PubMed Health⌕ Search

Biomedical subjects

Ling Zhang

Publications and source records attributed to Ling Zhang.

At least 19 recordsLinked to original sources
PubMed2026

ClearDepthIAS enables automated high-throughput quantification of roots in soil-grown taproot crops.

Understanding root system architecture is critical for improving crop productivity and resilience, yet phenotyping root traits such as root growth angle and rooting depth remains technically challenging, especially at high throughput. Here, we present ClearDepthIAS, a high-throughput imaging and analysis platform that enables nondestructive, automated quantification of root architecture traits in taproot system crops. By capturing and stitching 360° images of roots growing along the transparent walls of pots and applying deep learning-based segmentation (ClearDepth-WRT), we measured wall root shallowness (WRS)-a proxy for root growth angle-with high precision. We demonstrated for the tap root systems of soybean and canola that the system accurately detects root tips, quantifies their vertical distribution, and extracts biologically meaningful traits such as root area, distribution indices, and growth angles. Validation experiments in canola and soybean demonstrated that WRS can correlate with root crown architecture in mature plants, both in greenhouse and field settings. Furthermore, WRS and root distribution indices derived from ClearDepthIAS are predictors of early root architecture and can be correlated with root biomass distribution across soil depths under field conditions; however, environmental interactions may influence these relationships and weaken or even negate such correlations, as observed when comparing field to field variation in root system architecture. Our system enables efficient phenotyping of genetically diverse populations, with medium to high trait heritability, supporting its utility for genome-wide association studies and breeding. ClearDepthIAS accelerates the development of root ideotypes for improved resource acquisition and carbon sequestration, offering a scalable tool for supporting climate-resilient agriculture.

Plant Roots↗
PubMed2026

Specific Instruments for Caregiving Competence Among Family Caregivers of Cancer Patients: A COSMIN Systematic Review of Psychometric Properties.

OBJECTIVE: To evaluate and summarize the psychometric properties of specific instruments for caregiving competence among family caregivers of cancer patients. METHODS: Systematically searched eight databases for studies published up to November 2025. The methodological quality and psychometric properties of the instruments were evaluated using COSMIN 2.0. Evidence grades were rated using the modified GRADE system (four grades: "High," "Moderate," "Low," and "Very Low"), and recommendations were formulated (Category A: recommended, Category B: potential with further validation, and Category C: not recommended). RESULTS: Seven studies were included, comprising three specific instruments: the Care Competency Scale for Family Caregivers in Home Palliative Care (CCSHPC) (n = 1), the Caregiver Caregiving Self-Efficacy Scale-Oral Cancer (CSES-OC) (n = 1), and the Caring Ability of Family Caregivers of Patients with Cancer Scale (CAFCPCS) (n = 5). Both the CCSHPC and CAFCPCS received Category B recommendations, demonstrating "adequate" content validity with evidence grades rated "very low" and "low," respectively. The CAFCPCS also shows good structural validity ("moderate") and internal consistency ("low") in some cultural contexts. The CSES-OC is a Category C recommendation, with high-quality evidence indicating "inadequate" criterion validity. CONCLUSION: Few specific instruments exist, and most did not strictly follow COSMIN guidelines. The CAFCPCS is provisionally recommended based on relative evidence superiority rather than complete psychometric validation. Further cross-cultural and localized instrument development is warranted. IMPLICATIONS FOR NURSING PRACTICE: Use well-validated specific instruments to identify strengths and weaknesses in the caregiving competencies of family caregivers of cancer patients, enabling them to deliver high-quality home-based cancer care.

Female↗
PubMed2026

Clinical and molecular characterization of TCF12 variants in an Asian pediatric cohort with craniosynostosis.

