Microscopic image recognition of diatoms based on deep learning.

Diatoms are a crucial component in the study of aquatic ecosystems and ancient environmental records. However, traditional methods for identifying diatoms, such as morphological taxonomy and molecular detection, are costly, are time consuming, and have limitations. To address these issues, we developed an extensive collection of diatom images, consisting of 7983 images from 160 genera and 1042 species, which we expanded to 49,843 through preprocessing, segmentation, and data augmentation. Our study compared the performance of different algorithms, including backbones, batch sizes, dynamic data augmentation, and static data augmentation on experimental results. We determined that the ResNet152 network outperformed other networks, producing the most accurate results with top-1 and top-5 accuracies of 85.97% and 95.26%, respectively, in identifying 1042 diatom species. Additionally, we propose a method that combines model prediction and cosine similarity to enhance the model's performance in low-probability predictions, achieving an 86.07% accuracy rate in diatom identification. Our research contributes significantly to the recognition and classification of diatom images and has potential applications in water quality assessment, ecological monitoring, and detecting changes in aquatic biodiversity.

Effect of Peony (Paeonia ostii) Seed Meal Supplement on Enzyme Activities and Flavor Compounds of Chinese Traditional Soybean Paste during Fermentation.

Peony seed meal (PSM) is the by-product obtained from peony seeds after oil extraction. In this study, PSM was incorporated into traditional koji-making, and its impacts on koji enzyme activities and flavor compounds in final products were investigated. In the process of koji fermentation, the optimal addition ratio of PSM to soybean was determined as 7:3. Under this ratio, the maximum enzyme activities of neutral protease, amylase, and glucoamylase were 1177.85, 686.58, and 1564.36 U/g, respectively, and the koji obtained was subjected to maturation. During post-fermentation, changes in the fermentation characteristics of the paste samples were monitored, and it was found that compared to the soybean paste without PSM, the enzyme activities maintained at a relatively good level. The PSM soybean paste contained a total of 80 flavor compounds and 11 key flavor compounds (OAV ≥ 1), including ethyl isovalerate, isovaleric acid, hexanal, phenylacetaldehyde, 3-Methyl-1-butanol 4-heptanone, 2-pentylfuran, methanethiol ester caproate, isoamyl acetate, 3-methyl-4-heptanone, and isovaleraldehyde. These findings could be used to improve the quality of traditional fermented paste, enrich its flavor, and simultaneously promote PSM as a valuable resource for fermented foods.

Closing the Gap between Bio-Based and Petroleum-Based Plastic through Bioengineering.

Bioplastics, which are plastic materials produced from renewable bio-based feedstocks, have been investigated for their potential as an attractive alternative to petroleum-based plastics. Despite the harmful effects of plastic accumulation in the environment, bioplastic production is still underdeveloped. Recent advances in strain development, genome sequencing, and editing technologies have accelerated research efforts toward bioplastic production and helped to advance its goal of replacing conventional plastics. In this review, we highlight bioengineering approaches, new advancements, and related challenges in the bioproduction and biodegradation of plastics. We cover different types of polymers, including polylactic acid (PLA) and polyhydroxyalkanoates (PHAs and PHBs) produced by bacterial, microalgal, and plant species naturally as well as through genetic engineering. Moreover, we provide detailed information on pathways that produce PHAs and PHBs in bacteria. Lastly, we present the prospect of using large-scale genome engineering to enhance strains and develop microalgae as a sustainable production platform.

CDK1 serves as a therapeutic target of adrenocortical carcinoma via regulating epithelial-mesenchymal transition, G2/M phase transition, and PANoptosis.

BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare, aggressive tumor with few effective therapeutic options or drugs. Mitotane (Mtn), which is the only authorized therapeutic drug, came out in 1970 and is still the only first-line treatment for ACC in spite of serious adverse reaction and a high recurrence rate. METHODS: By in silico analysis of the ACC dataset in the cancer genome atlas (TCGA), we determined that high expression levels of cyclin-dependent kinase-1 (CDK1) were significantly related to the adverse clinical outcomes of ACC. In vitro and in vivo experiments were performed to evaluate the role of CDK1 in ACC progression through gain and loss of function assays in ACC cells. CDK1 inhibitors were screened to identify potential candidates for the treatment of ACC. RNA sequencing, co-immunoprecipitation, and immunofluorescence assays were used to elucidate the mechanism. RESULTS: Overexpression of CDK1 in ACC cell lines promoted proliferation and induced the epithelial-to-mesenchymal transition (EMT), whereas knockdown of CDK1 expression inhibited growth of ACC cell lines. The CDK1 inhibitor, cucurbitacin E (CurE), had the best inhibitory effect with good time-and dose-dependent activity both in vitro and in vivo. CurE had a greater inhibitory effect on ACC xenografts in nude mice than mitotane, without obvious adverse effects. Most importantly, combined treatment with CurE and mitotane almost totally eliminated ACC tumors. With respect to mechanism, CDK1 facilitated the EMT of ACC cells via Slug and Twist and locked ACC cells into the G2/M checkpoint through interaction with UBE2C and AURKA/B. CDK1 also regulated pyroptosis, apoptosis, and necroptosis (PANoptosis) of ACC cells through binding with the PANoptosome in a ZBP1-dependent way. CONCLUSIONS: CDK1 could be exploited as an essential therapeutic target of ACC via regulating the EMT, the G2/M checkpoint, and PANoptosis. Thus, CurE may be a potential candidate drug for ACC therapy with good safety and efficacy, which will meet the great need of patients with ACC.

Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis.

Apolipoprotein C1 (APOC1) has been found to play an essential part in proliferation and metastasis of numerous cancers, but related mechanism has not been elucidated, especially its function and role in tumor immunity. Through systematic pan-cancer analysis, we identified that APOC1 was closely associated with the infiltration of various immune cells in multiple cancers. Besides, APOC1 was significantly co-expressed with the immune checkpoints, major histocompatibility complex (MHC) molecules, chemokines and other immune-related genes. Furthermore, single-cell sequencing analysis suggested that the vast majority of APOC1 was expressed in macrophages or tumor-associated macrophages (TAMs). Additionally, the expression of APOC1 was significantly related to the prognosis of different cancers. Since APOC1 was most significantly abnormally expressed in renal cell cancer (RCC), subsequent experiments were carried out in RCC to explore the role of APOC1 in tumor immunity. The expression of APOC1 was significantly elevated in the tumor and serum of RCC patients. Besides, APOC1 was mainly expressed in the macrophage and it was closely related to the immune cell infiltration of RCC. Co-culture with RCC cells could induce the generation of TAMs with M2 phenotype which be blocked by silencing APOC1. The expression of APOC1 was elevated in the M2 or TAMs and APOC1 promoted M2 polarization of macrophages through interacting with CD163 and CD206. Furthermore, macrophages overexpressing APOC1 promoted the metastasis of RCC cells via secreting CCL5. Together, these data indicate that APOC1 is an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis.

Recent Progress on Systems and Synthetic Biology of Diatoms for Improving Algal Productivity.

Microalgae have drawn much attention for their potential applications as a sustainable source for developing bioactive compounds, functional foods, feeds, and biofuels. Diatoms, as one major group of microalgae with high yields and strong adaptability to the environment, have shown advantages in developing photosynthetic cell factories to produce value-added compounds, including heterologous bioactive products. However, the commercialization of diatoms has encountered several obstacles that limit the potential mass production, such as the limitation of algal productivity and low photosynthetic efficiency. In recent years, systems and synthetic biology have dramatically improved the efficiency of diatom cell factories. In this review, we discussed first the genome sequencing and genome-scale metabolic models (GEMs) of diatoms. Then, approaches to optimizing photosynthetic efficiency are introduced with a focus on the enhancement of biomass productivity in diatoms. We also reviewed genome engineering technologies, including CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing to produce bioactive compounds in diatoms. Finally, we summarized the recent progress on the diatom cell factory for producing heterologous compounds through genome engineering to introduce foreign genes into host diatoms. This review also pinpointed the bottlenecks in algal engineering development and provided critical insights into the future direction of algal production.

GABRP is a potential prognostic biomarker and correlated with immune infiltration and tumor microenvironment in pancreatic cancer.

