Biomedical subjects

Yao Xu

Publications and source records attributed to Yao Xu.

At least 19 recordsLinked to original sources

PubMed2025

MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer.

BACKGROUND: This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS: We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS: The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS: This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.

Humans↗

PubMed2025

Association of metabolic dysregulation with treatment response in rectal cancer patients undergoing chemoradiotherapy.

BACKGROUND: This study aimed to explore the metabolic changes during neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) by serum metabolomics analysis, and to provide new biomarkers for individualized treatment and efficacy prediction. METHODS: Serum samples from 20 patients with LARC before, during and after NCRT were collected for metabolomic analysis. The metabolites in the serum samples were analyzed qualitatively and quantitatively using gas chromatography-mass spectrometry (GC-MS). Meanwhile, the differences in metabolic profiles at different time points were compared and significantly changed metabolites were screened. RESULTS: The metabolic profiles of patients were significantly altered at different time points of NCRT. Through metabolomic analysis, we identified metabolites that were significantly altered during NCRT and revealed alterations in the associated metabolic pathways. The predictive power of pre-radiotherapy isocitric acid and pro-radiotherapy 3-hydroxy-3-(4'-hydroxy-3'-methoxyphenyl) propionic acid in distinguishing patients sensitive and non-sensitive to NCRT was markedly high, with AUC values of 0.875 and 0.75, respectively. Additional analysis indicated that a combined panel of serum metabolites yielded even higher AUC values, thereby enhancing the accuracy of predicting the efficacy of neoadjuvant NCRT. CONCLUSION: This study revealed metabolic changes and corresponding alterations in metabolic pathways during NCRT in patients with LARC by serum metabolomic analysis. The metabolic disorders may be associated with poor outcomes in patients treated with NCRT for rectal cancer, providing new biomarkers for individualized treatment and prognostic assessment. Further studies and validation will help to gain insight into the mechanism of these metabolic changes and provide more basis for clinical application.

Humans↗

PubMed2024

Clocking out and letting go to unleash green biotech applications in a photosynthetic host.

Cyanobacteria are photosynthetic bacteria whose gene expression patterns are globally regulated by their circadian (daily) clocks. Due to their ability to use sunlight as their energy source, they are also attractive hosts for "green" production of pharmaceuticals, renewable fuels, and chemicals. However, despite the application of traditional genetic tools such as the identification of strong promoters to enhance the expression of heterologous genes, cyanobacteria have lagged behind other microorganisms such as Escherichia coli and yeast as economically efficient cell factories. The previous approaches have ignored large-scale constraints within cyanobacterial metabolic networks on transcription, predominantly the pervasive control of gene expression by the circadian (daily) clock. Here, we show that reprogramming gene expression by releasing circadian repressor elements in the transcriptional regulatory pathways coupled with inactivation of the central oscillating mechanism enables a dramatic enhancement of expression in cyanobacteria of heterologous genes encoding both catalytically active enzymes and polypeptides of biomedical significance.

Photosynthesis↗

PubMed2007

Infrared temperature-jump study of the folding dynamics of alpha-helices and beta-hairpins.

The laser-induced temperature-jump (T-jump) technique in conjunction with infrared spectroscopy provides a versatile means to study the early events in protein folding. Compared with the commonly used stopped-flow kinetic methods, the T-jump initiation technique offers a faster time resolution. It allows the study of protein folding processes occurring on the nanosecond-to-microsecond time-scales. In addition, infrared spectroscopy is a powerful tool for characterizing backbone conformation and dynamics. In this chapter, we mainly discuss the application of this technique to the study of the helix-coil transition dynamics and the mechanism of beta-hairpin formation.

Amino Acid Sequence↗

PubMed2006

Nanosecond folding dynamics of a three-stranded beta-sheet.

We studied conformational stability and folding kinetics of a three-stranded beta-sheet containing two rigid turns. Static infrared measurements indicate that this beta-sheet undergoes a broad but cooperative thermal unfolding transition with a midpoint at approximately 53 degrees C. Interestingly, time-resolved infrared experiments show that its relaxation kinetics in response to a temperature-jump (T-jump) occur on the nanosecond time scale (e.g., the relaxation time is approximately 140 ns at 35.0 degrees C), thereby suggesting that the conformational relaxation encounters only a small free energy barrier or even proceeds in a downhill manner. Further Langevin dynamics simulations suggest that the observed T-jump relaxation kinetics could be modeled by a conformational diffusion process along a single-well free energy profile, which allowed us to determine the effective diffusion constant and also the roughness of the folding energy landscape.

Amino Acid Sequence↗

PubMed2006

Studies on a new carrier of trimethylsilyl-modified mesoporous material for controlled drug delivery.

