The HD-ZIP IV transcription factor GLABRA2 acts as an activator for proanthocyanidin biosynthesis in Medicago truncatula seed coat.

Proanthocyanidins (PAs), a group of flavonoids, are found in leaves, flowers, fruits, and seed coats of many plant species. PAs are primarily composed of epicatechin units in the seed coats of the model legume species, Medicago truncatula. It can be synthesized from two separate pathways, the leucoanthocyanidin reductase (MtLAR) pathway and the anthocyanidin synthase (MtANS) pathway, which produce epicatechin through anthocyanidin reductase (MtANR). These pathways are mainly controlled by the MYB-bHLH-WD40 (MBW) ternary complex. Here, we characterize a class IV homeodomain-leucine zipper (HD-ZIP IV) transcription factor, GLABRA2 (MtGL2), which contributes to PA biosynthesis in the seed coat of M. truncatula. Null mutation of MtGL2 results in dark brown seed coat, which is accompanied by reduced PAs accumulation and increased anthocyanins content. The MtGL2 gene is predominantly expressed in the seed coat during the early stages of seed development. Genetic and molecular analyses indicate that MtGL2 positively regulates PA biosynthesis by directly activating the expression of MtANR. Additionally, our results show that MtGL2 is strongly induced by the MBW activator complexes that are involved in PA biosynthesis. Taken together, our results suggest that MtGL2 acts as a novel positive regulator in PA biosynthesis, expanding the regulatory network and providing insights for genetic engineering of PA production.

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway.

INTRODUCTION: The diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. The aim of this study was to explore precise targets for improving the prognosis of TBI patients from a microglial perspective. OBJECTIVES: To assess whether the prognosis of TBI can be improved by modulating microglia function. RESULTS: In CD300LF-deficient mice, we observed an increase in glial cell proliferation, more extensive neuronal loss, and worsened neurological function post-TBI. Transcriptomic comparisons between CD300LF-positive and CD300LF-negative microglia illuminated that the neuroprotective role of CD300LF is principally mediated by the inhibition of the STING signaling pathway. In addition, this protective effect can be augmented using the STING pathway inhibitor C-176. CONCLUSIONS: Our research indicates that CD300LF reduces neuroinflammation and promotes neurological recovery after TBI, and that microglia are integral to the protective effects of CD300LF in this context. In summary, our findings highlight CD300LF as a critical molecular regulator modulating the adverse actions of microglia following acute brain injury and propose a novel therapeutic approach to enhance outcomes for patients with TBI.

Pan-cancer analysis of PSCA that is associated with immune infiltration and affects patient prognosis.

Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.

Application and advances of biomimetic membrane materials in central nervous system disorders.

Central nervous system (CNS) diseases encompass spinal cord injuries, brain tumors, neurodegenerative diseases, and ischemic strokes. Recently, there has been a growing global recognition of CNS disorders as a leading cause of disability and death in humans and the second most common cause of death worldwide. The global burdens and treatment challenges posed by CNS disorders are particularly significant in the context of a rapidly expanding global population and aging demographics. The blood-brain barrier (BBB) presents a challenge for effective drug delivery in CNS disorders, as conventional drugs often have limited penetration into the brain. Advances in biomimetic membrane nanomaterials technology have shown promise in enhancing drug delivery for various CNS disorders, leveraging properties such as natural biological surfaces, high biocompatibility and biosafety. This review discusses recent developments in biomimetic membrane materials, summarizes the types and preparation methods of these materials, analyzes their applications in treating CNS injuries, and provides insights into the future prospects and limitations of biomimetic membrane materials.

Rewiring of a KNOXI regulatory network mediated by UFO underlies the compound leaf development in Medicago truncatula.

Class I KNOTTED-like homeobox (KNOXI) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula. PINNATE-LIKE PENTAFOLIATA1 (PINNA1) represses the expression of MtKNOXI, while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS (MtUFO) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO, and leaf development, MtKNOXI, are involved in variation of pinnate-like compound leaves in M. truncatula.

Characteristics of number concentration, size distribution and components of particulate matter emitted from a typical large civil airport.

