Cycling and persistence of iron-bound organic carbon in subseafloor sediments.

Reactive iron (FeR) serves as an important sink of organic carbon (OC) in marine surface sediments, which preserves approximately 20% of total OC (TOC) as reactive iron-bound OC (FeR-OC). However, the fate of FeR-OC in subseafloor sediments and its availability to microorganisms, remain undetermined. Here, we reconstructed continuous FeR-OC records in two sediment cores of the northern South China Sea encompassing the suboxic to methanic biogeochemical zones and reaching a maximum age of ~100 kyr. The downcore FeR-OC contributes a relatively stable proportion of 13.3 ± 3.2% to TOC. However, distinctly lower values of less than 5% of TOC, accompanied by notable 13C depletion of FeR-OC, are observed in the sulfate-methane transition zone (SMTZ). FeR-OC is suggested to be remobilized by microbially mediated reductive dissolution of FeR and subsequently remineralized, the flux of which is 18-30% of the methane consumption in the SMTZ. The global reservoir of FeR-OC in microbially active Quaternary marine sediments could be 19-46 times the size of the atmospheric carbon pool. Thus, the FeR-OC pool may support subseafloor microorganisms and contribute to regulating Earth's carbon cycle.

A triphenylamine-benzofuran-derived fluorescent probe for monitoring sulfite in Chinese medicinal materials and bioimaging.

In this work, a triphenylamine-benzofuran-derived fluorescent probe TBSF was developed for monitoring the sulfite level in Chinese medicinal materials and imaging in living cells. In the testing system, under 445 nm excitation, TBSF responded to sulfite steadily with a 540 nm fluorescence reporting signal. The testing system showed advantages including high sensitivity, rapid response, and high selectivity. In particular, TBSF achieved the sulfite detection in the water decoction of Chinese medicinal materials from both addition and excessive fumigation. It also realized the intracellular imaging of both exogenous and endogenous sulfite in living HepG2 cells. The imaging in water decoction-treated cells inferred the potential for the interdisciplinary detection.

The role of HMGA2 in activating the IGFBP2 expression to promote angiogenesis and LUAD metastasis via the PI3K/AKT/VEGFA signaling pathway.

This study investigates the molecular mechanism of HMGA2-mediated regulation of IGFBP2 expression in the PI3K/AKT/VEGFA signaling pathway, which is involved in angiogenesis and LUAD metastasis. Target genes with prognostic implications for LUAD patients were selected using bioinformatics, and previously published literature was referenced to predict the molecular regulatory mechanisms. A549 cells were used for in vitro validation. Cell proliferation and viability were assessed using CCK-8 and EdU assays, while cell migration ability was evaluated using Transwell and wound healing assays. Changes in angiogenesis were examined using an angiogenesis assay. The targeted binding of HMGA2 with the IGFBP2 promoter was confirmed through dual luciferase reporter gene experiments and ChIP assays. In vivo validation was performed using a xenograft mouse model, and changes in angiogenesis and tumor metastasis were observed using western blot, immunofluorescence, and H&E staining. Bioinformatics analysis revealed that HMGA2 was one of the AAGs that differed between normal individuals and LUAD patients and could serve as a critical mRNA for predicting LUAD prognosis. Results from in vitro experiments demonstrated that the expression of the HMGA2 gene was significantly upregulated in LUAD cell lines. Through mediating the expression of IGFBP2, the HMGA2 gene activated the PI3K/AKT/VEGFA signaling pathway, promoting the proliferation, migration, and angiogenesis of A549 cells. In vivo, animal experiments further confirmed that HMGA2 facilitated angiogenesis and the development and metastasis of LUAD through mediating IGFBP2 expression and activating the PI3K/AKT/VEGFA signaling pathway. HMGA2 promotes angiogenesis and healthy growth and metastasis of LUAD by activating the PI3K/AKT/VEGFA signaling pathway by mediating IGFBP2 expression.

Description of the first cultured representative of "Candidatus Synoicihabitans" genus, isolated from deep-sea sediment of South China Sea.

