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Cong Wang

Publications and source records attributed to Cong Wang.

18 recordsLinked to original sources
PubMed2026

The N6-methyladenosine reader IGF2BP2 in T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous and aggressive lymphoid neoplasm that lacks pathogenic biomarkers of RNA modification with therapeutic potential. IGF2BP2 is recognized as an N6-methyladenosine reader critically involved in oncogenesis. In this study, we observed consistently high expression of IGF2BP2 across common nodal PTCL subtypes in 3 independent external cohorts, which was further confirmed in our RNA-sequencing (RNA-seq) data set of 196 patients with newly diagnosed PTCL. Both in vitro and in vivo, IGF2BP2 promoted tumor cell growth and inhibited CD8+ T-cell infiltration within the tumor microenvironment. Mechanistically, IGF2BP2 bound to endosome-related genes (RAB4, VPS35, RAB9, and STAM) to maintain their stability, which resulted in enhanced endocytic activity and increased internalization of membrane proteins, and ultimately induced tumor cell proliferation and inhibition of CD8+ T-cell-mediated tumor cytotoxicity. The relationship between IGF2BP2 and endocytosis-associated genes was confirmed using RNA-seq data from patients with PTCL. IGF2BP2 as an upstream regulator of both tumor growth and immune suppression was further demonstrated in patient-derived xenograft models and a coculture system established using tumor samples from patients with PTCL and peripheral blood mononuclear cells. Notably, therapeutic targeting of IGF2BP2 with CWI1-2 suppressed endocytosis and impeded tumor growth in both cell lines and patient-derived xenograft models. Collectively, our findings highlight IGF2BP2 as a clinically relevant oncogenic driver in PTCL that integrates tumor-intrinsic growth signals with immune evasion through endocytosis-centered regulation, providing a novel therapeutic rationale for RNA modification-based strategies that concurrently target tumor cells and the tumor microenvironment.

Humans↗
PubMed2026

A cfDNA fragmentomics classifier for noninvasive differentiation of benign and malignant renal masses.

Noninvasive differentiation of malignant and benign renal masses remains a major clinical challenge, particularly for radiologically indeterminate lesions. Here, we developed and validated a plasma cell-free DNA (cfDNA) fragmentomics-based machine learning classifier for renal mass characterization. The model was trained on 331 participants (171 cancer, 160 benign) and independently validated on 144 participants (73 cancer, 71 benign). Three cfDNA fragmentation features, including copy number variation (CNV), fragmentation-based methylation (FRAGMA), and nucleosome footprint (NF), derived from low-pass whole-genome sequencing, were integrated into an ensemble framework. The model achieved strong discriminative performance, with area under the curve (AUC) values of 0.956 in the training cohort and 0.946 in the validation cohort, outperforming individual feature-based models. At a predefined operating threshold corresponding to 90% sensitivity, specificity reached 0.90 and 0.87, respectively. Notably, most cancer samples exhibited low tumor fraction (TF&#x2009;<&#x2009;3%), yet the model maintained robust performance in low-TF samples (AUCs: 0.952 and 0.941, respectively). Performance remained consistent across tumor stage, grade, and histological subtypes. The classifier also demonstrated potential clinical utility in diagnostically challenging settings, including lipid-poor angiomyolipoma and oncocytoma, with 12 of 13 oncocytoma samples correctly classified in an independent cohort. In addition, the model correctly identified 85.3% of benign masses&#x2009;>&#x2009;4&#xa0;cm, for which surgical intervention is more commonly considered, and 84.6% of malignant tumors&#x2009;&#x2264;&#x2009;4&#xa0;cm, for which management can be challenging. Collectively, these findings support cfDNA fragmentomics as a promising noninvasive liquid biopsy approach for renal mass evaluation and clinical decision-making.

Humans↗
PubMed2026

Smoking Cue Reactivity in Relation to Uncertain-Threat and Reward-Anticipation Networks: A Coordinate-Based fMRI Meta-Analysis.

