Inhalation exposure to airborne PM attenuates hepatic metabolic pathways through -nitrosylation of the primary ER stress sensor.

Inhalation exposure to airborne fine particulate matter (aerodynamic diameter: <2.5 µm, PM) is known to cause metabolic dysfunction-associated steatohepatitis (MASH) and the associated metabolic syndrome. Hepatic lipid accumulation and inflammation are the key characteristics of MASH.

The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.

If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system.

The Digital World of Cytogenetic and Cytogenomic Web Resources.

The dynamic growth of technological capabilities at the cellular and molecular level has led to a rapid increase in the amount of data on the genes and genomes of organisms. In order to store, access, compare, validate, classify, and understand the massive data generated by different researchers, and to promote effective communication among research communities, various genome and cytogenetic online databases have been established. These data platforms/resources are essential not only for computational analyses and theoretical syntheses but also for helping researchers select future research topics and prioritize molecular targets.

Studying the Dynamics of Tunneling Tubes and Cellular Spheres.

Cancer cytogenetic analyses often involve cell culture. However, many cytogeneticists overlook interesting phenotypes associated with cultured cells. Given that cytogeneticists need to focus more on phenotypes to comprehend the genotypes, the biological significance of seemingly trivial cellular variations deserves attention.

Tracking Karyotype Changes in Treatment-Induced Drug-Resistant Evolution.

Karyotype coding, which encompasses the complete chromosome sets and their topological genomic relationships within a given species, encodes system-level information that organizes and preserves genes' function, and determines the macroevolution of cancer. This new recognition emphasizes the crucial role of karyotype characterization in cancer research. To advance this cancer cytogenetic/cytogenomic concept and its platforms, this study outlines protocols for monitoring the karyotype landscape during treatment-induced rapid drug resistance in cancer.

The Importance of Monitoring Non-clonal Chromosome Aberrations (NCCAs) in Cancer Research.

Cytogenetic analysis has traditionally focused on the clonal chromosome aberrations, or CCAs, and considered the large number of diverse non-clonal chromosome aberrations, or NCCAs, as insignificant noise. Our decade-long karyotype evolutionary studies have unexpectedly demonstrated otherwise. Not only the baseline of NCCAs is associated with fuzzy inheritance, but the frequencies of NCCAs can also be used to reliably measure genome or chromosome instability (CIN).

The New Era of Cancer Cytogenetics and Cytogenomics.

The promises of the cancer genome sequencing project, combined with various -omics technologies, have raised questions about the importance of cancer cytogenetic analyses. It is suggested that DNA sequencing provides high resolution, speed, and automation, potentially replacing cytogenetic testing. We disagree with this reductionist prediction.

Karyotype as code of codes: An inheritance platform to shape the pattern and scale of evolution.

Organismal evolution displays complex dynamics in phase and scale which seem to trend towards increasing biocomplexity and diversity. For over a century, such amazing dynamics have been cleverly explained by the apparently straightforward mechanism of natural selection: all diversification, including speciation, results from the gradual accumulation of small beneficial or near-neutral alterations over long timescales. However, although this has been widely accepted, natural selection makes a crucial assumption that has not yet been validated.

Challenges and Opportunities for Clinical Cytogenetics in the 21st Century.

The powerful utilities of current DNA sequencing technology question the value of developing clinical cytogenetics any further. By briefly reviewing the historical and current challenges of cytogenetics, the new conceptual and technological platform of the 21st century clinical cytogenetics is presented. Particularly, the genome architecture theory (GAT) has been used as a new framework to emphasize the importance of clinical cytogenetics in the genomic era, as karyotype dynamics play a central role in information-based genomics and genome-based macroevolution.

Questions to guide cancer evolution as a framework for furthering progress in cancer research and sustainable patient outcomes.

We appear to be faced with 'two truths' in cancer-one of major advances and successes and another one of remaining short-comings and significant challenges. Despite decades of research and substantial progress in treating cancer, most patients with metastatic cancer still experience great suffering and poor outcomes. Metastatic cancer, for the vast majority of patients, remains incurable.

Genome Chaos, Information Creation, and Cancer Emergence: Searching for New Frameworks on the 50th Anniversary of the "War on Cancer".

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national "war on cancer." Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, primarily through the characterization of cancer genes and the phenotypes associated with their pathways. Despite millions of publications and the overwhelming volume data generated from the Cancer Genome Project, clinical benefits are still lacking.

Further illusions: On key evolutionary mechanisms that could never fit with Modern Synthesis.

In light of illusions of the Modern Synthesis (MS) listed by Noble (2021a), MS's key concept, that gradual accumulation of gene mutations within microevolution leads to macroevolution, requires reexamination too. In this article, additional illusions of the MS are identified therein caused by the absence of system information and correct history. First, the MS lacks distinction among the two basic types of information: genome-defined system and gene-defined parts-information, as its treatment was based mostly on gene information.

Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells.

Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis.

Karyotype coding: The creation and maintenance of system information for complexity and biodiversity.

The mechanism of biological information flow is of vital importance. However, traditional research surrounding the genetic code that follows the central dogma to a phenotype faces challengers, including missing heritability and two-phased evolution. Here, we propose the karyotype code, which by organizing genes along chromosomes at once preserves species genome information and provides a platform for other genetic and nongenetic information to develop and accumulate.

Two-phased evolution: Genome chaos-mediated information creation and maintenance.

Cancer is traditionally labeled a "cellular growth problem." However, it is fundamentally an issue of macroevolution where new systems emerge from tissue by breaking various constraints. To study this process, we used experimental platforms to "watch evolution in action" by comparing the profiles of karyotypes, transcriptomes, and cellular phenotypes longitudinally before, during, and after key phase transitions.

Genome chaos: Creating new genomic information essential for cancer macroevolution.

Cancer research has traditionally focused on the characterization of individual molecular mechanisms that can contribute to cancer. Due to the multiple levels of genomic and non-genomic heterogeneity, however, overwhelming molecular mechanisms have been identified, most with low clinical predictability. It is thus necessary to search for new concepts to unify these diverse mechanisms and develop better strategies to understand and treat cancer.

Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival.

When discussing chromosomal instability, most of the literature focuses on the characterization of individual molecular mechanisms. These studies search for genomic and environmental causes and consequences of chromosomal instability in cancer, aiming to identify key triggering factors useful to control chromosomal instability and apply this knowledge in the clinic. Since cancer is a phenomenon of new system emergence from normal tissue driven by somatic evolution, such studies should be done in the context of new genome system emergence during evolution.

What Is Karyotype Coding and Why Is Genomic Topology Important for Cancer and Evolution?

While the importance of chromosomal/nuclear variations vs. gene mutations in diseases is becoming more appreciated, less is known about its genomic basis. Traditionally, chromosomes are considered the carriers of genes, and genes define bio-inheritance.

Micronuclei and Genome Chaos: Changing the System Inheritance.

Micronuclei research has regained its popularity due to the realization that genome chaos, a rapid and massive genome re-organization under stress, represents a major common mechanism for punctuated cancer evolution. The molecular link between micronuclei and chromothripsis (one subtype of genome chaos which has a selection advantage due to the limited local scales of chromosome re-organization), has recently become a hot topic, especially since the link between micronuclei and immune activation has been identified. Many diverse molecular mechanisms have been illustrated to explain the causative relationship between micronuclei and genome chaos.

Health and Disease-Emergent States Resulting From Adaptive Social and Biological Network Interactions.

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease.

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems.

Background: In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer.