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Liang Wang

Publications and source records attributed to Liang Wang.

At least 19 recordsLinked to original sources
PubMed2026

Hyperlactate-Associated Lysine Lactylome Remodeling in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) lacks reliable biomarkers, and the roles of lactate metabolism and lysine lactylation (Kla) remain largely unknown. We profiled the lysine lactylome of LSCC, paired it with adjacent normal tissues, and integrated the data with quantitative proteomic and transcriptomic analyses. LSCC exhibited a hyperlactate-associated phenotype characterized by dysregulated lactate-related genes (LRGs), altered protein abundance, increased tissue lactate, and globally increased Kla levels. Data-independent acquisition mass spectrometry (DIA-MS) identified 1616 Kla sites on 1468 peptides from 688 proteins, with most differential sites being upregulated in tumors. Differentially lactylated proteins were enriched in cell-matrix adhesion, cell migration, chromatin remodeling, and gene-regulatory processes and were clustered into cytoskeletal and nuclear regulatory modules. Multiple Kla sites were also detected on the core histones. Immunoblotting and tissue microarray analyses confirmed increased pan-Kla expression in the LSCC. Pan-Kla levels were independent of sex and age but positively correlated with the tumor stage and lymph-node metastasis. These findings provide a systematic resource for hyperlactate-associated lactylome remodeling in LSCCs and identify candidate Kla-related molecular features associated with clinicopathological progression for future functional and clinical evaluation.

Humans↗
PubMed2025

Proteome-wide association study of prostate cancer risk across populations.

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls of European population, 10,809 cases and 95,790 controls of Asian population, and 3931 cases and 26,405 controls of Hispanic/Latino population. We identify three, four, 15, and 73 PCa-associated proteins in African, Hispanic/Latino, Asian, and European populations, respectively, and 83 in trans-population meta-analysis. There are both pan-population and population-specific associations. Our findings provide valuable insights into etiology of PCa.

Humans↗
PubMed2025

Single-Molecule Nanopore Detection of Non-Canonical Thymine-Melamine Hydrogen Bonding Base Pair in DNA Abasic Site.

The binding of small molecules to DNA may represent a mutagenic process capable of inducing genomic structural alterations and functional impairment. Melamine (MA), a toxic small molecule, exhibits a hydrogen-bonding interface structurally analogous to adenine, enabling to form non-canonical thymine-melamine (T-MA) base pairs like Watson-Crick pairing. This property allows MA to program DNA nanostructure formation. Given MA's documented biological consequences, such as kidney disease, reproductive toxicity, and central nervous system dysfunction, sensitive detection of MA-DNA interactions has become critically important. However, such subtle structural changes remain challenging to identify because of the paucity of effective detection approaches in a high-resolution manner. To overcome this limitation, nanopore measurement is employed to identify T-MA hydrogen bonding base pairing in DNA. Results demonstrate that nanopore enables unambiguous identification of T-MA hydrogen bonding via mechanically unzipping thymine-melamine-thymine (T-MA-T) triplets in DNA structures. The approach achieves single-base-pair resolution, as evidenced by nucleotide substitutions flanking the abasic site in complex DNA structures. In addition, nanopore-based kinetic analysis reveals an enhanced intramolecular stability in MA-binding DNA compared to those consisting of complete canonical DNA pairs. This research establishes a powerful platform for high-resolution interrogation of DNA-small molecule interactions and quantitative biophysical characterization of mutagenic modifications at the nanoscale.

Single Molecule Imaging↗
PubMed2007

Loss of testicular orphan receptor 4 impairs normal myelination in mouse forebrain.

Testicular orphan nuclear receptor 4 (TR4) has been suggested to play important roles in the development and functioning of the central nervous system (CNS). We find reduced myelination in TR4 knockout (TR4(-/-)) mice, which is particularly obvious in forebrains and in early developmental stages. Further analysis reveals that CC-1-positive (CC-1+) oligodendrocytes are decreased in TR4(-/-) forebrains. The O4+ signals are also reduced in TR4(-/-) forebrains when examined at postnatal d 7. However, the number and proliferation rate of platelet-derived growth factor receptor alpha-positive (PDGFalphaR+) oligodendrocyte precursor cells (OPCs) remain unaffected in these regions, suggesting that loss of TR4 interrupts oligodendrocyte differentiation. This is further supported by the observation that CC-1+ oligodendrocytes derived from 5-bromo-2'-deoxyuridine incorporating OPCs are significantly reduced in TR4(-/-) forebrains. We also find higher Jagged1 expression levels in axon fiber-enriched regions in TR4(-/-) forebrains, suggesting a more activated Notch signaling in these regions that correlates with previous reports showing that Notch activation inhibits oligodendrocyte differentiation. Together, our results suggest that TR4 is required for proper myelination in the CNS and is particularly important for oligodendrocyte differentiation and maturation in the forebrain regions. The altered Jagged1-Notch signaling in TR4(-/-) forebrain underlies a potential mechanism that contributes to the reduced myelination in the forebrain.

