that can continuously monitor sodium ions in real-time. As the sodium ion concentration increased, the current–gate voltage characteristic curves shifted towards the negative direction, showing that sodium ions were captured and could be detected over a wide concentration range, from 10−8 to 10−1 M, with a sensitivity of 152.4 mV/dec. Time-dependent measurements and interfering experiments were conducted to validate the real-time measurements and the highly specific detection capability of our sensor. Our graphene ISFETs (G-ISFET) not only showed a fast response, but also exhibited remarkable selectivity against interference ions, including Ca2+, K+, Mg2+ and NH4+. The scalability, high sensitivity and selectivity synergistically make our G-ISFET a promising platform for sodium sensing in health monitoring.

We present a novel method for fabricating a high-density carbon nanotube microelectrode array (MEA) chip. Vertically aligned carbon nanotubes (VACNTs) were synthesized by microwave plasma-enhanced chemical vapor deposition and thermal chemical vapor deposition. The device was characterized using electrochemical experiments such as cyclic voltammetry, impedance spectroscopy and potential transient measurements. Through-silicon vias (TSVs) were fabricated and partially filled with polycrystalline silicon to allow electrical connection from the high-density electrodes to a stimulator microchip. In response to the demand for higher resolution implants, we have developed a unique process to obtain a high-density electrode array by making the microelectrodes smaller in size and designing new ways of routing the electrodes to current sources. Keywords: Microelectrode array, Neural implant, Carbon nanotubes, Through-silicon via interconnects, Microfabrication

Simpler and more rapid approaches for therapeutic drug-level monitoring are highly desirable to enable use at the point-of-care. We have developed an all-electronic approach for detection of the HIV drug tenofovir based on scalable fabrication of arrays of graphene field-effect transistors (GFETs) functionalized with a commercially available DNA aptamer. The shift in the Dirac voltage of the GFETs varied systematically with the concentration of tenofovir in deionized water, with a detection limit less than 1 ng/mL. Tests against a set of negative controls confirmed the specificity of the sensor response. This approach offers the potential for further development into a rapid and convenient point-of-care tool with clinically relevant performance.

Introduction: We aimed to assess our hypothesis that the expression changes of arginine vasopressin (AVP) in the magnocellular neurosecretory cells (MNCs) of hypothalamus and V2 receptor for AVP (RVP) in kidney may contribute to the pathogenesis of diabetic nephropathy (DN).Material and Methods: Twenty-five male Wistar rats were randomly assigned to the control group and the diabetes mellitus (DM) group. Periodic acid-Schiff (PAS) staining and electron microscopy were used for morphological studies. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is standard for visualization of reactive astrocytes in the hypothalamus. Hypothalamus was used for immunofluorescence of AVP. Kidney was used for immunohistochemical staining of RVP. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was used for quantitative determinations of AVP mRNA in hypothalamus and RVP mRNA in kidney. Western blot was used to measure the protein expression of AVP in hypothalamus and RVP in kidney.Results: Morphological studies showed abnormalities in kidney and hypothalamus in the DM group. The number of neurons and the gray value of astrocytes in hypothalamus in the DM group were markedly decreased. The expression level of AVP in hypothalamus and the expression level of RVP in kidney of DM rats were significantly increased. The positive correlations between the proteinuria and expression (mRNA and protein) of AVP, proteinuria and expression (mRNA and protein) of RVP, and the expression of AVP and RVP levels were found.Conclusions: AVP was upregulated in the MNCs of hypothalamus and RVP was upregulated in kidney in streptozotocin-induced DM rats, indicating their potential roles in the development of DN. [ABSTRACT FROM AUTHOR]

