PubMed Health⌕ Search

Biomedical subjects

Yu An

Publications and source records attributed to Yu An.

14 recordsLinked to original sources
PubMed2026

De novo variants in the poly(rC)-binding protein gene PCBP1 cause a neurodevelopmental disorder.

Poly(rC)-binding protein 1 (PCBP1), a splicing factor and key member of the hnRNP E family, was initially characterized for its tumor suppressive properties. More recently, its role in gene regulation in the brain and nervous system has attracted growing interest. Through an international multicenter collaboration, we identified 16 de novo pathogenic variants in PCBP1 across 17 subjects from 16 unrelated families. All affected individuals exhibited intellectual disability (ID), with autism spectrum disorder (ASD) as a prominent feature. Functional analysis in primary hippocampal mouse neuron cultures indicated that PCBP1 variants impair dendritic arborization, underscoring their deleterious effects. Transcriptomic profiling by RNA sequencing of subject-derived T cells showed a distinctive signature characterized by significantly increased exon skipping. These results highlight the contribution of PCBP1 in neurogenesis and neuritogenesis, which is impacted by loss-of-function variants expressed in neuronal cells, thereby supporting the link between splicing defects and neurodevelopmental disorders. Collectively, our findings demonstrate the prominent role of PCBP1 in neurodevelopment, reaffirming the importance of splicing regulation in mammalian neurodevelopment.

Journal Article↗
PubMed2026

Impact of NRSN2 deficiency on memory: Altered excitatory synaptic plasticity associated with reduced expression of NMDA receptor subunits and impaired LTP in the hippocampus.

Our earlier human studies identified NRSN2 (Neurensin-2), a neuronal-specific vesicular protein, as a candidate gene contributing to 20p13 microdeletion syndrome, yet the functional consequences of NRSN2 deficiency in the nervous system remain poorly understood. To explore the role of Nrsn2 in neurodevelopment and cognitive function, we utilized previously generated homozygous Nrsn2 knockout mice (Nrsn2-/-) and performed a series of behavioral, morphological, and electrophysiological analyses. Behaviorally, Nrsn2-/- mice exhibited mild locomotor impairment, as assessed by gait analysis at 4 and 8 weeks of age, as well as significant deficits in spatial learning and memory (Morris water maze) and fear memory (passive avoidance test) at 8 weeks. Morphometric analysis suggested no overt alterations in dendritic complexity or spine density in hippocampal CA1 pyramidal neurons or cerebellar Purkinje cells without developmental malformation. Electrophysiological recordings and immunoblotting analyses may reflect region-specific synaptic alterations. In the hippocampus, expression levels of the NMDA receptor subunits GluN1 and GluN2A were reduced at 4 weeks of age. Consistently, CA1 pyramidal neurons displayed decreased sEPSC frequency with unchanged amplitude under the conditions examined. In addition, an imbalance in hippocampal excitatory/inhibitory transmission was observed, as reflected by altered sEPSC frequency in the absence of changes in sIPSC frequency. In cerebellar Purkinje cells, GluA1-containing AMPA receptors were selectively downregulated, accompanied by reduced frequency and amplitude of sEPSCs and a selective decrease in sIPSC frequency, indicating both excitatory and inhibitory synaptic dysfunction in this region. Collectively, these findings indicate that Nrsn2 deficiency is accompanied by altered excitatory synaptic transmission and reduced long-term potentiation (LTP) at 8 weeks of age, despite preserved dendritic architecture as assessed by Golgi staining. These synaptic and plasticity deficits occur alongside the observed cognitive and motor impairments in Nrsn2⁻/⁻ mice. This study provides a descriptive phenotypic characterization of Nrsn2 deficiency and offers initial insights into the neurobiological role of NRSN2 and its contribution to neurodevelopment, learning, and memory.

Animals↗
PubMed2006

Sudan I induces genotoxic effects and oxidative DNA damage in HepG2 cells.

Sudan I, a synthetic lipid soluble azo pigment, is widely used in various industrial fields. However, Sudan I has not been approved at any level of food production, since there are many inconclusive reports relating to its genotoxicity and carcinogenicity in humans. The aim of this study was to assess the genotoxic effects of Sudan I and to identify and clarify the reaction mechanisms by use of human hepatoma HepG2 cells. To study the genotoxic effects of Sudan I, the comet assay and micronucleus test (MNT) were used. In the comet assay and MNT, we found increase of DNA migration and of the micronuclei frequencies at all tested concentrations (25-100 microM) of Sudan I in a dose-dependent manner. The data suggest that Sudan I caused DNA strand breaks and chromosome breaks. To elucidate the underlying mechanism of this difference, we monitored the level of reactive oxygen species (ROS) production with the 2,7-dichlorofluorescein diacetate assay. The level of the oxidative DNA damage and lipid peroxidation was evaluated using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS). Significantly increased levels of ROS, 8-OHdG and TBARS were observed in HepG2 cells at higher concentrations, the doses being 100, 50-100 and 50-100 microM, respectively. We conclude that Sudan I causes genotoxic effects, probably via ROS-induced oxidative DNA damage at the higher doses.

