The impact of the P2X7 receptor on the tumor immune microenvironment and its effects on tumor progression.

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.

ZmSMR10 Increases the Level of Endoreplication of Plants through Its Interactions with ZmPCNA2 and ZmCSN5B.

As a plant-specific endoreplication regulator, the SIAMESE-RELATED (SMR) family (a cyclin-dependent kinase inhibitor) plays an important role in plant growth and development and resistance to stress. Although the genes of the maize (Zea mays) SMR family have been studied extensively, the ZmSMR10 (Zm00001eb231280) gene has not been reported. In this study, the function of this gene was characterized by overexpression and silencing. Compared with the control, the transgenic plants exhibited the phenotypes of early maturation, dwarfing, and drought resistance. Expression of the protein in prokaryotes demonstrates that ZmSMR10 is a small protein, and the results of subcellular localization suggest that it travels functionally in the nucleus. Unlike ZmSMR4, yeast two-hybrid experiments demonstrated that ZmSMR10 does not interact strongly with with some cell cycle protein-dependent protein kinase (CDK) family members ZmCDKA;1/ZmCDKA;3/ZmCDKB1;1. Instead, it interacts strongly with ZmPCNA2 and ZmCSN5B. Based on these results, we concluded that ZmSMR10 is involved in the regulation of endoreplication through the interaction of ZmPCNA2 and ZmCSN5B. These findings provide a theoretical basis to understand the mechanism of the regulation of endoreplication and improve the yield of maize through the use of molecular techniques.

Photoinduced Site-Selective Aryl C-H Borylation with Electron-Donor-Acceptor Complex Derived from B2Pin2 and Isoquinoline.

Due to boron's metalloid properties, aromatic boron reagents are prevalent synthetic intermediates. The direct borylation of aryl C-H bonds for producing aromatic boron compounds offers an appealing, one-step solution. Despite significant advances in this field, achieving regioselective aryl C-H bond borylation using simple and readily available starting materials still remains a challenge. In this work, we attempted to enhance the reactivity of the electron-donor-acceptor (EDA) complex by selecting different bases to replace the organic base (NEt3) used in our previous research. To our delight, when using NH4HCO3 as the base, we have achieved a mild visible-light-mediated aromatic C-H bond borylation reaction with exceptional regioselectivity (rr > 40:1 to single isomers). Compared with our previous borylation methodologies, this protocol provides a more efficient and broader scope for aryl C-H bond borylation through the use of N-Bromosuccinimide. The protocol's good functional-group tolerance and excellent regioselectivity enable the functionalization of a variety of biologically relevant compounds and novel cascade transformations. Mechanistic experiments and theoretical calculations conducted in this study have indicated that, for certain arenes, the aryl C-H bond borylation might proceed through a new reaction mechanism, which involves the formation of a novel transient EDA complex.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

BACKGROUND AND OBJECTIVE: The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China. METHODS: Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect. RESULTS: Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1). CONCLUSION: Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

Interleukin-37b Suppressed ILC2s in Children with Allergic Rhinitis.

Background: Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods: We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results: We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years' SLIT, especially in the good response group. Conclusion: Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.

The positive feedback loop of furin and TGFß1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro.

Regulatory T cells (Tregs) can exert immunosuppressive activity. Furin can regulate Treg functions, hepatitis B virus (HBV) persistent infection, and hepatocellular carcinoma (HCC) development. However, it remains unknown whether furin can regulate the immune responses of Tregs to HBV and HCC cells. Here, coculture systems of HBV1.3P-HepG2.3P-HepG2 cells and Tregs transduced with or without lentiviral particles that could overexpress furin or knockdown furin/transforming growth factor ß1 (TGFß1) were established to investigate the regulatory relationship between furin and TGFß1 and the effect of furin/TGFß1 on Treg activity. Also, the effects of furin overexpression or furin/TGFß1 knockdown in Tregs on the immunological activity of effector T cells (Teffs)/cytotoxic T lymphocytes (CTLs) and HBV replication/expression were explored in the coculture system of Teff/CTL, Treg, and HBV1.3P-HepG2 cells. Our results showed that furin expression and TGFß1 secretion were notably increased in Tregs, and Furin and TGFß1 formed a positive feedback loop to activate Tregs in the coculture system of Tregs and HBV1.3P-HepG2 cells. Furin or TGFß1 knockdown in Tregs promoted Teff cell proliferation, stimulated interleukin-2 and interferon-γ secretion, and inhibited HBV replication/gene expression in the coculture system of Teff, Treg, and HBV1.3P-HepG2 cells. Moreover, furin or TGFß1 depletion in Tregs enhanced the killing activity of CTLs against HBV1.3P-HepG2 cells and curbed HBV replication/gene expression in the coculture system of Tregs, CTLs, and HBV1.3P-HepG2 cells. In conclusion, the positive feedback loop of furin and TGFß1 enhanced the immune responses of Tregs to HCC cells and HBV in vitro.

