Biology subjects

Wei, W.

Publications and source records attributed to Wei, W..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

immunology↗

bioRxiv2020

Impact of cell-type and context-dependent regulatory variants on human immune traits

The effects of trait-associated variants are often studied in a single relevant cell-type or context. However, for many complex traits, multiple cell-types are involved. This applies particularly to immune-related traits, for which many immune cell-types and contexts play a role. Here, we studied the impact of immune gene regulatory variants on complex traits to better understand genetic risk mediated through immune cell-types. We identified 26,271 expression quantitative trait loci (QTLs) and 23,121 splicing QTLs in 18 immune cell-types, and analyzed their overlap with trait-associated loci from 72 genome-wide association studies (GWAS). We showed that effects on RNA expression and splicing in immune cells colocalize with an average of 40.4% and 27.7% GWAS loci for immune-related and non-immune traits, respectively. Notably, we found that a large number of loci (mean: 14%) colocalize with splicing QTLs but not expression QTLs. The 60% GWAS loci without colocalization harbor genes that have lower expression levels, are less tolerant to loss-of-function mutations, and more enhancerrich than genes at colocalized loci. To further investigate the 60% GWAS loci not explained by our regulatory QTLs, we collected H3K27ac CUT&Tag data from rheumatoid arthritis (RA) and healthy controls. We found several unexplained GWAS hits lying within regions with higher H3K27ac activity in RA patients. We also observed that enrichment of RA GWAS heritability is greater in H3K27ac regions in immune cell-types from RA patients compared to healthy controls. Our study paves the way for future QTL studies to elucidate the mechanisms of as yet unexplained GWAS loci.

genomics↗

bioRxiv2020

Systematic evaluation of parameterization for genome-scale metabolic models of cultured mammalian cells

Genome-scale metabolic models describe cellular metabolism with mechanistic detail. Given their high complexity, such models need to be parameterized correctly to yield accurate predictions and avoid overfitting. Effective parameterization has been well-studied for microbial models, but it remains unclear for higher eukaryotes, including mammalian cells. To address this, we enumerated model parameters that describe key features of cultured mammalian cells - including cellular composition, bioprocess performance metrics, mammalian-specific pathways, and biological assumptions behind model formulation approaches. We tested these parameters by building thousands of metabolic models and evaluating their ability to predict the growth rates of a panel of phenotypically diverse Chinese Hamster Ovary cell clones. We found the following considerations to be most critical for accurate parameterization: (1) cells limit metabolic activity to maintain homeostasis, (2) cell morphology and viability change dynamically during a growth curve, and (3) cellular biomass has a particular macromolecular composition. Depending on parameterization, models predicted different metabolic phenotypes, including contrasting mechanisms of nutrient utilization and energy generation, leading to varying accuracies of growth rate predictions. Notably, accurate parameter values broadly agreed with experimental measurements. These insights will guide future investigations of mammalian metabolism.

systems biology↗

bioRxiv2020

Combined transient ablation and single cell RNA sequencing reveals the development of medullary thymic epithelial cells

Medullary thymic epithelial cells (mTECs) play a critical role in central immune tolerance by mediating negative selection of autoreactive T cells through the collective expression of the peripheral self-antigen compartment, including tissue-specific antigens (TSAs). Recent work has shown that gene expression patterns within the mTEC compartment are remarkably heterogenous and include multiple differentiated cell states. To further define mTEC development and medullary epithelial lineage relationships, we combined lineage tracing and recovery from transient in vivo mTEC ablation with single cell RNA-sequencing. The combination of bioinformatic and experimental approaches revealed a non-stem transit-amplifying population of cycling mTECs that preceded Aire expression. Based on our findings, we propose a branching model of mTEC development wherein a heterogeneous pool of transit-amplifying cells gives rise to Aire- and Ccl21a-expressing mTEC subsets. We further use experimental techniques to show that within the Aire-expressing developmental branch, TSA expression peaked as Aire expression decreased, implying Aire expression must be established before TSA expression can occur. Collectively, these data provide a higher order roadmap of mTEC development and demonstrate the power of combinatorial approaches leveraging both in vivo models and high-dimensional datasets.

