Biomedical subjects

Xiao Hu

Publications and source records attributed to Xiao Hu.

At least 19 recordsLinked to original sources

PubMed2026

Generation of an NKX2-1-EGFP reporter iPSC line with inducible Cas9 for lung progenitor cell tracing.

NK2 homeobox 1 (NKX2-1), a master regulator robustly expressed in lung, thyroid, and forebrain, is indispensable for specifying lung epithelial fate and serves as a definitive marker of lung progenitors. Here, we generated a human induced Pluripotent Stem Cell (iPSC) line harboring a doxycycline (dox)-inducible Cas9 and an NKX2-1-EGFP-puro reporter via CRISPR/Cas9-mediated homology-directed repair. This dual-function line combines inducible genome editing with real-time tracing of early lung progenitors, enabling their prospective isolation and screening for stage-specific maturation regulators. Therefore, this engineered iCas9-NKX2-1 EGFP line is a key resource for dissecting human lung development, modeling pulmonary disease, and advancing regenerative therapies.

Humans↗

PubMed2026

Proteomics Analysis of Plasma for Risk of Sepsis: Findings from the Atherosclerosis Risk in Communities Study.

BACKGROUND: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis. METHODS: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses. RESULTS: At ARIC visit three, 669 proteins were associated with the risk of sepsis; 175 were replicated at visit 5. Of these, 90 were validated in the CHS. The top 20 proteins ranked by P value were relevant to acute inflammatory signaling in innate immunity. Pathway analyses implicated activation of pro-inflammatory pathways (e.g., cytokine storm signaling) as well as inhibition of anti-inflammatory pathways (e.g., liver X receptor/retinoid X receptor [LXR/RXR] activation), which also play relevant roles in lipid metabolism. CONCLUSIONS: In this analysis, levels of acute inflammatory proteins measured during routine visits were associated with the subsequent incidence of sepsis. An increased risk of sepsis associated with the inhibition of anti-inflammatory pathways, such as LXR/RXR warrants further mechanistic investigation.

Humans↗

PubMed2025

Exploring prognostic genes in the immune microenvironment of acute myeloid leukemia via weighted gene co-expression network analysis.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous blood cancer that arises from transformed myeloid precursor cells in a compromised bone marrow microenvironment. This environment is essential for AML initiation, progression, and relapse. Alongside oncogenic changes in hematopoietic cells, immunological dysregulation also contributes to leukemogenesis. The present study is aimed to identify prognostic genes in stromal and immune cells associated with AML using the weighted gene co-expression network analysis (WGCNA). METHODS: Gene expression profiles were retrieved from The Cancer Genome Atlas database, and immune and stromal cell scores were calculated using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) method. These scores helped identify differentially expressed genes (DEGs), which were then used to create gene clusters through WGCNA. To explore the functions of genes linked to AML subtypes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. A protein-protein interaction network was developed to identify hub genes. The top 18 hub genes were identified using the cytoHubba plug-in in Cytoscape software, and survival analysis was conducted with the Gene Expression Profiling Interactive Analysis 2 online tool. RESULTS: A total of 1097 DEGs were identified, with 601 being upregulated and 496 downregulated. WGCNA analysis indicated that the gray module, comprising 165 genes, had the strongest association with AML subtypes (Cor > 0.3; P < .05). Gene Ontology enrichment analysis demonstrated that the 18 identified hub genes were predominantly associated with neutrophil activation, immune response, secretory granule membrane, and pattern recognition receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were mainly involved in pathways related to phagosome, lysosome, tuberculosis, leishmaniasis, and neutrophil extracellular trap formation. Kaplan-Meier survival analysis of the top 18 hub genes indicated that ITGAM, IL10, and CD163 were significantly correlated with survival outcomes in AML. CONCLUSION: Key stromal and immune-related genes influencing AML patient outcomes were identified, highlighting their potential as therapeutic targets. These discoveries provide deeper insights into the molecular mechanisms driving AML pathogenesis and subtype differentiation.

