Hydrogeochemical characteristics, driving factors, and health risk assessment of karst groundwater in Southwest Hubei Province, China.

In South China, karst groundwater is an important water resource for industrial, agricultural, and drinking purposes. However, karst aquifers are highly vulnerable to pollution, leading to deteriorating karst groundwater quality and posing potential health risks to local residents. In this study, 22 groundwater samples were collected from a karst aquifer in the southwestern part of Hubei Province. The hydrogeochemical characteristics and their controlling factors were examined, and the potential health risks associated with groundwater pollutant concentrations in karst groundwater were assessed. The results showed that the groundwater is slightly alkaline with low chemical oxygen demand values, indicating good water quality. The groundwater facies type was identified as HCO3-Ca at most sample spots, showing low total dissolved solids concentrations. Substantial spatial variations in Na+, CO3 2-, and NO2 - concentrations were found, whereas spatial variations in the K+, Ca2+, Cl-, HCO3 -, and F- concentrations were small. In addition, the dissolution of gypsum deposits and magnesium carbonate sedimentary rocks at sampling sites resulted in groundwater facies types of HCO3•SO4-Ca and HCO3-Ca•Mg, with low total dissolved solids concentrations. The karst groundwater chemistry in the study area was mainly controlled by water-rock interactions, as well as by the dissolution of gypsum deposits and magnesium carbonate sedimentary rocks at specific groundwater sampling sites. The groundwater Cl- concentrations were mainly affected by atmospheric precipitation. NO3 - was mainly derived from atmospheric precipitation, domestic sewage, septic tanks, and industrial activities, whereas SO4 2- was derived from atmospheric precipitation, sulfate rock dissolution, and sulfide mineral oxidation. These results highlight the absence of potential human health risks of NO3 - and F- to infants, children, and adults, as their concentrations are below the corresponding regional background values. In contrast, the potential health risks of Cl- cannot be ignored, particularly for infants. This study offers scientific guidelines for protecting and allocating local groundwater resources.

BMSC-derived exosomal miR-219-5p alleviates ferroptosis in neuronal cells caused by spinal cord injury via the UBE2Z/NRF2 pathway.

OBJECTIVE: The aim of this study was to investigate the molecular mechanism of exosomal miR-219-5p derived from bone marrow mesenchymal stem cells (BMSCs) in the treatment of spinal cord injury (SCI). METHODS: Basso Beattie Bresnahan (BBB) score and tissue staining were used to assess SCI and neuronal survival in rats. The contents of Fe2+, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected by a kit. The expression levels of ubiquitin-conjugating enzyme E2 Z (UBE2Z), nuclear factor erythroid 2-related Factor 2 (NRF2) and ferroptosis-related proteins were detected by Western blotting. In addition, the ability of BMSC-derived exosomes to inhibit ferroptosis in neuronal cells in rats with SCI was validated by in vivo injection of ferroptosis inhibitors/inducers. RESULTS: In this study, we found that miR-219-5p-rich BMSC-derived exosomes inhibited ferroptosis in SCI rats and that the alleviating effect of BMSC-Exos on SCI was achieved by inhibiting the ferroptosis signaling pathway and that NRF2 played a key role in this process. Our study confirmed that BMSC exosome-specific delivery of miR-219-5p can target UBE2Z to regulate its stability and that overexpression of UBE2Z reverses miR-219-5p regulation of NRF2. In addition, in vivo experiments showed that BMSC exosomes alleviated ferroptosis in neuronal SCI progression, and inhibiting the expression of miR-219-5p in BMSCs reduced the alleviating effect of exosomes on ferroptosis in neuronal cells and SCI. CONCLUSION: miR-219-5p in BMSC-derived exosomes can repair the injured spinal cord. In addition, miR-219-5p alleviates ferroptosis in neuronal cells induced by SCI through the UBE2Z/NRF2 pathway.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and kidney stones: a cross-sectional study.

