Biomedical subjects

Zhe Li

Publications and source records attributed to Zhe Li.

At least 19 recordsLinked to original sources

PubMed2025

Multi-omics reveals an ecdysone-activated Eip75B-FABP signaling axis coordinating nutrient metabolism for development in Hermetia illucens.

INTRODUCTION: Efficient nutrient storage is essential for insect development and energy homeostasis; however, the mechanisms coordinating nutrient allocation during ontogeny are not well understood. Elucidating these systems may yield valuable insights to insect metabolic adaptation. OBJECTIVES: This study aimed to identify regulatory modules governing nutrient metabolism in insects, focusing on hormonal and metabolic interplay. METHODS: Multi-omics profiling (proteomics, phosphoproteomics, and transcriptomics) was conducted throughout the life cycle, from egg to adult, to identify metabolic regulators. RNAi was utilized for gene knockdown, followed by qRT-PCR and mitochondrial DNA quantification to evaluate knockdown efficiency and its metabolic implications. Assessments of nutrient metabolism were performed using assays for triglycerides, crude protein, and fatty acid synthase. EMSA and BODIPY staining examined transcriptional regulation and lipid droplet dynamics. RESULTS: Utilizing an integrative multi-omics approach, this study elucidates the temporal metabolic regulators in insects. A conserved regulatory module was identified in which the PPAR homolog, ecdysone-induced protein 75B (Eip75B), functions as a transcriptional activator of fatty acid binding protein (FABP), sustaining lipid metabolic homeostasis during the larval stage. PPARγ modulators (rosiglitazone and GW9662) alter lipid accumulation, along with the expression of Eip75B and FABP, which was measured by qRT-PCR. Furthermore, the deficiency of FABP may reprogram metabolic pathways by inhibiting lipid storage and promoting mitochondrial β-oxidation, as supported by increased mitochondrial DNA copy number, as well as enhancing protein synthesis. This metabolic change could be modulated by ecdysone signaling, as hormonal supplementation effectively rescued the lipid loss phenotype. Our results establish the ecdysone-Eip75B-FABP signaling axis as a central regulatory module that integrates hormonal and nutrient-sensing signals to control insect nutritional metabolism. CONCLUSION: The ecdysone-Eip75B-FABP axis integrates hormonal and nutrient signals to regulate metabolic plasticity, underscoring a universal strategy for developmental energy allocation. The data also offer potential implications for research on metabolic disorders and bioenergy applications.

Animals↗

PubMed2025

Sphingobium yanoikuyae 41R9 Enhances Nitrogen Uptake by Modulating Transporter Genes and Root Development in Rapeseed.

Plant growth-promoting rhizobacteria (PGPR) are widely recognized for enhancing the absorption of mineral nutrients by crops. While Sphingobium species have been reported as PGPRs, their capacity to improve nitrogen use efficiency (NUE) and the underlying regulatory mechanisms are not yet fully understood. Here, a strain 41R9, isolated from the rhizosphere of N-deficient rapeseed, was found to significantly enhance the growth performance of rapeseed under both low and normal N conditions. Genomic analysis revealed that strain 41R9 was closely related to Sphingobium yanoikuyae. 15N isotope tracer experiments confirmed that inoculation with strain 41R9 significantly boosted N uptake and translocation in rapeseed roots. Transcriptome profiling demonstrated that strain 41R9 directly upregulated N transporter genes (NRT2.5 and SLAH1/3), facilitating efficient N acquisition. Furthermore, strain 41R9 maintained jasmonic acid (JA) homoeostasis via JAZ-mediated negative feedback, balancing defense responses and root development, thereby improving the plant's N acquisition capacity in the roots. Metabolomic and in vitro assays further demonstrated that strain 41R9 displayed strong chemotaxis towards kaempferol, a N-deficiency-induced root exudate, suggesting kaempferol might as a chemical effector for S. yanoikuyae recruitment. These findings advance our understanding of PGPR-driven mechanisms in enhancing crop NUE and highlight the potential of harnessing PGPRs for sustainable agriculture.