BACKGROUND: Smoking is a concerning medical and social problem, yet how the brain links stress to continued smoking is still not well understood. This coordinate-based meta-analysis identified convergent activations for smoking cues, uncertain threat, and reward anticipation, and examined co-activation patterns to clarify whether smoking-cue activity in smokers relates to threat and reward activity in non-addicted controls. METHODS: We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis of 102 fMRI studies (N = 3,068), including 30 studies on smoking cue reactivity (n = 945), 48 on reward anticipation (n = 1,413), and 24 on uncertain threat processing (n = 1,621). We performed single, conjunction, and contrast analyses, followed by meta-analytic connectivity modeling (MACM) of key regions. RESULTS: Single analysis revealed smoking engaged bilateral ACC (-1.1, 46.2, -1.1), uncertain threat engaged bilateral insula (left = -33.6, 22, 4.3, right = 41.3, 22, 1), reward anticipation activated thalamus (0.9, 1.3, -3.1) and medial frontal gyrus (2.7, 6.6, 52.1). Conjunction and contrast analyses showed shared or unique activation for each task in its respective regions. MACM showed ACC co-activation with thalamus and medial frontal gyrus, while insula co-activated with ACC and inferior frontal gyrus. CONCLUSIONS: Each process converged in a separate region, with no overlap between the smoking-cue map and either the threat or reward map. The ACC nonetheless co-activated with reward-related regions and shared network membership with the threat-related insula. On this basis we hypothesize a shift in motivation from stress-driven reward toward cue-driven craving, to be tested within subjects, and identify candidate neuromodulation targets for preventing stress-precipitated relapse.

fMRI↗
PubMed2026

PDE4DIP-Derived MMG8 Supports Proliferation, Migration, and Tumor Growth in Hepatocellular Carcinoma Models.

BACKGROUND: PDE4DIP encodes a scaffold protein that has been implicated in compartmentalized signaling and cytoskeletal organization, but the role of its myomegalin variant 8 (MMG8) isoform in hepatocellular carcinoma (HCC) remains unclear. To address this gap, we examined PDE4DIP expression in public HCC datasets and investigated the functional role of MMG8 in HCC models. METHODS: PDE4DIP expression was analyzed in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and two Gene Expression Omnibus (GEO) cohorts (GSE14520, GSE36376). MMG8 function was assessed in Huh7 cells using siRNA-mediated knockdown and in Hepa1-6 cells using lentiviral Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9)-mediated knockout. Cell proliferation in MMG8-KD Huh7 cells and MMG8-KO Hepa1-6 cells was assessed using Cell Counting Kit-8 (CCK-8) assays, while Huh7 cell migration was evaluated using Transwell assays. Tumor growth was assessed using a murine subcutaneous tumor model. Immunohistochemical staining for Ki67 and cleaved caspase-3 was employed to assess tumor cell proliferation and apoptosis-associated changes, respectively. Gene set enrichment analysis was performed in TCGA-LIHC tumors stratified based on PDE4DIP expression. RESULTS: PDE4DIP expression differed between tumor and non-tumor tissues across HCC cohorts, although the directionality of this difference was not uniform. MMG8 knockdown in Huh7 cells reduced proliferation and migratory activity. A single-cell-derived MMG8-KO Hepa1-6 clone exhibited reduced proliferation in vitro and formed smaller tumors in vivo, with lower Ki67 positivity but no significant difference in cleaved caspase-3 positivity between groups. In tumors from the TCGA-LIHC cohort, PDE4DIP expression was associated with distinct transcriptional programs. Specifically, PDE4DIP-high tumors presented with positive normalized enrichment score (NES) values for several metabolic pathways, whereas adhesion/extracellular matrix (ECM), cell cycle/proliferation, and translation/ribosome-related pathways exhibited negative NES values. CONCLUSIONS: These findings support a functional contribution of MMG8 to proliferative, migratory, and tumor-growth phenotypes in the tested HCC models. Bulk gene-level PDE4DIP expression in human tumors was associated with context-dependent transcriptional states and should not be interpreted as a direct surrogate for MMG8 function.

Liver Neoplasms↗
PubMed2025

Depth-dependent multi-kingdom microbial interactions and biogeochemical cycling genes in eutrophic shallow lake sediments.

Microorganisms are pivotal to lake ecosystem biogeochemical cycles, yet existing research often focuses on single microbial kingdoms or surface sediments, neglecting multi-kingdom interactions and depth-resolved dynamics. To address these gaps, we used metagenomic sequencing to characterize microbial communities and their functional associations across overlying water and 0-45 cm sediments in four shallow lakes of the middle Yangtze River basin, China. Despite increasing bacterial and fungal diversity with depth, the 0-9 cm surface sediments exhibited the strongest multi-kingdom network connectivity and the greatest microbial stability. Functional genes exhibited clear depth-dependent patterns: nitrogen cycling genes, including those involved in dissimilatory nitrate reduction to ammonium, were most enriched in the upper 0-9 cm of sediment; methane cycling genes were positively correlated with depth; phosphorus cycling genes and some sulfur cycling genes, such as assimilatory sulphate reduction, declined with depth. Sediment microbial assembly was dominated by deterministic processes, in which the vertical distribution of functional genes was primarily dictated by heavy metals and conventional environmental indicators. These findings highlight depth-specific multi-kingdom microbial interactions and their associations with biogeochemical cycling, advancing lacustrine microbial ecology understanding and providing references for lake conservation under environmental change.