BACKGROUND: Craniosynostosis is a genetically heterogeneous craniofacial disorder caused by the premature fusion of one or more cranial sutures. Pathogenic variants in TCF12, encoding a basic helix-loop-helix (bHLH) transcription factor, represent a major cause of autosomal dominant coronal craniosynostosis and are characterized by incomplete penetrance and marked phenotypic variability. However, clinical and molecular data from Asian pediatric populations remain limited. METHODS: Trio-based whole-exome sequencing was performed on ten pediatric patients with cranial deformities and their parents. The identified TCF12 variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by Sanger sequencing. Detailed clinical and radiological data were collected. In addition, a comprehensive literature review was conducted to summarize previously reported TCF12 variants and associated phenotypes. RESULTS: Ten distinct heterozygous TCF12 variants were identified in ten unrelated pediatric patients, all of which were classified as pathogenic or likely pathogenic according to ACMG criteria. Six variants were inherited, and four occurred de novo. Seven patients had imaging-confirmed craniosynostosis, predominantly involving the coronal sutures (five bilateral and one unilateral), while one patient presented with multisuture craniosynostosis (left coronal and sagittal sutures). Three patients showed cranial deformities without radiographic evidence of suture fusion. Phenotypic heterogeneity and incomplete penetrance were observed, including a mildly affected parent. Most pathogenic variants were truncating variants distributed mainly across exons 14-19 and predicted to induce loss of function, either through nonsense-mediated mRNA decay or the production of truncated proteins lacking the entire C-terminal bHLH domain. Structural modeling analysis further indicated that the bHLH-domain-located missense variant p.Arg603Trp alters the local DNA-binding conformation of TCF12 and impairs its binding affinity to the E-box DNA motif. CONCLUSIONS: This study provides additional clinical and molecular data on TCF12-related craniosynostosis in a pediatric cohort from an Asian population. Our findings support haploinsufficiency as the central pathogenic mechanism, primarily driven by truncating variants affecting the C-terminal bHLH domain. The marked clinical heterogeneity, the presence of mild or evolving phenotypes, and incomplete penetrance observed in our cohort underscore the importance of early diagnosis and longitudinal clinical surveillance in affected families.

Humans↗
PubMed2026

A comprehensive survey of genetic variants in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is characterized by marked clinical and molecular heterogeneity. Genomic alterations play a critical role in NB pathogenesis; however, population-specific mutational features remain insufficiently characterized, particularly among Chinese patients. METHODS: Whole-exome sequencing (WES) was performed on tumor, para-tumor, and matched peripheral blood samples from nine pathologically confirmed Chinese patients with NB. Somatic variant profiles were compared with four publicly available NB datasets from cBioPortal, published in 2012, 2013, 2015, and 2023. Mutational patterns, recurrently altered genes, and Gene Ontology (GO) enrichment were analyzed using R version 4.3.2 and clusterProfiler version 4.10.0. RESULTS: A total of 77 missense variants were identified in our cohort. Single-nucleotide polymorphisms (SNPs) represented the predominant variant type, and C > T substitutions were the most frequent nucleotide change. MAP1A variants, comprising two missense variants in one patient, and RBM33 variants, comprising two distinct variants in two patients, were detected in our cohort and, to the best of our knowledge, have not been previously reported in NB, although their frequencies were low. No MYCN amplification or variants in ALK, ATRX, or DAXX were detected. Comparative analysis with the cBioPortal datasets revealed no somatic variants universally shared across all cohorts. In addition, high-risk patients exhibited distinct mutational patterns, with enrichment of the Gene Ontology term "collagen-containing extracellular matrix." CONCLUSIONS: These findings highlight the molecular diversity of NB and suggest the presence of potential population-specific genetic features in Chinese patients. The low-frequency MAP1A and RBM33 variants identified in this cohort warrant further validation in larger, independent cohorts. Moreover, the enrichment of extracellular matrix-related pathways in high-risk NB supports further investigation of tumor-microenvironment interactions as potential therapeutic targets.

