Aqueous extract of Phellinus igniarius ameliorates hyperuricemia and renal injury in adenine/potassium oxonate-treated mice.

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.

A bibliometric analysis of the knowledge related to mental health during and post COVID-19 pandemic.

Objective: COVID-19 led to a horrific global pandemic, with strict lockdowns and prolonged indoor stays increasing the risk of mental health problems, affecting people of different ages, genders, regions, and types of work to varying degrees. This study provides a bibliometric summary of the knowledge map related to mental health during and post COVID-19 pandemic. Methods: Publications related to mental health during and post COVID-19 pandemic were searched in the Web of Science Core Collection (WoSCC) database through March 19, 2024. After screening the search results, the literature included in the final was first quantitatively analyzed using GraphPad Prism software and then visualized using VOSviewer, CiteSpace, and R (the bibliometrix package). Results: The 7,047 publications from 110 countries were included, with the highest number of publications from China and the United States, and the number of publications related to mental health during and post the COVID-19 pandemic increased annually until 2023, after which it began to decline. The major institutions were University of Toronto, University of London, Harvard University, King's College London, University College London, University of California System, University of Melbourne, Institut National De La Sante Et De La Recherche Medicale (Inserm), Mcgill University, and University of Ottawa; Frontiers in Psychiatry had the highest number of publications, and the Journal of Affective Disorders had the highest number of co-citations; 36,486 authors included, with Xiang, Yu-Tao, Cheung, Teris, Chung, Seockhoon published the most papers, and World Health Organization, Kroenke K, and Wang CY were the most co-cited; epidemiologically relevant studies on mental health related to COVID-19, and the importance of mental health during normalized epidemic prevention and control are the main directions of this research area, especially focusing on children's mental health; "pandemic," "sars-cov-2," "epidemic," "depression," "coronavirus anxiety," "anxiety," "longitudinal," "child," "coronavirus anxiety," "longitudinal," "child," and "coronavirus" are the top keywords in recent years. Conclusion: This comprehensive bibliometric study summarizes research trends and advances in mental health during and after the COVID-19 Pandemic. It serves as a reference for mental health research scholars during and after the COVID-19 pandemic, clarifying recent research preoccupations and topical directions.

LncRNA MALAT1-miR-339-5p-NIS axis is involved in the increased level of thyroid stimulating hormone (TSH) induced by combined exposure of high iodine and hyperlipidemia.

Hypothyroidism and subclinical hypothyroidism were both characterized by elevated levels of thyroid stimulating hormone (TSH). Previous studies had found that high iodine or hyperlipidemia alone was associated with increased TSH level. However, their combined effects on TSH have not been elucidated. In this study, combination of high iodine and hyperlipidemia was established through the combined exposure of high-water iodine and high fat diet in Wistar rats. The results showed that combined exposure of high iodine and high fat can induce higher TSH level. The mRNA and protein levels of sodium iodide transporters (NIS) and type 1 deiodinase (D1) in thyroid tissues, which were crucial genes in the synthesis of thyroid hormones, decreased remarkably in combined exposure group. Mechanistically, down-regulated long non-coding RNA (lncRNA) metastasis associated in lung denocarcinoma transcript 1 (MALAT1) may regulate the expression of NIS by increasing miR-339-5p, and regulating D1 by increasing miR-224-5p. Then, the above findings were explored in subjects exposed to high water iodine and hyperlipidemia. The results indicated that in population combined with high iodine and hyperlipidemia, TSH level increased to higher level and lncRNA MALAT1-miR-339-5p-NIS axis was obviously activated. Collectively, this study found that combined exposure of high iodine and hyperlipidemia induced a higher level of TSH, and lncRNA MALAT1-miR-339-5p-NIS axis may play important role.

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. METHODS: We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. RESULTS: A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. CONCLUSION: This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

Progress of mesenchymal stem cells (MSCs) & MSC-Exosomes combined with drugs intervention in liver fibrosis.

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.

Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.

Bio-inspired foveal super-resolution method for multi-focal-length images based on local gradient constraints.

Most existing super-resolution (SR) imaging systems, inspired by the bionic compound eye, utilize image registration and reconstruction algorithms to overcome the angular resolution limitations of individual imaging systems. This article introduces a multi-aperture multi-focal-length imaging system and a multi-focal-length image super-resolution algorithm, mimicking the foveal imaging of the human eye. Experimental results demonstrate that with the proposed imaging system and an SR imaging algorithm inspired by the human visual system, the proposed method can enhance the spatial resolution of the foveal region by up to 4 × compared to the original acquired image. These findings validate the effectiveness of the proposed imaging system and computational imaging algorithm in enhancing image texture and spatial resolution.