Background: Pancreatic cancer is one of the most commonly diagnosed and lethal malignancies worldwide and has few good biomarkers and therapeutic targets. GABRP is the π subunit of the gamma-aminobutyric acid (GABA) A receptor, which is expressed in a number of non-neuronal tissues. GABRP is significantly upregulated in pancreatic cancer, but its biological and immunological role as well as its clinical diagnostic and prognostic value in pancreatic cancer is still incompletely known. Methods: In this study, pancreatic adenocarcinoma (PAAD) cohorts from TCGA and GEO datasets were used to compare GABRP mRNA levels in cancerous and normal tissues and protein expression was evaluated using immunohistochemistry. The Kaplan-Meier plotter and GEPIA2 database were used to analyze the correlation between GABRP expression, overall survival, and disease-free survival in pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed with the Linked Omics database to explore the molecular mechanisms of GABRP in pancreatic cancer. And the correlation between GABRP expression and immune infiltration was explored using the TIMER database, CIBERSORT database and ESTIMATE algorithm. Results: GABRP mRNA was significantly overexpressed in TCGA-PAAD cohorts (P<0.0001) and enhanced GABRP expression predicted poorer overall survival according to Kaplan-Meier plotter database (P=0.0024) and GEPIA2 (P=0.038). Hypomethylation of promoter (P<0.01) and the regulation of hsa-miR-3655 may contribute to the overexpression of GABRP in pancreatic cancer. GSEA analysis revealed that GABRP played an important role in the immune response. GABRP expression was also correlated with immune infiltration and immune cell markers. Higher GABRP expression was significantly associated with greater infiltration of immune cells and stromal cells into pancreatic cancer microenvironments as well as higher expression of six important immune check point genes including PDCD1 (P<0.05), CD274 (P<0.05), CTLA4 (P<0.01), PDCD1LG2 (P<0.01), TIGHT (P<0.01) and TIM3 (P<0.01). Conclusions: GABRP is a potential prognostic biomarker and is correlated with immune infiltration and tumor microenvironment in pancreatic cancer. This suggests that GABRP may serve as a potential prognostic biomarker and therapeutic target in pancreatic cancer as well as a possible regulator of tumor microenvironment affecting the efficacy of immunotherapy. Further studies are needed to elucidate the molecular mechanism of the immunoregulatory role of GABRP.

Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis.

Glioblastoma (GBM), a malignant brain tumor, is a world-wide health problem because of its poor prognosis and high rates of recurrence and mortality. Apolipoprotein C1 (APOC1) is the smallest of apolipoproteins, implicated in many diseases. Recent studies have shown that APOC1 promotes tumorigenesis and development of several types of cancer. In this study we investigated the role of APOC1 in GBM tumorigenesis. Using in silico assays we showed that APOC1 was highly expressed in GBM tissues and its expression was closely related to GBM progression. We showed that APOC1 protein expression was markedly increased in four GBM cell lines (U251, U138, A172 and U87) compared to the normal brain glia cell lines (HEB, HA1800). In U251 cells, overexpression of APOC1 promoted cell proliferation, migration, invasion and colony information, which was reversed by APOC1 knockdown. APOC1 knockdown also markedly inhibited the growth of GBM xenografts in the ventricle of nude mice. We further demonstrated that APOC1 reduced ferroptosis by inhibiting KEAP1, promoting nuclear translocation of NRF2 and increasing expression of HO-1 and NQO1 in GBM cells. APOC1 also induced ferroptosis resistance by increasing cystathionine beta-synthase (CBS) expression, which promoted trans-sulfuration and increased GSH synthesis, ultimately leading to an increase in glutathione peroxidase-4 (GPX4). Thus, APOC1 plays a key role in GBM tumorigenesis, conferring resistance to ferroptosis, and may be a promising therapeutic target for GBM.

ADH1C inhibits progression of colorectal cancer through the ADH1C/PHGDH /PSAT1/serine metabolic pathway.

Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. CRC is the second leading cause of cancer-related deaths. Although some progress in the treatment of CRC has been achieved, the molecular mechanism of CRC is still unclear. In this study, alcohol dehydrogenase 1C(ADH1C) was first identified as a target gene closely associated with the development of CRC by the comprehensive application of transcriptomics, proteomics, metabonomics and in silico analysis. The ADH1C mRNA and protein expression in CRC cell lines and tumor tissues was lower than that in normal intestinal epithelial cell lines and healthy tissues. Overexpression of ADH1C inhibited the growth, migration, invasion and colony formation of CRC cell lines and prevented the growth of xenograft tumors in nude mice. The inhibitory effects of ADH1C on CRC cells in vitro were exerted by reducing the expression of PHGDH/PSAT1 and the serine level. This inhibition could be partially reversed by adding serine to the culture medium. These results showed that ADH1C is a potential drug target in CRC.

