Adsorption characteristics and mechanisms of bisphenol A on novel nitrogen-modified biochar derived from waste masks and biomass.

Resource utilization of waste masks has become an urgent scientific issue. In this work, with sustainably, waste masks and biomass were co-pyrolysis with oxygen limitation to prepare mask-based biochar (MB). Then, urea was introduced to prepare novel nitrogen modified mask-based biochar (NMB) via a one-step hydrothermal synthesis method. The adsorption characteristics of NMB on the emerging environmental pollutant, bisphenol A (BPA), were evaluated via batch adsorption tests. Moreover, the physicochemical properties of the materials were characterized with various advanced techniques. Also, the roles of waste masks and nitrogen modification were explored. The adsorption mechanisms of NMB on BPA were revealed as well as the performance differences between different adsorbents. The results showed that waste masks participated in thermochemical reactions, shaped the microsphere structure of biochar, and increased the types of surface functional groups. The nitrogen modification enriched the surface elemental composition and activated the specific surface area via the mesopore. These would enhance the adsorption performance. The maximum adsorption of BPA by NMB was 62.63 mg·g-1, which was approximately 2.35-5.58 times higher than that of the control materials. Temkin model and pseudo-second-order model optimally simulate the isothermal and kinetic adsorption, respectively. The adsorption mechanisms are jointly by physical and chemical adsorption, which mainly includes π-π interaction, hydrogen bonding, intraparticle diffusion, surface adsorption, and ion exchange. After discussion and evaluation, NMB has lower preparation process cost (7.21 USD·kg-1) and safety, with potential for environmental applications. This study aims to expand new ideas for the comprehensive utilization of waste masks and the preparation of eco-friendly materials. Moreover, it provides a theoretical basis for the removal of BPA.

Association between longitudinal biomarkers and major adverse liver outcomes in patients with non-cirrhotic metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AIMS: Non-invasive biomarkers provide prognostic information for the development of major adverse liver outcomes (MALO) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the predictive value of longitudinal biomarker measurements has not been evaluated. We assessed whether changes in biomarkers could predict incident MALO in MASLD. APPROACH AND RESULTS: We analyzed a cohort of 1,260 patients (71.7% on biopsy) with non-cirrhotic MASLD between 1974 and 2019. Data at baseline and follow-up visits were obtained from medical charts. MALO was determined through medical charts and linkage to national registers until the end of 2020. A joint modeling approach was used to quantify the associations between the trajectory of biomarkers with the risk of MALO. MASLD was diagnosed at median age of 52 years (IQR: 39-60), and 59% were male. During a median follow-up of 12.2 years, 111 (8.8%) patients developed MALO. The joint modeling showed that an elevated FIB-4 (HR 2.60, 95% CI 1.89-3.50), AST (HR 2.69, 95% CI 2.57-3.05), and lower platelet count (HR 0.93, 95% CI 0.90-0.97) at any time point were associated with an increased risk of MALO, whereas the rate of change in these biomarkers had no association with this risk. CONCLUSIONS: In addition to baseline measurements of non-invasive biomarkers such as FIB-4 and AST, and platelets taken at MASLD diagnosis, monitoring their values over time is important, as the latest value of these biomarkers is closely associated with the risk of future MALO. The rate of change may not be as important.

Synthesis of N-N Axially Chiral Pyrrolyl-oxoisoindolin via Isothiourea-Catalyzed Acylative Dynamic Kinetic Resolution.

The development of methods for the asymmetric synthesis of N-N axial chirality remains elusive and challenging. Here, we disclose a method for the construction of N-N axially chiral pyrrolyl-oxoisoindolins along with central chirality via the isothiourea (ITU)-catalyzed acylative dynamic kinetic resolution (DKR). Axial chirality was introduced into the acylative DKR of hemiaminals for the first time. This protocol features mild conditions with excellent yields and enantioselectivities.

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes.

Adipose tissue can recruit catabolic adipocytes that utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-adipocytes and UCP1-beige adipocytes. Importantly, we demonstrate that the FC-adipocyte subpopulation is highly metabolically active and utilizes FCs to dissipate energy, thus contributing to thermogenesis independent of Ucp1. Furthermore, FC-adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.

Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle.

