GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.

How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4 assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly.

Cells respond to environmental changes by toggling metabolic pathways, preparing for homeostasis, and anticipating future stresses. For example, in Saccharomyces cerevisiae, carbon stress-induced gluconeogenesis is terminated upon glucose availability, a process that involves the multiprotein E3 ligase GIDSR4 recruiting N termini and catalyzing ubiquitylation of gluconeogenic enzymes. Here, genetics, biochemistry, and cryoelectron microscopy define molecular underpinnings of glucose-induced degradation. Unexpectedly, carbon stress induces an inactive anticipatory complex (GIDAnt), which awaits a glucose-induced substrate receptor to form the active GIDSR4. Meanwhile, other environmental perturbations elicit production of an alternative substrate receptor assembling into a related E3 ligase complex. The intricate structure of GIDAnt enables anticipating and ultimately binding various N-degron-targeting (i.e., "N-end rule") substrate receptors, while the GIDSR4 E3 forms a clamp-like structure juxtaposing substrate lysines with the ubiquitylation active site. The data reveal evolutionarily conserved GID complexes as a family of multisubunit E3 ubiquitin ligases responsive to extracellular stimuli.

Study on the Performance of a Surface with Coupled Wettability Difference and Convex-Stripe Array for Improved Air Layer Stability.

The existence of an air layer reduces friction drag on superhydrophobic surfaces. Therefore, improving the air layer stability of superhydrophobic surfaces holds immense significance in reducing both energy consumption and environmental pollution caused by friction drag. Based on the properties of mathematical discretization and the contact angle hysteresis generated by the wettability difference, a surface coupled with a wettability difference treatment and a convex-stripe array is developed by laser engraving and fluorine modification, and its performance in improving the air layer stability is experimentally studied in a von Kármán swirling flow field. The results show that the destabilization of the air layer is mainly caused by the Kelvin-Helmholtz instability, which is triggered by the density difference between gas and liquid, as well as the tangential velocity difference between gas and liquid. When the air layer is relatively thin, tangential wave destabilization occurs, whereas for larger thicknesses, the destabilization mode is coupled wave destabilization. The maximum Reynolds number that keeps the air layer fully covering the surface of the rotating disk (with drag reduction performance) during the disk rotation process is defined as the critical Reynolds number (Rec), which is 1.62 × 105 for the uniform superhydrophobic surface and 3.24 × 105 for the superhydrophobic surface with a convex stripe on the outermost ring (SCSSP). Individual treatments of wettability difference and a convex-stripe array on the SCSSP further improve the air layer stability, but Rec remains at 3.24 × 105. Finally, the coupling of the wettability difference treatment with a convex-stripe array significantly improves the air layer stability, resulting in an increase of Rec to 4.05 × 105, and the drag reduction rate stably maintained around 30%.

Homogeneous Electrochemiluminescence for Highly Sensitive Determination of Demethylase FTO Based on Target-Regulated DNAzyme Cleavage and Host-Guest Interaction.

Fat mass and obesity-associated protein (FTO) is the first reported N6-methyladenosine (m6A) RNA demethylase. The dysregulation of FTO demethylation is strongly associated with various human cancers in a m6A-dependent manner. Herein, a homogeneous electrochemiluminescence (ECL) method for the determination of FTO was proposed based on the target-regulated DNAzyme cleavage. Moreover, the ECL signal was highly enhanced by host-guest interaction between ß-cyclodextrin (ß-CD) and tri-n-propylamine (TPrA). The m6A caged DNAzyme 17E-Me acted as a padlock, while the FTO served as the corresponding key. As the key, FTO could specifically remove m6A modification, restoring the cleavage activity of DNAzyme 17E. With the assistance of the Zn2+ cofactor, the substrate strand was cleaved at a specific site, and the ECL indicator of Ru(phen)32+ was discharged to produce an ECL signal. On the contrary, 17E-Me was blocked and no cleavage reaction occurred without the key. For the ECL detection, the electrode modification of ß-CD@AuNPs concentrated Ru(phen)32+ species through electrostatic adsorption and gathered TPrA molecules through host-guest interaction with ß-CD, which resulted in an intense ECL response. The results demonstrated the ECL intensity linearly correlated with the logarithm of the FTO concentration (from 0.0001 to 100 nM) with a low detection limit (30 fM). The IC50 value for FTO inhibitors rhein and meclofenamic acid were 35.6 µM and 20.3 µM, respectively. The strategy was further validated for FTO detection in MCF-7 cell lysates and Hela cell lysates. This work reveals that this strategy is promising for developing homogeneous ECL method for detection of FTO and screening of the demethylase inhibitors.

