Biomedical subjects

Xia Gao

Publications and source records attributed to Xia Gao.

At least 19 recordsLinked to original sources

PubMed2026

Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation.

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

Animals↗

PubMed2026

Thermal analysis techniques for microplastic mass quantification: Methodological challenges and standardization needs.

Microplastics (MPs, 1 μm-5 mm) and nanoplastics (NPs, <1 μm) are ubiquitous contaminants requiring standardized quantification methods. This systematic review evaluates thermal analysis techniques for mass-based MP detection, including pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), thermogravimetry-MS (TGA-MS), thermal extraction desorption-GC-MS (TED-GC-MS), and differential scanning calorimetry (DSC). Database searches (Web of Science, from inception to December 1, 2025) following PRISMA guidelines identified studies across seven environmental matrices (water, soil/sediment, atmosphere, biota, human tissues). We identify critical standardization gaps: inconsistent marker ion selection, unvalidated conversion factors for tire and road wear particles (TRWPs), and the absence of certified reference materials for complex matrices. Py-GC-MS demonstrates versatility but suffers from lipid interference in biological samples; TED-GC-MS offers superior sensitivity (sample capacity ∼200× Py-GC-MS) but lacks real-time chromatographic monitoring. To advance data comparability, we propose: (i) harmonized ion selection hierarchies based on specificity-sensitivity balance, (ii) matrix-specific TRWP quantification protocols, and (iii) inter-laboratory validation using environmental reference materials. This review provides a methodological roadmap for standardizing thermal analysis in MP research.

Humans↗

PubMed2025

AAV gene therapy for autosomal recessive deafness 9: a single-arm trial.

Gene therapy for congenital deafness has shown promising results in children but lacks data in older populations. We conducted a single-arm trial of adeno-associated virus (AAV)-OTOF gene therapy using the Anc80L65 capsid in ten participants with autosomal recessive deafness 9 aged 1.5 to 23.9 years at five sites in China. The primary endpoints were safety and tolerability within 5 years, and secondary endpoints assessed auditory function. Initial findings from the ten patients with 6-12 months of follow-up, including one patient who received two injections, revealed that the therapy was well tolerated, with 162 grade I/II adverse events. Decreased neutrophil percentage was the most common event (16 of 162). All ten participants had at least 6 months of follow-up and improved their pure-tone-average hearing level from baseline 106 ± 9 (mean ± s.d.) to 52 ± 30 decibels (dB). Other secondary endpoints showed similar improvements, including the average click auditory brainstem response (ABR) threshold, the tone-burst ABR threshold and the auditory steady-state response (101 ± 1 to 48 ± 26 dB, 91 ± 4 to 57 ± 19 dB and 80 ± 14 to 64 ± 21 dB, respectively). Post hoc analyses were conducted to evaluate the timecourse and factors contributing to the hearing improvement. Therapeutic effect was rapid, taking 1 month to achieve most of the overall hearing improvement. On an individual level, click and tone-burst ABR thresholds, but not the auditory steady-state response, reliably predicted the behavioral pure-tone-average thresholds after 4 months (R2 = 0.68, 0.73 and 0.17, respectively). An age-dependent therapeutic effect was observed, with optimal outcomes in 5- to 8-year-olds. These preliminary results show that AAV-OTOF was safe and well tolerated in patients ranging from toddlerhood to adulthood. The trial remains ongoing and requires extended follow-up to confirm the long-term safety and efficacy. ClinicalTrials.gov registration: NCT05901480 .

Humans↗

PubMed2024

Dynamics of antibiotic resistance genes during manure composting: Reduction in herbivores manure and accumulation in carnivores.

The elevated levels of antibiotic resistance genes (ARGs) in livestock manure represent a significant threat to both the environment and human health. Composting has been recognized as an effective strategy to mitigate the abundance of ARGs in manure. However, notable rebounds in ARGs abundance have been observed during this process. This study explored the changes in ARGs abundance and the underlying influencing factors during the composting of carnivore (chicken and pig) and herbivore (sheep and cow) manures, along with mushroom residues. The findings revealed that the total relative abundance of ARGs increased by 6.96 and 10.94 folds in chicken and pig manure composts, respectively, whereas it decreased by a remarkable 91.72% and 98.37% in sheep and cow manure composts. Nitrogen content emerged as the primary physicochemical factors governing the abundance of ARGs in chicken and pig manure composts. Conversely, carbon content played a pivotal role in determining ARGs abundance in chicken and pig manure composts. Furthermore, the presence of dominant hosts, such as Corynebacterium, Bacillus, and Clostridium, along with emerging bacteria like Thermobifida, Saccharomonospora, and Actinomadura, contributed significantly to the enrichment of total ARGs, including tetG, tetO, tetX, and sul2, in chicken and pig manure composts. The coexistence of these genes with mobile genetic elements and a plethora of host bacteria, coupled with their high abundance, renders them particularly high-risk ARGs. On the other hand, the observed decrease in the abundance of total ARGs in sheep and cow manure composts can be attributed to the decline in the population of host bacteria, specifically Atopostipes, Psychrobacter, and Corynebacterium. Collectively, these results provide crucial insights into the management of ARGs risks and offer essential theoretical support for enhancing the safe utilization of organic fertilizer in agriculture.

