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Hua Li

Publications and source records attributed to Hua Li.

At least 19 recordsLinked to original sources
PubMed2026

Multi-omics causal inference of childhood asthma triggered by ambient particulate matter.

BACKGROUND: The causal impact of fine particulate matter (PM2.5), an established environmental risk factor, on childhood asthma and its biological mechanisms remain to be elucidated. The objective of the present study was to evaluate the causal association between PM2.5 and childhood asthma and to dissect the mediating role of plasma proteins through a multi-omics integrated Mendelian randomisation (MR) framework. METHODS: Two-sample MR was performed on large-scale genome-wide association data to estimate the causal effect of PM2.5 on childhood asthma. Genes commonly associated with PM2.5 and childhood asthma were screened by transcriptome-wide association study (TWAS) and subjected to enrichment analyses and MR. Mediator proteins were identified by two-step MR. Potential adverse effects were scanned by phenome-wide MR (Phe-MR). RESULTS: MR revealed a significant positive causal effect of PM2.5 on childhood asthma (OR=1.897, 95% CI: 1.063-3.388, p=0.030). TWAS highlighted 70 genes co-expressed in PM2.5 and childhood asthma that were enriched in inflammatory pathways such as lysosome- and leukocyte-mediated immunity. MEAF6 was validated as a protective gene and RNF40 as a risk gene for childhood asthma. Two-step MR identified FUT10 as a positive mediator mediating 19.3% of the causal effect, and CD200 and MANBA as negative mediator proteins. Phe-MR indicated the association of these genes and proteins with multiple other diseases, implying possible adverse effects from therapeutic intervention. CONCLUSION: Long-term PM2.5 exposure is causally linked to childhood asthma with MEAF6, RNF40, CD200, MANBA and FUT10 identified as key molecules. The study provides new evidence for the biological mechanisms linking PM2.5 to childhood asthma.

Journal Article↗
PubMed2026

Genome-Wide Characterization and Salt-Responsive Expression Divergence of Chromosome Group 2 and Group 6 TaBADH Genes in Wheat.

Betaine aldehyde dehydrogenase (BADH) catalyzes the final step in glycine betaine biosynthesis, but the evolutionary divergence and differential salt responsiveness of BADH homeologs in bread wheat remain unclear. We identified six TaBADH genes and analyzed their phylogenetic relationships, conserved motifs, gene structures, promoter cis-acting elements and synteny. RNA-seq and qRT-PCR were used to compare expression in salt-tolerant Jimai 60 and salt-sensitive Chinese Spring under 200 mM NaCl, and BADH activity, glycine betaine, H2O2 and malondialdehyde (MDA) were measured during treatment. The genes separated into chromosome group 2 and group 6 clades with distinct structural and transcriptional patterns. TaBADH-2B encoded a shorter protein and lacked several conserved motifs. Group 6 genes showed stronger salt-responsive expression in Jimai 60, with TaBADH-6D displaying the strongest and most sustained induction. Jimai 60 also showed higher BADH activity and glycine betaine accumulation and lower H2O2 and MDA contents at later time points. Expression of TaBADH-6D improved E. coli growth under 200 mM NaCl. These findings identify homeolog-specific divergence within the BADH wheat family and support TaBADH-6D as a candidate for plant-level functional validation.

TaBADH-6D↗
PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗
PubMed2026

Functional role and regulatory network of miR-22-3p in chicken hepatic lipid metabolism.