To better control drug delivery rate, a simple and effective approach has been developed for controlled drug delivery carrier system through one-step surface modification of the ibuprofen-impregnated silica MCM-41 with 1, 1, 1, 3, 3, 3-hexamethyldisilazane (HMDS). The 29Si MAS NMR characterization demonstrated that different contents of trimethylsilyl (TMS) groups were successfully grafted onto the samples modified with different silylation times. The results obtained from in vitro tests exhibited that the introduction of TMS groups greatly retarded the ibuprofen release rate. Even after in vitro test for 48 h, only 75% of the impregnated ibuprofen could be released from the modified sample with TMS groups content of 14.5% (related to the total silicon atoms). However, the release of ibuprofen could be completed just after about 1 h from the pure silica MCM-41 under the same release conditions. Furthermore, the release rate of ibuprofen could be well modulated by changing the grafted content of TMS groups, and was found to decrease with increasing grafted amount of TMS groups.

Biological Availability↗

PubMed2006

Analysis of KaiA-KaiC protein interactions in the cyano-bacterial circadian clock using hybrid structural methods.

The cyanobacterial circadian clock can be reconstituted in vitro by mixing recombinant KaiA, KaiB and KaiC proteins with ATP, producing KaiC phosphorylation and dephosphorylation cycles that have a regular rhythm with a ca. 24-h period and are temperature-compensated. KaiA and KaiB are modulators of KaiC phosphorylation, whereby KaiB antagonizes KaiA's action. Here, we present a complete crystallographic model of the Synechococcus elongatus KaiC hexamer that includes previously unresolved portions of the C-terminal regions, and a negative-stain electron microscopy study of S. elongatus and Thermosynechococcus elongatus BP-1 KaiA-KaiC complexes. Site-directed mutagenesis in combination with EM reveals that KaiA binds exclusively to the CII half of the KaiC hexamer. The EM-based model of the KaiA-KaiC complex reveals protein-protein interactions at two sites: the known interaction of the flexible C-terminal KaiC peptide with KaiA, and a second postulated interaction between the apical region of KaiA and the ATP binding cleft on KaiC. This model brings KaiA mutation sites that alter clock period or abolish rhythmicity into contact with KaiC and suggests how KaiA might regulate KaiC phosphorylation.

Amino Acid Sequence↗

PubMed2006

Limitations of yeast surface display in engineering proteins of high thermostability.

Engineering proteins that can fold to unique structures remains a challenge. Protein stability has previously been engineered via the observed correlation between thermal stability and eukaryotic secretion level. To explore the limits of an expression-based approach, variants of the highly thermostable three-helix bundle protein alpha3D were studied using yeast surface display. A library of alpha3D mutants was created to explore the possible correlation of protein stability and fold with expression level. Five efficiently expressed mutants were then purified and further studied biochemically. Despite their differences in stability, most mutants expressed at levels comparable with that of wild-type alpha3D. Two other related sequences (alpha3A and alpha3B) that form collapsed, stable molten globules but lack a uniquely folded structure were similarly expressed at high levels by yeast display. Together these observations suggest that the quality control system in yeast is unable to discriminate between well-folded proteins of high stability and molten globules. The present study, therefore, suggests that an optimization of the surface display efficiency on yeast may yield proteins that are thermally and chemically stable yet are poorly folded.

Amino Acid Sequence↗

PubMed2006

Clinical application of plasma shock wave lithotripsy in treating impacted stones in the bile duct system.

AIM: To verify the safety and efficacy of plasma shock wave lithotripsy (PSWL) in fragmenting impacted stones in the bile duct system. METHODS: From September 1988 to April 2005, 67 patients (26 men and 41 women) with impacted stones underwent various biliary operations with tube (or T-tube) drainage. Remnant and impacted stones in the bile duct system found by cholangiography after the operation were fragmented by PSWL and choledochofiberscopy. A total of 201 impacted stones were fragmented by PSWL setting the voltage at 2.5-3.5 kV, and the energy output at 2-3 J for each pulse of PSWL. Then the fragmented stones were extracted by choledochofiberscopy. The safety and efficacy of PSWL were observed during and after the procedure. RESULTS: One hundred and ninety-nine of 201 impacted stones (99.0%) in the bile duct system were successfully fragmented using PSWL and extracted by choledochofiberscopy. The stone clearance rate for patients was 97% (65/67). Ten patients felt mild pain in the right upper quadrant of the abdomen, and could tolerate it well. Eleven patients had a small amount of bleeding from the mucosa of the bile duct. The bleeding was transient and stopped spontaneously within 2 min of normal saline irrigation. There were no significant complications during and after the procedure. CONCLUSION: PSWL is a safe and effective method for fragmenting impacted stones in the bile duct system.