Leukemia, Myeloid, Acute↗

PubMed2006

Transcriptional interference among the murine beta-like globin genes.

Mammalian beta-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity. To investigate the influence of transcription by the murine embryonic genes on transcription of the other beta-like genes, we generated mice with deletions of the promoter regions of Ey and betah1 and measured transcription of the remaining genes. Deletion of the Ey and betah1 promoters increased transcription of betamajor and betaminor 2-fold to 3-fold during primitive erythropoiesis. Deletion of Ey did not affect betah1 nor did deletion of betah1 affect Ey, but Ey deletion uniquely activated transcription from betah0, a beta-like globin gene immediately downstream of Ey. Protein analysis showed that betah0 encodes a translatable beta-like globin protein that can pair with alpha globin. The lack of transcriptional interference between Ey and betah1 and the gene-specific repression of betah0 did not support LCR competition among the embryonic genes and suggested that direct transcriptional interference from Ey suppressed betah0.

Animals↗

PubMed2006

Classification of surface EMG signals using harmonic wavelet packet transform.

In this paper, an efficient method based on the discrete harmonic wavelet packet transform (DHWPT) is presented to classify surface electromyographic (SEMG) signals. After the relative energy of SEMG signals in each frequency band had been extracted by the DHWPT, a genetic algorithm was utilized to select appropriate features in order to reduce the feature dimensionality. Then, the selected features were used as the input vectors to a neural network classifier to discriminate four types of prosthesis movements. Compared with other classification methods, the proposed method provided high classification accuracy in experimental research. In addition, this method could also save a lot of computational time because the DHWPT has a fast algorithm based on the fast Fourier transform for numerical implementation.

Animals↗

PubMed2006

Multifractal analysis of ventricular fibrillation and ventricular tachycardia.

A study of ventricular fibrillation and ventricular tachycardia was undertaken using multifractal analysis. By applying the method of direct determination of the f(alpha) singularity spectrum, the value of the area of the VF and VT singularity spectrum was calculated. The comparison between the results showed that the value of the area of the VF singularity spectrum tended to be larger than that of the value of the area of the VT singularity spectrum. This makes the multifractal singularity spectrum a powerful criterion for discriminating between VF and VT.

Algorithms↗

PubMed2006

Noise reduction based on ICA decomposition and wavelet transform for the extraction of motor unit action potentials.

We have studied methods for noise reduction of myoelectric signals and for extraction of motor unit action potentials from these signals. Effective MUAP peak detection is the first important step in EMG decomposition. We first combined independent component analysis and wavelet filtering to remove power line interference, and then applied a wavelet filtering method and threshold estimation calculated using wavelet transform to suppress background noise and Gaussian white noise. The technique was applied to single-channel, short-period real myoelectric signals from normal subjects and to artificially generated EMG recordings. In contrast to existing methods based on amplitude single-threshold filtering of the original myoelectric signal or a conventional digitally filtered signal, our technique is fast and robust. Moreover, the proposed algorithm is substantially automatic. The performance has been evaluated with a set of synthetic and experimentally recorded myoelectric signals. The basic tool for testing was power spectrum density (PSD) estimation by the Welch method, which allowed us to analyze the PSD of nonstationary signals.

Action Potentials↗

PubMed2006

MUAP extraction and classification based on wavelet transform and ICA for EMG decomposition.

We have developed an effective technique for extracting and classifying motor unit action potentials (MUAPs) for electromyography (EMG) signal decomposition. This technique is based on single-channel and short perioda9s real recordings from normal subjects and artificially generated recordings. This EMG signal decomposition technique has several distinctive characteristics compared with the former decomposition methods: (1) it bandpass filters the EMG signal through wavelet filter and utilizes threshold estimation calculated in wavelet transform for noise reduction in EMG signals to detect MUAPs before amplitude single threshold filtering; (2) it removes the power interference component from EMG recordings by combining independent component analysis (ICA) and wavelet filtering method together; (3) the similarity measure for MUAP clustering is based on the variance of the error normalized with the sum of RMS values for segments; (4) it finally uses ICA method to subtract all accurately classified MUAP spikes from original EMG signals. The technique of our EMG signal decomposition is fast and robust, which has been evaluated through synthetic EMG signals and real EMG signals.

