Biology subjects

Kong, H.

Publications and source records attributed to Kong, H..

17 recordsLinked to original sources

bioRxiv2026

Structure-aware deep learning predicts influenza antigenicity and guides vaccine strain recommendation

The continuous accumulation of genetic mutations in influenza A viruses (IAVs) drives antigenic drift, necessitating precise antigenic prediction for optimal vaccine strain selection. While sequence-based methods have advanced antigenic surveillance, they neglect the three-dimensional structural context that fundamentally dictates viral antigenicity. Here, we introduce Vir3D, which leverages ESMFold-derived structural information from amino acid sequences to precisely predict viral antigenicity and guide vaccine strain selection. Across both human H3 and highly pathogenic avian H5 subtypes, Vir3D not only accurately discriminates antigenic variants and infers pairwise antigenic distances, but also mechanistically delineates key structural residues driving viral immune evasion. In a decade-long retrospective analysis, Vir3D-prioritized vaccines consistently achieve broader antigenic coverage of circulating strains than World Health Organization (WHO) recommendations. Crucially, Vir3D successfully predicts that the emerging U.S. dairy cattle H5N1 virus (TX/24) remains antigenically stable relative to clade 2.3.4.4b vaccine strains, and subsequent wet-laboratory validation of hemagglutination inhibition (HI) assays definitively corroborates this finding. Overall, Vir3D establishes a powerful, structure-driven framework for proactive influenza surveillance and pandemic preparedness.

bioinformatics↗

bioRxiv2026

The genome of an aneuploid cultivar facilitates elucidating the genetic bases of trait polymorphisms in Phalaenopsis orchids

As an important ornamental crop, Phalaenopsis orchids exhibit extraordinary trait diversity with unclear genetic bases. Here, we present a haplotype-resolved, chromosome-level genome for an aneuploid cultivar Santiago. We reveal pervasive variation in the number and sequence among homoeologous genes. When serving as a reference, this genome facilitates the genetic understanding of trait variation in a hybrid population that is highly representative in trait polymorphisms. Specifically, nucleotide polymorphisms in a potential long-distance enhancer and the consequential expression variation of PsAGL6-2, presence/absence of PsMYB12 and b-type homoeologous gene of PsMYB2 determine lip morphology variation, presence/absence of venation-associated stripes and background pink color, respectively. Diverse functions of PsMYBx1 in repressing anthocyanin accumulation across different cultivars further enhances the color patterning diversity in Phalaenopsis. Our study provides a practical framework for using a highly heterogeneous, haplotype-resolved genome to decode phenotypic diversity and has the potential to promote marker-assisted breeding in Phalaenopsis.

genomics↗

bioRxiv2026

FluNexus: a versatile web platform for antigenic prediction and visualization of influenza A viruses

Influenza A viruses continuously undergo antigenic evolution to escape host immunity induced by previous infections or vaccinations, consequently causing seasonal epidemics and occasional pandemics. Antigenic prediction and visualization of influenza A viruses are crucial for precise vaccine strain selection and robust pandemic preparedness. However, a user-friendly online platform for these capabilities remains notably absent, despite widespread demand. Here, we present FluNexus (https://flunexus.com), the first-of-its-kind, one-stop-shop web platform designed to facilitate the prediction and visualization of the antigenic change in emerging variants. FluNexus features a data preprocessing module for hemagglutinin subunit 1 (HA1) and hemagglutination inhibition (HI) data across three major public health threat subtypes (H1, H3 and H5). Meanwhile, FluNexus provides an interactive interface for online antigenic prediction and offers practical guidance for researchers. Most notably, FluNexus offers the visualization of influenza A virus antigenic evolution, providing intuitive insights into its antigenic dynamics. Specially, FluNexus proposes a novel manifold-based method for positioning antigens and antisera, generating accurate antigenic cartographies even with sparse HI data. By alleviating the programming burden on biologists, FluNexus supports more informed decision-making in vaccine strain selection and strengthens surveillance and pandemic preparedness. HighlightsO_LIFluNexus features a data preprocessing module for HA1 and HI data spanning the H1, H3, and H5 subtypes. C_LIO_LIFluNexus facilitates online antigenic prediction utilizing ten state-of-the-art antigenic prediction tools, and offers practical guidance based on a comparative evaluation of their performance. C_LIO_LIFluNexus provides a visualization module for mapping antigenic evolution of influenza A viruses, incorporating a novel manifold-based method for antigenic cartography. C_LI

bioinformatics↗

bioRxiv2026

Functional characterization of a multi-cancer risk locus on chromosome band 2q33.1 near CASP8