Carcinogens↗
PubMed2006

Mechanism of single-bubble sonoluminescence.

Considering almost all the effective processes of physics and chemical reaction in our numerical computation model, we investigate the mechanism of single bubble sonoluminescence (SBSL). For those sonoluminescing single bubbles in water at its flashing phase, the numerical simulation reveals that if the temperature inside the bubble is not high enough which may result in the plenty oxygen molecules and OH radicals undissociated, such as the case of a single argon bubble in 20 degrees C or 34 degrees C water, the radiative attachment of electrons to oxygen molecules and OH radicals contributes most to the SBSL; if the temperature inside the bubble is higher which makes most of the water vapor inside the bubble dissociate into oxygen and hydrogen atoms, such as the case of an argon bubble or a helium bubble in 0 degrees C water, the radiative attachment of electrons to oxygen and hydrogen atoms dominates the SBSL; if the temperature is still higher, such as the case of a xenon bubble in 0 degrees C water, the contribution from electron-neutral atom bremsstrahlung and electron-ion bremsstrahlung and recombination would be comparable with the contribution from the radiative attachment of electrons to oxygen and hydrogen atoms, and they together dominate the SBSL. For sonoluminescing single bubbles in those low vapor pressure liquids, such as in 85 wt.% sulphuric acid, the electron-neutral atom bremsstrahlung and the electron-ion bremsstrahlung and recombination contribute most to the continuous spectrum part of SBSL. The present calculation also provides good interpretations to those observed phenomena, such as emitted photon numbers, the width of optical pulses, the blackbody radiation like spectra. The temperature fitted by the blackbody radiation formula is very different from that calculated by the gas dynamics equations. Besides, the effect of chemical dissociation on the shock wave is also discussed.

Journal Article↗
PubMed2006

Shape-persistent macrocyclic aromatic tetrasulfonamides: Molecules with nanosized cavities and their nanotubular assemblies in solid state.

Alkoxy side-chain-flanked diarylsulfonamide serves as a reliable structural motif for constructing macrocyclic aromatic tetrasulfonamides. This 90 degrees structural motif is persistent both in solution and in the solid state, which allows the one-step formation of tetrasulfonamide macrocycles. These macrocycles adopt a cone-shaped conformation in solution and in the solid state. For each molecule, an interior cavity surrounded by the aromatic residues is formed. The cavity sizes of the macrocycles can be tuned by incorporating aromatic residues of proper sizes. Guest (solvent) molecules are found in the cavities and bound by side chains. In solution, 1H NMR shows that the cone conformations undergo rapid interconversion at room temperature. The alkoxy side chains are found to be indispensable for maintaining the cone conformation. In addition, these porous molecules self-assemble into hollow tubular structures in the solid state. A variety of host molecules and building blocks for constructing nanoporous solid-state structures can be expected from these molecules.

Journal Article↗
PubMed2006

Plasma in sonoluminescing bubble.

With the new accommodation coefficient of water vapor evaluated by molecular dynamics model, the maximum temperature of a sonoluminescing bubble calculated with the full partial differential equations easily reaches few tens of thousands degrees. Though at this temperature the gas is weakly ionized (10% or less), the gas density inside a sonoluminescing bubble at the moment of the bubble's flashing is so high that there still forms a dense plasma. The light emission of the bubble is calculated by the plasma model which is compared with that by the bremsstrahlung (electron-ion, electron-neutral atom) and recombination model. The calculation by the two models shows that for the relatively low maximum temperature (< 30,000 K) of the bubble, the pulse width is independent of the wavelength and the spectrum deviates the black body radiation type; while for the relatively high maximum temperature (approximately 60,000 K), the pulse width is dependent of the wavelength and the spectrum is an almost perfect black body radiation spectrum. The maximum temperature calculated by the gas dynamics equations is much higher than the temperature fitted by the black body radiation formula.

Journal Article↗
PubMed2006

[Clinical application of sural neurocutaneous island flaps].