Manure↗

PubMed2006

The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta signaling.

Dapper1 and Dapper2, two divergent members of the Dapper family, have been suggested to modulate Wnt and TGF-beta/Nodal signaling in Xenopus and zebrafish. To get a better understanding of Dapper function in mammals, we have cloned the mouse ortholog of zebrafish Dapper2, mDpr2 and investigated its function in regulating TGF-beta signaling activity. Here, we showed that, like zebrafish Dapper2, overexpression of mDpr2 inhibited the TGF-beta-induced expression of the Smad-responsive reporters and targeted TGF-beta type I receptor ALK5 for degradation in mammalian cells. Overexpression of mDpr2 in the zebrafish embryos led to a decrease in expression of the mesoderm marker no tail and goosecoid at the shield stage and eye fusion later, implying that mDpr2 may have an intrinsic in vivo activity similar to fish Dapper2 activity. The expression of mDpr2 was detected throughout the epiblast around the onset of gastrulation and in somites, the neural tube and gut at later stages in mouse embryos, implying a role in early embryonic development. Our data indicate that the function of Dpr2 as a negative regulator of the TGF-beta/Nodal signal pathway is evolutionally conserved, at least in part, in fish and mammals.

Animals↗

PubMed2006

Cell-based screening and validation of human novel genes associated with cell viability.

In the present study, a cell-based high-throughput assay is established to identify novel human genes associated with cell viability. The assay relies on the down-regulation of Renilla luciferase (pRL) activity in a 96-well format. In addition, 2-color fluorescence probes were used to distinguish living and dead cells. As the positive control, the authors used the expression vectors encoding Bax, TNFRSF1A, and TAJ, which were widely known to effectively induce programmed cell death. They screened 409 novel genes (including alternative mRNA splicing forms) cloned in their laboratory and found that 39 genes could significantly down-regulate pRL activity. A subsequent fluorescence-based assay revealed that 4 of the 39 genes (PIP5KL1, OLFM1, RNF122, FAM26B) were associated with cell viability. Further function assays validated that the 4 genes were able to induce both necrosis and apoptosis. These results therefore indicate that a rapid and effective screening system has been developed, which should shed light on some functions of novel genes.

Apoptosis↗

PubMed2006

Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation.

Wnt signaling plays pivotal roles in the regulation of embryogenesis and cancer development. Xenopus Dapper (Dpr) was identified as an interacting protein for Dishevelled (Dvl), a Wnt signaling mediator, and modulates Wnt signaling. However, it is largely unclear how Dpr regulates Wnt signaling. Here, we present evidence that human Dpr1, the ortholog of Xenopus Dpr, inhibits Wnt signaling. We have identified the regions responsible for the Dpr-Dvl interaction in both proteins and found that the interaction interface is formed between the DEP (Dishevelled, Egl-10, and pleckstrin) domain of Dvl and the central and the C-terminal regions of Dpr1. The inhibitory function of human Dpr1 requires both its N and C terminus. Overexpression of the C-terminal region corresponding to the last 225 amino acids of Dpr1, in contrast to wild-type Dpr1, enhances Wnt signaling, suggesting a dominant negative function of this region. Furthermore, we have shown that Dpr1 induces Dvl degradation via a lysosome inhibitor-sensitive and proteasome inhibitor-insensitive mechanism. Knockdown of Dpr1 by RNA interference up-regulates endogenous Dvl2 protein. Taken together, our data indicate that the inhibitory activity of Dpr on Wnt signaling is conserved from Xenopus to human and that Dpr1 antagonizes Wnt signaling by inducing Dvl degradation.

Adaptor Proteins, Signal Transducing↗

PubMed2006

[Analysis of auditory function on normal growth children in city and rural areas].