Genome-wide association studies (GWAS) of melanoma have identified numerous susceptibility loci. However, causal genes and variants underlying risk have yet to be established for most. It is becoming apparent that many functional variants underlying complex traits act via cis-regulation that may be context-specific, dependent on availability of specific transcription factors/complexes in specific cell types and cell-states. To characterize a risk locus on chromosome band 2q33.1 associated with melanoma, breast cancer, and keratinocyte cancers, we integrated fine-mapping, cell-type specific expression quantitative trait locus (eQTL) analysis, a massively parallel reporter assay, individual luciferase assays, and SNP-based proteomics. Integrated analysis implicates the presence of multiple functional variants lying primarily within a promoter for CASP8. A haplotype containing rs3769823 appeared have the largest effect on expression. Strikingly, both tumor/normal context and this risk-associated haplotype play critical roles in mediating allelic cis-regulatory activity. Quantitative mass spectrometry for rs3769823 identified both E4F1, a transcriptional repressor, and IRF2, a transcriptional activator, as binding preferentially to risk-associated rs3969823-A. The binding of these transcription factors was validated via EMSA, supershift, and chromatin immunoprecipitation (ChIP) assays. The relative levels of E4F1 and IRF2 differ by cell-type and play a role in mediating transcriptional activity in a cell-type specific manner. Our results indicate that the top credible causal set variant rs3769823 likely influences expression of CASP8 and FLACC1 in a cell-type specific manner and may be a relevant functional variant for multiple cancers associated with this locus.

genetics↗

bioRxiv2025

Living Neurosheets: Engineering readily deployable neural architectures

Inspired by the ability of brain structures to support cognitive processing, the need for reliable queryable neural models, and emerging biohybrid applications, we present Living Neurosheets: practical, malleable, modular, and scalable systems for realizing living neural architectures, bio-inspired or beyond evolutionary precedent. By innervating porous sheets, paper-like substrates are endowed with neural function while retaining exceptional versatility. Pre-programmed porosity anchors deposited neurons for reliable spatial control. Cutting, folding, and stacking allow intuitive design, modular composition, and batch fabrication (by the hundreds) of complex neural motifs that preserve geometry and function for months. Reversible integration with tissue-matched optoelectronics enables both sample reuse across hardware and hardware multiplexing across samples, for high-throughput, multimodal investigations. We illustrate these aspects across tissue topologies, gyri-inspired manifolds, and laminar cortical mimics, attaining control over entrainment, synchronization, propagation, suppression, and augmentation dynamics--key features of in vivo neural activity. Finally, via cross-instrument portability, we fuse spatial transcriptomics and electrophysiology, linking gene programs to emergent dynamics.

neuroscience↗

bioRxiv2025

Interwoven DNA-MOF crystals for multi-millennial data storage

DNA has emerged as a promising medium for high-density and energy-efficient data storage, providing a promising solution to capacity constraints and energy demands resulting from the exponential growth of data. Long-term stable storage of DNA data in ambient conditions is a critical requirement for its practical application. Whereas strategies have been proposed to protect DNA from environmental degradation, they are often at the expense of data storage density. Here, we propose a strategy via interweaving metal-organic framework (MOF) and DNA to synthesize DNA-MOF crystal (DNA-MOF), a high-density and long-lifespan DNA-based information material. The uniform distribution of DNA molecules within the crystalline frameworks enables a high loading capacity of up to 30 wt%, corresponding to a theoretical information density of 106.6 exabytes/g. The crystal structure of MOF-DNA demonstrates efficient resistance to environmental damage such as heat, ultraviolet radiation, DNase, etc., achieving an estimated archival half-life over 24,000 years at 9.4 {degrees}C. The interwoven DNA-MOF crystals establish a material foundation for the reliable operation of DNA storage systems in open-field deployment and provide a new pathway toward sustainable long-term management of massive data.