Action Potentials↗

PubMed2006

A single-lead ECG enhancement algorithm using a regularized data-driven filter.

We presented a novel way of deriving a subspace filter for enhancing a noisy electrocardiogram (ECG) signal contaminated by electromyogram (EMG). The new subspace filter was based on a multiple cycle prediction (MCP) modeling of a single-lead ECG. The adoption of an MCP model resulted in a data matrix more suitable for separating noise and signal subspaces than the linear prediction (LP) model that is implicitly assumed in many existing subspace filters. Alignment of ECG cycles of different length is required for MCP modeling and was handled by a dynamic time warping (DTW) algorithm. A run-time procedure was designed for automatically determining the signal space dimension adaptively. To validate the new filter in a quantitative way, 12 clean realistic ECG segments with different degrees of heart rate variability generated using the ECGSyn program were mixed with different realizations of EMG noise in the MIT-BIH Noise Stress Test Database and locally acquired EMG at a typical 10-dB signal-to-noise ratio. The performance of the proposed method was compared to three existing ECG enhancement algorithms and achieved encouraging results. In addition, various ECG recordings from MIT-Arrythmia database were also mixed with EMG noise and subjected to the same four filters resulting in a qualitative comparison of them.

Algorithms↗

PubMed2006

Nonlinear analysis of cerebral hemodynamic and intracranial pressure signals for characterization of autoregulation.

The objective of this study was to determine whether or not the underlying physiological systems that generates spontaneous arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and intracranial pressure signals could be adequately approximated as a linear stochastic process. Furthermore, a new measure (C) capable of capturing the degree of nonlinear dependency between two ABP and CBFV signals (including a time-varying situation) was proposed for quantifying the degree of cerebral blood flow autoregulation. A surrogate data test of fifteen ABP, CBFV, and intracranial pressure (ICP) segments was conducted for detecting whether there exists a statistically significant deviation from the null hypothesis of linear signals. The extension of the established block computation method of C measure to an adaptive one was achieved. This new algorithm was then applied to study the C evolution using brain injury patients data from a hyperventilation study and two propofol studies. Nonlinearity has not been detected for all the fifteen recordings, neither has nonlinear dependency between CBFV and ABP. However, their presences in some of the signal segments justified the adoption of a nonlinear measure of dependency capable of characterizing both linear and nonlinear correlations for inferring autoregulation status. C measure started to decrease with the introduction of hypocapnia state indicating that hyperventilation may reduce the dependency of CBFV on ABP fluctuations. On the other hand, complex patterns of C measure evolution were observed among 14 cases of propofol data indicating a nontrivial effect of propofol on the dependency of CBFV on ABP.

Adaptation, Physiological↗

PubMed2006

Signaling, polyubiquitination, trafficking, and inclusions: sequestosome 1/p62's role in neurodegenerative disease.

Aggregated misfolded proteins are hallmarks of most neurodegenerative diseases. In a chronic disease state, including pathologic situations of oxidative stress, these proteins are sequestered into inclusions. Accumulation of aggregated proteins can be prevented by chaperones, or by targeting their degradation to the UPS. If the accumulation of these proteins exceeds their degradation, they may impair the function of the proteasome. Alternatively, the function of the proteasome may be preserved by directing aggregated proteins to the autophagy-lysosome pathway for degradation. Sequestosome 1/p62 has recently been shown to interact with polyubiquitinated proteins through its UBA domain and may direct proteins to either the UPS or autophagosome. P62 is present in neuronal inclusions of individuals with Alzheimer's disease and other neurodegenerative diseases. Herein, we review p62's role in signaling, aggregation, and inclusion formation, and specifically as a possible contributor to Alzheimer's disease. The use of p62 as a potential target for the development of therapeutics and as a disease biomarker is also discussed.