BACKGROUND: The relationship between the NHHR and kidney stone risk remains unknown. The purpose of this study was to evaluate the association between adult NHHR and kidney stone occurrence in USA. METHODS: This study used a variety of statistical techniques such as threshold effects, subgroup analysis, smooth curve fitting, multivariate logistic regression, and data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. We aimed to clarify the relationship between the NHHR and kidney stone risk. RESULTS: The average age of the 21,058 individuals in this research was 49.70 ± 17.64 years. The mean NHHR was 3.00 ± 1.47, and the overall prevalence of kidney stone occurrence was 9.05%. The prevalence within the quartile ranges (Q1-Q4) was 7.01%, 8.71%, 9.98%, and 10.49%, respectively. The overall average recurrence rate of kidney stones was 3.05%, demonstrating a significant increase with increasing NHHR (Q1: 1.92%, Q2: 2.92%, Q3: 3.35%, Q4: 4.00%, P < 0.01). The occurrence of kidney stones increased by 4% (95% CI: 1.00-1.08, P = 0.0373) and the chance of recurrence increased by 9% (95% CI: 1.03-1.14, P < 0.01) with each unit increase in NHHR. The interaction analysis results demonstrated that the relationship between the NHHR and the risk of kidney stones was not significantly impacted by the following factors: sex, body mass index, poverty income ratio, diabetes, or hypertension. Curve fitting and threshold effect analysis also demonstrated a non-linear association, with a breakpoint found at 3.17, between the NHHR and the risk of kidney stones. CONCLUSIONS: In adults in the USA, there is a substantial correlation between elevated NHHR levels and a higher probability of kidney stones developing and recurring. Timely intervention and management of NHHR may effectively mitigate the occurrence and recurrence of kidney stones.

Mechanistic study on the alleviation of postmenopausal osteoporosis by Lactobacillus acidophilus through butyrate-mediated inhibition of osteoclast activity.

In China, traditional medications for osteoporosis have significant side effects, low compliance, and high costs, making it urgent to explore new treatment options. Probiotics have demonstrated superiority in the treatment of various chronic diseases, and the reduction of bone mass in postmenopausal osteoporosis (PMOP) is closely related to the degradation and metabolism of intestinal probiotics. It is crucial to explore the role and molecular mechanisms of probiotics in alleviating PMOP through their metabolites, as well as their therapeutic effects. We aim to identify key probiotics and their metabolites that affect bone loss in PMOP through 16srDNA sequencing combined with non-targeted metabolomics sequencing, and explore the impact and possible mechanisms of key probiotics and their metabolites on the progression of PMOP in the context of osteoporosis caused by estrogen deficiency. The sequencing results showed a significant decrease in Lactobacillus acidophilus and butyrate in PMOP patients. In vivo experiments confirmed that the intervention of L. acidophilus and butyrate significantly inhibited osteoclast formation and bone resorption activity, improved intestinal barrier permeability, suppressed B cells, and the production of RANKL on B cells, effectively reduced systemic bone loss induced by oophorectomy, with butyric acid levels regulated by L. acidophilus. Consistently, in vitro experiments have confirmed that butyrate can directly inhibit the formation of osteoclasts and bone resorption activity. The above research results indicate that there are various pathways through which L. acidophilus inhibits osteoclast formation and bone resorption activity through butyrate. Intervention with L. acidophilus may be a safe and promising treatment strategy for osteoclast related bone diseases, such as PMOP.

Masked Spatial-Spectral Autoencoders Are Excellent Hyperspectral Defenders.

Deep learning (DL) methodology contributes a lot to the development of hyperspectral image (HSI) analysis community. However, it also makes HSI analysis systems vulnerable to adversarial attacks. To this end, we propose a masked spatial-spectral autoencoder (MSSA) in this article under self-supervised learning theory, for enhancing the robustness of HSI analysis systems. First, a masked sequence attention learning (MSAL) module is conducted to promote the inherent robustness of HSI analysis systems along spectral channel. Then, we develop a graph convolutional network (GCN) with learnable graph structure to establish global pixel-wise combinations. In this way, the attack effect would be dispersed by all the related pixels among each combination, and a better defense performance is achievable in spatial aspect. Finally, to improve the defense transferability and address the problem of limited labeled samples, MSSA employs spectra reconstruction as a pretext task and fits the datasets in a self-supervised manner. Comprehensive experiments over three benchmarks verify the effectiveness of MSSA in comparison with the state-of-the-art hyperspectral classification methods and representative adversarial defense strategies.

