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Di Wang

Publications and source records attributed to Di Wang.

At least 19 recordsLinked to original sources
PubMed2026

hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.

Enhancer RNAs interact with promoter-derived RNAs to dictate enhancer-promoter looping, but the RNA-binding protein that mediates this process has remained unidentified. Here we identify hnRNPK as a general structural regulator that preferentially binds to nascent RNAs transcribed from enhancer and promoter regions, promoting enhancer-promoter looping and transcriptional activation. We further show that hnRNPK forms phase-separated, cavity-containing condensates that encapsulate RNA polymerase II (Pol II) via its RPB3 subunit, facilitating chromatin looping and potentially enabling recruitment of Pol II from enhancers to promoters through protein dimerization. Notably, a mutation associated with Au-Kline syndrome in hnRNPK (c.953+1dupG) alters its condensates from a liquid-like to a gel-like state, leading to developmental defects in knock-in mice. Fibroblasts derived from these mutants display reduced enhancer-promoter looping and decreased Pol II recruitment at promoters of key developmental genes. These findings suggest that hnRNPK is a structural regulator of enhancer-promoter communication and highlight the importance of RNA-RNA interactions mediated by RNA-binding proteins in transcriptional regulation.

RNA Polymerase II↗
PubMed2026

Paired genomic profiling of primary tumor and lymph-node metastases identifies candidate prognostic features in penile squamous cell carcinoma.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited genomic data in Asian populations. Lymph node metastasis heavily dictates prognosis, yet molecular determinants of progression remain poorly understood. We aimed to characterize the genomic landscape and explore candidate prognostic genomic features using paired primary and metastatic PSCC tumors. PATIENTS AND METHODS: Targeted next-generation sequencing (437 cancer-related genes) was performed on primary tumors and matched lymph node metastases from 20 Chinese patients. Somatic alterations, intralesional heterogeneity, and tumor mutation burden (TMB) were analyzed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: The most frequent primary tumor mutations included TP53 (45%) and TERT (40%). Notably, CCND1/FGF19 co-amplification (20% of cases) was associated with inferior DFS (P = .027) and showed a trend toward shorter OS (P = .050). Conversely, T-cell receptor (TCR) pathway alterations correlated with markedly improved survival. Comparing paired lesions revealed 59.8% shared alterations. Elevated TMB in metastases relative to matched primary tumors was significantly associated with poorer DFS (P = .008), while higher intralesional heterogeneity showed a trend toward worse OS. CONCLUSION: Paired profiling revealed broadly conserved genomic features together with lesion-specific divergence in PSCC. Recurrent CCND1/FGF19-containing 11q13 amplification, TCR pathway alterations, and elevated metastatic TMB warrant evaluation as potential prognostic features in larger, independently validated cohorts with integrated HPV and immune profiling.

Humans↗
PubMed2026

Functions of tandem-repeat galectins and domain coordination governs galectin-4 activity in grass carp (Ctenopharyngodon idella).

Galectins are β-galactoside-binding lectins that play essential roles in innate immunity. Among them, tandem-repeat galectins (TrGals), typically composed of two distinct carbohydrate-recognition domains (CRDs) connected by a linker peptide, are well established as key regulators of pathogen recognition and host defense in mammals. However, their structural diversity and immunological functions in teleost fish remain poorly understood. In this study, five TrGals (Gal-4, Gal-8a, Gal-8b, Gal-9, and Gal-9like) were identified in grass carp. Sequence and structural analysis revealed that Gal-8a/b, Gal-9, and Gal-9like possess the canonical two-CRD architecture, whereas Gal-4 uniquely contains four highly similar tandem-repeat domains. All five TrGals were broadly expressed across examined tissues, with predominant expression in the liver. Upon Aeromonas hydrophila infection, Gal-4, Gal-8a, Gal-8b, and Gal-9 were rapidly up-regulated at early time points (3-6 h). To elucidate the functional significance of CRD number, recombinant full-length CiGal-4 (CiGal4-full) and three truncated variants containing one, two, or three CRDs (CiGal4-1CRD, CiGal4-2CRD, and CiGal4-3CRD) were generated and systematically characterized. All recombinant proteins contained the conserved β-sheet structure typical of galectin CRDs. Functional assays revealed that CiGal4-full displayed the strongest growth-inhibitory activity against all tested bacteria, whereas CiGal4-1CRD showed the weakest effect. Notably, CiGal4-2CRD exhibited the most potent bactericidal activity, surpassing the full-length protein, while CiGal4-3CRD showed no further enhancement. CiGal4-full and CiGal4-2CRD showed superior carbohydrate-binding activities compared with the other variants. Collectively, these results reveal that CRD copy number alone does not linearly determine galectin function. Instead, domain organization and conformational coordination are critical for optimizing antimicrobial activity. This study provides new insights into the structure-function relationships and evolutionary diversification of galectins in teleosts and highlights their potential as novel antimicrobial and immunomodulatory agents in aquaculture.

