Biomedical subjects

Xiang Liu

Publications and source records attributed to Xiang Liu.

At least 19 recordsLinked to original sources

PubMed2026

Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.

In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F₁ and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F₁-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F₁ hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.

cis-regulation↗

PubMed2026

Rapid glycomic analysis of serum EVs reveals altered N-glycosylation patterns in ASD.

Objective laboratory diagnostics for autism spectrum disorder (ASD) are lacking, necessitating rapid clinical screening tools. Because serum extracellular vesicle (EV) N-glycosylation captures critical neurodevelopmental signatures, we developed a fast, biologically interpretable diagnostic strategy. EVs from ASD patients with language impairment and neurotypical controls were isolated using a rapid extra-polyethylene glycol precipitation/filtration (EPF) workflow, benchmarked against ultracentrifugation. Following MALDI-TOF/MS profiling, machine learning was re-evaluated using repeated nested cross-validation to reduce optimistic bias and potential information leakage. Among five classifiers, Random Forest (RF) showed the best overall balance across discrimination, calibration, and classification metrics. RF-based SHAP analysis provided transparent interpretation, highlighting key discriminative glycans, including H4N3S1F1, H5N5S1F1, and H3N5F1. To elucidate molecular mechanisms, we integrated public EV transcriptomic data. This revealed significant dysregulation of N-glycosylation machinery genes (e.g., MAN1A1, NEU1, OSTC, RPN2), whose expression directionally aligned with observed glycan shifts in synaptic pathways. Collectively, this rapid serum EV N-glycomic workflow, combined with leakage-controlled RF-based interpretation, provides a promising foundation for non-invasive ASD biomarker discovery and future multicenter validation.

Humans↗

PubMed2026

Circle-seq analysis reveals the involvement of eccDNAs in salt stress response of bermudagrass (Cynodon dactylon).

Extrachromosomal circular DNAs (eccDNAs) have been identified in a wide variety of plant species and play a pivotal role in genomic plasticity, emerging as key drivers of stress adaptation. However, the putative roles of eccDNAs under environmental stress remain largely unexplored in plants. As a high-quality turfgrass, bermudagrass (Cynodon dactylon L.) is a pivotal species for the reclamation and improvement of saline-alkali soils. Therefore, we performed a comprehensive analysis of the eccDNA profiles in bermudagrass under salt stress. A total of 1,068 eccDNAs were identified across all chromosomes. These eccDNAs were characterized by short lengths (ranging from 100 bp to 1 kb) and low GC content. Their genomic distribution was not entirely random but rather exhibited a certain preference for intergenic regions and coding sequences (CDS). Crucially, null model analysis of A/T-rich junction sites revealed that these eccDNAs primarily originate from physically unstable scaffold/matrix attachment regions (S/MARs) via stochastic fragmentation, followed by opportunistic circularization predominantly mediated by the non-homologous end joining (NHEJ) pathway. Notably, salt stress specifically enriched eccDNAs derived from DNA transposons, including the Tc1/Mariner, CACTA and MITE superfamilies. Overall, our findings reveal complex extrachromosomal structural dynamics in bermudagrass, offering novel insights into its genomic adaptation under environmental stress.

Cynodon↗

PubMed2025

qcCHIP: an R package to identify clonal hematopoiesis variants using cohort-specific data characteristics.

SUMMARY: Clonal hematopoiesis (CH) is a molecular biomarker associated with various adverse outcomes in both healthy individuals and those with underlying conditions, including cancer. Detecting CH usually involves genomic sequencing of individual blood samples followed by robust bioinformatics data filtering. We report an R package, qcCHIP, a bioinformatics pipeline that implements permutation-based parameter optimization to guide quality control filtering and cohort-specific CH identification. We benchmark qcCHIP under various data settings, including different sequencing depths, ranges of cohort sizes, with and without normal-tumor paired samples, and across different cancer types. We show that qcCHIP allows users to customize analysis needs to generate CH calls based on cohort-specific data characteristics. AVAILABILITY AND IMPLEMENTATION: qcCHIP R package is freely accessible at GitHub https://github.com/tenglab/qcCHIP and DOI: 10.5281/zenodo.16421861.

Humans↗

PubMed2006

Replication-coupled repair of crotonaldehyde/acetaldehyde-induced guanine-guanine interstrand cross-links and their mutagenicity.