Circular RNA HIPK2 Promotes A1 Astrocyte Activation after Spinal Cord Injury through Autophagy and Endoplasmic Reticulum Stress by Modulating miR-124-3p-Mediated Smad2 Repression.

Glial scarring formed by reactive astrocytes after spinal cord injury (SCI) is the primary obstacle to neuronal regeneration within the central nervous system, making them a promising target for SCI treatment. Our previous studies have demonstrated the positive impact of miR-124-3p on neuronal repair, but it remains unclear how miR-124-3p is involved in autophagy or ER stress in astrocyte activation. To answer this question, the expression of A1 astrocyte-related markers at the transcriptional and protein levels after SCI was checked in RNA-sequencing data and verified using quantitative polymerase chain reaction (qPCR) and Western blotting in vitro and in vivo. The potential interactions among circHIPK2, miR-124-3p, and Smad2 were analyzed and confirmed by bioinformatics analyses and a luciferase reporter assay. In the end, the role of miR-124-3p in autophagy, ER stress, and SCI was investigated by using Western blotting to measure key biomarkers (C3, LC3, and Chop) in the absence or presence of corresponding selective inhibitors (siRNA, 4-PBA, TG). As a result, SCI caused the increase of A1 astrocyte markers, in which the upregulated circHIPK2 directly targeted miR-124-3p, and the direct downregulating effect of Smad2 by miR-124-3p was abolished, while Agomir-124 treatment reversed this effect. Injury caused a significant change of markers for ER stress and autophagy through the circHIPK2/miR-124-3p/Smad2 pathway, which might activate the A1 phenotype, and ER stress might promote autophagy in astrocytes. In conclusion, circHIPK2 may play a functional role in sequestering miR-124-3p and facilitating the activation of A1 astrocytes through regulating Smad2-mediated downstream autophagy and ER stress pathways, providing a new perspective on potential targets for functional recovery after SCI.

Transcriptomics Provides Novel Insights into the Regulatory Mechanism of IncRNA HIF1 A-AS1 on Vascular Smooth Muscle Cells.

INTRODUCTION: Thoracic aortic aneurysm is a potentially fatal disease with a strong genetic contribution. The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the formation of this aneurysm. Although previous studies suggested that long non-coding ribonucleic acid (RNA) hypoxia inducible factor 1 α-antisense RNA 1 (HIF1A-AS1) exerted a vital role in the progression and pathogenesis of thoracic aortic aneurysm, we managed to find a new regulatory mechanism of HIF1A-AS1 in VSMCs via transcriptomics. METHODS: Cell viability was detected by the cell counting kit-8 assay. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Transwell migration assay and wound healing assay were performed to check the migration ability of HIF1A-AS1 on VSMCs. The NextSeq XTen system (Illumina) was used to collect RNA sequencing data. Lastly, reverse transcription-quantitative polymerase chain reaction confirmed the veracity and reliability of RNA-sequencing results. RESULTS: We observed that overexpressing HIF1A-AS1 successfully promoted apoptosis, significantly altered cell cycle distribution, and greatly attenuated migration in VSMCs, further highlighting the robust promoting effects of HIF1A-AS1 to thoracic aortic aneurysm. Moreover, transcriptomics was implemented to uncover its underlying mechanism. A total of 175 differently expressed genes were identified, with some of them enriched in apoptosis, migration, and cell cycle-related pathways. Intriguingly, some differently expressed genes were noted in vascular development or coagulation function pathways. CONCLUSION: We suggest that HIF1A-AS1 mediated the progression of thoracic aortic aneurysm by not only regulating the function of VSMCs, but also altering vascular development or coagulation function.

lncRNA XIST inhibition promotes M2 polarization of microglial and aggravates the spinal cord injury via regulating miR-124-3p / IRF1 axis.

