Biomedical subjects

Rui Xiao

Publications and source records attributed to Rui Xiao.

At least 19 recordsLinked to original sources

PubMed2026

Evaluation of muscle microvascular perfusion in primary mitochondrial disease by contrast-enhanced ultrasound: Feasibility study.

BACKGROUND: Primary mitochondrial disease (PMD) are genetic disorders characterized by impaired oxidative metabolism and microvascular abnormalities that contribute to the myopathy. OBJECTIVES: This study evaluates the feasibility and utility of contrast-enhanced ultrasound (CEUS) for quantifying skeletal muscle perfusion in patients with PMD. In addition, we assessed exercise-induced changes following cardiopulmonary exercise testing (CPET) to characterize dynamic vascular responses. DESIGN: Prospective pilot feasibility study. METHODS: We enrolled genetically confirmed PMD and healthy control participants with ability to complete the CPET protocol. CEUS of the vastus lateralis muscle was performed at rest and following CPET. Imaging parameters were standardized across all CEUS scans, with a fixed mechanical index of 0.13. Perfusion parameters, including perfusion index (PI), peak enhancement (PE), and area under the curve (AUC) were quantified using delta projection analysis, and compared between PMD and control participants, and within each group, pre- and post-exercise. RESULTS: A total of 5 PMD and 5 control participants were evaluated. At rest, CEUS demonstrated a trend in higher muscle perfusion in PMD as compared to control participants on comparing PI (13.7 ± 2.7 vs. 10.7 ± 3.2; p = 0.42), PE (24.9 ± 11.5 vs. 14.3 ± 6.8; p = 0.22), and AUC (95,253.4 ± 35,072.8 vs. 73,591.2 ± 32,820.6; p = 0.31), which did not reach statistical significance, likely in part due to the small cohort size. Following CPET, PMD participants demonstrated exaggerated percentage increases in PI (+21.1% vs. +16.0%), PE (+11.2% vs. +7.6%), and AUC (+20.2% vs. +12.5%) as compared to control participants. Within group analysis revealed a significant post-exercise increase in AUC among PMD participants (p = 0.01) but did not reach significance in control participants. CONCLUSION: This is the first study to demonstrate the feasibility and utility of conducting CEUS to assess skeletal muscle perfusion in ambulatory PMD patients. The distinct perfusion patterns and exaggerated exercise-induced responses observed in PMD as compared to control participants suggest that reactive hyperemia occurs in PMD at rest and is further exaggerated by exercise. CEUS may serve as a sensitive tool for detecting microvascular alterations in PMD.

cardiopulmonary exercise testing (CPET)↗

PubMed2026

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction.

INTRODUCTION: Mitochondrial diseases are multisystem disorders in which defects in oxidative phosphorylation disrupt cellular bioenergetics and redox signaling across the vasculature and heart. Because mitochondrial function is closely linked to endothelial nitric oxide (NO) production, we hypothesized that mitochondrial diseases manifest as a NO-deficiency endotheliopathy affecting conduit and microvascular function. To evaluate this, we performed a systematic review with quantitative synthesis of human studies reporting vascular reactivity, biochemical NO production, or myocardial metabolic imaging, aiming to define the magnitude of impairment and responsiveness to NO-precursor therapy (l-arginine or l-citrulline). METHODS: Following PRISMA 2020 guidelines, we conducted a comprehensive search (inception-October 2025) identifying clinical studies of genetically or clinically confirmed mitochondrial disease with quantitative endothelial or bioenergetic endpoints. Eligible measures included flow-mediated dilation (FMD), reactive hyperemia index (RHI), passive-leg-movement (PLM) hyperemia, absolute synthesis rate of NO metabolites (ASR NOm), and positron emission tomography (PET)-derived myocardial oxidative indices (k mono , DP/k mono ). Quantitative synthesis used Hedges g for between-group comparisons and standardized mean change (SMC) for within-subject responses. Risk of bias was evaluated using ROBINS-I and a modified Newcastle-Ottawa Scale. RESULTS: Seven studies met these inclusion criteria, comprising 76 mitochondrial-disease subjects and 81 controls (ages 8-63 years). Across all vascular and metabolic domains, mitochondrial disease was associated with marked endothelial and bioenergetic impairment. Macro- and microvascular dysfunction, reflected by reduced FMD, RHI, and PLM hyperemia, demonstrated severe endothelium-specific abnormalities. Biochemical assays showed diminished NO synthesis. Myocardial PET imaging revealed reduced oxidative rate constants and increased energetic inefficiency despite preserved perfusion. Nitric oxide synthesis-precursor therapy was associated with improved endothelial reactivity (increased FMD, RHI, and ASR NOm) and significant, modest improvements in myocardial oxidative metabolism, consistent with partial restoration of endothelial NO signaling. Effect sizes collectively supported a reversible NO-deficiency endotheliopathy. The risk-of-bias assessment indicated moderate-to-good methodological quality, with limitations primarily related to small sample sizes and nonrandomized designs. CONCLUSIONS: Mitochondrial disease is characterized by significant impairments in vascular reactivity, NO signaling, and myocardial bioenergetics. Improvements in endothelial function and NO synthesis following l-arginine or l-citrulline supplementation are consistent with a role for impaired endothelial NO signaling in the vascular manifestations of mitochondrial disease. These findings highlight the vascular endothelium as a potential therapeutic target and underscore the need for future clinical intervention trials that use standardized vascular and bioenergetic endpoints.