Adult↗

PubMed2005

Hydrothermal synthesis, characterization, and photocatalytic performance of silica-modified titanium dioxide nanoparticles.

Silica-modified titanium dioxides were prepared by a hydrothermal method and then characterized by XRD, FT-IR, XPS, TEM, and UV-visible spectroscopy. The silica-modified titanium dioxides were in anatase phase and had large surface areas. There was strong interaction between SiO2 and TiO2, and TiOSi bonds formed during the hydrothermal process. The addition of silica in TiO2 particles could effectively suppress the formation of the rutile phase and the growth of titanium dioxide crystals. DRS spectra proved an increase in the band-gap transition with the increase of silica. The silica-modified TiO2 nanoparticles exhibited better photocatalytic activity, which increased with the silica amount, in comparison with pure TiO2 nanoparticles. Due to better thermal stability, the photocatalytic activity of the silica-modified TiO2 sample held good photocatalytic activity even after calcined at 1273 K.

Journal Article↗

PubMed2005

Superhydrophobic antireflective silica films: fractal surfaces and laser-induced damage thresholds.

Several superhydrophobic antireflective silica films have been prepared by a solgel method that uses hexamethyl-disilizane (HMDS) as a modifier. In a high-power laser, laser-induced damage thresholds (LIDTs) of 23-30 J/cm2 were obtained at 1064-nm wavelength with 1-ns pulse duration. By atomic-force microscopy and optical microscopy, the fractal surfaces of films were studied, and multifractal spectra (MFSs) were calculated both before and after laser damage. The two-sided effect of HMDS on particle growth determined the surface fractal of a particle and the multifractal structure of a film's surface. The bigger deltaalpha was, both before and after laser damage, the lower the LIDT was. The effect of methyl groups should be included in the determination of the MFS of the LIDT.

Journal Article↗

PubMed2004

Determining beta-sheet stability by Fourier transform infrared difference spectra.

We describe here a new method for determining the conformational stability of antiparallel beta-sheets. Due to coupling between the transition dipoles, beta-sheet conformations typically exhibit a characteristic high-frequency amide I component centered at approximately 1680 cm(-1). Using one beta-sheet protein and two small beta-hairpins, we demonstrate that this high-frequency component, which is fairly narrow (approximately 8-10 cm(-1)), can be quantitatively resolved and used in thermal stability determination. Compared with the commonly used CD and fluorescence techniques, this ir method offers advantages. Since the area of this high-frequency component is only proportional to the folded population, it eliminates the need for a priori information of the folded and unfolded baselines encountered in other methods. Thus, it is applicable to a variety of beta-sheet systems.

Magnetic Resonance Spectroscopy↗

PubMed2004

Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses.

In cyanobacteria, KaiC is an essential hexameric clock protein that forms the core of a circadian protein complex. KaiC can be phosphorylated, and the ratio of phospho-KaiC to non-phospho-KaiC is correlated with circadian period. Structural analyses of KaiC crystals identify three potential phosphorylation sites within a 10-A radius of the ATP binding regions that are at the T432, S431, and T426 residues in the KaiCII domains. When these residues are mutated by alanine substitution singly or in combination, KaiC phosphorylation is altered, and circadian rhythmicity is abolished. These alanine substitutions do not prevent KaiC from hexamerizing. Intriguingly, the ability of KaiC overexpression to repress its own promoter is also not prevented by alanine substitutions at these sites, implying that the capability of KaiC to repress its promoter is not sufficient to allow the clockwork to oscillate. The KaiC structure and the mutational analysis suggest that S431 and T426 may share a phosphate that can shuttle between these two residues. Because the phosphorylation status of KaiC oscillates over the daily cycle, and KaiC phosphorylation is essential for clock function as shown here, daily modulations of KaiC activity by phosphorylation at T432 and S431/T426 seem to be key components of the circadian clockwork in cyanobacteria.

Amino Acid Sequence↗

PubMed2004

Visualizing a circadian clock protein: crystal structure of KaiC and functional insights.

Circadian (daily) biological clocks express characteristics that are difficult to explain by known biochemical mechanisms, and will ultimately require characterizing the structures, functions, and interactions of their molecular components. KaiC is an essential circadian protein in cyanobacteria that forms the core of the KaiABC clock protein complex. We report the crystal structure of the KaiC homohexameric complex at 2.8 A resolution. The structure resembles a double doughnut with a central pore that is partially sealed at one end. The crystal structure reveals ATP binding, inter-subunit organization, a scaffold for Kai-protein complex formation, the location of critical KaiC mutations, and evolutionary relationships to other proteins. A key auto-phosphorylation site on KaiC (T432) is identified from the crystal structure, and mutation of this residue abolishes circadian rhythmicity. The crystal structure of KaiC will be essential for understanding this circadian clockwork and for establishing its links to global gene expression.

