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Animal models are commonly used for drug screening before clinical trials. However, developing these models is time-consuming, and the results obtained from these models may differ from clinical outcomes due to the differences between animals and humans. To this end, 3D bioprinting offers several advantages for drug screening, such as high reproducibility and improved throughput, in addition to the human cells that can be used to generate these models. Here, we report the development of an animal patient-derived in vitro breast cancer model for drug screening using digital light processing (DLP) bioprinting. These bioprinted models demonstrated good cytocompatibility and preserved phenotypes of the cells. DLP enabled rapid fabrication with blood vessel-like channels to replicate, to a good extent, the tumor microenvironment. Our findings suggested that the improved microenvironment, provided by vascular structures within the bioprinted models, played a crucial role in reducing the chemoresistance of drugs. In addition, the correlation of the in vitro and in vivo drug-screening results was preliminarily performed to evaluate the predictive feasibility of this bioprinted model, suggesting a potential strategy for the design of future drug-testing platforms. 

To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambient incubator oxygen level at 21%, which is higher than most if not all physiological oxygen concentrations. Additionally, the physiological oxygen level in each tissue is different ranging from 0.5 to 13%. Here, a closed-loop modular multiorgan-on-chips platform is developed to enable not only real-time monitoring of the oxygen levels but, more importantly, tight control of them in the range of 4 to 20% across each connected microtissue-on-a-chip in the circulatory culture medium. This platform, which consists of microfluidic oxygen scavenger(s), an oxygen generator, a monitoring/controller system, and bioreactor(s), allows for independent, precise upregulation and downregulation of dissolved oxygen in the perfused culture medium to meet the physiological oxygen level in each modular microtissue compartment, as needed. Furthermore, drug studies using the platform demonstrate that the oxygen level affects drug metabolism in the parallelly connected liver, kidney, and arterial vessel microtissues without organ–organ interactions factored in. Overall, this platform can promote the performances of organ-on-a-chip devices in drug screening by providing more physiologically relevant and independently adjustable oxygen microenvironments for desired organ types on a single- or a multiorgan-on-chip(s) configuration. 

Abstract Ancient whole-genome duplications (WGDs) are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent WGDs may contribute to evolvability within recent polyploids. Hybridization accompanying some WGDs may combine divergent gene content among diploid species. Some theory and evidence suggest that polyploids have a greater accumulation and tolerance of gene presence-absence and genomic structural variation, but it is unclear to what extent either is true. To test how recent polyploidy may influence pangenomic variation, we sequenced, assembled, and annotated twelve complete, chromosome-scale genomes of Camelina sativa, an allohexaploid biofuel crop with three distinct subgenomes. Using pangenomic comparative analyses, we characterized gene presence-absence and genomic structural variation both within and between the subgenomes. We found over 75% of ortholog gene clusters are core in Camelina sativa and <10% of sequence space was affected by genomic structural rearrangements. In contrast, 19% of gene clusters were unique to one subgenome, and the majority of these were Camelina-specific (no ortholog in Arabidopsis). We identified an inversion that may contribute to vernalization requirements in winter-type Camelina, and an enrichment of Camelina-specific genes with enzymatic processes related to seed oil quality and Camelina’s unique glucosinolate profile. Genes related to these traits exhibited little presence-absence variation. Our results reveal minimal pangenomic variation in this species, and instead show how hybridization accompanied by WGD may benefit polyploids by merging diverged gene content of different species. 

Abstract Fungi have evolved over millions of years and their species diversity is predicted to be the second largest on the earth. Fungi have cross-kingdom interactions with many organisms that have mutually shaped their evolutionary trajectories. Zygomycete fungi hold a pivotal position in the fungal tree of life and provide important perspectives on the early evolution of fungi from aquatic to terrestrial environments. Phylogenomic analyses have found that zygomycete fungi diversified into two separate clades, the Mucoromycota which are frequently associated with plants and Zoopagomycota that are commonly animal-associated fungi. Genetic elements that contributed to the fitness and divergence of these lineages may have been shaped by the varied interactions these fungi have had with plants, animals, bacteria, and other microbes. To investigate this, we performed comparative genomic analyses of the two clades of zygomycetes in the context of Kingdom Fungi, benefiting from our generation of a new collection of zygomycete genomes, including nine produced for this study. We identified lineage-specific genomic content that may contribute to the disparate biology observed in these zygomycetes. Our findings include the discovery of undescribed diversity in CotH, a Mucormycosis pathogenicity factor, which was found in a broad set of zygomycetes. Reconciliation analysis identified multiple duplication events and an expansion of CotH copies throughout the Mucoromycotina, Mortierellomycotina, Neocallimastigomycota, and Basidiobolus lineages. A kingdom-level phylogenomic analysis also identified new evolutionary relationships within the subphyla of Mucoromycota and Zoopagomycota, including supporting the sister-clade relationship between Glomeromycotina and Mortierellomycotina and the placement of Basidiobolus as sister to other Zoopagomycota lineages. 