Although microRNA-22-3p (miR-22-3p) is abundantly expressed in the avian liver, its epigenetic role in lipid homeostasis remains largely uncharacterized. To elucidate its in vivo function, 14-day-old female Qingyuan Partridge chickens were intravenously injected with lentiviral vectors to establish miR-22-3p overexpression and knockdown models. Phenotypic analysis demonstrated that miR-22-3p knockdown significantly elevated hepatic triglyceride (TG) levels (p&#xa0;<&#xa0;0.05) and drove marked steatosis, whereas its overexpression reduced TG content. Transcriptome sequencing (RNA-Seq) revealed profound metabolic remodeling, identifying 23 core lipid-associated genes (e.g., ELOVL6, FADS2, ACSBG2, and PTGIS) heavily enriched in steroid biosynthesis, fatty acid metabolism, and elongation pathways. In conclusion, miR-22-3p functions as a bidirectional epigenetic rheostat that negatively regulates hepatic lipid deposition by orchestrating a multilayered polygenic network, providing novel molecular targets for mitigating avian metabolic disorders and optimizing production traits in indigenous poultry breeds.

Animals↗
PubMed2025

STUPPIT is a proximity labeling tool for labeling intermediary proteins that bridge two non-interacting proteins.

Decoding the complexities of signaling pathways is fundamental for deciphering the mechanisms underlying tissue development, homeostasis, and disease pathogenesis. Proximity labeling tools have been instrumental in identifying upstream or downstream effectors of specific proteins within signaling pathways. However, currently, there are no tools available to directly label and capture intermediary proteins that bridge two non-interacting proteins. Here, we developed Split-TurboID and PUP-IT based Protein Identification Tool (STUPPIT), a novel method combining split-TurboID and PUP-IT to biotinylate intermediary proteins of two non-interacting proteins through a two-step enzymatic reaction. STUPPIT was validated using three well-characterized protein triads, including YAP1/AMOT/&#x3b2;-actin, YAP1/LATS1/MOB1A, and &#x3b2;-catenin/&#x3b1;-catenin/&#x3b2;-actin using HEK293T human cell lines. Combining STUPPIT and proteomics, we identified novel intermediary proteins including ERC1 and USP7, which interacted both with &#x3b2;-catenin and SMAD4, key components of the Wnt and BMP signaling pathways. In conclusion, STUPPIT represents a powerful tool for labeling and capturing intermediary proteins between non-interacting partners, offering new insights into protein-protein interactions and advancing signal transduction research.

Humans↗
PubMed2007

Activations of nPKCepsilon and ERK1/2 were involved in oxygen-glucose deprivation-induced neuroprotection via NMDA receptors in hippocampal slices of mice.

Accumulated reports have suggested that activation of protein kinase C (PKC) isoforms may involve the activation of extracellular signal-regulated kinases (ERKs) in the neuronal response to ischemic/hypoxic stimuli. We have previously demonstrated that the membrane translocation of novel PKC (nPKC) epsilon increased in the early phase of cerebral ischemic/hypoxic preconditioning of mice. In this study, we used Western blot analysis and propidium iodide stain to determine whether the activations of nPKCepsilon and ERKs were involved in oxygen-glucose deprivation (OGD)-induced neuroprotection via N-methyl-D-aspartate (NMDA) receptors. The hippocampal slices of mice were exposed to OGD for 10 (OGD10) or 45 minutes (OGD45) to mimic mild (causing ischemic/hypoxic preconditioning) and severe (causing severe OGD) ischemia/hypoxia, respectively. We found that OGD10-induced nPKCepslilon membrane translocation was mediated by NMDA receptors, and both OGD10 and NMDA (1 microM, 30 min) pretreatment could protect Cornu Ammonis region 1 neurons against the subsequent severe OGD45. In addition, nPKCepsilon translocation inhibitor, epsilonV1-2 (1 microM, 30 min), and ERKs upstream mitogen-activated protein/extracellular signal regulated kinase kinase inhibitor, PD-98059 (20 microM, 30 min), could significantly inhibit OGD10 and NMDA-induced neuroprotection. These results suggest that OGD10-induced neuroprotection against severe OGD45 in the Cornu Ammonis region 1 region of the hippocampal slices was mediated by the activations of NMDA receptors, nPKCepsilon, and the downstream ERKs.

Animals↗
PubMed2007

Local or global minima: flexible dual-front active contours.