OBJECTIVE: To study the auditory function of Chinese normal growth children, and to get a first hand data for protecting children's hearing. METHOD: The normal growth children (6 to 12 years old) in Qinling mountain area, pasturing area around Qinghai Lake and Nanjing city were included in the study, and their whole frequency auditory thresholds were examined on the spot. The auditory thresholds were analyzed. RESULT: There was significant difference between the boys' and girls' auditory thresholds among nearly the whole frequency in Qinling mountain. And there was significant difference between the boys' and girls' auditory thresholds among high frequency and super high frequency in pasturing area around Qinghai Lake, while the girls' auditory function was better than the boys'. In contrast, in Nanjing city no difference was found between the boys' and girls' auditory thresholds. The auditory thresholds in high frequency and super high frequency of the boys in Nanjing city were lower than those of the boys in mountain area and plateau pasturing area, while there was no difference between the girls except for low frequency. CONCLUSION: Worse auditory function was found in Chinese rural areas, especially among the boys. According to the local residents' living condition, the children in remote area nearly had no chance to receive the modern industrial noise and other strong noise. So the firecrackers' noise perhaps made this situation. And the education to avoid the firecrackers' noise must be put into practice in Chinese rural area since childhood.

Audiometry, Pure-Tone↗

PubMed2006

[Effect of nitric oxide and nitric oxide synthase on sensorineural hearing loss secondary to secretory otitis media].

OBJECTIVE: To evaluate the effect of nitric oxide synthase (NOS) and nitric oxide(NO) on sensorineural hearing loss (SNHL) secondary to secretory otitis media (SOM). METHOD: Samples of middle ear effusion were collected at the time of tympanocentesis from 16 cases of SOM with SNHL(group A) and 16 cases of SOM without SNHL(group B). And the concentration of NO and NOS activity in middle ear effusion were detected by colorimetric assay (Griess method). RESULT: The concentration of NO in group A (181.19 +/- 44.31) micromol/L was significantly higher than that in group B (137.00 +/- 40.67) micromol/L (P < 0.01). The NOS activity in group A (97.69 +/- 29.62)U was also significantly higher than that in group B (75.50 +/- 26.99)U (P < 0.05). CONCLUSION: Excess generation of NO in middle ear effusion which synthesized by NOS may hurt inner ear directly by its cytotoxic action or enhance local inflammatory reaction with other inflammatory factors. This study suggests that NO play a significant role in the process and pathogenesis of SNHL secondary to SOM.

Adult↗

PubMed2006

[Thyroid malignant tumor with flare up glottic paralysis for first symptom].

OBJECTIVE: To approach clinical feature of thyroid malignant tumor with Flare up glottic paralysis for first symptom, and analysis that should be avoided missed diagnosis and misdiagnosis during diagnosis and treatment. METHOD: Retrospective research five cases of thyroid malignant tumor with flare up glottic paralysis papillary adenocarcinoma of thyroid by pathology. Four cases had one side glottic paralysis, the same side thyroid were moved after dissecting the recurrent laryngeal nerve. Three cases of them recovered normal vocal cord function, the function of one case was compensated by another side vocal cord. The last one had right gliotic paralysis first, then both cricoarytenoid joint had been fixed, hoarse voice was worse and developed to dyspnea since the tumor invaded in larynx one year later. We only did cut the right thyroid and right half larynx, but the tumor came back again in larynx in three months, then had to removal whole larynx without recurrence follow up two years. CONCLUSION: For the flare up glottic paralysis with same side tiny thyroid tumor, we suggest that the thyroid must be made operation research if no other reasons, dissecting and protecting the recurrent laryngeal nerve during operation, and cut reasonable thyroid and others according to fast pathologic diagnosis.

Carcinoma, Papillary↗

PubMed2005

Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia.

Genetic studies in mouse and zebrafish have established the importance of activin receptor-like kinase 1 (ALK1) in formation and remodeling of blood vessels. Single-allele mutations in the ALK1 gene have been linked to the human type 2 hereditary hemorrhagic telangiectasia (HHT2). However, how these ALK1 mutations contribute to this disorder remains unclear. To explore the mechanism underlying effect of the HHT-related ALK1 mutations on receptor activity, we generated 11 such mutants and investigated their signaling activities using reporter assay in mammalian cells and examined their effect on zebrafish embryogenesis. Here we show that some of the HHT2-related mutations generate a dominant-negative effect whereas the others give rise to a null phenotype via loss of protein expression or receptor activity. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity.

Activin Receptors, Type I↗

PubMed2005

High-throughput limited proteolysis/mass spectrometry for protein domain elucidation.

