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Yong Wu

Publications and source records attributed to Yong Wu.

At least 19 recordsLinked to original sources
PubMed2026

Developmental and cellular vulnerabilities underlie genetic architecture of schizophrenia.

Schizophrenia (SZ) is a highly heritable neuropsychiatric condition with complex polygenic architecture. Elucidating the cellular and developmental substrates vulnerable to the genetic risk is essential for understanding the underlying neurobiological mechanisms. Here, we integrated genome-wide association study (GWAS) and whole-exome sequencing (WES) data with a developmental multi-omics atlas of the human cortex (including 5 cortical regions), comprising about 3 million single-nucleus RNA sequencing (snRNA-Seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-Seq) profiles across 8 neurodevelopmental processes, to map cell-type-specific enrichment of SZ genetic risk. Our enrichment analyses revealed that both common and rare genetic liabilities converged on broad excitatory and inhibitory neuronal classes. Across different statistical frameworks, we identified genetic enrichment within intratelencephalic (IT) projection neurons and layer 6b excitatory neurons (Ex-L6b) networks across multiple cortical regions. Stage-resolved developmental mapping in the frontal cortex showed that genetic liabilities, particularly the rare variants, are predominantly concentrated within early developmental processes, namely neurogenesis and neuronal migration. Differential expression analysis in postmortem frontal cortex snRNA-Seq datasets cross-validated the cellular substrates of the genetic liabilities. Collectively, our findings establish a high-resolution cellular and temporal framework of SZ susceptibility, implicating mature associative IT microcircuits, deep-layer thalamocortical-regulating networks, and early developmental specification windows as primary points of genetic convergence in SZ.

Journal Article↗
PubMed2026

Comprehensive analysis of metabolomics and transcriptomics of radiation-induced rectal injury.

Radiation-induced rectal injury (RRI) significantly affects the quality of life in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT). Non-targeted liquid chromatography-mass spectrometry metabolomics analysis and transcriptomic analysis were conducted to explore RRI characteristics. Hematoxylin-eosin and Masson staining confirmed radiation-induced injury in rectal tissue within the radiotherapy target region. Orthogonal partial least squares discriminant analysis identified 823 differentially expressed metabolites (DEMs). Transcriptomic analysis revealed 400 differentially expressed genes (DEGs). Enrichment analysis revealed that DEMs and DEGs were primarily involved in metabolic, immune, and signal transduction pathways. Integrated analysis demonstrated significant enrichment of DEMs and DEGs in the arachidonic acid metabolism pathway. Pearson's correlation and canonical correlation analyses were used to assess the association between DEMs and DEGs within this pathway. In conclusion, this study identified key biological regulatory pathways involved in RRI through a multi-omics approach, offering potential targets for its diagnosis and treatment.

Humans↗
PubMed2007

Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts.

A highly enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substituted quaternary stereocenter in excellent enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts could be smoothly converted to variously structured beta(2,2)-amino acid esters. Moreover, an interesting reaction model involving multiple hydrogen-bonding interactions amongst the thiourea/tertiary amine catalyst and the reactants has been proposed based on the absolute configuration of the adduct and computational studies.

Acetates↗
PubMed2007

Diversity of the O-superfamily conotoxins from Conus miles.

Conopeptides display prominent features of hypervariability and high selectivity of large gene families that mediate interactions between organisms. Remarkable sequence diversity of O-superfamily conotoxins was found in a worm-hunting cone snail Conus miles. Five novel cDNA sequences encoding O-superfamily precursor peptides were identified in C. miles native to Hainan by RT-PCR and 3'-RACE. They share the common cysteine pattern of the O-superfamily conotoxin (C-C-CC-C-C, with three disulfide bridges). The predicted peptides consist of 27-33 amino acids. We then performed a phylogenetic analysis of the new and published homologue sequences from C. miles and the other Conus species. Sequence divergence (%) and residue substitutions to view evolutionary relationships of the precursors' signal, propeptide, and mature toxin regions were analyzed. Percentage divergence of the amino acid sequences of the prepro region exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical with to highly divergent from inter- and intra-species. Despite the O-superfamily being a large and diverse group of peptides, widely distributed in the venom ducts of all major feeding types of Conus and discovered in several Conus species, it was for the first time that the newly found five O-superfamily peptides in this research came from the vermivorous C. miles. So far, conotoxins of the O-superfamily whose properties have been characterized are from piscivorous and molluscivorous Conus species, and their amino acid sequences and mode of action have been discussed in detail. The elucidated cDNAs of the five toxins are new and of importance and should attract the interest of researchers in the field, which would pave the way for a better understanding of the relationship of their structure and function.

Amino Acid Sequence↗
PubMed2006

Protective effect of verapamil on multiple hepatotoxic factors-induced liver fibrosis in rats.

