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Fan Wu

Publications and source records attributed to Fan Wu.

At least 19 recordsLinked to original sources
PubMed2026

Furmonertinib inhibits non-small cell lung cancer progression through ANGPT1-mediated regulation of cell migration and apoptosis.

BACKGROUND: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for effective therapeutic agents. This study investigates the antitumor effects and underlying mechanisms of furmonertinib (FUR) in lung cancer cells. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to identify FUR target genes, followed by functional enrichment, survival, and protein-protein interaction (PPI) network analyses. Human lung cancer cell line A549 was treated with FUR and/or ANGPT1-specific siRNA. Cell migration, apoptosis, and protein expression were assessed by wound healing, flow cytometry, and Western blotting. Cellular thermal shift assay (CETSA) and drug affinity response target stability (DARTS) assays were used to assess FUR-induced stabilization of angiopoietin-1 (ANGPT1) protein. RESULTS: FUR treatment significantly inhibited cell migration and increased apoptosis in NSCLC cells. Bioinformatics analysis revealed 12 overlapping target genes of FUR from the PharmMapper and SwissTargetPrediction databases, with ANGPT1 emerging as a key candidate. ANGPT1 expression was downregulated in tumor tissues and positively correlated with patient survival. Western blotting confirmed that FUR upregulated ANGPT1 protein levels in a dose-dependent manner. Knockdown of ANGPT1 enhanced migration and suppressed apoptosis, while FUR reversed these effects. FUR treatment enhanced the stability of ANGPT1 under high-temperature conditions while reducing its sensitivity to protease. ANGPT1 may have affected tumor cell migration through cell adhesion and extracellular matrix (ECM) pathways. CONCLUSIONS: FUR suppresses lung cancer progression by upregulating ANGPT1, thereby inhibiting cell migration and promoting apoptosis. ANGPT1 is a potential therapeutic target and provides new insights into the anti-tumor mechanism of FUR in lung cancer.

Lung cancer↗
PubMed2026

Multiomics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma With Enhanced Benefit From Adjuvant Therapy.

Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous liver cancer with a poor prognosis. Improved stratification is needed to guide postoperative therapy. In this study, we applied integrative multiomics analysis to classify iCCA and identify biomarkers predictive of adjuvant treatment benefit. Using publicly available datasets (including whole exome sequencing, RNA sequencing, proteomics, and phosphoproteomics from FU-iCCA cohort and a transcriptomic cohort GSE244807), we defined 3 robust molecular subtypes of iCCA. These subtypes exhibited distinct genomic alterations, pathway activation, and immune microenvironments, with significant differences in overall survival (OS). Through protein-protein interaction network analysis and consensus feature selection using 10 clustering algorithms, we prioritized 8 marker genes distinguishing the subtypes. A Cox proportional-hazards model constructed from these markers stratified patients into high- and low-risk groups. High-risk iCCA, characterized by elevated expression of markers such as CLDN18, MUC1, and MUC5AC, had significantly worse OS in the absence of adjuvant therapy. Notably, in an independent validation of 174 patients with iCCA who underwent resection (single-center cohort), high expression of any of these 3 markers were associated with markedly prolonged OS in patients who received adjuvant chemotherapy or chemoembolization, compared with those who did not. In contrast, marker-negative patients showed no clear benefit from adjuvant therapy. In conclusion, our multiomics approach identified a high-risk, mucin-enriched subtype of iCCA. CLDN18, MUC1, and MUC5AC emerge as candidate predictive biomarkers for adjuvant chemotherapy benefit in iCCA, warranting prospective validation to improve personalized postoperative management.

Humans↗
PubMed2026

Natural variation in Miniature5 determines mitochondrial nad1 splicing and seed development in maize.