High-resolution structural information is important for improving our understanding of protein function in vitro and in vivo and providing information to enable drug discovery. The process leading to X-ray structure determination is often time consuming and labor intensive. It requires informed decisions in expression construct design, expression host selection, and strategies for protein purification, crystallization and structure determination. Previously published studies have demonstrated that compact globular domains defined by limited proteolysis represent good candidates for production of diffraction quality crystals [1-7]. Integration of mass spectrometry and proteolysis experiments can provide accurate definition of domain boundaries at unprecedented rates. We have conducted a critical evaluation of this approach with 400 target proteins produced by SGX (Structural GenomiX, Inc.) for the New York Structural GenomiX Research Consortium (NYSGXRC; http://www.nysgxrc.org) under the auspices of the National Institute of General Medical Sciences Protein Structure Initiative (http://www.nigms.nih.gov/psi). The objectives of this study were to develop parallel/automated protocols for proteolytic digestion and data acquisition for multiple proteins, and to carry out a systematic study to correlate domain definition via proteolysis with outcomes of crystallization and structure determination attempts. Initial results from this work demonstrate that proteins yielding diffraction quality crystals are typically resistant to proteolysis. Large-scale sub cloning and subsequent testing of expression, solubility, and crystallizability of proteolytically defined truncations is currently underway.

Amino Acid Sequence↗

PubMed2005

New York-Structural GenomiX Research Consortium (NYSGXRC): a large scale center for the protein structure initiative.

Structural GenomiX, Inc. (SGX), four New York area institutions, and two University of California schools have formed the New York Structural GenomiX Research Consortium (NYSGXRC), an industrial/academic Research Consortium that exploits individual core competencies to support all aspects of the NIH-NIGMS funded Protein Structure Initiative (PSI), including protein family classification and target selection, generation of protein for biophysical analyses, sample preparation for structural studies, structure determination and analyses, and dissemination of results. At the end of the PSI Pilot Study Phase (PSI-1), the NYSGXRC will be capable of producing 100-200 experimentally determined protein structures annually. All Consortium activities can be scaled to increase production capacity significantly during the Production Phase of the PSI (PSI-2). The Consortium utilizes both centralized and de-centralized production teams with clearly defined deliverables and hand-off procedures that are supported by a web-based target/sample tracking system (SGX Laboratory Information Data Management System, LIMS, and NYSGXRC Internal Consortium Experimental Database, ICE-DB). Consortium management is provided by an Executive Committee, which is composed of the PI and all Co-PIs. Progress to date is tracked on a publicly available Consortium web site (http://www.nysgxrc.org) and all DNA/protein reagents and experimental protocols are distributed freely from the New York City Area institutions. In addition to meeting the requirements of the Pilot Study Phase and preparing for the Production Phase of the PSI, the NYSGXRC aims to develop modular technologies that are transferable to structural biology laboratories in both academe and industry. The NYSGXRC PI and Co-PIs intend the PSI to have a transforming effect on the disciplines of X-ray crystallography and NMR spectroscopy of biological macromolecules. Working with other PSI-funded Centers, the NYSGXRC seeks to create the structural biology laboratory of the future. Herein, we present an overview of the organization of the NYSGXRC and describe progress toward development of a high-throughput Gene-->Structure platform. An analysis of current and projected consortium metrics reflects progress to date and delineates opportunities for further technology development.

Cloning, Molecular↗

PubMed2005

Overexpression of the N-terminal end of the p55gamma regulatory subunit of phosphatidylinositol 3-kinase blocks cell cycle progression in gastric carcinoma cells.