Lakes↗
PubMed2025

Genome-wide identification and analysis of paclobutrazol-resistance gene family in cotton and the positive role of GhPRE3 in salt stress and drought stress resistance.

Compared with other transcription factors, much less studies have been performed on paclobutrazol-resistance (PRE), a subgroup of the extensive bHLH transcription factor gene family, and the research in cotton was also limited. By utilizing the PRE genes and their conserved domains identified in Arabidopsis, a total of 23, 22, 11, and 12 PRE genes were identified from two major cultivated cotton species and their two ancestors, respectively. The cotton PRE gene family was categorized into three subgroups based on evolutionary tree analysis. Motif and intron analyses indicated that the PRE gene has remained highly conserved throughout evolution. Collinearity analysis indicated that gene duplication, particularly through fragment replication, has significantly contributed to the expansion of the cotton PRE family. An exploration of the conserved elements within the PRE gene family uncovered numerous elements associated with plant stress resistance. Additionally, cotton transcriptome and qRT-PCR analysis showed that PRE genes were associated with a variety of abiotic stresses, including salt, drought, and cold treatments. Subcellular localization experiments indicated that the GhPRE3 gene is associated with membrane proteins. Finally, we selected the GhPRE3 gene for a VIGS experiment, which revealed that under salt stress and drought stress conditions, the wilting of leaves in the GhPRE3-silenced plants was significantly more severe than that observed in the control group, with T-AOC levels notably lower and MDA levels significantly higher. Overexpression of GhPRE3 enhanced seed germination and root development in transgenic Arabidopsis thaliana under salt stress and drought stresses. This suggests that GhPRE3 plays a positive regulatory role in cotton tolerance to salt and drought stressed, providing a reference for molecular genetic breeding of cotton with salt and drought tolerance.

Gossypium↗
PubMed2019

Profiling the long noncoding RNA interaction network in the regulatory elements of target genes by chromatin in situ reverse transcription sequencing.

Long noncoding RNAs (lncRNAs) can regulate the activity of target genes by participating in the organization of chromatin architecture. We have devised a "chromatin-RNA in situ reverse transcription sequencing" (CRIST-seq) approach to profile the lncRNA interaction network in gene regulatory elements by combining the simplicity of RNA biotin labeling with the specificity of the CRISPR/Cas9 system. Using gene-specific gRNAs, we describe a pluripotency-specific lncRNA interacting network in the promoters of Sox2 and Pou5f1, two critical stem cell factors that are required for the maintenance of pluripotency. The promoter-interacting lncRNAs were specifically activated during reprogramming into pluripotency. Knockdown of these lncRNAs caused the stem cells to exit from pluripotency. In contrast, overexpression of the pluripotency-associated lncRNA activated the promoters of core stem cell factor genes and enhanced fibroblast reprogramming into pluripotency. These CRIST-seq data suggest that the Sox2 and Pou5f1 promoters are organized within a unique lncRNA interaction network that determines the fate of pluripotency during reprogramming. This CRIST approach may be broadly used to map lncRNA interaction networks at target loci across the genome.

Animals↗
PubMed2006

Bone morphogenetic protein-4 expression in the adult rat brain.

Bone morphogenetic protein-4 (BMP4) is a member of the transforming growth factor-beta (TGF-beta) superfamily and plays important roles in multiple biological events. Although BMP4 expression has been well described in the early development of the central nervous system (CNS), little information is available on its expression in the adult CNS. Therefore, we investigated BMP4 expression in the adult rat CNS by using immunohistochemistry. BMP4 is intensely expressed in most neurons and their dendrites. In addition, intense BMP4 expression was also observed in the neuropil of the gray matters where high plasticity is reported, such as the molecular layer of the cerebellum and the superficial layer of the superior colliculus. Furthermore, we found that astrocytes also express BMP4 protein. These data indicate that BMP4 is more widely expressed throughout the adult CNS than previously reported, and its continued abundant expression in the adult brain strongly supports the idea that BMP4 plays pivotal roles also in the adult brain.

Animals↗
PubMed2006

Learning from neural control.