Plant Roots↗

PubMed2006

Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth.

JAK2(V617F), a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The JAK2 mutant displays a much increased kinase activity and generates a PV-like phenotype in mouse bone marrow transplant models. This study shows that the anti-cancer drug erlotinib (Tarceva) is a potent inhibitor of JAK2(V617F) activity. In vitro colony culture assays revealed that erlotinib at micro-molar concentrations effectively suppresses the growth and expansion of PV hematopoietic progenitor cells while having little effect on normal cells. Furthermore, JAK2(V617F)-positive cells from PV patients show greater susceptibility to the inhibitor than their negative counterparts. Similar inhibitory effects were found with the JAK2(V617F)-positive human erythroleukemia HEL cell line. These data suggest that erlotinib may be used for treatment of JAK2(V617F)-positive PV and other myeloproliferative disorders.

Amino Acid Substitution↗

PubMed2006

Statistical inference of chromosomal homology based on gene colinearity and applications to Arabidopsis and rice.

BACKGROUND: The identification of chromosomal homology will shed light on such mysteries of genome evolution as DNA duplication, rearrangement and loss. Several approaches have been developed to detect chromosomal homology based on gene synteny or colinearity. However, the previously reported implementations lack statistical inferences which are essential to reveal actual homologies. RESULTS: In this study, we present a statistical approach to detect homologous chromosomal segments based on gene colinearity. We implement this approach in a software package ColinearScan to detect putative colinear regions using a dynamic programming algorithm. Statistical models are proposed to estimate proper parameter values and evaluate the significance of putative homologous regions. Statistical inference, high computational efficiency and flexibility of input data type are three key features of our approach. CONCLUSION: We apply ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions within each species and homologous fragments between these two species. We find many more homologous chromosomal segments in the rice genome than previously reported. We also find many small colinear segments between rice and Arabidopsis genomes.

Algorithms↗

PubMed2006

A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBFbeta regulation.

The Runt domain is the DNA binding domain of the core binding factor (CBF) Runx subunits. The CBFs are transcription factors that play critical roles in hematopoiesis, bone, and neuron development in mammals. A common non-DNA binding CBFbeta subunit heterodimerizes with the Runt domain of the Runx proteins and allosterically regulates its affinity for DNA. Previous NMR dynamics studies suggested a model whereby CBFbeta allosterically regulates DNA binding by quenching conformational exchange in the Runt domain, particularly in the S-switch region and the betaE'-F loop. We sought to test this model, and to this end introduced all possible single amino acid substitutions into the S-switch region and the betaE'-F loop, and screened for mutations that enhanced DNA-binding. We demonstrate that one Runt domain mutant, R164N, binds both DNA and CBFbeta with higher affinity, but it is less sensitive to allosteric regulation by CBFbeta. Analysis of NMR relaxation data shows that the chemical exchange exhibited by the wild-type Runt domain is largely quenched by the R164N substitution. These data support a model in which the dynamic behavior of a network of residues connecting the CBFbeta and DNA binding sites on the Runt domain plays a critical role in the mechanism of allosteric regulation. This study provides an important functional link between dynamic behavior and protein allosteric function, consistent with results on other allosterically regulated proteins.

Allosteric Regulation↗

PubMed2006

T-lymphoid, megakaryocyte, and granulocyte development are sensitive to decreases in CBFbeta dosage.

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFbeta. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFbeta levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFbeta levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFbeta levels, and were virtually absent when CBFbeta levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4- CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFbeta threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.

Alleles↗

PubMed2006

N,N-dimethyl-beta-alanine as an inexpensive and efficient ligand for palladium-catalyzed Heck reaction.

