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Ye Zhang

Publications and source records attributed to Ye Zhang.

At least 19 recordsLinked to original sources

From detection to action: ctDNA-MRD surveillance and translational strategies in early breast cancer.

Recurrence remains a major cause of mortality in early breast cancer (EBC), and conventional follow-up often identifies relapse only after clinically detectable disease has emerged. Circulating tumor DNA-based minimal residual disease (ctDNA-MRD) testing offers the possibility of detecting molecular relapse earlier and refining recurrence-risk assessment during follow-up. This narrative review examines the evolving role of ctDNA-MRD in EBC, focusing on assay interpretation, longitudinal surveillance, MRD-guided trial design, and clinical implementation. Prospective studies consistently show that postoperative or surveillance ctDNA positivity is associated with an increased risk of recurrence. However, test performance and interpretation vary with assay characteristics and sampling strategies, and whether treatment initiated solely on the basis of MRD positivity can improve patient outcomes remains unresolved. The central challenge is no longer simply to detect residual disease earlier, but to determine when and how that information should influence care. Further prospective validation, assay standardization, clear pathways for uncertain findings, and patient-centered implementation will be needed before ctDNA-MRD can be integrated into routine management of EBC.

circulating tumor DNA↗

A single-nucleus transcriptome atlas of soybean anthers.

Anther development is crucial for plant sexual reproduction. However, a high-resolution, cell-type-specific transcriptomic atlas of this process is lacking for the legume crop soybean (Glycine max). Here, we construct a comprehensive transcriptional atlas of developing soybean anthers using single-nucleus RNA sequencing (snRNA-seq). We identify and characterize nine distinct cell types spanning both somatic and reproductive lineages. Our analysis reveals robust transcriptional continuity across anther developmental stages and dynamic reprogramming during key transitions. Notably, the shift from diploid meiocytes to haploid unicellular microspores is marked by the induction of previously inactive genes, despite an overall reduction in transcript abundance. Subsequently, within bicellular microspores, generative and vegetative cell lineages exhibit sharply divergent transcriptional programs: generative cells specialize in mRNA export and turnover, whereas vegetative cells up-regulate translational machinery. Evolutionary analysis further indicates that generative-cell-specific genes are subject to more relaxed purifying selection compared to those specific to vegetative cells. Functional validation using mutants generated by CRISPR/Cas9-mediated genome editing and EMS mutagenesis reveals the essential roles of OSD1A and PKSA in pollen development and fertility. This high-resolution atlas provides fundamental insights into the transcriptional regulation of soybean anther development and serves as a valuable resource for manipulating male fertility to advance hybrid breeding programs. The data are available at https://databases.genedenovo.com/pollen.

Glycine max↗

Deep learning-based multimodal pathogenomics integration for precision cancer prognosis.

BACKGROUND: Recent studies have revealed valuable prognostic insights in haematoxylin and eosin (H&E)-stained histological sections and transcriptomic profiles, suggesting potential applications in machine learning. However, existing methods lack sufficient intra- and inter-modal interactions, and face challenges in clinical validation due to incomplete multimodal data. METHODS: We proposed PathoGems (PathoGenomics-based integrative survival prediction), a weakly-supervised, interpretable multimodal learning framework that integrates histology and genomic profiles for precise cancer prognosis prediction. To evaluate the robustness of PathoGems, we initially curated a dataset of 1965 cases across four cohorts from The Cancer Genome Atlas (TCGA), including breast, colorectal, glioblastoma, and esophageal cancers. For external validation, PathoGems was further evaluated on four independent cohorts, consisting of 76 breast cancer and 41 esophageal squamous cell carcinoma cases from Zhejiang Cancer Hospital, as well as 102 colorectal cancer and 58 glioblastoma cases from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). RESULTS: PathoGems effectively stratified patients into favorable and unfavorable risk groups, revealing significant differences in histological patterns, genomic features, and overall survival (log-rank test, p&#x2009;<&#x2009;0.05). Moreover, the model&#x2019;s predictions are further supported by visualization and transcriptomic analysis, enhancing interpretability and reliability. CONCLUSIONS: By fusing histological and clinicogenomic multimodal models, PathoGems will provide a solid foundation for developing an innovative tool that aids clinicians in making informed decisions and selection personalized treatment strategies for cancer patients.