Benzimidazoles induce concurrent apoptosis and pyroptosis of human glioblastoma cells via arresting cell cycle.

Glioblastoma multiforme (GBM) is the most malignant and lethal primary brain tumor in adults accounting for about 50% of all gliomas. The only treatment available for GBM is the drug temozolomide, which unfortunately has frequent drug resistance issue. By analyzing the hub genes of GBM via weighted gene co-expression network analysis (WGCNA) of the cancer genome atlas (TCGA) dataset, and using the connectivity map (CMAP) platform for drug repurposing, we found that multiple azole compounds had potential anti-GBM activity. When their anti-GBM activity was examined, however, only three benzimidazole compounds, i.e. flubendazole, mebendazole and fenbendazole, potently and dose-dependently inhibited proliferation of U87 and U251 cells with IC50 values below 0.26 µM. Benzimidazoles (0.125-0.5 µM) dose-dependently suppressed DNA synthesis, cell migration and invasion, and regulated the expression of key epithelial-mesenchymal transition (EMT) markers in U87 and U251 cells. Benzimidazoles treatment also dose-dependently induced the GBM cell cycle arrest at the G2/M phase via the P53/P21/cyclin B1 pathway. Furthermore, the drugs triggered pyroptosis of GBM cells through the NF-κB/NLRP3/GSDMD pathway, and might also concurrently induced mitochondria-dependent apoptosis. In a nude mouse U87 cell xenograft model, administration of flubendazole (12.5, 25, and 50 mg · kg-1 · d-1, i.p, for 3 weeks) dose-dependently suppressed the tumor growth without obvious adverse effects. Taken together, our results demonstrated that benzimidazoles might be promising candidates for the treatment of GBM.

High-Throughput Metabolic Profiling for Model Refinements of Microalgae.

Metabolic models are reconstructed based on an organism's available genome annotation and provide predictive tools to study metabolic processes at a systems-level. Genome-scale metabolic models may include gaps as well as reactions that are unverified experimentally. Reconstructed models of newly isolated microalgal species will result in weaknesses due to these gaps, as there is usually sparse biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology is an effective, high-throughput method that functionally determines cellular metabolic activities in response to a wide array of entry metabolites. Combining the high throughput phenotypic assays with metabolic modeling can allow existing metabolic network models to be rapidly reconstructed or optimized by providing biochemical evidence to support and expand genomic evidence. This work will show the use of PM assays for the study of microalgae by using the green microalgal model species Chlamydomonas reinhardtii as an example. Experimental evidence for over 254 reactions obtained by PM was used in this study to expand and refine a genome-scale C. reinhardtii metabolic network model, iRC1080, by approximately 25 percent. The protocol created here can be used as a basis for functionally profiling the metabolism of other microalgae, including known microalgae mutants and new isolates.

The biology, function, and applications of exosomes in cancer.

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.

Tumorigenic bacteria in colorectal cancer: mechanisms and treatments.

Colorectal cancer (CRC) is the third most common and the second most fatal cancer. In recent years, more attention has been directed toward the role of gut microbiota in the initiation and development of CRC. Some bacterial species, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, Enterococcus faecalis, and Salmonella sp. have been associated with CRC, based upon sequencing studies in CRC patients and functional studies in cell culture and animal models. These bacteria can cause host DNA damage by genotoxic substances, including colibactin secreted by pks + Escherichia coli, B. fragilis toxin (BFT) produced by Bacteroides fragilis, and typhoid toxin (TT) from Salmonella. These bacteria can also indirectly promote CRC by influencing host-signaling pathways, such as E-cadherin/ß-catenin, TLR4/MYD88/NF-κB, and SMO/RAS/p38 MAPK. Moreover, some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function, creating a proinflammatory environment, or influencing the autophagy process. Treatments with the classical antibacterial drugs, metronidazole or erythromycin, the antibacterial active ingredients, M13@ Ag (electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13), berberine, and zerumbone, were found to inhibit tumorigenic bacteria to different degrees. In this review, we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria, as well as progress in developing effective antibacterial therapies. Specific bacteria have been shown to be active in the oncogenesis and progression of CRC, and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC. These bacteria may be useful as biomarkers or therapeutic targets for CRC.