Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism.

Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.

The transmembrane protein LbRSG from the recretohalophyte Limonium bicolor enhances salt gland development and salt tolerance.

Salt glands are the unique epidermal structures present in recretohalophytes, plants that actively excrete excess Na+ by salt secretory structures to avoid salt damage. Here, we describe a transmembrane protein that localizes to the plasma membrane of the recretohalophyte Limonium bicolor. As virus-induced gene silencing of the corresponding gene LbRSG in L. bicolor decreased the number of salt glands, we named the gene Reduced Salt Gland. We detected LbRSG transcripts in salt glands by in situ hybridization and transient transformation. Overexpression and silencing of LbRSG in L. bicolor pointed to a positive role in salt gland development and salt secretion by interacting with Lb3G16832. Heterologous LbRSG expression in Arabidopsis enhanced salt tolerance during germination and the seedling stage by alleviating NaCl-induced ion stress and osmotic stress after replacing or deleting the (highly) negatively charged region of extramembranous loop. After screened by immunoprecipitation-mass spectrometry and verified using yeast two-hybrid, PGK1 and BGLU18 were proposed to interact with LbRSG to strengthen salt tolerance. Therefore, we identified (highly) negatively charged regions in the extramembrane loop that may play an essential role in salt tolerance, offering hints about LbRSG function and its potential to confer salt resistance.

MYC promotes cancer progression by modulating m6 A modifications to suppress target gene translation.

The MYC oncoprotein activates and represses gene expression in a transcription-dependent or transcription-independent manner. Modification of mRNA emerges as a key gene expression regulatory nexus. We sought to determine whether MYC alters mRNA modifications and report here that MYC promotes cancer progression by down-regulating N6-methyladenosine (m6 A) preferentially in transcripts of a subset of MYC-repressed genes (MRGs). We find that MYC activates the expression of ALKBH5 and reduces m6 A levels in the mRNA of the selected MRGs SPI1 and PHF12. We also show that MYC-regulated m6 A controls the translation of MRG mRNA via the specific m6 A reader YTHDF3. Finally, we find that inhibition of ALKBH5, or overexpression of SPI1 or PHF12, effectively suppresses the growth of MYC-deregulated B-cell lymphomas, both in vitro and in vivo. Our findings uncover a novel mechanism by which MYC suppresses gene expression by altering m6 A modifications in selected MRG transcripts promotes cancer progression.

Bracelet salt glands of the recretohalophyte Limonium bicolor: Distribution, morphology, and induction.

Halophytes complete their life cycles in saline environments. The recretohalophyte Limonium bicolor has evolved a specialized salt secretory structure, the salt gland, which excretes Na+ to avoid salt damage. Typical L. bicolor salt glands consist of 16 cells with four fluorescent foci and four secretory pores. Here, we describe a special type of salt gland at the base of the L. bicolor leaf petiole named bracelet salt glands due to their beaded-bracelet-like shape of blue auto-fluorescence. Bracelet salt glands contain more than 16 cells and more than four secretory pores. Leaf disc secretion measurements and non-invasive micro-test techniques indicated that bracelet salt glands secrete more salt than normal salt glands, which helps maintain low Na+ levels at the leaf blade to protect the leaf. Cytokinin treatment induced bracelet salt gland differentiation, and the developed ones showed no further differentiation when traced with a living fluorescence microscopy imager, even though new salt gland development and leaf expansion were observed. Transcriptome revealed a NAC transcription factor gene that participates in bracelet salt gland development, as confirmed by its genome editing and overexpression in L. bicolor. These findings shed light on bracelet salt gland development and may facilitate the engineering of salt-tolerant crops.

The Role of Transmembrane Proteins in Plant Growth, Development, and Stress Responses.

Transmembrane proteins participate in various physiological activities in plants, including signal transduction, substance transport, and energy conversion. Although more than 20% of gene products are predicted to be transmembrane proteins in the genome era, due to the complexity of transmembrane domains they are difficult to reliably identify in the predicted protein, and they may have different overall three-dimensional structures. Therefore, it is challenging to study their biological function. In this review, we describe the typical structures of transmembrane proteins and their roles in plant growth, development, and stress responses. We propose a model illustrating the roles of transmembrane proteins during plant growth and response to various stresses, which will provide important references for crop breeding.

A novel bacterial phylum that participates in carbon and osmolyte cycling in the Challenger Deep sediments.

Large amounts of detrital organic matter and osmolytes accumulate in the sediments of hadal trenches (>6000 m depth) due to the funnelling effect. It is still unknown whether there are novel active microbes that depend on specific carbon sources in extreme and isolated environments. In this study, we present a novel active bacterial phylum, Candidatus Tianyabacteria in the FCB superphylum, which was enriched in sediments collected from the Challenger Deep. Genome binning resulted in high-quality Ca. Tianyabacteria genomes representing two Ca. Tianyabacteria lineages (L1 and L2) in sediments 0-21 cm below the surface (cmbsf); L1 tends to be abundant in the upper layers (0-9 cmbsf), and L2 seems to be more prevalent in the deeper layers (12-21 cmbsf). Gene annotation and transcriptomics results indicate that the two lineages might import and catalyse amino acids and myo-inositol into central carbon metabolism for a heterotrophic lifestyle. Probably due to differences in environmental oxygen levels, the L2 genomes harbour gene clusters responsible for denitrification and fermentation, while the L1 genomes encode octahaem cytochrome c and multicopper oxidase using unknown substrates. The Ca. Tianyabacteria are thus novel heterotrophic organisms that participate in processes of carbon, nitrogen and organic osmolyte cycling in hadal sediments.

Microbial ecology of sulfur cycling near the sulfate-methane transition of deep-sea cold seep sediments.

Microbial sulfate reduction is largely associated with anaerobic methane oxidation and alkane degradation in sulfate-methane transition zone (SMTZ) of deep-sea cold seeps. How the sulfur cycling is mediated by microbes near SMTZ has not been fully understood. In this study, we detected a shallow SMTZ in three of eight sediment cores sampled from two cold seep areas in the South China Sea. One hundred ten genomes representing sulfur-oxidizing bacteria (SOB) and sulfur-reducing bacteria (SRB) strains were identified from three SMTZ-bearing cores. In the layers above SMTZ, SOB were mostly constituted by Campylobacterota, Gammaproteobacteria and Alphaproteobacteria that probably depended on nitrogen oxides and/or oxygen for oxidation of sulfide and thiosulfate in near-surface sediment layers. In the layers below the SMTZ, the deltaproteobacterial SRB genomes and metatranscriptomes revealed CO2 fixation by Wood-Ljungdahl pathway, sulfate reduction and nitrogen fixation for syntrophic or fermentative lifestyle. A total of 68% of the metagenome assembled genomes were not adjacent to known species in a phylogenomic tree, indicating a high diversity of bacteria involved in sulfur cycling. With the large number of genomes for SOB and SRB, our study uncovers the microbial populations that potentially mediate sulfur metabolism and associated carbon and nitrogen cycles, which sheds light on complex biogeochemical processes in deep-sea environments.

A novel gene LbHLH from the halophyte Limonium bicolor enhances salt tolerance via reducing root hair development and enhancing osmotic resistance.

BACKGROUND: Identifying genes involved in salt tolerance in the recretohalophyte Limonium bicolor could facilitate the breeding of crops with enhanced salt tolerance. Here we cloned the previously uncharacterized gene LbHLH and explored its role in salt tolerance. RESULTS: The 2,067-bp open reading frame of LbHLH encodes a 688-amino-acid protein with a typical helix-loop-helix (HLH) domain. In situ hybridization showed that LbHLH is expressed in salt glands of L. bicolor. LbHLH localizes to the nucleus, and LbHLH is highly expressed during salt gland development and in response to NaCl treatment. To further explore its function, we heterologously expressed LbHLH in Arabidopsis thaliana under the 35S promoter. The overexpression lines showed significantly increased trichome number and reduced root hair number. LbHLH might interact with GLABRA1 to influence trichome and root hair development, as revealed by yeast two-hybrid analysis. The transgenic lines showed higher germination percentages and longer roots than the wild type under NaCl treatment. Analysis of seedlings grown on medium containing sorbitol with the same osmotic pressure as 100 mM NaCl demonstrated that overexpressing LbHLH enhanced osmotic resistance. CONCLUSION: These results indicate that LbHLH enhances salt tolerance by reducing root hair development and enhancing osmotic resistance under NaCl stress.