The purpose of the present work was to investigate the effect of verapamil on liver fibrosis induced by multiple hepatotoxic factors in rats. Male Wistar rats were divided into a normal control group, a liver fibrosis model control group, and verapamil groups with different dosages. Multiple hepatotoxic factors including carbon tetrachloride (CCl(4)), ethanol and high cholesterol were used to make the animal model of liver fibrosis. The parameters of serum l-alanine aminotransferase (ALT), liver malondialdehyde and hydroxyproline contents were measured. Samples of the liver obtained by biopsy were subjected to histological and immunohistochemical studies for the expressions of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta(1) (TGF-beta(1)). Results showed that verapamil induced a dose-dependent decrease of serum ALT, liver malondialdehyde and hydroxyproline compared with liver fibrosis model control. Verapamil reduced hepatocyte degeneration and necrosis, and delayed the formation of liver fibrosis. The levels of expression of alpha-SMA and TGF-beta(1) in the hepatic tissue of three of the verapamil-treated groups were significantly less than those of the liver fibrosis model control group. The results showed that verapamil acts against the formation of liver fibrosis, the mechanism might be due to a protective effect for hepatocytes and through decreasing TGF-beta(1) to block the activation of hepatic stellate cells (HSCs) and collagen gene expression.

Actins↗
PubMed2006

Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms.

OBJECTIVES: We investigated the effects of the orally bioavailable non-immunosuppressive immunophilin ligand GPI 1046 (GPI) on erectile function and cavernous nerve (CN) histology following unilateral or bilateral crush injury (UCI, BCI, respectively) of the CNs. METHODS: Adult male Sprague-Dawley rats were administered GPI 15 mg/kg intraperitoneally (ip) or 30 mg/kg orally (po), FK506 1 mg/kg, ip, or vehicle controls for each route of administration just prior to UCI or BCI and daily up to 7 d following injury. At day 1 or 7 of treatment, erectile function induced by CN electrical stimulation was measured, and electron microscopic analysis of the injured CN was performed. RESULTS: Intraperitoneal administration of GPI to rats with injured CN protected erectile function, in a fashion similar to the prototypic immunophilin ligand FK506, compared with vehicle-treated animals (93%+/-9% vs. 70%+/-5% vs. 45%+/-1%, p<0.01, respectively). Oral administration of GPI elicited the same level of significant protection from CN injury. GPI administered po at 30 mg/kg/d, dosing either once daily or four times daily with 7.5 mg/kg, provided nearly complete protection of erectile function. In a more severe BCI model, po administration of GPI maintained erectile function at 24 h after CN injury. Ultrastructural analysis of injured CNs indicated that GPI administered at the time of CN injury prevents degeneration of about 83% of the unmyelinated axons at 7 d after CN injury. CONCLUSIONS: The orally administered immunophilin ligand GPI neuroprotects CNs and maintains erectile function in rats under various conditions of CN crush injury.

Administration, Oral↗
PubMed2006

Quality of life of nasopharyngeal carcinoma survivors in Mainland China.

The aim of this study is to evaluate the quality of life (QoL) of nasopharyngeal carcinoma (NPC) survivors. 192 NPC survivors treated in 1999 and 2000 were enrolled in this study. Median follow up was 3.6 years (range 2.4-4.6 years). The Chinese SF-36 questionnaire and a self-reported symptom checklist consisting of 14 items were completed at clinics. Sociodemographic factors and clinical information were also collected. Most functional domains of the Chinese SF-36 were significantly worse in NPC survivors compared to the normal population. Xerostomia, hearing loss, hypomnesia, dysphagia, and trismus were frequently reported symptoms. Sociodemographic variables including gender, age, dialect, educational level, monthly income, economic status, and number of comorbidities were univariate predictors of different SF-36 domains and symptoms. Patients with earlier T and N stage, irradiated by linear accelerator, with lower dose and weekly dose to nasopharynx and neck, and those who had anterior nasal radiation field reported better QoL. Multiple stepwise regression analysis showed that the number of comorbidities, monthly income, age, and T stage were independent factors affecting global QoL. We concluded that NPC survivors had worse QoL than the normal population and improving radiotherapy might increase physical and functional domain of QoL.

Adolescent↗
PubMed2006

Sequence diversity of O-superfamily conopetides from Conus marmoreus native to Hainan.