Neural circuit mechanisms of acupuncture effect: where are we now?

Recently, there has been increasing attention on the impact of acupuncture on the dysregulated neural circuits in different disease. This has led to new understandings of how acupuncture works. This review presents a comprehensive analysis of research that have examined the impact of acupuncture on abnormal neural circuits associated with pain, anxiety, Parkinson's disease, addiction disorders, cognitive problems, and gastrointestinal disorders. These studies have shown that acupuncture's therapeutic effects are mediated by specific brain areas and neurons involved in neural circuit mechanisms, emphasising its wide-ranging influence. The positive impacts of acupuncture can be ascribed to its ability to modify the functioning of neurocircuits in various physiological conditions. Nevertheless, contemporary studies on acupuncture neural circuits frequently overlook the comprehensive circuit mechanism including the periphery, central nervous system, and target organ. Additionally, the scope of diseases studied is restricted. Future study should focus on broadening the range of diseases studied and exploring the neural circuit mechanisms of these diseases in depth in order to enhance our understanding of acupuncture's neurobiological impacts.

The effect of cross-regional transport on ozone and particulate matter pollution in China: A review of methodology and current knowledge.

China is currently one of the countries impacted by severe atmospheric ozone (O3) and particulate matter (PM) pollution. Due to their moderately long lifetimes, O3 and PM can be transported over long distances, cross the boundaries of source regions and contribute to air pollution in other regions. The reported contributions of cross-regional transport (CRT) to O3 and fine PM (PM2.5) concentrations often exceed those of local emissions in the major regions of China, highlighting the important role of CRT in regional air pollution. Therefore, further improvement of air quality in China requires more joint efforts among regions to ensure a proper reduction in emissions while accounting for the influence of CRT. This review summarizes the methodologies employed to assess the influence of CRT on O3 and PM pollution as well as current knowledge of CRT influence in China. Quantifying CRT contributions in proportion to O3 and PM levels and studying detailed CRT processes of O3, PM and precursors can be both based on targeted observations and/or model simulations. Reported publications indicate that CRT contributes by 40-80 % to O3 and by 10-70 % to PM2.5 in various regions of China. These contributions exhibit notable spatiotemporal variations, with differences in meteorological conditions and/or emissions often serving as main drivers of such variations. Based on trajectory-based methods, transport pathways contributing to O3 and PM pollution in major regions of China have been revealed. Recent studies also highlighted the important role of horizontal transport in the middle/high atmospheric boundary layer or low free troposphere, of vertical exchange and mixing as well as of interactions between CRT, local meteorology and chemistry in the detailed CRT processes. Drawing on the current knowledge on the influence of CRT, this paper provides recommendations for future studies that aim at supporting ongoing air pollution mitigation strategies in China.

Newborn readmissions and virtual primary care delivery: a population-based case-control study.

BACKGROUND: Early post-discharge assessments for newborns are recommended. Virtual care has become more prevalent during the pandemic, providing an opportunity to better understand its impact on the quality of post-discharge newborn care. The objective of this study was to understand whether primary care visit modality (in-person vs. virtual) is associated with early newborn hospital readmissions and emergency department (ED) visits. METHODS: We conducted a population-based, case-control study using linked health administrative databases between September 1, 2020 and March 31, 2022 in Ontario, Canada. We compared the modality of primary care visits among cases (hospital readmission within 14 days of life) and controls (newborns without a readmission), matched on infant sex, gestational age, and maternal parity. We included an alternative definition of cases as a composite of either a newborn hospital readmission or emergency department (ED) visit or in-hospital death within the first 14 days of life. Conditional logistic regression models were used to model odds ratios (ORs), comparing those exposed to a virtual visit versus in-person visit, adjusting for infant birth weight, birth hospitalization length of stay, neighbourhood level material deprivation, rurality and presence of active maternal comorbidities. RESULTS: Among 73,324 eligible newborns, 2,220 experienced a hospital readmission within 14 days of life and were matched to 8,880 controls. Jaundice was the primary reason for readmission (75% of readmissions). Compared to newborns who were seen in-person post-discharge, newborns who were seen virtually had higher odds of hospital readmission (adjusted odds ratio [aOR] 1.41 (95% CI 1.09, 1.83); the magnitude of effect was not different using the composite outcome (aOR 1.35, 95% CI 1.05, 1.75). CONCLUSIONS: Newborns who receive a virtual post-discharge visit are more likely than those who receive an in-person visit to require hospital readmission.