and stroke-like episodes (MELAS)↗

PubMed2025

Genetic crosses reveal genomic loci responsible for virulence in Cryptosporidium parvum infection.

The relationship between parasite genotype and pathogenesis is largely unknown for Cryptosporidium, a leading cause of diarrheal disease in children. An array of parasites with similar genomes produces varied disease outcomes in different hosts. Here, we isolate and characterize Cryptosporidium parvum strains that show marked differences in virulence and persistence in mice. Taking advantage of the sexual life cycle of this eukaryotic pathogen, we use genetic crosses to discover the underlying chromosomal loci. Whole-genome sequencing and bulk segregant analysis of infection-selected progeny mapped three loci on chromosomes 2, 6, and 7 associated with the ability to colonize and persist in mice and the positions of drug resistance genes. The chromosome 6 locus encodes the hyper-polymorphic surface glycoprotein GP60. Reverse genetic studies in both parental strains demonstrate that GP60 controls parasite burden and virulence, but not persistence, and reveal the dominance of the less virulent allele, suggesting it restricts virulence.

Cryptosporidium parvum↗

PubMed2025

Recognizing the evolution of clinical syndrome spectrum progression in individuals with single large-scale mitochondrial DNA deletion syndromes (SLSMDS).

PURPOSE: Single large-scale mtDNA deletions (SLSMD) result in single large-scale deletion syndromes (SLSMDS). SLSMDS presentations have classically been recognized to encompass at least 3 distinct clinical phenotypes: Pearson syndrome (PS), Kearns-Sayre syndrome (KSS), and chronic progressive ophthalmoplegia. METHODS: A facilitated review of electronic medical records, manual charts, and Research Electronic Data Capture research databases was performed to complete a retrospective natural history study of 30 participants with SLSMDS in a single health system between 2002 and 2020. The evaluated characteristics included genetic and clinical laboratory test values, growth parameters, signs and symptoms, demographics, and patient-reported outcome measures of fatigue, quality of life, and overall function. RESULTS: Detailed cohort characterization highlighted that a recurrent deleted region involving MT-ND5 (HGNC:7641) occurs in 96% of participants with SLSMDS regardless of the clinical phenotype, which tends to evolve over time. Higher blood heteroplasmy correlated with an earlier age of onset. Growth differentiation factor 15 levels were elevated in all participants with SLSMDS. A history of PS was associated with poor survival prognosis. Furthermore, increased fatigue and decreased quality of life have been reported in patients with SLSMD with advanced age. CONCLUSION: A retrospective natural history study of patients with SLSMDS demonstrated the evolution of classically considered PS, Kearns-Sayre syndrome, and chronic progressive ophthalmoplegia clinical presentations in affected individuals, which may inform future clinical trial developments.

Humans↗

PubMed2007

[Effects of Dengue virus infection on PGIS expression and PGI2 secretion of human vascular endothelial cells].

AIM: To elucidate the effects of Dengue virus on the expression and secretion of prostacyclin (PGI(2)) in endothelial cells. METHODS: Cultured human umbilical vein endothelial cells (HUVEC) were infected by Dengue virus II(DV(2)) for different duration. PGI(2) level in the supernatant was determined by radioimmune assay. Cytoplasmic RNA of the infected HUVEC was prepared using the Trizol method and was assayed for prostacyclin synthase (PGIS) by RT-PCR. RESULTS: PGIS expression as well as PGI(2) secretion of the DV(2) group were significantly increased (P<0.05) at 48 h, 72 h and 96 h post-infection compared to the control group. CONCLUSION: DV(2) could promote the expression of PGIS mRNA in HUVEC and increase the level of PGI(2), which may increase the vascular permeability. The dysfunction of vascular endothelial cell (EC) induced by DV may be related to the pathogenesis of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome(DSS).