The repair of acetaldehyde/crotonaldehyde-induced guanine (N2)-guanine (N2) interstrand cross-links (ICLs), 3-(2-deoxyribos-1-yl)-5,6,7,8-(N2-deoxyguanosyl)-6(R or S)-methylpyrimido[1,2-alpha]purine-10(3H)-one, was studied using a shuttle plasmid bearing a site-specific ICL. Since the authentic ICLs can revert to monoadducts, a chemically stable model ICL, 1,3-bis(2'-deoxyguanos-N2-yl)butane derivative, was also employed to probe the ICL repair mechanism. Since the removal of ICL depends on the nucleotide excision repair (NER) mechanism in Escherichia coli, the plasmid bearing the model ICL failed to yield transformants in NER-deficient host cells, proving the stability of this ICL in cells. The authentic ICLs yielded transformants in the NER-deficient hosts; therefore, these transformants are produced by plasmid bearing spontaneously reverted monoadducts. In contrast, in NER-deficient human cells, the model ICL was removed by an NER-independent repair pathway, which is unique to higher eukaryotes. This repair did not associate with a transcriptional event, but with replication. The analysis of repaired molecules revealed that the authentic and model ICLs were repaired mostly (>94%) in an error-free manner in both hosts. The major mutations that were observed were G --> T transversions targeting the cross-linked dG located in the lagging strand template. These results support one of the current models for the mammalian NER-independent ICL repair mechanism, in which a DNA endonuclease(s) unhooks an ICL from the leading strand template at a stalled replication fork site by incising on both sides of the ICL and then translesion synthesis is conducted across the "half-excised" ICL attached to the lagging strand template to restore DNA synthesis.

Acetaldehyde↗

PubMed2006

Trishomocubanes: novel sigma ligands modulate cocaine-induced behavioural effects.

Trishomocubane analogues TC1 (N-(3'-fluorophenyl)ethyl-4-azahexacyclo [5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol) and TC4 (N-(3'-fluorophenyl)methyl-4-azahexacyclo [5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol) were evaluated for their modulatory effects on locomotor activity as well as interactions with cocaine-induced responses. TC1 and TC4 have high affinity and moderate to high selectivity for sigma(1) (Ki=10 nM, sigma1/sigma2=0.03) and sigma2 (Ki=20 nM, sigma1/sigma2=7.6) receptor subtypes respectively. Both compounds have negligible affinity for the dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. In behavioural studies, TC1 produced a dose-related inhibition in spontaneous locomotor activity measured in a Digiscan apparatus. TC1 attenuated the stimulatory locomotor effect of 20 mg/kg cocaine with a half-maximal depressant activity (ID50) of 38.6 mg/kg. TC1 (dose range of 25 to 100 mg/kg) also partially substituted for the effect of cocaine (10 mg/kg) in a discriminative stimulus task, involving the trained discrimination between cocaine and saline using a two-lever choice method. Following a dose of 50 mg/kg TC1, a maximum of 31% substitution was reached. The response rate was reduced to 56% of vehicle control following a TC1 dose of 100 mg/kg. These behavioural effects suggest that TC1 can act as an antagonist via the sigma1 receptor. In contrast to TC1, TC4 produced a stimulant effect in locomotor activity with the ED50 estimated at 0.94 mg/kg. In addition, TC4 failed to inhibit cocaine-induced stimulation; neither did it substitute for the discriminative stimulus effects of cocaine. TC4 thus appears to interact predominantly with the sigma2 receptor subtype (sigma1/sigma2=7.6) which may result in dopamine stimulation independent of the effects of cocaine. The differential effect of TC1 and TC4 warrants further study of the mechanism of these actions. Present data also suggests a potential role for trishomocubane analogues in developing medication or research tools for cocaine addiction.

Animals↗

PubMed2006

Synthesis of poly(ethylene glycol)-metaxalone conjugates and study of its controlled release in vitro.