Humans↗

A prediction model for metachronous colorectal cancer: development and validation.

BACKGROUND: Being able to estimate the risk of metachronous disease in a patient with colorectal cancer (CRC) could enable risk-appropriate surveillance. The aim of this study was to develop a risk-prediction model to estimate individual 10-year risk of metachronous disease following a CRC diagnosis. METHODS: A population-based cohort of patients with CRC was recruited soon after diagnosis between 1997 and 2012 from the United States, Canada, and Australia. Cox regression with the least absolute shrinkage and selection operator penalization was used to identify factors that predicted the risk of a new primary CRC diagnosed at least 1 year after the initial CRC diagnosis. Potential predictors included demography, anthropometry, lifestyle factors, comorbidities, personal and family cancer history, medication use, age at diagnosis, and pathological features of the first CRC. Internal validation through bootstrapping was used to evaluate the discrimination and calibration. RESULTS: We included 6085 CRC cases; 138 (2.3%) of these cases were diagnosed with metachronous disease over a median of 12&#x2009;years (IQR&#x2009;=&#x2009;5-17&#x2009;years). Metachronous CRC risk was predicted by body mass index; smoking status; level of physical activity; family history of cancer and synchronous CRC; stage, grade, histological type, and DNA mismatch repair status; and age at diagnosis of the first CRC. The model was valid with a C statistic of 0.65 (95% CI&#x2009;=&#x2009;0.63 to 0.68) and a calibration slope of 0.873 (SD = 0.087). CONCLUSIONS: Metachronous CRC can be predicted with reasonable accuracy using a prediction model that consists of clinical variables collected as part of routine practice.

Humans↗

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

Astrocytes become reactive in response to insults to the central nervous system by adopting context-specific cellular signatures and outputs, but a systematic understanding of the underlying molecular mechanisms is lacking. In this study, we developed CRISPR interference screening in human induced pluripotent stem cell-derived astrocytes coupled to single-cell transcriptomics to systematically interrogate cytokine-induced inflammatory astrocyte reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-&#x3ba;B activation drove two distinct inflammatory reactive signatures, one promoted by STAT3 and the other inhibited by STAT3. These signatures overlapped with those observed in other experimental contexts, including mouse models, and their markers were upregulated in human brains in Alzheimer's disease and hypoxic-ischemic encephalopathy. Furthermore, we validated that markers of these signatures were regulated by STAT3 in vivo using a mouse model of neuroinflammation. These results and the platform that we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.

Humans↗

Isolation and characterization of hydrogen-oxidizing bacteria induced following exposure of soil to hydrogen gas and their impact on plant growth.

In many legumes, the nitrogen fixing root nodules produce H2 gas that diffuses into soil. It has been demonstrated that such exposure of soil to H2 can promote plant growth. To assess whether this may be due to H2-oxidizing microorganisms, bacteria were isolated from soil treated with H2 under laboratory conditions and from soils collected adjacent to H2 producing soybean nodules. Nineteen isolates of H2-oxidizing bacteria were obtained and all exhibited a half-saturation coefficient (Ks) for H2 of about 1 ml l(-1). The isolates were identified as Variovorax paradoxus, Flavobacterium johnsoniae and Burkholderia spp. using conventional microbiological tests and 16S rRNA gene sequence analysis. Seventeen of the isolates enhanced (57-254%) root elongation of spring wheat seedlings. Using an Arabidopsis thaliana bioassay, plant biomass was increased by 11-27% when inoculated by one of four isolates of V. paradoxus or one isolate of Burkholderia that were selected for evaluation. The isolates of V. paradoxus found in both H2-treated soil and in soil adjacent to soybean nodules had the greatest impact on plant growth. The results are consistent with the hypothesis that H2-oxidizing bacteria in soils have plant growth promoting properties.

