The Plio-Pleistocene evaporitic lacustrine succession in the Qaidam Basin, which was recovered by drill core SG-1, provides the material for understanding the maturation of dolomite since dolomite is ...present in the core from 7.6 to 870 m depth, spanning a time interval of 0.1–2.8 Ma. Twenty-two samples were collected at different burial depths. The samples were examined by thin-section petrography and SEM for textures, and analyzed for mineralogy (XRD), trace elements and carbon and oxygen isotopes. The main mineral compositions of each sample are dolomite, quartz, halite and gypsum. Dolomite is mostly scattered with spheroidal to ellipsoidal shapes, several microns in diameter, partially encapsulated in gypsum. Microbial micropores and calcified microorganisms are observed on and within the dolomite crystals and in the thin sections. The degree of ordering of the dolomite gradually increases with burial depth, which basically conforms to the first-order reaction function. The crystal constants of dolomite decrease with burial depth, indicating recrystallisation with increasing overburden. The trace elements of the dolomites are significantly different from those of hydrothermal dolomites, but close to lacustrine microbial carbonate. It is concluded that the dolomites in core SG-1 are mainly authigenic, with microbial processes a likely facilitator of dolomite precipitation. The dolomite formed and then evolved in crystal structure during burial, gradually approaching ordered stochiometric dolomite. This study gives clues to link microbial dolomite to the massive ideal dolomite rock encountered in the geological record.
•The Plio-Pleistocene dolomite in the core SG-1 is authigenic in the Qaidam paleo lake.•The formation of dolomite crystals in the core SG-1 was associated with microbially mediation process.•The microbial dolomite crystals continued to mature toward ideal state during burial.
Malignant progression is the major cause of poor prognosis in breast cancer (BC) patients. Plasma exosomal miRNAs have been reported to be involved in tumor progression, but their roles in BC remain ...unclear.
We performed plasma exosomal miRNA sequencing on 45 individuals, including healthy controls and nonmetastatic and metastatic BC patients. We examined the correlation between miRNA expression in tumor tissues and plasma exosomes in BC patients by qRT‒PCR. The effects of exosomal miR-361-3p on BC cells were determined by CellTiter-Glo, migration and wound healing assays. The target genes of miR-361-3p and downstream pathways were explored by dual-luciferase reporter assay, RNA knockdown, rescue experiments, and western blotting. We utilized murine xenograft model to further assess the impact of plasma exosomal miR-361-3p on the malignant progression of BC.
We found that the expression level of plasma exosomal miR-361-3p gradually increased with malignant progression in BC patients, and the expression of miR-361-3p in plasma exosomes and BC tissues was positively correlated. Consistently, exosomal miR-361-3p enhanced the migration and proliferation of two BC cell lines, MDA-MB-231 and SK-BR-3. Furthermore, our data showed that miR-361-3p inhibited two novel target genes, ETV7 and BATF2, to activate the PAI-1/ERK pathway, leading to increased BC cell viability. Finally, the consistency of the in vivo experimental results supported that elevated plasma exosomal miR-361-3p promote the malignant progression of BC.
We found for the first time that plasma exosomal miR-361-3p was associated with malignant progression in BC patients. Mechanistically, exosomal miR-361-3p can enhance the migration and proliferation of BC cells by targeting the ETV7 and BATF2/PAI-1/ERK pathways. Our data suggest that plasma exosomal miR-361-3p has the potential to serve as a biomarker for predicting malignant progression in BC patients.
The whole process of cell membrane calcification of Bacillus licheniformis DB1–9 was studied by molecular dynamics (MD) and microbially-induced carbonate precipitation (MICP) laboratory experiments. ...Typical metabolitic products of Bacillus licheniformis DB1–9 were used as the calcium carbonate nucleation template to establish the organic constituents and a water‑calcium carbonate two-phase system model for MD simulation, and to characterize the early stages of calcium carbonate nucleation on the surfaces of extracellular polymeric substances (EPS). The surface minerals of calcified bacteria obtained by MICP were prepared by focused ion-beam (FIB) and further analyzed using high-resolution transmission electron microscopy-selected area electron diffraction (HRTEM-SAED). We propose that the evolution process of cell membrane calcification is: ions → ion-pairs → multi-ion complexes (MIC) of large-size topological structures → pre-nucleated clusters (PNC) → amorphous calcium carbonate (ACC) → carbonate minerals (monohydrocalcite, vaterite, aragonite). In addition, ACC and the state before ACC were adsorbed on to the surface of the cell membrane after self-assembly in the aqueous solution; the ACC then underwent maturation and crystallized into ordered carbonate minerals with a crystal structure. Our study reveals the processes of microbial calcification, which has implications for the calcification of microorganisms in modern aqueous environments and for the formation of microbialites throughout the geological record.