In this study we describe the first cultured representative of Candidatus Synoicihabitans genus, a novel strain designated as LMO-M01T, isolated from deep-sea sediment of South China Sea. This bacterium is a facultative aerobe, Gram-negative, non-motile, and has a globular-shaped morphology, with light greenish, small, and circular colonies. Analysis of the 16S rRNA gene sequences of strain LMO-M01T showed less than 93% similarity to its closest cultured members. Furthermore, employing advanced phylogenomic methods such as comparative genome analysis, average nucleotide identity (ANI), average amino acids identity (AAI), and digital DNA-DNA hybridization (dDDH), placed this novel species within the candidatus genus Synoicihabitans of the family Opitutaceae, Phylum Verrucomicrobiota. The genomic analysis of strain LMO-M01T revealed 175 genes, encoding putative carbohydrate-active enzymes. This suggests its metabolic potential to degrade and utilize complex polysaccharides, indicating a significant role in carbon cycling and nutrient turnover in deep-sea sediment. In addition, the strain's physiological capacity to utilize diverse biopolymers such as lignin, xylan, starch, and agar as sole carbon source opens up possibilities for sustainable energy production and environmental remediation. Moreover, the genome sequence of this newly isolated strain has been identified across diverse ecosystems, including marine sediment, fresh water, coral, soil, plants, and activated sludge highlighting its ecological significance and adaptability to various environments. The recovery of strain LMO-M01T holds promise for taxonomical, ecological and biotechnological applications. Based on the polyphasic data, we propose that this ecologically important strain LMO-M01T represents a novel genus (previously Candidatus) within the family Opitutaceae of phylum Verrucomicrobiota, for which the name Synoicihabitans lomoniglobus gen. nov., sp. nov. was proposed. The type of strain is LMO-M01T (= CGMCC 1.61593T = KCTC 92913T).

METTL14 drives growth and metastasis of non-small cell lung cancer by regulating pri-miR-93-5p maturation and TXNIP expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy responsible for a significant number of cancer-related deaths worldwide. Unraveling the molecular mechanisms governing NSCLC growth and metastasis is crucial for the identification of novel therapeutic targets and the development of effective anti-cancer strategies. One such mechanism of interest is the involvement of METTL14, an RNA methyltransferase implicated in various cellular processes, in NSCLC progression. OBJECTIVE: The objective of this study was to investigate the role of METTL14 in NSCLC development and metastasis and to elucidate the underlying molecular mechanisms. By understanding the impact of METTL14 on NSCLC pathogenesis, the study aimed to identify potential avenues for targeted therapies in NSCLC treatment. METHODS: We used bioinformatics and high-throughput transcriptome sequencing analyses to screen regulatory mechanisms affecting NSCLC. The Kaplan-Meier method assessed the correlation between METTL14 expression and the prognosis of NSCLC patients. The effects of manipulated METTL14 on malignant phenotypes of NSCLC cells were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay. The tumorigenic capacity and metastatic potential of NSCLC cells in vivo were evaluated in nude mice. RESULTS: METTL14 was overexpressed in NSCLC tissues and cell lines. Its high expression indicated a poor prognosis for NSCLC patients. METTL14 silencing promoted apoptosis and repressed proliferation, migration, and invasion of NSCLC cells. miR-93-5p targeted and inhibited TXNIP. METTL14 increased miR-93-5p expression and matured pri-miR-93-5p through m6A alteration to inhibit TXNIP, thereby inhibiting NSCLC cell apoptosis. By controlling the miR-93-5p/TXNIP axis, METTL14 increased the tumorigenic potential and lung metastasis of NSCLC cells in nude mice. CONCLUSION: This study revealed a role for METTL14 in the contribution to NSCLC development and metastasis and identified METTL14 as a potential target for NSCLC treatment.

METTL3 promotes non-small-cell lung cancer growth and metastasis by inhibiting FDX1 through copper death-associated pri-miR-21-5p maturation.