Most variational active contour models are designed to find local minima of data-dependent energy functionals with the hope that reasonable initial placement of the active contour will drive it toward a "desirable" local minimum as opposed to an undesirable configuration due to noise or complex image structure. As such, there has been much research into the design of complex region-based energy functionals that are less likely to yield undesirable local minima when compared to simpler edge-based energy functionals whose sensitivity to noise and texture is significantly worse. Unfortunately, most of these more "robust" region-based energy functionals are applicable to a much narrower class of imagery compared to typical edge-based energies due to stronger global assumptions about the underlying image data. Devising new implementation algorithms for active contours that attempt to capture more global minimizers of already proposed image-based energies would allow us to choose an energy that makes sense for a particular class of energy without concern over its sensitivity to local minima. Such implementations have been proposed for capturing global minima. However, sometimes the completely-global minimum is just as undesirable as a minimum that is too local. In this paper, we propose a novel, fast, and flexible dual front implementation of active contours, motivated by minimal path techniques and utilizing fast sweeping algorithms, which is easily manipulated to yield minima with variable "degrees" of localness and globalness. By simply adjusting the size of active regions, the ability to gracefully move from capturing minima that are more local (according to the initial placement of the active contour/surface) to minima that are more global allows this model to more easily obtain "desirable" minimizers (which often are neither the most local nor the most global). Experiments on various 2D and 3D images and comparisons with some active contour models and region-growing methods are also given to illustrate the properties of this model and its performance in a variety of segmentation applications.

Algorithms↗
PubMed2006

Chemiluminescence determination of sodium new houttuyfonate in pharmaceutical preparations based on tween 80-rhodamine B system.

Strong chemiluminescence (CL) emission was observed when sodium new houttuyfonate (SNH) was mixed with Tween 80 in sulfuric acid medium in the presence of rhodamine B. Base on this phenomenon, a sensitive flow injection-CL method for the determination of SNH was developed. Under the optimum conditions, the CL emission is linearly with SNH concentration in the range 8.0-4000 ng mL(-1), with a detection limit of 2.7 ng mL(-1) (3sigma). As a preliminary application, the proposed method was successfully applied to the determination of SNH in pharmaceutical preparations. The possible CL mechanism was also discussed in this paper.

Alkanes↗
PubMed2006

QSAR study of a large set of 3-pyridyl ethers as ligands of the alpha4beta2 nicotinic acetylcholine receptor.

Extensive 3D-QSAR studies were performed on 158 diverse analogues of 3-pyridyl ethers, which are excellent ligands of alpha4beta2 neuronal nicotinic acetylcholine receptor (NnAChR). Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques were used to relate the binding affinities with the ligand structures. Two QSAR models were obtained using CoMFA and CoMSIA techniques. The two QSAR models were proved to be statistically significant and have high predictive power. The best CoMFA model yielded the cross-validated q(2)=0.605 and the non-cross-validated r(2)=0.862. The derived model indicated the importance of steric (85.9%) as well as electrostatic (14.1%) contributions. The CoMFA model demonstrated the steric field as the major descriptor of the ligand binding. The best CoMSIA model gave q(2)=0.723 and r(2)=0.685. This model showed that steric (30.3%) and H-bond interaction (61.8%) properties played major roles in ligand binding process. The squares of correlation coefficient for external test set of 28 molecules were 0.723 and 0.685 for the CoMFA model and the CoMSIA model, respectively. The two models were further graphically interpreted in terms of field contribution maps. SAR studies were also performed on different series of compounds in order to get a more reasonable understanding of the interactions between the ligands and the receptor. With the results, we have also presumed some assistant elements as supplements to the traditional pharmacophoric elements. A crude vision of ligand localization in the ligand-binding pocket of the receptor was also obtained, which would favor for the docking study of this kind of ligands.

Binding Sites↗
PubMed2006

Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion.