Journal Article↗

PubMed2006

[Classification of surface EMG signal based on wavelet transform with nonlinear scale].

Surface EMG (sEMG) signal is a complex nonlinear, non-stationary signal. In this paper, wavelet transform with nonlinear scale (NWT) is introduced. Due to the gradual shortening of its time-resolution, NWT is good at extracting the precise time-frequency information from sEMG signal. First, every sEMG signal (30 sets are for forearm supination and 30 sets are for forearm pronation) is transformed into intensity distribution (time-frequency distribution) by NWT. And then the feature vector is determined from the characteristic roots which are obtained from the intensity distribution by principle component analysis. At last, the two patterns of sEMG signals are identified by BP neural network. The results show that the accurate classification rate is higher gained by NWT than by two conventional time-frequency distributions. At the same time, the calculating complexity of neural network is decreased greatly.

Electromyography↗

PubMed2005

Spectral analysis of blood perfusion in the free latissimus dorsi myocutaneous flap and in normal skin.

To find the properties in the oscillatory components of the cutaneous blood flow on the successful free flap, a wavelet transform was applied to the laser Doppler flowmetry (LDF) signals which were measured simultaneously on the surfaces of the free latissimus dorsi myocutaneous flap and on the adjacent intact skin of the healthy limb, of 18 patients. The frequency interval from 0.0095 to 1.6 Hz was examined and was divided into five subintervals (I: 0.0095-0.021 Hz; II: 0.021-0.052 Hz; III: 0.052-0.145 Hz; IV: 0.145-0.6 Hz and V: 0.6-1.6 Hz) corresponding to endothelial metabolic, neurogenic, myogenic, respiratory and cardiac origins. The average amplitude and total power in the frequency range 0.0095-1.6 Hz as well as within subintervals I, II, IV and V were significantly lower for signals measured on the free flap than those obtained in the healthy limb. However in interval III, they were significantly higher. The normalized spectral amplitude and power in the free flap were significantly lower in only two intervals, I and II, yet in interval III they were significantly higher; no statistical significance was observed in intervals IV and V. The distinctive finding made in this study, aside from the decrease of endothelial metabolic processes and sympathetic control, was the significant increase of myogenic activity in the free flap. It is hoped that this work will contribute towards knowledge on blood circulation in free flaps and make the monitoring by LDF more reliable.

Adolescent↗

PubMed2005

Robust half-metallic character and large oxygen magnetism in a perovskite cuprate.

The new perovskite cuprate material Sr8CaRe3Cu4O24, which behaves ferrimagnetically and shows an unusually high Curie temperature (T(C) approximately 440 K), is found from density-functional theory calculation to display several surprising properties after hole doping or chemical substitution: (1) Half metal (HM) is realized by replacing Re with W or Mo while T(C) remains high; (2) hole-doped Sr8CaRe3Cu4O24 is also HM with high T(C). Moreover, we find that the O atoms will carry a large magnetic moment after hole doping, which is in sharp contrast to the generally accepted concept that magnetism in solids requires partially filled shells of d or f electrons in cations. The material Sr8CaRe3Cu4O24 is therefore expected to provide a very useful platform for material design and development.

Journal Article↗

PubMed2005

The evolution of mineralocorticoid receptors.