Seed size is a key determinant of cereal grain yield, but natural variations in defective-kernel genes have rarely been applied in maize breeding. Here, we report the positional cloning of maize Miniature5 (Mn5), which encodes a mitochondrial-targeted P-class pentatricopeptide repeat (PPR) protein. Further analysis shows that a missense mutation of Mn5, Mn5Val109, presents in maize populations and correlates with reduced seed size. The Mn5Val109 variant exhibits compromised function in the miniature5 (mn5-ref) mutant, failing to trans-splice mitochondrial nad1 intron1, drastically reducing the abundance and activity of respiratory complex I, accompanied by disorganized mitochondrial cristae. Mn5 directly binds to domain IV of the pre-nad1.1 transcript. Notably, this binding site is located downstream of the previously presumed 3'-terminus bound by MITOCHONDRIA STABILITY/PROCESSING PPR FACTOR1 (MSP1), thus redefining the 3'-end of the nad1.1 pre-RNA. Furthermore, Mn5 physically interacts with the maturases ZmnMAT1 and ZmnMAT3, as well as the PPR proteins PPR-SMR1 and SPR2, which are broadly involved in organellar group II intron splicing. Together, our results suggest that Mn5 recruits maturases and PPR proteins to form spliceosomal complexes responsible for the trans-splicing of nad1 intron1. Importantly, natural variations in Mn5 confer differences in seed size control, offering potential for breeding high-yield maize varieties.

Zea mays↗
PubMed2024

The genome of Lespedeza potaninii reveals biased subgenome evolution and drought adaptation.

Lespedeza potaninii, a xerophytic subshrub belonging to the legume family, is native to the Tengger Desert and is highly adapted to drought. It has important ecological value due to its drought adaptability, but the underlying molecular mechanisms remain largely unknown. Here, we report a 1.24 Gb chromosome-scale assembly of the L. potaninii genome (contig N50 = 15.75 Mb). Our results indicate that L. potaninii underwent an allopolyploid event with 2 subgenomes, A and B, presenting asymmetric evolution and B subgenome dominance. We estimate that the 2 diploid progenitors of L. potaninii diverged around 3.6 million years ago (MYA) and merged around 1.0 MYA. We revealed that the expansion of hub genes associated with drought responses, such as the binding partner 1 of accelerated cell death 11 (ACD11) (BPA1), facilitated environmental adaptations of L. potaninii to desert habitats. We found a novel function of the BPA1 family in abiotic stress tolerance in addition to the known role in regulating the plant immune response, which could improve drought tolerance by positively regulating reactive oxygen species homeostasis in plants. We revealed that bZIP transcription factors could bind to the BPA1 promoter and activate its transcription. Our work fills the genomic data gap in the Lespedeza genus and the tribe Desmodieae, which should provide theoretical support both in the study of drought tolerance and in the molecular breeding of legume crops.

Genome, Plant↗
PubMed2006

Comparison of annular wavefront interpretation with Zernike circle polynomials and annular polynomials.

A general wavefront fitting procedure with Zernike annular polynomials for circular and annular pupils is proposed. For interferometric data of typical annular wavefronts with smaller and larger obscuration ratios, the results fitted with Zernike annular polynomials are compared with those of Zernike circle polynomials. Data are provided demonstrating that the annular wavefront expressed with Zernike annular polynomials is more accurate and meaningful for the decomposition of aberrations, the calculation of Seidel aberrations, and the removal of misalignments in interferometry. The primary limitations of current interferogram reduction software with Zernike circle polynomials in analyzing wavefronts of annular pupils are further illustrated, and some reasonable explanations are provided. It is suggested that the use of orthogonal basis functions on the pupils of the wavefronts analyzed is more appropriate.

Journal Article↗
PubMed2006

Preparation of hemoglobin-loaded nano-sized particles with porous structure as oxygen carriers.

Hb (hemoglobin)-loaded particles (HbP) encapsulated by a biodegradable polymer used as oxygen carrier were prepared. A modified double emulsion and solvent diffusion/evaporation method was adopted. All experiments were performed based on two types of biodegradable polymers, poly(epsilon-caprolactone) (PCL) and poly(epsilon-caprolactone-ethylene glycol) (PCL-PEG). The biodistribution and the survival time in blood of the particles were investigated in a mouse model. Encapsulation efficiency and pore-connecting efficiency were evaluated by a novel sulfocyanate potassium method. The influence of process parameters on the particle size and pore-connecting efficiency (PCE%) of nanoparticles have been discussed. The prepared conditions: solvent, external aqueous phase, pressure were discussed. The system utilizing dichloromethane (DCM)/ethyl acetate (EA) as a solvent with an unsaturated external aqueous phase yielded the highest encapsulation efficiency (87.35%) with a small mean particle size (153 nm). The formation of porous channels was attributed to the diffusion of solvent. The PCE% was more sensitive to the rate of solvent diffusion that was obviously affected by the preparation temperature. The PCE% reached 87.47% when PCL-PEG was employed at 25 degrees C. P(50) of HbP was 27 mmHg, which does not seem to be greatly affected by the encapsulation procedure. In vivo, following intravenous injection of 6-coumarin labeled HbP, the major organ accumulating Hb-loaded particles was the liver. The half-life of nano-sized PCL HbP was 3.1 times as long as the micro-sized PCL HbP. Also, Nano-sized as well as a PEGylated surface on HbP is beneficial for prolonged blood residence (7.2 fold increase).