N,N-Dimethyl-beta-alanine was found to be a more powerful phosphine-free ligand than the previously reported ligand, N,N-dimethylglycine, in the Pd-catalyzed Heck reaction for a variety of aryl bromides, aryl iodides, and activated aryl chlorides with a practical turnover number of 10(3). Both kinetic and theoretical studies suggested that N,N-dimethyl-beta-alanine led to faster oxidative addition of an aryl halide to Pd than N,N-dimethylglycine. [reaction: see text]

Catalysis↗

PubMed2006

Antagonism or synergism. Role of tyrosine phosphatases SHP-1 and SHP-2 in growth factor signaling.

SHP-1 and SHP-2 are two Src homology 2 domain-containing tyrosine phosphatases with major pathological implications in cell growth regulating signaling. They share significant overall sequence identity, but their biological functions are often opposite. SHP-1 is generally considered as a negative signal transducer and SHP-2 as a positive one. However, the precise role of each enzyme in shared signaling pathways is not well defined. In this study, we investigated the interaction of these two enzymes in a single cell system by knocking down their expressions with small interfering RNAs and analyzing the effects on epidermal growth factor signaling. Interestingly, knockdown of either SHP-1 or SHP-2 caused significant reduction in the activation of ERK1/2 but not Akt. Furthermore, SHP-1, SHP-2, and Gab1 formed a signaling complex, and SHP-1 and SHP-2 interact with each other. The interaction of SHP-1 with Gab1 is mediated by SHP-2 because it was abrogated by knockdown of SHP-2, and SHP-2, but not SHP-1, binds directly to tyrosine-phosphorylated Gab1. Together, the data revealed that both SHP-1 and SHP-2 have a positive role in epidermal growth factor-induced ERK1/2 activation and that they act cooperatively rather than antagonistically. The interaction of SHP-1 and SHP-2 may be responsible for previously unexpected novel regulatory mechanism of cell signaling by tyrosine phosphatases.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Nucleotide substitution pattern in rice paralogues: implication for negative correlation between the synonymous substitution rate and codon usage bias.

Understanding the correlation between synonymous substitution rate and GC content is essential to decipher the gene evolution. However, it has been controversial on their relationship. We analyzed the GC content and synonymous substitution rate in 1092 paralogues produced by two large-scale duplication events in the rice genome. According to the GC content at the third codon sites (GC3), the paralogues were classified into GC3-rich and GC3-poor genes. By referring to their outgroup sequences, we inferred the last common ancestor of sister paralogues and, consequently, calculated the average synonymous substitution rate for two gene classes. The results suggest that average synonymous substitution rate is lower in GC3-rich genes than that in GC3-poor genes, indicating that the synonymous substitution rate is negatively correlated with GC content in the rice genome. Through characterizing the synonymous nucleotide substitution pattern, we found a strong synonymous nucleotide substitution frequency bias from AT to GC in GC3-rich genes. This indicates possible limitations of commonly used methods developed to estimate the synonymous substitution rate. Their estimates might produce misleading results on correlation between the synonymous substitution rate and GC content.

Base Composition↗

PubMed2006

Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain.

In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription factor, is expressed in most nociceptors during embryonic development but in adult mice, becomes restricted to nociceptors marked by expression of the neurotrophin receptor Ret. In these neurons, Runx1 regulates the expression of many ion channels and receptors, including TRP class thermal receptors, Na+-gated, ATP-gated, and H+-gated channels, the opioid receptor MOR, and Mrgpr class G protein coupled receptors. Runx1 also controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy.

Analysis of Variance↗

PubMed2006

Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene.