biochemistry↗

bioRxiv2024

An immunomechanical checkpoint PYK2 governs monocyte-to-macrophage differentiation in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic, stiff tumor microenvironment (TME), where tumor-associated macrophages (TAMs) drive ECM remodeling, progression, and immune evasion. The contribution of mechanical cues to monocyte differentiation into TAMs remains largely unexplored. Here we show that mechanical force is required for monocyte-to-macrophage differentiation. PYK2, as an innovative immunomechanical checkpoint, de facto governs this differentiation process. We demonstrated that PYK2 senses mechanical signals via Piezo1 and integrins, triggering F-actin polymerization and translocating to the nucleus to regulate mechanotransduction and differentiation genes (e.g., ACTR3, RELA). Targeted deletion of PYK2 impairs the differentiation and polarization of monocyte-derived macrophages, reshapes the PDAC microenvironment, and enhances the efficacy of anti-PD-1 immunotherapy. These findings underscore the critical role of mechanical cues in monocyte differentiation and suggest that targeting PYK2 is a promising strategy to modulate TAM function and improve immunotherapy outcomes in patients with PDAC. Statement of significanceThis study identifies PYK2 as an immunomechanical checkpoint that drives monocyte-to-macrophage differentiation in PDAC via Piezo1/integrin-mediated mechanical cues. Targeted deletion of PYK2 reshapes the PDAC microenvironment, and enhances the efficacy of anti-PD-1 immunotherapy, suggesting PYK2 as a promising therapeutic target to overcome immunotherapy resistance.

immunology↗

bioRxiv2024

Multi-modal profiling identifies CD4+CXCR5+PD-1- Tfh cells as prognostic and predictive biomarkers for response to R-CHOP therapy in human DLBCL

Despite the improvements in clinical outcomes for patients with Diffuse Large B-Cell Lymphoma (DLBCL), a significant proportion of those patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. Characterizing the heterogeneity of the tumor microenvironment (TME) in diffuse large B cell lymphoma (DLBCL) is crucial for understanding relapsed/refractory disease. However, the complex and diverse nature of the TME has impeded progress. Here, using single-cell RNA sequencing(scRNA-seq), we explored the DLBCL landscape at single-cell resolution, profiling 77,344 cells from both primary and relapsed DLBCL patients. We further investigated the shared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors by integrating next-generation DNA sequencing data and multiple scRNA-seq datasets from total 72,351 cells. Our results demonstrated that there was a significant decrease of CD4+CXCR5+PD-1- Tfh cells, along with excessive activation of the TNF-NF{kappa}B signaling pathways in malignant B cells in R/R disease. Furthermore, by using multiplex IHC, we confirmed that CD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment. As a proof of concept, we successfully generated mutilplexed images of CD4+CXCR5+PD-1- Tfh cells from a single DAPI staining in human DLBCL tissues through using generative artificial intelligence. Our study offers critical insights into the heterogeneity and molecular features of DLBCL, shedding light on the crucial role of CD4+CXCR5+PD-1- Tfh cells in the recurrent process. HighlightsO_LIShared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors; C_LIO_LIThe characteristic of relapsed DLBCL TME is a dysfunctional immune microenvironment with a significant decrease of CD4+CXCR5+PD-1- Tfh cells. C_LIO_LICD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment C_LIO_LIDetermination of CD4+CXCR5+PD-1- Tfh cells in human DLBCL tissues through using generative artificial intelligence. C_LI

immunology↗

bioRxiv2024

Nuclear FAK aggravates CD8+ T cell exhaustion via the SP1-IL-6 axis in colorectal cancer

