Comparison of three concentrations of ropivacaine in posterior quadratus lumborum block: A randomized clinical trial.

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

SASAN: Spectrum-Axial Spatial Approach Networks for Medical Image Segmentation.

Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss (LSM), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.

Monomeric far-red and near-infrared fluorescent biliproteins of ultrahigh brightness.

Far-red and near-infrared fluorescent proteins have regions of maximum transmission in most tissues and can be widely used as fluorescent biomarkers. We report that fluorescent phycobiliproteins originating from the phycobilisome core subunit ApcF2 can covalently bind biliverdin, named BDFPs. To further improve BDFPs, we conducted a series of studies. Firstly, we mutated K53Q and T144A of BDFPs to increase their effective brightness up to 190% in vivo. Secondly, by homochromatic tandem fusion of high-brightness BDFPs to achieve monomerization, which increases the effective brightness by up to 180% in vivo, and can effectively improve the labeling effect. By combining the above two approaches, the brightness of the tandem BDFPs was much improved compared with that of the previously reported fluorescent proteins in a similar spectral range. The tandem BDFPs were expressed stably while maintaining fluorescence in mammalian cells and Caenorhabditis elegans. They were also photostable and resistant to high temperature, low pH, and chemical denaturation. The tandem BDFPs advantages were proved in applications as biomarkers for imaging in super-resolution microscopy.

Research on the tilt-to-length coupling noise suppression method inside the gravitational wave detection telescope.

As an integral component of the laser interferometry measurement system, the tilt-to-length (TTL) coupling noise inside the telescope stands out as a critical noise factor that requires meticulous consideration. In the TianQin project, the non-geometric TTL-coupled noise inside the telescope should be less than 0.22 pm/Hz1/2. Additionally, the wavefront aberration RMS at the small pupil of the telescope needs to be better than 0.0065 λ. These requirements set for the telescope are exceptionally stringent. To address this challenge, this study aims to relax the wavefront aberration requirements by mitigating non-geometric TTL coupling noise, while ensuring the non-geometric TTL coupling noise remains below 0.22 pm/Hz1/2. By controlling the coupling aberration proportion, the wavefront aberration RMS at the small pupil of the telescope can be relaxed to 0.014 λ. Alternatively, optimizing the Gaussian beam waist radius can relax the wavefront aberration RMS to 0.016 λ. By simultaneously utilizing two optimization methods, the wavefront aberration at the small pupil of the telescope can be reduced to 0.033 λ, resulting in an impressive success rate of 91.15% in meeting the noise requirements.

B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

A Novel Approach for Glioblastoma Treatment by Combining Apoptosis Inducers (TMZ, MTX, and Cytarabine) with E.V.A. (Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1.

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches. Apoptosis induction in GB cells is inefficient, due to an excess of anti-apoptotic XPO1/Bcl-2-family proteins. We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs). Using CellTiter-Glo® and Caspase-3 activity assays, we generated dose-response curves and analyzed the gene and protein regulation of anti-apoptotic proteins via PCR and Western blots. Optimal drug combinations were examined for their impact on the cell cycle and apoptosis induction via FACS analysis, paralleled by the assessment of potential toxicity in healthy mouse brain slices. Ara-C and MTX proved to be 150- to 10,000-fold more potent in inducing apoptosis than TMZ. In response to inhibitors Eltanexor (XPO1; E), Venetoclax (Bcl-2; V), and A1210477 (Mcl-1; A), genes encoding for the corresponding proteins were upregulated in a compensatory manner. TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study.

BACKGROUND: Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. METHODS: For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. RESULTS: We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02-2.55, P = 4.07 × 10-2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53-0.89, P = 5.74 × 10-3) and CD19 (OR = 0.59, 95%CI = 1.02-2.55, P = 4.07 × 10-2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01-1.09, P = 1.19 × 10-2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00-1.08, P = 2.83 × 10-2). CONCLUSIONS: Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.

Development of calcium-modified biochar for enhanced phytoremediation of human-induced salt pollutants (HISPs).