Extracellular matrix↗
PubMed2026

Machine learning-guided risk stratification in elderly AML based on genomic, immunophenotypic and therapeutic profiles.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) exhibit considerable biological and clinical heterogeneity, hindering precise prognosis. Existing prognostic systems inadequately capture the complexity of elderly AML due to their reliance on data from younger cohorts and omission of key factors like immunophenotypic markers and therapeutic profiles. This study aimed to develop and internally validate a machine learning-based prognostic model specifically tailored to elderly AML patients. METHODS: A total of 156 patients were analyzed using a two-stage modeling strategy. Clinical and genomic variables were modeled first, followed by independent analysis of immunophenotypic features. Feature selection was performed using multilayer perceptron (MLP) and random forest (RF), while multivariate Cox regression was used for final model construction. Internal validation was conducted using 1000 bootstrap iterations to assess model stability and performance. RESULTS: The model demonstrated strong predictive performance, with a concordance index (C-index) of 0.702. Time-dependent area under the curve (AUC) and calibration plots confirmed accurate prediction of 1-, 3-, and 5-year overall survival. Decision curve analysis indicated favorable net benefit across a range of threshold probabilities. Key independent prognostic factors identified included TP53 mutations, high CD13 expression, and IDH2 mutations. CONCLUSION: This model provides a robust and interpretable tool for individualized risk stratification in elderly AML. By integrating genomic, immunophenotypic, and therapeutic variables, it may help optimize treatment decisions and improve outcomes for this vulnerable population. Future efforts should focus on external validation and integration of dynamic biomarkers.

Humans↗
PubMed2026

Genetic Profile, Treatment Response, and Outcomes of BCR::ABL1-Positive Mixed-Phenotype Acute Leukemia: A Study From the BCR::ABL1 Pathology Group.

Mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion is rare, and its clinicopathological features, genetic landscape, therapeutic response, and patient outcomes remain incompletely defined, as does its relationship to blast-phase chronic myeloid leukemia. In this multicenter study of 44 patients, 86.4% had B/myeloid MPAL, 72.7% showed lymphoid predominance, 40.9% had complex karyotypes, and 68.3% harbored somatic mutations, most commonly RUNX1 mutations (46.3%). RUNX1 mutations frequently co-occurred with acute myeloid leukemia (AML)-associated alterations, whereas DNMT3A, TET2, and BCORL1 mutations were restricted to RUNX1-mutated cases. In contrast, acute lymphoblastic leukemia (ALL)-associated alterations (IKZF1 mutation/deletion and ETV6 mutations) were confined to RUNX1-wild-type patients. TP53 and signaling pathway mutations (NRAS, KRAS, PTPN11, and FLT3) were not detected. Forty-two patients received induction chemotherapy and/or immunotherapy combined with tyrosine kinase inhibitors: 74.2% of lymphoid-predominant patients and 63.6% of myeloid-predominant patients received ALL- and AML-type therapies, respectively. Ten patients relapsed, and 2 had primary refractory disease; some exhibited a dynamic shift in predominant lineage immunophenotype, chromosomal alterations, and somatic mutations at the relapse or refractory stage. The overall remission rate was 86.8%, with no significant differences across ALL-, AML-, or hybrid-type regimens. After a median follow-up of 24.2 months, the median overall survival was 52.5 months. Complex karyotype was associated with inferior overall survival compared with cases lacking additional chromosomal alterations (P = .02), whereas RUNX1 mutations were not. No significant differences in genetic profiles, treatment response, or outcomes were observed between patients with and without chronic myeloid leukemia-like features. This study provides a comprehensive genomic and clinical characterization of BCR::ABL1-positive MPAL, supporting improved risk stratification and future therapeutic strategies.

Adolescent↗
PubMed2026

A single small molecule-based human embryo model reveals V-ATPase requirement in mammalian blastocyst cavitation.