Objective: We probed into the significance of METTL3 in the maturation process of pri-miR-21-5p. We specifically investigated its impact on the regulation of FDX1 and its involvement in the progression of non-small-cell lung cancer (NSCLC). Methods: The Cancer Genome Atlas (TCGA) identified NSCLC factors. Methylation-specific PCR (MSP), clonogenic tests and flow cytometry analyzed cells. Methylated RNA immunoprecipitation (Me-RIP) and dual-luciferase studied miR-21-5p/FDX1. Mice xenografts showed METTL3's tumorigenic effect. Results: METTL3, with high expression but low methylation in NSCLC, influenced cell behaviors. Its suppression reduced oncogenic properties. METTL3 enhanced miR-21-5p maturation, targeting FDX1 and boosting NSCLC tumorigenicity in mice. Conclusion: METTL3 may promote NSCLC development by facilitating pri-miR-21-5p maturation, upregulating miR-21-5p and targeting inhibition of FDX1.

We investigated a protein called METTL3, which is overly active in lung cancer cells, and how it affects the function of other small molecules. We discovered that as the activity of METTL3 increases, the growth and mobility of lung cancer cells also enhance, potentially accelerating the progression of lung cancer. Through a series of experiments, we observed how METTL3 interacts with other small molecules and further influences the behavior of lung cancer cells. This study helps us understand the role of METTL3 in the development of lung cancer and may offer new strategies for future treatments.

Mariluticola halotolerans gen. nov., sp. nov., a novel member of the family Devosiaceae isolated from South China Sea sediment.

A novel member of class Alphaproteobacteria was isolated from marine sediment of the South China Sea. Cells of strain LMO-2T were Gram-stain negative, greyish in colour, motile, with a single lateral flagellum and short rod in shape with a slight curve. Strain LMO-2T was positive for oxidase and negative for catalase. The bacterium grew aerobically at 10-40 °C (optimum, 25-30 °C), pH 5.5-10.0 (optimum, pH 7.0) and 0-9 % NaCl (w/v; optimum, 2-3 %). Phylogenetic analysis of the 16S rRNA gene sequence and phylogenomic analysis of the whole genome sequence indicated that strain LMO-2T represents a new genus and a new species within the family Devosiaceae, class Alphaproteobacteria, phylum Pseudomonadota. Comparisons of the 16S rRNA gene sequences of strain LMO-2T showed 94.8 % similarity to its closest relative. The genome size is ~3.45 Mbp with a DNA G+C content of 58.17 mol%. The strain possesses potential capability for the degradation of complex organic matter, i.e. fatty acid and benzoate. The predominant cellular fatty acids (>10 %) were C16 : 0 and C18 : 1 ω7c 11-methyl. The sole respiratory quinone was ubiquinone-10. The major identified polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phospholipid. Based on the polyphasic taxonomic data, strain LMO-2T represents a novel genus and a novel species for which the name Mariluticola halotolerans gen. nov., sp. nov., was proposed in the family Devosiaceae. The type strain is LMO-2T (=CGMCC 1.19273T=JCM 34934T).

Reconstruction and Analysis of Thermodynamically Constrained Models Reveal Metabolic Responses of a Deep-Sea Bacterium to Temperature Perturbations.

Microbial acclimation to different temperature conditions can involve broad changes in cell composition and metabolic efficiency. A systems-level view of these metabolic responses in nonmesophilic organisms, however, is currently missing. In this study, thermodynamically constrained genome-scale models were applied to simulate the metabolic responses of a deep-sea psychrophilic bacterium, Shewanella psychrophila WP2, under suboptimal (4°C), optimal (15°C), and supraoptimal (20°C) growth temperatures. The models were calibrated with experimentally determined growth rates of WP2. Gibbs free energy change of reactions (ΔrG'), metabolic fluxes, and metabolite concentrations were predicted using random simulations to characterize temperature-dependent changes in the metabolism. The modeling revealed the highest metabolic efficiency at the optimal temperature, and it suggested distinct patterns of ATP production and consumption that could lead to lower metabolic efficiency under suboptimal or supraoptimal temperatures. The modeling also predicted rearrangement of fluxes through multiple metabolic pathways, including the glycolysis pathway, Entner-Doudoroff pathway, tricarboxylic acid (TCA) cycle, and electron transport system, and these predictions were corroborated through comparisons to WP2 transcriptomes. Furthermore, predictions of metabolite concentrations revealed the potential conservation of reducing equivalents and ATP in the suboptimal temperature, consistent with experimental observations from other psychrophiles. Taken together, the WP2 models provided mechanistic insights into the metabolism of a psychrophile in response to different temperatures. IMPORTANCE Metabolic flexibility is a central component of any organism's ability to survive and adapt to changes in environmental conditions. This study represents the first application of thermodynamically constrained genome-scale models in simulating the metabolic responses of a deep-sea psychrophilic bacterium to various temperatures. The models predicted differences in metabolic efficiency that were attributed to changes in metabolic pathway utilization and metabolite concentration during growth under optimal and nonoptimal temperatures. Experimental growth measurements were used for model calibration, and temperature-dependent transcriptomic changes corroborated the model-predicted rearrangement of metabolic fluxes. Overall, this study highlights the utility of modeling approaches in studying the temperature-driven metabolic responses of an extremophilic organism.