Cells, Cultured↗

PubMed2006

Potentiation of TRPV3 channel function by unsaturated fatty acids.

Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31-39 degrees C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel.

Animals↗

PubMed2006

International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor.

The nuclear receptors of the NR1H and NR1I subgroups include the constitutive androstane receptor, pregnane X receptor, farnesoid X receptors, liver X receptors, and vitamin D receptor. The newly emerging functions of these related receptors are under the control of metabolic pathways, including metabolism of xenobiotics, bile acids, cholesterol, and calcium. This review summarizes results of structural, pharmacologic, and genetic studies of these receptors.

Animals↗

PubMed2006

[Expression of tissue factor induced by IL-6 in HUVEC].

OBJECTIVE: To investigate the effects of IL-6 at the expression of tissue factor (TF) in human vein endothelial cells(HUVECs). METHODS: HUVECs were incubated with IL-6 at the concentration of 0.5 ng/mL. Cell viability was measured by CCK-8 assay. The TF mRNA was detected by reverse transcript-polymerase chain reaction(RT-PCR) method. RESULTS: When HUVECs were exposed to IL-6 (0.5 ng/mL) within a period of 72 h, their viability did not decrease in comparison with the control; there was no statistical difference between the two groups. After the HUVECs were exposed to IL-6 (0.5 ng/mL) for 6 h, the TF mRNA level increased, and it reached the peak at 12 h; then it began to decline. The expression of TF mRNA induced by IL-6 was evidently detected from 6 h to 48 h. After the HUVECs were treated by IL-6 over 72 h, the expression of TF mRNA was no longer detected in HUVECs. CONCLUSION: IL-6 at the concentration of 0.5 ng/mL did not exert direct effect on cell viability. The increase of TF mRNA expression in HUVECs induced by IL-6 could play an important role in the modulation of blood coagulation disorder and in the mechanism related to coagulation system changes during

Cells, Cultured↗

PubMed2005

Identification of genes differentially expressed in wild type and Purkinje cell degeneration mice.

Purkinje cell degeneration (pcd) mice are characterized by death of virtually all cerebellar Purkinje cells by postnatal day 30. In this study, we used DNA microarray analysis to investigate differences in gene expression between the brains of wild type and pcd mice on postnatal day 20, before the appearance of clear-cut phenotypic abnormalities. We identified 300 differentially expressed genes, most of which were involved in metabolic and physiological processes. Among the differentially expressed genes were several calcium binding proteins including calbindin-28k, paravalbumin, matrix gamma-carboxyglutamate protein and synaptotagamins 1 and 13, suggesting the involvement of abnormal Ca2+ signaling in the pcd phenotype.

Alleles↗

PubMed2005

An algorithm to construct genetically similar subsets of families with the use of self-reported ethnicity information.

We present a simple algorithm that uses self-reported ethnicity information, pedigree structure, and affection status to group families into genetically more homogeneous subsets. This algorithm should prove useful to researchers who wish to perform genetic analyses on more-homogeneous subsets when they suspect that ignoring heterogeneity could lead to false-positive results or loss of power. We applied our algorithm to the self-reported ethnicity information of 159 families from the Veterans Affairs Cooperative Study of schizophrenia. We compared these estimates of population membership with those obtained using the program structure in an analysis of 378 microsatellite markers. We found excellent concordance between family classifications determined using self-reported ethnicity information and our algorithm and those determined using genetic marker data and structure; 158 of the 159 families had concordant classifications. In addition, the degree of admixture estimated using our algorithm and self-reported ethnicity information correlated well with that predicted using the genotype information.

Algorithms↗

PubMed2005

Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation.

TRPC5 forms Ca2+-permeable nonselective cation channels important for neurite outgrowth and growth cone morphology of hippocampal neurons. Here we studied the activation of mouse TRPC5 expressed in Chinese hamster ovary and human embryonic kidney 293 cells by agonist stimulation of several receptors that couple to the phosphoinositide signaling cascade and the role of calmodulin (CaM) on the activation. We showed that exogenous application of 10 microM CaM through patch pipette accelerated the agonist-induced channel activation by 2.8-fold, with the time constant for half-activation reduced from 4.25 +/- 0.4 to 1.56 +/- 0.85 min. We identified a novel CaM-binding site located at the C terminus of TRPC5, 95 amino acids downstream from the previously determined common CaM/IP3R-binding (CIRB) domain for all TRPC proteins. Deletion of the novel CaM-binding site attenuated the acceleration in channel activation induced by CaM. However, disruption of the CIRB domain from TRPC5 rendered the channel irresponsive to agonist stimulation without affecting the cell surface expression of the channel protein. Furthermore, we showed that high (>5 microM) intracellular free Ca2+ inhibited the current density without affecting the time course of TRPC5 activation by receptor agonists. These results demonstrated that intracellular Ca2+ has dual and opposite effects on the activation of TRPC5. The novel CaM-binding site is important for the Ca2+/CaM-mediated facilitation, whereas the CIRB domain is critical for the overall response of receptor-induced TRPC5 channel activation.

Amino Acid Sequence↗

PubMed2005

Inhibition of TRPC5 channels by Ca2+-binding protein 1 in Xenopus oocytes.

The transient receptor potential canonical type 5 (TRPC5) channel is a member of the channels that has been implicated in neurite extension and growth cone morphology of hippocampal neurons. Although homomeric TRPC5 channels are activated following stimulation of G(q/11)-coupled receptors, the exact mechanism for this activation remains unresolved. Using two-electrode voltage clamp recordings, we show that the activity of TRPC5 channels expressed in Xenopus oocytes is dependent on the presence of Ca2+ at the extracellular as well as the cytoplasmic side of the plasma membrane. TRPC5 was activated by the stimulation of coexpressed M5 muscarinic receptors or by ionomycin. The TRPC5 activity was detectable with the presence of submillimolar levels of extracellular Ca2+, but it was eliminated by the injection of 5 mM 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid into the oocytes. Lanthanum could substitute for extracellular Ca2+ to support TRPC5 activity. Coexpression of Ca2+-binding protein 1 (CaBP1), but not calmodulin (CaM), inhibited the TRPC5 activity, without affecting the cell surface expression of TRPC5 proteins. Using in vitro binding assays, we demonstrated direction interactions between CaBP1 and TRPC5. The CaBP1-binding sites at the C terminus of TRPC5 are closely localized, but not identical, to CaM-binding sites. We conclude that TRPC5 is a Ca2+-regulated channel, and its activity is negatively controlled by CaBP1.

Animals↗

PubMed2005

New adaptive color quantization method based on self-organizing maps.

Color quantization (CQ) is an image processing task popularly used to convert true color images to palletized images for limited color display devices. To minimize the contouring artifacts introduced by the reduction of colors, a new competitive learning (CL) based scheme called the frequency sensitive self-organizing maps (FS-SOMs) is proposed to optimize the color palette design for CQ. FS-SOM harmonically blends the neighborhood adaptation of the well-known self-organizing maps (SOMs) with the neuron dependent frequency sensitive learning model, the global butterfly permutation sequence for input randomization, and the reinitialization of dead neurons to harness effective utilization of neurons. The net effect is an improvement in adaptation, a well-ordered color palette, and the alleviation of underutilization problem, which is the main cause of visually perceivable artifacts of CQ. Extensive simulations have been performed to analyze and compare the learning behavior and performance of FS-SOM against other vector quantization (VQ) algorithms. The results show that the proposed FS-SOM outperforms classical CL, Linde, Buzo, and Gray (LBG), and SOM algorithms. More importantly, FS-SOM achieves its superiority in reconstruction quality and topological ordering with a much greater robustness against variations in network parameters than the current art SOM algorithm for CQ. A most significant bit (MSB) biased encoding scheme is also introduced to reduce the number of parallel processing units. By mapping the pixel values as sign-magnitude numbers and biasing the magnitudes according to their sign bits, eight lattice points in the color space are condensed into one common point density function. Consequently, the same processing element can be used to map several color clusters and the entire FS-SOM network can be substantially scaled down without severely scarifying the quality of the displayed image. The drawback of this encoding scheme is the additional storage overhead, which can be cut down by leveraging on existing encoder in an overall lossy compression scheme.

Algorithms↗

PubMed2005

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids.

The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree. Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.

