Identification of anoikis-related subtypes and development of risk stratification system in skin cutaneous melanoma.

Background: Anoikis, a form of apoptosis induced by cell detachment, plays a key role in cancer metastasis. However, the potential roles of anoikis-related genes (ARGs) in assessing the prognosis of skin cutaneous melanoma (SKCM) and the tumor microenvironment (TME) remain unclear. Methods: The data from TCGA corresponding to transcriptomic expression patterns for patients with SKCM were downloaded and utilized to screen distinct molecular subtypes by a non-negative matrix factorization algorithm. The prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in SKCM patients from the GEO cohort. Moreover, the relationship of the ARG_score with prognosis, tumor-infiltrating immune cells, gene mutation, microsatellite instability (MSI), and immunotherapy efficacy. Results: We screened 100 anoikis-related differentially expressed genes between SKCM tissues and normal skin tissues, which could divide all patients into three different subtypes with significantly distinct prognosis and immune cell infiltration. Then, an anoikis-related signature was developed based on subtype-related DEGs, which could classify all SKCM patients into low and high ARG_score groups with differing overall survival (OS) rates. ARG_score was confirmed to be a strong independent prognostic indicator for SKCM patients. By combining ARG_score with clinicopathological features, a nomogram was constructed, which could accurately predict the individual OS of patients with SKCM. Moreover, low ARG_score patients presented with higher levels of immune cell infiltration, TME score, higher tumor mutation burden, and better immunotherapy responses. Conclusions: Our comprehensive analysis of ARGs in SKCM provides important insights into the immunological microenvironment within the tumor of SKCM patients and helps to forecast prognosis and the response to immunotherapy in SKCM patients, thereby making it easier to tailor more effective treatment strategies to individual patients.

Diversity of Trichoderma species associated with green mold contaminating substrates of Lentinula edodes and their interaction.

Introduction: The contamination of Trichoderma species causing green mold in substrates poses a significant obstacle to the global production of Lentinula edodes, adversely impacting both yield and quality of fruiting bodies. However, the diversity of Trichoderma species in the contaminated substrates of L. edodes (CSL) in China is not clear. The purpose of this study was to assess the biodiversity of Trichoderma species in CSL, and their interactions with L. edodes. Methods: A comprehensive two-year investigation of the biodiversity of Trichoderma species in CSL was conducted with 150 samples collected from four provinces of China. Trichoderma strains were isolated and identified based on integrated studies of phenotypic and molecular data. Resistance of L. edodes to the dominant Trichoderma species was evaluated in dual culture in vitro. Results: A total of 90 isolates were obtained and identified as 14 different Trichoderma species, including six new species named as Trichoderma caespitosus, T. macrochlamydospora, T. notatum, T. pingquanense, T. subvermifimicola, and T. tongzhouense, among which, T. atroviride, T. macrochlamydospora and T. subvermifimicola were identified as dominant species in the CSL. Meanwhile, three known species, namely, T. auriculariae, T. paraviridescens and T. subviride were isolated from CSL for the first time in the world, and T. paratroviride was firstly reported to be associated with L. edodes in China. Notebly, the in vitro evaluation of L. edodes resistance to dominant Trichoderma species showed strains of L. edodes generally possess poor resistance to Trichoderma contamination with L. edodes strain SX8 relatively higher resistant. Discussion: This study systematically investigated the diversity of Trichoderma species in the contaminated substrate of L. edodes, and a total of 31 species so far have been reported, indicating that green mold contaminated substrates of edible fungi were undoubtedly a biodiversity hotspot of Trichoderma species. Results in this study will provide deeper insight into the genus Trichoderma and lay a strong foundation for scientific management of the Trichoderma contamination in L. edodes cultivation.

Disulfidptosis-related classification patterns and tumor microenvironment characterization in skin cutaneous melanoma.

Aim: To identify distinct disulfidptosis-molecular subtypes and develop a novel prognostic signature. Methods/materials: We integrated into this study multiple SKCM transcriptomic datasets from the Cancer Genome Atlas database and Gene Expression Omnibus dataset. The consensus clustering algorithm was applied to categorize SKCM patients into different DRG subtypes. Results: Three distinct DRG subtypes were identified, which were correlated to different clinical outcomes and signaling pathways. Then, a disulfidptosis-relaed signature and nomogram were constructed, which could accurately predict the individual OS of patients with SKCM. The high-risk group was less sensitive to immunotherapy than the low-risk group. Conclusion: The signature can assist healthcare professionals in making more accurate and individualized treatment choices for patients with SKCM.

Three New Trichoderma Species in Harzianum Clade Associated with the Contaminated Substrates of Edible Fungi.

Trichoderma is known worldwide as biocontrol agents of plant diseases, producers of enzymes and antibiotics, and competitive contaminants of edible fungi. In this investigation of contaminated substrates of edible fungi from North China, 39 strains belonging to 10 Trichoderma species isolated from four kinds of edible fungi were obtained, and three novel species belonging to the Harzianum clade were isolated from the contaminated substrates of Auricularia heimuer and Pholiota adipose. They were recognized based on integrated studies of phenotypic features, culture characteristics, and molecular analyses of RNA polymerase II subunit B and translation elongation factor 1-α genes. Trichoderma auriculariae was strongly supported as a separate lineage and differed from T. vermifimicola due to its larger conidia. Trichoderma miyunense was closely related to T. ganodermatigerum but differed due to its smaller conidia and higher optimum mycelial growth temperature. As a separate lineage, T. pholiotae was distinct from T. guizhouense and T. pseudoasiaticum due to its higher optimum mycelial growth temperature and larger conidia. This study extends the understanding of Trichoderma spp. contaminating substrates of edible fungi and updates knowledge of species diversity in the group.

Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth.

Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth; however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.

Transcriptional Control of Metastasis by Integrated Stress Response Signaling.

As a central cellular program to sense and transduce stress signals, the integrated stress response (ISR) pathway has been implicated in cancer initiation and progression. Depending on the genetic mutation landscape, cellular context, and differentiation states, there are emerging pieces of evidence showing that blockage of the ISR can selectively and effectively shift the balance of cancer cells toward apoptosis, rendering the ISR a promising target in cancer therapy. Going beyond its pro-survival functions, the ISR can also influence metastasis, especially via proteostasis-independent mechanisms. In particular, ISR can modulate metastasis via transcriptional reprogramming, in the help of essential transcription factors. In this review, we summarized the current understandings of ISR in cancer metastasis from the perspective of transcriptional regulation.