Biomedical subjects

Jie Zhou

Publications and source records attributed to Jie Zhou.

At least 19 recordsLinked to original sources

PubMed2026

hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.

Enhancer RNAs interact with promoter-derived RNAs to dictate enhancer-promoter looping, but the RNA-binding protein that mediates this process has remained unidentified. Here we identify hnRNPK as a general structural regulator that preferentially binds to nascent RNAs transcribed from enhancer and promoter regions, promoting enhancer-promoter looping and transcriptional activation. We further show that hnRNPK forms phase-separated, cavity-containing condensates that encapsulate RNA polymerase II (Pol II) via its RPB3 subunit, facilitating chromatin looping and potentially enabling recruitment of Pol II from enhancers to promoters through protein dimerization. Notably, a mutation associated with Au-Kline syndrome in hnRNPK (c.953+1dupG) alters its condensates from a liquid-like to a gel-like state, leading to developmental defects in knock-in mice. Fibroblasts derived from these mutants display reduced enhancer-promoter looping and decreased Pol II recruitment at promoters of key developmental genes. These findings suggest that hnRNPK is a structural regulator of enhancer-promoter communication and highlight the importance of RNA-RNA interactions mediated by RNA-binding proteins in transcriptional regulation.

RNA Polymerase II↗

PubMed2026

A cooperative regulatory module between TAGL2 and JMJC1 activates specific defense genes against root-knot nematodes in tomato.

Plant-parasitic nematodes (PPNs) threaten global food security. Although epigenetic modifications are crucial for plant immunity, how histone modifiers contribute to root-knot nematodes (RKNs, Meloidogyne incognita) resistance remains unclear. Here, using genetic, molecular and biochemical approaches, we investigated the epigenetic and transcriptional mechanisms underlying RKN resistance mediated by the histone demethylase (HDM) JMJC1 and the MADS-box transcription factor TAGL2 in tomato (Solanum lycopersicum). We identified JMJC1 as an RKN-induced positive defense regulator targeting H3K9me3 and H3K27me3 histone marks. JMJC1 physically interacts with TAGL2, which also positively regulates RKN resistance. Transcriptomic analysis indicated that TAGL2 regulates multiple layers of the plant defense network, transcriptionally activating representative genes from distinct pathways (including PUB10, bHLH98, CCaMK, and SAUR3), which we validated as positive regulators of RKN resistance via virus-induced gene silencing (VIGS). At the chromatin level, TAGL2 and JMJC1 co-regulate these loci, associating with localized H3K9me3 and H3K27me3 reduction. Furthermore, TAGL2 directly activates JMJC1 transcription, establishing a positive feedback loop that amplifies immune signaling. Our findings reveal a cooperative model wherein a HDM and a transcription factor coordinate at specific loci to fine-tune multiple defense layers at both epigenetic and transcriptional levels, providing insights for breeding durable nematode-resistant plants.

Solanum lycopersicum↗

PubMed2026

The relationships between figure rating scale, anthropometric measures, and cardiometabolic outcomes: the AADM study.

INTRODUCTION: Direct measurement of anthropometrics can be impractical in research. Validated Figure Rating Scales (FRS) offer an alternative, but their validity across populations remains limited. OBJECTIVES: This study aimed to analyze the relationships between figure rating scale (FRS) and anthropometric measures (body mass index (BMI); waist circumference (WC), and waist-to-hip ratio (WHR)) and to specifically evaluate FRS at the time of enrollment and lifetime body size, an FRS-derived score as risk factors for cardiometabolic traits including type 2 diabetes (T2D). METHODS: Participants consisted of 650 adults from the America Africa Diabetes Mellitus study. Kendall's tau coefficient (τ) was used to analyze correlations between FRS at the time of enrollment, overall obesity, and abdominal obesity. Regression models were used to evaluate FRS at the time of enrollment and lifetime body size as risk factors for T2D, and related traits. RESULTS: BMI and WHR increased monotonically with increasing body size. FRS at the time of enrollment showed a stronger correlation with BMI (τ = 0.48, p < 0.0001) than with WHR (τ = 0.17, p < 0.0001) in women. Lifetime body size was significantly associated with T2D (OR = 1.044, 95% Confidence Limit: [1.006, 1.08]; both FRS at the time of enrollment and lifetime body size were associated with insulin resistance. Diastolic blood pressure was associated with FRS at the time of enrollment. CONCLUSIONS: FRS at the time of enrollment is significantly associated with BMI and WHR in this population and lifetime body size, a novel composite score, shows promising utility as a predictor of T2D.

