Changhao Zhou

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR–Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR–Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine. Analysis of 43,191 genomes obtained from publicly available marine bacterial and archaeal metagenome data provides insights into marine bacterial evolution, CRISPR–Cas defence and antibiotic resistance genes, and demonstrates the potential of marine metagenomes for biotechnological applications.

Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

Systematic exploration of the hadal zone, Earth's deepest oceanic realm, has historically faced technical limitations. Here, we collected 1,648 sediment samples at 6-11 km in the Mariana Trench, Yap Trench, and Philippine Basin for the Mariana Trench Environment and Ecology Research (MEER) project. Metagenomic and 16S rRNA gene amplicon sequencing generated the 92-Tbp MEER dataset, comprising 7,564 species (89.4% unreported), indicating high taxonomic novelty. Unlike in reported environments, neutral drift played a minimal role, while homogeneous selection (HoS, 50.5%) and dispersal limitation (DL, 43.8%) emerged as dominant ecological drivers. HoS favored streamlined genomes with key functions for hadal adaptation, e.g., aromatic compound utilization (oligotrophic adaptation) and antioxidation (high-pressure adaptation). Conversely, DL promoted versatile metabolism with larger genomes. These findings indicated that environmental factors drive the high taxonomic novelty in the hadal zone, advancing our understanding of the ecological mechanisms governing microbial ecosystems in such an extreme oceanic environment.

BACKGROUND: There is much evidence that confirms the inextricable link between inflammation and malignancy. Inflammation-related regulators were involved in the progression of kidney renal clear cell carcinoma (KIRC). However, the predictive role of single gene biomarkers is inadequate, and more accurate prognostic models are necessary. We undertook the current research to construct a robust inflammation-related gene signature that could stratify patients with KIRC. METHODS: The transcriptome sequencing data along with clinicopathologic information of KIRC were obtained from TCGA. A list of inflammation-related genes was acquired from the Molecular Signatures Database. Using the RNA-seq and survival time data from the TCGA training cohort, an inflammation-related gene signature was built using bioinformatic methods, and its performance in predicting patient prognosis was assessed by Kaplan-Meier and ROC curve analyses. Furthermore, we explored the association of risk score with immune score, stromal score, tumor immune-infiltrating cells (TIICs), immunosuppressive molecules, m6A regulators, and autophagy-related biomarkers. RESULTS: Herein, nine inflammation-related hub genes (ROS1, PLAUR, ACVR2A, KLF6, GABBR1, APLNR, SPHK1, PDPN, and ADORA2B) were determined and used to build a predictive model. All sets, including training set, four testing sets, and the entire TCGA group, were divided into two groups (low and high risk), and Kaplan-Meier curves all showed an adverse prognosis for patients in the high-risk group. ESTIMATE algorithm revealed a higher immune score in the high-risk subgroup. CIBERSORT algorithm illustrated that the high-risk group showed higher-level immune infiltrates. Furthermore, LAG3, TIGIT, and CTLA4 were overexpressed in the high-risk subgroup and positively associated with risk scores. Moreover, except for METTL3 and ALKBH5, the other m6A regulators decreased in the high-risk subgroup. CONCLUSIONS: In conclusion, a novel inflammation-related gene signature comprehensively constructed in the current study may help stratify patients with KIRC.

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio , Escherichia , and Paeniclostridium , whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas , Enterococcus , and Intestinimonas . Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale ( Globicephala macrorhynchus ) and a stranded rough-toothed dolphin ( Steno bredanensis ) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin ( Stenella attenuata ), Blainville’s beaked whale ( Mesoplodon densirostris ), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.