Phylogenomics of expanding uncultured environmental Tenericutes provides insights into their pathogenicity and evolutionary relationship with Bacilli.

BACKGROUND: The metabolic capacity, stress response and evolution of uncultured environmental Tenericutes have remained elusive, since previous studies have been largely focused on pathogenic species. In this study, we expanded analyses on Tenericutes lineages that inhabit various environments using a collection of 840 genomes. RESULTS: Several environmental lineages were discovered inhabiting the human gut, ground water, bioreactors and hypersaline lake and spanning the Haloplasmatales and Mycoplasmatales orders. A phylogenomics analysis of Bacilli and Tenericutes genomes revealed that some uncultured Tenericutes are affiliated with novel clades in Bacilli, such as RF39, RFN20 and ML615. Erysipelotrichales and two major gut lineages, RF39 and RFN20, were found to be neighboring clades of Mycoplasmatales. We detected habitat-specific functional patterns between the pathogenic, gut and the environmental Tenericutes, where genes involved in carbohydrate storage, carbon fixation, mutation repair, environmental response and amino acid cleavage are overrepresented in the genomes of environmental lineages, perhaps as a result of environmental adaptation. We hypothesize that the two major gut lineages, namely RF39 and RFN20, are probably acetate and hydrogen producers. Furthermore, deteriorating capacity of bactoprenol synthesis for cell wall peptidoglycan precursors secretion is a potential adaptive strategy employed by these lineages in response to the gut environment. CONCLUSIONS: This study uncovers the characteristic functions of environmental Tenericutes and their relationships with Bacilli, which sheds new light onto the pathogenicity and evolutionary processes of Mycoplasmatales.

Tumor necrosis factor receptor-associated factor 3 from Anodonta woodiana is an important factor in bivalve immune response to pathogen infection.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional adaptor protein in innate and acquired immune system that plays a key role in the regulation of the RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling pathway in mammals. However, the immune function of TRAF3 homologs in freshwater mollusks is not well understood. In this study, we identified a bivalve TRAF3 gene (AwTRAF3) from Anodonta woodiana and investigated its potential roles during immune challenges. The present AwTRAF3 encoded a polypeptide of 562 amino acids with predicted molecular mass of 64.5 kDa and PI of 7.9. Similar to other reported TRAF3s, AwTRAF3 contained a RING finger domain, two TRAF domains with zinc finger domains, a coiled coli region and a conserved C-terminal meprin and TRAF homology (MATH) domain. Quantitative real-time PCR (qRT-PCR) analysis revealed that AwTRAF3 mRNA was broadly expressed in all of the examined tissues, with high expression in hepatopancreas, gill and heart. In addition, immune challenge experiments directly showed that transcript levels of AwTRAF3 in hepatopancreas were significantly regulated upon bacterial (Vibrio alginolyticus and Staphylococcus aureus) and viral (poly (I:C)) challenges, respectively. Moreover, GFP-tagged AwTRAF3 fusion protein was found to be located primarily in the cytoplasm in HEK293T cells. Altogether, these data provided the first experimental demonstration that freshwater mollusks possess a functional TRAF3 that was involved in the innate defense against bacterial and viral infection.

A molluscan TNF receptor-associated factor 2 (TRAF2) was involved in host defense against immune challenges.

Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a member of the TRAF superfamily that acted as a key signal transduction protein and has been implicated in inflammatory and apoptosis processes in mammals. However, identification of TRAF2s in invertebrates is very limited and its function, in particular that under immune challenges, is still unknown. In this report, a molluscan TRAF2 gene (referred to as AwTRAF2) was cloned and characterized from the freshwater bivalve, Anodonta woodiana. The open reading frame (ORF) of AwTRAF2 was 1683 bp in length, which encoded a putative 560 amino acid-protein. The deduced AwTRAF2 sequence shared similar structural characteristics and close evolutionary relationship with mollusk TRAF2s. The tissue-specific expression analysis revealed that AwTRAF2 mRNA was broadly expressed in all tested tissues, with high expression in gill and hepatopancreas. In addition, in vivo injection experiments directly showed that AwTRAF2 mRNA levels in hepatopancreas were significantly up-regulated in response to bacterial pathogen (Vibrio alginolyticus and Staphylococcus aureus) and PAMPs (Lipopolysaccharides and Peptidoglycan) challenges. Moreover, fluorescence microscopy observations revealed that AwTRAF2 was mainly located in cytoplasm of HEK293T cells and its overexpression significantly increased the transcriptional activities of the NF-κB-Luc reporter gene in HEK293T cells. Taken together, this study provided the experimental evidence of the presence of a functional TRAF2 in freshwater bivalves, which revealed its involvement in host response to immune challenges in A. woodiana.