Human naïve pluripotent stem cells (nPSCs) can be induced by various combinations of signaling factors to generate blastocyst-like structures, termed blastoids. Despite rapid progress in human blastoid models, their potential to uncover fundamental mechanisms of early human development remains limited, leaving key morphogenetic processes poorly understood. Here, we describe a simple and robust system in which dimethyl sulfoxide (DMSO) alone induces blastoid formation from human nPSCs. This model recapitulates key pre- and post-implantation features and exhibits enhanced polar trophectoderm (TE) organization, more efficient attachment within an implantation-relevant window, improved epiblast lumenogenesis associated with amniotic cavity formation, and more robust, sustained expansion of embryonic lineages following attachment. Using this system, we reveal a previously unrecognized mechanism underlying TE cavitation and identify lysosome-associated genes - particularly subunits of the proton pump V-ATPase - as essential regulators of blastoid cavitation. DMSO treatment upregulates key V-ATPase subunits (ATP6V0A4 and ATP6V1B1), which are also enriched in the TE of human embryos. Genetic or pharmacological inhibition of V-ATPase activity disrupts lysosomal acidification, blocks intracellular vacuole formation, and impairs blastoid cavitation, whereas overexpression of V-ATPase subunits rescues this phenotype. Furthermore, genetic and pharmacological perturbations of V-ATPase function significantly compromise cavitation in both mouse and human blastocysts. Finally, DMSO treatment induces membrane biomechanical changes characteristic of early embryonic development, suggesting a mode of action distinct from conventional small-molecule, signaling pathway-based induction strategies. This simple DMSO-based blastoid model recapitulates key aspects of human blastocyst development and reveals a conserved requirement for V-ATPase-mediated lysosomal acidification during early mammalian embryogenesis.

Humans↗
PubMed2026

Effect of Tertiary Lymphoid Structures on Immune Cell Infiltration in the Tumor Microenvironment and Prognosis in Lung Adenocarcinoma.

Tertiary lymphoid structures (TLSs) modulate immune responses in various solid tumors, but their comprehensive role in lung adenocarcinoma (LUAD) remains unclear. In this study, we analyzed RNA-seq data from 539 LUAD patients in The Cancer Genome Atlas (TCGA) and microarray data from 223 samples from the Gene Expression Omnibus (GEO, GSE13213, and GSE37745). TLS signatures were evaluated via unsupervised consensus clustering based on 12 chemokine transcriptome signatures. The relationships between TLS and clinical characteristics, tumor microenvironment (TME) cell infiltration, and prognosis were assessed using ESTIMATE and CIBERSORT. A prognostic model was established using LASSO regression and validated with external datasets. Additionally, H&E and IHC analyses were performed to explore associations between intratumoral TLS density, immune-related molecular expression, and patient prognosis in LUAD. Consensus clustering of the TCGA cohort revealed two distinct LUAD patient clusters according to TLS abundance. Cluster 1 exhibited greater immune cell infiltration, more favorable prognosis, and increased expression of immune checkpoint molecules. We developed a prognostic model comprising eight survival-associated genes that act as independent prognostic factors for patient survival. H&E/IHC analyses revealed that TLS density-regardless of pathological stage-was associated with better prognosis; higher intratumoral TLS density/proportion was also related to more favorable outcomes. IHC confirmed that survival-associated genes (CD5, HLA-DMB, and P2RY13) are independent prognostic indicators in LUAD. Our study demonstrated the close relationship between TLS signatures and an active immune microenvironment, highlighting their potential as independent prognostic indicators in LUAD.

Humans↗
PubMed2025

Inferring metabolic objectives and trade-offs in single cells during embryogenesis.

While proliferating cells optimize their metabolism to produce biomass, the metabolic objectives of cells that perform non-proliferative tasks are unclear. The opposing requirements for optimizing each objective result in a trade-off that forces single cells to prioritize their metabolic needs and optimally allocate limited resources. Here, we present single-cell optimization objective and trade-off inference (SCOOTI), which infers metabolic objectives and trade-offs in biological systems by integrating bulk and single-cell omics data, using metabolic modeling and machine learning. We validated SCOOTI by identifying essential genes from CRISPR-Cas9 screens in embryonic stem cells, and by inferring the metabolic objectives of quiescent cells, during different cell-cycle phases. Applying this to embryonic cell states, we observed a decrease in metabolic entropy upon development. We further uncovered a trade-off between glutathione and biosynthetic precursors in one-cell zygote, two-cell embryo, and blastocyst cells, potentially representing a trade-off between pluripotency and proliferation. A record of this paper's transparent peer review process is included in the supplemental information.