Nuclear abnormalities such as nuclear deformation are hallmarks of many diseases, including cancer. Accumulating evidence suggests that the dense and mechanically stiff tumor microenvironment promotes nuclear deformation in cancer cells. However, little is known about how nuclear deformation in neoplastic cells regulates immune exhaustion in the tumor microenvironment. Here, we found that lamin A/C-mediated nuclear stiffening in neoplastic cells promotes the nuclear translocation of phosphorylated focal adhesion kinase (pFAK), which is strongly correlated with the heterogeneity and exhaustion of CD8+ T cells within the spatial context of the tumor microenvironment in human colorectal cancer. Mechanistically, we revealed that increased nuclear tension within tumor cells promotes pFAK nuclear translocation, where nuclear pFAK was found to regulate SP1/IL-6-mediated T-cell exhaustion and the transcription of proinflammatory cytokines/chemokines. Pharmacological inhibition or disruption of pFAK nuclear translocation enhanced antitumor immune responses and synergistically potentiated PD-1 and TIM-3 immunotherapy by increasing CD8+ T-cell cytotoxicity and restoring exhaustion in preclinical models of colorectal cancer. These findings highlight the pivotal role of nuclear tension-mediated pFAK translocation into the tumor cell nucleus in regulating CD8+ T-cell exhaustion, suggesting that pFAK is a promising target for advancing cancer immunotherapy.

immunology↗

bioRxiv2024

Pre-Assembly NGS Correction of ONT Reads Achieves HiFi-Level Assembly Quality

BackgroundRecently developed hybrid assemblies can achieve Telomere-to-Telomere (T2T) completeness of some chromosomes. However, such approaches involve sequencing a large volume of both Pacific Biosciences high-fidelity (HiFi) and Oxford Nanopore Technologies (ONT) sequencing reads. Along with this, third-generation sequencing techniques are rapidly advancing, increasing the available length and accuracy. To reduce the final cost of genome assembly, here we investigated the possibility of assembly from low-coverage samples and with only ONT corrected by Next-Generation Sequencing (NGS) sequencing reads. We demonstrated that ONT-based assembly approaches corrected by NGS can achieve performance metrics comparable to more expensive hybrid approaches based on HiFi sequencing. ResultsWe investigated the assembly of different chromosomes of HG002 and the low-coverage performance of state-of-the-art hybrid assembly tools, including Verkko and Hifiasm, and ONT-based assemblers Shasta and Flye. Our study shows that even with the best NG50, Hifiasm has many misassemblies in the centromere region, raising doubts about its T2T capabilities. Additionally, ONT-based assemblies perform well at low coverage, offering a cost-effective solution. To achieve better assembly quality, we evaluated the performance of different NGS technologies across various aspects of hybrid genome assembly, including pre-assembly correction, haplotype phasing, and polishing, and found them to be similarly effective. For the NGS technology stLFR, we proposed two-round assembly methods that utilize stLFR linked-read data to achieve assembly phasing performance comparable to that obtained with trio data. ConclusionWe found that assemblies based on ONT corrected by NGS can match or exceed HiFi-based assemblies in accuracy. It appears that no assembly tool investigated here can achieve T2T completeness, even with 50X coverage. Therefore, we recommend using a combination of regular R9 or R10 simplex ONT reads and accurate NGS reads for assembly without aiming for T2T completeness. These ONT-based assemblies perform well even at low coverage, offering a cost-effective solution.

genomics↗

bioRxiv2024

Gene-modified NK Cells Expressing CD64 and Pre-loaded with HIV-specific BNAbs Target Autologous HIV-1 Infected CD4+ T Cells by ADCC.

NK cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target cells via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase antibody retention and facilitate targeted ADCC, we genetically modified human NK cells with the high-affinity Fc receptor, CD64, so that we could pre-load them with HIV-specific BNAbs and enhance their capacity to target HIV infected cells via ADCC. Purified NK cells from the peripheral blood of Control Donors or Persons Living with HIV (PLWH) were activated with IL-2/IL-15/IL-21 cytokines and transduced with a lentivirus encoding CD64. High levels of CD64 surface expression were maintained for multiple weeks on NK cells and CD64 transduced NK cells were similar to control NK cells with strong expression of CD56, CD16, NKG2A, NKp46, CD69, HLA-DR, CD38, and CD57. CD64 transduced NK cells exhibited significantly greater capacity to bind HIV-specific BNAbs in short-term antibody binding assay as well as retain the BNAbs over time (1 week antibody retention assay) compared to Control NK cells only expressing CD16. BNAb pre-loaded CD64 transduced NK cells showed a significantly enhanced capacity to mediate ADCC against autologous HIV-1 infected CD4+ primary T cells in both a short term 3 hour degranulation assay as well as a 24 hour HIV p24 HIV Elimination Assay when compared to control NK cells. A chimeric CD64 enhanced NK cell strategy (NK Enhancement Strategy, "NuKES") retaining bound HIV-specific antibody and targeted ADCC represents a novel autologous primary NK cell immuno-therapy strategy against HIV.

