Several blood-based biomarkers are promising to be used in the diagnosis of Alzheimer's disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the ...clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic performance of these biomarkers before clinical implementation, which is important for the establishment of reference ranges and the interpretation of results.
This study is a cross-sectional analysis based on ADNI cohort. Renal function was determined by the estimated glomerular filtration rate (eGFR). Plasma Aβ42/40 was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma p-tau181 and NfL were analyzed by Single Molecule array (Simoa) technique. 18F florbetapir-PET (Aβ-PET) was used as a reference standard to estimate the brain amyloid load. The cutoff of Aβ-PET positivity was defined as ≥1.11. Linear regression models were used to investigate the associations of continuous eGFR with each plasma biomarker separately. The diagnostic accuracies of plasma biomarkers for positive brain amyloid across different renal function groups were analyzed by Receiver operating characteristic (ROC) curve. Youden-Index was used to determine the cutoff levels.
A total of 645 participants were included in this study. The levels and diagnostic performance of Aβ42/40 were not affected by renal function. eGFR was only found negatively associated with p-tau181 levels in Aβ-PET negetive sample (
= -0.09,
= 0.039). eGFR was found negatively associated with NfL levels both in whole sample and Aβ-PET stratified groups (
= -0.27,
< 0.001 in whole sample;
= -0.28,
= 0.004 in A
;
= -0.27,
< 0.001 in A
). The diagnostic accuracies of p-tau181 and NfL were not affected by renal function. But the cutoff values of p-tau181 and NfL changed in participants with mild to moderate eGFR decline compared to participants with normal eGFR.
Plasma Aβ42/40 was a robust biomarker for AD which was not affected by renal function. Plasma p-tau181 and NfL levels were affected by renal function, specific reference values of them should be considered in populations with different renal function stages.
Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. Preeclampsia affects 5–8% of pregnancies in the United States, ...causing a significant public health and economic burden. Despite extensive research, the etiology and pathogenesis of preeclampsia remain elusive, but have been correlated with maternal conditions such as obesity. In recent decades, the incidence of preeclampsia increased along with the prevalence of obesity among women of reproductive age. Maternal obesity has been shown to negatively affect pregnancy in almost all aspects. However, the precise mechanisms by which obesity influences preeclampsia are unclear. Ankyrin repeat and SOCS Box Containing protein 4 (ASB4) is an E3 ubiquitin ligase that can promote the degradation of a wide range of target proteins. ASB4-null mice display a full spectrum of preeclampsia-like phenotypes during pregnancy including hypertension, proteinuria, and decreased litter size. Furthermore, maternal obesity induced by a high-fat diet aggravates preeclampsia-like phenotypes in pregnant mice lacking ASB4. Variants in the ASB4 gene have been associated with obesity in humans, and a functional connection between the ASB4 gene and obesity has been established in mice. This review discusses the connections between preeclampsia, obesity, and ASB4.
Vascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment ...biological processes and pathways, key targets, and the underlying mechanism by microarray bioinformatic analysis. We selected GSE122063 related to the autopsy samples of VaD for analysis. We first took use of Weighted Gene Co-expression Network Analysis (WGCNA) to achieve modules related to VaD and hub genes. Second, we filtered out significant differentially expressed genes (DEGs). Third, significant DEGs then went through Geno Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Fourth, Gene Set Enrichment Analysis (GSEA) was performed. At last, we constructed the protein–protein interaction (PPI) network. The results showed that the yellow module had the strongest correlation with VaD, and we finally identified 21 hub genes. Toll-like receptor 2 (TLR2) was the top hub gene and was strongly correlated with other possible candidate genes. In total, 456 significant DEGs were filtered out and these genes were found to be enriched in the Toll receptor signaling pathway and several other immune-related pathways. In addition, Gene Set Enrichment Analysis results showed that similar pathways were significantly over-represented in TLR2-high samples. In the PPI network, TLR2 was still an important node with high weight and combined scores. We concluded that the TLR2 acts as a key target in neuroinflammation which may participate in the pathophysiological process of VaD.
