Remediation of Acid Mine Drainage in the Haizhou Open-Pit Mine through Coal-Gangue-Loaded SRB Experiments

To address the pollution problem of acid mine drainage (AMD) characterized by high concentrations of Fe2+, Mn2+, and SO42−, a combination of coal gangue (CG) and sulfate-reducing bacteria (SRB) was employed. The effects of coal-gangue dosage, SRB inoculation concentration, and temperature on AMD treatment with coal-gangue-loaded SRB were determined through single-factor experiments and response surface methodology (RSM) experiments. By considering the principles of adsorption isotherms, adsorption kinetics, and reduction kinetics, the removal mechanisms of SO42−, Fe2+, and Mn2+ in AMD using coal gangue-loaded SRB in the the Haizhou open-pit mine was revealed. The results showed that the overall effectiveness of the four types of coal-gangue-loaded SRB in repairing AMD was as follows: 3# CG-loaded SRB > 2# CG-loaded SRB > 1# CG-loaded SRB > 4# CG-loaded SRB, with coal-gangue-loaded SRB in the the Haizhou open-pit mine showing the best performance. According to the RSM test, the optimum conditions for repairing AMD with coal-gangue-loaded SRB in the open-pit mine were a coal-gangue dosage of 52 g, SRB inoculation concentration of 11.7%, and temperature of 33.4 °C. The order of factors affecting the removal of SO42− and Fe2+ from AMD by SRB loaded on coal gangue was SRB inoculation concentration > temperature > coal-gangue dosage. For Mn2+, the order of influence was temperature > SRB inoculation concentration > coal-gangue dosage. In the process of repairing Fe2+ with coal-gangue-loaded SRB in the the Haizhou open-pit mine, the biological activity metabolism of SRB played a leading role, while the adsorption isotherm of Mn2+ followed the Freundlich model. The adsorption kinetics of coal-gangue-loaded SRB in the the Haizhou open-pit mine for Fe2+ and Mn2+ in AMD conformed to Lagergren’s second-order kinetic model, while the reduction kinetics of SO42− conformed to a first-order reaction model

Cerebral Microvascular Injury Induced by Lag3‐Dependent α‐Synuclein Fibril Endocytosis Exacerbates Cognitive Impairment in a Mouse Model of α‐Synucleinopathies

Abstract The pathological accumulation of α‐synuclein (α‐Syn) and the transmission of misfolded α‐Syn underlie α‐synucleinopathies. Increased plasma α‐Syn levels are associated with cognitive impairment in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies, but it is still unknown whether the cognitive deficits in α‐synucleinopathies have a common vascular pathological origin. Here, it is reported that combined injection of α‐Syn preformed fibrils (PFFs) in the unilateral substantia nigra pars compacta, hippocampus, and cerebral cortex results in impaired spatial learning and memory abilities at 6 months post‐injection and that this cognitive decline is related to cerebral microvascular injury. Moreover, insoluble α‐Syn inclusions are found to form in primary mouse brain microvascular endothelial cells (BMVECs) through lymphocyte‐activation gene 3 (Lag3)‐dependent α‐Syn PFFs endocytosis, causing poly(ADP‐ribose)‐driven cell death and reducing the expression of tight junction proteins in BMVECs. Knockout of Lag3 in vitro prevents α‐Syn PFFs from entering BMVECs, thereby reducing the abovementioned response induced by α‐Syn PFFs. Deletion of endothelial cell‐specific Lag3 in vivo reverses the negative effects of α‐Syn PFFs on cerebral microvessels and cognitive function. In short, this study reveals the effectiveness of targeting Lag3 to block the spread of α‐Syn fibrils to endothelial cells in order to improve cognition

Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes

Summary: α-Synuclein preformed fibrils (α-syn PFF) in the blood can cross the blood–brain barrier and invade the central nervous system. Our previous study proved that α-syn PFF can be taken up by brain microvascular endothelial cells (BMVECs). Here, we found that α-syn PFF spread from BMVECs to pericytes with the highest transmission efficiency. We observed abundant tunneling nanotubes (TNTs) connecting BMVECs and pericytes, and α-syn PFF transmitted through these TNTs. Furthermore, α-syn PFF accumulation in BMVECs did not promote TNT formation, but activated the molecular motor Myo1d. Inhibition of Myo1d prevented α-syn PFF transfer from BMVECs to pericytes and decreased the colocalization of Myo1d and F-actin in BMVECs. In summary, we are the first to demonstrate that α-syn PFF spread from BMVECs to pericytes through a mechanism involving TNTs and myosin. Targeting Myo1d may be a promising approach to prevent α-syn spreading from the blood to the brain

De novo generation of macrophage from placenta-derived hemogenic endothelium.