Arabidopsis↗

Theoretical investigation of the tunable behavior of p-n copolymers based on oligothiophenes and 1,4-bis(oxadiazolyl)-benzene.

Semiempirical calculations were carried out on several model oligomers to investigate the tunable behavior of p-n copolymers with the repeating units constructed by oligothiophenes as the pi-excessive type blocks and 1,4-bis(oxadiazolyl) benzene as the pi-deficient type block. The calculated evolutions of the HOMO and LUMO of the model oligomers were in good agreement with the experimental oxidation and reduction potentials of the corresponding polymers. The effect of the length of the oligothiophene on the electronic structures and optical properties was elucidated by analyzing the HOMO and LUMO spatial distribution patterns of the model oligomers. When the number of thiophene rings increases, the HOMO and LUMO are contributed mostly from the oligothiophene segments and either the introduced single positive or negative charge focuses on the oligothiophene segments. The absorption spectra of polymers were also simulated by performing calculations on the corresponding oligomers. Good matches were observed between the calculated absorption spectra and the experimental UV-vis spectra of the corresponding polymers. The study shows that the backbone modification of the p-n copolymer, that is, changing the number of thiophene unit in the p-n diblock copolymer, greatly modifies the optical properties of the polymer.

Journal Article↗

RNAi screen in mouse astrocytes identifies phosphatases that regulate NF-kappaB signaling.

Regulation of NF-kappaB activation is controlled by a series of kinases; however, the roles of phosphatases in regulating this pathway are poorly understood. We report a systematic RNAi screen of phosphatases that modulate NF-kappaB activity. Nineteen of 250 phosphatase genes were identified as regulators of NF-kappaB signaling in astrocytes. RNAi selectively regulates endogenous chemokine and cytokine expression. Coimmunoprecipitation identified associations of distinct protein phosphatase 2A core or holoenzymes with the IKK, NF-kappaB, and TRAF2 complexes. Dephosphorylation of these complexes leads to modulation of NF-kappaB transcriptional activity. In contrast to IKK and NF-kappaB, TRAF2 phosphorylation has not been well elucidated. We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity. These results provide direct evidence for TNF-induced TRAF2 phosphorylation and demonstrate that phosphorylation is regulated at multiple levels in the NF-kappaB pathway.

Animals↗

Wnt/beta-catenin signaling pathway is active in pancreatic development of rat embryo.

AIM: To elucidate the role of Wnt/beta-catenin signaling pathway in pancreatic development of rat embryo. METHODS: The mRNAs of beta-catenin, APC, cyclin D1 genes were amplified by means of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) from embryonic pancreas in different periods and normal pancreas of rat, respectively. Protein expression of these genes in embryonic pancreas of E14.5-E18.5 was examined by immunohistochemical method. RESULTS: In embryonic pancreas of E14.5, the transcript amplification of beta-catenin and cyclinD1 genes was detected. In embryonic pancreas of E18.5, the transcription levels of beta-catenin and cyclinD1 genes became much higher than in other periods. But in adult rat pancreas the transcription of cyclinD1 gene could not be observed. Only until E18.5, the transcript amplification of mRNA of APC gene could be detected. Surprisingly, the transcription level of APC gene became much higher in adult rat pancreas than in embryonic pancreas. By means of immunohistochemical staining, identical results were obtained to the above by RP-PCR, except for beta-catenin protein in adult rat pancreas. CONCLUSION: Active Wnt/beta-catenin signaling occurs in rat embryonic pancreas and is probably important for pancreatic development and organ formation.

Adenomatous Polyposis Coli Protein↗

Monte Carlo simulation study of the kinetics of brush formation by irreversible adsorption of telechelic polymers onto a solid substrate.