Although uncoupling protein 1 (UCP1) is established as a major contributor to adipose thermogenesis, recent data have illustrated an important role for alternative pathways, particularly the futile creatine cycle (FCC). How these pathways co-exist in cells and tissues has not been explored. Beige cell adipogenesis occurs in vivo but has been difficult to model in vitro; here, we describe the development of a murine beige cell line that executes a robust respiratory response, including uncoupled respiration and the FCC. The key FCC enzyme, tissue-nonspecific alkaline phosphatase (TNAP), is localized almost exclusively to mitochondria in these cells. Surprisingly, single-cell cloning from this cell line shows that cells with the highest levels of UCP1 express little TNAP, and cells with the highest expression of TNAP express little UCP1. Immunofluorescence analysis of subcutaneous fat from cold-exposed mice confirms that the highest levels of these critical thermogenic components are expressed in distinct fat cell populations.

An Overview of Infectious and Non-Infectious Causes of Pregnancy Losses in Equine.

Equine breeding plays an essential role in the local economic development of many countries, and it has experienced rapid growth in China in recent years. However, the equine industry, particularly large-scale donkey farms, faces a significant challenge with pregnancy losses. Unfortunately, there is a lack of systematic research on abortion during equine breeding. Several causes, both infectious and non-infectious, of pregnancy losses have been documented in equines. The infectious causes are viruses, bacteria, parasites, and fungi. Non-infectious causes may include long transportation, ingestion of mycotoxins, hormonal disturbances, twinning, placentitis, umbilical length and torsion, etc. In current review, we discuss the transmission routes, diagnostic methods, and control measures for these infectious agents. Early detection of the cause and appropriate management are crucial in preventing pregnancy loss in equine practice. This review aims to provide a comprehensive understanding of the potential causes of abortion in equines, including infectious agents and non-infectious factors. It emphasizes the importance of continued research and effective control measures to address this significant challenge in the equine industry.

Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p.

OBJECTIVE: Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. METHODS: Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth. RESULTS: It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay. CONCLUSIONS: The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.

Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8.

Introduction: Equid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control. Methods: In this study, we investigated the in vitro and in vivo antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8. Results: Our results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, in vivo experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model. Conclusion: Collectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge.

Immunoglobulin Superfamily Containing Leucine-Rich Repeat (ISLR) Serves as a Redox Sensor That Modulates Antioxidant Capacity by Suppressing Pyruvate Kinase Isozyme M2 Activity.

Cells defend against oxidative stress by enhancing antioxidant capacity, including stress-activated metabolic alterations, but the underlying intracellular signaling mechanisms remain unclear. This paper reports that immunoglobulin superfamily containing leucine-rich repeat (ISLR) functions as a redox sensor that responds to reactive oxygen species (ROS) stimulation and modulates the antioxidant capacity by suppressing pyruvate kinase isozyme M2 (PKM2) activity. Following oxidative stress, ISLR perceives ROS stimulation through its cysteine residue 19, and rapidly degrades in the autophagy-lysosome pathway. The downregulated ISLR enhances the antioxidant capacity by promoting the tetramerization of PKM2, and then enhancing the pyruvate kinase activity, PKM2-mediated glycolysis is crucial to the ISLR-mediated antioxidant capacity. In addition, our results demonstrated that, in triple-negative breast cancer, cisplatin treatment reduced the level of ISLR, and PKM2 inhibition sensitizes tumors to cisplatin by enhancing ROS production; and argued that PKM2 inhibition can synergize with cisplatin to limit tumor growth. Our results demonstrate a molecular mechanism by which cells respond to oxidative stress and modulate the redox balance.

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.

Mindfulness Meditation Training Reduces Gaming Cravings by Reshaping the Functional Connectivity Between the Default Mode Network and Executive Control-Related Brain Regions.