Humans↗

PubMed2026

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved ∼80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans↗

PubMed2025

Metagenomic analysis of microbial community dynamics in konjac rhizosphere during soft rot disease progression.

Amorphophallus konjac, the sole glucomannan-rich species in the Araceae family, faces significant yield and quality losses due to soft rot disease. Understanding the relationship between soil microbial communities and soft rot incidence is critical for sustainable konjac production. Metagenomic profiling was employed to systematically characterize the spatiotemporal dynamics of rhizosphere microbiomes during disease progression. Microbial alpha diversity (Chao1 index) exhibited a significant peak in the rhizosphere of diseased plants at the mature stage, contrasting with stable diversity patterns in healthy and latently infected groups, indicating dysbiosis-associated richness inflation during disease progression. Principal coordinate analysis (PCoA) revealed significant divergence in rhizosphere microbial structures between diseased and healthy/latently infected groups, with higher compositional variability observed in diseased samples. At the phylum level, Chloroflexi and Acidobacteria abundances in healthy mature plants exceeded those in diseased plants by 11.54% and 4.6%, respectively, while pathogenic Rhizopus arrhizus and Rhizopus microsporus were significantly enriched in diseased mature plants. Correlation analyses demonstrated predominantly negative associations between bacterial species and soil factors, contrasting with positive fungal correlations. KEGG pathway annotation identified carbohydrate metabolism and amino acid synthesis as core microbial functions in the konjac rhizosphere. Collectively, Chloroflexi and Acidobacteria were validated as putative biocontrol agents, while Rhizopus spp. emerged as key drivers of soft rot development. These findings provide mechanistic insights for designing microbiome-based biocontrol strategies to mitigate konjac soft rot, offering a sustainable alternative to conventional agrochemical reliance. KEY POINTS: • Diseased konjac microbial richness peaks; healthy plants enrich Chloroflexi/Acidobacteria. • Rhizopus pathogens drive soft rot; bacteria and fungi show opposing soil factor links. • Lays groundwork for microbiome approaches to cut agrochemicals in konjac rot control.

Rhizosphere↗

PubMed2007

Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1alpha.

Hypoxia inducible factor 1 (HIF-1), a key regulator for adaptation to hypoxia, is composed of HIF-1alpha and HIF-1beta. In this study, we present evidence that overexpression of mitochondria-located thioredoxin 2 (Trx2) attenuated hypoxia-evoked HIF-1alpha accumulation, whereas cytosolic thioredoxin 1 (Trx1) enhanced HIF-1alpha protein amount. Transactivation of HIF-1 is decreased by overexpression of Trx2 but stimulated by Trx1. Inhibition of proteasomal degradation of HIF-1alpha in Trx2-overexpressing cells did not fully restore HIF-1alpha protein levels, while HIF-1alpha accumulation was enhanced in Trx1-overexpressing cells. Reporter assays showed that cap-dependent translation is increased by Trx1 and decreased by Trx2, whereas HIF-1alpha mRNA levels remained unaltered. These data suggest that thioredoxins affect the synthesis of HIF-1alpha. Trx1 facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and eIF-4E, known to control cap-dependent translation. In contrast, Trx2 attenuated activities of Akt, p70S6K, and eIF-4E and provoked an increase in mitochondrial reactive oxygen species production. MitoQ, a mitochondria specific antioxidant, reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2 cells, supporting the notion of translation control mechanisms in affecting HIF-1alpha protein accumulation.

Cells, Cultured↗

PubMed2007

Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution.