AIM: To examine the existence of Nitric oxide/cGMP sensitive store-operated Ca(2+) entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fibroblasts. METHODS: NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca(2+) entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were employed to detect the involvement of [Ca(2+)]i and NO/cGMP in MMP secretion. The involvement of NO/cGMP-sensitive Ca(2+) entry in adhesion was determined using matrigel-coated culture plates. RESULTS: 8-bromo-cGMP inhibited the thapsigargin-induced Ca(2+) entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1 micromol/L). A similar effect on the Ca(2+) entry was observed in 3T3 cells in response to a NO donor, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca(2+) entry was also observed, indicating NO/cGMP-regulated Ca(2+) entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca(2+) concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates. CONCLUSION: NO/cGMP sensitive store-operated Ca(2+) entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion.

Animals↗
PubMed2006

Immunomodulatory therapy of cytomegalovirus pneumonia after liver transplantation.

BACKGROUND: There has been increasing interest in the research into cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT. METHODS: Six patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased. The liver function of the patients was monitored closely during the treatment. RESULTS: In this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place. CONCLUSIONS: Poor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppressants should be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.

Adjuvants, Immunologic↗
PubMed2006

Transient simulation of kinetics of electric-sensitive hydrogels.

Kinetics of the hydrogels responsive to electric stimulus due to an externally applied electric field is modeled for the first time through transient simulation. The mathematical model employed is called the multi-effect-coupling electric-stimulus (MECe) model, which is developed with consideration of multi-phases and multi-physics. Transient simulation by the MECe model is examined with available experimental data and good agreement is achieved. The kinetics of ionic concentration of diffusive species is simulated. The simulation also predicts the influences of several important parameters on the hydrogel deformation, including the externally applied electric voltage, initially fixed charge density and surrounding bath solution concentration.

Biosensing Techniques↗
PubMed2006

Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by progressive degeneration of the right ventricular myocardium, ventricular arrhythmias, fibrous-fatty replacement, and increased risk of sudden death. Mutations in 6 genes, including 4 encoding desmosomal proteins (Junctional plakoglobin (JUP), Desmoplakin (DSP), Plakophilin 2, and Desmoglein 2), have been identified in patients with ARVD/C. Mutation analysis of 66 probands identified 4 variants in DSP; V30M, Q90R, W233X, and R2834H. To establish a cause and effect relationship between those DSP missense mutations and ARVD/C, we performed in vitro and in vivo analyses of the mutated proteins. Unlike wild-type (WT) DSP, the N-terminal mutants (V30M and Q90R) failed to localize to the cell membrane in desomosome-forming cell line and failed to bind to and coimmunoprecipitate JUP. Multiple attempts to generate N-terminal DSP (V30M and Q90R) cardiac-specific transgenes have failed: analysis of embryos revealed evidence of profound ventricular dilation, which likely resulted in embryonic lethality. We were able to develop transgenic (Tg) mice with cardiac-restricted overexpression of the C-terminal mutant (R2834H) or WT DSP. Whereas mice overexpressing WT DSP had no detectable histologic, morphological, or functional cardiac changes, the R2834H-Tg mice had increased cardiomyocyte apoptosis, cardiac fibrosis, and lipid accumulation, along with ventricular enlargement and cardiac dysfunction in both ventricles. These mice also displayed interruption of DSP-desmin interaction at intercalated discs (IDs) and marked ultra-structural changes of IDs. These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development.

Animals↗
PubMed2006

[The distribution and pathogen of bacteria infection in patients after liver transplantation].

OBJECTIVE: To find out the epidemiology of bacteria infection after orthotopic liver transplantation (OLT). METHOD: Postoperative bacteria infection of 451 OLT cases were retrospectively analyzed. RESULT: Bacteria infection were detected in 239 OLT cases, and the infection rate was 52.9%. Sum up to 304 bacilli lines were separated from all above cases. Among them, the detectable Gram-positive bacilli (G(+)) accounted for 59.9% (182/304), while Gram-negative bacilli (G(-)) accounted for 40.2% (122/304). The impressionable organ were respiratory tract and bile duct, which occupying 81.5% (248/304) and 15.1% (46/304) among all infective cases respectively. The main infected strain were G(+) bacteria in respiratory tract, account for 65.3%; while G(-) bacteria were mainly in bile duct, account for 60.9%. There was significant difference between each other (P = 0.018). CONCLUSIONS: The bacteria infection rate was high after OLT, and the main infected strain was the G(+) bacteria. Most fo them were the opportunistic pathogenic bacteria and the antibiotic multi-resistant bacteria. The bacteria category was significantly related to the infected tissue, according to which we could adopt corresponding antibacterial approach.

