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Yao Lu

Publications and source records attributed to Yao Lu.

14 recordsLinked to original sources
PubMed2026

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female↗
PubMed2026

Causal relationship between asthma and hernia risk: A Mendelian randomization study.

Epidemiological associations between asthma and various hernia subtypes have been reported, but the causality and direction remain unclear. This study employs a two&#x2011;sample Mendelian randomization (MR) approach to systematically assess the causal associations between asthma and 6 hernia subtypes. Using publicly available summary data of genome-wide association studies, asthma was selected as the exposure, and diaphragmatic hernia, umbilical hernia, femoral hernia, hiatus hernia, inguinal hernia, and ventral hernia were selected as outcomes. Instrumental variables were strictly screened (F-statistic&#x2005;>&#x2005;10). The inverse&#x2011;variance weighted method was used as the primary analytical approach, supplemented with MR Egger and weighted median methods. Sensitivity analyses included heterogeneity tests, horizontal pleiotropy tests, Steiger directionality tests, leave&#x2011;one&#x2011;out analyses, and Radial MR. Reverse MR was performed for validation. Forward MR analyses revealed a significant positive causal effect of asthma on diaphragmatic hernia (odds ratio [OR]&#x2005;=&#x2005;1.19, 95% confidence interval [CI]: 1.08-1.31, P&#x2005;<&#x2005;.001) and a suggestive association with umbilical hernia (OR&#x2005;=&#x2005;1.19, 95% CI: 1.05-1.34, P&#x2005;=&#x2005;.007). The umbilical hernia association was significant only by the inverse&#x2011;variance weighted method; weighted median (P&#x2005;=&#x2005;.102) and MR-Egger (P&#x2005;=&#x2005;.210) estimates were not statistically significant, and the estimate attenuated after outlier removal (confirmatory OR&#x2005;=&#x2005;1.13, 95% CI: 1.01-1.26, P&#x2005;=&#x2005;.028). Sensitivity analyses showed no significant heterogeneity or pleiotropy. Reverse MR did not identify significant causal effects of hernias on asthma, although power limitations for certain hernia subtypes should be considered. No significant associations were observed between asthma and the other hernia subtypes, although the null findings for femoral and ventral hernias should be interpreted with caution due to limited statistical power. This study provides genetic evidence supporting asthma as a causal risk factor for diaphragmatic hernia, with a suggestive association for umbilical hernia. The diaphragmatic hernia finding was robust across multiple sensitivity analyses, whereas the umbilical hernia association was less consistent and requires further confirmation. These findings contribute to a deeper understanding of the mechanistic links between asthma and specific hernia subtypes.

Mendelian Randomization Analysis↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed2006

[Spectroscopic studies on the binding of sibutramine hydrochloride and bovine serum albumin].

AIM: To study the binding of sibutramine hydrochloride (SH) and bovine serum albumin (BSA) in physiological condition by spectroscopic method. METHODS: The quenching mechanism of the fluorescence of bovine serum albumin by sibutramine hydrochloride was studied with the fluorescence and the absorption spectroscopy. The binding constants K and the number of binding sites were determined at different temperatures according to Scatchard equation and the main binding force was discussed by thermodynamic equations. The effect of the drug on bovine serum albumin conformation was also studied by using synchronous fluorescence spectroscopy. RESULTS: The quenching mechanism of sibutramine hydrochloride to bovine serum albumin was static quenching. The binding constants K at 8 degrees C, 25 degrees C, 37 degrees C were 1.21 x 10(5), 8.31 x 10(4), 6.97 x 10(4) L x mol(-1) with one binding site, respectively. The thermodynamic parameters of the reaction were deltaH = -9.70 kJ x mol(-1), deltaS = 56.41 J x mol(-1) x K(-1). CONCLUSION: The binding force is electrostatic interaction. Sibutramine hydrochloride can be deposited and transported by serum protein in vivo. Sibutramine hydrochloride has nearly no effect on the serum protein conformation.

Animals↗
PubMed2006

Association between the polymorphism in the promoter region of dopamine D4 receptor gene and chronic tic disorder.