The full-length cDNAs of six new O-superfamily conotoxins (CTX) were cloned and sequenced from Conus marmoreus native to Hainan in China South Sea using RT-PCR and 3'-RACE. Six novel conotoxin precursors encoded by these cDNAs consist of three typical regions of signal, pro-peptide and mature peptide. All the six toxin regions share a common O-superfamily cysteine pattern (C-C-CC-C-C, with three disulfide bridges). The predicted precursors are composed of 73-88 amino acids, and the predicted mature peptides consist of 26-34 amino acids. Phylogenetic analysis of new conotoxins from C. marmoreus from the present study and published homologue T-superfamily sequences from other Conus species was performed systematically. Patterns of sequence divergence for three regions of signal, pro-region and mature peptides, as well as Cys codon usage define the major O-superfamily branches and suggest how these separate branches arose. Percent identities of the amino acid sequences of the signal region exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical to highly divergent between inter- and intra-species. Notably, the diversity of the pro-region was also high with intermediate divergence between that observed in signal and toxin regions. Amino acid sequences and their mode of action (target) of previously identified conotoxins from molluscivorous C. marmoreus for the known conotoxins classes are discussed in detail. The data presented are new and should pave the way for chemical synthesis of these unique conotoxins for to allow determination of the molecular targets of these peptides, and also to provide clues for a better understanding of the phylogeny of these peptides.

Amino Acid Sequence↗
PubMed2006

N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

Acetylcysteine↗
PubMed2006

Cyclic stretch translocates the alpha2-subunit of the Na pump to plasma membrane in skeletal muscle cells in vitro.

The Na+-K+-ATPase and its regulation is important for maintaining membrane potential and transmembrane Na(+) gradient in all skeletal muscle cells and thus is essential for cell survival and function. In our previous study, cyclic stretch activated the Na pump in cultured skeletal muscle cells. Presently, we investigated whether this stimulation was the result of translocation of Na+-K+-ATPase from endosomes to the plasma membrane, and also evaluated the role of phosphatidylinositol 3-kinase (PI 3-kinase), the activation of which initiated vesicular trafficking and targeting of proteins to specific cell compartments. Skeletal muscle cells were stretched at 25% elongation continuous for 24h using the Flexercell Strain Unit. The plasma membrane and endosome fractions were isolated and Western blotted to localize the Na+-K+-ATPase alpha1- and alpha2-subunit protein. The results showed stretch increased Na+-K+-ATPase alpha1- and alpha2-subunit protein expression in plasma membrane fractions and decreased it in endosomes. The alpha2-subunit had a more dynamic response to mechanical stretch. PI 3-kinase inhibitors (LY294002) blocked the stretch-induced translocation of the Na+-K+-ATPase alpha2-subunit, while LY294002 had no effect on the transfer of alpha1-subunit. We concluded that cyclic stretch mainly stimulated the translocation of the alpha2-subunit of Na+-K+-ATPase from endosomes to the plasma membrane via a PI 3-kinase-dependent mechanism in cultured skeletal muscle cells in vitro, which in turn increased the activity of the Na pump.

Animals↗
PubMed2006

[Diagnosis and treatment of the femoral shaft fractures combined with ipsilateral occult femoral neck fractures].

OBJECTIVE: To improve the ability of recognizing, diagnosing and treatment for the femoral shaft fractures combined with ipsilateral occult femoral neck fractures, and reduce the rate of loss-diagnosis. METHODS: By retrospective study of 50 patients who sustained ipsilateral femoral shaft and neck fractures from March 1998 to October 2003, 9 cases were femoral shaft fractures combined ipsilateral femoral neck fractures. The neck fractures were diagnosed separately before, during and after operation. Among the 9 cases, 5 cases treated with reconstructive intramedullary nail to fix both shaft and neck fractures; 3 cases were treated with retrograted intramedullary nail to fix shaft fractures and with canulated screws to fix neck fractures; another one was sustained two operations, after the fixation of shaft by intramedullary nail, the neck fracture was found, the neck fracture was fixed with canulated screws anterior and posterior of the nail. RESULTS: Nine cases were followed up for average 20 months. All femoral shaft fractures were united during 6 months; and all neck fractures were united during 3 months. CONCLUSIONS: Femoral shaft fractures combined with ipsilateral occult femoral neck fractures have a high rate of loss-diagnosis during the early stage after injure, the orthopaedic surgeons should consider the femoral neck fracture by analyzing the mechanism of high energy injury patient with femoral shaft fracture. The occult femoral neck fractures can be diagnosed by CT scan before operation. During and after the operation of fixing the femoral shaft fractures, the femoral neck should be observed intensively to identify the exist of fractures.

Adult↗
PubMed2006

Unexpected ring-opening reactions of aziridines with aldehydes catalyzed by nucleophilic carbenes under aerobic conditions.

[reaction: see text] The chemoselective ring opening of N-tosyl aziridines with aldehydes catalyzed by an N-heterocyclic carbene was investigated under aerobic conditions. Unexpected carboxylates of 1,2-amino alcohols from the corresponding aldehydes, rather than the acyl anion ring-opened beta-amino ketones, were exclusively obtained. A plausible mechanism for this unprecedented carbene-mediated reaction was also proposed.