Adenosine Triphosphate↗

PubMed2004

In vivo detection of protein-protein interaction in plant cells using BRET.

The emerging technique of bioluminescence resonance energy transfer (BRET) allows us to detect protein interactions in live cells and in real time, thus providing a new window into cellular signal transduction processes. We present experimental protocols for expressing fusion proteins between luciferase and fluorescent proteins that are the basis for BRET measurement, as well as for measuring and imaging BRET in a variety of cell types. Despite our focus on plant cells, the techniques described here are easily adaptable to other cell systems that have yet to benefit from the BRET technique.

Arabidopsis↗

PubMed2004

[Study of genes related to gastric cancer and its premalignant lesions with fluorescent differential display].

BACKGROUND & OBJECTIVE: It is generally recognized that development of gastric cancer arises gradually from premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia). Differential display of mRNA is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa tissue that may precede the development of gastric cancer. METHODS: The differentially expressed cDNA bands were isolated and identified by fluorescent differential display in 2 gastric cancer, 2 premalignant lesions, and 2 normal gastric mucosa tissues and then reamplified by PCR. After being cloned, all cDNA fragments were sequenced. Through BLAST software, the sequencing results were compared with GenBank database for homology analysis. Expression of SPTAN1 in 7 gastric cancer tissues, 7 premalignant lesions, and 7 normal gastric mucosa tissues were identified by RT-PCR. RESULTS: Four differentially expressed cDNA fragments were found. Three of them were over-expressed in the gastric cancer tissue. One of them was over-expressed in premalignant lesions and normal gastric mucosa tissue. One cDNA fragment over-expressed in gastric cancer was homologous to SPTAN1 and its over-expression in gastric cancer was confirmed by RT-PCR. The other three cDNA fragments showed significant homology to known gene sequences in GenBank but their functions are unknown. CONCLUSION: Three of the four differentially expressed genes over-expressed in gastric cancer. SPTAN1gene was significantly higher in gastric cancer tissue than in normal gastric mucosa tissue and dysplasia tissue.

Base Sequence↗

PubMed2004

[Differential expression of motility-related protein-1/CD9 gene in gastric cancers and premalignant lesions].

OBJECTIVE: To clone and identify gastric cancer-related genes and explore the possible pathogenic mechanism of gastric cancer. METHODS: The differentially expressed cDNA bands were isolated by fluorescent mRNA differential display in gastric cancer specimens, matched normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated genes. MRP-1/CD9 gene expression in different kinds of gastric tissue was analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: MRP-1/CD9 expression was down-regulated in all gastric cancer tissues. Northern blot analysis confirmed this differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene expression was much lower in gastric cancers(0.31+/-0.18) than in the matched normal gastric tissue (0.49+/-0.24) and in the premalignant lesions (0.47+/-0.18) (P<0.05), and its expression in intestinal type gastric cancer (0.38+/-0.16) was higher than that in diffuse type gastric cancer (0.22+/-0.17) (P<0.05). CONCLUSION: The MRP-1/CD9 gene expression was down-regulated in gastric cancer, its expression was probably related to the carcinogenesis and histology types of gastric cancer.

Antigens, CD↗

PubMed2003

Infrared study of the stability and folding kinetics of a 15-residue beta-hairpin.

The thermal stability and folding kinetics of a 15-residue beta-hairpin (SESYINPDGTWTVTE) have been studied by using infrared (IR) spectroscopy coupled with laser-induced temperature-jump (T-jump) technique for rapid folding-unfolding initiation. An alternative method based on analyzing IR difference spectra was also introduced to obtain thermodynamic properties of beta-sheets, which complements the commonly used circular dichroism (CD) and fluorescence techniques. Equilibrium IR measurements indicate that the thermal unfolding of this beta-hairpin is fairly broad. However, it can be described by a two-state transition with a thermal melting temperature of approximately 29 degrees C. Time-resolved IR measurements following a T-jump, probed at 1634 cm(-1), indicate that the folding of this beta-hairpin follows first-order kinetics and is amazingly fast. At 300 K, the folding time is approximately 0.8 micros, which is only 2-3 times slower than that of alpha-helix formation. Additionally, the energetic barrier for folding is small (approximately 2 kcal mol(-1)). These results, in conjunction with results from other studies, support a view that the details of native contacts play a dominant role in the kinetics of beta-hairpin folding.

Amino Acid Sequence↗