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•The non-classical nucleation process of calcium carbonate at the biological interface was explored in experiments and using molecular dynamics (MD).•The pre-nucleation state of calcium carbonate was characterized by MD.•Multi-ion complexes were the precursors of amorphous calcium carbonate.•The mineral components of calcified cell membranes include monohydrocalcite，vaterite and aragonite.
•Upregulated miR-361-3p in primary breast cancer was associated with poor prognosis.•miR-361-3p promoted proliferation and inhibited apoptosis of breast cancer cells.•miR-361-3p inhibited the ...E2F1/P73 signalling pathway in breast cancer cells.
Analysis of the microRNA (miRNA) expression signature of breast cancer based on RNA sequencing demonstrated that miR-361-3p was significantly upregulated in breast cancer tissues. miR-361-3p is a novel miRNA, and its role in breast cancer is currently unclear. The aim of the present study was to investigate the functions of miR-361-3p in breast carcinoma. In this study, it was observed that the expression of miR-361-3p in cancer tissues was significantly higher compared with that in para-cancerous tissues and was correlated with advanced TNM stage, Ki-67 overexpression and shorter disease-free survival. Overexpression of miR-361-3p promoted proliferation and inhibited apoptosis of breast cancer cells. Through RNA sequencing, multi-library retrieval, luciferase reporter assays, quantitative polymerase chain reaction analysis, western blotting and other methods, it was verified that E2F1 was directly downregulated by miR-361-3p. The knockdown of E2F1 by siRNA promoted breast cancer cell proliferation and inhibited apoptosis, similar to miR-361-3p. In addition, miR-361-3p was able to decrease the expression of P73 by targeting E2F1, whereas overexpression of P73 reversed the effect of miR-361-3p on the viability of breast cancer cell lines. Thus, the present study demonstrated that miR-361-3p acts as an oncomiR in breast cancer to promote proliferation and inhibit apoptosis through inhibiting the P73 pathway by downregulating E2F1 expression, which may uncover valuable prognostic factors or treatment targets.
Bacterial activities have been demonstrated as critical for protodolomite precipitation in specific aqueous conditions, whereas the relationship between the various hydrochemical factors and ...bacterial activity has not been fully explored. In this study, biomineralization experiments were conducted using a newly isolated extreme halophilic bacterium from salina mud,
QPL2, under various Mg/Ca molar ratios (0, 3, 6, 10, and 12) and a salinity of 200‰. The mineral phases, elemental composition, morphology, and crystal lattice structure of the precipitates were analyzed by XRD, SEM, and HRTEM, respectively. The organic weight and functional groups in the biominerals were identified by TG-DSC, FTIR, and XPS analysis. The amounts of amino acids and polysaccharides in the EPS of QPL2 cultured at various Mg/Ca molar ratios were quantified by an amino acid analyzer and high-performance liquid chromatography. The results confirm that disordered stoichiometric protodolomite was successfully precipitated through the activities of bacteria in a medium with relatively high Mg/Ca molar ratios (10 and 12) but it was not identified in cultures with lower Mg/Ca molar ratios (0, 3, and 6). That bacterial activity is critical for protodolomite formation as shown by the significant bacterial relicts identified in the precipitated spherulite crystals, including pinhole structures, a mineral coating around cells, and high organic matter content within the crystals. It was also confirmed that the high Mg/Ca molar ratio affects the composition of the organic components in the bacterial EPS, leading to the precipitation of the protodolomite. Specifically, not only the total EPS amount, but also other facilitators including the acidic amino acids (Glu and Asp) and polysaccharides in the EPS, increased significantly under the high Mg/Ca molar ratios. Combined with previous studies, the present findings suggest a clear link between high Mg/Ca molar ratios and the formation of protodolomite through halophilic bacterial activity.