Animals↗
PubMed2024

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

INTRODUCTION: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized. METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. HIGHLIGHTS: Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water-corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non-carriers.

Humans↗
PubMed2006

Growth and decomposition of aligned and ordered PdO nanoparticles.

The formation, thermal decomposition, and reduction of small PdO particles were studied by high-resolution transmission electron microscopy and selected area electron diffraction. Well-defined Pd particles (mean size of 5-7 nm) were grown epitaxially on NaCl (001) surfaces and subsequently covered by a layer of amorphous SiO2 (25 nm), prepared by reactive deposition of SiO in 10(-2) Pa O2. The resulting films were exposed to molecular O2 in the temperature range of 373-673 K, and the growth of PdO was studied. The formation of a PdO phase starts at 623 K and is almost completed at 673 K. The high-resolution experiments suggest a topotactic growth of PdO crystallites on top of the original Pd particles. Subsequent reaction of the PdO in 10 mbar CO for 15 min and thermal decomposition in 1 bar He for 1 h were also investigated in the temperature range from 373 to 573 K. Reductive treatments in CO up to 493 K do not cause a significant change in the PdO structure. The reduction of PdO starts at 503 K and is completed at 523 K. In contrast, PdO decomposes in 1 bar He at around 573 K. The mechanism of PdO growth and decay is discussed and compared to results of previous studies on other metals, e.g., on rhodium.

Journal Article↗
PubMed2006

Effects of flufenamic acid on fictive locomotion, plateau potentials, calcium channels and NMDA receptors in the lamprey spinal cord.

A Ca(2+)-activated, non-selective cation current (I(CAN)) has been suggested to contribute to plateau potentials in lamprey reticulospinal neurons, providing the drive for locomotor initiation. Flufenamic acid (FFA) is commonly used as a blocker of I(CAN). To explore the effects of FFA on spinal locomotor pattern generation, we induced fictive locomotion in the isolated lamprey spinal cord. Bath-applied FFA (100-200microM) caused a marked reduction of amplitude and regularity of the locomotor burst activity. We next analyzed the NMDA-induced membrane potential oscillations in single spinal neurons. The duration of depolarizing plateaus was markedly reduced when applying FFA, suggesting an involvement of I(CAN). However, in experiments with intracellular injection of the Ca(2+) chelator BAPTA, and in the presence of the K(Ca)-channel blocker apamin, no support was found for an involvement of I(CAN). We therefore explored alternative explanations of the effects of FFA. FFA reduced the size of the slow, Ca(2+)-dependent afterhyperpolarization, suggesting an influence on calcium channels. FFA also reduced the NMDA component of reticulospinal EPSPs as well as NMDA-induced depolarizing responses, demonstrating an influence on NMDA receptors. These non-selective effects of FFA can account for its influence on fictive locomotion and on membrane potential oscillations and thus, a specific involvement of the I(CAN) current in the lamprey spinal cord is not supported.

Animals↗
PubMed2006

Transcription of human zinc finger ZNF268 gene requires an intragenic promoter element.

Human ZNF268 gene is a typical Krüppel-associated box/C2H2 zinc finger gene whose homolog has been found only in higher mammals and not in lower mammals such as mouse. Its expression profiles have suggested that it plays a role in the differentiation of blood cells during early human embryonic development and the pathogenesis of leukemia. To gain additional insight into the molecular mechanisms controlling the expression of the ZNF268 gene and to provide the necessary tools for further genetic studies of leukemia, we have mapped the 5'-end of the human ZNF268 mRNA by reverse transcription-PCR and primer extension assays. We then cloned the 5'-flanking genomic DNA containing the putative ZNF268 gene promoter and analyzed its function in several different human and mouse tissue culture cell lines. Interestingly, our studies show that the ZNF268 gene lacks a typical eukaryotic promoter that is present upstream of the transcription start site and directs a basal level of transcription. Instead, the functional promoter requires an essential element that is located within the first exon of the gene. Deletion and mutational analysis reveals the requirement for a cAMP response-element-binding protein (CREB)-binding site within this element for promoter function. Gel mobility shift and chromatin immunoprecipitation assays confirm that CREB-2 binds to the site in vitro and in vivo. Furthermore, overexpression of CREB-2 enhances the promoter activity. These results demonstrate that the human ZNF268 gene promoter is atypical and requires an intragenic element located within the first exon that mediates the effect of CREB for its activity.