One of the amazing successes of biological systems is their ability to "learn by doing" and so adapt to their environment. In this paper, first, a deterministic learning mechanism is presented, by which an appropriately designed adaptive neural controller is capable of learning closed-loop system dynamics during tracking control to a periodic reference orbit. Among various neural network (NN) architectures, the localized radial basis function (RBF) network is employed. A property of persistence of excitation (PE) for RBF networks is established, and a partial PE condition of closed-loop signals, i.e., the PE condition of a regression subvector constructed out of the RBFs along a periodic state trajectory, is proven to be satisfied. Accurate NN approximation for closed-loop system dynamics is achieved in a local region along the periodic state trajectory, and a learning ability is implemented during a closed-loop feedback control process. Second, based on the deterministic learning mechanism, a neural learning control scheme is proposed which can effectively recall and reuse the learned knowledge to achieve closed-loop stability and improved control performance. The significance of this paper is that the presented deterministic learning mechanism and the neural learning control scheme provide elementary components toward the development of a biologically-plausible learning and control methodology. Simulation studies are included to demonstrate the effectiveness of the approach.

Algorithms↗
PubMed2005

Macroporous calcium phosphate glass-ceramic prepared by two-step pressing technique and using sucrose as a pore former.

Macroporous calcium phosphate glass-ceramic with an initial glass composition of 60CaO.30P2O5.3TiO2.7Na2O in mol% was successfully prepared by sintering the mixture compact consisting of calcium phosphate glass and sucrose powders, which was formed using a two-step pressing technique. After burning off the sucrose phase, a 3D interconnected macroporous structure was formed in the sintered body, in which the skeleton consisting of the calcium phosphate glass-ceramic (including beta-calcium pyrophosphate and beta-tricalcium phosphate as the crystalline phases) was transformed from the initial glass during the sintering. The macropores with several hundred microns in diameter and the large interconnection size (approximately 100 microm), which result from the controllably large-sized sucrose particles and the hot-pressing at a little higher temperature than the sucrose's melting point, are believed to meet the requirements for cell adhesion and bone tissue regeneration well. Moreover, in vitro dissolution behavior study indicates that the calcium phosphate glass-ceramic is soluble to an acetic acid solution of pH 5-7. These, together with the simplicity and feasibility of the innovative fabrication method itself, show that the formed porous glass-ceramic has a promising potential for application to a scaffold for bone tissue engineering.

Biocompatible Materials↗
PubMed2005

Constitutive modeling of the densification and the grain growth of hydroxyapatite ceramics.

In the present work, constitutive models for densification and grain growth were employed to investigate the sintering behavior of pure hydroxyapatite ceramics. For densification study, lattice diffusion, grain-boundary diffusion, and interface reaction mechanisms, and for grain-growth study, surface diffusion mechanism, were considered respectively. Hydroxyapatite ceramics were pressurelessly sintered. The sintering results were discussed and compared with the modeling results. Based on the constitutive models employed and the experimental results obtained, grain-boundary diffusion was identified as the dominant mechanism for the densification of the investigated hydroxyapatite. The grain-growth model provided a good prediction to the grain growth of the investigated hydroxyapatite. The activation energies for densification and grain growth of hydroxyapatite ceramics were evaluated as 1150+/-40 and 1020+/-40 KJ mol(-1), respectively.

Biocompatible Materials↗
PubMed2005

Differential expression of KCC2 accounts for the differential GABA responses between relay and intrinsic neurons in the early postnatal rat olfactory bulb.

The rat olfactory bulb is anatomically immature at birth, and considerable neurogenesis and synaptogenesis are known to take place postnatally. In addition, significant physiological changes have also been reported in this period. For example, granule cell-mediated inhibition following electrical stimulations to the lateral olfactory tract is robust during the first postnatal week, and then decreases abruptly after the second week. However, the mechanism underlying this enhanced inhibition remains to be elucidated. To know the cause of this phenomenon, we investigated the expression patterns of cation-Cl(-) co-transporters (KCC1, KCC2 and NKCC1) mRNAs, which are responsible for the regulation of [Cl(-)](i). In addition, responses to gamma-aminobutyric acid (GABA) were measured by gramicidin-perforated patch-clamp recordings and Ca(2+) imaging using fura-2. We found that in the early postnatal period, mitral cells expressing KCC2 mRNA were inhibited by GABA, while granule cells lacking KCC2 mRNA expression were depolarized or excited by GABA. These results indicate that transient GABA-mediated excitation on granule cells might be the main cause of the enhanced inhibition on mitral cells, and suggest that these differential GABA responses between relay and intrinsic neurons play pivotal roles in the early postnatal rat olfactory bulb.

Animals↗
PubMed2004

Adaptive neural control of uncertain MIMO nonlinear systems.

