TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer.

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

[The Identification Idea of Antibodies Against Ku and Other High-Frequency Antigens].

OBJECTIVE: This study was aimed to provide ideas for identifying the antibodies to high-frequency antigens by analyzing a female case of high-frequency antigen antibody (anti-Ku) using serological and sequencing method. METHODS: The methods for identification of blood group, erythrocyte antigen, screening and identification of antibody were used to detect the blood type and antibody in the proband. The proband's serum and reagent screening cells treated with Sulfhydryl reagent were applied to judge the type and characteristics of this antibodies when reacted with the regaent screening cells or proband's serum respectively. Gene sequencing was used to determine the genotype of the proband's blood group. RESULTS: The proband's red blood cells were determined as O type RhD positive, whose serum showed strong positive reaction to antibody-screening cells and antibody identification cells with the same intensity in saline and IAT medium, however, the self-cells showed negative effect. The Direct Antihuman Globulin of proband's red blood cells also showed weak positive reaction, and the other blood types were CcEe, Jk(a+b-), P1-, Le(a-b -), Lu (a-b +), K-, k-, Kp(a-b-). Serum of the proband treated with 2-ME still react with three groups of screening cells in IAT medium. The reaction intensity of proband's serum was also unchanged with the cells modified with papain and bromelain, but showed negative effect when the cells were treated with sulfhydryl agents including DTT and 2-ME. Gene sequencing revealed that the KEL genotype of the patient was KEL*02N.24 . This patient had a rare K0 phenotype. CONCLUSION: The rare Kell-null blood group (also known as K0) were identified by serological and molecular tests in the proband who produced both IgG and IgM type of antibody to high-frequency antigen (anti-Ku). These two methods are of great significance in the identification of this rare blood group as well as the antibody to high frequency antigen.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Iodine(III)-Mediated Trifluoroacetylation of a C(sp2)-H or C(sp)-H Bond with Masked Trifluoroacyl Reagents.

A novel strategy for incorporating a trifluoroacetyl functionality into a range of structurally varied unsaturated bonds was developed by using PhI(OCOMe)2 as an oxidant with a masked trifluoroacyl reagent as a trifluoroacetyl radical precursor. The oxidative decarboxylation of the masked trifluoroacyl precursor followed by a tandem radical process provides versatile access to 5-exo-trig cyclization of N-arylacrylamides, direct C(sp2)-H trifluoroacetylation of quinolines, isoquinoline, 2H-indazole, and quinoxalin-2(1H)-ones, and C(sp)-H trifluoroacetylation of alkynes. This protocol is characterized by mild reaction conditions, operational simplicity, and broad functional group compatibility.

Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Intestinal microbiota and gene expression alterations in leopard coral grouper (Plectropomus leopardus) under enteritis.

Enteritis poses a significant threat to fish farming, characterized by symptoms of intestinal and hepatic inflammation, physiological dysfunction, and dysbiosis. Focused on the leopard coral grouper (Plectropomus leopardus) with an enteritis outbreak on a South China Sea farm, our prior scrutiny did not find any abnormalities in feeding or conventional water quality factors, nor were any specific pathogen infections related to enteritis identified. This study further elucidates their intestinal flora alterations, host responses, and their interactions to uncover the underlying pathogenetic mechanisms and facilitate effective prevention and management strategies. Enteritis-affected fish exhibited substantial differences in intestinal flora compared to control fish (P = 0.001). Notably, norank_f_Alcaligenaceae, which has a negative impact on fish health, predominated in enteritis-affected fish (91.76 %), while the probiotic genus Lactococcus dominated in controls (93.90 %). Additionally, certain genera with pathogenesis potentials like Achromobacter, Sphingomonas, and Streptococcus were more abundant in diseased fish, whereas Enterococcus and Clostridium_sensu_stricto with probiotic potentials were enriched in control fish. At the transcriptomic level, strong inflammatory responses, accompanied by impaired metabolic functions, tissue damage, and iron death signaling activation were observed in the intestines and liver during enteritis. Furthermore, correlation analysis highlighted that potential pathogen groups were positively associated with inflammation and tissue damage genes while presenting negatively correlated with metabolic function-related genes. In conclusion, dysbiosis in the intestinal microbiome, particularly an aberrantly high abundance of Alcaligenaceae with pathogenic potential may be the main trigger for this enteritis outbreak. Alcaligenaceae alongside Achromobacter, Sphingomonas, and Streptococcus emerged as biomarkers for enteritis, whereas some species of Lactococcus, Clostridium_sensu_stricto, and Enterococcus showed promise as probiotics to alleviate enteritis symptoms. These findings enhance our understanding of enteritis pathogenesis, highlight intestinal microbiota shifts in leopard coral grouper, and propose biomarkers for monitoring, probiotic selection, and enteritis management.

