LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway.

Background: Corneal neovascularization (CNV) is a sight-threatening condition that necessitates epigenetic control. The role of lysine-specific demethylase 1 (LSD1) in CNV remains unclear, despite its established significance in tumor angiogenesis regulation. Methods: An alkali burn-induced CNV mouse model was used in vivo. The effects of LSD1 inhibitor tranylcypromine hydrochloride (TCP) were examined through slit lamp, histological staining, and immunofluorescence. The expression of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed in corneal tissues. Oxidative stress and ferrous ion expression during CNV were determined using 4-HNE, GPX4, and FerroOrange staining. In vitro, a hypoxia-reoxygenation (H/R) model was established using human umbilical vein endothelial cells (HUVECs) to study LSD1 or hypoxia-inducible factor (HIF-1α) knockdown and lentiviral overexpression of HIF-1α. The effects on HUVECs migration, invasion, and angiogenesis were evaluated through cell scratching assay, transwell migration assay and tube formation assay. The role of ferroptosis was investigated using ROS staining, FerroOrange staining, and key ferroptosis proteins. Further, The JAK2/STAT3 pathway's involvement in CNV regulation was explored through in vivo experiments with subconjunctival injection of AG490. Results: The results showed a substantial correlation between corneal damage and LSD1 levels. In addition, HIF-1α expression was also elevated after alkali burns, and subconjunctival injection of TCP reduced corneal inflammation and neovascularization. Corneal alkali burns increased ROS levels and reduced antioxidative stress indicators, accompanied by elevated ferrous ion levels, which were reversed by TCP injection. In vitro, TCP or siRNAs inhibited H/R-induced ferroptosis and angiogenesis in HUVECs by affecting specific protein expressions and MDA, SOD, and GSH levels. HIF-1α levels, associated with ROS production, ferroptosis, and angiogenesis, increased during H/R, but were reversed by TCP or siRNA administration. HIF-1α overexpression counteracted the effects of LSD1 inhibition. Additionally, AG490 injection effectively reduced HIF-1α and VEGFA expression in the CNV model. Discussion: These findings suggest that LSD1 inhibition via the HIF-1α-driven pathway prevents angiogenesis, oxidative stress, and ferroptosis in corneal alkali burn-induced CNV, highlighting LSD1 as a potential therapeutic target.

Longer-term Effect of Physical Activity Intervention on Sleep Quality: A Secondary Analysis of Cluster Randomized Controlled Trial.

STUDY OBJECTIVES: To examine the longer-term effect of physical activity (PA) intervention on sleep quality and whether the effect was heterogeneous between daytime nappers and non-nappers. METHODS: This study was a secondary analysis of a cluster randomized controlled trial in China. Eight villages were randomized 1:1 to intervention or control group. The intervention group received an 8-week PA intervention, while the control group did not. The primary outcome of this study was the change in the Pittsburgh Sleep Quality Index (PSQI) global score at 24 months. RESULTS: The 511 participants had a mean age of 70.94 years (SD 5.73) and 55.6% were female. The intervention showed improvements in the PSQI global score at 8 weeks (adjusted mean difference -1.05; P=0.002), and the effect diminished at 24 months (-0.64; P=0.06). There were statistically significant improvements in the PSQI global score for daytime nappers, but not for non-nappers at 8 weeks (adjusted mean difference -0.98; P=0.01 vs -1.27; P=0.05), 12 months (-0.86; P=0.03 vs -0.84; P=0.21), and 24 months (-0.80; P=0.04 vs -0.14; P=0.84), although these improvements were below the minimum detectible level of the PSQI which is 1 point. CONCLUSION: The 8-week PA intervention was effective in improving sleep quality, while the effect was diminished and below the minimum detectible level of the PSQI which is 1 point after 24 months. The effect of PA intervention on sleep quality was more pronounced in daytime nappers. Additional interventions (e.g., focusing on multiple behavioral interventions such as PA and healthy diet) are needed to maintain the beneficial effect of PA on sleep quality in the general older populations. Further research is required to confirm the mechanisms of the effect of napping and develop tailored interventions.

Caffeic acid inhibits the tumorigenicity of triple-negative breast cancer cells through the FOXO1/FIS pathway.

Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.

The relationship between mentally active sedentary behavior and cognitive function across different educational levels.