Civil airports are recognized as significant contributors to fine particulate matter, especially ultra-fine particulate matter (UFP). The pollutants from airport activities have a notable adverse impact on global climate, urban air quality, and public health. However, there is a lack of practical observational studies on the characterization of integrated pollutant emissions from large civil airports. This study aims to focus on the combined emission characteristics of particulate number concentration (PNC), size distribution, and components at a large civil airport, especially UFP. The findings reveal that airport activities significantly contribute to elevated PNC levels during aircraft activity in downwind conditions (four times higher than background levels) and upwind conditions (7.5 times higher). UFP dominates the PNC around the airport. The particle size distribution shows two peaks occurring around 10-30 nm and 60-80 nm. Notably, particles within the ranges of 17-29 nm and 57-101 nm account for 65.9 % and 12.0 % of the total PNC respectively. Aircraft landing has the greatest impact on particles sized between 6 and 17 nm while takeoff affects particles sized between 29 and 57 nm resulting in a respective increase in PNC by factors of approximately 3.27 and 35.4-fold increase compared to background levels. Different aircraft types exhibit varying effects on PNC with A320 and A321 showing more pronounced effects during takeoff and landing.The presence of airports leads to roughly five-fold rise in elemental component concentrations with Si being highest followed by OC, Ca, Al, Fe, Ca2+, EC, and Mg2+. The OC/EC ratio under high aircraft activity in downwind conditions falls within range of approximately 2.5-3.5. These characteristic components and ratio can be considered as identifying species for civil airports. PMF model show about 75 % of the particulate emissions at the airport boundary were related to airport activities.

Individualized anti-thrombotic therapy for acute myocardial infarction complicated with left ventricular thrombus: A case report.

BACKGROUND: Presently, there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). While vitamin K antagonists are the preferred choice for oral blood thinning, determining the best course of blood-thinning medication remains challenging. It is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating LVT. This study significantly contributes to the medical community. CASE SUMMARY: The blood-thinning treatment of a patient with AMI and LVT was analyzed. Triple blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g, daily clopidogrel hydrogen sulfate at 75 mg, and dabigatran etexilate at 110 mg twice daily. After 15 d, the patient's LVT did not decrease but instead increased. Clinical pharmacists comprehensively analyzed the cases from the perspective of the patient's disease status and drug interaction. The drug regimen was reformulated for the patient, replacing dabigatran etexilate with warfarin, and was administered for six months. The clinical pharmacist provided the patient with professional and standardized pharmaceutical services. The patient's condition was discharged after meeting the international normalized ratio value (2-3) criteria. The patient fully complied with the follow-up, and the time in the therapeutic range was 78.57%, with no serious adverse effects during pharmaceutical monitoring. CONCLUSION: Warfarin proves to be an effective drug for patients with AMI complicated by LVT, and its blood-thinning course lasts for six months.

One-pot synthesis of 4-pyrimidone-2-thioether through base/acid-mediated condensation of S-alkylisothiourea and ß-ketoester.

4-Pyrimidone-2-thioethers can be useful synthetic precursors to densely functionalized pyrimidines, commonly encountered in bioactive molecules. A convenient one-pot access to 4-pyrimidone-2-thioethers is reported herein, which utilizes a sequential base- and acid-mediated condensation of alkylisothioureas with ß-ketoesters. Owing to mild reaction conditions, good to excellent functional group tolerance and yields are achieved. The utility of this approach is demonstrated by the synthesis of the crucial adagrasib intermediate on a 200 gram scale.

Astrocyte-derived Interleukin-31 causes poor prognosis in elderly patients with intracerebral hemorrhage.

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH.

Targeting the AKT-P53/CREB pathway with epicatechin for improved prognosis of traumatic brain injury.

AIMS: The aim of this study was to evaluate the effect of epicatechin, on neurological recovery and neuroinflammation after traumatic brain injury (TBI) to investigate its potential value in clinical practice. METHODS: TBI model was established in adult rats by CCI method. The effect of epicatechin was evaluated after intraperitoneal injection. Neurological recovery after TBI was assessed by Morris Water Maze, mNSS score, Rotarod test and Adhesive removal test. Protein and gene expression was assessed by Western blot, ELISA, PCR and immunofluorescence. Furthermore, the use of AKT pathway inhibitors blocked the therapeutic effects of epicatechin clarifying AKT-P53/CREB as a potential pathway for the effects of epicatechin. RESULTS: Administering epicatechin after TBI prevented neuronal death, reduced neuroinflammation, and promoted neurological function restoration in TBI rats. Network pharmacology study suggested that epicatechin may exert its therapeutic benefits through the AKT-P53/CREB pathway CONCLUSION: These results indicate that epicatechin, a monomeric compound derived from tea polyphenols, possesses potent antioxidant and anti-inflammatory properties after TBI. The mechanism may be related to the regulation of the AKT-P53/CREB signal pathway.