All-electronic DNA biosensors based on graphene field-effect transistors (GFETs) offer the prospect of simple and cost-effective diagnostics. For GFET sensors based on complementary probe DNA, the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ~20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction. This enables detection of 21 mer target DNA at sub-fM concentration and provides superior specificity against single-base mismatched oligomers. The work is based on a scalable fabrication process for biosensor arrays that is suitable for multiplexed detection. This approach overcomes the binding-affinity-dependent sensitivity of nucleic acid biosensors and offers a pathway toward multiplexed and label-free nucleic acid testing with high accuracy and selectivity. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the major causes of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are known to act as antioxidants. The current study aimed to determine the effects of GSPE on the streptozotocin (STZ)-induced diabetic rat model and to explore the underlying mechanism of its action. Wistar rats were induced into a diabetic state by injection of STZ and were treated with 250 mg⋅kg-1⋅day-1 GSPE for 24 weeks. Kidney samples were collected for observation of renal pathological changes by light microscope (periodic acid-Schiff staining) and electron microscopy. Reverse transcription-polymerase chain reaction, western blotting, and immunohistochemical staining were used to detect the mRNA and protein expression of the receptor for advanced glycation end-products (RAGE), nephrin and podocin. The results indicated that diabetic rats treated with GSPE had markedly reduced Ccr, urinary albumin excretion, ratio of kidney weight to body weight, AGEs and ECM accumulation (P<0.01) compared with that in the diabetic rats. GSPE treatment can also reverse the renal pathological damage in diabetic rats. Further results indicated that GSPE treatment significantly decreased the RAGE expression level (P<0.01), and significantly increased the expression level of nephrin in the kidney and glomeruli of diabetic rats (P<0.01). However, no significant differences were identified in the expression of podocin following GSPE treatment (P>0.05). In conclusion, the results demonstrated that GSPE exerts a reno-protective effect by decreasing urinary albumin excretion and reversing renal pathological damage in diabetic rats. The underlying mechanism of GSPE activity is associated with the decreased expression of the AGEs/RAGE axis and the increased expression of nephrin in diabetic rats. [ABSTRACT FROM AUTHOR]

Simpler and more rapid approaches for therapeutic drug-level monitoring are highly desirable to enable use at the point-of-care. We have developed an all-electronic approach for detection of theHIVdrug tenofovir based on scalable fabrication of arrays of graphene field-effect transistors (GFETs) functionalized with a commercially available DNA aptamer. The shift in the Dirac voltage of the GFETs varied systematically with the concentration of tenofovir in deionized water, with a detection limit less than 1 ng/mL. Tests against a set of negative controls confirmed the specificity of the sensor response. This approach offers the potential for further development into a rapid and convenient point-of-care tool with clinically relevant performance. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is used as an antineoplastic drug in the clinic, but its nephrotoxicity limits its use. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant. In this study, we investigated whether GSPE can prevent CP-induced nephrotoxicity and explored the underlying mechanism. Male C57/BL6 mice were randomly divided into four groups: control group (N), CP group (C), receiving an intraperitoneal (ip) injection of 20 mg/kg CP, GSPE group (G), receiving an intragastric (ig) dose of 500 mg/kg GSPE, and CP+GSPE group (C+G), where ig administration of GSPE was performed 30 min prior to ip injection of CP, followed by an additional ig administration of GSPE 72 h later. Blood and kidney samples were collected 120 h after treatment. The pathological changes in the kidney were examined by periodic acid-Schiff (PAS) staining, while the protein levels of glucose-regulated protein 78 (GRP78), phosphorylated-extracellular signal-regulated kinase (p-ERK) and caspase-12 were examined by western blotting and immunohistochemical staining. Apoptosis was examined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Compared to the CP group, the CP+GSPE group had a significant decrease in the level of blood urea nitrogen (BUN), serum creatinine (Scr) and reduced renal index (RI) (P<0.05), and showed limited histopathological damage. The number of TUNEL-positive cells was significantly reduced in the CP+GSPE group compared to the CP group (P<0.05), and the protein expression of GRP78, p-ERK and caspase-12 was significantly reduced in the CP+GSPE group (P<0.05). We conclude that GSPE can protect the renal function from CP-induced nephrotoxicity and can attenuate the endoplasmic reticulum (ER) stress-induced apoptosis via regulation of the caspase-12 pathway. [ABSTRACT FROM AUTHOR]

We present experimental evidence of electronic and optical interlayer resonances in graphene van der Waals heterostructure interfaces. Using the spectroscopic mode of a low-energy electron microscope (LEEM), we characterized these interlayer resonant states up to 10 eV above the vacuum level. Compared with nontwisted, AB-stacked bilayer graphene (AB BLG), an ≈0.2  Å increase was found in the interlayer spacing of 30° twisted bilayer graphene (30°-tBLG). In addition, we used Raman spectroscopy to probe the inelastic light-matter interactions. A unique type of Fano resonance was found around the D and G modes of the graphene lattice vibrations. This anomalous, robust Fano resonance is a direct result of quantum confinement and the interplay between discrete phonon states and the excitonic continuum. [ABSTRACT FROM AUTHOR]