HLA Alleles Associate with Insulin Autoimmune Syndrome.

In recent years, there have been hundreds of reports on insulin autoimmune syndrome (IAS) globally; however, fewer than a hundred patients have undergone genetic testing. Our objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302.

Overexpression of ZFP69B promotes hepatocellular carcinoma growth by upregulating the expression of TLX1 and TRAPPC9.

BACKGROUND: T-cell leukemia homeobox protein 1 (TLX1) has been revealed as a hub transcription factor in leukemia, while its function in hepatocellular carcinoma (HCC) has not been well described. Here, we investigated the regulation and function of TLX1 in HCC. METHODS: TLX1 and its possible upstream and downstream molecules in HCC were identified using bioinformatics tools, which were then verified by RT-qPCR assay. CCK-8, wound healing, and Transwell invasion assays were performed to detect the effects of TLX1 knockdown on HCC cells. The interactions between TLX1 and trafficking protein particle complex subunit 9 (TRAPPC9) or Zinc finger protein 69 homolog B (ZFP69B) were further probed by ChIP and luciferase reporter assays. Rescue experiments were finally conducted in vitro and in vivo. RESULTS: TLX1 was highly expressed in HCC cells, and the knockdown of TLX1 led to reduced malignant biological behavior of HCC cells. TLX1 bound to the promoter region of TRAPPC9, thereby promoting TRAPPC9 expression. Overexpression of TRAPPC9 attenuated the effect of TLX1 reduction on suppressing malignant behavior of HCC cells. ZFP69B was also highly expressed in HCC cells and bound to the promoter region of TLX1 to induce TLX1 expression. Knockdown of ZFP69B inhibited the viability and mobility of HCC cells in vitro and tumor growth in vivo, and overexpression of TLX1 rescued this inhibition. CONCLUSION: These findings suggest that ZFP69B promotes the proliferation of HCC cells by directly upregulating the expression of TLX1 and the ensuing TRAPPC9.

[Estimation of Regional Background Ozone in Henan Province from 2019 to 2021].

Clarifying the regional transmission and local generation contributions of ozone （O3） is important for controlling O3 pollution. To quantify the regional background and spatial-temporal variations of O3, a comprehensive study was conducted using multiple methods including principal component analysis （PCA） and TCEQ, with Henan Province as a case study. Based on monitoring data from 59 national sites in Henan Province during 2019-2021, four methods were employed to estimate the regional background of O3. Method 1 was the traditional method, performing O3 univariate-multisite PCA analysis. Method 2 was a multivariate-single-site PCA analysis considering nitrogen dioxide and meteorological conditions as constraints. Method 3 combined PCA and multiple linear regression （MLR） to determine regional background contributions, drawing on the idea of source apportionment. Method 4 was the TCEQ method that used the lowest measured O3-8h concentration as the regional background. The estimation results showed that Methods 1 and 2 were basically equal, and Methods 3 and 4 were approximately 37-60 µg·m-3 lower than Method 1. From 2019 to 2021, the changes in regional background ρ（O3-8h） estimated by Methods 1-4 were 1.6, -13.4, 5.9, and -3.5 µg·m-3, respectively. The average estimations derived from multiple methods showed that the regional background ρ（O3-8h） in Henan Province from 2019 to 2021 concentrations were 82.0, 79.0, and 79.7 µg·m-3, accounting for 75.9%, 76.4%, and 78.7% of the total regional O3-8h, respectively. The regional background O3-8h estimated by the four methods showed obvious seasonal changes, characterized by summer > spring > fall > winter.

Untargeted metabolomics study of mature human milk from women with and without gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy that alters the metabolites in human milk. Integrated Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed for comprehensive identification and comparison of metabolites in mature human milk (MHM) from women with and without GDM. A total of 268 differentially expressed metabolites (DEMs) were identified. Among these, linoleic acid, arachidonic acid, 9R-HODE and L-glutamic acid were significantly elevated and 12,13-DHOME was significantly decreased in MHM of women with GDM. These metabolites are significantly enriched in linoleic acid metabolism, fatty acid biosynthesis, galactose metabolism and ABC transporters pathways. Disorders in these metabolic pathways are associated with insulin resistance and poor glucose metabolism indicating these conditions may persist postpartum.