Piezo1 Forms Specific, Functionally Important Interactions with Phosphoinositides and Cholesterol.

Touch, hearing, and blood pressure regulation require mechanically gated ion channels that convert mechanical stimuli into electrical currents. One such channel is Piezo1, which plays a key role in the transduction of mechanical stimuli in humans and is implicated in diseases, such as xerocytosis and lymphatic dysplasia. There is building evidence that suggests Piezo1 can be regulated by the membrane environment, with the activity of the channel determined by the local concentration of lipids, such as cholesterol and phosphoinositides. To better understand the interaction of Piezo1 with its environment, we conduct simulations of the protein in a complex mammalian bilayer containing more than 60 different lipid types together with electrophysiology and mutagenesis experiments. We find that the protein alters its local membrane composition, enriching specific lipids and forming essential binding sites for phosphoinositides and cholesterol that are functionally relevant and often related to Piezo1-mediated pathologies. We also identify a number of key structural connections between the propeller and pore domains located close to lipid-binding sites.

Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

Tumor-associated macrophage infiltration and prognosis in colorectal cancer: systematic review and meta-analysis.

BACKGROUND: Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined. OBJECTIVE: This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC. METHODS: Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status. RESULTS: A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68+ TAM subset correlated with better 5-year OS, while neither CD68+NOS2+ M1 subset nor CD163+ M2 subset was correlated with 5-year OS. Increased CD68+ TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS. CONCLUSIONS: High infiltration of CD68+ TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68+ TAM infiltration may be promising in CRC treatment.

[Study on Automatic Venipuncture Device and Control system].

According to clinical PICC(Peripherally Inserted Central Catheter) catheter surgery, this project introduces a new scheme for vein puncturing device and its controlling system. This device adopts ultrasonic image guided by the microcontroller, to achieve automatic venous catheterization. This kind of automatic vein puncture device adopts double stepping motors and screws as its transmission. One motor drives the needle and the hose to puncture into vein through skin. The other one drives the hose to specified location, then triggers withdrawal button and then the needle withdraws back into its cylinder. Several key points were set in the process of puncturing, the velocity period and the acceleration period can be preselected respectively. Moving distance and velocity of the needle in vein puncturing were setup automatically according to diameter and depth of the vein, achieving controlling puncturing and placing hose accurately.

PKCδ null mutations in a mouse model of osteoarthritis alter osteoarthritic pain independently of joint pathology by augmenting NGF/TrkA-induced axonal outgrowth.

OBJECTIVES: A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterised by cartilage degeneration and debilitating pain, is that the severity of joint pain does not strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase Cδ (PKCδ), a key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease. METHODS: OA was induced in 10-week-old PKCδ null (PKCδ-/-) and wild-type mice by destabilisation of the medial meniscus (DMM) followed by comprehensive examination of the histology, molecular pathways and knee-pain-related-behaviours in mice, and comparisons with human biopsies. RESULTS: In the DMM model, the loss of PKCδ expression prevented cartilage degeneration but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading enzymes in the joints of PKCδ-deficient DMM mice. Hyperalgesia was associated with stimulation of nerve growth factor (NGF) by fibroblast-like synovial cells and with increased synovial angiogenesis. Results from tissue specimens of patients with symptomatic OA strikingly resembled our findings from the OA animal model. In PKCδ null mice, increases in sensory neuron distribution in knee OA synovium and activation of the NGF-tropomyosin receptor kinase (TrkA) axis in innervating dorsal root ganglia were highly correlated with knee OA hyperalgesia. CONCLUSIONS: Increased distribution of synovial sensory neurons in the joints, and augmentation of NGF/TrkA signalling, causes OA hyperalgesia independently of cartilage preservation.