Iron (oxyhydr)oxides shift the methanogenic community in deep sea methanic sediment - insights from long-term high-pressure incubations.

Intermittent increases of dissolved ferrous iron concentrations have been observed in deep marine methanic sediments which is different from the traditional diagenetic electron acceptor cascade, where iron reduction precedes methanogenesis. Here we aimed to gain insight into the mechanism of iron reduction and the associated microbial processes in deep sea methanic sediment by setting up long-term high-pressure incubation experiments supplemented with ferrihydrite and methane. Continuous iron reduction was observed during the entire incubation period. Intriguingly, ferrihydrite addition shifted the archaeal community from the dominance of hydrogenotrophic methanogens (Methanogenium) to methylotrophic methanogens (Methanococcoides). The enriched samples were then amended with 13C-labeled methane and different iron (oxyhydr)oxides in batch slurries to test the mechanism of iron reduction. Intensive iron reduction was observed, the highest rates with ferrihydrite, followed by hematite and then magnetite, however, no anaerobic oxidation of methane (AOM) was observed in any treatment. Further tests on the enriched slurry showed that the addition of molybdate decreased iron reduction, suggesting a link between iron reduction with sulfur cycling. This was accompanied by the enrichment of microbes capable of dissimilatory sulfate reduction and sulfur/thiosulfate oxidation, which indicates the presence of a cryptic sulfur cycle in the incubation system with the addition of iron (oxyhydr)oxides. Our work suggests that under low sulfate conditions, the presence of iron (oxyhydr)oxides would trigger a cascade of microbial reactions, and iron reduction could link with the microbial sulfur cycle, changing the kinetics of the methanogenesis process in methanic sediment.

The Significance of Crescents on the Clinical Features and Outcomes of Primary Immunoglobin A Nephropathy.