Aldehydes↗
PubMed2006

Mallory body (cytokeratin aggresomes) formation is prevented in vitro by p38 inhibitor.

Microarray analysis of livers from mice fed diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) to induce Mallory body (MB) cytokeratin aggresome formation showed that gene expression for cellular adhesion molecules, cytokeratins, kinases and aggresome forming proteins were upregulated, when MBs were formed in vivo. This response was enhanced when the DDC was refed (mice fed DDC for 10 weeks followed by DDC withdrawal for 1 month, then refed DDC for 7 days). Immunofluorescent antibody staining of the MBs that formed showed that MAPK p38 was colocalized with ubiquitin and p62 in the MBs. To investigate further the mechanisms of MB formation, primary cultures derived from DDC primed mice and their controls were incubated for 6 days. Liver cells cultured for 3 h and 6 days were used for microarray analysis. At 3 h, there were no MBs formed, but MBs were numerous after 6 days of culture. At 3 h, the expression of a large number of genes was different when the control, and the DDC primed hepatocytes were compared, which indicates that the primed hepatocytes were phenotypically changed. The gene expression of many kinases including p38 was upregulated after 6 days where the gene expression of cytokeratins, adhesion molecules and aggresome forming proteins were upregulated when MBs formed. An inhibitor of p38 phosphorylation (SB202190) completely prevented MB formation. Western blot showed that phosphorylated p38 MAPK and total p38 were absent in vitro after the p38 inhibitor treatment. Immunostaining of 6-day DDC-primed hepatocyte cultures stained with antibodies to p62 and phospho-p38 MAPK showed that phosphorylated p38 MAPK was concentrated within the MBs. Antibodies to specific serine phosphorylated sites 73 and 431, located in cytokeratin 8, localized to Mallory bodies in vivo, indicating that cytokeratin 8 was hyperphosphorylated. The data supported the concept that MBs form as the result of hyperphosphorylation of cytokeratin 8 by p38.

Animals↗
PubMed2006

Mallory body forming cells express the preneoplastic hepatocyte phenotype.

The livers of mice fed diethyl 1,4-dihydro-2,4,6,-trimethyl-3,5-pyridinedicarboxylate (DDC) for 10 weeks formed Mallory bodies (MBs) in clusters of hepatocytes. Mice withdrawn from DDC for 9 months developed liver tumors. In the present study, the phenotype of the hepatocytes that formed MBs and tumors was characterized. Immunoperoxidase and immunofluorescent stains were done on the DDC-treated mouse livers, as well as mouse liver tumors and a human hepatocellular carcinoma that formed MBs. Antibodies to markers of hepatocellular neoplasms such as alpha-fetoprotein (AFP), ubiquitin B (UbB) fatty acid synthase (FAS) and alpha2 macroglobulin (A2m) stained the MB forming cells positive. Quantitative real-time RT-PCR assay was used to measure AFP, UbB, FAS and GCP-3 A2m mRNA levels in the livers of DDC fed mice and the DDC-induced mouse liver tumors. The FAS, UbB, GPC-3 and AFP mRNA levels were significantly increased in the MB forming liver cells. The in vitro model of MB formation was used to correlate MB formation with gene and protein expression. Primary cultures of DDC-primed hepatocytes were compared with the controls. A2m and UbB expression increased in the primary cultures of DDC-primed hepatocytes when MBs formed. Thus, the tumor markers used to identify hepatocellular carcinoma were upregulated in cells forming MBs in vivo and in vitro, suggesting that MB forming cells express preneoplastic phenotypic features.

Animals↗
PubMed2006

Identification of novel phosphoproteins in signaling pathways triggered by latent membrane protein 1 using functional proteomics technology.

Previous studies have shown that the Epstein-Barr virus-encoded latent membrane protein1 (LMP1) could activate nuclear factor kappa B, activator protein-1, and Janus kinases/signal transducer and activation of transcription factors pathways. However, many signaling molecules and downstream target proteins triggered by LMP1 have not been identified. To determine the functional components in signaling pathways triggered by LMP1, we combined the novel strategy of phosphoprotein enrichment with proteomics technology to elucidate the signaling cascade activated by LMP1. We found that LMP1 could increase the quantity of total phosphoproteins by 18.03%, and 43 proteins showed significant changes in the degree of phosphorylation when LMP1 was expressed. Twenty-five signaling molecules or downstream targets of signaling pathways triggered by LMP1 were identified, several of which had previously been implicated in LMP1 signal pathways. The other proteins, including annexin A2, heat shock protein 27, stathmin, annexin I, basic transcription factor 3, and porin, were novel signaling molecules or targets with no previously known function in LMP1 signal transduction. The method used here has proven to be suitable for the identification of molecules involved in various signaling pathways.

Blotting, Western↗