Metaxalone (Met), a drug for treatment of pain and stiffness due to muscular injuries, was covalently linked to poly(ethylene glycols) (PEG) via a chloroacetyl chloride spacer. The average weight molecular weights used for PEG are 4000, 6000 and 10,000, respectively, and the procedure of chemical modification for PEGs was conducted by a two-step protocol: (1) synthesis of N-chloroacetyl-metaxalone; (2) synthesis of PEG(4000)-Met, PEG(6000)-Met and PEG(10000)-Met. The controlled drug release studies were performed in buffer solutions with pH values equal to 1.1, 7.4 and 10.0. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG(10000)-Met is the slowest among three prodrugs, and more amount of metaxalone can be detected releasing from prodrug matrices at the presence of alpha-chymotrypsin in a buffer solution with pH 8.0. It was also found that these novel prodrugs can effectively improve the metaxalone's pharmacokinetics, and furthermore can markedly increase its half-life period.

Acetates↗

PubMed2006

Wound measurement by curvature maps: a feasibility study.

A non-contact wound measurement method by laser scanner and curvature maps is presented. A patient's foot ulcer is scanned by FastSCAN ten times over a three-week period. With the surface's 3D coordinates, curvature maps of the ulcerous area are calculated. Utilizing a specified rim curvature value, the wound edge is detected and processed via cubic spline smoothing, which is qualitatively verified by a photograph. Subsequently, the depth, area and volume of the wound can be calculated. The results indicate that laser scanning followed by curvature analysis might be a potential clinical tool for non-contact measurement of wounds.

Feasibility Studies↗

PubMed2006

Involvement of sphingolipids in apoptin-induced cell killing.

The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 muM) attenuated (30%; P<0.01) apoptin-induced cell death. Apoptin was also able to induce a significant decline in sphingosine content by inhibition of ceramide deacylation through down-regulation of acid ceramidase at the protein level. Supporting the role of ceramide in apoptin action, treatment of cells with the combination of an exogenous cell-permeable ceramide analog (C6-ceramide) and Ad-GFPApoptin infection yielded a significant increase (P<0.01) in apoptosis over either treatment modality alone. Together, these data suggest that apoptin modulates ceramide/sphingolipid metabolism as part of its mechanism of action.

Adenoviridae↗

PubMed2006

New insights on the use of desipramine as an inhibitor for acid ceramidase.

Treatment of different cancer cell lines with desipramine induced a time- and dose-dependent downregulation of acid ceramidase. Desipramine's effect on acid ceramidase appeared specific for amphiphilic agents (desipramine, chlorpromazine, and chloroquine) but not other lysomotropic agents such as ammonium chloride and bafilomycin A1, and was not transcriptionally regulated. The cathepsin B/L inhibitor, CA074ME, but not the cathepsin D inhibitor, pepstatin A, blocked desipramine's effect on acid ceramidase. Desipramine led to a more pronounced downregulation of sphingosine compared to ceramide suggesting acid ceramidase inhibition is important to desipramine's mechanism of action. This study reveals a new mechanism of action for desipramine.

Antidepressive Agents, Tricyclic↗

PubMed2006

Development of gas chromatography-mass spectrometry with microwave distillation and simultaneous solid-phase microextraction for rapid determination of volatile constituents in ginger.

In this study, gas chromatography-mass spectrometry (GC-MS) following microwave distillation and solid-phase microextraction (MD-SPME) was developed for the analysis of essential oil compounds in fresh ginger. In the proposed method, the isolation, extraction and concentration of volatile components in ginger were carried out in one single step, using the MD-SPME technique, and the analytes on the SPME fiber were analyzed by GC-MS. Some parameters, including SPME fiber coating, microwave power and irradiation time, were optimized. The optimal experiment parameters obtained were: 65 microm PDMS/DVB SPME fiber, a microwave power of 400 W and an irradiation time of 2 min. To demonstrate its feasibility, MD-SPME was compared with conventional SPME for the extraction of essential oil compounds in fresh ginger. Using MD-SPME followed by GC-MS, 54 compounds were separated and identified in ginger, which mainly included geranial (5.25%), zingiberene (15.48%), beta-sesquiphellandrene (5.54%) and beta-phellandrene (22.84%), whereas only 39 compounds were separated and identified by conventional SPME followed by GC-MS. The relative standard deviation (R.S.D.) values of less than 10% show that the proposed method has good repeatability. The result show that MD-SPME, followed by GC-MS, is a simple, rapid, solvent-free method for the determination of volatile compounds in ginger.

