Biomedical subjects

Yan Liang

Publications and source records attributed to Yan Liang.

At least 19 recordsLinked to original sources

PubMed2026

The R2R3-MYB transcription factor ScMYB20 negatively regulates drought and salt tolerance through a dual-repression of ScCHALCONE SYNTHASE-1 (ScCHS1)-mediated flavonoid biosynthesis in the desert moss Syntrichia caninervis.

The desert moss Syntrichia caninervis is one of the most desiccation-tolerant land plants known and provides a powerful system for dissecting the molecular foundations of extreme stress adaptation in early-diverging land lineages. The MYB transcription factor superfamily orchestrates secondary metabolism and stress signaling across plants, yet its lineage-specific evolution and mechanistic deployment in bryophytes remain poorly understood. Here, we identified 65 ScMYB genes in the S. caninervis genome and showed that the family expanded predominantly through dispersed duplication, with no detectable synteny to vascular-plant MYBs, indicating bryophyte-specific neo-functionalization. Integrating phylogenetic clustering, cis-element architecture and stress-responsive expression profiling, we pinpointed ScMYB20, a nuclear-localized, S13-subgroup R2R3-MYB that is rapidly and strongly induced by dehydration and salinity. Heterologous overexpression in Arabidopsis, together with overexpression and RNAi in S. caninervis, demonstrated that ScMYB20 negatively regulates drought and salt tolerance by suppressing antioxidant capacity, osmotic adjustment and photosynthetic performance, while concomitantly elevating ROS and MDA accumulation. Mechanistically, ScMYB20 directly binds a TAACCA motif in the ScCHS1 promoter to repress its transcription, and simultaneously sequesters the WD40 protein ScTTG1, a positive transcriptional activator of ScCHS1, thereby antagonising ScTTG1-mediated activation. Transient ScCHS1 overexpression restored flavonoid accumulation, antioxidant capacity and stress tolerance. Together, our findings define a dual-repression module (ScMYB20-ScTTG1-ScCHS1) that fine-tunes flavonoid flux under abiotic stress, and provide evolutionary and mechanistic insights into how R2R3-MYB repressors evolved to balance metabolic investment and stress survival in land plants.

Syntrichia caninervis↗

PubMed2026

Phytochrome-interacting factor 1b (SlPIF1b) affects the fruit quality of tomato by regulating chloroplast development.

The increased abundance and functionality of fruit chloroplasts could promote the accumulation of nutrients and flavor in the fruit. Tomato fruit has fully developed fruit chloroplasts, whose abundance and functionality have much untapped potential in improving fruit quality by controlling fruit chloroplast development. Previous studies have identified many regulatory factors that specifically regulate fruit chloroplast development in tomatoes, but there are fewer reports on tomato phytochrome-interacting factors (SlPIFs). Arabidopsis AtPIFs have been implicated in chloroplast development and chlorophyll biosynthesis. In this study, we identified and characterized an SlPIF1b mutant in tomato, named GS, which exhibited a dark green fruit shoulder with enhanced chloroplast development. RNA-seq and genotyping analysis identified a - 21 bp (A → T) mutation in the promoter of SlPIF1b, resulting in the absence of the TATA-box core transcriptional element and inhibiting SlPIF1b transcription. The overexpression of SlPIF1b in GS inhibited chloroplast development of fruits, leading to a lighter green shoulder color, decreased chlorophyll content, reduced photosynthetic activity, diminished starch accumulation, and compromised fruit quality upon ripening. Conversely, the down expression of SlPIF1b significantly enhanced fruit chloroplast development and functionality in fruits, resulting in increased chlorophyll and carotenoid accumulation. Further analysis of expression profile and transcriptional activity indicated that SlPIF1b could bind to G/PBE-box elements present in SlGLK2, SlTKN4, SlCAO1a, SlPOR1, SlPOR3, SlCAB1 and SlCAB1b promoters, thereby inhibiting their expression. This study revealed the specific regulatory mechanism by which SlPIF1b modulates chloroplast development and chlorophyll synthesis in tomato fruit and provided valuable genetic resources and a theoretical basis for tomato quality improvement.

Solanum lycopersicum↗

PubMed2025

Cell fate specification modes shape transcriptome evolution in the highly conserved spiral cleavage.