Animals↗

PubMed2005

Investigation of polycyclic aromatic hydrocarbons from coal gasification.

The hazardous organic pollutants generated from coal gasification, such as polycyclic aromatic hydrocarbons(PAHs), are highly mutagenic and carcinogenic. More researchers have paid particular attention to them. Using air and steam as gasification medium, the experiments of three kinds of coals were carried out in a bench-scale atmospheric fluidized bed gasifier. The contents of the 16 PAHs specified by US EPA in raw coal, slag, bag house coke, cyclone coke and gas were measured by HPLC to study the contents of PAHs in raw coal and the effects of the inherent characters of coals on the formation and release of PAHs in coal gasification. The experimental results showed that the distributions of PAHs in the gasified products are similar to raw coals and the total-PAHs content in coal gasification is higher than in raw coal(except Coal C). The total-PAHs contents increase and then decrease with the rise of fixed carbon and sulfur of coal while there has an opposite variation when volatile matters content increase. The quantities of PAHs reduce with the increase of ash content or the drop of heating value during coal gasification.

Air Pollutants↗

PubMed2005

[Treatments of tibial Pilon fractures with a combination of limited internal fixation and external fixation].

OBJECTIVE: To summarize the effect and complication of treatment for Pilon fracture using limited internal fixation combined with external fixation. METHODS: From April 1996 to June 2003, 20 patients with Pilon fracture were treated with limited internal fixation combined with external fixation as the treatment group and 22 patients with Pilon fracture with other methods as the control group. The X-ray films, clinical effect and complication were analyzed and compared between 2 groups. RESULTS: All cases were followed up for 8 to 26 months (15.2 months on average). According to Helfet's criterion for clinical effect, the excellent and good rates were 75% in the treatment group and 72.7% in the control group, being no significant difference (P > 0.05). According to Burwell-charnley criterion for reduction, the X-ray film results showed the excellent and good rates were 90% in the treatment group and 86.4% in the control group, being no significant difference (P > 0.05). But there was significant difference in complications between 2 groups (P < 0.05). CONCLUSION: Limited internal fixation combined with external fixation is better in resuming ankle joint function and remarkably reducing complication, especially in reducing soft tissue complication and collapse of bone joint; it is useful in the treatment of Pilon fracture.

Adult↗

PubMed2005

[A preliminary clinical study on absorbable screws].

To evaluate the application of self-reinforced ploy-DL-lactide (SR-PDLLA) absorbable screws in the treatment of spongy bone and intra-articular fractures, the internal fixation with SR-PDLLA absorbable screw was performed on 58 cases,of which 25 were medial malleolus fractures, 14 condyle of humerus fractures, 9 tibial plateau fractures, 7 ulnar olecranon fractures, and 3 lateral malleolus fractures. Observations were made on the orthopaedic operation sites and overall conditions frequently and radiography was performed for periodic analysis. The results showed that SR-PDLLA absorbable screws were particularly effective and reliable, they had good biocompatibility in the treatment of spongy bone and intra-articular fractures and could be used safely in clinical practice.

Absorbable Implants↗

PubMed2004

Experimental study on the removal of PAHs using in-duct activated carbon injection.

This paper presents the incineration tests of municipal solid waste (MSW) in a fluidized bed and the adsorption of activated carbon (AC) on polycyclic aromatic hydrocarbons (PAHs). An extraction and high performance liquid chromatography (HPLC) technique was used to analyze the concentrations of the 16 US EPA specified PAHs contained in raw MSW, flue gas, fly ash, and bottom ash. The aim of this work was to decide the influence of AC on the distribution of PAHs during the incineration of MSW. Experimental researches show that there were a few PAHs in MSW and bottom ash. With the increase of AC feeding rate, the concentrations of three- to six-ring PAHs in fly ash increased, and the concentration of two-ring PAH decreased. The total-PAHs in flue gas were dominated by three-, and four-ring PAHs, but a few two-, five-ring PAHs and no six-ring PAHs were found. PAHs could be removed effectively from flue gas by using in-duct AC injection and the removal efficiencies of PAHs were about 76-91%. In addition, the total toxic equivalent (TEQ) concentrations of PAH in raw MSW, bottom ash, fly ash, and flue gas were 1.24 mg TEQ kg-1, 0.25 mg TEQ kg-1, 6.89-9.67 mg TEQ kg-1, and 0.36-1.50 microg TEQ Nm-3, respectively.

Adsorption↗