INTRODUCTION: How education affects the relationship between sedentary behavior and cognitive function remains unclear. The aim of this study was to investigate the relationship between mentally active sedentary behavior and cognitive function in rural older Chinese across different levels of education. METHODS: Data from 517 participants aged 60 years and older in rural China at baseline, 4 weeks, 8 weeks, 6 months, 12 months, and 24 months were analyzed. Univariate analysis was carried out using descriptive statistical techniques and bivariate analysis was performed using Linear mixed effects models. RESULTS: Total mentally active sedentary behavior time and playing cards/mahjong time were significantly associated with global cognition (0.27 points (95% CI, 0.15 to 0.39), P＜0.001; 0.30 points (95% CI, 0.18 to 0.41), P＜0.001, respectively), the attention dimension (0.08 points (95% CI, 0.02 to 0.14), P = 0.005; 0.10 points (95% CI, 0.04 to 0.16), P = 0.001, respectively), and the memory dimension (0.18 points (95% CI, 0.05 to 0.31), P < 0.001; 0.19 points (95% CI, 0.13 to 0.25), P＜0.001, respectively). Such associations were more pronounced in illiterate participants. CONCLUSION: Our study suggested a positive association between mentally active sedentary behavior and cognitive function, with the association being more pronounced among illiterate older adults compared to the relatively well-educated. Future cognitive interventions should focus more on mentally active behavior. In addition, education-specific intervention strategy may be considered in cognitive interventions.

Waldenström macroglobulinemia presenting as bilateral bloody pleural effusion: A case report.

RATIONALE: Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has many causes, such as infection, tumor invasion of the pleura, and rupture of the thoracic duct or its branches. Patients with WM presenting to the respiratory department with chest tightness and shortness of breath need more differential diagnosis by respiratory physicians, which is helpful for effective treatment. Herein, we present a case of MV diagnosis in a patient with bilateral bloody pleural effusion. PATIENT CONCERN: Our patient is a 59-year-old man with WM presenting as having bilateral bloody pleural effusion. INTERVENTIONS: The patient was treated with pleural effusion drainage. After confirming the diagnosis, the patient was treated with rituximab, cyclophosphamide, and dexamethasone. OUTCOMES: Following these treatments, the patient's symptoms improved, and ultrasound showed a decrease in pleural effusion. LESSONS: Despite its favorable prognosis, the cause of pleural effusion in a patient with WM can be challenging to diagnose. The cause of pleural effusion should be considered a differential diagnosis when diagnosing patients diagnosed with WM.

Multicomponent supervised tele-rehabilitation versus home-based self-rehabilitation management after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial.

INTRODUCTION: Our study aims to assess the effectiveness of multicomponent supervised tele-rehabilitation compared to home-based self-rehabilitation management in patients following anterior cruciate ligament reconstruction (ACLR). METHODS: The current study is designed as a single-center, single-blinded, randomized controlled, two-arm trial. Participants will be randomized and allocated at a 1:1 ratio into either a multicomponent supervised tele-rehabilitation group or a home-based self-rehabilitation group. All participants receive uniform preoperative education through the HJT software. Participants in the intervention group undergo multicomponent supervised tele-rehabilitation, while those in the control group follow a home-based self-rehabilitation program. All the participants were assessed and measured for the included outcomes at the outpatient clinic before the procedure, and in 2, 4, 8, 12, and 24 weeks after ACLR by two assessors. The primary outcome was the percentage of patients who achieve a satisfactory active ROM at the 12 weeks following the ACLR. The satisfactory active ROM was also collected at 2, 4, 8, and 24 weeks after ACLR. The secondary outcomes were active and passive range of motion (ROM), pain, muscle strength, and function results. REGISTRATION DETAILS: Ethical approval has been obtained from the West China Hospital Ethics Committee (approval number 2023-1929, December 2023). The trial has been registered on ClinicalTrials.gov (registration number NCT06232824, January 2024).

What are the differences in paraspinal muscle morphometry among degenerative spondylolisthesis patients, isthmic spondylolisthesis patients, and healthy individuals? A propensity score matching analysis.

