Sarcopenia among the older population has been growing over the last few years. In addition, the incidence of cancers increases with age and, consequently, the development of cachexia related cancer. Therefore, the elucidation of the metabolic derangements of sarcopenia and cachexia are important to improve the survival and life quality of cancer patients. We performed the ¹H-NMR based serum metabolomics in adult (A) and ageing (S) Walker 256 tumour-bearing rats in different stages of tumour evolution, namely intermediated (Wi) and advanced (Wa). Among 52 serum metabolites that were identified, 21 were significantly increased in S and 14 and 19 decreased in the Wi and Wa groups, respectively. The most impacted pathways by this metabolic alteration were related by amino acid biosynthesis and metabolism, with an upregulation in S group and downregulation in Wi and Wa groups. Taken together, our results suggest that the increase in metabolic profile in ageing rats is associated with the higher muscle protein degradation that releases several metabolites, especially amino acids into the serum. On the other hand, we hypothesise that the majority of metabolites released by muscle catabolism are used by tumours to sustain rapid cell proliferation and tumorigenesis.

Trichoderma harzianum , whose gene expression is tightly controlled by the transcription factors (TFs) XYR1 and CRE1, is a potential candidate for hydrolytic enzyme production. Here, we performed a network analysis of T. harzianum IOC-3844 and T. harzianum CBMAI-0179 to explore how the regulation of these TFs varies between these strains. In addition, we explored the evolutionary relationships of XYR1 and CRE1 protein sequences among Trichoderma spp. The results of the T. harzianum strains were compared with those of Trichoderma atroviride CBMAI-0020, a mycoparasitic species. Although transcripts encoding carbohydrate-active enzymes (CAZymes), TFs, transporters, and proteins with unknown functions were coexpressed with cre1 or xyr1 , other proteins indirectly related to cellulose degradation were identified. The enriched GO terms describing the transcripts of these groups differed across all strains, and several metabolic pathways with high similarity between both regulators but strain-specific differences were identified. In addition, the CRE1 and XYR1 subnetworks presented different topology profiles in each strain, likely indicating differences in the influences of these regulators according to the fungi. The hubs of the cre1 and xyr1 groups included transcripts not yet characterized or described as being related to cellulose degradation. The first-neighbor analyses confirmed the results of the profile of the coexpressed transcripts in cre1 and xyr1 . The analyses of the shortest paths revealed that CAZymes upregulated under cellulose degradation conditions are most closely related to both regulators, and new targets between such signaling pathways were discovered. Although the evaluated T. harzianum strains are phylogenetically close and their amino acid sequences related to XYR1 and CRE1 are very similar, the set of transcripts related to xyr1 and cre1 differed, suggesting that each T. harzianum strain used a specific regulation strategy for cellulose degradation. More interestingly, our findings may suggest that XYR1 and CRE1 indirectly regulate genes encoding proteins related to cellulose degradation in the evaluated T. harzianum strains. An improved understanding of the basic biology of fungi during the cellulose degradation process can contribute to the use of their enzymes in several biotechnological applications and pave the way for further studies on the differences across strains of the same species.

Trichoderma atroviride and Trichoderma harzianum are widely used as commercial biocontrol agents against plant diseases. Recently, T. harzianum IOC-3844 (Th3844) and T. harzianum CBMAI-0179 (Th0179) demonstrated great potential in the enzymatic conversion of lignocellulose into fermentable sugars. Herein, we performed whole-genome sequencing and assembly of the Th3844 and Th0179 strains. To assess the genetic diversity within the genus Trichoderma , the results of both strains were compared with strains of T. atroviride CBMAI-00020 (Ta0020) and T. reesei CBMAI-0711 (Tr0711). The sequencing coverage value of all genomes evaluated in this study was higher than that of previously reported genomes for the same species of Trichoderma . The resulting assembly revealed total lengths of 40 Mb (Th3844), 39 Mb (Th0179), 36 Mb (Ta0020), and 32 Mb (Tr0711). A genome-wide phylogenetic analysis provided details on the relationships of the newly sequenced species with other Trichoderma species. Structural variants revealed genomic rearrangements among Th3844, Th0179, Ta0020, and Tr0711 relative to the T. reesei QM6a reference genome and showed the functional effects of such variants. In conclusion, the findings presented herein allow the visualization of genetic diversity in the evaluated strains and offer opportunities to explore such fungal genomes in future biotechnological and industrial applications.

Lignocellulosic biomass is a complex carbon source with recalcitrant properties whose degradation via industrial enzymatic hydrolysis is challenging, directly affecting the cost of reliable energy production. In nature, filamentous fungi, including Trichoderma species, degrade lignocellulose via an arsenal of hydrolytic and oxidative enzymes that act synergistically to process it into soluble sugar monomers. This work explored the genomic content of Trichoderma atroviride and Trichoderma harzianum strains with hydrolytic abilities by identifying regions possessing degradative enzyme-encoding genes, namely, hydrolytic clusters. We employed bacterial artificial chromosome (BAC) methodology to target specific genomic regions and explore their genetic organization, proximal gene context, and gene expression under degradative conditions. With this tool, it was possible to inspect the linear structure and expression profile of target hydrolytic-rich genomic regions. The present work offers a perspective on the organization of genome regions related to carbohydrate metabolism. This study revealed novel genes and genome regions that are positively regulated during cellulose degradation, contributing to elucidating differences in gene organization that potentially impact hydrolysis among Trichoderma species.

In filamentous fungi, light plays a key role in regulating physiological processes such as growth, conidiation, secondary metabolism, and the expression of hydrolytic enzymes. The processes that depend on light are controlled by photoreceptors, including BLR1, BLR2, and ENV1, as well as by signaling pathways involving heterotrimeric G-proteins and cyclic adenosine monophosphate (cAMP). Trichoderma harzianum is a promising candidate for biotechnological use and is able to promote hydrolytic reactions under biomass degradation conditions. However, the genetic mechanisms underlying its response to light remain poorly understood, especially under degradative conditions. This study aimed to assess the expression of carbohydrate-active enzymes (CAZymes), transcription factors (TFs), and signaling pathway proteins under different light conditions and carbon sources. The results revealed distinct patterns of relative gene expression influenced by these environmental factors, highlighting the complex regulatory mechanisms at play in T. harzianum . Moreover, our results suggested that env1 , cre1 , and blr2 are critical for adjusting to different light conditions and carbon sources. This highlights the importance of both factors in regulating gene expression and supporting metabolic adaptation in T. harzianum . To our knowledge, such findings have not been previously reported in the context of cellulose degradation for this species. Overall, these results offer valuable insights into how T. harzianum responds to environmental changes, revealing a complex regulatory network that is not only crucial for optimizing fungal growth in industrial applications but also deepens our understanding of its biology and ecological interactions. Highlights: ▪ Trichoderma harzianum is a key candidate for biotechnology applications. ▪ Light and carbon control CAZymes, photoreceptors, key regulators, and signaling. ▪ T. harzianum has distinct gene expression patterns under different light conditions and carbon sources. ▪ env1 , cre1 , and blr2 regulate metabolic adaptation in T. harzianum . Graphical