BACKGROUND: Internet gaming disorder (IGD) can lead to psychological problems and cause behavioral problems in individuals. Traditional interventions have been ineffective in treating IGD. Meanwhile, mindfulness meditation (MM) is an emerging method that has proven to be effective for treating psychiatric disorders. In this study, MM was used to intervene in IGD and to explore its neural mechanism. METHODS: Eighty participants were recruited through advertisements. Eventually, 61 completed the 1-month training (MM group, n = 31; progressive muscle relaxation [PMR] group, n = 30), including a pretest, 8 training sessions, and a posttest. Regional homogeneity and degree centrality were calculated, and the tests (pre- and post-) and group (MM and PMR) analysis of variance was performed. The overlapping results were obtained as region of interest for functional connectivity (FC) analyses. Behavioral data and neurotransmitter availability maps were correlated with FC. RESULTS: Compared with PMR, MM decreased the severity of addiction and game craving in IGD. Brain imaging results showed that the FC between and within the executive control and default mode networks/reward-related regions were enhanced. Significant negative correlations were observed between FC and dopamine receptor D2, dopamine transporter, and vesicular acetylcholine transporter. Significant positive correlations were observed between FCs and serotonin and aminobutyric acid receptors. CONCLUSIONS: This study confirmed the effectiveness of MM in treating IGD. MM altered the default mode and enhanced top-down control over game cravings. These findings were revealed by the correlations between brain regions and behavioral and biochemical effects. The results show the neural mechanism of MM in reducing IGD and lay the foundation for future research.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus.

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1's function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating ß-catenin signaling. The reactivation of ß-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.

Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.

X-Ray-Triggered CO-Release from Gold Nanocluster: All-in-One Nanoplatforms for Cancer Targeted Gas and Radio Synergistic Therapy.

Glycolysis-dominant metabolic pathway in cancer cells can promote their therapeutic resistance against radiotherapy (RT). Carbon monoxide (CO) as a glycolysis inhibitor can enhance the efficiency of RT. Herein, an X-ray responsive CO-releasing nanocomposite (HA@AuNC@CO) based on strong host-guest interactions between the radiosensitizer and CO donor for enhanced RT is developed. The encapsulated gold nanoclusters (CD-AuNCs) can effectively generate cytotoxic reactive oxygen species (ROS) under X-ray radiation, which not only directly inactivate cancer cells but also induce in situ CO gas generation from adamantane modified metal carbonyl (Ada-CO) for glycolysis inhibition. Both in vitro and in vivo results demonstrate that HA@AuNC@CO exhibits active targeting toward CD44 overexpressed cancer cells, along with excellent inhibition of glycolysis and efficient RT against cancer. This study offers a new strategy for the combination of gas therapy and RT in tumor treatment.

Effect of ethanol addition on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes.

The effects of ethanol on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes (e-TBSQ and e-TBSR) were investigated. Ethanol restricted the gelatinization of Tartary buckwheat starch (TBS), which resulted an increase in ∆H, G' and G" as well as a decrease in apparent viscosity of e-TBSQ and e-TBSR. The particle size, scanning electron microscopy and X-ray diffraction results showed that ethanol influenced the morphological structure of TBS granules and the starch crystalline structure in e-TBSQ and e-TBSR changed from B-type to V-type when the ethanol concentration was 25%. Saturation transfer difference-nuclear magnetic resonance results revealed that ethanol weakened the binding ability of quercetin/rutin to TBS in e-TBSQ and e-TBSR, leading to a change in the binding site on the quercetin structural unit. The residual ungelatinized TBS granules in e-TBSQ and e-TBSR induced a high slowly digestible starch content, and thus displayed a "resistant-to-digestion".

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

[Intravascular Large B-cell Lymphoma Presenting with Lung Adenocarcinoma:
A Case Report and Literature Review].

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive extranodal large B-cell lymphoma, cocurrence in the same organ with other malignancies is very rare, especially in the lung. Here, we report a rare case of lung adenocarcinoma with IVLBCL. The patient was admitted to the hospital due to diarrhea associated with fever and cough. A computed tomography (CT) scan of the chest showed an irregular patchy high-density shadow in the upper lobe of the right lung with ground-glass opacity at the margin. After admission, the patient was given anti-infection treatment, but still had intermittent low fever (up to 37.5 °C). The pathological diagnosis of percutaneous lung biopsy (PLB) was lepidic-predominant adenocarcinoma with local infiltration, which was proved to be invasive nonmucinous adenocarcinoma of the lung with IVLBCL after surgery. This paper analyzed the clinicopathological characteristics and reviewed the relevant literature to improve the knowledge of clinicians and pathologists and avoid missed diagnosis or misdiagnosis.
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Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.