The detection for small molecules with low concentrations is known to be challenging for current chemical and biological sensors. In this work, we designed a highly sensitive plasmonic biosensor ...based on the symmetric metal cladding plasmonic waveguide (SMCW) structure for the detection of biomolecules. By precisely designing the configuration and tuning the thickness of the guiding layer, ultra-high order modes can be excited, which generates a steep phase change and a large position shift from the Goos−Hänchen effect (with respect to refractive index changes). This position shift is related to the sharpness of the optical phase change from the reflected signal of the SPR sensing substrate and can be directly measured by a position sensor. Based on our knowledge, this is the first experimental study done using this configuration. Experimental results showed a lateral position signal change > 90 µm for glycerol with a sensitivity figure-of-merit of 2.33 × 104 µm/RIU and more than 15 µm for 10−4 M biotin, which is a low molecular weight biomolecule (less than 400 Da) and difficult to be detected with traditional SPR sensing techniques. Through integrating the waveguide with a guiding layer, a strong improvement in the electric field, as well as sensitivity have been achieved. The lateral position shift has been further improved from 14.17 µm to 284 µm compared with conventional SPR substrate with 50 nm gold on single side. The as-reported sensing technique allows for the detection of ultra-small biological molecules and will play an important role in biomedical and clinical diagnostics.
In this study, the texture evolutions of two Mg materials during tension are explored. In-situ X-ray synchrotron and Visco-Plastic Self-Consistent (VPSC) modeling are employed to investigate the ...different deformation modes between pure Mg and Mg–15Gd (wt.%) alloy. These two materials with a strong extrusion texture show large different slip/twinning activity behaviors during tensile deformation. The basal 〈a〉 slip has the highest contribution to the initial stage of plastic deformation for pure Mg. During the subsequent plastic deformation, the prismatic slip is dominant due to the strong ED // 〈100〉 fiber texture. In contrast, the deformation behavior of Mg–15Gd alloy is more complex. Twinning and basal slip are dominant at the early stage of plastic deformation, but further deformation results in the increased activation of prismatic and pyramidal slips. In comparison to pure Mg, the ratios of the critical resolved shear stress (CRSS) between non-basal slip and basal slip of the Mg–15Gd alloy are much lower.
Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and ...N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.
Depth imaging using single-photon lidar (SPL) is crucial for long-range imaging and target recognition. Subtractive-dithered SPL breaks through the range limitation of the coarse timing resolution of ...the detector. Considering the weak signals at kilometer distances, we present a novel imaging method based on blending subtractive dither with a total variation image restoration algorithm. The spatial correlation is well-considered to obtain more accurate depth profile images with fewer signal photons. Subsequently, we demonstrate the subtractive dither measurement at ranges up to 1.8 km using an array of avalanche photodiodes (APDs) operating in the Geiger mode. Compared with the pixel-wise maximum-likelihood estimation, the proposed method reduces the depth error, which has great promise for high-depth resolution imaging at long-range imaging.
Single-photon light detection and ranging (LiDAR) has widespread applications due to the ultra-high sensitivity of the single-photon detector. However, the reconstruction has been plagued by multiple ...types of noise caused by crosstalk, dark counts, and background light. Artifacts produced by crosstalk are particularly difficult to distinguish directly from the signal for single photon avalanche diode (SPAD) array detector. This work proposes a waveforms-guided depth image estimation method to remove the signal artifacts effectively. Experiments show that a region of interest recognition ratio of 1.02 is achieved at 4.2 km. The study demonstrates that this waveform-guided method has excellent potential for accurate target recognition in a long range.
Research has long centered on the pathophysiology of pain. The Transient Receiver Potential (TRP) protein family is well known for its function in the pathophysiology of pain, and extensive study has ...been done in this area. One of the significant mechanisms of pain etiology and analgesia that lacks a systematic synthesis and review is the ERK/CREB (Extracellular Signal-Regulated Kinase/CAMP Response Element Binding Protein) pathway. The ERK/CREB pathway-targeting analgesics may also cause a variety of adverse effects that call for specialized medical care. In this review, we systematically compiled the mechanism of the ERK/CREB pathway in the process of pain and analgesia, as well as the potential adverse effects on the nervous system brought on by the inhibition of the ERK/CREB pathway in analgesic drugs, and we suggested the corresponding solutions.
For developing a continuous-wave (CW) tunable Terahertz-wave (THz-wave) source using difference-frequency generation (DFG) in highly nonlinear optical crystals, we proposed and demonstrated a ...dual-wavelength fiber ring laser system operating around 1060 nm based on wideband chirped fiber Bragg gratings (CFBGs) and semiconductor optical amplifier (SOA). Thermo-induced phase shift along the CFBG produces a very sharp transmission spike therefore two lasing wavelengths with single longitudinal mode operation are oscillating simultaneously within the fiber ring cavity. Due to the inhomogeneous gain broadening property of SOA, the wavelength spacing of our dual-wavelength fiber laser can be continuously adjusted from 0.3 to 9.5 nm. By using this single emitter dual-wavelength fiber laser to pump an organic nonlinear DAST crystal, type-0 collinear phase matching of DFG process can be fulfilled and monochromatic THz wave ranging from 0.5 to 2 THz has been successfully generated.
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