Animals↗
PubMed2006

Increased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma.

PURPOSE: Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. EXPERIMENTAL DESIGN: Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. RESULTS: Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001). CONCLUSIONS: WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.

Adolescent↗
PubMed2006

Oxidative ATP synthesis in skeletal muscle is controlled by substrate feedback.

Data from (31)P-nuclear magnetic resonance spectroscopy of human forearm flexor muscle were analyzed based on a previously developed model of mitochondrial oxidative phosphorylation (PLoS Comp Bio 1: e36, 2005) to test the hypothesis that substrate level (concentrations of ADP and inorganic phosphate) represents the primary signal governing the rate of mitochondrial ATP synthesis and maintaining the cellular ATP hydrolysis potential in skeletal muscle. Model-based predictions of cytoplasmic concentrations of phosphate metabolites (ATP, ADP, and P(i)) matched data obtained from 20 healthy volunteers and indicated that as work rate is varied from rest to submaximal exercise commensurate increases in the rate of mitochondrial ATP synthesis are effected by changes in concentrations of available ADP and P(i). Additional data from patients with a defect of complex I of the respiratory chain and a patient with a deficiency in the mitochondrial adenine nucleotide translocase were also predicted the by the model by making the appropriate adjustments to the activities of the affected proteins associates with the defects, providing both further validation of the biophysical model of the control of oxidative phosphorylation and insight into the impact of these diseases on the ability of the cell to maintain its energetic state.

Adenosine Triphosphate↗
PubMed2006

Full-aperture wavefront reconstruction from annular subaperture interferometric data by use of Zernike annular polynomials and a matrix method for testing large aspheric surfaces.

We propose a more accurate and efficient reconstruction method used in testing large aspheric surfaces with annular subaperture interferometry. By the introduction of the Zernike annular polynomials that are orthogonal over the annular region, the method proposed here eliminates the coupling problem in the earlier reconstruction algorithm based on Zernike circle polynomials. Because of the complexity of recurrence definition of Zernike annular polynomials, a general symbol representation of that in a computing program is established. The program implementation for the method is provided in detail. The performance of the reconstruction algorithm is evaluated in some pertinent cases, such as different random noise levels, different subaperture configurations, and misalignments.

Journal Article↗
PubMed2006

[Clinical study of repair the defect of immediate implant by acellular dermal matrix].

OBJECTIVE: To evaluate the clinical effect of acellular dermal matrix allograft in repairing the oral mucosal defect of immediate implant. METHODS: 51 cases underwent immediate implant surgery for 67 implants right after the teeth or roots extracted. The mucosal defect of implant areas were repaired by acellular dermal matrix. The basal membrane side of acellular dermal matrix was exposed to oral cavity, and another side was attached to the implant and alveolar crest surface. It was intercalated between mucosal flap and alveolar and fixed by iodoform pack or base plate. To understand condition of wound healing the patients were followed up from 4 months to 6 months after operation. The acellular dermal matrix closed wound and histological changes were observed. The implant was followed up months to 4 years. RESULTS: The wounds were completely healed in 54 implant areas, partially healed in 11 implant areas, not healed 2 implant areas. histological examination wasn't differentiation between mucous epithelium and graft epithelium. None of 67 implants showed deterioration in the follow-up of one year. It was no obvious sign of immune rejection. CONCLUSION: The clinical result of acellular dermal matrix in repair the mucosal defect of immediate implant is good, the advantages are not to affect the integration bone with implant, less operation trauma, good esthetics results.