Early animal development can be remarkably variable, influenced by lineage-specific reproductive strategies and adaptations. Yet, early embryogenesis is also strikingly conserved in certain groups, such as Spiralia. In this clade, a shared cleavage program (i.e., spiral cleavage) and similar cell lineages are ancestral to at least seven phyla. Why early development is so conserved in specific groups and plastic in others is not fully understood. Here, we investigated two annelid species (Owenia fusiformis and Capitella teleta) with spiral cleavage but different modes of specifying their primary progenitor cells. By generating high-resolution transcriptomic time courses from the oocyte to gastrulation, we demonstrate that transcriptional dynamics differ markedly between these species during spiral cleavage and instead reflect their distinct timings of embryonic organiser specification. However, the end of cleavage and gastrulation exhibit high transcriptomic similarity, when orthologous transcription factors share gene expression domains, suggesting this period is a previously overlooked mid-developmental transition in annelid embryogenesis. Together, our data reveal hidden transcriptomic plasticity during spiral cleavage, indicating an evolutionary decoupling of morphological and transcriptomic conservation during early embryogenesis.

Animals↗

PubMed2024

Putative rhamnogalacturonan-II glycosyltransferase identified through callus gene editing which bypasses embryo lethality.

Rhamnogalacturonan II (RG-II) is a structurally complex and conserved domain of the pectin present in the primary cell walls of vascular plants. Borate cross-linking of RG-II is required for plants to grow and develop normally. Mutations that alter RG-II structure also affect cross-linking and are lethal or severely impair growth. Thus, few genes involved in RG-II synthesis have been identified. Here, we developed a method to generate viable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants in callus tissue via CRISPR/Cas9-mediated gene editing. We combined this with a candidate gene approach to characterize the male gametophyte defective 2 (MGP2) gene that encodes a putative family GT29 glycosyltransferase. Plants homozygous for this mutation do not survive. We showed that in the callus mutant cell walls, RG-II does not cross-link normally because it lacks 3-deoxy-D-manno-octulosonic acid (Kdo) and thus cannot form the α-L-Rhap-(1→5)-α-D-kdop-(1→sidechain). We suggest that MGP2 encodes an inverting RG-II CMP-β-Kdo transferase (RCKT1). Our discovery provides further insight into the role of sidechains in RG-II dimerization. Our method also provides a viable strategy for further identifying proteins involved in the biosynthesis of RG-II.

Arabidopsis↗

PubMed2023

Emerging trends in the study of spiralian larvae.

Many animals undergo indirect development, where their embryogenesis produces an intermediate life stage, or larva, that is often free-living and later metamorphoses into an adult. As their adult counterparts, larvae can have unique and diverse morphologies and occupy various ecological niches. Given their broad phylogenetic distribution, larvae have been central to hypotheses about animal evolution. However, the evolution of these intermediate forms and the developmental mechanisms diversifying animal life cycles are still debated. This review focuses on Spiralia, a large and diverse clade of bilaterally symmetrical animals with a fascinating array of larval forms, most notably the archetypical trochophore larva. We explore how classic research and modern advances have improved our understanding of spiralian larvae, their development, and evolution. Specifically, we examine three morphological features of spiralian larvae: the anterior neural system, the ciliary bands, and the posterior hyposphere. The combination of molecular and developmental evidence with modern high-throughput techniques, such as comparative genomics, single-cell transcriptomics, and epigenomics, is a promising strategy that will lead to new testable hypotheses about the mechanisms behind the evolution of larvae and life cycles in Spiralia and animals in general. We predict that the increasing number of available genomes for Spiralia and the optimization of genome-wide and single-cell approaches will unlock the study of many emerging spiralian taxa, transforming our views of the evolution of this animal group and their larvae.

Animals↗

PubMed2007

Pharmacokinetics of the ginkgo B following intravenous administration of ginkgo B emulsion in rats.