NEU (ERBB2) and other members of the epidermal growth factor receptor (EGFR) family have been implicated in human prostate cancer (CAP) development and progression to an androgen-independent state, but the extent of involvement and precise role of this signaling pathway remain unclear. To begin addressing such open questions in an animal model, we have developed a transgenic line in which an oncogenic Neu cDNA (Neu*) driven by the probasin gene promoter is overexpressed in the mouse prostate and causes development of prostatic intraepithelial neoplasia (PIN) that progresses to invasive carcinoma. Expression profiling using microarrays, which was selectively validated and extended by immunophenotyping of Neu*-induced PIN and CAP, led to the identification of some novel biomarkers and also revealed increased expression of Egfr, Erbb3 and phosphorylated androgen receptor. In view of this information from our mouse model, which can be used to analyze further the role of Erbb signaling in prostatic tumorigenesis, we examined human prostate cancer tissue arrays by immunohistochemistry. Based on statistical analyses of the results, we propose the testable hypothesis that ERBB3, shown to be expressed in 86% of the human CAP cases that we examined, is the pivotal element of the Erbb pathway promoting tumorigenesis by heterodimerization with NEU or EGFR, while a NEU/EGFR dimer does not appear to play a significant role in CAP.

Adenocarcinoma↗

PubMed2006

[Study on pharmacokinetics of PVP coated beta-elemene liposome in rats].

OBJECTIVE: To study the pharmacokinetics of PVP costed beta-elemente liposmes in rats. METHODS: Gas chromatography was established to determine the concentration of beta-elemene in plasma of rats after administered through i.g. RESULTS: The pharmacokinetics parameters was: T(1/2) = 95.07 +/- 20.46 min, AUC = 348.72 +/- 32.49 microg x min/ml, Cmax = 4.39 +/- 0.33 microg/ml, Tmax = 60 min. CONCLUSION: The bioavailability of PVP coated beta-elemene liposomes is 140.2 +/- 7.5% compared with conventional liposomes.

Animals↗

PubMed2006

[Effects of different polishing methods on surface roughness of pure titanium castings].

OBJECTIVE: To evaluate the effects of different polishing methods on surface roughness of pure titanium castings. METHODS: 35 pure titanium castings were devided into 7 groups, used for control, mechanic polishing and electrolytic polishing, respectively. Surface roughness (Ra value) of each castings was measured with a profilometer. Surface microstructure was studied by a scaning electron microscopy, and the weight loss (Wt%) and height loss on unit area (H) before and after polishing was calculated. RESULTS: The effects of mechanic polishing with aluminium oxide or chromium oxide were acceptable. Surface smoothness was improved with acid treatment followed by electrolytic polishing. CONCLUSION: Aluminium oxide and chromium oxide can be used in mechanic polishing of pure titanium castings, and improvement should be made on electrolytic polishing methods.

Aluminum Oxide↗

PubMed2006

[Relationship between sperm motility parameters and sperm morphology].

OBJECTIVE: To evaluate the relationship between sperm motility parameters and sperm morphology. METHODS: Seven hundred and eighty-three semen samples were tested. Sperm motility parameters were analyzed by computer-aided sperm analysis (CASA) , and sperm morphology assessed by automated sperm morphology analyzer (ASMA). The cases were classified based on the World Health Organization criteria. Morphologically 241 of the samples were normal and the other 542 abnormal. RESULTS: VCL, WOB, VAP of the morphologically abnormal group were significantly higher than those of the normal group (P < 0.05, P < 0.001), while MAD, LIN, STR of the abnormal group were significantly lower (P < 0.05, P < 0.001). There were significant positive correlations between the morphologically normal sperm rates and MAD, LIN, WOB, STR, and a significant negative correlation between the morphologically normal sperm rate and ALH. CONCLUSION: Morphological abnormality of sperm is often accompanied with weak motility, which is probably attributed more to some factors that coact on both sperm motility and morphology than to the influence of sperm morphological abnormality on sperm motility.

Adult↗

PubMed2006

[Study of pharyngeal anatomical diameter in patients with obstructive sleep apnea-hypopnea syndrome before and after uvulopalatopharyngoplasty].