Background: It is still controversial whether the proportion of crescents below 50% can be an independent predictive risk factor for poor prognosis in IgAN patients. We reported the significance of different proportions of crescents on the clinical features and the cut-off value of crescents in predicting the occurrence of end-stage kidney disease (ESKD) in patients with IgAN. Methods: We retrospectively analyzed biopsy-proven primary IgAN patients in Sichuan Provincial People's Hospital from 2007 to 2019. The patients were divided into 5 groups on the basis of crescent proportion as follows: 0 (n = 647), < 10% (n = 221), 10 to 24% (n = 272), 25 to 49% (n = 80), and ≥50% (n = 22). The primary endpoint was defined as ESKD, and the secondary endpoint was the combined renal endpoint (≥50% reduction in eGFR or ESKD). A validation cohort of 346 patients were enrolled from Affiliated Hospital of Southwest Medical University. Cox regression model and Kaplan-Meier survival analysis were performed. Results: A total of 1242 eligible patients with biopsy-proven IgAN were recorded in the database, compared with the non-crescent group, patients in the crescent group had lower levels of hemoglobin (Hb) and albumin (Alb), higher levels of blood urea nitrogen (BUN), 24h urinary protein and hematuria, a higher proportion of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubular atrophy/interstitial fibrosis (T1/T2) (p < 0.05). A higher crescent proportion was associated with lower levels of Hb, ALB, eGFR and serum IgG (p < 0.05), higher levels of SCr, BUN, increasing amounts of 24 h urinary protein, increasing proportion of M1 and E1, and increasing severity of interstitial inflammatory infiltration. During the median follow-up of 43 months (range 6-151), 63 individuals (7.0%) reached the primary outcome of ESKD and 99 patients (11.1%) reached the combined renal endpoint. 34(7.5%), 21 (13.3%), 24(12.2%), 14(21.5%) and 6(31.6%) patients reached the combined renal endpoint in the above five groups in crescents 0, <10%, 10∼24%, 25∼49% and ≥50%, respectively. A total of 274(62.6%) cases in the crescent group and 254 (55.7%) cases in the non-crescent group received immunosuppressive therapy. Multivariate Cox regression showed that crescents ≥50% was an independent risk factor for the progression of ESKD (p = 0.003) and crescents ≥25% was an independent risk factor for the combined renal endpoint(p < 0.001). The receiver operating characteristic curve showed that IgAN patients with crescents ≥43.7% had a higher risk of ESKD, even with immunosuppressants (Sensitivity = 75.7%,specificity = 89.6%,p < 0.001). This discovery cohort and the validation cohort further confirmed that patients with crescents <43.7% had better renal prognosis than those with crescents ≥43.7% in the whole group and those with immunosuppressants (p < 0.001). Conclusion: IgAN patients with crescents had more severe clinicopathological features and poorer prognosis. Crescents ≥50% was an independent risk factor for the progression of ESKD and crescents ≥25% was an independent risk factor for ≥50% reduction in eGFR or ESKD in treated and untreated IgAN patients. Crescents ≥43.7% was an independent risk factor for ESKD in those with immunosuppressants.

Self-assembly of peptide nanofibers with chirality-encoded antimicrobial activity.

The nanostructured antimicrobial agents, self-assembled by the antimicrobial peptides (AMPs), represent an intriguing platform for the treatment of pathogens. Although the structural characteristics significantly influence antimicrobial functionality, the role of chirality is usually ignored and still unclear. Herein, two homochiral AMPs (all L- or all D-amino acids), including C16-LV4LR4 (LL) and C16-DV4DR4 (DD), and a heterochiral AMP with alternating D-/L-amino acids, C16-DV4LR4 (DL), were self-assembled into left-handed, right-handed, and right-handed helical nanofibers, respectively. The valine configuration determined the supramolecular chirality of the nanofibers. However, the DL molecules exhibited a highly aggregated propensity to form more stable helical nanofibers with a lower degree of twist and a larger helical pitch. This characteristic resulted in the optimal antimicrobial activity of the DL nanofibers against both Gram-negative and Gram-positive bacteria. Furthermore, the membrane permeability assay confirmed the higher activity for damaging the cell membrane by the DL nanofibers. These results demonstrated the significance of molecular chirality in directing the self-assembly of the amphiphilic peptides, eventually affecting their antimicrobial activity. This study opens up the possibility to fabricate promising nanostructured antimicrobial materials by controlling the chirality and structure of the materials.

Potential metabolic and genetic interaction among viruses, methanogen and methanotrophic archaea, and their syntrophic partners.

The metabolism of methane in anoxic ecosystems is mainly mediated by methanogens and methane-oxidizing archaea (MMA), key players in global carbon cycling. Viruses are vital in regulating their host fate and ecological function. However, our knowledge about the distribution and diversity of MMA viruses and their interactions with hosts is rather limited. Here, by searching metagenomes containing mcrA (the gene coding for the α-subunit of methyl-coenzyme M reductase) from a wide variety of environments, 140 viral operational taxonomic units (vOTUs) that potentially infect methanogens or methane-oxidizing archaea were retrieved. Four MMA vOTUs (three infecting the order Methanobacteriales and one infecting the order Methanococcales) were predicted to cross-domain infect sulfate-reducing bacteria. By facilitating assimilatory sulfur reduction, MMA viruses may increase the fitness of their hosts in sulfate-depleted anoxic ecosystems and benefit from synthesis of the sulfur-containing amino acid cysteine. Moreover, cell-cell aggregation promoted by MMA viruses may be beneficial for both the viruses and their hosts by improving infectivity and environmental stress resistance, respectively. Our results suggest a potential role of viruses in the ecological and environmental adaptation of methanogens and methane-oxidizing archaea.