PURPOSE: To compare the morphometry of paraspinal muscles in patients with degenerative spondylolisthesis (DS), isthmic spondylolisthesis (IS), and healthy individuals. METHODS: Thirty-seven pairs of DS patients were selected using propensity score matching with IS patients, while 37 healthy individuals matched for age, sex, and BMI were selected as controls. The relative cross-sectional area (rCSA), and relative functional cross-sectional area (rfCSA) of paraspinal muscles were measured, and the degree of fatty infiltration (FI) was calculated. Based on occupational differences, the patients were also divided into worker and farmer groups, and the same measurements were taken on them. RESULTS: At the L3/L4 level, the multifidus (MF) FI was greater in the DS and IS groups than in the control group, the erector spinae (ES) rfCSA was higher in the IS group than in the DS and control groups. At the L4/L5 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS and control groups. At the L5/S1 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS group. At the L3/L4, L4/L5 level, MF rfCSA were higher in the worker group than in the farmer group (p < 0.05). CONCLUSION: The morphological changes in paraspinal muscles in patients with DS were dominated by selective atrophy of the MF, while in patients with IS, the morphological changes in paraspinal muscle showed selective atrophy of the MF accompanied by compensatory hypertrophy of the ES. The surgeon should consider the morphological differences in paraspinal muscle between different types of lumbar spondylolisthesis when establishing the appropriate surgical program.

A ß-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer.

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.

Inhibiting PRMT1 protects against CoNV by regulating macrophages through the FGF2/PI3K/Akt pathway.

Corneal neovascularization (CoNV) is predominantly initiated by inflammatory processes, resulting in aberrant vascular proliferation and consequent visual impairment. Existing therapeutic interventions for CoNV demonstrate limited efficacy and potential for adverse reactions. Protein arginine methyltransferase 1 (PRMT1) is associated with the regulation of inflammation and M2 macrophage polarization. Nevertheless, the precise mechanism by which PRMT1 operates in CoNV remains uncertain. This study explored the impact of PRMT1 inhibition in a murine model of CoNV induced by alkali burn. Our findings indicated a direct relationship between PRMT1 levels and corneal damage. Moreover, our observations indicated an increase in fibroblast growth factor 2 (FGF2) expression in CoNV, which was reduced after treatment with a PRMT1 inhibitor. The inhibition of PRMT1 alleviated both corneal injury and CoNV, as evidenced by decreased corneal opacity and neovascularization. Immunofluorescence analysis and evaluation of inflammatory factor expression demonstrated that PRMT1 inhibition attenuated M2 macrophage polarization, a phenomenon that was reversed by the administration of recombinant FGF2 protein. These results were confirmed through experimentation on Human Umbilical Vein Endothelial Cells (HUVECs) and Mouse leukemia cells of monocyte macrophage cells (RAW264.7). Furthermore, it was established that FGF2 played a role in PI3K/Akt signal transduction, a critical regulatory pathway for M2 macrophage polarization. Importantly, the activity of this pathway was found to be suppressed by PRMT1 inhibitors. Mechanistically, PRMT1 was shown to promote M2 macrophage polarization, thereby contributing to CoNV, through the FGF2/PI3K/Akt pathway. Therefore, targeting PRMT1 may offer a promising therapeutic approach.

Correlation between omega-3 intake and the incidence of diabetic retinopathy based on NHANES from 2005 to 2008.

AIMS: To identify correlations between omega-3 intake and incidence of diabetic retinopathy (DR). METHODS: This was a cross-sectional study using data from participants over age 40 in the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Metrics included participants' intake of omega-3 fatty acids, specifically three types of representative polyunsaturated fatty acids, DR prevalence, and demographic characteristics. Multiple logistic regression models were used to assess the relationship between omega-3 intake and DR. RESULTS: Of the 1243 participants included in this study, omega-3 intake was lower in patients with DR relative to those without DR. Of the three polyunsaturated fatty acids within the omega-3 fatty acid family that we focused on, participants without DR consumed more docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) than those with DR. In contrast, there was no significant difference in the intake of eicosapentaenoic acid (EPA). Higher omega-3 intake was associated with a decreased risk of DR. In a crude model, the odds ratio (OR) was 0.548 (95% CI 0.315, 0.951; p = 0.033). In the fully adjusted model of omega-3 (model II), the adjusted OR was 0.525 (95% CI 0.306, 0.901; p = 0.021). DPA and DHA were also associated with a decreased risk of DR. In the full adjustment model (model II) of DPA and DHA, the adjusted ORs were 0.0002 (95% CI 0.000, 0.166; p = 0.014) and 0.293 (95% CI 0.105, 0.819; p = 0.020). Subgroup analysis showed that the protective effect of omega-3 against DR was more significant in younger patients (p value = 0.015). CONCLUSIONS: In this cross-sectional study of the U.S. general population, we found that increased intake of omega-3 and its components, specifically DPA and DHA were negatively associated with DR incidence. This suggests that omega-3 may be a potential protective factor for DR and may help to prevent or delay the onset and progression of DR.

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway.

