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Fei Gao

Publications and source records attributed to Fei Gao.

At least 19 recordsLinked to original sources

Transcriptomic characterization of the intestine in Stichopus monotuberculatus under gradient temperature stress and HSP gene family-mediated molecular adaptation.

The increasing frequency of extreme temperature events under climate change poses a growing threat to the stability of tropical sea cucumber aquaculture. To characterize the molecular responses of the tropical sea cucumber Stichopus monotuberculatus to acute temperature stress, juveniles were exposed for 96 h to 15 °C, 20 °C, 25 °C, 30 °C, and 35 °C, followed by transcriptomic profiling of the intestine. By transcriptomic analysis, 2258, 634, 1618, and 2980 differentially expressed genes (DEGs) were identified at 15, 20, 30, and 35 °C compared to control, respectively. More DEGs were generally detected at temperatures further from 25 °C, with the 35 °C group showing the largest transcriptional response. Although cold and heat stress both affected metabolism and protein homeostasis, their enrichment profiles differed. At 15 °C, DEGs were mainly enriched in the spliceosome and p53 signaling pathways, highlighting RNA processing and p53 signaling as prominent features of the cold-stress response. At 35 °C, DEGs were mainly enriched in the PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, and mitophagy, indicating enhanced regulation of cell survival, protein turnover, and mitochondrial quality control. HSP genes also responded differently to cold and heat stress. Most HSP70 and HSP90 family members were downregulated at low temperatures, whereas HSP70 genes and small heat shock proteins were markedly upregulated at high temperatures. Overall, the intestinal transcriptome showed distinct responses to cold and heat stress. These results identify pathways and HSP genes potentially involved in the temperature response of S. monotuberculatus and provide useful information for evaluating temperature tolerance and defining suitable temperatures for its aquaculture.

Heat shock protein↗

Complete telomere-to-telomere genome assembly of Guazuma ulmifolia uncovers evolutionary mechanisms, drought adaptation, and flavonoid biosynthesis.

The first T2T reference genome of Guazuma ulmifolia is reported, which serves as a core genomic resource for stress adaptation research and stress-tolerant breeding in cacao wild relatives. Climate change, particularly increased incidence of drought, poses a major threat to food security. Understanding the genomic basis of environmental adaptation in crop wild relatives can provide valuable resources for improving stress resilience. Guazuma ulmifolia, a wild relative of Theobroma cacao with important ecological and medicinal value, lacks high-quality reference genomic resources. Here, we report the first telomere-to-telomere (T2T) chromosome-level genome assembly of G. ulmifolia, with a genome size of 311.31 Mb, contig N50 of 35.19 Mb, and 98.70% BUSCO completeness. Repetitive sequences constitute 27.43% of the G. ulmifolia genome, with LTR retrotransposons as the predominant class. Comparative genomic analyses revealed that genome-size variation among Malvaceae species is associated with differences in polyploidization history and TE dynamics. Ancestral karyotype reconstruction identified five lineage-specific chromosome fusion events distinguishing G. ulmifolia from T. cacao. Comparative analyses further identified tandem duplication-associated expansion of stress-related LEA and GST gene families, suggesting potential genomic features associated with stress responses. Flavonoid biosynthesis genes were largely conserved in copy number but showed tissue-specific expression patterns, providing candidate genes for investigating secondary metabolism. Together, this study establishes a high-quality T2T genome resource for exploring genome evolution, chromosome organization, and stress-related genomic features in Malvaceae.

Genome, Plant↗

A base editor facilitates simultaneous purine and pyrimidine substitutions for ex vivo and in vivo mutagenesis screens.

Genetic mutations are closely linked to human diseases, yet the relationship between many mutations and their corresponding phenotypes remains poorly understood. Furthermore, tools to study the connection between nucleotide variations and phenotypes are limited. To address this issue, we developed ACGBEmax by fusing the dual-functional deaminase, engineered N-methylpurine DNA glycosylase, and evolved SOS response associated peptidase domain with nCas9(D10A). ACGBEmax enables the precise conversion of A, C, and G to other bases in mammalian cells, thereby generating an extensive range of base mutations types. We used ACGBEmax to generate HPRT variants, identifying mutations conferring resistance to 6-thioguanine. Additionally, we performed in situ mutagenesis of Ctnnb1 in mouse liver, identifying both known and potential oncogenic mutations. Our results prove that ACGBEmax is a powerful tool for generating a wide spectrum of mutation types at specific gene loci, highlighting its significant potential for applications in functional screening and the directed evolution of protein variants.

Animals↗

Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.

Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.