OBJECTIVE: To explore the clinical application characteristics of sural neurocutaneous island flaps. METHODS: Sural neurocutaneous island flaps were used to repair the skin defect accompanied bone and tendon exposure in the lower leg, around the ankle and foot in 21 cases, including 4 cases to repair the foreside of the foot back . Direct flap was used in 5 cases and reverse flap in 16 cases. Meanwhile the coverage and formation of sural nerve were surveyed together with the starting point of peroneal perforator. RESULTS: All the 21 sural flaps were survived, including sural nerve (18 cases) anastomose 12 cases, single trunk 4 cases, double trunk 2 cases. The anastomose site of medial sural cutaneous nerve and the communicating branch of lateral sural cutaneous nerve was at the point of 11 - 14 cm above the ankle in 12 cases. The lower was the anastomose site, the shorter was the sural nerve. The site is 4 - 7 cm above the ankle in 15 out of 18 sural nerve perforator branch cases, and the other 3 cases is 10, 11, 11.5 cm above the ankle respectively. CONCLUSIONS: Sural neurocutaneous island flaps are easy to separate. Major arteries are not injured. It is the ideal flap to repair the skin defect accompanied by bone and tendon exposure in lower leg, around ankle and foot. The nerve must be anastomosed when repairing the heel.

Adult↗
PubMed2005

Model of single bubble sonoluminescence.

The temperature within and the sonoluminescence characteristics of a stable inert-gas single bubble grown in water under some given conditions are computed by using a model that is as sufficiently complete as we can manage, except that possible chemical reactions within the bubble are neglected. We work with several different versions of the equation describing the motion of the bubble wall, which are usually considered to give merely slight differences; or vary a parameter in the formula calculating the net increment of the water condensed at the bubble wall. It is found that the final outcomes of the temperature and the sonoluminescence can be significantly different in some cases. This illustration points to the importance of differentiating among the various seemingly similar equations and of adopting the correct value of the parameter used in the computation model of a single bubble.

Journal Article↗
PubMed2005

Instability of sonoluminescing bubbles under a nonspherical symmetrical acoustic-pressure perturbation.

The perturbation of nonspherical symmetrical acoustic pressure is added to the equation governing the spherical stability of sonoluminescing bubbles. The numerical calculations of the shape instability of sonoluminescing bubbles with the modified equation are conducted and the results are illustrated accordingly in the p(a) - R0 phase diagrams. The calculated results indicate that the stability region vanishes as the amplitude of the driving acoustic pressure p(a) arrives at the upper threshold ( approximately 1.6 atm) due to the perturbation of a small nonspherical symmetrical acoustic pressure (about a few Pa), which is in consistence with the experimental observations.

Journal Article↗
PubMed2005

[The expanded cross-leg flap for repairing the soft tissue defects of the instep].

OBJECTIVE: To explore the clinical application of the expanded cross-leg flap for repairing instep soft tissue defects with bone exposure. METHODS: The expanded cross-leg flap was used to repair instep defects in 10 patients. After flap transferring the donor site was closed directly without skin grafting. RESULTS: Satisfactory results were achieved in all the cases. The flaps survived well. The donor site had less scar and kept good appearance. CONCLUSIONS: The expanded cross-leg flap is a better choice for repairing the soft tissue defects of the instep. It is simple and easy with less trauma to the donor site. After the operation, both the recipient and the donor areas had good appearance.

Adult↗
PubMed2004

COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code.

Cystic fibrosis (CF) is a childhood hereditary disease in which the most common mutant form of the CF transmembrane conductance regulator (CFTR) DeltaF508 fails to exit the endoplasmic reticulum (ER). Export of wild-type CFTR from the ER requires the coat complex II (COPII) machinery, as it is sensitive to Sar1 mutants that disrupt normal coat assembly and disassembly. In contrast, COPII is not used to deliver CFTR to ER-associated degradation. We find that exit of wild-type CFTR from the ER is blocked by mutation of a consensus di-acidic ER exit motif present in the first nucleotide binding domain. Mutation of the code disrupts interaction with the COPII coat selection complex Sec23/Sec24. We propose that the di-acidic exit code plays a key role in linking CFTR to the COPII coat machinery and is the primary defect responsible for CF in DeltaF508-expressing patients.

Animals↗
PubMed2003

Geranylgeranyl switching regulates GDI-Rab GTPase recycling.

Rab GTPases, key regulators of membrane targeting and fusion, require the covalent attachment of geranylgeranyl lipids to their C terminus for function. To elucidate the role of lipid in Rab recycling, we have determined the crystal structure of Rab guanine nucleotide dissociation inhibitor (alphaGDI) in complex with a geranylgeranyl (GG) ligand (H(2)N-Cys-(S-GG)-OMe). The lipid is bound beneath the Rab binding platform in a shallow hydrophobic groove. Mutation of the binding pocket in the brain-specific alphaGDI leads to mental retardation. Strikingly, lipid binding acts through a conserved allosteric switching mechanism to promote release of the GDI-Rab[GDP] complex from the membrane.

Diterpenes↗