BACKGROUND: The treatment of spinal cord injury (SCI) has always been a significant research focus of clinical neuroscience, with inhibition of microglia-mediated neuro-inflammation as well as oxidative stress key to successful SCI patient treatment. Caffeic acid phenethyl ester (CAPE), a compound extracted from propolis, has both anti-inflammatory and anti-oxidative effects, but its SCI therapeutic effects have rarely been reported. METHODS: We constructed a mouse spinal cord contusion model and administered CAPE intraperitoneally for 7 consecutive days after injury, and methylprednisolone (MP) was used as a positive control. Hematoxylin-eosin, Nissl, and Luxol Fast Blue staining were used to assess the effect of CAPE on the structures of nervous tissue after SCI. Basso Mouse Scale scores and footprint analysis were used to explore the effect of CAPE on the recovery of motor function by SCI mice. Western blot analysis and immunofluorescence staining assessed levels of inflammatory mediators and oxidative stress-related proteins both in vivo and in vitro after CAPE treatment. Further, reactive oxygen species (ROS) within the cytoplasm were detected using an ROS kit. Changes in mitochondrial membrane potential after CAPE treatment were detected with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide. Mechanistically, western blot analysis and immunofluorescence staining were used to examine the effect of CAPE on the SIRT1/PGC1α/DRP1 signaling pathway. RESULTS: CAPE-treated SCI mice showed less neuronal tissue loss, more neuronal survival, and reduced demyelination. Interestingly, SCI mice treated with CAPE showed better recovery of motor function. CAPE treatment reduced the expression of inflammatory and oxidative mediators, including iNOS, COX-2, TNF-α, IL-1ß, 1L-6, NOX-2, and NOX-4, as well as the positive control MP both in vitro and in vivo. In addition, molecular docking experiments showed that CAPE had a high affinity for SIRT1, and that CAPE treatment significantly activated SIRT1 and PGC1α, with down-regulation of DRP1. Further, CAPE treatment significantly reduced the level of ROS in cellular cytoplasm and increased the mitochondrial membrane potential, which improved normal mitochondrial function. After administering the SIRT1 inhibitor nicotinamide, the effect of CAPE on neuro-inflammation and oxidative stress was reversed.On the contrary, SIRT1 agonist SRT2183 further enhanced the anti-inflammatory and antioxidant effects of CAPE, indicating that the anti-inflammatory and anti-oxidative stress effects of CAPE after SCI were dependent on SIRT1. CONCLUSION: CAPE inhibits microglia-mediated neuro-inflammation and oxidative stress and supports mitochondrial function by regulating the SIRT1/PGC1α/DRP1 signaling pathway after SCI. These effects demonstrate that CAPE reduces nerve tissue damage. Therefore, CAPE is a potential drug for the treatment of SCI through production of anti-inflammatory and anti-oxidative stress effects.

Identifying Protein Phosphorylation Site-Disease Associations Based on Multi-Similarity Fusion and Negative Sample Selection by Convolutional Neural Network.

As one of the most important post-translational modifications (PTMs), protein phosphorylation plays a key role in a variety of biological processes. Many studies have shown that protein phosphorylation is associated with various human diseases. Therefore, identifying protein phosphorylation site-disease associations can help to elucidate the pathogenesis of disease and discover new drug targets. Networks of sequence similarity and Gaussian interaction profile kernel similarity were constructed for phosphorylation sites, as well as networks of disease semantic similarity, disease symptom similarity and Gaussian interaction profile kernel similarity were constructed for diseases. To effectively combine different phosphorylation sites and disease similarity information, random walk with restart algorithm was used to obtain the topology information of the network. Then, the diffusion component analysis method was utilized to obtain the comprehensive phosphorylation site similarity and disease similarity. Meanwhile, the reliable negative samples were screened based on the Euclidean distance method. Finally, a convolutional neural network (CNN) model was constructed to identify potential associations between phosphorylation sites and diseases. Based on tenfold cross-validation, the evaluation indicators were obtained including accuracy of 93.48%, specificity of 96.82%, sensitivity of 90.15%, precision of 96.62%, Matthew's correlation coefficient of 0.8719, area under the receiver operating characteristic curve of 0.9786 and area under the precision-recall curve of 0.9836. Additionally, most of the top 20 predicted disease-related phosphorylation sites (19/20 for Alzheimer's disease; 20/16 for neuroblastoma) were verified by literatures and databases. These results show that the proposed method has an outstanding prediction performance and a high practical value.

Spatiotemporal heterogeneity in meteorological and hydrological drought patterns and propagations influenced by climatic variability, LULC change, and human regulations.