Soil salinization is a major environmental hazard that limits land availability. Human-induced salt pollutants (HISPs) are regularly presented in large quantities on the contaminated site (such as brine leakages and salt-water spills), causing a devastating shock with high salt stress to the ecosystem. For instance, Saskatchewan resulted in a 48% drop in wheat production and a 0.3% decline in provincial GDP. As the calcium-modified biochar can potentially ameliorate the negative effects of HISPs on plants and improve the plant, phytoremediation with calcium-modified biochar can have increased detoxification of hazardous pollutants from sites. Therefore, the objective of our study was to develop a biochar-assisted phytoremediation employing diverse approaches to calcium modification for the sustainable removal of HISPs. The co-pyrolyzed calcium biochar achieved a remarkable removal rate of 18.06%, reducing salinity from 9.44 to 7.81 dS/m. During a 90-day long-term phytoremediation, the overall reduction rate of calcium-modified biochar stimulated the germination and growth of Thinopyrum ponticum. The result of post-treatment further indicated that co-pyrolyzed biochar with Ca transferred salt into the plant compared to Ca-coated biochar, which only immobilized HISPs on its surface. These results offer two different treatment approaches for diverse situations involving HISPs contamination, addressing current in-situ spills and providing a calcium-related biochar technology for further research in desalination.

Disaster literacy in disaster emergency response: a national qualitative study among nurses.

BACKGROUND: As the largest group of healthcare professionals, nurses play an indispensable and crucial role in disaster response. The enhancement of nurses' disaster literacy is imperative for effective disaster emergency management. However, there is currently a lack of knowledge regarding nurses' disaster literacy. This study represents the first attempt to explore the key components and characteristics of disaster literacy among nurses. METHODS: A qualitative descriptive design was employed, and the reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (refer to File S1). The purposive sampling method was utilized. Thirty-one rescue nurses from 31 medical institutions across 25 provinces and regions in China were recruited to participate in the study. The respondents were requested to share their experiences and insights regarding disaster rescue operations. Inductive content analysis was employed for data examination. RESULTS: The results indicated that rescue nurses universally recognized that there was a pressing need to enhance the level of disaster literacy among nurses. The disaster literacy of nurses encompasses nine dimensions: physical and mental quality, disaster rescue general knowledge, professional and technical competence, professional ethics, teamwork, emotional ability, information literacy, leadership, and knowledge transformation. CONCLUSIONS: To ensure national sustainability, government departments, healthcare organizations, and hospital administrators can accurately evaluate the disaster literacy of individual clinical nurses, groups, and the workforce as a whole through nine dimensions, which also can provide evidence to support the development of precision strategies to strengthen the disaster literacy of nurses.

The combination of deep learning and pseudo-MS image improves the applicability of metabolomics to congenital heart defect prenatal screening.

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.

Risk factors for inadequate bowel preparation before colonoscopy: A meta-analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). METHODS: We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. RESULTS: A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. CONCLUSIONS: We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

[Construction and Optimization of CD19 Chimeric Antigen Receptor T Cells Derived from C57BL/6J Mice].

OBJECTIVE: To explore the stimulation conditions, optimal culture time and infection time of C57BL/6J mice CD3+ T cells in vitro, so as to improve the infection efficiency of CD19 chimeric antigen receptor T cells (mCD19 CAR-T). METHODS: Purified C57BL/6J mice CD3+ T cells were cultured in anti-CD3/CD28 coated, anti-CD3 coated+soluble anti-CD28 and anti-CD3 coated, respectively. The cells were stimulated in above three conditions for 12 h and 24 h, following with 24 h, 48 h and 72 h incubation and then the number of cell clones was recorded. C57BL/6J mice CD3+ T cells were stimulated for 12 h, 24 h, and 36 h under the above three conditions, then interleukin (IL)-2 (100 U/ml) was added. The number of cell clones was recorded under microscope at 24 h, 48 h, and 72 h of culture. After 24 h of stimulation, CD3+ T cells derived from C57BL/6J mice were infected with retrovirus for 48 h to establish mCD19 CAR-T cells, and the percentage of GFP+ CAR-T cells was detected by flow cytometry. RESULTS: The infection efficiency of mCD19 CAR-T cells derived from C57BL/6J mice was only 5.23% under the optimized conditions of mCD19 CAR-T cells derived from BALB/c mice. The number of clones of C57BL/6J mice CD3+ T cells was the highest in anti-CD3 coated+soluble anti-CD28 group after stimulated for 24 h and followed cultured for 48 h. After 24 hours of stimulation under the above conditions and 48 hours of culture with IL-2, the number of T cell proliferating clones in the anti-CD3 coated+soluble anti-CD28 group was significantly increased compared with the same group without IL-2, and the infection efficiency of CAR-T cells in this group reached 17.63%±4.17%. CONCLUSION: The optimal conditions for constructing CAR-T cells from C57BL/6J mice CD3+ T cells are different from those of BABL/c mice. T cells stimulated by anti-CD3 coated+soluble anti-CD28+IL-2 can obtain mCD19 CAR-T cells with the highest efficiency after retrovirus infection.

INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis.

RNA sequencing (RNA-Seq) is widely used to capture transcriptome dynamics across tissues, biological entities, and conditions. Currently, few or no methods can handle multiple biological variables (e.g., tissues/ phenotypes) and their interactions simultaneously, while also achieving dimension reduction (DR). We propose INSIDER, a general and flexible statistical framework based on matrix factorization, which is freely available at https://github.com/kai0511/insider. INSIDER decomposes variation from different biological variables and their interactions into a shared low-rank latent space. Particularly, it introduces the elastic net penalty to induce sparsity while considering the grouping effects of genes. It can achieve DR of high-dimensional data (of > = 3 dimensions), as opposed to conventional methods (e.g., PCA/NMF) which generally only handle 2D data (e.g., sample × expression). Besides, it enables computing 'adjusted' expression profiles for specific biological variables while controlling variation from other variables. INSIDER is computationally efficient and accommodates missing data. INSIDER also performed similarly or outperformed a close competing method, SDA, as shown in simulations and can handle complex missing data in RNA-Seq data. Moreover, unlike SDA, it can be used when the data cannot be structured into a tensor. Lastly, we demonstrate its usefulness via real data analysis, including clustering donors for disease subtyping, revealing neuro-development trajectory using the BrainSpan data, and uncovering biological processes contributing to variables of interest (e.g., disease status and tissue) and their interactions.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.

Domestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes.

Purpose To evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI. Methods Twenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests. Results At baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide - pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively). Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

The Impact of Income Inequality on Health Levels: Empirical Evidence from China:2002-2016.

Income inequality had been one of the important manifestations of social inequality, which can affect the health level by affecting savings, health care and living standards. Existing researches about the relationship between income inequality and health ignored the comprehensive characteristic of health concept, and did not consider the intrinsic relationship between health and income inequality. This paper attempts to re-shed light on the relationship. Firstly, this paper constructs a new health level evaluation system from three aspects: health basis, health environment and behavior, and health security. By means of the combination evaluation method, the health levels can be obtained. Then, considering the interaction between health and income inequality, a simultaneous equation group model is constructed to empirically test the relationship between income inequality and health levels in China. The results reveal that health level is negatively correlated with income inequality. Reducing income inequality plays an important role in improving health levels in China.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Promote the Recovery of Spinal Cord Injury and Inhibit Ferroptosis by Inactivating IL-17 Pathway.

Mesenchymal stem cell (MSC)-derived exosomes are considered as alternative to cell therapy in various diseases. This study aimed to understand the effect of bone marrow MSC-derived exosomes (BMMSC-exos) on spinal cord injury (SCI) and to unveil its regulatory mechanism on ferroptosis. Exosomes were isolated from BMMSCs and the uptake of BMMSCs-exos by PC12 cells was determined using PKH67 staining. The effect of BMMSC-exos on SCI in rats was studied by evaluating pathological changes of spinal cord tissues, inflammatory cytokines, and ferroptosis-related proteins. Transcriptome sequencing was used to discover the differential expressed genes (DEGs) between SCI rats and BMMSC-exos-treated rats followed by functional enrichment analyses. The effect of BMMSC-exos on ferroptosis and interleukin 17 (IL-17) pathway was evaluated in SCI rats and oxygen-glucose deprivation (OGD)-treated PC12 cells. The results showed that particles extracted from BMMSCs were exosomes that could be taken up by PC12 cells. BMMSC-exos treatment ameliorated injuries of spinal cord, suppressed the accumulation of Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS), with the elevated glutathione (GSH). Also, BMMSC-exos downregulated the expression of acyl-CoA synthetase long chain family member 4 (ACSL4) and upregulated glutathione peroxidase 4 (GPX4) and cysteine/glutamate antiporter xCT. A total of 110 DEGs were discovered and they were mainly enriched in IL-17 signaling pathway. Further in vitro and in vivo experiments showed that BMMSC-exos inactivated IL-17 pathway. BMMSC-exos promote the recovery of SCI and inhibit ferroptosis by inhibiting the IL-17 pathway, which provides BMMSC-exos as an alternative to the management of SCI.