N-Acyl-N-Alkyl Sulfonamide Probes for Ligand-Directed Covalent Labeling of GPCRs: The Adenosine A2B Receptor as Case Study.

Small molecular tool compounds play an essential role in the study of G protein-coupled receptors (GPCRs). However, tool compounds most often occupy the orthosteric binding site, hampering the study of GPCRs upon ligand binding. To overcome this problem, ligand-directed labeling techniques have been developed that leave a reporter group covalently bound to the GPCR, while allowing subsequent orthosteric ligands to bind. In this work, we applied such a labeling strategy to the adenosine A2B receptor (A2BAR). We have synthetically implemented the recently reported N-acyl-N-alkyl sulfonamide (NASA) warhead into a previously developed ligand and show that the binding of the A2BAR is not restricted by NASA incorporation. Furthermore, we have investigated ligand-directed labeling of the A2BAR using SDS-PAGE, flow cytometric, and mass spectrometry techniques. We have found one of the synthesized probes to specifically label the A2BAR, although detection was hindered by nonspecific protein labeling most likely due to the intrinsic reactivity of the NASA warhead. Altogether, this work aids the future development of ligand-directed probes for the detection of GPCRs.

Metal-Free Cascade Formation of C-C and C-N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties.

A straightforward and efficient methodology has been developed for the synthesis of 3-cyano-2-pyridones via the C-C and C-N bond formation processes. A total of 51 diverse 3-cyano-2-pyridone derivatives were obtained in moderate to excellent yields. This reaction featured advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions. A plausible mechanism for the reaction was proposed. 3-cyano-2-pyridones as ricinine analogues for insecticidal properties were evaluated, and the compound 3ci (LC50 = 2.206 mg/mL) showed the best insecticidal property.

Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.

Current prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs. We found that recruitment of 10E8 precursors to germinal centers (GCs) required a minimum affinity for germline-targeting immunogens, but the GC residency of MPER precursors was brief due to displacement by higher-affinity endogenous B cell competitors. Higher-affinity germline-targeting immunogens extended the GC residency of MPER precursors, but robust long-term GC residency and maturation were only observed for MPER-HuGL18, an MPER precursor clonotype able to close the affinity gap with endogenous B cell competitors in the GC. Thus, germline-targeting immunogens could induce MPER-targeting antibodies, and B cell residency in the GC may be regulated by a precursor-competitor affinity gap.

Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models.

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.

Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

Dietary fiber may benefit chondrocyte activity maintenance.

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

Comparative Analysis of the Effect of Dietary Supplementation with Fermented and Water-Extracted Leaf Extracts of Eucommia ulmoides on Egg Production and Egg Nutrition.

Although the water extract of Eucommia ulmoides leaf (WEE) promotes egg laying in hens, its palatability is poor. To improve the palatability of E. ulmoides leaf, probiotic fermentation was used, and fermented extract E. ulmoides leaf (FEE) was prepared using Lactiplantibacillus plantarum. The safety of FEE was investigated using a long-term toxicity test, and no oxidative damage, inflammatory reactions, or histological lesions were observed in the experimental rats receiving dietary supplementation of FEE at 200 mg/kg, suggesting that FEE is suitable for long-term feeding. Subsequently, dietary supplementation of FEE (group C) in comparison with dietary supplementation of WEE (group B), as well as a control (group A), was applied in the hen industry. Laying performance, egg quality, egg nutrition, egg flavor, and the gut microbiome were analyzed comparatively. Interestingly, the laying rate was observed to be four percentage points higher with dietary supplementation of FEE at 200 mg/kg compared with the control and two percentage points higher compared with the dietary addition of WEE at the same dosage. Simultaneously, a slight upregulation in daily feed consumption was determined in the FEE-supplemented group compared with the blank control and the WEE-supplemented group, indicating that the inclusion of FEE stimulated the hens' appetite. Moreover, variations in egg amino acids, fatty acids, and volatile components were obtained with either dietary addition, FEE or WEE, implying that dietary supplementation of the fermented and water-extracted E. ulmoides leaf extracts contributed to egg flavor change. Furthermore, variations in the gut microbiota were mediated by FEE, increasing the relative abundance of the genus Lactobacillus. These alterations in gut microbiota were tightly related to improved laying performance and egg flavor changes. Our results indicate that FEE is a better alternative feed additive in the hen industry than WEE.