A novel long noncoding RNA (lncRNA), LINC02657(LASTR), is a prognostic biomarker associated with immune infiltrates of lung adenocarcinoma based on unsupervised cluster analysis.

Non-small cell lung cancer (NSCLC) has long been the deadliest malignancy worldwide, with adenocarcinoma (AD) being the most common pathological subtype. Here we focused on the value of LASTR in LUAD. Using expression analysis, enrichment analysis, immune cell infraction analysis, we found that the expression level of LASTR was significantly increased in LUAD tissue. Meanwhile, LASTR was significantly associated with differential infiltration of various immune cells. Kaplan-Meier survival analysis showed that LUAD related with a poor prognosis in terms of OS, PFI, and DSS compared with high-expression LASTR. The enrichment analysis showed that LASTR is related to the pathays like PI3K-AKT signaling pathway. Thus, the present findings could be helpful in a better understand of LASTR in LUAD. RT-PCR was used to verify the high expression of LASTR in LUAD tissues, and the apoptosis of LUAD cell lines was promoted by CCK8 and Transwell experiments to verify the ability of LASTR to promote the migration and invasion of lung cancer cells in vitro.

Myricetin suppresses traumatic brain injury-induced inflammatory response via EGFR/AKT/STAT pathway.

Traumatic brain injury (TBI) is a common disease in neurosurgery with a high fatality and disability rate which imposes a huge burden on society and patient's family. Inhibition of neuroinflammation caused by microglia activation is a reasonable strategy to promote neurological recovery after TBI. Myricetin is a natural flavonoid that has shown good therapeutic effects in a variety of neurological disease models, but its therapeutic effect on TBI is not clear. We demonstrated that intraperitoneal injection of appropriate doses of myricetin significantly improved recovery of neurological function after TBI in Sprague Dawley rats and inhibited excessive inflammatory responses around the lesion site. Myricetin dramatically reduced the expression of toxic microglia markers generated by TBI and LPS, according to the outcomes of in vivo and in vitro tests. In particular, the expression of inducible nitric oxide synthase, cyclooxygenase 2, and some pro-inflammatory cytokines was reduced, which protected learning and memory functions in TBI rats. Through network pharmacological analysis, we found that myricetin may inhibit microglia hyperactivation through the EGFR-AKT/STAT pathway. These findings imply that myricetin is a promising treatment option for the management of neuroinflammation following TBI.

GAMMA challenge: Glaucoma grAding from Multi-Modality imAges.

Glaucoma is a chronic neuro-degenerative condition that is one of the world's leading causes of irreversible but preventable blindness. The blindness is generally caused by the lack of timely detection and treatment. Early screening is thus essential for early treatment to preserve vision and maintain life quality. Colour fundus photography and Optical Coherence Tomography (OCT) are the two most cost-effective tools for glaucoma screening. Both imaging modalities have prominent biomarkers to indicate glaucoma suspects, such as the vertical cup-to-disc ratio (vCDR) on fundus images and retinal nerve fiber layer (RNFL) thickness on OCT volume. In clinical practice, it is often recommended to take both of the screenings for a more accurate and reliable diagnosis. However, although numerous algorithms are proposed based on fundus images or OCT volumes for the automated glaucoma detection, there are few methods that leverage both of the modalities to achieve the target. To fulfil the research gap, we set up the Glaucoma grAding from Multi-Modality imAges (GAMMA) Challenge to encourage the development of fundus & OCT-based glaucoma grading. The primary task of the challenge is to grade glaucoma from both the 2D fundus images and 3D OCT scanning volumes. As part of GAMMA, we have publicly released a glaucoma annotated dataset with both 2D fundus colour photography and 3D OCT volumes, which is the first multi-modality dataset for machine learning based glaucoma grading. In addition, an evaluation framework is also established to evaluate the performance of the submitted methods. During the challenge, 1272 results were submitted, and finally, ten best performing teams were selected for the final stage. We analyse their results and summarize their methods in the paper. Since all the teams submitted their source code in the challenge, we conducted a detailed ablation study to verify the effectiveness of the particular modules proposed. Finally, we identify the proposed techniques and strategies that could be of practical value for the clinical diagnosis of glaucoma. As the first in-depth study of fundus & OCT multi-modality glaucoma grading, we believe the GAMMA Challenge will serve as an essential guideline and benchmark for future research.