Short-term glycemic control is effective in reducing surgical site infection in diabetic rats.

BACKGROUND: Patients and animals with diabetes exhibit enhanced vulnerability to bacterial surgical infections. Despite multiple retrospective studies demonstrating the benefits associated with glycemic control in reducing bacterial infection after cardiac surgery, there are fewer guidelines on the use of glycemic control for noncardiac surgeries. In the current study, we investigated whether long-term (begun 2 weeks before surgery) or immediate (just before surgery) glycemic controls, continued postoperatively, can reduce surgical site infection in type 1 diabetic-induced rats. METHODS: Rats were injected with streptozotocin to induce type 1 diabetes. Four groups of animals underwent surgery and thigh muscle Staphylococcus aureus bacteria challenge (1 × 10 colony forming units) at the time of surgery. Group 1 diabetic rats received insulin treatment just before surgery and continued until the end of study (short-term glycemic control group). Group 2 diabetic rats received insulin treatment 2 weeks before surgery and continued until the end of study (long-term glycemic control). Group 3 diabetic rats received no insulin treatment (no glycemic control group). Group 4 nondiabetic rats served as a healthy control group. Rats were euthanized at 3 or 6 days after surgery. Blood glucose and muscle bacterial burden were measured at 3 or 6 days after surgery. RESULTS: Glycemic control was achieved in both long- and short-term insulin-treated diabetic rats. Compared with untreated diabetic rats, the bacterial burden in muscle was significantly lower in both groups of glycemic controlled diabetic rats at 3 (all P < 0.003) and 6 (all P < 0.0001) days after surgery. CONCLUSIONS: A short-term glycemic control regimen, initiated just before surgery and bacterial exposure, was as effective in reducing surgical site infection as a long-term glycemic control in type 1 diabetic rats. These data suggest that immediately implementing glycemic control in type 1 diabetic surgical patients before undergoing noncardiac surgery may decrease the risk of infection.

[The rescue effect of RANKL on zoledronate induced acid inhibition of osteoclastogenesis and gene expression of NF-kappaB p50 and c-Jun].

In this study, the rescue effect of receptor activator for nuclear factor-kappaB ligand (RANKL) on zoledronate acid (ZOL) induced inhibition of osteoclastogenesis and gene expression of NF-kappaB p50 and c-Jun was investigated. Mice calvarial osteoblasts (OBs) were harvested and co-cultured with RAW264.7 cells and the cells were divided into 4 groups and received treatment with ZOL and RANKL, either single or combined. The formation of multi-nucleated osteoclast (OC) was examined and gene expression of NF-kappaB p50 and c-Jun was detected. Group B (ZOL) showed least multi-nucleated OC and resorption lacunae among the 4 groups (P < 0.05 or P < 0.01) and it was followed by group C (ZOL+RANKL). Group D (RANKL) showed highest OC and resorption lacunae while it was similar to Group A (control) (P > 0.05). Gene expression of NF-kappaB p50 and c-Jun was the lowest in group B (P < 0.05 or P < 0.01) among the four groups and was significantly increased in group C when compared with group B (P < 0.05). Group A and D showed highest gene expression and they were similar to each other (P > 0.05). This study suggest that RANKL might partly rescue ZOL induced inhibition of osteoclastogenesis, and the effect of RANKL and ZOL on osteoclastogenesis may be mediated by NF-kappaB p50 and c-Jun.

Inhibitory Effect of Apolipoprotein A-I on Eosinophils in Allergic Rhinitis in vitro and in vivo.

Purpose: Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain. Methods: Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils. Results: Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines. Conclusion: Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies.

Apolipoprotein A-I inhibited group II innate lymphoid cell response mediated by microRNA-155 in allergic rhinitis.

Background: Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting TH2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized. Objective: We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism. Methods: The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo. Results: Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes ABCA1 expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. Apo-AI-/- mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI-/- mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI-treated mice. Conclusion: Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation.