Animals↗

Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma.

Programmed cell death 4 (PDCD4) was recently identified as a novel tumor suppressor gene. The loss of PDCD4 expression was found in several types of human cancer cell lines. To date, however, the status of PDCD4 expression in human glioma tissue is not known. In the present study, the expression of PDCD4 in 30 glioma samples was determined at both mRNA and protein levels by means of RT-PCR, Western blotting, and immunohistochemistry. Herein, we demonstrate, for the first time, that 47% (14/30) of glioma samples lost the expression of PDCD4 mRNA, and 77% (23/30) of glioma samples lacked the PDCD4 protein expression, whereas adjacent normal glial tissues expressed high levels of PDCD4 mRNA and protein. Furthermore, the loss of PDCD4 expression does not significantly correlate with the pathological and clinical features of the glioma. Our new data suggest that the loss of PDCD4 expression is a frequent event in human glioma and may partially contribute to the development of the tumor.

Adult↗

Solid substrate-room temperature phosphorescence method for the determination of trace Mn(II) based on oxidizing reaction of hydrogen peroxide using alpha,alpha'-bipyridine as sensitizer.

A new solid substrate-room temperature phosphorescence (SS-RTP) method for the determination of trace manganese (II) has been established. It bases on the fact that fullerol (R) emits strong and stable room temperature phosphorescence (RTP) on filter paper substrate. H2O2 can oxidize R to cause the SS-RTP quenching. But manganese (II) can obstruct H2O2 to oxidize R, and enhance the RTP of R. alpha,alpha'-Bipyridine (Bipy) can sensitize the RTP. After adding Bipy, the DeltaI(p) enhances 7 times than that without Bipy. Under the optimum conditions, the linear dynamic range of this method is 0.016-1.12 pg spot(-1) with a detection limit (L.D.) of 4.6 fg spot(-1) (m(Mn(2+) is the absolute mass of Mn(2+)), and the regression equation of working curve is DeltaI(p)=25.20 + 63.55 m(Mn(2+) (pg spot(-1)), n=6, r=0.9983. For 0.016 and 1.12 pg spot(-1) Mn(2+), RSDS are 4.3 and 4.8%, respectively (n=7). This method has been applied to the determination of trace manganese (II) in actual sample with high sensitivity and good selection. And the reaction mechanism of SS-RTP is discussed.

2,2'-Dipyridyl↗

Neddylation of a breast cancer-associated protein recruits a class III histone deacetylase that represses NFkappaB-dependent transcription.

Neddylation has an important role in ubiquitin-mediated protein degradation through modification of cullins, which are the main substrates for NEDD8 modification. Here, we show that breast cancer-associated protein 3 (BCA3) is a NEDD8 substrate. BCA3 suppressed NFkappaB-dependent transcription through its ability to bind to p65 and the cyclin D1 promoter in a neddylation-dependent manner. Transcriptional suppression mediated by BCA3 may be attributed to the ability of neddylated BCA3 to recruit SIRT1, a class III histone deacetylase. Silencing of endogenous BCA3 in DU145 and MCF7 cells enhanced NFkappaB transcription and inhibited tumour necrosis factor (TNF)alpha-induced apoptosis. Conversely, BCA3 silencing could be reversed by over-expression of wild-type BCA3 and SENP8, a NEDD8-specific protease, but not by neddylation-deficient BCA3 or a SENP8 mutant. These results provide a crucial link between neddylation and transcriptional regulation by SIRT1, a NAD-dependent histone deacetylase that prolongs life span in yeast and worms.

Adaptor Proteins, Signal Transducing↗

Structural analysis of the regulatory dithiol-containing domain of the chloroplast ATP synthase gamma subunit.

The gamma subunit of the F1 portion of the chloroplast ATP synthase contains a critically placed dithiol that provides a redox switch converting the enzyme from a latent to an active ATPase. The switch prevents depletion of intracellular ATP pools in the dark when photophosphorylation is inactive. The dithiol is located in a special regulatory segment of about 40 amino acids that is absent from the gamma subunits of the eubacterial and mitochondrial enzymes. Site-directed mutagenesis was used to probe the relationship between the structure of the gamma regulatory segment and its function in ATPase regulation via its interaction with the inhibitory epsilon subunit. Mutations were designed using a homology model of the chloroplast gamma subunit based on the analogous structures of the bacterial and mitochondrial homologues. The mutations included (a) substituting both of the disulfide-forming cysteines (Cys199 and Cys205) for alanines, (b) deleting nine residues containing the dithiol, (c) deleting the region distal to the dithiol (residues 224-240), and (d) deleting the entire segment between residues 196 and 241 with the exception of a small spacer element, and (e) deleting pieces from a small loop segment predicted by the model to interact with the dithiol domain. Deletions within the dithiol domain and within parts of the loop segment resulted in loss of redox control of the ATPase activity of the F1 enzyme. Deleting the distal segment, the whole regulatory domain, or parts of the loop segment had the additional effect of reducing the maximum extent of inhibition obtained upon adding the epsilon subunit but did not abolish epsilon binding. The results suggest a mechanism by which the gamma and epsilon subunits interact with each other to induce the latent state of the enzyme.