Gas Chromatography-Mass Spectrometry↗

PubMed2006

Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer.

Despite local and systemic therapies, the National Cancer Institute estimates that prostate cancer will cause over 30,000 deaths in 2006. This suggests that additional therapeutic approaches are needed. The chicken anemia viral protein Apoptin causes tumor-selective apoptosis in human tumor lines independent of p53 and Bcl-2 status. Tet-regulated expression of Apoptin from an adenoviral vector showed cytotoxicity in DU145, PC-3, and LNCaP tumor cells regardless of expression of p53, Bcl-2, Bcl-xL, Bax, survivin, FLIP(S), XIAP, or CIAP. Apoptin expression caused an increase in the tumor suppressor lipid ceramide, which regulates the cellular stress response. Interestingly, 10 of 15 primary prostate cancers examined by Western blotting overexpressed acid ceramidase (AC), suggesting that ceramide deacylation might serve to negate elevated levels of ceramide, creating a more antiapoptotic phenotype. This was confirmed in AC-overexpressing cells in which we observed decreased sensitivity to apoptosis following treatment with Apoptin. Addition of the AC inhibitor LCL204, in combination with Apoptin, augmented cell killing. This effect was also demonstrated in vivo in that Apoptin and LCL204 cotreatment significantly reduced tumor growth in DU145 xenografts (P<0.05). Taken together, our data demonstrated that Apoptin is a promising therapeutic agent for prostate cancer and that its function is improved when combined with acid ceramidase inhibitors.

Adenoviridae↗

PubMed2006

Dicer-2 and R2D2 coordinately bind siRNA to promote assembly of the siRISC complexes.

In Drosophila melanogaster, the Dicer-2/R2D2 complex initiates RNA interference (RNAi) by processing long double-stranded RNA (dsRNA) into small interfering RNA (siRNA). Recent biochemical studies suggest that the Dcr-2/R2D2 complex also facilitates incorporation of siRNA into the RNA-induced silencing complex (siRISC). Here we present genetic evidence that R2D2 and Dcr-2 are both required for loading siRNA onto the siRISC complex. Consistent with this, only the Dcr-2/R2D2 complex, but neither Dcr-2 nor R2D2 alone, can efficiently interact with duplex siRNA. Furthermore, both dsRNA-binding domains of R2D2 are critical for binding to siRNA and promoting assembly of the siRISC complexes.

Animals↗

PubMed2006

In situ localization and substrate specificity of earthworm protease-II and protease-III-1 from Eisenia fetida.

Recently, the function in fibrinolysis of earthworm proteases has been studied. In our experiments, earthworm protease-II (EfP-II) and earthworm protease-III-1 (EfP-III-1) were isolated and purified from Eisenia fetida. As shown by the assay of sections of the earthworm on fibrin plates, the enzymic activity was mainly detected around the clitellum. In the presence of anti-EfP-II or anti-EfP-III-1 serum, the immunological signals of the two isozymes were clearly found in the anterior alimentary mucosa, suggesting that EfP-II and -III-1 are localized and expressed in intestinal epithelial cells. The Michaelis-Menten constant (K(m)) for EfP-III-1 reacting with BAEE is smaller (1.7x10(-5)M) in comparison with the K(m) values of other substrates such as Chromozym-Try and -TH (3.3-6.0x10(-5)M). This indicates that EfP-III-1 is a trypsin-like protein. EfP-II shows a strong trypsin-like, moderate elastase-like and weak chymotrypsin-like serine function. The relative broad substrate specificity of EfP-II and EfP-III-1 is consistent with their localization in the anterior alimentary canal where different micro-organisms and ingested proteins require to be digested.

Animals↗

PubMed2006

Cloning and characterization of cDNAS encoding carboxypeptidase-like proteins from the gut of Hessian fly larvae [Mayetiola destructor (Say)].