Single-Cell Analysis↗
PubMed2007

Use of luminescence probing for the study of the interaction of polytitanasiloxane with trivalent rare earth ions.

Luminescent probing methods were employed to investigate the interaction of the Ti-O chains of polytitanasiloxane with europium ions in the mixture of ethanol and water. The UV-vis absorption, the luminescence intensity, and the luminescence lifetimes of the Eu3+ ions in PTS solutions were all found to increase with the increase of TBT/TEOS molar ratio. The results indicated that the incorporation of TBT can result in the increase of absorption energy of the Ti-O group by near-UV excitation and in the increase of energy transfer to the metal ion, and that the Ti-O chains due to the site binding of Eu3+ ions can expel six to nine solvent molecules from the first coordination solvation shell of the ion. The investigation of the energy transfer from europium to neodymium ions in polytitanasiloxane solutions revealed the formation of aggregates consisting of seven rare earth ions (together with the polytitanasiloxane countercharges).

Deuterium Oxide↗
PubMed2007

Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases.

Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The -1031C allele of TNF-alpha was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR): 0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries. Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.

Aged↗
PubMed2007

Successful transfection of hepatoma cells after encapsulation of plasmid DNA into negatively charged liposomes.

The application of conventional cationic liposomes/DNA complexes in gene transfer was hampered due to their large size, instability, and limited transfection site in vivo. In this report, we described a dialysis-based method and produced small, stable, and negatively charged DNA-containing liposomes composed of low content of cationic lipid and high content of fusogenic lipid. The liposomes were relatively spherical with a condensed core inside, and exhibited small size with narrow particle size distribution. The encapsulation efficiency of the liposomes was 42.53 +/- 2.29%. They were stable and showed enough protective ability to plasmid DNA from degradation after incubation with different amounts of DNase. Twenty-fold higher transfection efficiency for the liposomes was achieved when compared with that of naked plasmid DNA and no toxicities to hepatocellular carcinoma cells were observed. Our results indicate that the negatively charged DNA-containing liposomes can facilitate gene transfer in cultured cells, and may alleviate the drawbacks of the conventional cationic liposomes/DNA complexes for gene delivery in vivo.

Capsules↗
PubMed2007

Effect of oestrogen on reactive oxygen species production in the aortas of ovariectomized Dahl salt-sensitive rats.

OBJECTIVE: In the present study, we examined whether ovariectomy increases reactive oxygen species (ROS) and the expression of nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase and modulates the scavenger enzymes for ROS in the aortas of Dahl salt-sensitive (DSS) rats fed a high salt diet. METHODS: DSS female rats were ovariectomized and fed a high salt diet (8% NaCl), or a high salt diet plus oestrogen supplement for 4 weeks. Urinary levels of hydrogen peroxide (H2O2) were measured by using 2',7'-dichlorofluorescein. The expression of an NADPH oxidase subunit p22phox, extracellular superoxide dismutase (ecSOD), glutathione peroxidase (GPx)1, GPx4 and monocyte chemoattractant protein 1 (MCP-1) messenger RNA was assessed by reverse transcription-polymerase chain reaction. The expression of MCP-1, and macrophage infiltration were examined by immunohistochemical analysis. RESULTS: Ovariectomy increased superoxide production and the expression of NADPH oxidase subunit p22phox mRNA and protein in the aortas of DSS rats fed a high salt diet. In contrast, ovariectomy reduced the expression of ecSOD mRNA and protein and the expression of GPx1 and GPx4 mRNA in the aorta. Ovariectomy increased MCP-1 mRNA and protein expression and ED1-positive cells in the aorta. CONCLUSIONS: Ovariectomy leads to an amplification of oxidative stress in DSS rats fed a high salt diet synergistically by an increase in the ROS-generating system and a decrease in the ROS-eliminating system, as shown in the increase in superoxide production and the urinary excretion of H2O2. Oestrogen supplementation counteracted these alterations, showing how oestrogen is antioxidative.