5' Flanking Region↗
PubMed2006

[A research on Ig heavy chain constant region of five Acipenseridae].

Analyzed the immunoglobulin (Ig) heavy chain constant regions of Russian sturgeon (A. gueldenstaedtii); Sterlte sturgeon (A. ruthenus); Amur sturgeon (A. schrenckii); Chinese sturgeon (A. sinensis) and Great sturgeon (Huso huso) with molecular biology and bioinformatics methods. We cloned IgH nucleic acid sequences by RT-PCR using the specific primer, then determined the characteristics and functions of the amino acid sequences and plotted out the sequence into four sub-regions (CH1-CH4), of which CH4 sub-regions one another had the highest identity. According to the analysis of the variation expectation value (Kaa), species differentiation time (T) in the CH4 sub-region phylogenetic tree, we found that Chinese sturgeon and the theoretical common ancestor of the other five sturgeon form the first bifurcation of the tree, while, among the five left, Amur sturgeon and Huso sturgeon, Russian sturgeon and Siberian sturgeon, Siberian sturgeon (sequence from GenBank), Sterlte itself form another three bifurcations respectively. This result can clearly explain the relations of taxonomic status, geographical distribution and evolution among the species studied.

Amino Acid Sequence↗
PubMed2006

KRAB-containing zinc finger gene ZNF268 encodes multiple alternatively spliced isoforms that contain transcription regulatory domains.

The ZNF268 gene was originally isolated from an early human embryo cDNA library. Several different transcripts have been isolated for the ZNF268 gene and developmental expression studies suggest that ZNF268 plays a role in the development of human fetal liver and the differentiation of blood cells. In our effort to study the functions of ZNF268 in different organs during development and in pathogenesis, we have now identified 3 novel splicing isoforms, ZNF268e, ZNF268f and ZNF268g, in human fetal tissues and human tumor derived cell lines. The 8 alternatively spliced mRNAs discovered so for are predicted to encode 3 protein isoforms. Expression analysis showed that different mRNA isoforms have different expression profiles. In particular, ZNF268c mRNA was detected only in tumor cells, and ZNF268f appeared to be tissue-specific. By Western blot analysis, all 3 ZNF268 protein isoforms, ZNF268a, ZNF268b1 and ZNF268b2, were expressed in tumor cell lines, while only two protein products, ZNF268b1 and ZNF268b2, were detected in human fetal tissues. Subcellular localization analysis showed that ZNF268a and ZNF268b2 distributed diffusely throughout the cell, while ZNF268b1 mainly localized in the cytoplasm. Moreover, using a CAT reporter system fused to the Gal4 DNA binding domain of the ZNF268 gene, the ZNF268a and b2 activated the CAT reporter gene expression, while the KRAB domain, corresponding to the ZNF268b1 repressed the reporter gene expression. Taken together, our results showed that multiple ZNF268 splicing products encode multiple ZNF268 protein isoforms with different subcellular localization, and that the ZNF268 gene may function as a transcriptional activator in the growth and differentiation of cells in development and/or pathogenesis.

Alternative Splicing↗
PubMed2005

New tumor-associated antigen SC6 in pancreatic cancer.

AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb) in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases. METHODS: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95 patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV) of 41, 80, and 118 U/mL were used. RESULTS: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of SC6-Ag. Decreased expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% CT. CONCLUSION: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of SC6-Ag is valuable in the diagnosis of pancreatic cancer before and after surgery.

Adult↗
PubMed2005

Highly diastereoselective hydrostannylation of allyl and homoallyl alcohols with dibutyl(trifluoromethanesulfoxy)stannane.

Dibutyl(trifluoromethanesulfoxy)stannane (Bu2Sn(OTf)H, 1a) was found to be very valuable for highly diastereoselective homolytic hydrostannylation of allyl and homoallyl alcohols. alpha,beta-Disubstituted allyl alcohols and alpha,gamma-disubstituted homoallyl alcohols were converted into gamma- and delta-stannylated alcohols with high 1,2-syn and 1,3-syn diastereoselectivity, respectively. The origin of the stereochemical outcomes can be rationalized by conformational fixation of the intermediary beta-stannylalkyl radical by coordination of the hydroxy group to the Lewis acidic tin center.

Journal Article↗
PubMed2005

Highly regio- and stereoselective hydrostannylation of alkynols with a new Lewis acidic hydrostannane.