The oxidative potential of fine ambient particulate matter in Xinxiang, North China: Pollution characteristics, source identification and regional transport.

Atmospheric fine particulate matter (PM2.5) can trigger the production of cytotoxic reactive oxygen species (ROS), which can trigger or exacerbate oxidative stress and pulmonary inflammation. We collected 111 daily (∼24 h) ambient PM2.5 samples within an urban region of North China during four seasons of 2019-2020. PM2.5 samples were examined for carbonaceous components, water-soluble ions, and elements, together with their oxidative potential (represent ROS-producing ability) by DTT assay. The seasonal peak DTTv was recorded in winter (2.86 ± 1.26 nmol min-1 m-3), whereas the DTTm was the highest in summer (40.6 ± 8.7 pmol min-1 µg-1). WSOC displayed the highest correlation with DTT activity (r = 0.84, p < 0.0001), but the influence of WSOC on the elevation of DTTv was extremely negligible. Combustion source exhibited the most significant and robust correlation with the elevation of DTTv according to the linear mixed-effects model result. Source identification investigation using positive matrix factorization displayed that combustion source (36.2%), traffic source (30.7%), secondary aerosol (15.7%), and dust (14.1%) were driving the DTTv, which were similar to the results from the multiple linear regression (MLR) analysis. Backward trajectory analysis revealed that the major air masses originate from local and regional transportation, but PM2.5 OP was more susceptible to the influence of short-distance transport clusters. Discerning the influence of chemicals on health-pertinent attributes of PM2.5, such as OP, could facilitate a deep understanding of the cause-and-effect relationship between PM2.5 and impacts.

Clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound for breast fibroadenoma: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to assess the clinical efficacy and safety of ultrasound (US)-guided high intensity focused ultrasound (HIFU) in the treatment of breast fibroadenoma in different studies. METHODS: Studies evaluating the efficacy and safety of US-guided HIFU in the treatment of histologically-proven FA with follow-up outcomes of more than 3 months were searched through MEDLINE/PubMed databases. Volume reduction rate (VRR) and side effects were extracted and compared for further analysis. RESULTS: Of 29 identified articles, 10 studies involving 385 women and more than 545 FAs met the inclusion criteria. The mean VRR at 6 months and 12 months after HIFU was 52.00% and 72.00%. In terms of intraoperative safety, nine studies reported mild to moderate pain, with an average visual analogue scale (VAS) score ranging from 1.60 to 7.10. The most common postoperative side effect associated with HIFU was subcutaneous ecchymosis and less frequent were pain, erythema, and skin pigmentation, most of which disappeared within weeks. No serious side effects were observed. CONCLUSION: S-guided HIFU is an effective and safe noninvasive treatment for breast FA that does not cause serious side effects. Further studies are needed to explore crucial influencing factors of VRR.

Topological Network Modes in a Twisted Moiré Phononic Crystal.

Twisted moiré materials, a new class of layered structures with different twist angles for neighboring layers, are attracting great attention because of the rich intriguing physical phenomena associated with them. Of particular interest are the topological network modes, first proposed in the small angle twisted bilayer graphene under interlayer bias. Here we report the observations of such topological network modes in twisted moiré phononic crystals without requiring the external bias fields. Acoustic topological network modes that can be constructed in a wide range of twist angles are both observed in the domain walls with and without reconstructions, which serve as the analogy of the lattice relaxations in electronic moiré materials. Topological robustness of the topological network modes is observed by introducing valley-preserved defects to the network channel. Furthermore, the network can be reconfigured into two-dimensional patterns with any desired connectivity, offering a unique prototype platform for acoustic applications.

