Quiescent cancer cells (QCCs) reversibly reside in G0 phase, thus allowing them to survive chemotherapy and radiotherapy, which generally target proliferating cells. Surviving QCCs may re-proliferate, and consequently result in cancer progression, recurrence, and metastasis. Therefore, understanding the key players governing QCC survival and activation is crucial for developing QCC-targeting agents. This review presents an overview of (1) the mechanisms underlying the regulation of QCC status and (2) recent advances in the development of QCC-targeting therapeutic agents and their underlying mechanisms. The development of effective therapeutic modalities that target QCCs may enable new cancer treatments to prevent cancer progression and recurrence.

Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.

The presences of ammonia tolerant ammonia-oxidizing archaea (AOA) in environments are always underestimated and their adaption to complex habitats has also rarely been reported. Here we present the physiological and genomic characteristics of an ammonia tolerant soil AOA strain Candidatus Nitrosocosmicus agrestis. This strain was able to form aggregates and adhere on the surface of hydrophobic matrix. Ammonia-oxidizing activities were still observed at 200 mM NH4+ (> 1500 μM of free ammonia) and 50 mM NO2-. Urea could be used as sole energy source but exogenous organics had no significant effect on the ammonia oxidation. Besides the genes involving in ammonia oxidation, carbon fixation and urea hydrolysis, the genome also encodes a full set of genes (GTs, GHs, CEs, MOP, LPSE, etc) that responsible for polysaccharide metabolism and secretion, suggesting the potential production of extracellular polymeric substances (EPS). Moreover, a pathway connecting urea cycle, polyamines synthesis and excretion was identified in the genome, which indicates the NH4+ in cytoplasm could potentially be converted into polyamines and excreted out of cell, and then contributes to the high ammonia tolerance. Genes encoding the cytoplasmic carbonic anhydrase and putative polyamine exporter are unique in Ca. Nitrosocosmicus agrestis or the genus Ca. Nitrosocosmicus, suggesting the prevalence of ammonia tolerance in this clade. The proposed mechanism of ammonia tolerance via polyamines synthesis and export was verified by using transcriptional gene regulation and polyamines determination.IMPORTANCEAOA are ubiquitous in different environments and play a major role in nitrification. Though AOA have higher affinities for ammonia, their maximum specific cell activity and ammonia tolerance are usually much lower than AOB, resulting in low contribution to the global ammonia oxidation and N2O production. However, in some agricultural soils, the AOA activity would not be suppressed by the fertilization with high concentration of ammonium nitrogen, suggesting the presence of some ammonia tolerant species. This study provides some physiological and genomic characteristics for an ammonia tolerant soil AOA strain Ca. Nitrosocosmicus agrestis and proposes some mechanisms of this AOA adapting to a variety of environments and tolerating to high ammonia. Ammonia tolerance of AOA was always underestimated in many previous studies, physiological and genomic analyses of this AOA clade are benefit to uncover the role of AOA playing in global environmental patterns.

Ammonia tolerance is a universal characteristic among the ammonia-oxidizing bacteria (AOB); in contrast, the known species of ammonia-oxidizing archaea (AOA) have been regarded as ammonia sensitive, until the identification of the genus “Candidatus Nitrosocosmicus.” However, the mechanism of its ammonia tolerance has not been reported. In this study, the AOA species “Candidatus Nitrosocosmicus agrestis,” obtained from agricultural soil, was determined to be able to tolerate high concentrations of NH3 (>1,500 μM). In the genome of this strain, which was recovered from metagenomic data, a full set of genes for the pathways of polysaccharide metabolism, urea hydrolysis, arginine synthesis, and polyamine synthesis was identified. Among them, the genes encoding cytoplasmic carbonic anhydrase (CA) and a potential polyamine transporter (drug/metabolite exporter [DME]) were found to be unique to the genus “Ca. Nitrosocosmicus.” When “Ca. Nitrosocosmicus agrestis” was grown with high levels of ammonia, the genes that participate in CO2/HCO3− conversion, glutamate/glutamine syntheses, arginine synthesis, polyamine synthesis, and polyamine excretion were significantly upregulated, and the polyamines, including putrescine and spermidine, had significant levels of production. Based on genome analysis, gene expression quantification, and polyamine determination, we propose that the production and excretion of polyamines is probably one of the reasons for the ammonia tolerance of “Ca. Nitrosocosmicus agrestis,” and even of the genus “Ca. Nitrosocosmicus.” IMPORTANCE Ammonia tolerance of AOA is usually much lower than that of the AOB, which makes the AOB rather than AOA a predominant ammonia oxidizer in agricultural soils, contributing to global N2O emission. Recently, some AOA species from the genus “Ca. Nitrosocosmicus” were also found to have high ammonia tolerance. However, the reported mechanism for the ammonia tolerance is very rare and indeterminate for AOB and for AOA species. In this study, an ammonia-tolerant AOA strain of the species “Ca. Nitrosocosmicus agrestis” was identified and its potential mechanisms for ammonia tolerance were explored. This study will be of benefit for determining more of the ecological role of AOA in agricultural soils or other environments.

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Bone metastasis occurs when tumour cells dissociate from primary tumours, enter the circulation (circulating tumour cells, CTCs), and colonize sites in bone (disseminated tumour cells, DTCs). The bone marrow seems to be a particularly dormancy-inducing environment for DTCs, yet the mechanisms of dormancy initiation, reactivation, and interaction within the bone marrow have to be elucidated. Intriguingly, some evidence has suggested that dormancy is a reversible state that is switched ‘on’ or ‘off’ depending on the presence of various bone marrow resident cells, particularly osteoclasts and osteoblasts. It has become clear that these two cells contribute to regulating dormant tumour cells in bone both directly (interaction) and indirectly (secreted factors). The involved mechanisms include TGFβ signalling, the Wnt signalling axis, the Notch2 pathway, etc. There is no detailed review that specifically focuses on ascertaining the dynamic interactions between tumour cell dormancy and bone remodelling. In addition, we highlighted the roles of inflammatory cytokines during this ‘cell-to-cell’ communication. We also discussed the potential clinical relevance of remodelling the bone marrow niche in controlling dormant tumour cells. Understanding the unique role of osteoclasts and osteoblasts in regulating tumour dormancy in bone marrow will provide new insight into preventing and treating tumour bone metastasis.

Gastrointestinal cancers refer to a group of deadly malignancies of the gastrointestinal tract and organs of the digestive system. Over the past decades, considerable amounts of medicinal plants have exhibited potent anticancer effects on different types of gastrointestinal cancers. OMICS, systems biology approaches covering genomics, transcriptomics, proteomics and metabolomics, are broadly applied to comprehensively reflect the molecular profiles in mechanistic studies of medicinal plants. Single- and multi-OMICS approaches facilitate the unravelling of signalling interaction networks and key molecular targets of medicinal plants with anti-gastrointestinal cancer potential. Hence, this review summarizes the applications of various OMICS and advanced bioinformatics approaches in examining therapeutic targets, signalling pathways, and the tumour microenvironment in response to anticancer medicinal plants. Advances and prospects in this field are also discussed.

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