OBJECTIVE: To study a possible association between the three functional polymorphisms in the promoter region of dopamine D4 receptor (DRD4) gene and chronic tic disorder. METHODS: Genomic DNA was isolated from the venous blood leukocytes of 84 unrelated patients with chronic tic disorder (Study group) and 100 healthy unrelated individuals (Control group). Polymorphisms of DRD4, 1240L/S, 616C/G and 521C/T, were genotyped by the allele-specific primer (ASP) PCR. Genotype, allele and haplotype frequencies were analysed by SHEsis online. RESULTS: There were significant differences in both allele and genotype frequencies (chi(2) = 8.419, P < 0.01; chi(2) = 7.860, P < 0.05 respectively) of DRD4-616C/G between the Study and the Control groups. Haplotypic frequencies of LCT (1240L/S, 616C/G, 521C/T) in the Study group were noticeably higher than in the Control group (chi(2) = 6.371, P < 0.05). CONCLUSIONS: There is an association between the DRD4-616C/G polymorphism and chronic tic disorder. The individuals with haplotype LCT (1240L/S, 616C/G, 521C/T) are susceptible to this disorder.

Adolescent↗
PubMed2005

Mini-electrochemical detector for microchip electrophoresis.

This paper presents the development of a mini-electrochemical detector for microchip electrophoresis. The small size (3.6 x 5.0 cm2, W x L) of the detector is compatible with the dimension of the microchip. The use of universal serial bus (USB) ports facilitates installation and use of the detector, miniaturizes the detector, and makes it ideal for lab-on-a-chip applications. A fixed 10 M ohm feedback resistance was chosen to convert current of the working electrode to voltage with second gain of 1, 2, 4, 8, 16, 32, 64 and 128 for small signal detection instead of adopting selectable feedback resistance. Special attention has been paid to the power support circuitry and printed circuit board (PCB) design in order to obtain good performance in such a miniature size. The working electrode potential could be varied over a range of +/-2.5 V with a resolution of 0.01 mV. The detection current ranges from -0.3 x 10(-7) A to 2.5 x 10(-7) A and the noise is lower than 1 pA. The analytical performance of the new system was demonstrated by the detection of epinephrine using an integrated PDMS/glass microchip with detection limit of 2.1 microM (S/N = 3).

Computers↗
PubMed2005

Mediated electrochemical measurement of the inhibitory effects of furfural and acetic acid on Saccharomyces cerevisiae and Candida shehatae.

The toxic effects of furfural and acetic acid on two yeasts, Saccharomyces cerevisiae and Candida shehatae, were evaluated using an electrochemical method. Intracellular redox activities were lowered by 40% and 78% for S. cerevisiae and C. shehatae, respectively, by 8 g furfural l(-1), and by 46% and 67%, respectively, by 8 g acetic acid l(-1). The proposed method can accurately measure the effects of inhibitors on cell cultures.

Acetic Acid↗
PubMed2004

Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats.

Enteric glia share morphological, biochemical, and functional properties with astrocytes. Thus, like astrocytes, transplantation of enteric glia into the central nervous system (CNS) might facilitate the development of the characteristics of the blood brain barrier (BBB) in endothelial cells. This study explored this possibility by examining barrier formation after implantation into the spinal cord of rats. Phaseolus vulgaris leucoagglutin (PHAL)-treated enteric glia suspensions were injected into the spinal cord at the T11-T12 level of adult Wistar female rats. Control animals were injected with either 3T3 fibroblast, glioma C6 cells, or culture medium. Evan's blue, a dye excluded by the BBB, was injected intravenously from 1 week to 2 months after implantation. Leakage of dye was determined macroscopically and the ultrastructure of the capillaries was examined. During the first week leakage of dye correlated ultrastructurally with predominantly non-overlapping endothelial cell junctions, even with clefts between adjacent cells. Tight junctions were fully formed by 2 months and no dye leaked. Electron microscopic analysis showed that enteric glia had end-feet in close contact with endothelial cells. In contrast, the injection sites in all control animals leaked dye until 2 months, and most of the tight junctions that did form were incomplete. Furthermore, most 3T3 or C6 control cells had died at 2 months and those that survived, unlike enteric glia, had no anatomical relationship to blood vessels. These data demonstrate that implantation of enteric glia accelerates the formation of the characteristics of the BBB in spinal cord capillaries.

Animals↗
PubMed2004

Electrochemical evaluation of the inhibitory effects of weak acids on Zygosaccharomyces bailii.