Ginkgo B (GB) is an extract from the leaves of Ginkgo biloba, used in the treatment of dementia, cerebral insufficiency or related cognitive decline. In this paper, the main features of the pharmacokinetics of GB emulsion in rats were reviewed and the binding rate of GB to rat plasma and human plasma protein were investigated meanwhile. The concentrations of GB in plasma, tissue, and excretion of rats after i.v. administration of GB were measured using HPLC-ESI-MS. The metabolite was qualitated by LC-MS/MS. Intravenously administered GB was eliminated in a biphasic manner with a prominent initial phase (half-life of 0.3 h) followed by a slower terminal phase (half-life of 1.5 h). After i.v. 4, 12 and 36 mg/kg GB emulsion, the pharmacokinetic parameters from a two compartment model analysis of plasma samples were AUC(0-tau) (microg x min/ml): 53.7, 165.5 and 649.7; CL (l/min/kg): 0.07, 0.07 and 0.05; V(C) (l/kg): 2.27, 3.27 and 2.76, respectively. Peak concentrations generally occurred at 10 min except brain and fat. Tissue concentration then declined by several-fold during 6 h although still present in most tissues at 6 h. Single intravenous dose was mainly excreted in the urine (40-50%), feces contained less than 30%. The binding rate to rat plasma was little higher than to human plasma, but the difference was negligible. Some metabolites were found in urine and bile through qualitative analysis on the urine and bile by LC-MS/MS.

Animals↗

PubMed2006

HPLC determination of four triterpenoids in rat urine after oral administration of total triterpenoids from Ganoderma lucidum.

A sensitive and simple high-performance liquid chromatography (HPLC) method was applied for the quantitative determination of four major triterpenoids (ganoderic acids C(2), B, K and H) in rat urine after oral administration of total triterpenoids from Ganoderma lucidum. The urine sample was extracted with dichloromethane-ethyl acetate (90:10) after acidification by hydrochloric acid (0.2 mol/ml). Chromatographic separation was achieved on a Zorbax SB-C(18) column (250 mm x 4.6 mm, 5 microm) at 35 degrees C, with a linear gradient of acetonitrile and 0.03% aqueous phosphoric acid (v/v), at a flow rate of 1.2 ml/min. The four triterpenoids and internal standard (hydrocortisone) were detected at a wavelength 252 nm. The within- and between-day assay coefficients of variation for the four triterpenoids in urine were less than 9% and the extraction recovery of this method was higher than 90%. Using this method, the excretion profile of the triterpenoids in rat urine after oral administration of total triterpenoids of G. lucidum was revealed for the first time.

Animals↗

PubMed2006

Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome.

Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT-PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders.

Apraxias↗

PubMed2006

Effects of cytotoxic T lymphocyte antigen 4 (CTLA4) signaling and locally applied steroid on retinal dysfunction by recoverin, cancer-associated retinopathy antigen.

PURPOSE: To assess the cytotoxic T lymphocyte antigen 4 (CTLA4) pathway in the recoverin peptide (R64; AYAQHVFRSF) mouse model of cancer-associated retinopathy (CAR) and to assess the protective effects of subconjunctival triamcinalone injections in this model. METHODS: To study the role of the CTLA4 pathway on the R64-induced mouse model of CAR, BALB/c mice were immunized with R64. The mice were further intraperitoneally treated with anti-CTLA4 antibody to get stronger immunoreaction. The development of CAR was evaluated by electroretinogram (ERG) examinations 21 days after treatment. A cytotoxicity assay was employed to detect induction of R64-specific cytotoxic T lymphocytes (CTLs). Immunoblotting to assess the development of anti-recoverin antibody and a T cell proliferation assay to determine the activity of lymphocytes against R64 were examined in two experimental groups, anti-CTLA4 antibody treated and untreated mice.To study the protective effect of subconjunctival triamcinalone in this model, mice immunized with R64 peptide and anti-CTLA4 antibody were either treated with 50 mg/kg/body weight of triamcinalone or phosphate buffered saline (PBS). These mice were assayed using ERG and histological examination 35 days after the first R64 immunization. RESULTS: When mice were challenged with R64 peptide and anti-CTLA4 antibody, R64 peptide-specific CTLs were induced and decreased b-wave amplitudes were observed in ERG. Conversely, no CAR symptoms were detected in mice not treated with anti-CTLA4 antibody. Anti-CTLA4 antibody treatment did not give any significant differences in T cell proliferation and humoral reaction against recoverin. Subconjunctival triamcinalone treated mice show a trend toward improved survival of outer nuclear layer cell bodies, but did not show significant improvement of ERG amplitudes compared to the untreated mice. CONCLUSIONS: Inhibition of the CTLA4 pathway is essential for the development of recoverin-induced murine CAR, suggesting that strengthening negative T cell signaling through CTLA4 may lessen the retinal degenerations in CAR-affected subjects. The positive effects of attenuation of the CTLA4 pathway must be weighed against a potential negative effect on survival since this pathway may also provide natural immunotherapy against the underlying malignancy. Subconjunctival injections of triamcinalone may have beneficial effects on the integrity of the outer nuclear layer (ONL) of the retina in the CAR model, although there was no significant effect on the ERG recordings.

Animals↗

PubMed2006

Diffusion-weighted magnetic resonance imaging in diagnosis of Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD), a rare disease, is uncharacterized by computed tomography (CT) and magnetic resonance imaging (MRI). This study was aimed to evaluate the diffusion-weighted MRI (DWI) manifestations of CJD and to discuss their diagnostic value. METHODS: The findings of T(1)-weighted MRI (T(1)WI), T(2)-weighted MRI (T(2)WI), DWI and post-contrast MRI in 5 patients (3 patients with biopsy-proven CJD and 2 patients with clinically-proven CJD) were retrospectively analyzed in this study. RESULTS: Four out of the 5 patients had cerebral atrophy of various degrees. One patient showed symmetric high signal intensity at the bilateral globus pallidus and the head of the caudate nucleus, with very high signal in the cerebral cortex on the DWI. This patient only had symmetric slightly high signal at the bilateral globus pallidus and putamen on T(2)WI. One patient had high signal intensity at the basal ganglia and cerebral cortex on DWI, but abnormal T(2) signal intensity at the bilateral paraventricular white matter on MRI. Two patients presented with widely gyri-like high signal intensity at the cortex on DWI, but routine MRI showed bilateral paraventricular long T(2) signal intensity in 1 patient and no abnormal findings in another. No abnormalities were shown by both routine MRI and DWI in the last patient. CONCLUSIONS: DWI is more sensitive than its conventional counterpart in the depiction of CJD. DWI is more sensitive to detect cortical abnormal signal intensity in CJD not detected by T(2)WI.

Adult↗

PubMed2006

Simple, sensitive and rapid LC-MS method for the quantitation of indapamide in human plasma--application to pharmacokinetic studies.

A sensitive and specific method using liquid chromatography with electrospray ionization mass spectrometry (LC-ESI-MS) has been developed and validated for the identification and quantification of indapamide in human plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts on to a C18 column with gradient elution and detection using a single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The method was tested using six different plasma batches. Linearity was established for the concentration range 0.5-100.0 ng/ml, with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision (RSD%) was lower than 10%, and accuracy ranged from 85 to 115%. The lower limit of quantification was reproducible at 0.2 ng/ml with 0.2 ml plasma. The proposed method enables the unambiguous identification and quantification of indapamide for pre-clinical and clinical studies.

Antihypertensive Agents↗

PubMed2006

Identification of human liver mitochondrial aldehyde dehydrogenase as a potential target for microcystin-LR.

Microcystins (MCs) are hepatotoxins produced by a variety of freshwater cyanobacteria. The toxicity of these hepatotoxins is a severe health issue for both humans and livestock; MCs have been implicated in the development of liver cancer, necrosis, and even deadly intrahepatic bleeding. Microcystin-LR (MC-LR) is the MC variant most commonly encountered in a contaminated aquatic system. Thus far, MC-LR has only been shown to target the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A) and it is still unknown whether MC-LR can bind and inhibit any other protein targets inside the cell. To find potential MC-LR targets, we screened a phage display library for peptide ligands that specifically recognize MC-LR. Using these peptide sequences as guides, we performed a series of bioinformatics analyses revealing that MC-LR binds human liver aldehyde dehydrogenase 2 (ALDH2) at residues 447-451. We confirmed MC-LR binding of ALDH2 via automated docking computation, which yielded results matching our experimental and bioinformatics analyses. ALDH2 dysfunction may lead to aldehyde-induced reactive oxygen species (ROS) generation and, in turn, apoptosis. Therefore, ALDH2 could potentially be a target of MC-LR associated with the process of ROS-induced apoptosis. Our current study presents a new approach to the study of interactions of biological molecules by combining phage display technology with computational methods.

Aldehyde Dehydrogenase↗

PubMed2006

Liquid chromatographic/mass spectrometry assay of triptolide in dog plasma and its application to pharmacokinetic study.