immunology↗

bioRxiv2020

Spatially displaced excitation contributes to the encoding of interrupted motion by the retinal direction-selective circuit

Spatially distributed excitation and inhibition collectively shape a visual neurons receptive field (RF) properties. In the direction-selective circuit of the mammalian retina, the role of strong null-direction inhibition of On-Off direction-selective ganglion cells (ON-OFF DSGCs) on their direction selectivity is well-studied. However, how excitatory inputs influence the On-Off DSGCs visual response is underexplored. Here, we report that On-Off DSGCs have a spatially displaced glutamatergic receptive field along their preferred-null motion axis. This displaced receptive field contributes to DSGC null-direction spiking during interrupted motion trajectories. Theoretical analyses indicate that population responses during interrupted motion may help populations of On-Off DSGCs signal the spatial location of moving objects in complex, naturalistic visual environments. Our study highlights that the direction-selective circuit exploits separate sets of mechanisms under different stimulus conditions, and these mechanisms may help encode multiple visual features.

neuroscience↗

bioRxiv2020

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2high/CKneg) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients. HK2high/CKneg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CKpos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

cancer biology↗

bioRxiv2020

Lysosomal activity regulates Caenorhabditis elegans mitochondrial dynamics through vitamin B12 metabolism

Mitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern in Caenorhabditis elegans muscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of the C. elegans dynamin mutant on an E. coli strain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the two C. elegans enzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of the sams-1 S-adenosylmethionine synthase also suppresses the drp-1 fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways. SIGNIFICANCE STATEMENTThe balance of mitochondrial fission and fusion, two aspects of mitochondrial dynamics, is important for mitochondrial function. Here we show that Caenorhabditis elegans lysosomal activity regulates mitochondrial dynamics by affecting mitochondrial fission through interfering the metabolism of a micronutrient, vitamin B12. Vitamin B12 is exclusively obtained from diets in animals including C. elegans and humans, and its uptake is mediated by the lysosome. We show that lysosomal dysfunction causes vitamin B12 deficiency that leads to reduction of methionine and S-adenosylmethionine to in turn increase mitochondrial biogenesis and fission. Our study provides an insight on the interactions between mitochondrial function and micronutrient metabolism.

cell biology↗

bioRxiv2020

Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China

The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.

microbiology↗

bioRxiv2020

High-fidelity base editor with no detectable genome-wide off-target effects

Base editors hold promise for correcting pathogenic mutations, while substantial single nucleotide variations (SNVs) on both DNA and RNA were generated by cytosine base editors (CBEs). Here we examined possibilities to reduce off-target effects by engineering cytosine deaminases. By screening 24 CBEs harboring various rAPOBEC1 (BE3) or human APOBEC3A (BE3-hA3A) mutations on the ssDNA or RNA binding domain, we found 8 CBE variations could maintain high on-target editing efficiency. Using Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI) method and RNA sequencing analysis, we found DNA off-target SNVs induced by BE3 could be completely eliminated in BE3R126E but the off-target RNA SNVs was only slightly reduced. By contrast, BE3-hA3AY130F abolished the RNA off-target effects while could not reduce the DNA off-target effects. Notably, BE3R132E, BE3W90Y+R126E and BE3W90F+R126E achieved the elimination of off-target SNVs on both DNA and RNA, suggesting the feasibility of engineering base editors for high fidelity deaminases.

genomics↗

bioRxiv2020

P4HA2, a prognostic factor, promotes glioma proliferation, invasion, migration and EMT through collagen regulation and PI3K/AKT pathway