Recent progress in plant-based proteins: From extraction and modification methods to applications in the food industry.

Plant proteins can meet consumers' demand for healthy and sustainable alternatives to animal proteins. It has been reported to possess numerous health benefits and is widely used in the food industry. However, conventional extraction methods are time-consuming, energy-intensive, as well as environmentally unfriendly. Plant proteins are also limited in application due to off-flavors, allergies, and anti-nutritional factors. Therefore, this paper discusses the challenges and limitations of conventional extraction processes. The current advances in green extraction technologies are also summarized. In addition, methods to improve the nutritional value, bioactivity, functional and organoleptic properties of plant proteins, and strategies to reduce their allergenicity are mentioned. Finally, examples of applications of plant proteins in the food industry are presented. This review aims to stimulate thinking and generate new ideas for future research. It will also provide new ideas and broad perspectives for the application of plant proteins in the food industry.

The causal relationship between gut microbiota and alopecia areata: a Mendelian randomization analysis.

Background: Increasing evidence suggests a robust correlation between the gut microbiome and alopecia areata. In light of the extensive diversity of gut microbiota, this study aims to utilize state-of-the-art and comprehensive data to explore the causative association between gut microbiota and alopecia areata. Objective: We conducted a Mendelian randomization (MR)-based two-sample study to elucidate the causal relationship between gut microbiota and alopecia areata. Method: Summary information on Ncase = 767 and Ncontrol = 394,105 cases of alopecia areata was obtained from the FinnGen study. A total of 473 gut microbial taxa were summarized from the genome-wide association study (GWAS) catalog. The study comprised a forward Mendelian randomization (MR) analysis with the gut microbiome as the exposure factor and alopecia areata as the outcome, as well as a reverse MR analysis with alopecia areata as the exposure factor and the gut microbiome as the outcome. Various analytical methods including inverse variance weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed. Subsequently, sensitivity analysis was conducted to ensure the robustness of our research findings. Result: This study has established a causal relationship between gut microbiota and alopecia areata. Forward causal analysis revealed causality relationships between 16 gut microbial taxa and alopecia areata, while reverse causal analysis found that there may be a causal relationship between alopecia areata and 16 gut microbial taxa (not statistically significant). Conclusion: Our study findings suggest a causal relationship between gut microbiota and alopecia areata, providing potential guidance for future clinical trials.

Exploration of GmDof11-lncRNA13082 Module Regulating Oil Synthesis in Plants.

Soybean (Glycine max [Linn.] Merr.) is an important oilseed crop. Although transcription factors (TFs) can coordinate the expression of mRNA and lncRNA, their coordination in the soybean oil synthesis pathway remains unclear. This study examined the interaction between the TF GmDof11 and lncRNA13082 and found that overexpression of GmDof11 led to an increase in the number of Arabidopsis seeds, thousand seed weight, crude protein, hydrolysis amino acid, and soluble sugar. Additionally, it reduced the triglyceride and starch contents and affected the proportion of fatty acids, increasing the contents of palmitic acid, stearic acid, and linolenic acid. The yeast two-hybrid experiments revealed that GmDof11 interacts with GmBCCP1, GmLEC1b, and GmFAB2 proteins. In the RT-qPCR analysis of transgenic soybean roots, it was found that GmDof11 can activate the production of lncRNA13082 and work in conjunction with lncRNA13082 to oversee oil synthesis and nutrient storage. Our research provides robust theoretical evidence for a comprehensive resolution of TF-lncRNA regulation in the soybean oil synthesis network.

PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.