Alanine↗

The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis.

Mutation of the transcription factor and tumor suppressor gene WT1 results in a range of genitourinary anomalies in humans, including 46,XY gonadal dysgenesis, indicating that WT1 plays a critical role in sex determination. However, because knockout of Wt1 in mice results in apoptosis of the genital ridge, it is unknown whether WT1 is required for testis development after the initial steps of sex determination. To address this question, we generated a mouse strain carrying a Wt1 conditional knockout allele and ablated Wt1 function specifically in Sertoli cells by embryonic day 14.5, several days after testis determination. Wt1 knockout resulted in disruption of developing seminiferous tubules and subsequent progressive loss of Sertoli cells and germ cells such that postnatal mutant testes were almost completely devoid of these cell types and were severely hypoplastic. Thus, Wt1 is essential for the maintenance of Sertoli cells and seminiferous tubules in the developing testes. Of particular note, expression of the testis-determining gene Sox9 in mutant Sertoli cells was turned off at embryonic day 14.5 after Wt1 ablation, suggesting that WT1 regulates Sox9, either directly or indirectly, after Sry expression ceases. Our data, along with previous work demonstrating the role of Wt1 at early stages of gonadal development, thus indicate that Wt1 is essential at multiple steps in testicular development.

Alleles↗

[Cytokine-induced killer cell fusion to lower recurrence of hepatocellular carcinoma after transcatheter arterial chemoembolization sequentially combined with radiofrequency ablation: a randomized trial].

OBJECTIVE: To ed evaluate the clinical effects of autologous cytokine-induced killer cell (CIK) fusion to lower recurrence of primary hepatocellular carcinoma (HCC) and the anti-hepatitis B virus (HBV) effect after transcatheter arterial chemoembolization (TACE) sequentially combined with radiofrequency ablation (RFA). METHODS: Sixty-four HCC patients underwent TACE sequentially combined with RFA without residual tumor or extrahepatic metastasis were randomly divided into 2 groups: study group (n = 33), receiving autologous CIK fusion of the dose of (1.1 - 1.5) x 10(10) via the peripheral vein or hepatic artery, firstly once every 3 - 4 weeks for 4 times, and then once every 4 weeks for 4 times; and control group (n = 31). All patients were followed up for 1 year. RESULTS: In the study group, 29 patients (29/33) were recurrence-free during the 1 year follow-up, 3 had recurrence in the liver 5, 6, and 7 months later respectively, and 1 patient had lymphoadenopathy in the hepatic portal 9 months later. In the control group, 23 patients (68.01%) were recurrence-free, 7 had recurrence in the liver within 1 year, and 1 had lung metastasis 11 months later. In the study group, the number of the patients with the HBV DNA content < 1 x 10(3) before treatment was 19, and increased to 29 after the treatment; 2 of the 19 patients who were HBsAg positive before the treatment became HBsAg negative after the treatment, and number of the patients with the HBV DNA content of 10(3) - 10(4) was 3 before the treatment, and became 13 after the treatment among which 1 patient had his HBV DNA content dropping from 1.6 x 10(7) to 1.6 x 10(4). In the control group, only 1 patient showed his HBV DNA content dropping from 1.1 x 10(5) to below 10(3). CONCLUSION: Capable of reducing recurrence, prolonging the recurrence-free span, and attacking HBV, autologous CIK fusion after TACE sequentially combined with RFA is an effective novel therapeutic strategy for HCC.

Adult↗

Separation of hydrophobic solutes by organic-solvent-based micellar electrokinetic chromatography using cation surfactants.