Animals↗
PubMed2007

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study.

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.

Aged↗
PubMed2007

Incremental value of multiplanar cross-referencing for prostate cancer staging with endorectal MRI.

OBJECTIVE: The purpose of this study was to assess whether use of the PACS cross-referencing tool in 3D MRI improves tumor staging of prostate cancer when pathologic findings are used as the reference standard. MATERIALS AND METHODS: The institutional review board granted a waiver of informed consent for the study. Endorectal MRI at 1.5 T was performed before radical prostatectomy in 255 consecutive patients. Two radiologists unaware of the clinical data retrospectively and independently interpreted MR images without and with cross-referencing to predict the presence of extracapsular extension (ECE) and seminal vesicle invasion (SVI). Histopathologic findings were used as the reference standard. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity, and weighted kappa statistics were calculated. RESULTS: At histologic examination, 68 (27%) of the patients were found to have ECE and 13 (5%) of the patients to have SVI; the latter all had ECE. In detecting ECE, both reviewers had a higher AUC using cross-referencing (p < 0.001 for both). The weighted kappa value was 0.56 for MRI alone and 0.76 for MRI with cross-referencing, indicating fair to good interobserver agreement. Sensitivity and specificity for ECE with MRI alone and with cross-referencing were 43% and 94% and 57% and 100% for reviewer 1 and 40% and 93% and 59% and 98% for reviewer 2, respectively. In detecting SVI, both reviewers had a higher AUC with cross-referencing (p = 0.007 and p = 0.056 for reviewers 1 and 2, respectively). Reviewer 1 benefited much more from cross-referencing than did reviewer 2. The weighted kappa statistic was 0.69 for MRI alone and the same with cross-referencing, indicating good interobserver agreement. Sensitivity and specificity for SVI with MRI alone and with cross-referencing, respectively, were 23% and 83% and 46% and 93% for reviewer 1 and 31% and 91% and 54% and 95% for reviewer 2. CONCLUSION: PACS cross-referencing significantly improves tumor staging of prostate cancer with 3D MRI. Some reviewers benefit more than others from use of this tool.

Adult↗
PubMed2006

A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a 'universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that 'high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways.

Bacterial Physiological Phenomena↗
PubMed2006

Prediction of seminal vesicle invasion in prostate cancer: incremental value of adding endorectal MR imaging to the Kattan nomogram.

PURPOSE: To retrospectively determine whether endorectal magnetic resonance (MR) imaging findings contribute incremental value to the Kattan nomogram for predicting seminal vesicle invasion (SVI) in patients with prostate cancer. MATERIALS AND METHODS: The institutional review board issued a waiver of authorization, which included a waiver of informed consent, for this HIPAA-compliant study. From October 2000 through January 2005, 573 patients (mean age, 58.3 years; age range, 36-86 years) underwent endorectal MR imaging before prostate cancer surgery. The endorectal MR imaging results had been prospectively interpreted by seven radiologists, and the likelihood of SVI was retrospectively scored on the basis of radiologists' written reports. MR imaging findings, individual clinical variables (serum prostate-specific antigen [PSA] level, Gleason grade, clinical stage, greatest percentage of cancer in all biopsy cores, percentage of positive cores in all biopsy cores, and perineural invasion), and the Kattan nomogram were evaluated with respect to SVI prediction; surgical pathologic analysis was used as the reference standard. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: At pathologic analysis, 28 (4.9%) of 573 patients had SVI. At univariate analysis, endorectal MR imaging results and all clinical variables except the percentage of positive biopsy cores were significantly associated with SVI (P<.02); endorectal MR imaging (0.76) had a larger area under the ROC curve (AUC) than any clinical variable (0.62-0.73). At multivariate analysis, endorectal MR imaging results, Gleason grade, PSA level, and the percentage of cancer in all biopsy cores were significantly associated with SVI (P<or=.02). The Kattan nomogram plus endorectal MR imaging (0.87) had a significantly larger (P<.05) AUC than either endorectal MR imaging alone (0.76) or the Kattan nomogram alone (0.80). CONCLUSION: The addition of endorectal MR imaging contributes significant incremental value to the Kattan nomogram for predicting SVI.

Adult↗
PubMed2006

Truncating variants in p53AIP1 disrupting DNA damage-induced apoptosis are associated with prostate cancer risk.