Macrophages play pivotal roles in immunity, hematopoiesis, and tissue homeostasis. In mammals, macrophages have been shown to originate from yolk-sac-derived erythro-myeloid progenitors and aorta-gonad-mesonephros (AGM)-derived hematopoietic stem cells. However, whether macrophages can arise from other embryonic sites remains unclear. Here, using single-cell RNA sequencing, we profile the transcriptional landscape of mouse fetal placental hematopoiesis. We uncover and experimentally validate that a CD44+ subpopulation of placental endothelial cells (ECs) exhibits hemogenic potential. Importantly, lineage tracing using the newly generated Hoxa13 reporter line shows that Hoxa13-labeled ECs can produce placental macrophages, named Hofbauer cell (HBC)-like cells. Furthermore, we identify two subtypes of HBC-like cells, and cell-cell interaction analysis identifies their potential roles in angiogenesis and antigen presentation, separately. Our study provides a comprehensive understanding of placental hematopoiesis and highlights the placenta as a source of macrophages, which has important implications for both basic and translational research

Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics.

Limited knowledge of cellular and molecular mechanisms underlying hematopoietic stem cell and multipotent progenitor (HSC/MPP) expansion within their native niche has impeded the application of stem cell-based therapies for hematological malignancies. Here, we constructed a spatiotemporal transcriptome map of mouse fetal liver (FL) as a platform for hypothesis generation and subsequent experimental validation of novel regulatory mechanisms. Single-cell transcriptomics revealed three transcriptionally heterogeneous HSC/MPP subsets, among which a CD93-enriched subset exhibited enhanced stem cell properties. Moreover, by employing integrative analysis of single-cell and spatial transcriptomics, we identified novel HSC/MPP 'pocket-like' units (HSC PLUS), composed of niche cells (hepatoblasts, stromal cells, endothelial cells, and macrophages) and enriched with growth factors. Unexpectedly, macrophages showed an 11-fold enrichment in the HSC PLUS. Functionally, macrophage-HSC/MPP co-culture assay and candidate molecule testing, respectively, validated the supportive role of macrophages and growth factors (MDK, PTN, and IGFBP5) in HSC/MPP expansion. Finally, cross-species analysis and functional validation showed conserved cell-cell interactions and expansion mechanisms but divergent transcriptome signatures between mouse and human FL HSCs/MPPs. Taken together, these results provide an essential resource for understanding HSC/MPP development in FL, and novel insight into functional HSC/MPP expansion ex vivo.National Key Research and Development Program of Chin

Presentation_1_Management of intervenable factors to reduce vascular complications in patients with internal carotid artery occlusion treated by non-emergency endovascular treatment.pdf

ObjectiveThis study aims to identify risk factors for vascular complications during non-emergency endovascular treatment in patients with internal carotid artery occlusion (ICAO) and to propose potential interventions.MethodA retrospective analysis of 92 patients with ICAO who received non-emergency endovascular treatment in our center from 1 January 2018 to 31 June 2023, was conducted. The correlation between intraoperative vascular complications and potential risk factors was studied, and interaction analysis was performed.ResultsOur findings revealed that the use of non-neurology guide wires to open vessels (adjusted OR: 4.1, 95%CI: 1.3–12.8; p = 0.014) and glycosylated hemoglobin (HbA1c) ≥ 6.5 mmol/L (adjusted OR: 3.2, 95%CI: 1.2–8.9; p = 0.023) was significantly associated with vascular complications in non-emergency endovascular treatment of ICAO patients. The restricted cubic spline (RCS) showed that the higher the HbA1c level, the higher the risk of vascular complications.ConclusionThe use of non-neurology guide wires for vessel opening during non-emergency endovascular treatment in patients with ICAO increases the risk of vascular complications. Preoperative assessment and management of HbA1c levels can reduce the incidence of intraoperative vascular complications.</p