Transcriptomic analysis of the gut from Hessian fly larvae [Mayetiola destructor (Say)] identified nine cDNA clones that encode different carboxypeptidase-like proteins. Sequence comparison revealed that five of the nine cDNAs encoded very similar proteins with amino acid sequence identity over 96%. The other four cDNAs encoded diversified proteins with amino acid sequence identity less than 60%. Further sequence comparison with well characterized carboxypeptidases from other organisms revealed that these cDNAs encoded MDCP (M. destructor carboxypeptidase)-A1, MDCP-A2, MDCP-B, MDCP-BL, and MDCP-D. All residues characteristic of metallocarboxypeptidases including the HXXE motif were conserved among members. Northern blot analysis revealed various expression patterns for different gene groups in different developmental stages of M. destructor, suggesting that individual carboxypeptidases perform specific functions or have different specificities. Enzymatic activity assays demonstrated that both carboxypeptidases A and B are predominant in the larval stage, the only feeding stage of M. destructor, indicating a role in food digestion. The digestive role is further supported by the fact that 80% of the enzymatic activity in larvae occurred in the gut. Among these two types of enzymes, the activity of carboxypeptidase A was at least four times higher than that of carboxypeptidase B under the same conditions, suggesting that carboxypeptidase A is the major digestive enzyme in the gut of M. destructor larvae.

Amino Acid Sequence↗

PubMed2006

Extension of wavelength-modulation spectroscopy to large modulation depth for diode laser absorption measurements in high-pressure gases.

Tunable diode laser absorption measurements at high pressures by use of wavelength-modulation spectroscopy (WMS) require large modulation depths for optimum detection of molecular absorption spectra blended by collisional broadening or dense spacing of the rovibrational transitions. Diode lasers have a large and nonlinear intensity modulation when the wavelength is modulated over a large range by injection-current tuning. In addition to this intensity modulation, other laser performance parameters are measured, including the phase shift between the frequency modulation and the intensity modulation. Following published theory, these parameters are incorporated into an improved model of the WMS signal. The influence of these nonideal laser effects is investigated by means of wavelength-scanned WMS measurements as a function of bath gas pressure on rovibrational transitions of water vapor near 1388 nm. Lock-in detection of the magnitude of the 2f signal is performed to remove the dependence on detection phase. We find good agreement between measurements and the improved model developed for the 2f component of the WMS signal. The effects of the nonideal performance parameters of commercial diode lasers are especially important away from the line center of discrete spectra, and these contributions become more pronounced for 2f signals with the large modulation depths needed for WMS at elevated pressures.

Journal Article↗

PubMed2006

Intrachannel four-wave mixing in highly dispersed return-to-zero differential-phase-shift-keyed transmission with a nonsymmetric dispersion map.

Nonlinear penalties due to intrachannel four-wave mixing (IFWM) in highly dispersed return-to-zero differential-phase-shift-keyed transmission are studied for both symmetric and nonsymmetric dispersion maps. As the dispersion map changes from symmetric to nonsymmetric, the nonlinear amplitude fluctuation overtakes the effect of the nonlinear phase fluctuation and dominates the system's nonlinear performance. The effect of IFWM on the bit error rate is assessed by using the semianalytical method.

Journal Article↗

PubMed2006

Diagnosis and management of skull base osteoradionecrosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: The objective of this study was to investigate the diagnosis and management of skull base osteoradionecrosis (ORN) after radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: The general information, clinical manifestations, and treatment outcomes were retrospectively evaluated in 15 patients with skull base ORN after radiotherapy for NPC. RESULTS: The common symptoms of skull base ORN included foul odor, headache, and epistaxis. Endoscopic examination showed exposed bone or sequestration in the nasopharynx. The characteristic findings according to computed tomography included the following: bone was destroyed extensively and symmetrically or regionally; bone was exposed to the air cavity; sequestration can be observed; and small air bladder was present in the parenchyma. There were nine patients regional skull base ORN receiving surgery, two of whom died of postradiation temporal lobe necrosis and seven of whom survived for 2 to 7 years. Conservative treatments were provided to six patients, including five patients with extensive skull base ORN and one patient with regional ORN, among which three patients died of nasopharyngeal bleeding, one patient died of exhaustion, and two patients survived for 3 to 5 years. CONCLUSIONS: Clinical diagnosis of skull base ORN was based on symptoms, computed tomography, or magnetic resonance imaging and endoscopy. The final confirmation was according to pathologic examination. Surgery had the best effect. Extensive ORN accompanied by radiation brain damage or cranial nerves damage had poor prognosis. Nasopharyngeal bleeding and exhaustion were the main causes of death.

Endoscopy↗