Abstract Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two immiscible aqueous phases of gelatin methacryloyl (GelMA) and dextran, further endowed with anti-bacterial and anti-inflammatory properties. This micropore-forming GelMA-dextran (PGelDex) bioink exhibited excellent printability with vat-polymerization, extrusion, and handheld bioprinting methods. The porous structure was confirmed after bioprinting, which promoted the spreading of the encapsulated cells, exhibiting the exceptional cytocompatibility of this bioink formulation. To extend the applications of such a micropore-forming bioink, interleukin-4 (IL-4)-loaded silver-coated gold nanorods (AgGNRs) and human mesenchymal stem cells (MSCs) were simultaneously incorporated, to display synergistic anti-infection behavior and immunomodulatory function. The results revealed the anti-bacterial properties of the AgGNR-loaded PGelDex bioink for both Gram-negative and Gram-positive bacteria. The data also indicated that the presence of IL-4 and MSCs facilitated macrophage M2-phenotype differentiation, suggesting the potential anti-inflammatory feature of the bioink. Overall, this unique anti-bacterial and immunomodulatory micropore-forming bioink offers an effective strategy for the inhibition of bacterial-induced infections as well as the ability of immune-regulation, which is a promising candidate for broadened tissue bioprinting applications. 

As the continuation of Fungal Diversity Notes series, the current paper is the 16th contribution to this series. A total of 103 taxa from seven classes in Ascomycota and Basidiomycota are included here. Of these 101 taxa, four new genera, 89 new species, one new combination, one new name and six new records are described in detail along with information of hosts and geographic distributions. The four genera newly introduced are Ascoglobospora, Atheliella, Rufoboletus and Tenuimyces. Newly described species are Akanthomyces xixiuensis, Agaricus agharkarii, A. albostipitatus, Amphisphaeria guttulata, Ascoglobospora marina, Astrothelium peudostraminicolor, Athelia naviculispora, Atheliella conifericola, Athelopsis subglaucina, Aureoboletus minimus, A. nanlingensis, Autophagomyces incertus, Beltrania liliiferae, Beltraniella jiangxiensis, Botryobasidium coniferarum, Calocybella sribuabanensis, Calonarius caesiofulvus, C. nobilis, C. pacificus, C. pulcher, C. subcorrosus, Cortinarius flaureifolius, C. floridaensis, C. subiodes, Crustomyces juniperi, C. scytinostromoides, Cystostereum subsirmaurense, Dimorphomyces seemanii, Fulvoderma microporum, Ginnsia laricicola, Gomphus zamorinorum, Halobyssothecium sichuanense, Hemileccinum duriusculum, Henningsomyces hengduanensis, Hygronarius californicus, Kneiffiella pseudoabdita, K. pseudoalutacea, Laboulbenia bifida, L. tschirnhausii, L. tuberculata, Lambertella dipterocarpacearum, Laxitextum subrubrum, Lyomyces austro-occidentalis, L. crystallina, L. guttulatus, L. niveus, L. tasmanicus, Marasmius centrocinnamomeus, M. ferrugineodiscus, Megasporoporia tamilnaduensis, Meruliopsis crystallina, Metuloidea imbricata, Moniliophthora atlantica, Mystinarius ochrobrunneus, Neomycoleptodiscus alishanense, Nigrograna kunmingensis, Paracremonium aquaticum, Parahelicomyces dictyosporus, Peniophorella sidera, P. subreticulata, Phlegmacium fennicum, P. pallidocaeruleum, Pholiota betulicola, P. subcaespitosa, Pleurotheciella hyalospora, Pleurothecium aseptatum, Resupinatus porrigens, Russula chlorina, R. chrysea, R. cruenta, R. haematina, R. luteocarpa, R. sanguinolenta, Synnemellisia punensis, Tenuimyces bambusicola, Thaxterogaster americanoporphyropus, T. obscurovibratilis, Thermoascus endophyticus, Trechispora alba, T. perminispora, T. subfarinacea, T. tuberculata, Tremella sairandhriana, Tropicoporus natarajaniae, T. subramaniae, Usnea kriegeriana, Wolfiporiella macrospora and Xylodon muchuanensis. Rufoboletus hainanensis is newly transferred from Butyriboletus, while a new name Russula albocarpa is proposed for Russula leucocarpa G.J. Li & Chun Y. Deng an illegitimate later homonym of Russula leucocarpa (T. Lebel) T. Lebel. The new geographic distribution regions are recorded for Agaricus bambusetorum, Bipolaris heliconiae, Crinipellis trichialis, Leucocoprinus cretaceus, Halobyssothecium cangshanense and Parasola setulosa. Corresponding to morphological characters, phylogenetic evidence is also utilized to place the above-mentioned taxa in appropriate taxonomic positions. The current morphological and phylogenetic data is helpful for further clarification of species diversity and exploration of evolutionary relationships in the related fungal groups. 

Abstract Decellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM‐based materials. In this study, heart‐derived dECM (h‐dECM) and meniscus‐derived dECM (Ms‐dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2‐bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low‐concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte‐laden h‐dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms‐dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.