A Multilayered Magnetoelectric Transmitter with Suppressed Nonlinearity for Portable VLF Communication.

Acoustically actuated magnetoelectric (ME) antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency communications. However, the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME antenna. In this work, we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter (ME-MLTx) design. With a driving voltage of 50 Vpp at the resonance frequency of 21.2 kHz, a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single ME-MLTx. In addition, ME-MLTx performs a decreased mechanical quality factor (Q m) less than 40.65, and, thus, a broadened bandwidth of 500 Hz is generated. Finally, a communication link transmitting binary American Standard Code for Information Interchange-coded message is built, which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment noise. The communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field receiver. The obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications.

Experimental Study of the Shear Performance of Combined Concrete-ECC Beams without Web Reinforcement.

BACKGROUND: Shear damage of beams is typically brittle damage that is significantly more detrimental than flexural damage. PURPOSE: Based on the super-high toughness and good crack control ability of engineered cementitious composites (ECC), the shear performance of concrete-ECC beams was investigated by replacing a portion of the concrete in the tensile zone of reinforced concrete beams with ECC and employing high-strength reinforcing bars to design concrete-ECC beams. The purpose of this investigation is to elucidate and clarify the shear performance of concrete-ECC beams. METHODOLOGY/APPROACH: Experimental and FE analyses were conducted on the shear performance of 36 webless reinforced concrete-ECC composite beams with varied concrete strengths, shear-to-span ratios, ECC thicknesses, and interfacial treatments between the layers. RESULTS: The results indicate that the effect of the shear-to-span ratio is greater, the effect of the form of interface treatment is smaller, the effect is weakened after the ECC thickness is greater than 70 mm (i.e., the ratio of the replacement height to section height is approximately 0.35), the shear resistance is reduced when the hoop rate is greater, and the best shear resistance is obtained when the ECC 70 mm thickness and the hoop rate of 0.29% are used together. CONCLUSIONS: This study can serve as a technical reference for enhancing the problems of low durability and inadequate fracture control performance of RC beams in shear and as a guide for structural design research.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Thermally stable threshold selector based on CuAg alloy for energy-efficient memory and neuromorphic computing applications.

As a promising candidate for high-density data storage and neuromorphic computing, cross-point memory arrays provide a platform to overcome the von Neumann bottleneck and accelerate neural network computation. In order to suppress the sneak-path current problem that limits their scalability and read accuracy, a two-terminal selector can be integrated at each cross-point to form the one-selector-one-memristor (1S1R) stack. In this work, we demonstrate a CuAg alloy-based, thermally stable and electroforming-free selector device with tunable threshold voltage and over 7 orders of magnitude ON/OFF ratio. A vertically stacked 64 × 64 1S1R cross-point array is further implemented by integrating the selector with SiO2-based memristors. The 1S1R devices exhibit extremely low leakage currents and proper switching characteristics, which are suitable for both storage class memory and synaptic weight storage. Finally, a selector-based leaky integrate-and-fire neuron is designed and experimentally implemented, which expands the application prospect of CuAg alloy selectors from synapses to neurons.

Late Elongated Hypocotyl Positively Regulates Salt Stress Tolerance in Medicago truncatula.