A rapid and sensitive method for the determination of triptolide in dog plasma was developed and validated, using high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI/MS). Sample preparation consisted of liquid-liquid extraction with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Detection was performed on a triple quadrupole mass spectrometer using selected-ion monitoring (SIM) mode on the deprotonated ions [M-H]- at m/z 359. Calibration curves were linear over the concentration range of 0.5-200 ng/mL of triptolide with the intra- and inter-day precision (the relative standard deviation values) were being less than 7%. Triptolide was stable under different conditions. The intra-day and inter-day accuracy were 99.3-105.2% and 101.3-107.0%, respectively. The lower limit of quantification was 0.5 ng/mL. The method was successfully applied to a pharmacokinetic study after an intragastric administration (i.g.) of triptolide to dogs with a dose of 0.05 mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of triptolide.

Animals↗

PubMed2006

Clinical and genetic study of a Brazilian family with spastic paraplegia (SPG6 locus).

We describe a Brazilian family in which inheritance of a G106R mutation in the SPG6 gene (also know as NIPA1) resulted in an autosomal dominant form of hereditary spastic paraplegia (ADHSP). Clinical investigations indicated that this family has a pure form of spastic paraplegia. All patients presented with gait difficulty in their twenties, progressing to frank spastic paraplegia during the next decade. Our report further supports evidence that mutations in SPG6 cause ADHSP.

Adult↗

PubMed2006

Novel SPG6 mutation p.A100T in a Japanese family with autosomal dominant form of hereditary spastic paraplegia.

We describe a Japanese family in which inheritance of a novel mutation p.A100T in SPG6 resulted in an autosomal dominant form of hereditary spastic paraplegia (ADHSP). Clinical investigation showed a pure form of HSP. Our study demonstrates further allelic heterogeneity of SPG6.

Adult↗

PubMed2006

Simple, sensitive and rapid liquid chromatography/atmospheric pressure chemical ionization mass spectrometric method for the quantitation of Ranolazine in rat plasma.

A sensitive and specific method using liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) has been developed and validated for the identification and quantification of Ranolazine in rat plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts onto a C18 column with isocratic elution and detection using a single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The method was tested using six different batches of blank plasma. Linearity was established for the concentration range 0.02-10.0 microg/mL, with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision (relative standard deviation (RSD) %) was lower than 10%, and accuracy ranged from 85 to 115%. The lower limit of quantification was reproducible at 0.01 microg/mL with 20 microL plasma. The proposed method enables the unambiguous identification and quantification of Ranolazine for pre-clinical and clinical studies.

Acetanilides↗

PubMed2006

Efficacy of subcutaneous administration of gonadotropin-releasing hormone agonist on idiopathic central precocious puberty.

In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significantly from 6.3+/-1.4 cm/year to 5.8+/-1.2 cm/year in group SC and 6.7+/-1.3 cm/year to 5.4+/-1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2+/-0.2 or 1.3+/-0.3 at the onset of therapy and decreased significantly after the treatment to 0.7+/-0.2 or 0.9+/-0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6-12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP

Bone Development↗

PubMed2006

Chimeric Japanese encephalitis virus/dengue 2 virus infectious clone: biological properties, immunogenicity and protection against dengue encephalitis in mice.

A molecular clone of Japanese encephalitis virus (JE virus) was derived from the JE virus Nakayama strain and used to produce infectious JE virus in cell culture. The engineered JE virus resembled the parental JE virus in cell-culture properties and was related closely to other JE virus strains based on nucleotide sequence analysis. The JE virus clone was used as a genetic background for construction of a chimeric virus containing the structural proteins prM and E of Dengue virus, serotype 2. The chimeric JE/dengue 2 virus generated authentic dengue 2 structural proteins as assessed by immunoassays for the dengue E protein. It exhibited a small plaque size and less efficient growth in various cell lines than the parental JE virus. JE/dengue 2 virus was non-neuroinvasive for young adult mice, but displayed partial neurovirulence at doses up to 4 log p.f.u. given intracerebrally. Immunization of 3-week-old mice with JE/dengue 2 virus yielded neutralizing-antibody titres against dengue 2 virus and conferred protection against dengue encephalitis caused by neuroadapted dengue 2 virus. A rise in post-challenge neutralizing-antibody titres against dengue 2 virus in surviving mice suggests that immunization is associated with establishment of a memory antibody response in this model. This study demonstrates the capacity of JE virus to serve as a vector for expression of heterologous flavivirus structural proteins. Similar to previous studies with other chimeric flaviviruses, this approach may be useful as a genetic system for engineering experimental vaccines against Dengue virus and other medically important flaviviruses.

Animals↗