In the Upper Ediacaran Dengying Formation of the Sichuan Basin, the presence of abundant, well-preserved microbial carbonates provides a unique opportunity to study Precambrian paleoceanography and ...microbial carbonate origins. Particularly, the underexplored coated grain dolostones of this formation, characterized by distinct microbially induced fabrics and intragranular dissolution, offer crucial insights for understanding late Ediacaran microbial mineralization and diagenetic sequences. Utilizing selected typical samples, we conducted detailed petrographic and geochemical analyses, revealing a dynamic interplay between microbial processes and sedimentary dynamics. We observe the coexistence of constructive micrite envelopes with microbially induced fabrics such as clots and laminations, highlighting microbial biomineralization's key role in fabric formation. The sedimentary dynamics critically determines the formation processes of the coated grains: low-energy settings foster grain agglomeration and consolidation through clot precipitation between grains, while high-energy settings favor smaller grains binding to microbial mats. Geochemically, micrite envelopes play an essential role in preserving distinct rare earth element (REE) signatures. The weak negative Ce anomalies and positive Eu anomalies within these envelopes point to a suboxic to anoxic depositional environment, directly indicative of the microenvironmental conditions conducive to microbial mineralization processes. Furthermore, our study sheds light on the structural evolution of coated grains with hollow nuclei, proposing that their internal pore formations are influenced by both mineral instability and selective dissolution by meteoric freshwater. These findings not only provide fresh insights into complex diagenetic processes in the Dengying Formation but also substantially advance our understanding of early microbial life and environmental adaptations during the Precambrian.
•Revealed the relationship between micrite envelopes and microbially induced fabrics•Proposed a novel formation mechanism for coated grain dolostone in the Dengying Fm.•Investigated the diverse environmental responses of microbiolite fabrics•Established micrite envelopes as dependable records of seawater REE compositions
To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role ...in patients with septic shock.
Thirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study. Baseline information and clinical outcomes were obtained prospectively. Lactylation levels of all proteins and H3K18 from peripheral blood mononuclear (PBMC) were determined by western blotting and serum levels of inflammatory cytokines by flow cytometry. Arginase-1 (
) and Krüppel-like factor-4 (
) mRNA expression was evaluated by quantitative real-time PCR (qRT-PCR).
Lactylation was found to be an all-protein post-translational modification and was detected in PBMCs from both healthy volunteers and critically ill patients, with a significantly higher relative density in shock patients (
=2.172,
=0.045). H3K18la was expressed in all subjects, including healthy volunteers, with the highest level in septic shock patients (compared with non-septic shock patients, critically ill without shock patients and healthy volunteers
=0.033, 0.000 and 0.000, respectively). Furthermore, H3K18la protein expression correlated positively with APACHE II scores, SOFA scores on day 1, ICU stay, mechanical ventilation time and serum lactate (
=0.42, 0.63, 0.39, 0.51 and 0.48, respectively,
=0.012, 0.000, 0.019, 0.003 and 0.003, respectively). When we matched patients with septic shock and with non-septic shock according to severity, we found higher H3K18la levels in the former group (
=-2.208,
=0.040). Moreover, H3K18la exhibited a close correlation with procalcitonin levels (
=0.71,
=0.010). Patients with high H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels (
=0.33, 0.37, 0.62, 0.55, 0.65, 0.49 and 0.374 respectively,
=0.024, 0.011, 0.000, 0.000, 0.000 and 0.000 respectively). H3K18la expression also displayed a positive correlation with the level of
mRNA (
=0.561,
=0.005).
Lactylation is an all-protein post-translational modification occurring in both healthy subjects and critically ill patients. H3K18la may reflect the severity of critical illness and the presence of infection. H3K18la might mediate inflammatory cytokine expression and
overexpression and stimulate the anti-inflammatory function of macrophages in sepsis.
Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression ...is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.
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