The irreversible adsorption of telechelic polymer chains from solution and melts onto solid substrates has been studied using the bond fluctuation Monte Carlo model. Complex brush formation kinetics dominated by diffusion of chains to the substrate at short times (diffusion-limited regime or DLR) and by penetration of chains through the maturing brush at longer times (penetration-limited regime or PLR) were observed. During the entire adsorption process, the rate of chain adsorption decreases monotonically with time. In the DLR, characterized by a maximum in the concentration of singly bound chains and a rapidly increasing fraction of doubly bound chains (loops), this decrease is due primarily to the depletion of free chains near the substrate and the formation of concentration gradients of free (nonadsorbed) chains in the bulk solution. The DLR and PLR are separated by an intermediate regime during which the brush becomes dominated by doubly bound chains and both penetration of the maturing brush and diffusion of chains to the brush surface play a role in determining the kinetics of brush growth. The PLR is characterized by steep gradients of free chains within the growing brush and the disappearance of concentration gradients for free chains in the bulk solution. In the PLR, the concentration of singly bound chains is low and decreases slowly while surface coverage and the fraction of doubly bound chains increase slowly. The rates of adsorption of new chains and the formation of loops in the PLR slow dramatically with increasing surface coverage and increasing chain length and less dramatically with decreasing bulk concentration.

Journal Article↗

Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cells.

STATs play key roles in immune function. We examined the role of STAT5a/b in allograft rejection. STAT5a/b-deficient mice showed a 4-fold increased survival time of heart allografts (p < 0.01). Unlike wild type, purified STAT5a/b-/- T cells transferred to Rag1-/- recipients failed to mediate heart allograft rejection until supplemented with STAT5a/b-/- B cells. In vitro, STAT5a/b-/- T cells did not proliferate in response to Con A or alloantigens but entered apoptosis within 48 h (95%). Activated STAT5a/b-/- T cells showed increased expression of proapoptotic (caspases, DNA repair genes, TNF/TNFR-associated factor family genes) and decreased antiapoptotic mRNAs in microarrays, while Western blots confirmed reduced antiapoptotic Bcl-2 and elevated proapoptotic Bax protein expression. Interestingly, at 24 h postactivation, STAT5a/b+/+ and STAT5a/b-/- T cells produced similar levels of IL-2, IL-4, IL-10, and IFN-gamma mRNA; ELISPOT assay showed an equivalent number of IL-4- and IFN-gamma-producing T cells in both STAT5a/b+/+ and STAT5a/b-/- splenic populations. Sera from STAT5a/b+/+ and STAT5a/b-/- rejectors had donor-specific IgM, IgG1, IgG2a, and IgG2b Ab, while STAT5a/b deficiency had no impact on B cell survival or proliferation in response to LPS. Compared with allografts from STAT5a/b+/+ recipients, heart allografts from STAT5a/b-/- recipients had markedly reduced infiltration by CD4 and CD8 T cells but increased infiltration by B cells and dense endothelial deposition of C4d, a marker of humoral rejection. Thus, activated STAT5a/b-/- T cells produce cytokines prior to entering apoptosis, thereby promoting differentiation of B cells yielding donor-specific IgM and IgG Ab that mediate allograft rejection.