Prolyl-4-hydroxylase subunit 2 (P4HA2), as a member of collagen modification enzymes, is induced under hypoxic conditions with essential roles in the collagen maturation, deposition as well as the remodeling of extracellular matrix(ECM). Mounting evidence has suggested that deregulation of P4HA2 is common in cancer. However, the expression pattern and molecular mechanisms of P4HA2 in glioma remain unknown. Here, we demonstrate that P4HA2 is overexpressed in glioma and inversely correlates with patient survival. Knockdown of P4HA2 inhibits proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT)-like phenotype of glioma cells in vitro and suppressed tumor xenograft growth in vivo. Mechanistically, bioinformatics analysis shows that ECM-receptor interaction and PI3K/AKT pathway are the most enriched pathways of the co-expressed genes with P4HA2. Furthermore, P4HA2 mRNA was positively correlated with mRNA expressions of a series of collagen genes, but not mRNA of PI3K or AKT1/2. Conversely, both the protein expressions of collagens and phosphorylated PI3K/AKT could be downregulated either by silencing of P4HA2 expression or inhibition of its prolyl hydroxylase. Moreover, the inhibitory effects on the migration, invasion and the EMT-related molecules by P4HA2 knockdown can be recapitulated by the Akt phosphorylation activator. Taken together, our findings for the first time reveal an oncogenic role of P4HA2 in the glioma malignancy. By regulating the expression of fibrillar collagens and the downstream PI3K/AKT signaling pathway, it may serve as a potential anti-cancer target for the treatment of glioma. HighlightsP4HA2 is overexpressed and correlated with poor prognosis in glioma. P4HA2 depletion inhibits glioma proliferation, migration, invasion and EMT-like phenotype in vitro and tumorigenesis in vivo. P4HA2 depletion attenuates the PI3K/AKT signaling pathway in a collagen-dependent manner.

cancer biology↗

bioRxiv2020

A global map of root biomass across the world's forests

Abstract (150 words limits)Root plays a key role in plant growth and functioning. Here we combine 10307 field measurements of forest root biomass worldwide with global observations of forest structure, climatic conditions, topography, land management and soil characteristics to derive a spatially-explicit global high-resolution (~ 1km) root biomass dataset, including fine and coarse roots. In total, 142 {+/-} 32 Pg of live dry matter biomass is stored below-ground, that is a global average root:shoot biomass ratio of 0.25 {+/-} 0.10. Our estimations of total root biomass in tropical, temperate and boreal forests are 44-226% smaller than earlier studies1-3. The smaller estimation is attributable to the updated forest area, spatially explicit above-ground biomass density used to predict the patterns of root biomass, new root measurements and upscaling methodology. We show specifically that the root shoot allometry is one underlying driver that leads to methodological overestimation of root biomass in previous estimations.

ecology↗

bioRxiv2019

Improved transcriptome annotation and read-through transcript identification with TIF-Seq2

Eukaryotic transcriptomes are complex involving thousands of overlapping transcripts. The interleaved nature of the transcriptome limits our ability to identify regulatory regions and, in some cases, can lead to misinterpretation of gene expression. To improve the understanding of the overlapping transcriptome, we have developed an optimized method, TIF-Seq2, able to sequence simultaneously the 5 and 3 ends of individual RNA molecules at single-nucleotide resolution. We investigated the transcriptome of a well characterized human cell line (K562) and identify thousands of unannotated transcript isoforms. By focusing on transcripts which are challenging to be investigated with RNA-seq, we accurately defined boundaries of lowly expressed unannotated and read-though transcripts putatively encoding fusion genes. We validated our results by targeted long-read sequencing and standard RNA-Seq for chronic myeloid leukaemia patient samples. Taking the advantage of TIF-Seq2, we explore transcription regulation among the overlapping units and investigate their crosstalk. We show that most overlapping upstream transcripts use poly(A) sites within the first 2 kb of the downstream transcription unit. Our work shows that, by paring the 5 and 3 end of each RNA, TIF-Seq2 can improve the annotation of complex genomes, facilitates accurate assignment of promoters to genes and easily identify transcriptionally fused genes. Key pointsO_LIStudy of TSS-PAS co-occurrence allows dissecting complex overlapping transcription units. C_LIO_LIPartially overlapping transcription units in human commonly use PAS within the first 2Kb. C_LIO_LITIF-Seq2 facilitates the identification of lowly expressed and transcriptionally fused genes. C_LI

genomics↗

bioRxiv2019

A portable and cost-effective microfluidic system for massively parallel single-cell transcriptome profiling

Single-cell technologies are becoming increasingly widespread and have been revolutionizing our understanding of cell identity, state, diversity and function. However, current platforms can be slow to apply to large-scale studies and resource-limited clinical arenas due to a variety of reasons including cost, infrastructure, sample quality and requirements. Here we report DNBelab C4 (C4), a negative pressure orchestrated, portable and cost-effective device that enables high-throughput single-cell transcriptional profiling. C4 system can efficiently allow discrimination of species-specific cells at high resolution and dissect tissue heterogeneity in different organs, such as murine lung and cerebral cortex. Finally, we show that the C4 system is comparable to existing platforms but has huge benefits in cost and portability and, as such, it will be of great interest for the wider scientific community.