The changes in intracellular redox activity or in mitochondrial electron transport could be taken as indications of the changes in the physiological state of living cells, based on which a mediated electrochemical method was purposed to evaluate the inhibitory effects of weak acids on Zygosaccharomyces bailii, a known food spoilage yeast. The dual mediator systems menadione/ferricyanide and 2,6-dichlorophenolindophenol/ferricyanide were employed as probes to detect the variance in intracellular redox activity and in mitochondrial electron flux, respectively. Measurements were made with a microelectrode voltammetric method to assay the ferrocyanide accumulations arising from menadione- or 2,6-dichlorophenolindophenol-mediated reduction of ferricyanide by Z. bailii suspensions by the presence or absence of increasing concentrations of weak acids. The results obtained from 2 h of incubation showed that the variance in electrochemical response revealed some physiological information underlying the inhibitory effects of weak acid on the yeast. For the first time, it was shown that the mediated electrochemical method provides an adjunct to the conventional method based on respiration inhibition for establishing levels for the utilization of preservatives in the food industry.

2,6-Dichloroindophenol↗
PubMed2004

[Measurement of tissue (correction of tissne) tension and ventilation resistance in eustachian (correction of eustachiam) tube opened by positive pressure in respiratory tract and the study on mechanism of ventilation].

OBJECTIVE: To determine the ventilation resistance of the Eustachian tube (VRET) and the lowest positive pressure to maintain the opening of the tube. Through which to elucidate the mechanism of positive ventilation. METHOD: To determine the tissue tension, 24 male flyers. Middle ear pressure was measured by a Zodiac 901 analyzer. To determine the VRET: when the Eustachian tube was opened, the change of pressure in the nasopharynx during the change of pressure in the external auditory canal was the VRET. In order to understand the relationship between middle ear barotraumas and VRET, 160 ears were tested in flight, and 60 ears were tested in the hypobaric chamber. RESULT: The Eustachian tube ventilation resistance was found to have a large respective divergence (1.20-6.86 kPa). When the tube was opened, the pressure of the middle ear changed with the change of the mask pressure. When the mask pressure dropped to 0.70 kPa, the middle ear pressure dropped down to 0 kPa. The individual difference was comparatively small. Among 160 ears of 80 combat aircraft flyers in flight, 19 ears had presentations of middle ear barotalgia. 141 ears had no presentation of barotalgia. The VRET's were significantly different (P<0.001). Among the 60 ears of 30 flyers tested in the low-pressure chamber, 9 ears had presentations of middle ear barotraumas. 51 ears had no presentation of barotalgia. The difference between the VRET's were also significant (P<0.001). CONCLUSION: If there is enough positive pressure in the mask, it will open the Eustachian tube. Then, it needs only a small positive pressure (about 0.70 kPa) to maintain the tube open. The airflow in the tube follows the law of pneumatics. The occurrence of barotalgia and VRET are correlative.

Adult↗
PubMed2003

Guanosine promotes myelination and functional recovery in chronic spinal injury.

Functional loss after spinal cord injury (SCI) is caused, in part, by demyelination of axons surviving the trauma. Administration of guanosine (8 mg/kg/day, i.p.) for 7 consecutive days, starting 5 weeks after moderate SCI in rats, improved locomotor function and spinal cord remyelination. Myelinogenesis was associated with an increase in the number of mature oligodendrocytes detected in guanosine-treated spinal cord sections in comparison with controls. These data indicate that guanosine-induced remyelination resulted, at least in part, from activation of endogenous oligodendrocyte lineage cells. These findings may have significant implications for chronic demyelinating diseases.

Animals↗
PubMed2003

[Transmission disequilibrium test for congenital dislocation of the hip and HOXB9 gene or COL1AI gene].

OBJECTIVE: To detect the correlation between the congenital dislocation of the hip (CDH) and HOXB9 gene or COL1AI gene. METHODS: A microsatellite DNA marker D17S1820 was chosen in the region of chromosome 17q21 where exists the HOXB9 gene which regulates the embryonic limb development and exists the COL1AI gene. The genotypes of 303 members in 101 CDH nuclear family trios were analyzed by the techniques of polymerase chain reaction(PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test (TDT) was used to test the data of genotypes. RESULTS: There exist 12 alleles at this polymorphic locus. Transmission disequilibrium was found between CDH and the fourth allele of D17S1820 (chi-square=6.025,P=0.014). CONCLUSION: CDH is associated with the region of chromosome 17q21. HOXB9 gene and/or COL1AI gene may be susceptibility genes of CDH.

Bone Diseases, Developmental↗