Occult deterioration of an aortic annular abscess: how do we diagnose a pseudoaneurysm periaortic valve? A case report.

BACKGROUND: Infectious endocarditis (IE) is a disease caused by the colonization of toxic microorganisms on the endocardium of heart valves [1]. Although much progress has been made in the diagnosis and treatment of IE, its complications, such as annular abscesses [2], still have a high mortality rate. In this case, we describe a patient with infective endocarditis complicated by occult deteriorated aortic annular abscess. CASE PRESENTATION: A 44-year-old man was admitted due to weakness of his right limbs and unclear speech for 10 h. He had recurrent fevers for 1 month before admission. Transthoracic echocardiography showed a mix-echoic vegetation attached to the bicuspid aortic valve, moderate aortic regurgitation and a possible aortic annular abscess. Blood cultures were negative and empiric antibiotic therapy was begun. The patient did not have fever again and seem to be clinically improved. However, follow-up transesophageal echocardiography revealed a large periaortic abscess led to aortic sinus pseudoaneurysm. The patient underwent mechanical prosthetic valve replacement and annulus reconstruction successfully. Perivalvular abscess may be insidious deterioration in patients who seem to be clinically improved, which requires us to pay more attention. DISCUSSION: Occult deterioration of an aortic annular abscess is rare and more attention should be paid. Re-evaluation of echocardiography is required even if the patient's symptoms improve.

"Ghost imaging" in pericardial cavity: Disappeared "tumor-like" masses in tuberculous pericarditis.

A 66-year-old woman was admitted to our hospital due to chest distress and shortness of breath during 1 week. Transthoracic echocardiography (TTE) revealed massive pericardial effusion and multiple, irregular and high-density echo "tumor-like" masses on the heart, with the largest one on the apex. However, there were no masses found by computed tomography (CT) scan, except for increased lipids around the coronary artery. We performed emergency pericardiocentesis and drainage to relieve symptoms. The positron emission tomography/CT (PET/CT) also showed several ununiformly high accumulations in pericardial cavity. However, the high-density echo "tumor-like" masses cannot be seen by TTE after pericardiocentesis, and also cannot be detected when surgery. Pericardiotomy was performed due to severe pericardial adhesion. The diagnosis of tuberculosis (TB) was confirmed by pericardiotomy and pericardial biopsy.

Transcriptome analysis of sweet potato responses to potassium deficiency.