In this study, the separation of 13 homologous stick-like hydrophobic solutes, i.e., biphenyl nitrile derivatives, by organic-solvent-based micellar electrokinetic chromatography (MEKC) was investigated in terms of separation medium composition, species and concentration of surfactant, other additives, separation voltage and temperature. The results showed that the 13 strong hydrophobic compounds were baseline separated in 25 min with a repeatability of less than 1.3% (RSD) for migration time. The separation medium was a mixture of methanol, 2-propanol and water (58.5:10:31.5), containing 150 mM cetyltrimethylammonium bromide (CTAB) and 20 mM sodium borate. Variety of solvent composition, temperature and applied voltage all showed remarkable effect on the separation. The organic-solvent-based MEKC method proved to be superior to the aqueous MEKC and microemulsion electrokinetic chromatography (MEEKC) methods for the separation of strongly hydrophobic compounds.

Cations↗

Mycoplasma fermentans and TNF-beta interact to amplify immune-modulating cytokines in human lung fibroblasts.

Mycoplasma can establish latent infections and are associated with arthritis, leukemia, and chronic lung disease. We developed an experimental model in which lung cells are deliberately infected with Mycoplasma fermentans. Human lung fibroblasts (HLF) were exposed to live M. fermentans and immune-modulating cytokine release was assessed with and without known inducers of cytokine production. M. fermentans increased IL-6, IL-8/CXCL8, MCP-1/CCL2, and Gro-alpha/CXCL1 production. M. fermentans interacted with TNF-beta to release more IL-6, CXCL8, and CXCL1 than predicted by the responses to either stimulus alone. The effects of live infection were recapitulated by exposure to M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a Toll-like receptor-2- and receptor-6-specific ligand. The synergistic effect of combined stimuli was more pronounced with prolonged incubations. Preexposure to TNF-beta sensitized the cells to subsequent MALP-2 challenge, but preexposure to MALP-2 did not alter the IL-6 response to TNF-beta. Exposure to M. fermentans or MALP-2 did not enhance nuclear localization, DNA binding, or transcriptional activity of NF-kappaB and did not modulate early NF-kappaB activation in response to TNF-beta. Application of specific inhibitors of various MAPKs suggested that p38 and JNK/stress-activated protein kinase were involved in early IL-6 release after exposure to TNF-beta and M. fermentans, respectively. The combined response to M. fermentans and TNF-beta, however, was uniquely sensitive to delayed application of SP-600125, suggesting that JNK/stress-activated protein kinase contributes to the amplification of IL-6 release. Thus M. fermentans interacts with stimuli such as TNF-beta to amplify lung cell production of immune-modulating cytokines. The mechanisms accounting for this interaction can now be dissected with the use of this in vitro model.

Cells, Cultured↗

Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity.

PURPOSE: Tobacco smoke is a definite causative agent for lung cancer. It is increasingly being recognized that never-smokers can be afflicted with non-small-cell lung cancer (NSCLC). We aim to assess survival differences between smokers and never-smokers with NSCLC. PATIENTS AND METHODS: We analyzed 975 NSCLC patients who presented from January 1999 to December 2002. Clinical characteristics among current-, former- and never-smokers were tested using chi2 or Kruskal-Wallis test. The hazard ratio (HR) for death and its 95% CI were calculated by Cox regression. RESULTS: Of 975 patients, 59 had no smoking history and 33 had no quit time recorded. Of 883 patients analyzed, 286 patients (32.4%) were never-smokers. One hundred ninety-six never-smokers (68.5%) were females compared with 12% among current- and 13% among former-smokers (P < .001). There was a significant difference in histologic subtype between never-smokers and smokers: 69.9% with adenocarcinoma versus 39.9% (current-smokers) versus 47.3% (former-smokers); 5.9% with squamous cell carcinoma versus 35.7% (current-smokers) versus 28% (former-smokers; P < .001). Smokers had significantly poorer performance status (P = .002) and higher median age at diagnosis (P < .001) while more never-smokers presented with advanced disease (P = .002). Eight hundred and five patients (82.6%) died by May 30, 2005. The HR for smokers was significantly higher on both univariate and multivariate analysis (HR, 1.297; 95% CI, 1.040 to 1.619). CONCLUSION: Never-smokers comprised a high proportion of NSCLC patients in Singapore. Definite epidemiologic differences exist between never-smokers and smokers. Differences in survival outcome further suggest that the biology underlying the pathogenesis and behavior of the disease may be different for never-smokers.

Adenocarcinoma↗

On the application of the von Mises distribution and angular regression methods to investigate the seasonality of disease onset.