Spinal cord injury (SCI) has a high disability rate and mortality rate. Recently, LncRNA XIST has been found to be involved in the regulation of inflammatory responses. Therefore, we aimed to investigate the role of XIST in the occurrence and development of SCI and the specific regulation mechanism. Methods: 100 ng/mL lipopolysaccharide (LPS) was used to treat mouse microglia BV2 cells. Hitting spinal cord was performed to C57BL/6 mice for establishing SCI model. Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), Western blot, Immunofluorescence (IF) and Enzyme linked immunosorbent assay (ELISA) experiments were used to explore the function of XIST, miR-124-3p and IRF1 in LPS-induced BV2 cells. RT-qPCR, Nissl staining, IF, Western blot and ELISA experiment were performed to study the function of XIST in SCI mice. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), RT-qPCR and Western blot assays were utilized to identify the interaction among XIST, miR-124-3p and IRF1. Results: XIST was upregulated in LPS-induced BV2 cells and spinal cord tissues of SCI mice. Overexpression of XIST promoted the M1 microphages polarization and cytokines concentration in LPS-stimulated BV2 cells, aggravated SCI of mice. Downregulated XIST promoted M1-to-M2 conversion of microglial and relieved the injury of SCI mice. Mechanism verification indicated that XIST acted as a molecular sponge of miR-124-3p and regulated IRF1 expression. Increased miR-124-3p or reduced IRF1 inhibited M1 polarization of microglial and decreased the production of inflammatory cytokines in LPS-induced BV2 cells. Increased XIST or decreased miR-124-3p had an opposite of on LPS-induced BV2 cells. Conclusion: Overexpression of XIST enhanced M1 polarization of microglia and promoted the level of inflammatory cytokines through sponging miR-124-3p and regulating IRF1 expression.

Graphdiyne nanoplatforms for photothermal-ferroptosis combination therapy against glioblastoma.

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system and has a poor prognosis. GBM cells are highly sensitive to ferroptosis and heat, suggesting thermotherapy-ferroptosis as a new strategy for GBM treatment. With its biocompatibility and photothermal conversion efficiency, graphdiyne (GDY) has become a high-profile nanomaterial. Here, the ferroptosis inducer FIN56 was employed to construct GDY-FIN56-RAP (GFR) polymer self-assembled nanoplatforms against GBM. GDY could effectively load FIN56 and FIN56 released from GFR in a pH-dependent manner. The GFR nanoplatforms possessed the advantages of penetrating the BBB and acidic environment-induced in situ FIN56 release. Moreover, GFR nanoplatforms induced GBM cell ferroptosis by inhibiting GPX4 expression, and 808 nm irradiation reinforced GFR-mediated ferroptosis by elevating the temperature and promoting FIN56 release from GFR. In addition, the GFR nanoplatforms were inclined to locate in tumor tissue, inhibit GBM growth, and prolong lifespan by inducing GPX4-mediated ferroptosis in an orthotopic xenograft mouse model of GBM; meanwhile, 808 nm irradiation further improved these GFR-mediated effects. Hence, GFR may be a potential nanomedicine for cancer therapy, and GFR combined with photothermal therapy may be a promising strategy against GBM.

Risk Factors of Postoperative Cerebrospinal Fluid Leak After Craniovertebral Junction Anomalies Surgery: A Case-Control Study.

OBJECTIVE: To identify potential risk factors for cerebrospinal fluid (CSF) leakage after craniovertebral junction (CVJ) anomaly surgery and to provide a reference for clinical practice. METHODS: Sixty-six patients who underwent elective CVJ anomaly surgery during a 6-year period (April 2013 to September 2019) were retrospectively included. Research data were collected from the patients' medical records and imaging systems. Patients were divided into CSF leak and no CSF leak groups. Univariate tests were performed to identify potential risk factors. For statistically significant variables in the univariate tests, a logistic regression test was used to identify independent risk factors for CSF leakage. RESULTS: The overall prevalence of CSF leakage was 13.64%. Univariate tests showed that a basion-dental interval (BDI) > 10 mm and occipitalized atlas had significant intergroup differences (p < 0.05). Multivariate analysis indicated that a BDI > 10 mm was an independent risk factor for CSF leakage, and patients with CVJ anomalies with a BDI > 10 mm were more likely to have postoperative CSF leaks (odds ratio, 14.67; 95% confidence interval, 1.48-30.88; p = 0.004). CONCLUSION: It is necessary to maintain vigilance during CVJ anomaly surgery in patients with a preoperative BDI > 10 mm to avoid postoperative CSF leaks.