A molluscan extracellular signal-regulated kinase is involved in host response to immune challenges in vivo and in vitro.

Extracellular signal-regulated kinases (ERKs) are a group of highly conserved serine/threonine-specific protein kinases that function as important signaling intermediates in mitogen-activated protein kinase (MAPK) pathways, which are involved in a wide variety of cellular activities, including proliferation, inflammation and cytokine production. However, little is known about the roles of this kinase in mollusk immunity. In this study, we identified a molluscan ERK homolog (ChERK) in the Hong Kong oyster (Crassostrea hongkongensis) and investigated its biological functions. The open reading frame (ORF) of ChERK encoded a polypeptide of 365 amino acids, with a predicted molecular weight of 41.96 kDa and pI of 6.43. The predicted ChERK protein contained typical characteristic motifs of the ERK family, including a dual threonine-glutamate-tyrosine (TEY) phosphorylation motif and an ATRW substrate binding site. Phylogenetic analysis revealed that ChERK belonged to the mollusk cluster and shared a close evolutionary relationship with ERK from Crassostrea gigas. In addition, quantitative real-time PCR analysis revealed that ChERK expression was detected in all of the examined tissues and stages of embryonic development; its transcript level was significantly induced upon challenge with bacterial pathogens (Vibrio alginolyticus and Staphylococcus haemolyticus) in vivo and PAMPs (lipopolysaccharide and peptidoglycan) in vitro. Moreover, ChERK was mainly located in the cytoplasm of HEK293T cells. Taken together, these findings may provide novel insights into the functions of molluscan ERKs, especially their roles in response to immune challenge in oyster.

Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

The treatment of Klebsiella pneumoniae, particularly extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.

Mechanistic aspects of the photodynamic inactivation of vancomycin-resistant Enterococci mediated by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

Vancomycin-resistant Enterococci (VRE) is a serious concern for public health. Serious infections with VRE have very limited effective antimicrobial therapy, and alternative treatment approaches are highly desirable. One promising approach might be the photodynamic antimicrobial chemotherapy. In the present study, we investigated the photodynamic inactivation (PDI) of two VRE strains mediated by 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL). The photodynamic damages to bacteria on the level of genomic DNA, the leakage of cell components, and the changes of membrane structure were investigated. After treated with 10 mM 5-ALA and irradiated by the 633 ± 10 nm LED for 60 min, 5.37 and 5.22 log10 reductions in bacterial survival were achieved for the clinical isolate of VRE and E. faecalis (ATCC 51299), respectively. After treated with 10 mM MAL and irradiated by the LED for 60 min, 5.02 and 4.91 log10 reductions in bacterial survival were observed for the two VRE strains, respectively. In addition, the photocleavage on genomic DNA and the rapid release of intracellular biopolymers were detected in PDI-treated bacteria. The intensely denatured cytoplasm and the aggregated ribosomes were also found in PDI-treated bacteria by transmission electron microscopy. Although 5-ALA and MAL-mediated PDI could induce the photocleavage on genomic DNA, the PDI of the two VRE strains might be predominantly attributed to the envelope injury, the intracellular biopolymers leakage, and the cytoplasm denature.

Associations between systemic immunity-inflammation index and heart failure: Evidence from the NHANES 1999-2018.