pRb and its family members p130 and p107 regulate cell cycle progression and direct G1/S transition in mammalian cells through interaction with the transcription factor E2F. Phosphatidylinositol 3-kinase (PI3K) is an essential component of growth factor-regulated pathways and plays a crucial role in the regulation of cellular proliferation and differentiation. It has been demonstrated that PI3K can regulate cell cycle progression via Akt-mediated pathway. However, the possible interactions between PI3K and Rb pathways remain to be defined. It was reported that the unique 24-amino-acid N-terminal end of the p55 regulatory subunits of PI3K is an Rb-binding domain and affects Rb action or Rb-E2F interaction. The 24 N-terminal amino acids of p55gamma encoded by a cDNA construct could compete with the endogenous p55gamma for binding to Rb, which influences Rb-mediated signaling and blocks cell cycle progression. In the current study, we investigated the effects of this 24-peptide on cell proliferation in human gastric carcinoma MKN-28 cells by means of cell cycle analysis, BrdU incorporation, and determining the levels of cell cycle regulatory molecule expression. Our results showed that p55gammaPI3K and the Rb family members p130 and p107 exist in MKN-28 cells, while the p110PI3K was not detected. Moreover, p55gammaPI3K was found binding to p130/p107 in these cells. We demonstrated that the introduction of the plasmid N24p55-GFP (harboring the cDNA for the 24 N-terminal amino acids of p55gamma) into MKN-28 cells caused cell cycle arrest at G1. Furthermore, we showed that the over-expression of the 24-peptide in MKN-28 cells decreased the population of cells incorporating BrdU and reduced the levels of cyclin D1 and cyclin A. These observations suggest that PI3K can regulate cell cycle progression and cell proliferation in human gastric tumor cells via Rb-mediated pathway, and that this effect of PI3K is mediated through a direct association with Rb via the N-terminal end of its p55 kDa regulatory subunits and modulating Rb-E2F interactions. Taken together with previous studies, our data provide a new therapeutic target in human stomach cancer. Strategies targeting PI3K signal transduction or the association of PI3K with Rb, or regulating PI3K-Rb interactions could be employed for gene therapy or chemotherapy of gastric cancer and other tumors.

Carcinoma↗

PubMed2005

[Antibacterial activity and cytotoxicity of polypeptide dhvar4].

OBJECTIVE: To investigate the antibacterial activity and the cytotoxicity of polypeptide dhvar4. METHODS: Solid-phase synthesized dhvar4 was manufactured by MeiLian Biotech Co. Ltd.; we evaluated its antibacterial effect, using the growth curve of bacteria after the bacteria being treated with different concentration of dhvar4. The cytotoxicity of dhvar4 on L-02, ECV-304, 293, 3T3 cells was investigated by MTT assay, and human erythrocytes were subimitted to hemolytic assay. RESULTS: dhvar4 inhibited the growth of Enterococcus faecium 36418 and Staphylococcus aureus BAA42 only at the concentration of 4 microg/ml. The viability of mammalian cells remained 68%-92% even when the concentration of dhvar4 reached 150 microg/ml. The LD50 (median lethal dose) was determined to be higher than 150 microg/ml. And very low hemolytic activity of dhvar4 was detected even at the highest protein concentration tested (180 microg/ml). CONCLUSION: dhvar4 possesses antibacterial activity and has little cytotoxicity to mammalian cells. These results suggest that dhvar4 has great potential in the development of

Antifungal Agents↗

PubMed2005

[Observation of the relationship between systemic hypotension and sudden sensorineural deafness in young subjects].

OBJECTIVE: To confirm whether systemic hypotension influences the genesis of sudden sensorineural deafness(SSD) in young people. METHOD: Twenty-eight untreated young patients diagnosed as SSD in experimental group were compared with 30 age- and sex- matched subjects in control group. Both groups have received the clinic BP testing, 24 hour BP monitoring and their indexes about lipid metabolism were examined and recorded. The statistical analysis was carried out on the data obtained from 2 groups. RESULT: The average clinic and 24 hour BP values in patients with SSD were significantly lower. The hypotension (diagnosed according to ISD standard) occurred more frequently in SSD group. There was no difference in metabolism indexes between 2 groups. CONCLUSION: Systemic hypotension which can cause perfusion damage in cochlea can be considered as a possible cause responsible for the development of SSD in young subjects. It's necessary to keep blood pressure monitoring and avoid applying vasodilating drugs until a suspecting or known hypotensive condition is associated with hearing loss.

Adult↗

PubMed2004

A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine --> phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.

Animals↗

PubMed2004

[EGG and acoustic test for the diagnosis of laryngeal diseases].

OBJECTIVE: To explore the relationship between electroglottography/acoustic test parameter and disease diagnosis. METHOD: 3.0 software by Dr. Speech was used to test synchronically the electroglottography and acoustic test parameter of 503 cases so as to make a statistical analysis and comparison. RESULT: The shimmer was similar with the jitter on the inspection of polyp of vocal cord and vocal nodules, but the shimmer was more susceptive than the jitter. Compared with the healthy group, mean F0, jitter and shimmer of polyp of vocal cord increased, while the Harmonic-to-Noise decreased, so did the vocal nodules and carcinoma of larynx. Compared with the normal, the contact index of carcinoma of larynx increased, but the contact quotient remained on the same level. CONCLUSION: EGG, acoustic test number comparison and wave change provide an objective quantized index for the diagnosis of laryngeal diseases.

Adolescent↗