This study aims to quantify meteorological-hydrological drought propagations and examine the potential impacts by climatic variability, LULC change (LULC), and human regulations. An integrated observation-modeling framework quantifies drought propagation intervals and assesses mechanisms influencing hydrological droughts. Meteorological droughts are characterized using the Standardized Precipitation Evapotranspiration Index (SPEI), and hydrological droughts are assessed through the Standardized Streamflow Index (SSI) across diverse climatic zones. Cross-correlation analysis between SPEI and SSI time series identifies the lag time associated with the highest correlation as the drought propagation interval. Mechanisms are investigated via a coupled empirical-process modeling framework incorporating the Soil and Water Assessment Tool (SWAT). Discrepancies between simulated and observed SSI time series help quantify the extent of human regulation impacts on hydrological drought characteristics and propagation. The Yellow River Basin (YRB), divided into six subzones based on climate characteristics, is selected as the case study. Key findings include: (1) Meteorological droughts were extremely severe across most YRB during the 1990s, while the 2000s showed some mitigation primarily due to precipitation increases. (2) Hydrological droughts and propagation times from meteorology to hydrology demonstrated substantial spatiotemporal variability. In general, summer propagation times were shorter than other seasons. (3) Propagation times were shorter in arid regions with cropland or built-up land cover versus grassland and woodland, while the reverse held for humid regions. (4) Human regulations prolonged propagation times, likely due to reservoir regulations designed to overcome water deficits. While the YRB is the focus of this paper, the methodologies and findings are applicable to other regions worldwide to enhance drought forecasting and water resource management. In various hydrological and climatic contexts worldwide.

Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. / ç”µé’ˆå¯¹ç³–å°¿ç— è®¤çŸ¥åŠŸèƒ½éšœç¢å¤§é¼ PI3K/Akt/CREBä¿¡å·é€šè·¯å’Œæµ·é©¬ç¥žç»å ƒå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. METHODS: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. RESULTS: Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). CONCLUSIONS: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

A real-time augmented reality system integrated with artificial intelligence for skin tumor surgery: experimental study and case series.

BACKGROUND: Skin tumors affect many people worldwide, and surgery is the first treatment choice. Achieving precise preoperative planning and navigation of intraoperative sampling remains a problem and is excessively reliant on the experience of surgeons, especially for Mohs surgery for malignant tumors. MATERIALS AND METHODS: To achieve precise preoperative planning and navigation of intraoperative sampling, we developed a real-time augmented reality (AR) surgical system integrated with artificial intelligence (AI) to enhance three functions: AI-assisted tumor boundary segmentation, surgical margin design, and navigation in intraoperative tissue sampling. Non-randomized controlled trials were conducted on manikin, tumor-simulated rabbits, and human volunteers in Hunan Engineering Research Center of Skin Health and Disease Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation was 0.9556 and 0.9548, respectively, and the average AR navigation mapping error was 0.644 mm. The proposed surgical system was applied in 106 skin tumor surgeries, including intraoperative navigation of sampling in 16 Mohs surgery cases. Surgeons who have used this system highly recognize it. CONCLUSIONS: The surgical system highlighted the potential to achieve accurate treatment of skin tumors and to fill the gap in global research on skin tumor surgery systems.

Hispolon inhibits neuronal ferroptosis by promoting the expression of Nrf-2.

Research has shown that neuronal ferroptosis is associated with various central nervous system diseases, including Parkinson's disease, acute brain injury, and spinal cord injury. Inhibiting neuronal ferroptosis can greatly alleviate the progression of these diseases. However, there is currently a lack of effective drugs to inhibit neuronal ferroptosis. In this study, we pretreated neuronal cells with Hispolon and subsequently induced a neuronal ferroptosis model using Erastin. We further assessed the changes in the protein expression levels of SLC7A11, GPX4, ACSL4, Nrf-2, and HO-1 using Western blot and immunofluorescence techniques. Additionally, we measured the intracellular levels of Fe2+, GSH, and MDA using relevant assay kits. The research findings revealed that after Hispolon treatment, the expression of the pro-ferroptosis protein ACSL4 decreased, while the expression of the ferroptosis-regulating proteins GPX4 and SLC7A11 increased. Moreover, the use of an Nrf-2-specific inhibitor was able to reverse the effects of Hispolon as mentioned above. In this study, we discovered that Hispolon can promote the expression of Nrf-2 and inhibit the occurrence of neuronal ferroptosis induced by Erastin.