BACKGROUND: Heart failure (HF) is a disease closely associated with inflammation, and the systemic immune-inflammation index (SII) is a novel inflammatory marker. Therefore, this study aims to explore the relationship between SII and HF. METHODS: We used National Health and Nutrition Examination Survey data from 1998 to 2018 to include adults who reported a diagnosis of HF and complete information on the calculation of SII. SII was calculated as platelet count × neutrophil count/lymphocyte count. We used multiple logistic regression models to examine the association between SII and HF and explored possible influencing factors by subgroup analysis. In addition, we performed smoothed curve fitting and threshold effect analysis to describe the nonlinear relationship. RESULTS: The population-based study involved a total of 48,155 adults ages 20-85. Multivariate logistic regression showed that participants with the highest SII had a statistically significant 32% increased risk of HF prevalence compared to those with the lowest SII (OR = 1.32; 95% CI, 1.06-1.65, P = 0.0144) in a fully adjusted model. Subgroup analysis revealed no significant interactions between SII and specific subgroups (p > 0.05 for all interactions). Furthermore, the association between SII and HF was non-linear; the inflection point was 1104.78 (1000 cells/µl). CONCLUSIONS: Based on our findings, elevated SII levels were found to be strongly associated with the risk of HF, and SII was nonlinearly associated with HF. To validate these findings, a larger prospective investigation is needed to support the results of this study and investigate potential problems.

Association of per- and polyfluoroalkyl substance exposure with metabolic syndrome and its components in adults and adolescents.

Per- and polyfluoroalkyl substances (PFAS) are widespread contaminants, but few studies have explored the relationship between PFAS and levels of metabolic syndrome (MetS) in the population. The available evidence of an association is also conflicting. We selected adults and adolescents with complete PFAS data from the National Health and Nutrition Examination Survey conducted between 2003 and 2018. We analyzed the association between PFAS and MetS using multivariate logistic regression models and evaluated potential nonlinear relationships with restricted cubic spline models. Additionally, we employed weighted quantile sum (WQS) regressions to uncover the multiple exposure effects and relative weights of each PFAS. Finally, we conducted a series of sensitivity analyses to test the robustness of our findings. In this population-based study, we analyzed data from a total of 4,973 adults, aged 20-85 years, and 1,381 adolescents, aged 12-19 years. Using fully adjusted multivariate logistic regression models, we found that serum levels of perfluorodecanoate (PFDA) [0.65 (0.50, 0.85)] and total PFAS [0.92 (0.85, 0.99)] were negatively associated with the prevalence of MetS in adults. Similarly, in adolescents, we observed negative correlations between the prevalence of MetS and levels of PFDA [0.55 (0.38, 0.80)], perfluorooctanoic acid (PFOA) [0.62 (0.39, 1.00)], perfluorooctane sulfonic acid (PFOS) [0.59 (0.36, 0.96)], and total PFAS [0.61 (0.37, 0.99)]. Additionally, our study identified statistically significant negative associations between serum levels of PFAS and certain components of MetS, primarily elevated fasting glucose and lower high-density lipoprotein cholesterol. Our study found that PFAS was associated with a lower prevalence of MetS in both adults and adolescents, offering new insights into the relationship between PFAS and metabolic health. Interestingly, however, we observed conflicting findings across the components of MetS. Specifically, we observed that PFAS had a negative correlation with some metrics and a positive correlation with others. These conflicting results point to a complex interplay between PFAS and various metrics of metabolic health.

Microbial gene expression in Guaymas Basin subsurface sediments responds to hydrothermal stress and energy limitation.

Analyses of gene expression of subsurface bacteria and archaea provide insights into their physiological adaptations to in situ subsurface conditions. We examined patterns of expressed genes in hydrothermally heated subseafloor sediments with distinct geochemical and thermal regimes in Guaymas Basin, Gulf of California, Mexico. RNA recovery and cell counts declined with sediment depth, however, we obtained metatranscriptomes from eight sites at depths spanning between 0.8 and 101.9 m below seafloor. We describe the metabolic potential of sediment microorganisms, and discuss expressed genes involved in tRNA, mRNA, and rRNA modifications that enable physiological flexibility of bacteria and archaea in the hydrothermal subsurface. Microbial taxa in hydrothermally influenced settings like Guaymas Basin may particularly depend on these catalytic RNA functions since they modulate the activity of cells under elevated temperatures and steep geochemical gradients. Expressed genes for DNA repair, protein maintenance and circadian rhythm were also identified. The concerted interaction of many of these genes may be crucial for microorganisms to survive and to thrive in the Guaymas Basin subsurface biosphere.

Genome-centric view of the microbiome in a new deep-sea glass sponge species Bathydorus sp.