immunology↗

bioRxiv2024

Effect of Circadian Rhythm Modulated Blood Flow on Nanoparticle based Targeted Drug Delivery in Virtual In Vivo Arterial Geometries

Delivery of drug using nanocarriers tethered with vasculature-targeting epitopes aims to maximize the therapeutic efficacy of the drug while minimizing the drug side effects. Circadian rhythm which is governed by the central nervous system has implications for targeted drug delivery due to sleep-wake cycle changes in blood flow dynamics. This paper presents an advanced fluid dynamics modeling method that is based on viscous incompressible shear-rate fluid (blood) coupled with an advection-diffusion equation to simulate the formation of drug concentration gradients in the blood stream and buildup of concentration at the targeted site. The method is equipped with an experimentally calibrated nanoparticle-endothelial cell adhesion model that employs Robin boundary conditions to describe nanoparticle retention based on probability of adhesion, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model based on Taylor-Aris expression for effective diffusion in the boundary layer. The computational model is first experimentally validated and then tested on engineered bifurcating arterial systems where impedance boundary conditions are applied at the outflow to account for the downstream resistance at each outlet. It is then applied to a virtual geometric model of an in vivo arterial tree developed through MRI-based image processing techniques. These simulations highlight the potential of the computational model for drug transport, adhesion, and retention at multiple sites in virtual in vivo models. The model provides a virtual platform for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the in vivo experimentation. Statement of SignificanceA novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI based in vivo carotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the in vivo experimentation.

biophysics↗

bioRxiv2022

The SUMO-interacting Motif in NS2 promotes adaptation of avian influenza virus to mammals

Species differences in the host factor ANP32A/B result in the restriction of avian influenza virus polymerase (vPol) in mammalian cells. Efficient replication of avian influenza viruses in mammalian cells often requires adaptive mutations, such as PB2-E627K, to enable the virus to utilize mammalian ANP32A/B. However, the molecular basis for the productive replication of avian influenza viruses without prior adaptation in mammals remain poorly understood. We show that influenza A virus protein NS2 help to overcome mammalian ANP32A/B-mediated restriction to avian vPol activity by promoting avian vRNP assembly and enhancing mammalian ANP32A/B-vRNP interactions. A conserved SUMO interaction motif (SIM) in NS2 is required for its avian polymerase-enhancing properties. We also demonstrate that disrupting SIM integrity in NS2 impairs avian influenza virus replication and pathogenicity in mammalian hosts, but not in avian hosts. Our results identify NS2 as a cofactor in the adaptation process of avian influenza viruses to mammals.

microbiology↗

bioRxiv2021

Empowering Engineered Muscle in Biohybrid Pump by Extending Connexin 43 Duration with Reduced Graphene Oxides

Engineered skeletal muscle act as therapeutics invaluable to treat injured or diseased muscle and a "living" material essential to assemble biological machinery. For normal development, skeletal myoblasts should express connexin 43, one of the gap junction proteins that promote myoblast fusion and myogenesis, during the early differentiation stage. However, myoblasts cultured in vitro often down-regulate connexin 43 before differentiation, limiting myogenesis and muscle contraction. This study demonstrates that tethering myoblasts with reduced graphene oxide (rGO) slows connexin 43 regression during early differentiation and increases myogenic mRNA synthesis. The whole RNA sequencing also confirms that the rGO on cells increases regulator genes for myogenesis, including troponin, while decreasing negative regulator genes. The resulting myotubes generated a three-fold larger contraction force than the rGO-free myotubes. Accordingly, a valveless biohybrid pump assembled with the rGO-tethered muscle increased the fluid velocity and flow rate considerably. The results of this study would provide an important foundation for developing physiologically relevant muscle and powering up biomachines that will be used for various bioscience studies and unexplored applications.