When the human mineralocorticoid receptor (hMR) was cloned and sequenced by the Evans laboratory, its close homology with the human glucocorticoid receptor (hGR) was noted; subsequently, on the basis of its higher sequence similarity to the GR than to the progesterone receptor (PR) or androgen receptor (AR), MR and GR have commonly been considered to share an immediate common ancestral "corticoid receptor." When, however, homology is determined for the full-length receptor, or helices 3/4/5/12, MR is least like any of the other three receptors; for the ligand binding domain, AR is clearly the least homologous. When relative binding and activation capacity of a broad panel of LXXLL cofactor peptides are compared by mammalian two-hybrid assay, GR and PR show a highly similar profile, interacting with many of the 39 peptides, with MR and AR binding very few, supporting a close functional homology between PR and GR. In addition, recent studies by He et al. on FXXLF binding by GR and PR mutants suggest that these two receptors may be closer to AR than to MR. The sequence and transcriptional activity of the S810L mutant reported by Geller et al. can be interpreted as supporting MR as being closer than GR/PR/AR to estrogen receptor/retinoid X receptor, and thus potentially the first rather than the last branch from a common MR/GR/PR/AR ancestor. On the basis of these studies together, we propose reconsideration of the evolutionary tree for the MR/GR/PR/AR subfamily, with MR closest to the primordial ancestral receptor, GR/PR sharing a common immediate ancestor, and a higher degree of evolutionary drift in the AR ligand binding domain to accommodate C(19) rather than C(21) steroids as physiological ligands.

Amino Acid Sequence↗

PubMed2005

Deletion of the core region of 5' HS2 of the mouse beta-globin locus control region reveals a distinct effect in comparison with human beta-globin transgenes.

The beta-globin locus control region (LCR) is a large DNA element that is required for high-level expression of beta-like globin genes from the endogenous mouse locus or in transgenic mice carrying the human beta-globin locus. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. These HSs each contain a core of a few hundred base pairs (bp) that has most of the functional activity and exhibits high interspecies sequence homology. Adjoining the cores are 500- to 1000-bp "flanks" with weaker functional activity and lower interspecies homology. Studies of human beta-globin transgenes and of the endogenous murine locus show that deletion of an entire HS (core plus flanks) moderately suppresses expression. However, human transgenes in which only individual HS core regions were deleted showed drastic loss of expression accompanied by changes in chromatin structure. To address these disparate results, we have deleted the core region of 5'HS2 from the endogenous murine beta-LCR. The phenotype was similar to that of the larger 5'HS2 deletion, with no apparent disruption of chromatin structure. These results demonstrate that the greater severity of HS core deletions in comparison to full HS deletions is not a general property of the beta-LCR.

Animals↗

PubMed2005

Reduction of compartment compliance increases venous flow pulsatility and lowers apparent vascular compliance: implications for cerebral blood flow hemodynamics.

The global compliance of a fixed-volume, incompressible compartment may play a significant role in determining the inherent vascular compliance. For the intracranial compartment, we propose that the free-displacement of the cerebral spinal fluid (CSF) directly relates to cerebral vascular compliance. To test this hypothesis, an in vivo surrogate intracranial compartment was made by enclosing a rabbit's kidney within a rigid, fluid-filled container. Opening/closing a port atop the box modulated the free flow of box fluid (open-box state). We observed that the pulsatility of the renal venous outflow increased in response to hampering the free flow of fluid in-and-out of the container (closed-box state). To associate the observed pulsatility changes with the compliance changes, a parametric method was proposed for the computation of the apparent compliance (C(app)) of the whole renal vascular system. The calculated C(app) for each experiment's closed-box state was favorably compared to a time-domain compliance assessment method at the mean heart rate. In addition, it was revealed that C(app) in the open-box state was greater than that in the closed-box state only when the calculations were performed at frequencies lower than the heart rate and closer to the ventilation rate. These experimental results support the concept that the vessel compliance of vascular systems enclosed within a rigid compartment is a function of the global compartment compliance.

Animals↗

PubMed2005

Many-body spin Berry phases emerging from the pi-flux state: competition between antiferromagnetism and the valence-bond-solid state.

We uncover new topology-related features of the pi-flux saddle-point solution of the D=2+1 Heisenberg antiferromagnet. We note that symmetries of the spinons sustain a built-in competition between antiferromagnetic (AFM) and valence-bond-solid (VBS) orders, the two tendencies central to recent developments on quantum criticality. An effective theory containing an analogue of the Wess-Zumino-Witten term is derived, which generates quantum phases related to AFM monopoles with VBS cores, and reproduces Haldane's hedgehog Berry phases. The theory readily generalizes to pi-flux states for all D.

Journal Article↗