Sponges are widely distributed in the global ocean and harbor diverse symbiotic microbes with mutualistic relationships. However, sponge symbionts in the deep sea remain poorly studied at the genome level. Here, we report a new glass sponge species of the genus Bathydorus and provide a genome-centric view of its microbiome. We obtained 14 high-quality prokaryotic metagenome-assembled genomes (MAGs) affiliated with the phyla Nitrososphaerota, Pseudomonadota, Nitrospirota, Bdellovibrionota, SAR324, Bacteroidota, and Patescibacteria. In total, 13 of these MAGs probably represent new species, suggesting the high novelty of the deep-sea glass sponge microbiome. An ammonia-oxidizing Nitrososphaerota MAG B01, which accounted for up to 70% of the metagenome reads, dominated the sponge microbiomes. The B01 genome had a highly complex CRISPR array, which likely represents an advantageous evolution toward a symbiotic lifestyle and forceful ability to defend against phages. A sulfur-oxidizing Gammaproteobacteria species was the second most dominant symbiont, and a nitrite-oxidizing Nitrospirota species could also be detected, but with lower relative abundance. Bdellovibrio species represented by two MAGs, B11 and B12, were first reported as potential predatory symbionts in deep-sea glass sponges and have undergone dramatic genome reduction. Comprehensive functional analysis indicated that most of the sponge symbionts encoded CRISPR-Cas systems and eukaryotic-like proteins for symbiotic interactions with the host. Metabolic reconstruction further illustrated their essential roles in carbon, nitrogen, and sulfur cycles. In addition, diverse putative phages were identified from the sponge metagenomes. Our study expands the knowledge of microbial diversity, evolutionary adaption, and metabolic complementarity in deep-sea glass sponges.

Riddles of Lost City: Chemotrophic Prokaryotes Drives Carbon, Sulfur, and Nitrogen Cycling at an Extinct Cold Seep, South China Sea.

Deep-sea cold seeps are one of the most productive ecosystems that sustained by hydrocarbons carried by the fluid. Once the seep fluid ceases, the thriving autotrophic communities die out, terming as the extinct seep. But heterotrophic fauna can still survive even for thousands of years. The critical role of prokaryotes in active seeps are well defined, but their functions in extinct seeps are poorly understood to date. Here, we clarified the diversity, taxonomic specificity, interspecies correlation, and metabolic profiles of sediment prokaryotes at an extinct seep site of Haima cold seep, South China Sea. Alpha diversity of archaea significantly increased, while that of bacteria remained unchanged in extinct seep compared to active seep. However, archaea composition did not differ significantly at extinct seep from active or nonseep sites based on weighted-unifrac dissimilarity, while bacteria composition exhibited significant difference. Distribution of archaea and bacteria showed clear specificity to extinct seeps, indicating the unique life strategies here. Prokaryotes might live chemolithoautotrophically on cycling of inorganic carbon, sulfur, and nitrogen, or chemoorganotrophically on recycling of hydrocarbons. Notably, many of the extinct seep specific species and networked keystone lineages are classified as Proteobacteria. Regarding the functional diversity and metabolic flexibility of this clade, Proteobacteria is supposed to integrate the geochemical cycles and play a critical role in energy and resource supplement for microbiome in extinct seep. Collectively, our findings shed lights on the microbial ecology and functional diversity in extinct seeps, providing new understanding of biogeochemical cycling after fluid cessation. IMPORTANCE This research paper uncovered the potential mechanisms for microbiota mediated geochemical cycling in extinct cold seep, advancing our understanding in deep sea microbiology ecology.

Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps.

Hepatocytes function largely through the secretion of proteins that regulate cell proliferation, metabolism, and intercellular communications. During the progression of hepatocellular carcinoma (HCC), the hepatocyte secretome changes dynamically as both a consequence and a causative factor in tumorigenesis, although the full scope of secreted protein function in this process remains unclear. Here, we show that the secreted pseudo serine protease PRSS35 functions as a tumor suppressor in HCC. Mechanistically, we demonstrate that active PRSS35 is processed via cleavage by proprotein convertases. Active PRSS35 then suppresses protein levels of CXCL2 through targeted cleavage of tandem lysine (KK) recognition motif. Consequently, CXCL2 degradation attenuates neutrophil recruitment to tumors and formation of neutrophil extracellular traps, ultimately suppressing HCC progression. These findings expand our understanding of the hepatocyte secretome's role in cancer development while providing a basis for the clinical translation of PRRS35 as a therapeutic target or diagnostic biomarker.