Adolescent↗
PubMed2005

Preventing chronic diseases in China.

Chronic diseases now account for an estimated 80% of deaths and 70% of disability-adjusted life-years lost in China. Cardiovascular diseases and cancer are the leading causes of both death and the burden of disease, and exposure to risk factors is high: more than 300 million men smoke cigarettes and 160 million adults are hypertensive, most of whom are not being treated. An obesity epidemic is imminent, with more than 20% of children aged 7-17 years in big cities now overweight or obese. The government of the People's Republic of China must confront these major challenges. The national cancer prevention and control plan (2004-10) is being implemented, and a national chronic disease prevention and control plan is due to be completed this year. Encouraging progress has been made in some areas, with current smoking prevalence in men declining at about 1% per year for a decade, and even better results in large demonstration programmes. Much remains to be done, and resources and sustainability are major issues. However, the surveillance and intervention mechanisms needed to ameliorate the increasing burden of chronic diseases are developing rapidly, taking account of the lessons learned over the past two decades.

Adolescent↗
PubMed2005

Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro.

AIM: To study the protective effect of non-mitogenic human acidic fibroblast growth factor (FGF) on cardiac oxidative injury in vivo. METHODS: Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco's minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37 degrees, as well as assessed by immunocytochemical assay. We constructed the cardiomyocyte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase (SOD) activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS: Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to the toxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION: Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.

Animals↗
PubMed2005

Regulation of CFTR channels by HCO(3)--sensitive soluble adenylyl cyclase in human airway epithelial cells.

CFTR channels conduct HCO(3)(-) in addition to Cl(-) in airway epithelial cells. A defective HCO(3)(-)-transporting function of CFTR may underlie the pathogenesis of cystic fibrosis. In the present study, we have investigated whether a HCO(3)(-)-sensitive soluble adenylyl cyclase (sAC) is functionally coupled with CFTR and thus forms an autoregulatory mechanism for HCO(3)(-) transport in human airway epithelial Calu-3 cells. A reverse transcriptase-polymerase chain reaction showed that transcripts of both full-length and truncated sACs are present in Calu-3 cells. Truncated sAC protein is the predominant, if not the only, isoform expressed in Calu-3 cells. HCO(3)(-) stimulated a modest increase in cAMP production, and the increase was sensitive to 2-hydroxyestradiol (2-HE), a sAC inhibitor, but not to SQ22,536, a blocker of conventional transmembrane adenylyl cyclases. These results suggest that sAC is functional in Calu-3 cells. Adding 25 mM HCO(3)(-) to the bath stimulated CFTR-mediated whole cell currents in the absence, but not in the presence, of 2-HE. In cell-attached membrane patches, 25 or 50 mM HCO(3)(-) in the bath markedly increased the product of channel number and open probability of CFTR, and this activation was attenuated by 2-HE. These findings demonstrate that sAC signaling pathway is involved in the regulation of CFTR function in human airway epithelium and thereby provides a link between the level of intracellular HCO(3)(-)/CO(2) and the modulation of HCO(3)(-)-conductive CFTR function by cAMP/PKA.

Adenylyl Cyclase Inhibitors↗
PubMed2005

Readily available sulfamide-amine alcohols for enantioselective phenylacetylene addition to aldehydes in the absence of Ti(O(i)Pr)4.

Ephedrine-derived sulfamide-amine alcohol 3 was found to be an effective catalyst for the asymmetric phenylacetylene addition to aldehydes at room temperature without using Ti(O(i)Pr)4 and Zn(OTf)2. It afforded the propargylic alcohols in high yields (up to 99%) and good enantioselectivities (up to 84% ee), which were much higher than that based on N-methylephedrine under the same reaction conditions. Its weakly coordinative sulfonamide moiety of the ligand plays an important role for further acceleration and stereocontrol in the alkynylation.

Acetylene↗
PubMed2005

Variations of very low-density lipoprotein receptor subtype expression in gastrointestinal adenocarcinoma cells with various differentiations.

AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiations. METHODS: Thirty-one cases of gastroenteric carcinoma/adjacent normal tissues were enrolled in the study, which were diagnosed and classified by the clinicopathological diagnosis. The expression of VLDLR subtypes was detected in gastroenteric carcinoma/adjacent normal tissues and three various differentiated human gastric adenocarcinoma cell lines (MKN28, SGC7901 and MKN45) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. RESULTS: Two VLDLR subtypes, namely, type II VLDLR and type I VLDLR, were found to express changes in gastroenteric carcinoma tissues, their adjacent normal tissue, and gastric adenocarcinoma cell lines as well. Type II VLDLR is predominantly expressed in poorly- or moderately-differentiated gastroenteric carcinoma tissues and gastric adenocarcinoma cell lines, whereas type I VLDLR is mainly detected in well-differentiated intestinal carcinoma tissues and gastric adenocarcinoma cells compared with the adjacent normal tissues. CONCLUSION: The results suggested that the variations of the VLDLR subtype expression might be correlated with the progress and differentiation of gastroenteric carcinoma.

Adenocarcinoma↗
PubMed2005

Acrylonitrile insertion reactions of cationic palladium alkyl complexes.

The reactions of acrylonitrile (AN) with "L(2)PdMe+" species were investigated; (L(2) = CH(2)(N-Me-imidazol-2-yl)(2) (a, bim), (p-tolyl)(3)CCH(N-Me-imidazol-2-yl)(2) (b, Tbim), CH(2)(5-Me-2-pyridyl)(2) (c, CH(2)py'(2)), 4,4'-Me(2)-2,2'-bipyridine (d), 4,4'-(t)Bu(2)-2,2'-bipyridine (e), (2,6-(i)Pr(2)-C(6)H(3))N=CMeCMe=N(2,6-(i)Pr(2)-C(6)H(3)) (f)). [L(2)PdMe(NMe(2)Ph)][B(C(6)F(5))(4)] (2a-c) and [{L(2)PdMe}(2)(mu-Cl)][B(C(6)F(5))(4)] (2d-f) react with AN to form N-bound adducts L(2)Pd(Me)(NCCH=CH(2))(+) (3a-f). 3a-e undergo 2,1 insertion to yield L(2)Pd{CH(CN)Et}+, which form aggregates [L(2)Pd{CH(CN)Et}](n)(n)(+) (n = 1-3, 4a-e) in which the Pd units are proposed to be linked by PdCHEtCN- - -Pd bridges. 3f does not insert AN at 23 degrees C. 4a-e were characterized by NMR, ESI-MS, IR and derivatization to L(2)Pd{CH(CN)Et}(PR(3))+ (R = Ph (5a-e), Me (6a-c)). 4a,b react with CO to form L(2)Pd{CH(CN)Et}(CO)+ (7a,b). 7a reacts with CO by slow reversible insertion to yield (bim)Pd{C(=O)CH(CN)Et}(CO)+ (8a). 4a-e do not react with ethylene. (Tbim)PdMe+ coordinates AN more weakly than ethylene, and AN insertion of 3b is slower than ethylene insertion of (Tbim)Pd(Me)(CH(2)=CH(2))(+) (10b). These results show that most important obstacles to insertion polymerization or copolymerization of AN using L(2)PdR+ catalysts are the tendency of L(2)Pd{CH(CN)CH(2)R}+ species to aggregate, which competes with monomer coordination, and the low insertion reactivity of L(2)Pd{CH(CN)CH(2)R}(substrate)+ species.

Journal Article↗
PubMed2005

Effects of oxidized low density lipoprotein on the expression and function of ABCA1 in macrophages.

In the present study, we examined the regulation of the expression and function of ABCA1 by modified LDL (ox-LDL) in vitro. After incubation with apoA-I for 24 h, RAW264.7 cells effluxed 37.65% cholesterol loaded by acetyl LDL (ac-LDL), and 9.78% cholesterol in ox-LDL group. The level of ABCA1 mRNA increased about three times either when cells were incubated with -100 microg /mL ac-LDL or with 100 microg /mL ox-LDL. However, the level of ABCA1 protein rose by 1.57 times in ac-LDL group and 1.26 times in ox-LDL group. These results demonstrated that ox-LDL had different effect on the expression and function of ABCA1, ox-LDL might decrease the cholesterol efflux mediated by ABCA1 through other unknown mechanisms.

ATP Binding Cassette Transporter 1↗