Structure and genome editing of type I-B CRISPR-Cas.

Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Their ability to cause long fragment deletions have led to increasing interests in eukaryotic genome editing. While the Cascade structures of all other six type I systems have been determined, the structure of the most evolutionarily conserved type I-B Cascade is still missing. Here, we present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation. Remarkably, a loop of Cas5 directly intercalated into the major groove of the PAM and facilitated PAM recognition. We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells.

Packaged structure optimization for enhanced light extraction efficiency and reduced thermal resistance of ultraviolet B LEDs.

Ultraviolet B light-emitting diodes (UVB LEDs) hold promise in medical and agricultural applications. The commonly used sapphire substrate for their epitaxy growth possesses a high refractive index and excellent UV light absorption characteristics. However, this high refractive index can induce total internal reflection (TIR) within the substrate, leading to decreased Light Extraction Efficiency (LEE) due to light absorption within the material. In this study, UVB LED chips were detached from the sub-mount substrate and directly affixed onto an aluminum nitride (AlN) substrate with superior heat dissipation using a eutectic process. This was undertaken to diminish packaged thermal resistance (PTR). Simultaneously, optimization of the UVB LED packaging structure was employed to alleviate LEE losses caused by the TIR phenomenon, with the overarching goal of enhancin external quantum efficiency (EQE). The final experimental findings suggest that optimal LEE is achieved with packaging dimensions, including a length (ELL) of 2 mm, a width (ELW) of 1.62 mm, and a height (ELH) of 0.52 mm. At an input current of 200 mA, the output power reaches 50 mW, resulting in an EQE of 6.3%. Furthermore, the packaged thermal resistance from the chip to the substrate surface can be reduced to 4.615 K/W.

Full-angle chip scale package of mini LEDs with a V-shape packaging structure.

The light distribution of light-emitting diodes (LEDs) generally resembles that of a Lambertian light source. When used as large-area light sources, the light distribution angle of LEDs must be modified through secondary optics design to achieve uniformity and minimize the number of light sources. However, secondary optical components pose several challenges such as demanding alignment accuracy, material aging, detachment, and lower reliability. Therefore, this paper proposes a primary optical design approach to achieve full-angle emission in LEDs without the need for lenses. The design employs a flip-chip as the light source and incorporates a V-shaped packaged structure, including a white wall layer, optical structure layers, and a V-shaped diffuse structure. With this design, the LEDs achieve full-angle emission without relying on lenses. Our experimental results demonstrated a peak intensity angle of 77.7°, a 20.3% decrease in the intensity of the central point ratio, and a full width at half maximum (FWHM) of the light distribution of 175.5°. This design is particularly suitable for thin, large-area, and flexible backlight light sources. Moreover, the absence of secondary optical components allows for a thinner light source module.

O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.

Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptotic cell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI.

Wide heart-shaped mini-LEDs without a second lens as a large area, ultra-high luminance, and flat light source.

In recent years, the demand for outdoor advertising and industrial display applications has been steadily increasing. Outdoor environments require higher brightness levels, thus requiring a reduction in the thermal resistance of the light source package. However, using secondary optical lenses to decrease the number of light sources is not a suitable solution because it may lead to the issue of lens detachment. Therefore, this paper proposes a packaging structure for wide heart-shaped angular light distribution mini-light emitting diodes (WHS mini-LEDs) with a primary optical design to enhance the light-emitting angle. The chips are directly bonded to an aluminum substrate using the metal eutectic process to minimize thermal resistance in the packaging. The experimental results indicated that the WHS mini-LED package had a total thermal resistance of 6.7 K/W. In a 55-inch backlight module (BLM), only 448 WHS mini-LEDs coupled with a quantum dot (QD) film and a brightness enhancement film (BEF) were required. Each lamp board was operated at 20.5 V and 5.5 A. The average luminance of the liquid crystal module (LCM) can reach 2234.2 cd/m2 with a uniformity of 90% and an NTSC value of 119.3%. This design offers a competitive advantage for outdoor advertising displays and industrial displays that require large areas, high brightness, and high color saturation.

Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

Submerged Culture of Edible and Medicinal Mushroom Mycelia and Their Applications in Food Products: A Review.

Edible mushrooms have rich nutrition (e.g., proteins, dietary fibers, polysaccharides) and they can be potential sources of important ingredients in food processing. However, the cultivation of mushroom fruiting bodies needs a relatively long time, and they can be easily polluted during the growth process. At the same time, a lot of labor and larger planting areas are also required. As we all know, submerged fermentation is a good way to produce edible mushroom mycelia with less environmental pollution and small footprint, which are also rich in nutrition and bioactive components that are used as dietary supplements or health care products in the food industry. Therefore, it can be considered that the replacement of edible mushroom fruiting bodies with edible mushroom mycelia produced through submerged fermentation has great application potential in food production. At present, most of the research about edible mushroom mycelia focuses on the production of bioactive metabolites in fermentation liquid, but there are few reports that concentrate on their applications in food. This paper reviews the research progress of submerged culture of edible mushroom mycelia and their applications in food products.

Synthesis and Selective Anticancer Activity Evaluation of 2-phenylacrylonitrile Derivatives as Tubulin Inhibitors.

OBJECTIVE: This study aimed at synthesizing 13 series of novel derivatives with 2-phenylacrylonitrile, evaluating antitumor activity both in vivo and in vitro, and obtaining novel tubulin inhibitors. METHOD: The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel condensation and the anti-proliferative activities were determined by MTT assay. The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration was performed using 24-well Boyden chambers. The proteins were detected by western blotting. in vitro kinetics of microtubule assembly was measured using ELISA kit for Human ß-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS) 2017 Client online tool. RESULTS: Among the derivatives, compound 1g2a possessed strong inhibitory activity against HCT116 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 7.8 nM) cells. Compound 1g2a exhibited better selective antiproliferative activities and specificities than all the positive control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound 1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit tubulin to exert anticancer effects. CONCLUSION: Compound 1g2a shows outstanding antitumor activity both in vivo and in vitro and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

Exosomes from Hypoxia-treated Mesenchymal Stem Cells: Promoting Neuroprotection in Ischemic Stroke Through miR-214-3p/PTEN Mechanism.

Stroke stands as the second leading cause of death globally, surpassed only by ischemic heart disease. It accounts for 9% of total worldwide deaths. Given the swiftly evolving landscape, medical professionals and researchers are devoting increased attention to identifying more effective and safer treatments. Recent years have witnessed a focus on exosomes derived from mesenchymal stem cells cultivated under hypoxic conditions, referred to as Hypo-Exo. These specialized exosomes contain an abundance of components that facilitate the restoration of ischemic tissue, surpassing the content found in normal exosomes. Despite advancements, the precise role of Hypo-Exo in cases of cerebral ischemia remains enigmatic. Therefore, this study was designed to shed light on the potential efficacy of Hypo-Exo in stroke treatment. Our investigations unveiled promising outcomes, as the administration of Hypo-Exo led to improved behavioral deficits and reduced infarct areas in mice affected by ischemic conditions. Notably, these positive effects were hindered when Hypo-Exo loaded with anti-miR-214-3p were introduced, implying that the neuroprotective attributes of Hypo-Exo are reliant on miR-214-3p. This conclusion was substantiated by the high levels of miR-214-3p detected within Hypo-Exo. Furthermore, our examination of the ischemic penumbra zone revealed a gradual and sustained escalation in PTEN expression, a phenomenon effectively countered by Hypo-Exo treatment. Collectively, our findings suggest the existence of a regulatory pathway centered on miR-214-3p within Hypo-Exo. This pathway exerts a downregulating influence on the PTEN/Akt signaling pathway, thereby contributing to the amelioration of neurological function subsequent to ischemia-reperfusion events.