Adoptive Transfer↗

Use of unfractionated heparin and a low-molecular-weight heparin following thrombolytic therapy for acute ST-segment elevation myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases, with acute ST-segment elevation myocardial infarction (STEMI) showing a higher mortality rate than non-ST-segment elevation myocardial infarction (NSTEMI). There is evidence that low-molecular-weight heparin (LMWH) shows greater efficacy than unfractionated heparin (UFH). This open-label, single-centre, randomised study was conducted to compare the efficacy and safety of parnaparin sodium, a LMWH, with UFH in patients with STEMI. PATIENTS AND METHODS: Patients with STEMI were randomised to receive either parnaparin sodium (4250IU aXa subcutaneously every 12 hours for 7 days, initiated 12 hours after thrombolysis) or UFH (100 U/kg intravenous bolus, initiated 12 hours after thrombolytic therapy, followed by 1000 U/hour as a continuous infusion for 3 days, then 7500U subcutaneously every 12 hours for 4 days). Patients were followed up for 45 days (> or =14 days in hospital). RESULTS: In total, 186 patients were randomised to receive parnaparin sodium (n = 96) or UFH (n = 90). A significantly greater reduction in the composite primary endpoint (sum of all deaths, first occurrence of recurrent MI, and first occurrence of emergency revascularisation) was seen with parnaparin sodium compared with UFH at day 45 (27.08% vs 42.22%; p = 0.03). A lower incidence of composite endpoint was seen as early as day 2 with parnaparin sodium, but this did not reach significance versus UFH. The rate of individual endpoint events (death, first occurrence of non-fatal recurrent MI and first occurrence of emergency revascularisation) was lower in the parnaparin sodium group than the UFH group at 2, 7, 14 and 45 days, but the differences were not statistically significant. At day 7, the incidences of any bleeding and heparin-induced thrombocytopenia were also lower in the parnaparin sodium group compared with the UFH group (3.13% vs 10.0%; p = 0.06 and 0% vs 3.33%; p = 0.07, respectively). CONCLUSION: The results of this study indicate that parnaparin sodium is more effective than UFH in reducing composite cardiac events in patients with STEMI following thrombolytic therapy. There was also a lower incidence of bleeding and heparin-induced thrombocytopenia with parnaparin sodium than with UFH. In view of these findings, parnaparin sodium represents an effective, convenient and well tolerated alternative to UFH.

Aged↗

[Genome-wide search for linkage to attention deficit hyperactivity disorder (ADHD) on the X chromosome].

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral. Boys are more often affected than girls. Family, twin and adoption studies have supported a strong genetic basis. The etiology of this disorder is not clear. Molecular genetic and pharmacological studies suggest the involvement of dopaminergic and noradrenergic neurotransmitter systems in ADHD, e.g , Several reports have found association between ADHD and the dopamine receptor gene DRD-4.the dopamine transporter gene DAT1, and the catechol-o-methyltransferase. Our previous studies showed an association between ADHD and the DXS7 locus, which is located in closely linked to the MAO gene, and MAOA gene on chromosome X. To test this hypothesis, we used the genome scan for a predisposing locus on chromosome X to ADHD. We used the tramsmission/disequilibrium test (TDT) to test for linkage between a VNTR polymorphism at the 48 markers of chromosome X and DSM-III-R oliagnosed ADHD in 84 nuclear families of the Chinese population. The TDT analysis revealed linkage between ADHD and the DXS1214(TDT: Chi2=18.1, df=7, P<0.01), DXS8102(TDT: Chi2=7.9, df=3, P<0.05), DXS1068(TDT: Chi2=21.9, df=9, P<0.01), DXS8015(TDT: Chi2=14.6, df=7, P<0.05), DXS1059(TDT: Chi2=27.8, df=10, P<0.01) and DXS8088(TDT: Chi2=20.4, df=3, P<0.01).The data showed that susceptibility loci might reside in chromosome Xp11.4-Xp21 and Xq23 for ADHD.

Attention Deficit Disorder with Hyperactivity↗

[Inducement effect of synthetic indiosides from Solanum indicum L.on apoptosis of human hepatocarcinoma cell line Bel-7402 and its mechanism].