bioengineering↗

bioRxiv2019

A bibliometric analysis of Soil remediation Based on Massive research literature data During 1988-2018

Soil is an important part of the ecosystem with significant roles that help human population sustain. Research on prevention and remediation of soil pollution has been carried out when 1985. This study analyzed the 1988-2018 soil remediation dataset in the Web of Science database by bibliometric methods to illustrate the current research trends and hot topics of quantitative analysis and soil remediation in the world. To further identify the major soil contamination topics, we employed social network analysis. The results indicate that the field of soil remediation has entered a stage of rapid progress. The United States has a strong overall strength with the largest number of published articles and larger impact. China ranks second. We identified Journal of hazardous materials as the most influential journal and Chinese academy of sciences as the most influential institution. Academic cooperation showed an increasing trend at the author, institutional, and national levels with an average level of cooperation of 3.57, 1.66, and 1.16, respectively. However, the growth rate of cooperation at the national level is relatively low. In addition, the frequency and co-word analyses of keywords revealed the important research topics. \"heavy metals\", \"PAH\", \"bioremediation\", \"Phytoremediation\" and \"Electrokinetic remediation\" were identified as the hot topics. The findings of this study will help researchers understand the status of soil remediation as well as provide guidance for future research.

ecology↗

bioRxiv2018

Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contribute to gastritis

Adrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis, accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-{gamma}-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-{gamma}-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-{gamma} or knockout of IFN-{gamma} decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-{gamma}, which collectively exert a pro-inflammatory effect within the gastric microenvironment.\n\nAuthor summaryH. pylori infect almost half the worlds population. Once infected, most of people carry the bacteria lifelong if left untreated, so that persistent H. pylori infection can lead to chronic gastritis, peptic ulceration and ultimately gastric cancer. H. pylori infection is accompanied with increased inflammation in gastric mucosa, but the mechanisms of chronic gastritis induced by H. pylori infection remains poorly understood. We studied a multifunctional peptide known as adrenomedullin (ADM) in gastric epithelial cells, which was known as a key factor of regulating gastrointestinal physiology and pathology. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice, and was positively correlated with the degree of gastritis. ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner. Blockade of ADM during H. pylori infection resulted in decreased gastric inflammation that was characterized by the increased IFN-{gamma}-producing T cells which was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-{gamma}-producing T-cell responses. These data demonstrate that H. pylori-induced ADM modulates FN-{gamma}-producing T-cell responses and contribute to gastritis.

immunology↗

bioRxiv2017

LncRNA-TUG1/EZH2 Axis Promotes Cell Proliferation, Migration And The EMT Phenotype Formation Through Sponging miR-382

Pancreatic carcinoma (PC) is the one of the most common and malignant cancer in the world. Despite many effort have been made in recent years, the survival rate of PC still remains unsatisfied. Therefore, investigating the mechanisms underlying the progression of PC might facilitate the development of novel treatments that improve patient prognosis. LncRNA Taurine Up-regulated Gene 1 (TUG1) was initially identified as a transcript up - regulated by taurine, siRNA - based depletion of TUG1 suppresses mouse retinal development, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in pancreatic carcinoma (PC) still needs to be further investigated. In the current study, the expression of TUG1 in the PC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and loss-of-function and gain-of-function approaches were applied to investigate the function of TUG1 in PC cell. Online database analysis tools showed that miR-382 could interact with TUG1 and we found an inverse correlation between TUG1 and miR-382 in PC specimens. Moreover, dual luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and applied biotin-avidin pulldown system further provide evidence that TUG1 directly targeted miR-382 by binding with microRNA binding site harboring in the TUG1 sequence. Furthermore, gene expression array analysis using clinical samples and RT-qPCR proposed that EZH2 was a target of miR-382 in PC. Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression at least partially through function as an endogenous sponge by competing for miR-382 binding to regulate the miRNA target EZH2.

cancer biology↗