BACKGROUND: As one of three essential nutrients, potassium is regarded as a main limiting factor for growth and development in plant. Sweet potato (Ipomoea batatas L.) is one of seven major food crops grown worldwide, and is both a nutrient-rich food and a bioenergy crop. It is a typical 'K-favoring' crop, and the level of potassium ion (K+) supplementation directly influences its production. However, little is known about the transcriptional changes in sweet potato genes under low-K+ conditions. Here, we analyzed the transcriptomic profiles of sweet potato roots in response to K+ deficiency to determine the effect of low-K+ stress on this economically important crop. RESULTS: The roots of sweet potato seedlings with or without K+ treatment were harvested and used for transcriptome analyses. The results showed 559 differently expressed genes (DEGs) in low and high K+ groups. Among the DEGs, 336 were upregulated and 223 were downregulated. These DEGs were involved in transcriptional regulation, calcium binding, redox-signaling, biosynthesis, transport, and metabolic process. Further analysis revealed previously unknow genes involved in low-K+ stress, which could be investigated further to improve low K+ tolerance in plants. Confirmation of RNA-sequencing results using qRT-PCR displayed a high level of consistency between the two experiments. Analysis showed that many auxin-, ethylene- and jasmonic acid-related genes respond to K+ deficiency, suggesting that these hormones have important roles in K+ nutrient signaling in sweet potato. CONCLUSIONS: According to the transcriptome data of sweet potato, various DEGs showed transcriptional changes in response to low-K+ stress. However, the expression level of some kinases, transporters, transcription factors (TFs), hormone-related genes, and plant defense-related genes changed significantly, suggesting that they have important roles during K+ deficiency. Thus, this study identifies potential genes for genetic improvement of responses to low-K+ stress and provides valuable insight into the molecular mechanisms regulating low K+ tolerance in sweet potato. Further research is required to clarify the function of these DEGs under low-K+ stress.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

Prevalence, influencing factors and adverse consequences of workplace violence against nurses in China: A cross-sectional study.

AIMS: The primary objective of this study was to determine the prevalence of workplace violence among nurses in China and its association with demographic characteristics, quality of work life and coping styles. The secondary objective was to explore how nurses deal with workplace violence and the emotional/psychological impact of workplace violence on nurses. BACKGROUND: Workplace violence is a common occupational hazard that causes physical and psychological harm to nurses. METHODS: A cross-sectional study was conducted with 2769 nurses from China. A demographic information questionnaire, hospital workplace violence questionnaire, Chinese version of the work-related quality of life scale and coping style scale were used in this study. The Chi-squared test, Mann-Whitney U test and binary logistic regression analysis were used to investigate the effects of demographic characteristics, quality of work life and coping styles on nurses' workplace violence. RESULTS: A total of 49.12% of the nurses (n = 1360) had experienced at least one type of workplace violence in the past 6 months. Night shifts, work department, chronic diseases (odds ratio [OR] = 1.53, p < .001), sleep disorders (OR = 1.54, p < .001), frequent overtime (OR = 1.78, p < .001), adverse nursing events (OR = 2.01, p < .001) and passive coping (OR = 1.47, p < .001) were risk factors for workplace violence. Working conditions (OR = 0.61, p < .001), general well-being (OR = 0.65, p < .001) and positive coping (OR = 0.76, p < .001) were identified as protective factors for workplace violence. Nurses exposed to workplace violence experience various negative emotional and psychological consequences. CONCLUSIONS: Workplace violence is common among nurses in China. Good working conditions, general well-being and positive coping may help prevent workplace violence injuries. IMPLICATIONS FOR NURSING MANAGEMENT: Efforts should be made to improve and optimize existing workplace violence prevention measures, create and maintain a good working environment for health care workers and develop various coping styles or strategies to manage stress to reduce workplace violence. The cross-sectional study has been approved by the Ethics Committee of the First Affiliated Hospital of China Medical University, with the registration number 2019-221-2. Written informed consent was obtained prior to the survey.

A retrospective study of neck rejuvenation using a noninsulated microneedle radiofrequency in Chinese subjects.