Germ line mutations in several genes (BRCA1, BRCA2, and CHEK2) whose products are involved in the DNA damage-signaling pathway have been implicated in prostate cancer risk. To identify additional genes in this pathway that might confer susceptibility to this cancer, we analyzed a recently identified DNA damage-response gene, p53AIP1 (a gene encoding for p53-regulated apoptosis-inducing protein 1), for genetic variants in prostate cancer. Five novel germ line variants were identified. The two truncating variants (Ser(32)Stop and Arg(21)insG) were found in 3% (4 of 132) of unselected prostate tumor samples. Genotyping of the two variants in an additional 393 men with sporadic prostate cancer showed a frequency of 3.1% (12 of 393) in contrast to 0.6% (2 of 327) in 327 unaffected men (Fisher's exact test, P = 0.018), with an odds ratio (OR) of 5.1 [95% confidence interval (95% CI), 1.1-23.0]. In addition, two of six tumors carrying the truncating variants were associated with loss of heterozygosity of the wild-type alleles, suggesting that p53AIP1 may act as a tumor suppressor. We also showed that the truncated p53AIP1 was unable to induce apoptosis and suppress cell growth in HeLa and COS-7 cells. These results suggest that loss-of-function variants in p53AIP1 associated with the risk of sporadic prostate cancer and further support the concept that the genetic defects in the DNA damage-response genes play an important role in the development of prostate cancer.

Aged↗
PubMed2006

Selection of donor nuclei in somatic cell-mediated gene transfer using a co-transfection method.

In this study, we introduced a co-transfection method for the selection of donor nuclei in somatic cell-mediated nuclear transfer. Two vectors were constructed in our experiment. One was pMSCV-GFP carrying the neomycin-resistant gene (Neo(r)) and the green fluorescent protein (GFP) reporter gene; the other was pBC1-GFP carrying the mammary gland-specific promoter and target gene GFP. Ovine adult fibroblasts were co-transfected with pMSCV-GFP and pBC1-GFP. The data from this work demonstrated that the GFP genes in both vectors could successfully co-integrate into the genomes of ovine adult fibroblasts in three of the four transgenic cell clones assayed. Furthermore, PCR analysis of transgenic embryos proved that the GFP genes in both vectors could co-integrate into the genomes of the reconstructed embryos. Subsequently, analysis of the developmental rate of the reconstructed embryos after nuclear transfer indicated that the blastocyst rate from the co-transfected donor cells was similar (approximate 8 percent) to that from individual pMSCV-GFP transfected donor cells. The influence of co-transfection resulting in modification of donor nuclei on development of reconstructed embryos was also investigated. The results of flow cytometric analysis indicated that the co-transfected ovine fibroblasts had similar quiescent characteristics in terms of cell cycle (G0+G1 percent: 73.20 +/- 4.04) to the individual pMSCV-GFP transfected fibroblasts (G0+G1 percent: 70.77 +/- 1.19) after they were treated with serum starvation for five days. Our results suggest that the co-transfection method can be used for selection of donor cell clones in somatic cell-mediated gene transfer experiments. It can be potentially extended to applications related to expression of functional protein in mammary glands and other transgenic research relevant to nuclear transfer.

Animals↗
PubMed2006

Constituents of the flowers of Punica granatum.

A new polyphenol compound named pomegranatate (1), together with, ellagic acid, 3,3',4'-tri-O-methylellagic acid, ethyl brevifolincarboxylate, urolic and maslinic acids, and daucosterol were isolated from the ethanolic extract of the flowers of Punica granatum. The structure of compound 1 was determined by spectroscopic analysis. Maslinic acid exhibited antioxidant activity, evaluated by measurement of LDL susceptibility to oxidation.

Animals↗
PubMed2006

Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI.

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in "default mode network" previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.

Aged↗
PubMed2006

Palladium-catalyzed homocoupling and cross-coupling reactions of aryl halides in poly(ethylene glycol).

The direct coupling of aryl halides to prepare symmetrical and unsymmetrical biaryls were performed successfully in poly(ethylene glycol) (PEG) using Pd(OAc)2 as the catalyst in the absence of other additives or reductants. The selectivity toward biaryl depended on the amount of PEG used. Excessive PEGs induce the increase of hydrodehalogenation product, and the best selectivity to biaryl is obtained when the concentration of the hydroxyl group in PEG achieves 100 mol % relative to aryl halides. The catalyst system could be recycled and reused up to five times with no loss of catalytic activity.

Catalysis↗
PubMed2006

Smac/DIABLO promotes mitomycin C-induced apoptosis of bladder cancer T24 cells.