BACKGROUND & OBJECTIVE: Solanum indicum L., an anti-inflammatory and wound-healing herb in traditional Chinese medicine, is enriched of unique dioscins, that is, indiosides. Our previous studies revealed that several synthetic indiosides from Solanum indicum L. have potent anticancer effects. This study was to investigate the anticancer mechanism of synthetic indiosides I from Solanum indicum L. METHODS: Human hepatocarcinoma Bel-7402 cells were treated with different concentrations of indiosides. The inhibitory rate of cell proliferation and 50% inhibitory concentration (IC50) of indiosides were detected by the acid phosphatase assay (APA). Cell morphology was observed under optical microscope with crystal violet staining. The expression of apoptosis-related proteins was detected by Western blot. RESULTS: Indiosides significantly inhibited proliferation of Bel-7402 cells: when treated with indioside I for 72 h, the IC50 value was 4.2 microg/ml, cell density was decreased, and bubbles were observed in cytoplasm. Western blot showed that the cytoplasmic level of cytochrome c was increased significantly, Caspase-3 was activated, and poly (ADR-ribose) polymerase (PARP) was cleavaged after indioside I treatment. CONCLUSION: Indiosides have dose-dependent inhibitory effect on proliferation of Bel-7402 cells, and can induce cell apoptosis through mitochondria-dependent pathway.

Antineoplastic Agents, Phytogenic↗

[Expression levels of APP and PS1 genes in patients with Alzheimer's disease].

The gene expression levels of amyloid precursor protein (APP) and presenilin 1 (PS1) in the peripheral blood samples of patients with Alzheimer's disease(AD) and their association with the disease were studied. The absolute expression levels of APP and PS1 genes were quantified in 45 AD patients, 25 patients with vascular dementia (VD) and 60 healthy controls by real-time quantitative PCR using SYBR Green I. The APP expression levels in healthy controls, AD cases and VD cases are 0.026+/-0.005, 0.044+/-0.006 and 0.072+/-0.013 amol/microg cDNA, respectively; and the PS1 expression levels are 0.026+/-0.004, 0.051+/-0.011 and 0.039+/-0.005 amol/microg cDNA, respectively. Both APP and PS1 expression levels were significantly elevated in AD or in VD cases (APP, AD vs Control, t=2.639, P<0.01, VD vs Control, t=3.028P<0.01; PS1, AD vs Control, t=2.173P<0.05, VD vs Control, t=2.012P<0.05). It seems that elevated APP and PS1 gene expression is associated with dementia but not especially with AD.

Aged↗

[Application of single radial hemolysis technique for diagnosis of influenza A (H5N1)].

BACKGROUND: To understand the optimal condition of single radial hemolysis (SRH) for diagnosis of avian influenza A (H5N1) virus in order that SRH could be performed in general laboratories. METHODS: The effect of different concentration of virus and species of red blood cells, as well as kind and concentration of agarose on testing sensitivity of SRH was determined. Meanwhile the sensitivity and specificity of this method were compared with those of micro-neutralization test. RESULTS: The optimal condition of SRH included the viral concentration of 1000 HA units per 0.1 ml packed chicken red blood cells, the agarose concentration of 1.0%, the compliment added into agarose-virus-rbc slides after diffusion of sera. The sensitivity and specificity of SRH were very similar to those of micro-neutralization test. Meanwhile, no cross reaction between antibodies, especially antibodies against N1 antigens, H5N1 and H1N1 viruses was detected. CONCLUSION: The sensitivity and specificity of SRH were very similar to those of micro-neutralization assay. SRH could be performed in normal laboratories and be used for testing large scale serum samples.

Animals↗

[Analysis of human H5N1 virus hemagglutinin gene isolated from the mainland of China].

BACKGROUND: To analyze the genetic and antigenic characteristics of human H5N1 virus isolated from the mainland of China. METHODS: The hemagglutinin (HA) gene of human H5N1 virus were sequenced and analyzed. RESULTS: The results of HA gene sequencing showed that all the virus isolates belong to the same group because of the high similarity, but they were different from the virus isolated from Thailand and Vietnam. The sequence data also showed that the receptor specificity and the connecting peptide between HA1 and HA2 are still avian influenza origin. CONCLUSION: The virus isolates from mainland of China until now belong to the same group and are different from the virus isolated from Thailand and Vietnam, and there is no evidence showing the human-avian influenza reassortant and recombination.

Animals↗