Animals↗
PubMed2007

Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes.

BACKGROUND: Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). METHODS AND RESULTS: The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-alpha, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography. CONCLUSIONS: The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.

Adiponectin↗
PubMed2006

Intracellular Tat of human immunodeficiency virus type 1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus: role of JAK/STAT signaling.

Human immunodeficiency virus type 1 (HIV-1) infection significantly increases the risk of Kaposi's sarcoma (KS) occurrence in individuals infected with Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV infection appears to be necessary but not sufficient for KS development without other cofactors. However, factors that facilitate KSHV to cause KS have not been well defined. Previously, we determined that human herpesvirus 6 was one of the cofactors that activated lytic cycle replication of KSHV. Here, we demonstrate that the Tat protein of HIV-1 is a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts and viral proteins in BCBL-1 cells. Mechanistic studies showed ectopic expression of Tat induced the production of human interleukin-6 (huIL-6) and its receptor (huIL-6Ra) and activated STAT3 signaling. Neutralization of huIL-6 or huIL-6R or inhibition of STAT3 signaling enhanced the replication. In addition, IL-4/STAT6 signaling also partially contributed to Tat-induced KSHV replication. These findings suggest that Tat may participate in KS pathogenesis by inducing KSHV replication and increasing KSHV viral load. These data also suggest that JAK/STAT signaling may be of therapeutic value in AIDS-related KS patients.

Animals↗
PubMed2006

The potent inhibitory activity of histone H1.2 C-terminal fragments on furin.

Many physiologically important proproteins, pathogenic bacterial exotoxins and viral envelope glycoproteins are activated by the proprotein convertase furin, which makes furin inhibitor a hot target for basic research and drug design. Although synthetic and bioengineered inhibitors of furin have been well characterized, its endogenous inhibitor has not been directly purified from mammalian tissues to date. In this study, three inhibitors were purified from the porcine liver by using a combination of chromatographic techniques, and identified to be the C-terminal truncated fragments with different sizes of histone H1.2. The gene of porcine histone H1.2 was cloned and sequenced, further confirming the determined sequences. These three C-terminal fragments inhibited furin with Ki values around 2 x 10(-7) m while the full-length histone H1.2 inhibited it with a lesser activity, suggesting that the inhibitory activity relies on the C-terminal lysine-rich domain. Though the inhibition was temporary, these inhibitors were specific, and the reactive site of one C-terminal fragment was identified. A 36 amino acid peptide around the reactive site was synthesized, which could still inhibit furin with a Ki of 5.2 x 10(-7) m.

Amino Acid Sequence↗
PubMed2006

STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils.

Granulocyte colony-stimulating factor (G-CSF) is essential for the host response to bacterial infection by controlling neutrophil production in the bone marrow. The G-CSF receptor (G-CSFR) activates the Jak/STAT pathway, although little is understood about how these signals regulate basal and stress-induced granulopoiesis. We examined STAT3 function in granulocytes using a bone marrow conditional knockout mouse model. Our results show that STAT3 has a crucial role in emergency granulopoiesis and mature neutrophil function. STAT3-deficient mice have an aberrant response to G-CSF in vivo, characterized by failure to accumulate immature granulocytes and an increased ratio of mature to immature neutrophils in the bone marrow, peripheral blood, and spleen. Acute neutrophil mobilization is impaired in STAT3-deficient mice as judged by their failure to up-regulate circulating neutrophils following short-term G-CSF exposure. STAT3 also controls neutrophil chemotactic responses to natural ligands for CXCR2 and regulates the magnitude of chemoattractant-induced actin polymerization. These functions of STAT3 are independent of its principal target gene Socs3, which encodes a crucial feedback inhibitor of cytokine signaling. Our results demonstrate the existence of distinct STAT3 target pathways in neutrophils required for granulopoiesis and innate immunity.

Animals↗