In this paper, adaptive neural control schemes are proposed for two classes of uncertain multi-input/multi-output (MIMO) nonlinear systems in block-triangular forms. The MIMO systems consist of interconnected subsystems, with couplings in the forms of unknown nonlinearities and/or parametric uncertainties in the input matrices, as well as in the system interconnections without any bounding restrictions. Using the block-triangular structure properties, the stability analyses of the closed-loop MIMO systems are shown in a nested iterative manner for all the states. By exploiting the special properties of the affine terms of the two classes of MIMO systems, the developed neural control schemes avoid the controller singularity problem completely without using projection algorithms. Semiglobal uniform ultimate boundedness (SGUUB) of all the signals in the closed-loop of MIMO nonlinear systems is achieved. The outputs of the systems are proven to converge to a small neighborhood of the desired trajectories. The control performance of the closed-loop system is guaranteed by suitably choosing the design parameters. The proposed schemes offer systematic design procedures for the control of the two classes of uncertain MIMO nonlinear systems. Simulation results are presented to show the effectiveness of the approach.

Neural Networks, Computer↗
PubMed2002

Developmental changes in KCC1, KCC2, and NKCC1 mRNA expressions in the rat brain.

We investigated the expressions of KCC1, KCC2 and NKCC1 mRNAs in the developing rat brain. The neuroepithelium showed abundant KCC1 and NKCC1 mRNA expressions, while KCC2 mRNA was not detected there. In contrast, KCC2 mRNA was preferentially expressed in postmitotic mature neurons. These results suggest that the appearance of KCC2 expression mainly depends on the maturation of individual neurons.

Animals↗
PubMed2002

Developmental changes in KCC1, KCC2 and NKCC1 mRNAs in the rat cerebellum.

Cation chloride cotransporters are considered to play pivotal roles in controlling the intracellular and extracellular ionic environments of neurons, hence controlling neuronal function. To establish how these cotransporters are involved in cerebellum development, we investigated the expression of KCC1, KCC2 and NKCC1 mRNAs in the developing rat cerebellum using in situ hybridization histochemistry. In the external germinal layer, where premature cells exist, we found substantial KCC1 and NKCC1 mRNA expression on P7 and P14, while KCC2 mRNA was not detected. In contrast, KCC2 mRNA was already expressed in Purkinje cells on P1. We also observed KCC2 mRNA expression in postmigratory granule cells after P7. The expression of KCC1, KCC2, and NKCC1 mRNAs reached adult patterns by P21. In the adult cerebellum, KCC2 mRNA was expressed in most neurons, including Purkinje cells, granule cells, and stella/basket cells, while KCC1 and NKCC1 mRNAs were only detected in granule cells and glial cells. These findings suggest that in the rat cerebellum KCC2 mRNA expression is induced when neurons arrive their final destinations.

Aging↗
PubMed2002

A neuronal inhibitory domain in the N-terminal half of agrin.

Agrin is required for appropriate pre- and postsynaptic differentiation of neuromuscular junctions. While agrin's ability to orchestrate postsynaptic differentiation is well documented, more recent experiments have suggested that agrin is also a "stop signal" for the presynaptic neuron, and that agrin has actions on neurons in the CNS. To elucidate the neuronal activities of agrin and to define the receptor(s) responsible for these functions, we have examined adhesions of neurons and their neurite-outgrowth responses to purified agrin in vitro. We find that both full-length agrin and the C-terminal 95 kDa of agrin (agrin c95), which is sufficient to induce postsynaptic differentiation, are adhesive for chick ciliary ganglion (CG) and forebrain neurons. Consistent with previous findings, our results show that N-CAM binds to full-length agrin, and suggest that alpha-dystroglycan is a neuronal receptor for agrin c95. In neurite outgrowth assays, full-length agrin inhibited both laminin- and N-cadherin-induced neurite growth from CG neurons. The N-terminal 150 kDa fragment of agrin, but not agrin c95, inhibited neurite outgrowth, indicating that domains in the N-terminal portion of agrin are sufficient for this function. Adhesion assays using protein-coated beads and agrin-expressing cells revealed differential interactions of agrin with members of the immunoglobulin superfamily of cell adhesion molecules. However, none of these, including N-CAM, appeared to be critical for neuronal adhesion. In summary, our results suggest that the N-terminal half of agrin is involved in agrin's ability to inhibit neurite outgrowth. Our results further suggest that neither alpha-dystroglycan nor N-CAM, two known binding proteins for agrin, mediate this effect.

Agrin↗