We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

Asian People↗

PubMed2007

Comparison of the performance of chiral stationary phase for separation of fluoxetine enantiomers.

Separation of fluoxetine enantiomers on five chiral stationary phases (chiralcel OD-H, chiralcel OJ-H, chiralpak AD-H, cyclobond capital I, Ukrainian 2000 DM and kromasil CHI-TBB) was investigated. The optimal mobile phase compositions of fluoxetine separation on each column were hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), hexane/isopropanol/diethyl amine (99/1/0.1, v/v/v), hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), methanol/0.2% triethylamine acetic acid (TEAA) (25/75, v/v; pH 3.8) and hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), respectively. Experimental results demonstrated that baseline separation (R(S)>1.5) of fluoxetine enantiomers was obtained on chiralcel OD-H, chiralpak AD-H, and cyclobond capital I, Ukrainian 2000 DM while the best separation was obtained on the last one. The eluate orders of fluoxetine enantiomers on the columns were determined. The first eluate by chiralcel OJ-H and kromasil CHI-TBB is the S-enantiomer, while by chiralpak AD-H and cyclobond I 2000 DM is the R-enantiomer.

Journal Article↗

PubMed2006

Effects of nitric oxide on fatty acid composition in peach fruits during storage.

Peach (Prunus persica (L.) Batsch., cv. Feicheng) fruits were fumigated with 0, 5, 10, and 15 microL/L nitric oxide (NO), and the effects of NO on rot index, ion leakage, and the lipid compositions in peach fruits were studied. The results showed that the treatment with 10 microL/L NO significantly increased the contents of the palmitoleic (16:1), oleic (18:1), and linolenic (18:3) acid in phospholipid (PL), while it decreased the contents of linoleic (18:2) acid in PL. The content of monoacylglycerol (MG) in fruit fumigated with 10 microL/L NO were higher than in the control but lower in fruit fumigated with 15 microL/L NO. The treatment with 10 microL/L NO increased the content of MG, decreased the contents of diacylglycerol (DG) and triacylglycerol (TG). However, there was no significant difference in the contents of free fatty acid (FFA). The compositions of MG, DG, TG, and FFA in peach fruit were also changed by the treatment with 10 microL/L NO. It could preserve the content of 18:3, maintain the integrity of membrane, and prevent the softening and rotting of peach fruit. The content of 18:1 was detected in PL and FFA but not in MG, DG, and TG. This might be due to the different compositions of MG, DG, and TG.

Fatty Acids↗

PubMed2006

Therapeutic effect of hepatitis B surface antigen-antibody complex is associated with cytolytic and non-cytolytic immune responses in hepatitis B patients.

To study the responses of chronic hepatitis B patients to yeast-derived HBsAg-HBIG complexes (YIC) and the mechanisms involved, twenty HBeAg-positive chronic hepatitis B patients were immunized with 60microg of YIC or alum as the control at 4-week intervals, for 24 weeks. Five of ten patients responded to 60microg YIC immunization showing > or =2 logs decrease of serum HBV DNA with loss or marked reduction of HBeAg and appearance of anti-HBe; two of these patients developed anti-HBs. Flares of alanine aminotransferase were observed in 4 of the 5 responders, and in 2 out of 10 control patients. HBsAg-stimulated peripheral blood mononuclear cells (PBMCs) secreted Th1/Th2 cytokines around 24 weeks after immunization. Dendritic cells incubated with YIC showed the highest levels of IL-12 secretion and up-regulation of functional markers. Thus, the therapeutic effect of YIC is associated with cytolytic and non-cytolytic responses in patients.

Adolescent↗

PubMed2006

PlantQTL-GE: a database system for identifying candidate genes in rice and Arabidopsis by gene expression and QTL information.