genomics↗

bioRxiv2019

LARP7 is a BRCA1 ubiquitinase substrate and regulates genome stability and tumorigenesis

Attenuated DNA repair leads to genomic instability and tumorigenesis. BRCA1/BARD1 are the best known tumor suppressors that promote homology recombination (HR) and arrest cell cycle at G2/M checkpoint. As E3 ubiquitin ligases, their ubiquitinase activity has been known to involve in the HR and tumor suppression, but the mechanism remains ambiguous. Here, we demonstrated upon genotoxic stress, BRCA1 together with BARD1 catalyzed the K48 ployubiquitination on LARP7, a 7SK RNA binding protein known to control RNAPII pausing, and thereby degraded it through 26S ubiquitin-proteasome pathway. Depleting LARP7 suppressed the expression of CDK1 complex, arrested cell at G2/M DNA damage checkpoint and reduced BRCA2 phosphorylation which thereby facilitated RAD51 recruitment to damaged DNA to enhance HR. Importantly, LARP7 depletion observed in breast patients lead to the chemoradiotherapy resistance both in vitro and in vivo. Together, this study unveils a mechanism by which BRCA1/BARD1 utilizes their E3 ligase activity to control HR and cell cycle, and highlights LARP7 as a potential target for cancer prevention and therapy.\n\nHighlightsO_LIDNA damage response downregulates LARP7 through BRCA1/BARD1\nC_LIO_LIBRCA1/BARD1 catalyzes the K48 polyubiquitination on LARP7\nC_LIO_LILARP7 promotes G2/M cell cycle transition and tumorigenesis via CDK1 complex\nC_LIO_LILARP7 disputes homology-directed repair that leads to tumor therapy resistance\nC_LI

molecular biology↗

bioRxiv2019

Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice

AbstractNEAT1 is a highly and ubiquitously expressed long non-coding RNA (lncRNA) which serves as an important regulator of cellular stress response. However, the physiological role of NEAT1 in the central nervous system (CNS) is still poorly understood. In the current study, we addressed this by characterising the CNS function in the Neat1 knockout mouse model (Neat1-/- mice), using a combination of behavioural phenotyping, electrophysiology and expression analysis. RNAscope(R) in situ hybridisation revealed that in wild-type mice, Neat1 is expressed evenly across the CNS, with high expression in glial cells and low expression in neurons. Loss of Neat1 in mice results in an inadequate reaction to physiological stress manifested as hyperlocomotion and panic escape response. In addition, Neat1-/- mice display deficits in social interaction and rhythmic patterns of activity but retain normal motor function and memory. Neat1-/- mice do not present with neuronal loss, overt neuroinflammation or gross synaptic dysfunction in the brain. However, cultured Neat1-/- neurons are characterised by hyperexcitability and dysregulated calcium homeostasis, and stress-induced neuronal activity is also augmented in Neat1-/- mice in vivo. Gene expression analysis showed that Neat1 may act as a weak positive regulator of multiple genes in the brain. Furthermore, loss of Neat1 affects alternative splicing of genes important for the CNS function and implicated in neurological diseases. Overall, our data suggest that Neat1 is involved in stress signaling in the brain and fine-tunes the CNS functions to enable adaptive behaviour in response to physiological stress.

neuroscience↗

bioRxiv2019

Trajectories from Snapshots: Integrated proteomic and metabolic single-cell assays reveal multiple independent adaptive responses to drug tolerance in a BRAF-mutant melanoma cell line