INTRODUCTION: To investigate the role of a novel type of protein kinase C delta (PKCδ) in the neuroinflammation of Alzheimer's disease (AD). METHODS: We analyzed PKCδ and inflammatory cytokines levels in cerebrospinal fluid (CSF) of AD and normal controls, as well as their correlations. The cellular expression pattern of PKCδ and the effects of PKCδ modulation on microglia-mediated neuroinflammation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, RNA sequencing (RNA-seq), and immunofluorescence staining. RESULTS: PKCδ levels were increased dramatically in the CSF of AD patients and positively correlated with cytokines. PKCδ is expressed mainly in microglia in the brain. Amyloid beta (Aß) stimulation increased PKCδ expression and secretion, which led to upregulation of the nuclear factor kappa B (NF-κB) pathway and overproduction of proinflammatory cytokines. Downregulation or inhibition of PKCδ attenuated Aß-induced microglial responses and improved cognitive function in an AD mouse model. DISCUSSION: Our study identifies PKCδ as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD. HIGHLIGHTS: Protein kinase C delta (PKCδ) levels increase in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), and positively correlate with elevated inflammatory cytokines in human subjects. PKCδ is expressed mainly in microglia in vivo, whereas amyloid beta (Aß) stimulation increases PKCδ expression and secretion, causing upregulation of the nuclear factor kappa B (NF-κB) pathway and production of inflammatory cytokines. Downregulation or inhibition of PKCδ attenuates Aß-enhanced NF-κB signaling and cytokine production in microglia and improves cognitive function in AD mice. PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD.

Recyclable V2O5/g-C3N4 Heterojunction-Catalyzed Visible-Light-Promoted C3-H Trifluoromethylation of Quinoxalin-2-(1H)-ones.

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Sivelestat Inhibits Vascular Endothelial Injury Induced by Inflammatory Response and Improves the Prognosis of Hemorrhagic Fever with Renal Syndrome in Children: An Ambispective Cohort Study.

Background: In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear. Methods: An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children's Hospital Affiliated to Xi'an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher's exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups. Results: No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5±3 vs 34.5±3.5) and 72 h (21.3±4.5 vs 31.5±5.6) (P<0.05), as well as the ICAM-1 level at 48 h (553±122 vs 784±187) and 72 h (452±130 vs 623±85) (P<0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760±289 vs 2180±445), 48 h (1450±441 vs 1890±267), and 72 h (1149±338 vs 1500±396) (P<0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT). Conclusion: Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.

Update on functional analysis of long non-coding RNAs in common crops.

With the rapid advances in next-generation sequencing technology, numerous non-protein-coding transcripts have been identified, including long noncoding RNAs (lncRNAs), which are functional RNAs comprising more than 200 nucleotides. Although lncRNA-mediated regulatory processes have been extensively investigated in animals, there has been considerably less research on plant lncRNAs. Nevertheless, multiple studies on major crops showed lncRNAs are involved in crucial processes, including growth and development, reproduction, and stress responses. This review summarizes the progress in the research on lncRNA roles in several major crops, presents key strategies for exploring lncRNAs in crops, and discusses current challenges and future prospects. The insights provided in this review will enhance our comprehension of lncRNA functions in crops, with potential implications for improving crop genetics and breeding.

The protective mechanism of Tao Hong Si Wu decoction against breast cancer through regulation of EGFR/ERK1/2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Tao Hong Si Wu Decoction (THSWD), a traditional Chinese herbal medicine, is widely utilized in clinical settings, either alone or in combination with other medications, for the treatment of breast cancer. AIM OF THE STUDY: The specific targeting molecule(s) of THSWD and its associated molecular mechanisms remain unclear. This research aims to elucidate the underlying molecular mechanisms of THSWD in the treatment of breast cancer. MATERIALS AND METHODS: The pharmacological properties of THSWD were investigated in breast cancer cells and tumor tissues using a range of methods including Acridine Orange/Ethidium Bromide (AO/EB) staining, Transwell assay, flow cytometry, immunofluorescence assay, and breast cancer mice models. RESULTS: Our findings demonstrate that THSWD induces necrosis and/or apoptosis in breast cancer cells, while significantly inhibiting cell migration. Target proteins of THSWD in anticancer activity include EGFR, RAS, and others. THSWD treatment for breast cancer is associated with the EGFR/ERK1/2 signaling pathway. CONCLUSION: Our findings offer initial insights into the primary mechanism of action of THSWD in breast cancer treatment, indicating its potential as a complementary therapy deserving further investigation.

Chiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination.

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

A real-world analysis of stereotactic body radiotherapy combined with immunotherapy in advanced or recurrent non-small cell lung cancer (NSCLC): A single-center experience.

Background: We aimed to assess the value of stereotactic body radiotherapy (SBRT) delivered under the situation of controlled or progressed disease during ICI therapy in advanced or recurrent NSCLC. Methods: We retrospectively collected patients with advanced or recurrent NSCLC who received SBRT concurrently with ICI in our institution between January 2017 and December 2021. Patients were divided into two groups, including those for whom SBRT was delivered initially or to the residual tumors during the first- or later-line ICI treatment (Group 1), and those for whom SBRT was given to the progressed tumors irrespective of first- or later-line ICI treatment (Group 2). Results: A total of 144 patients were included. With median follow-up duration of 25.6 (range: 3.6 to 56.2) months, median progression-free survival (PFS) was 13.7 (95 % CI: 10.4 to 17.1) months and median overall survival (OS) was 52.8 [95 % CI: 30.6 to not available (NA)] months. In Group 1 (n = 78), median PFS was 17.9 (95 % CI: 14.5 to 29.8) months while median OS was not reached and 5-year OS rate was 61.2 %. In Group 2 (n = 66), median PFS was 8.0 (95 % CI: 6.0 to 13.1) months and median OS was 30.6 (95 % CI: 21.5 to NA) months. Conclusions: SBRT combined with ICI demonstrated favorable survival for advanced or recurrent NSCLC, delivered in a controlled-disease situation as well as to progressed diseases with salvage-intent. Future prospective studies are warranted to investigate the optimal SBRT dose regimen and appropriate combination strategy to synergize ICI.

Icariside II alleviates lipopolysaccharide-induced acute lung injury by inhibiting lung epithelial inflammatory and immune responses mediated by neutrophil extracellular traps.

AIMS: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI. MAIN METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence. KEY FINDINGS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells. SIGNIFICANCE: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.

Heme Oxygenase-1 Regulates Zearalenone-Induced Oxidative Stress and Apoptosis in Sheep Follicular Granulosa Cells.

Zearalenone (ZEA) is a common non-steroidal estrogenic mycotoxin found in a range of animal feeds and poses a serious threat to the reproductive health of farm animals and humans. However, the mechanism underlying ZEA-induced reproductive toxicity in sheep remains unknown. Granulosa cells are crucial for egg maturation and the fertility of female sheep. In this study, we aimed to examine the impact of different ZEA concentrations on sheep follicular granulosa cells and to elucidate the potential molecular mechanism underlying ZEA-induced toxicity using transcriptome sequencing and molecular biological approaches. Treating primary sheep follicular granulosa cells with different concentrations of ZEA promoted the overproduction of reactive oxygen species (ROS), increased lipid peroxidation products, led to cellular oxidative stress, decreased antioxidant enzyme activities, and induced cell apoptosis. Using transcriptome approaches, 1395 differentially expressed genes were obtained from sheep follicular granulosa cells cultured in vitro after ZEA treatment. Among them, heme oxygenase-1 (HMOX1) was involved in 11 biological processes. The protein interaction network indicated interactions between HMOX1 and oxidative and apoptotic proteins. In addition, N-acetylcysteine pretreatment effectively reduced the ZEA-induced increase in the expression of HMOX1 and Caspase3 by eliminating ROS. Hence, we suggest that HMOX1 is a key differential gene involved in the regulation of ZEA-induced oxidative stress and apoptosis in follicular granulosa cells. These findings provide novel insights into the prevention and control of mycotoxins in livestock.