We have designed and implemented a web-based database system, called PlantQTL-GE, to facilitate quantitatine traits locus (QTL) based candidate gene identification and gene function analysis. We collected a large number of genes, gene expression information in microarray data and expressed sequence tags (ESTs) and genetic markers from multiple sources of Oryza sativa and Arabidopsis thaliana. The system integrates these diverse data sources and has a uniform web interface for easy access. It supports QTL queries specifying QTL marker intervals or genomic loci, and displays, on rice or Arabidopsis genome, known genes, microarray data, ESTs and candidate genes and similar putative genes in the other plant. Candidate genes in QTL intervals are further annotated based on matching ESTs, microarray gene expression data and cis-elements in regulatory sequences. The system is freely available at http://www.scbit.org/qtl2gene/new/.

Arabidopsis↗

PubMed2006

Surface reactivity and energetics of CH radicals during plasma deposition of hydrogenated diamondlike carbon films.

The surface reactivity of CH radicals was measured during plasma deposition of hydrogenated diamondlike carbon (DLC) films using the imaging of radicals interacting with surfaces (IRIS) method. In this technique, spatially resolved laser-induced fluorescence (LIF) is used to determine surface reactivity, R, of plasma species. The measured reactivity of CH is near unity and shows no dependence on the applied rf power (P), argon fraction, substrate temperature, or substrate bias. Kinetic translational temperatures, (T), of CH in the molecular beam were also measured. Modeling of the kinetic data yields ThetaT(CH) values of approximately 2200-2500 K and 1600-1700 K for CH4/Ar plasmas at pressures of 50 and 110 mTorr, respectively, with no clear dependence on the argon fraction (at P = 100 W). The average ThetaT(CH) does, however, change with P, (T) = approximately 2050-9050 K, over the range P = 180-20 W. These results indicate that ThetaT(CH) is associated with the electron temperature in the plasma. The rotational temperature, (R), determined from the CH rotational excitation spectrum is approximately 1450 K with no clear dependence on P or the Ar fraction in the feed. The difference between ThetaT(CH) and ThetaR(CH) can be explained by the different relaxation rates after the dissociation of CH4 by electron impact.

Journal Article↗

PubMed2006

Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection.

BACKGROUND/AIMS: Exposure to HBV leads to a distinct clinical course which is partially pertained to host genetic variability. We aimed to study polymorphisms of type I interferon receptor 1 (IFNAR1) promoter and their potential effects on chronic HBV infection. METHODS: Polymorphisms of IFNAR1 promoter were identified in 320 chronic hepatitis B patients, 148 spontaneously recovered individuals, 148 healthy Chinese donors and 114 Caucasians. Their functional capability in driving reporter gene expression was analyzed. RESULTS: Four polymorphic alleles were identified at loci -568, -408, -77 and -3. Association analysis revealed that carriers of alleles -568G, -408C and their related haplotype I were less susceptible to chronic HBV infection whereas those of alleles -568C, -408T and related haplotype III were significantly associated with higher risk to chronic hepatitis B (P<0.01). In a reporter-driven system, the promoter variants with alleles -408C and -3C could drive higher expression of the reporter gene than those with alleles -408T and -3T (P<0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability. CONCLUSIONS: Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.

Asian People↗

PubMed2006

Collapse transition of two-dimensional flexible and semiflexible polymers.

The nature of the globule-coil transition of surface-confined polymers has been an issue of debate. Here this 2D collapse transition is studied through a partially directed lattice model. In the general case of polymers with positive bending stiffness (Delta>0), the collapse transition is first order; it becomes second order only in the limiting case of zero bending stiffness (Delta triple bond 0). These analytical results are confirmed by Monte Carlo simulations. We also suggest some possible future experiments.

DNA↗

PubMed2006

Voluntary participation and informed consent to international genetic research.

OBJECTIVES: We compared voluntary participation and comprehension of informed consent among individuals of African ancestry enrolled in similarly designed genetic studies of hypertension in the United States and Nigeria. METHODS: Survey questionnaires were used to evaluate factors associated with voluntariness (the number of people volunteering) and understanding of the study's genetic purpose. A total of 655 individuals (United States: 348; Nigeria: 307) were interviewed after participation in the genetic studies. RESULTS: Most US respondents (99%), compared with 72% of Nigerian respondents, reported being told the study purpose. Fewer than half of the respondents at both sites reported that the study purpose was to learn about genetic inheritance of hypertension. Most respondents indicated that their participation was voluntary. In the United States, 97% reported that they could withdraw, compared with 67% in Nigeria. In Nigeria, nearly half the married women reported asking permission from husbands to enroll in the hypertension study; no respondents sought permission from local elders to participate in the study. CONCLUSIONS: Our findings highlight the need for more effective approaches and interventions to improve comprehension of consent for genetic research among ethnically and linguistically diverse populations in all settings.