Adolescent↗
PubMed2006

Major gene detection for fusiform rust resistance using Bayesian complex segregation analysis in loblolly pine.

The presence of major genes affecting rust resistance of loblolly pine was investigated in a progeny population that was generated with a half-diallel mating of six parents. A Bayesian complex segregation analysis was used to make inference about a mixed inheritance model (MIM) that included polygenic effects and a single major gene effect. Marginalizations were achieved by using Gibbs sampler. A parent block sampling by which genotypes of a parent and its offspring were sampled jointly was implemented to improve mixing. The MIM was compared with a pure polygenic model (PM) using Bayes factor. Results showed that the MIM was a better model to explain the inheritance of rust resistance than the pure PM in the diallel population. A large major gene variance component estimate (> 50% of total variance), indicated the existence of major genes for rust resistance in the studied loblolly pine population. Based on estimations of parental genotypes, it appears that there may be two or more major genes affecting disease phenotypes in this diallel population.

Basidiomycota↗
PubMed2006

[Diagnosis and treatment of invasive aspergillosis infection following orthotopic liver transplantation].

OBJECTIVE: To explore the treatment and appropriate management of invasive aspergillosis infection following orthotopic liver transplantation. METHODS: The clinical data of 576 cases who underwent orthotopic liver transplantation consecutively between January 2000 and January 2005 were analyzed retrospectively. RESULTS: The prevalence of invasive aspergillosis infection was 1.74 (9/576), included 8 cases with pulmonary aspergillosis and 1 case with cerebral aspergillosis. The interval between transplantation and diagnosis were from 10 days to 2 months. Persistent or discontinuous low fever maybe the main clinical presentation after operation. Liposomal amphotericin B (AmBisome) is the mainly treatment for invasive aspergillosis infections, 5 patients were cured and 2 patients developed multi-organ aspergillosis infection died. CONCLUSIONS: The clinical features of invasive aspergillosis infection following orthotopic liver transplantation were un-typical presentations in the early stage and easy to disseminate. Appropriate modification of immunosuppression therapy and early, high dose and long-term application of antifungal treatment is effective and safe to cure the disease.

Adult↗
PubMed2006

[The treatment strategy of early ALI after liver transplantation].

OBJECTIVE: To investigate the treatment strategy of early acute lung injury (ALI) after liver transplantation. METHODS: 18 patients complicated with ALI after liver transplantation were given comprehensive therapies and two minutes of recruitment maneuver (RM) to open previously collapsed lung units and then lung protective ventilatory strategy within 3 hours of hypoxemia. The inspiratory pressure was 25 cm H2O and PEEP 17 cm H2O. Optimal PEEP were maintained after RM to stabilize lung volume. RESULTS: The PaO(2), SaO(2) and PaO(2)/FiO(2) of all 18 patients were improved greatly. RM was effective in 17 patients except one case of severe pulmonary infection, whose PaO(2)/FiO(2) was only improved by 40%. PaO(2), SaO(2) and PaO(2)/FiO(2) were increased by 68 mm Hg, 9.5%, and 104.7% respectively. And the improved oxygenation can be maintained 2 - 24 hours. The effective rate of RM was 94.4%. All 18 patients were weaned and extubated successfully with the survival rate of 100%. RM was well tolerated without complications. CONCLUSION: ALI post liver transplantation should be diagnosed and treated in early stage. RM combined with lung protective ventilatory strategy is a safe and effective treatment for early ALI after liver transplantation.

Combined Modality Therapy↗