Abiotic stress, such as drought, osmotic, and salinity stresses, seriously affects plant growth and crop production. Studying stress-resistant genes that enhance plant stress tolerance is an efficient way to facilitate the breeding of crop species with high stress tolerance. In this study, we reported that the core circadian clock component, the LATE ELONGATED HYPOCOTYL (LHY) orthologue MtLHY, plays a positive role in salt stress response in Medicago truncatula. The expression of MtLHY was induced by salt stress, and loss-of-function mutants of MtLHY were shown to be hypersensitive to salt treatment. However, overexpression of MtLHY improved salt stress tolerance through a higher accumulation of flavonoids. Consistently, exogenous flavonol application improved the salt stress tolerance in M. truncatula. Additionally, MtLHY was identified as a transcriptional activator of the flavonol synthase gene, MtFLS. Our findings revealed that MtLHY confers plant salt stress tolerance, at least by modulating the flavonoid biosynthesis pathway, which provides insight into salt stress tolerance that links the circadian clock with flavonoid biosynthesis.

Comparison of C-Arm-Free Oblique Lumbar Interbody Fusion L5-S1 (OLIF51) with Transforaminal Lumbar Interbody Fusion L5-S1 (TLIF51) for Adult Spinal Deformity.

Background and Objectives: Adult spinal deformity (ASD) surgery, L5-S1 lordosis is very important factor. The main objective of the research is to retrospectively compare symptomatic presentation and radiological presentation in the sequelae of oblique lumbar inter-body spinal fusion at L5-S1 (OLIF51) and transforaminal lumbar interbody fusion (TLIF) for ASD. Materials and Methods: We retrospectively evaluated 54 patients who underwent corrective spinal fusion for ASD between October 2019 and January 2021. Thirteen patients underwent OLIF51 (average 74.6 years old, group O) and 41 patients underwent TLIF51 (average 70.5 years old, group T). Mean follow-up period was 23.9 months for group O and 28.9 months for group T, ranging from 12 to 43 months. Clinical and radiographic outcomes are assessed using values including visual analogue scale (VAS) for back pain and Oswestry disability index (ODI). Radiographic evaluation was also collected preoperatively and at 6, 12, and 24 months postoperatively. Results: Surgical time in group O was less than that in group T (356 min vs. 492 min, p = 0.003). However, intraoperative blood loss of both groups were not significantly different (1016 mL vs. 1252 mL, p = 0.274). Changes in VAS and ODI were similar in both groups. L5-S1 angle gain and L5-S1 height gain in group O were significantly better than those of group T (9.4° vs. 1.6°, p = 0.0001, 4.2 mm vs. 0.8 mm, p = 0.0002). Conclusions: Clinical outcomes were not significantly different in both groups, but surgical time in OLIF51 was significantly less than that in TLIF51. The radiographic outcomes showed that OLIF51 created more L5-S1 lordosis and L5-S1 disc height compared with TLIF 51.

Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway.

Chronic pain has attracted wide interest because it is a major obstacle affecting the quality of life. Consequently, safe, efficient, and low-addictive drugs are highly desirable. Nanoparticles (NPs) with robust anti-oxidative stress and anti-inflammatory properties possess therapeutic possibilities for inflammatory pain. Herein, a bioactive zeolitic imidazolate framework (ZIF)-8-capped superoxide dismutase (SOD) and Fe3 O4 NPs (SOD&Fe3 O4 @ZIF-8, SFZ) is developed to achieve enhanced catalytic, antioxidative activities, and inflammatory environment selectivity, ultimately improving analgesic efficacy. SFZ NPs reduce tert-butyl hydroperoxide (t-BOOH)-induced reactive oxygen species (ROS) overproduction, thereby depressing the oxidative stress and inhibiting the lipopolysaccharide (LPS)-induced inflammatory response in microglia. After intrathecal injection, SFZ NPs efficiently accumulate at the lumbar enlargement of the spinal cord and significantly relieve complete Freund's adjuvant (CFA)-induced inflammatory pain in mice. Moreover, the detailed mechanism of inflammatory pain therapy via SFZ NPs is further studied, where SFZ NPs inhibit the activation of the mitogen-activated protein kinase (MAPK)/p-65 signaling pathway, leading to reductions in phosphorylated protein levels (p-65, p-ERK, p-JNK, and p-p38) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-1ß), thereby preventing microglia and astrocyte activation for acesodyne. This study provides a new cascade nanoenzyme for antioxidant treatments and explores its potential applications as non-opioid analgesics.