OBJECTIVE: To explore the changes of oropharynx in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS) before and after long-term uvulopalatopharyngoplasty with uvula reserved completely. METHOD: Thirty-one patients with OSAHS were studied. The following indexes were measured before and after uvulopalatopharyngoplasty: length of uvula, width of uvula base, distance between two-side pillars (DBTP), distance between uvula and posterior pharyngeal wall(DBUP), length of soft palate, perimeter of neck and body mass index (BMI). RESULT: The postoperative length of uvula, width of uvula base, DBTP, DBUP changed significantly after uvulopalatopharyngoplasty( P <0.05). The postoperative length of soft palate was significantly less than that before uvulopalatopharyngoplasty( P <0.05). There was no significance difference in BMI and perimeter of neck between preoperative and postoperative patients( P >0.05). CONCLUSION: The uvulopalatopharyngoplasty with uvula reserved completely is an effective method to solve the airway constriction, especially the oropharynx constriction. Transverse diameter could be enlarged to the length of normal adults.

Adult↗

PubMed2005

Volume-sensitive outwardly rectifying chloride channels are involved in oxidative stress-induced apoptosis of mesangial cells.

Volume-sensitive outwardly rectifying (VSOR) Cl- channels have been electrophysiologically identified in human and mouse mesangial cells, but the functional role of VSOR Cl- channels in mesangial cell apoptosis is not clear. The aim of the present study was to demonstrate the role of VSOR Cl- channels in oxidative stress-induced mesangial cell apoptosis. H2O2-induced Cl- currents showed phenotypic properties of VSOR Cl- channels, including outward rectification, voltage-dependent inactivation at more positive potentials, sensitivity to hyperosmolarity, and inhibition by VSOR Cl- channel blockers. Moreover, blockage of VSOR Cl- channels by DIDS (100 microM), NPPB (10 microM) or niflumic acid (10 microM) rescued mesangial cell apoptosis induced by H2O2. Treatment with 150 microM H2O2 for 2h resulted in significant reduction of cell volume, in contrast, nuclear condensation and/or fragmentation were not observed and the caspase-3 activity was also not increased. The early-phase alterations in cell volume were markedly abolished by pretreatment with VSOR Cl- channel blockers. We conclude that VSOR Cl- channels are involved in H2O2-induced apoptosis in cultured mesangial cells and its mechanism is associated with apoptotic volume decrease processes.

Apoptosis↗

PubMed2005

Runx1 function in hematopoiesis is required in cells that express Tek.

Runx1 expression marks the putative hemogenic endothelium between embryonic days (E) 8.5 to 11.5 of mouse gestation and is required for the formation of intra-aortic hematopoietic clusters, leading to the hypothesis that Runx1 is required for the transition from endothelial to hematopoietic cell. To address this hypothesis, we ablated the Runx1 gene by Cre-recombinase-mediated excision, with Cre expression under the control of the Tek promoter and enhancer. Most embryos died between E12.5 and E13.5 with a phenotype almost identical to Runx1 deficiency. We conclude that Runx1 function in establishing definitive hematopoiesis is required in a Tek+ cell.

Animals↗

PubMed2005

Induction of immunological tolerance in chickens inoculated with xenogeneic antigens at an early stage of embryonic development.

To induce immunotolerance, laboratory chicken embryos were inoculated with casein via embryonic blood vessel microinjection or with bovine serum albumin (BSA) by either embryonic blood vessel or yolk sac injection. All hatched chickens were challenged with the same protein four times at 10-day intervals beginning at 3 weeks old. Serum anti-casein and anti-BSA antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA). Significantly reduced serum specific antibody, demonstrating immunotolerance, was observed in 53.8% of chickens exposed to casein in embryo by microinjection at 65-70 h of incubation; and in 62.5% (inoculating at 65-67 h of incubation) and 33.33% (inoculating at 67-70 h of incubation) of chickens exposed to BSA. Tolerant chickens presented in those groups inoculated with BSA at 5-7 days of embryogenesis by in ovo injection. The results showed tolerance could be induced by injecting xenogeneic protein into early developing embryo by both inoculation methods.

Animals↗