The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the bladder cancer cell line T24 were investigated. The Smac gene was transfected into bladder cancer cell line T24 under the induction of liposome. The intrinsic Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro cellular growth activities were assayed by MTT colorimetry. Apoptosis was assayed by the flow cytometry. The results showed that as compared with the control cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was 18.84% and 33.52%, and 10.72% and 26.24% respectively in blank and transfected cells treated with 0.05 or 0.005 mg/mL mitomycin C (P < 0.05). It was concluded that Smac could enhance the apoptosis of T24 by mitomycin C, which could provide a useful experimental evidence for bladder cancer therapy.

Apoptosis↗
PubMed2006

Nanolithography using high transmission nanoscale bowtie apertures.

We demonstrate that bowtie apertures can be used for contact lithography to achieve nanometer scale resolution. The bowtie apertures with a 30 nm gap size are fabricated in aluminum thin films coated on quartz substrates. Lithography results show that holes of sub-50-nm dimensions can be produced in photoresist by illuminating the apertures with a 355 nm laser beam polarized in the direction across the gap. Experimental results show enhanced transmission and light concentration of bowtie apertures compared to square and rectangular apertures of the same opening area. Finite different time domain simulations are used to explain the experimental results.

Journal Article↗
PubMed2006

Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells.

Our aim was to prepare curcumin derivatives and study their apoptosis-inducing effects on bladder cancer cells in order to establish a basis for targeted chemotherapy of cancer. n-Maleoyl-L-valine-curcumin (NVC) and n-maleoyl-glycine-curcumin (NGC) were chemically synthesized. Intracellular esterase activity of the human bladder cancer EJ cell line and renal tubular epithelial (HKC) cells was examined by 6-carboxyfluorescein diacetate fluorometry. After incubation with NVC or NGC for 6-24 h, cell viability was detected by MTT colorimetry. Cell apoptosis and apoptotic rates were measured by acridine orange/ethidium bromide staining, TUNEL labeling and flow cytometry. Intracellular caspase-3 activities were determined by spectrophotometry. The esterase activity within EJ cells was 10.2-fold higher than that of HKC cells, which was abolished by bis-p-nitrophenylphosphate, an esterase inhibitor, resulting in decreases in NVC- and NGC-mediated cell viability arrest. For EJ cells, the IC50 values of NVC (20.1 micromol/l) and NGC (18.7 micromol/l) were close to curcumin (16.5 micromol/l). Meanwhile, their IC50 values on HKC cells were, respectively, 4.06- and 3.23-fold higher than curcumin. Moreover, NVC and NGC induced apoptosis of EJ cells by 10.13-23.36 and 12.42-28.56%, respectively. Administration of these two derivatives resulted in decreased apoptosis of HKC cells compared with curcumin. The caspase-3 activities of EJ cells, but not of HKC cells, were 5.21- and 5.63-fold enhanced by NVC and NGC, respectively. Thus, novel esterase-sensitive curcumin derivatives were synthesized, which induced extensive apoptosis of bladder cancer EJ cells, but not normal cells.

Apoptosis↗
PubMed2006

Shape-constraint region growing for delineation of hepatic metastases on contrast-enhanced computed tomograph scans.

OBJECTIVES: The objectives of this study were to develop a shape-constraint region-growing algorithm to automatically delineate liver metastases on computed tomography images and to compare automated tumor measurements with those outlined manually by radiologists. METHODS: The algorithm starts with a manual selection of a seed lesion region of interest (ROI). Based on intensity distributions of the seed ROI and the liver parenchyma, several parameters are computed and used to adaptively guide the region growing. To prevent the region growing from leaking into surrounding tissues of similar characteristics, specific shape constraints, including a local shape, a global shape, and a gravity-shift index, are developed to jointly control the iteration of the region growing. The algorithm was applied to 59 lesions in 14 patients with liver metastases. The maximal diameter (unidimension), the product of the maximal and maximal perpendicular diameters (bidimension), and the area in the axial plane were calculated for each of the segmented lesions. Three independent radiologists manually measured all the lesions once, and one of the radiologists measured each lesion 3 times. For each measurement, the concordance correlation coefficient (CCC) was used to assess the pairwise agreement between the computer and the different radiologists, and the overall concordance correlation coefficient (OCCC) was used to assess the agreement between the computer and the multiple radiologists and between the one radiologist's 3 readings. RESULTS: Fifty-three of 59 (89.8%) lesions in 14 patients with liver metastases were successfully segmented using this algorithm. The algorithm achieved a median accuracy of 88.0%. CCCs/OCCCs ranged from 0.943 to 0.999 with 95% confidence intervals. CONCLUSIONS: High accuracy and CCCs/OCCCs suggested that measurements made by the computer were very similar to those made by the radiologists.

Algorithms↗