Wernicke encephalopathy following advanced caecum cancer.

A 26-year-old lactating mother presented with a 3-week history of abdominal pain, constipation, and vomiting. She denied any history of alcohol abuse or other gastrointestinal problems. Contrast-enhanced CT identified a small-bowel obstruction caused by a cecum cancer (Fig. 1A). Therefore, she underwent right hemicolectomy and ileocolic anastomosis. Post-operatively, she gradually developed drowsiness, fainting, and a rapid heart rate at 130 bpm. However, blood tests were all normal.

Prognostic factors for ovarian metastases in colorectal cancer patients.

PURPOSE: The aim of this study was to analyze prognostic factors for ovarian metastases (OM) in colorectal cancer (CRC) using data from a Chinese center. In addition, the study aimed at developing a new clinical scoring system for prognosis of OM of CRC patients after surgery. PATIENTS AND METHODS: Data of CRC patients with OM were collected from a single Chinese institution (n = 67). Kaplan-Meier analysis was used to evaluate cumulative survival of patients. Factors associated with prognosis of overall survival (OS) were explored using Cox's proportional hazard regression models. A scoring system to determine effectiveness of prognosis was developed. RESULTS: Median OS values for patients with or without surgery were 22 and 7 months, respectively. Size of OM, number of OM, peritoneal metastasis (PM), Peritoneal cancer index (PCI), and completeness of cytoreduction (CC) were associated with OS of patients through univariate analysis. Multivariate analysis using a Cox regression model showed that only CC was an independent predictor for OS. Three variables (the size of OM >15cm, PCI ≥ 10, and carcinoembryonic antigen (CEA) >30 ng/mL) assigned one point each were used to develop a risk score. The resulting score was used for prognosis of OS. CONCLUSION: Surgical treatment of metastatic sites is effective and safe for CRC patients with OM. CC-0 is recommended for improved prognosis. The scoring system developed in this study is effective for prediction of OS of patients after surgery.

[Significance of spinal sagittal balance for guiding acetabular prosthesis positioning].

Since the concept of "safe area" put forward by Lewinnek, it has been widely recognized. While in recent years, many scholars have found that even if the acetabular prosthesis was placed on the "safe area", there were still many unexplained dislocation after total hip arthroplasty. And scholars began to question whether the "safe area" is really suitable for all patients. Spinal degeneration, deformity, lumbar fusion, etc. will lead to spine sagittal imbalance and changes in pelvic activity, which could lead to changes in acetabular orientation, and ultimately lead to edge loading, wear, impact, and even dislocation after total hip replacement. From the perspective of wear, impact and dislocation, it is determined by the functional positioning of the acetabular cup, not the anatomical positioning. The anatomical positioning and functional positioning of the neutral pelvic acetabular cup in the standing position can be considered equivalent. For pelvic rotation more than 20°, functional placement needs to be considered. In recent years, as the understanding of the internal relationship between the spine-pelvis-hip joint has become more and more profound, some scholars further classify the hip-spine relationship according to whether the spine is stiff or deformed, and propose corresponding acetabulums according to different types of hip-spine relationships The function of placement, so as to achieve a stable artificial hip joint. Therefore, it is of great significance to fully assess whether the patient's sagittal plane is balanced before surgery to guide artificial hip replacement surgery.

Sustainable, superhydrophobic membranes based on bacterial cellulose for gravity-driven oil/water separation.