Large-scale long-term retrospective study of noninsulated microneedle radiofrequency treatment on neck rejuvenation is lacking. We conducted a 3-year retrospective observation of subjects treated with noninsulated microneedle radiofrequency (NIMNRF) for neck rejuvenation in Chinese subjects. Of all subjects, 28 subjects (28.6%) received only 1 session of treatment. About 50% subjects achieved ≥ 50% improvement, and average improvements were 37.0% at 3 months follow-up (M3) and 41.6% at 6 months follow-up (M6). Seventy subjects (71.4%) accepted 3 sessions of treatments. The neck aging scores were 3.57 ± 1.28 at baseline, and significantly decreased to 1.10 ± 0.84 at M3 (p < 0.05), 1.04 ± 0.86 (p < 0.05) at M6, separately. The average improvements were 73.3% at M3 and 75.1% at M6. It showed a trend of better efficacy with the increasing number of sessions (p < 0.05). Among of 6 subjects who was followed up for 1 year, 5 subjects who received 3 sessions of treatment achieved about 70% improvement after final session, and another 1 subject who received 1 session remained the improvement up to 40%. The results demonstrate NIMNRF treatment has significant and long-lasting effect on neck laxity and wrinkle reduction with minimal discomfort and downtime.

Structural basis for lipopolysaccharide insertion in the bacterial outer membrane.

One of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. In Gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (LPS). The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surface. Of the seven Lpt proteins, the LptD-LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane. Here we report the crystal structure of the ∼110-kilodalton membrane protein complex LptD-LptE from Shigella flexneri at 2.4 Å resolution. The structure reveals an unprecedented two-protein plug-and-barrel architecture with LptE embedded into a 26-stranded ß-barrel formed by LptD. Importantly, the secondary structures of the first two ß-strands are distorted by two proline residues, weakening their interactions with neighbouring ß-strands and creating a potential portal on the barrel wall that could allow lateral diffusion of LPS into the outer membrane. The crystal structure of the LptD-LptE complex opens the door to new antibiotic strategies targeting the bacterial outer membrane.

The wild sweetpotato (Ipomoea trifida) genome provides insights into storage root development.

BACKGROUND: Sweetpotato (Ipomoea batatas (L.) Lam.) is the seventh most important crop in the world and is mainly cultivated for its underground storage root (SR). The genetic studies of this species have been hindered by a lack of high-quality reference sequence due to its complex genome structure. Diploid Ipomoea trifida is the closest relative and putative progenitor of sweetpotato, which is considered a model species for sweetpotato, including genetic, cytological, and physiological analyses. RESULTS: Here, we generated the chromosome-scale genome sequence of SR-forming diploid I. trifida var. Y22 with high heterozygosity (2.20%). Although the chromosome-based synteny analysis revealed that the I. trifida shared conserved karyotype with Ipomoea nil after the separation, I. trifida had a much smaller genome than I. nil due to more efficient eliminations of LTR-retrotransposons and lack of species-specific amplification bursts of LTR-RTs. A comparison with four non-SR-forming species showed that the evolution of the beta-amylase gene family may be related to SR formation. We further investigated the relationship of the key gene BMY11 (with identity 47.12% to beta-amylase 1) with this important agronomic trait by both gene expression profiling and quantitative trait locus (QTL) mapping. And combining SR morphology and structure, gene expression profiling and qPCR results, we deduced that the products of the activity of BMY11 in splitting starch granules and be recycled to synthesize larger granules, contributing to starch accumulation and SR swelling. Moreover, we found the expression pattern of BMY11, sporamin proteins and the key genes involved in carbohydrate metabolism and stele lignification were similar to that of sweetpotato during the SR development. CONCLUSIONS: We constructed the high-quality genome reference of the highly heterozygous I. trifida through a combined approach and this genome enables a better resolution of the genomics feature and genome evolutions of this species. Sweetpotato SR development genes can be identified in I. trifida and these genes perform similar functions and patterns, showed that the diploid I. trifida var. Y22 with typical SR could be considered an ideal model for the studies of sweetpotato SR development.

Starch content differences between two sweet potato accessions are associated with specific changes in gene expression.