The prognostic value of miR-21 and miR-155 in non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: miR-21 and miR-155 have been implicated in the prognosis of non-small-cell lung cancer, but the results are controversial. To resolve this issue, we performed a meta-analysis on miR-21 and miR-155 and  non-small-cell lung cancer prognosis and lymphoid metastasis. METHODS: Eligible data were extracted and the correlation between miR-21 and miR-155 and non-small-cell lung cancer survival was analyzed by calculating a pooled hazard ratio and sensitivity analysis. The heterogeneity was detected by Q statistic and I-squared statistic, and the publication bias was tested by funnel plots and Egger's test. RESULTS: Nineteen studies were included. High miR-21 level (hazard ratio = 2.00, 95% confidence interval = 1.38-2.89, P = 0.000 for heterogeneity test, I(2) = 84.9%) and high miR-155 level (hazard ratio = 1.65, 95% confidence interval = 1.11-2.44, P = 0.004 for heterogeneity test, I(2) = 68.3%) were significantly associated with worse non-small-cell lung cancer survival. Furthermore, a high miR-21 level was associated with an increased risk of lymphoid infiltration for non-small-cell lung cancer (odds ratio = 1.93; 95% confidence interval = 1.31-2.85). Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. CONCLUSIONS: This meta-analysis provides evidence that miR-21 and miR-155 are predicting factors for non-small-cell lung cancer prognosis and lymphoid infiltration.

Starch granular size and multi-scale structure determine population patterns in bivariate flow cytometry sorting.

Bivariate flow cytometry (FC) sorting with forward scatter (FSC) and side scatter (SSC) is a recently established novel technique to separate starch granules. However, the forming mechanism of starch FC-dependent population patterns (i.e. the number of subgroups (NS) and FSC/SSC-dependent distribution patterns) remain partly elusive. For this, the correlation of granular size and multi-scale structure of native starches and FC-dependent population patterns was investigated through employing a wide range of native starches originating from different species involving cereal-, pulse-, and tuber crops. Results showed NS was pertinent with particle size, amylose content (AC), amylopectin chains length distribution, lamellar structure, short-range ordered structure. The distinct NS was determined by impacts of native starch FSC / SSC-dependent distribution patterns. Specifically, starch granular size significantly correlated with both FSC and SSC-dependent distribution patterns. The proportion of chains with DP 6-12 was the intra-molecular decisive factor to influence short-range ordered structure, finally leading to FSC-dependent distribution patterns. By contrast, AC was another intra-molecular index to determine SSC-dependent distribution patterns through affecting lamellar structure and short-range ordered structure.

14, 15-EET alleviates neurological impairment through maintaining mitochondrial dynamics equilibrium via AMPK/SIRT1/FoxO1 signal pathways in mice with cerebral ischemia reperfusion.

AIM: To explore whether 14, 15-EET regulates mitochondrial dynamics to exert neuroprotective effects after cerebral ischemia-reperfusion and its underlying mechanisms. METHODS: The mouse middle cerebral artery occlusion reperfusion model was used to observe brain infarct volume and neuronal apoptosis by TTC staining and Tunel assay, modified neurological severity score to detect neurological impairment, HE staining and Nissl staining to observe neuron damage, western blot and immunofluorescence methods to detect the expression of mitochondrial dynamics-related proteins, transmission electron microscopy, and Golgi-Cox staining to detect mitochondrial morphology and neuronal dendritic spines. RESULTS: 14, 15-EET reduced the neuronal apoptosis and cerebral infarction volume induced by middle cerebral artery occlusion reperfusion (MCAO/R), inhibited the degradation of dendritic spines, maintained the structural integrity of neurons, and alleviated neurological impairment. Cerebral ischemia-reperfusion induces mitochondrial dynamics disorders, upregulates the expression of the mitochondrial division protein Fis 1, and inhibits the expression of mitochondrial fusion proteins MFN1, MFN2, and OPA1, while 14, 15-EET treatment reverses this process. Mechanistic studies have shown that 14, 15-EET promotes the phosphorylation of AMPK, upregulates the expression of SIRT1 and phosphorylation of FoxO1, thereby inhibiting mitochondrial division and promoting mitochondrial fusion, preserving mitochondrial dynamics, maintaining neuronal morphological and structural integrity, and alleviating neurological impairment induced by middle cerebral artery occlusion reperfusion. Compound C treatment diminishes the neuroprotective effect of 14, 15-EET following MCAO/R in mice. CONCLUSION: This study elucidates the novel neuroprotective mechanism of 14, 15-EET, providing a novel approach for the development of drugs based on mitochondrial dynamics.

Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis.

Background: Allergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. Methods: This retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months-1 year), the 2 years group (1-2 years), and the 3 years group (2-3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. Results: The total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. Conclusion: Our results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.