[reaction: see text] Bu2Sn(OTf)H (1a), easily prepared from Bu2SnH2 and TfOH, was found to be very valuable for highly regio- and stereoselective hydrostannylation of various propargyl alcohols leading to (Z)-gamma-stannylated allyl alcohols. The stannylation with 1a is applicable to the synthesis of hydroxy-substituted (Z)-vinylstannanes from terminal alkynes bearing a hydroxy group at the homoallylic or bishomoallylic position. The coordination of the hydroxy group to the Lewis acidic tin center plays an important role for the observed regio- and stereochemistry.

Allyl Compounds↗
PubMed2005

[Effects of in vitro PTEN transfection on proliferation of human pancreatic cancer ASPC-1 cells].

OBJECTIVE: To investigate the effect of phosphatase and ensinhomology deleted on chromosome ten (PTEN) on the human pancreatic cancer cell line without or low PTEN expression. METHODS: We selected the lowest PTEN gene expressive pancreatic cancer cell line among the four pancreatic cancer cell lines (Miapaca I, Miapaca II, JF305 and ASPC-1) through RT-PCR assay method, and transfected plasmid (Peak8) inserting PTEN or not in vitro into it by lipofectin. The effect of PTEN transfection on the lowest PTEN gene expressive pancreatic cancer cell line was carried out by flow cytometry, immunohistochemical staining, cloning survival assay, as well as tumorigenicity in nude mice. RESULTS: The lowest PTEN gene expression was found in ASPC-1 cells. PTEN mRNA expression and cloning plating efficiency in the ASPC-1, A-pE and A-pE-P cells were 20.3%, 15.0%, 56.8% and 33.3%, 31.7%, 24.0% respectively. We found that ASPC-1 cells transfected with PTEN exhibited significantly more protein, less vascular endothelial growth factor protein, and non-changed epidermal growth factor receptor protein comparing with vector-transfected cells. The tumor volumes were 202.7 mm(3) and 142.4 mm(3), pre-and post-transfection with significance (P < 0.01) within 5 weeks. CONCLUSIONS: Our findings suggested that PTEN mRNA exhibited the lowest expression in ASPC-1 cell line, exogenous PTEN dramatically inhibits the growth of ASPC-1 cells transfected with PTEN gene in nude mice.

Animals↗
PubMed2005

KAI1 inhibits anchorage-dependent and -independent pancreatic cancer cell growth.

Decreased expression of the tumor suppressor gene, KAI1, is associated with metastasis formation in pancreatic cancer. The aim of the present study was to investigate whether KAI1 influences pancreatic cancer cell growth and colony formation. A full-length KAI1 cDNA expression vector was stably transfected into Panc-1 and MiaPaCa-2 pancreatic cancer cell lines. Transfection was confirmed by Western blot analysis and immunohistochemistry. Tumor cell growth and cell cycle distribution were determined by MTT cell growth assays, colony formation assays, and flow cytometric analysis. KAI1-transfected, but not control-transfected pancreatic cancer cells displayed cytoplasmic KAI1 immunoreactivity. Cell proliferation decreased in the KAI1-transfected cells compared to parental and control cells together with a Go/G1-phase cell cycle arrest. Colony formation was reduced by 2.6- and 3.5-fold in the KAI1-transfected Panc-1 and MiaPaCa-2 pancreatic cancer cells, respectively, compared with parental cells. KAI1 blocks pancreatic cancer cell growth through cell cycle arrest and inhibits anchorage-independent cell growth. These findings support the premise that KAI1 functions as a tumor suppressor in this malignancy.

Antigens, CD↗
PubMed2004

[The mechanism of KAI1 gene in inhibition of metastasis of primary pancreatic cancer].

OBJECTIVE: To study the effect on invasive and motor ability of MiaPaCa II pancreatic cancer cell transfected by recombinant plasmid pCMV-KAI1, alteration of KAI1 in the transfecting cancer cells, and the metastatic mechanism in the malignancy. METHODS: MiaPaCa II pancreatic cancer cell was transfected with pCMV-KAI1 by liposome, the invasive and gelatinase ability of two pancreatic cancer cell lines were analyzed with transwell culture cell and polyacrylamided gel electrophoresis (PAGE) before and after KAI1 cDNA transfection. RESULTS: After KAI1 cDNA transfected into MiaPaCa II, the migrative ability of passing through the membrane filter decreased evidently (P < 0.05). The width of negative staining band narrowed, the intensity level of tape weakened through PAGE. These results showed that reduced the ability of degrading basement membrane and extra-cell base and metastasis were influenced after MiaPaCa II pancreatic cancer cells were transfected. CONCLUSION: The suppressed invasion and motor function of pancreatic cancer cells seems to influence their metastatic ability and thereby entrances the malignant potential of pancreatic cancer.

Antigens, CD↗