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important root crops in the world. Initial formation and development of storage roots (SRs) are key factors affecting its yields. In order to study the molecular mechanism and regulatory networks of the SRs development process, we have analyzed root transcriptomes between the high and low starch content sweet potato accessions at three different developmental stages. In this study, we assembled 46,840 unigenes using Illumina paired-end sequencing reads and identified differentially expressed genes (DEGs) between two accessions. The numbers of DEGs were increased with the development of SRs, indicating that the difference between two accessions is enlarging with the maturation. DEGs were mainly enriched in starch biosynthesis, plant hormones regulatory, and genetic information processing pathways. Then, expression patterns of DEGs that are most significant and starch biosynthesis related were validated using qRT-PCR. Our results provide valuable resources to future study on molecular mechanisms of SRs development and candidate genes for starch content improvement in sweet potato.

Highly sensitive and selective demethylase FTO detection using a DNAzyme-mediated CRISPR/Cas12a signal cascade amplification electrochemiluminescence biosensor with C-CN/PCNV heterojunction as emitter.

Fat mass and obesity-associated protein (FTO) has gained attention as the first RNA N6-methyladenosine (m6A) modification eraser due to its overexpression being associated with various cancers. In this study, an electrochemiluminescence (ECL) biosensor for the detection of demethylase FTO was developed based on DNAzyme-mediated CRISPR/Cas12a signal cascade amplification system and carboxylated carbon nitride nanosheets/phosphorus-doped nitrogen-vacancy modified carbon nitride nanosheets (C-CN/PCNV) heterojunction as the emitter. The biosensor was constructed by modifying the C-CN/PCNV heterojunction and a ferrocene-tagged probe (ssDNA-Fc) on a glassy carbon electrode. The presence of FTO removes the m6A modification on the catalytic core of DNAzyme, restoring its cleavage activity and generating activator DNA. This activator DNA further activates the trans-cleavage ability of Cas12a, leading to the cleavage of the ssDNA-Fc and the recovery of the ECL signal. The C-CN/PCNV heterojunction prevents electrode passivation and improves the electron-hole recombination, resulting in significantly enhanced ECL signal. The biosensor demonstrates high sensitivity with a low detection limit of 0.63 pM in the range from 1.0 pM to 100 nM. Furthermore, the biosensor was successfully applied to detect FTO in cancer cell lysate and screen FTO inhibitors, showing great potential in early clinical diagnosis and drug discovery.

Estrogen alleviates liver fibrosis and restores metabolic homeostasis in ovariectomy-induced liver injury and carbon tetrachloride (CCl4) exposure.

AIM: Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations. METHODS: Female mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl4) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-ß (TGF-ß), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes. RESULTS: Ovary removal exacerbated CCl4-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl4 treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl4. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment. CONCLUSION: Estrogen supplementation alleviates liver injury induced by OVX and CCl4, highlighting its protective effects against fibrosis and associated metabolic alterations.

Structures and ion transport mechanisms of plant high-affinity potassium transporters.

Plant high-affinity K+ transporters (HKTs) mediate Na+ and K+ uptake, maintain Na+/K+ homeostasis, and therefore play crucial roles in plant salt tolerance. In this study, we present cryoelectron microscopy structures of HKTs from two classes, class I HKT1;1 from Arabidopsis thaliana (AtHKT1;1) and class II HKT2;1 from Triticum aestivum (TaHKT2;1), in both Na+- and K+-bound states at 2.6- to 3.0-Å resolutions. Both AtHKT1;1 and TaHKT2;1 function as homodimers. Each HKT subunit consists of four tandem domain units (D1-D4) with a repeated K+-channel-like M-P-M topology. In each subunit, D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry. Although both TaHKT2;1 and AtHKT1;1 have only one putative Na+ ion bound in the selectivity filter with a similar coordination pattern, the two HKTs display different K+ binding modes in the filter. TaHKT2;1 has three K+ ions bound in the selectivity filter, but AtHKT1;1 has only two K+ ions bound in the filter, which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif. These structures, along with computational, mutational, and electrophysiological analyses, enable us to pinpoint key residues that are critical for the ion selectivity of HKTs. The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1ß/IL-18 Signaling Cascade.

Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1ß/IL-18 signaling cascade.