This paper describes an approach to summarize the data arising from studies investigating the pattern of disease onset within a calendar year. Such data have been traditionally summarized into monthly counts summated over the complete years studied and patterns often examined by use of Pearson's chi(2) tests with 11 degrees of freedom. This test and others commonly used in practice are reviewed. As an alternative, we suggest that by first representing the date of onset for an individual as a point on a unit circle that the von Mises distribution with a single peak may provide a useful description of such data. Further an extension to angular regression including covariates, analogous to that used routinely in other areas of clinical research, potentially allows a more systematic and detailed investigation of possible seasonal patterns in patient subgroups. The methodology is applied to examples from the date of onset of primary angle-closure glaucoma and date of diagnosis of acute lymphoblastic leukaemia and examines in both situations how the peak onset varies with covariates. Difficulties associated with convergence to the maximum likelihood estimates of the associated parameters are described. Finally, we emphasize the need for individualized (rather than grouped) patient data to be available for study, a clear specification of the particular 'onset' time studied, and suggest that further case studies are required to evaluate the approach.

Adult↗

Analysis of phospholipid species in rat peritoneal surface layer by liquid chromatography/electrospray ionization ion-trap mass spectrometry.

The main phospholipids in rat peritoneal surface layer were analyzed by normal-phase high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) ion-trap mass spectrometry (MS). By using a silica gel column and a gradient of hexane/isopropanol/water as mobile phase containing 5 mmol/L ammonium formate as modifiers, a baseline separation of glycerophosphoehtanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC), sphingomyelin (SM) and lyso-phosphatidylcholine (LPC) was obtained and more than 90 phospholipid constituents in rat peritoneal surface were identified and determined by on-line ion-trap MS detection. The major ethanolamine glycerophospholipids in rat peritoneal surfaces were plasmalogens that were highly enriched in polyunsaturated fatty acids at the sn-2 position. In addition, the fragmentation patterns for each phospholipid class by the ion-trap MS were discussed.

Animals↗

Solid pseudopapillary tumor of the pancreas: report of 8 cases in a single institution and review of the Chinese literature.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare disease with a low-grade malignant potential. In recent years, the incidence has been increasing. No consensus has been reached regarding diagnostic or therapeutic strategies. METHODS: Eight cases of SPTP, admitted from 1996 to March 2005, were analyzed retrospectively, and all the literature concerning SPTP published in Chinese medical journals from January 1994 to March 2005 were analyzed. RESULTS: A total of 186 cases have been reported since 1995, among which 162 were females (87.1%), with a male to female ratio of 1:6.8. A histogram of the ages at onset illustrated an approximately smooth skewed distribution with a single peak, which was located between 10 and 19 years. The number of diseases located at the pancreatic head is similar to that located at the body and the tail. Malignancy was pathologically diagnosed in 22 cases (11.6%). Major clinical presentations included abdominal pain of varying degree (43.5%) and palpable abdominal masses (37.1%). Treatment strategies include different types of resection, ranging from tumor enucleation to multiple organ resection, and the prognosis is generally good. CONCLUSIONS: SPTP occurs predominantly in adolescent and young females, and a satisfactory effect could be achieved with active and appropriate surgeries.

Adolescent↗

Separation of phospholipids by capillary zone electrophoresis with indirect ultraviolet detection.

A simple method for separation of different anionic and zwitterionic phospholipid classes by capillary zone electrophoresis (CZE), using indirect UV detection with adenosine monophosphate (AMP) as background electrolyte and the UV-absorbing additive, was successfully developed in this study. The separation conditions including apparent pH (pH*) of running buffer, concentration of AMP, organic solvent, applied voltage and capillary temperature were systematically optimized. The application of this method to human blood sample was also briefly examined.

Adenosine Monophosphate↗

Cancer patients' preferences for communication of unfavourable news: an Asian perspective.

It is important to understand cancer patients' preferences for communication as it impacts on how unfavourable news should be delivered in such a way as not to demoralize the patients while at the same time maintain good doctor-patient relationships. However, few studies have been undertaken in the Asian countries. This study aims to determine the preferences of cancer patients regarding the disclosure of unfavourable news in an Asian population in Singapore. Two hundred cancer patients at the National Cancer Centre, Singapore, completed a Measure of Patients' Preferences (MPP) questionnaire on how they would like their physicians to tell them unfavourable news about their condition. The patients rated the content and context of the communication as well as the physicians' characteristics on a five-point Likert scale. Items that scored the highest mostly related to physicians' expertise and content of the interaction, while those relating to the supportive aspects scored the lowest. Gender was significantly associated with scores on the support subscale of the MPP such that women reported that the supportive elements were more important than the men did. No other demographic and medical characteristics were associated with patients' preferences. Exploratory factor analysis yielded two main factors, which accounted for 79.38% of the common variance. Patients' preferences in our local Asian population are fairly similar to those obtained from other studies conducted in the West, despite possible socio-cultural differences such as the use of euphemisms.

Adult↗