Adult↗

PubMed2006

Origin of mitochondrial DNA diversity of domestic yaks.

BACKGROUND: The domestication of plants and animals was extremely important anthropologically. Previous studies have revealed a general tendency for populations of livestock species to include deeply divergent maternal lineages, indicating that they were domesticated in multiple, independent events from genetically discrete wild populations. However, in water buffalo, there are suggestions that a similar deep maternal bifurcation may have originated from a single population. These hypotheses have rarely been rigorously tested because of a lack of sufficient wild samples. To investigate the origin of the domestic yak (Poephagus grunnies), we analyzed 637 bp of maternal inherited mtDNA from 13 wild yaks (including eight wild yaks from a small population in west Qinghai) and 250 domesticated yaks from major herding regions. RESULTS: The domestic yak populations had two deeply divergent phylogenetic groups with a divergence time of > 100,000 yrs BP. We here show that haplotypes clustering with two deeply divergent maternal lineages in domesticated yaks occur in a single, small, wild population. This finding suggests that all domestic yaks are derived from a single wild gene pool. However, there is no clear correlation of the mtDNA phylogenetic clades and the 10 morphological types of sampled yaks indicating that the latter diversified recently. Relatively high diversity was found in Qinghai and Tibet around the current wild distribution, in accordance with previous suggestions that the earliest domestications occurred in this region. Conventional molecular clock estimation led to an unrealistic early dating of the start of the domestication. However, Bayesian estimation of the coalescence time allowing a relaxation of the mutation rate are better in agreement with a domestication during the Holocene as supported by archeological records. CONCLUSION: The information gathered here and the previous studies of other animals show that the demographic histories of domestication of livestock species were highly diverse despite the common general feature of deeply divergent maternal lineages. The results further suggest that domestication of local wild prey ungulate animals was a common occurrence during the development of human civilization following the postglacial colonization in different locations of the world, including the high, arid Qinghai-Tibetan Plateau.

Animals↗

PubMed2006

Activation of pregnane X receptor disrupts glucocorticoid and mineralocorticoid homeostasis.

The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis. Activation of PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin) markedly increased plasma concentrations of corticosterone and aldosterone, the respective primary glucocorticoid and mineralocorticoid in rodents. The increased levels of corticosterone and aldosterone were associated with activation of adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1, CYP11b2, and 3beta-hydroxysteroid dehydrogenase. The PXR-activating transgenic mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid circadian rhythm, and lack of glucocorticoid responses to psychogenic stress. Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the corticosterone-suppressing effect of dexamethasone was intact, suggesting a functional hypothalamus-pituitary-adrenal axis despite a severe disruption of adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR-activating transgenic mice is reminiscent of the pseudo-Cushing's syndrome in patients. The glucocorticoid effect appears to be PXR specific, as the activation of constitutive androstane receptor in transgenic mice had little effect. We propose that PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions.

3-Hydroxysteroid Dehydrogenases↗

PubMed2006

Condensation in a zero range process on weighted scale-free networks.

We study the condensation phenomenon in a zero range process on weighted scale-free networks in order to show how the weighted transport influences the particle condensation. Instead of the approach of grand canonical ensemble which is generally used in a zero range process, we introduce an alternate approach of the mean-field equations to study the dynamics of particle transport. We find that the condensation on the scale-free network is easier to occur in the case of weighted transport than in the case of weight-free networks. In the weighted transport, especially, a dynamical condensation is even possible for the case of no interaction among particles, which is impossible in the case of weight-free networks.

Journal Article↗