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge, with relevance towards understanding biological changes ranging from cellular differentiation to epigenetic (adaptive) responses of diseased cells to drugging. We report on a combined experimental and theoretic method for determining the trajectories that specific highly plastic BRAFV600E mutant patient-derived melanoma cancer cells take between drug-naive and drug-tolerant states. Recent studies have implicated non-genetic, fast-acting resistance mechanisms are activated in these cells following BRAF inhibition. While single-cell highly multiplex omics tools can yield snapshots of the cell state space landscape sampled at any given time point, individual cell trajectories must be inferred from a kinetic series of snapshots, and that inference can be confounded by stochastic cell state switching. Using a microfludic-based single-cell integrated proteomic and metabolic assay, we assayed for a panel of signaling, phenotypic, and metabolic regulators at four time points during the first five days of drug treatment. Dimensional reduction of the resultant data set, coupled with information theoretic analysis, uncovered a complex cell state landscape and identified two distinct paths connecting drug-naive and drug-tolerant states. Cells are shown to exclusively traverse one of the two pathways depending on the level of the lineage restricted transcription factor MITF in the drug-naive cells. The two trajectories are associated with distinct signaling and metabolic susceptibilities, and are independently druggable. Our results update the paradigm of adaptive resistance development in an isogenic cell population and offer insight into the design of more effective combination therapies.

bioengineering↗

bioRxiv2019

Genome-wide analysis of GATA factors in moso bamboo (Phyllostachys edulis) unveils that PeGATAs regulate shoot rapid-growth and rhizome development

BackgroundMoso bamboo is well-known for its rapid-growth shoots and widespread rhizomes. However, the regulatory genes of these two processes are largely unexplored. GATA factors regulate many developmental processes, but its role in plant height control and rhizome development remains unclear.\n\nResultsHere, we found that bamboo GATA factors (PeGATAs) are involved in the growth regulation of bamboo shoots and rhizomes. Bioinformatics and evolutionary analysis showed that there are 31 PeGATA factors in bamboo, which can be divided into three subfamilies. Light, hormone, and stress-related cis-elements were found in the promoter region of the PeGATA genes. Gene expression of 12 PeGATA genes was regulated by phytohormone-GA but there was no correlation between auxin and PeGATA gene expression. More than 27 PeGATA genes were differentially expressed in different tissues of rhizomes, and almost all PeGATAs have dynamic gene expression level during the rapid-growth of bamboo shoots. These results indicate that PeGATAs regulate rhizome development and bamboo shoot growth partially via GA signaling pathway. In addition, PeGATA26, a rapid-growth negative regulatory candidate gene modulated by GA treatment, was overexpressed in Arabidopsis, and over-expression of PeGATA26 significantly repressed Arabidopsis primary root length and plant height. The PeGATA26 overexpressing lines were also resistant to exogenous GA treatment, further emphasizing that PeGATA26 inhibits plant height from Arabidopsis to moso bamboo via GA signaling pathway.\n\nConclusionsOur results provide an insight into the function of GATA transcription factors in regulating shoot rapid-growth and rhizome development, and provide genetic resources for engineering plant height.

plant biology↗

bioRxiv2019

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

Drug-induced dedifferentiation towards a drug-tolerant persister state is a common mechanism cancer cells exploit to escape therapies, posing a significant obstacle to sustained therapeutic efficacy. The dynamic coordination of epigenomic and transcriptomic programs at the early-stage of drug exposure, which initiates and orchestrates these reversible dedifferentiation events, remains largely unexplored. Here we employ high-temporal-resolution multi-omics profiling, information-theoretic approaches, and dynamic system modeling to probe these processes in BRAF-mutant melanoma models and patient specimens. We uncover a hysteretic transition trajectory of melanoma cells in response to oncogene inhibition and subsequent release, driven by the sequential operation of two tightly coupled transcriptional waves, which orchestrate genome-scale chromatin state reconfiguration. Modeling of the transcriptional wave interactions predicts NF-{kappa}B/RelA-driven chromatin remodeling as the underlying mechanism of cell-state dedifferentiation, a finding we validate experimentally. Our results identify critical RelA-target genes that are epigenetically modulated to drive this process, establishing a quantitative epigenome gauge to measure cell-state plasticity in melanomas, which supports the potential use of drugs targeting epigenetic machineries to potentiate oncogene inhibition. Extending our investigation to other cancer models, we identify oxidative stress-mediated NF-{kappa}B/RelA activation as a common mechanism driving cellular transitions towards drug-tolerant persister states, revealing a novel and pivotal role for the NF-{kappa}B signaling axis in linking cellular oxidative stress to cancer progression.

cancer biology↗