Bacterial cellulose (BC) is a substrate material with high purity and robust mechanical strength, but due to its small pore size and relatively expensive price, it is restricted as an oil-/water separation membrane. In this study, cheaper plant cellulose needle-leaf bleached kraft pulp (NBKP) was added to BC to increase the pore size of the composite membrane, and a superhydrophobic/superoleophilic membrane was prepared for oil-/water separation. The modified membrane surface displayed a petal-like micro-structure and a water contact angle (WCA) of 162.3°, while the oil contact angle was decreased to 0°. What's more, the membrane exhibited excellent oil-/water separation under gravity, recyclability, and a separation efficiency (>95 %), and it was both pH and salt resistant. The membrane also remained durably hydrophobic after 10 separation cycles. And the separation methodology is expected to be highly energy-efficient.

miR-204/COX5A axis contributes to invasion and chemotherapy resistance in estrogen receptor-positive breast cancers.

Breast cancer is the most common cancer among women worldwide, with 70% being estrogen receptor-positive (ER+). Although ER-targeted treatment is effective in treating ER + breast cancer, chemoresistance and metastasis still prevail. Outcome-predictable biomarkers can help improve patient prognosis. Through the analysis of the Array Express database, The Cancer Genome Atlas-Breast Cancer datasets, and breast tumor tissue array results, we found that cytochrome c oxidase subunit 5a (COX5A) was related to poor prognosis of ER + breast cancer. Further studies revealed that COX5A was positively associated with metastasis and chemoresistance in ER + breast cancer. In vitro experiments showed that knockdown of COX5A was accompanied by a decrease in ERα expression, cell cycle arrest, and epithelial-mesenchymal transition blockade, resulting in an inhibition of proliferation and invasion. Knockdown of COX5A enhanced the chemosensitivity of breast cancer cells by decreasing adenosine triphosphate and increasing reactive oxygen species levels. We report that miR-204 can target and inhibit the expression of COX5A, thus, reversing the functions of COX5A in ER + breast cancer cells. We found that COX5A may serve as a prognostic biomarker in ER + breast cancer.

Microbial succession during the transition from active to inactive stages of deep-sea hydrothermal vent sulfide chimneys.

BACKGROUND: Deep-sea hydrothermal vents are highly productive biodiversity hotspots in the deep ocean supported by chemosynthetic microorganisms. Prominent features of these systems are sulfide chimneys emanating high-temperature hydrothermal fluids. While several studies have investigated the microbial diversity in both active and inactive sulfide chimneys that have been extinct for up to thousands of years, little is known about chimneys that have ceased activity more recently, as well as the microbial succession occurring during the transition from active to inactive chimneys. RESULTS: Genome-resolved metagenomics was applied to an active and a recently extinct (~ 7 years) sulfide chimney from the 9-10° N hydrothermal vent field on the East Pacific Rise. Full-length 16S rRNA gene and a total of 173 high-quality metagenome assembled genomes (MAGs) were retrieved for comparative analysis. In the active chimney (L-vent), sulfide- and/or hydrogen-oxidizing Campylobacteria and Aquificae with the potential for denitrification were identified as the dominant community members and primary producers, fixing carbon through the reductive tricarboxylic acid (rTCA) cycle. In contrast, the microbiome of the recently extinct chimney (M-vent) was largely composed of heterotrophs from various bacterial phyla, including Delta-/Beta-/Alphaproteobacteria and Bacteroidetes. Gammaproteobacteria were identified as the main primary producers, using the oxidation of metal sulfides and/or iron oxidation coupled to nitrate reduction to fix carbon through the Calvin-Benson-Bassham (CBB) cycle. Further analysis revealed a phylogenetically distinct Nitrospirae cluster that has the potential to oxidize sulfide minerals coupled to oxygen and/or nitrite reduction, as well as for sulfate reduction, and that might serve as an indicator for the early stages of chimneys after venting has ceased. CONCLUSIONS: This study sheds light on the composition, metabolic functions, and succession of microbial communities inhabiting deep-sea hydrothermal vent sulfide chimneys. Collectively, microbial succession during the life span of a chimney could be described to proceed from a "fluid-shaped" microbial community in newly formed and actively venting chimneys supported by the oxidation of reductants in the hydrothermal fluid to a "mineral-shaped" community supported by the oxidation of minerals after hydrothermal activity has ceased. Remarkably, the transition appears to occur within the first few years, after which the communities stay stable for thousands of years. Video Abstract.