Engineering natural microbiomes toward enhanced bioremediation by microbiome modeling.

Engineering natural microbiomes for biotechnological applications remains challenging, as metabolic interactions within microbiomes are largely unknown, and practical principles and tools for microbiome engineering are still lacking. Here, we present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes. We show that application of herbicide and herbicide-degrader inoculation drives a convergent succession of different natural microbiomes toward functional microbiomes (e.g., enhanced bioremediation of herbicide-contaminated soils). We develop a metabolic modeling pipeline, SuperCC, that can be used to document metabolic interactions within microbiomes and to simulate the performances of different microbiomes. Using SuperCC, we construct bioremediation-enhanced synthetic microbiomes based on 18 keystone species identified from natural microbiomes. Our results highlight the importance of metabolic interactions in shaping microbiome functions and provide practical guidance for engineering natural microbiomes.

Recombinant Beauveria bassiana expressing Bacillus thuringiensis toxin Cyt1Aa: a promising approach for enhancing Aedes mosquito control.

The entomopathogenic fungus Beauveria bassiana provides an eco-friendly substitute to chemical insecticides for mosquito control. Nevertheless, its widespread application has been hindered by its comparatively slow efficacy in eliminating mosquitoes. To augment the potency of B. bassiana against Aedes mosquitoes, a novel recombinant strain, Bb-Cyt1Aa, was developed by incorporating the Bacillus thuringiensis toxin gene Cyt1Aa into B. bassiana. The virulence of Bb-Cyt1Aa was evaluated against Aedes aegypti and Aedes albopictus using insect bioassays. Compared to the wild-type (WT) strain, the median lethal time (LT50) for A. aegypti larvae infected with Bb-Cyt1Aa decreased by 33.3% at a concentration of 1 × 108 conidia/mL and by 22.2% at 1 × 107 conidia/mL. The LT50 for A. aegypti adults infected with Bb-Cyt1Aa through conidia ingestion was reduced by 37.5% at 1 × 108 conidia/mL and by 33.3% at 1 × 107 conidia/mL. Likewise, the LT50 for A. aegypti adults infected with Bb-Cyt1Aa through cuticle contact decreased by 33.3% and 30.8% at the same concentrations, respectively. Furthermore, the Bb-Cyt1Aa strain also demonstrated increased toxicity against both larval and adult A. albopictus, when compared to the WT strain. In conclusion, our study demonstrated that the expression of B. thuringiensis toxin Cyt1Aa in B. bassiana enhanced its virulence against Aedes mosquitoes. This suggests that B. bassiana expressing Cyt1Aa has potential value for use in mosquito control. IMPORTANCE: Beauveria bassiana is a naturally occurring fungus that can be utilized as a bioinsecticide against mosquitoes. Cyt1Aa is a delta-endotoxin protein produced by Bacillus thuringiensis that exhibits specific and potent insecticidal activity against mosquitoes. In our study, the expression of this toxin Cyt1Aa in B. bassiana enhances the virulence of B. bassiana against Aedes aegypti and Aedes albopictus, thereby increasing their effectiveness in killing mosquitoes. This novel strain can be used alongside chemical insecticides to reduce dependence on harmful chemicals, thereby minimizing negative impacts on the environment and human health. Additionally, the potential resistance of B. bassiana against mosquitoes in the future could be overcome by acquiring novel combinations of exogenous toxin genes. The presence of B. bassiana that expresses Cyt1Aa is of significant importance in mosquito control as it enhances genetic diversity, creates novel virulent strains, and contributes to the development of safer and more sustainable methods of mosquito control.

Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy.

CFIRL is a long noncoding RNA (lncRNA), we previously identified as the most significantly upregulated lncRNA in the failing hearts of patients with dilated cardiomyopathy (DCM). In this study, we determined the function of CFIRL and its role in DCM. Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts. Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction (TAC)-induced cardiac dysfunction and fibrosis in vivo. Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts. CFIRL knockdown attenuated these effects. Mechanistically, RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1, a newly identified noncanonical transcriptional factor, to activate IL-6 transcription. IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy, which can be prevented by CFIRL knockdown. These findings uncover the critical role of CFIRL, a fibroblast-associated lncRNA, in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes. CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure, particularly in DCM.

ABA-mediated regulation of rice grain quality and seed dormancy via the NF-YB1-SLRL2-bHLH144 Module.

Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

Uneven agricultural contraction within fast-urbanizing urban agglomeration decreases the nitrogen use efficiency of crop production.

Diverse development paths among cities within an urban agglomeration can lead to uneven changes in their agricultural production scale, which reshape the inter-city food supply patterns and the spatiotemporal characteristics of nitrogen (N) pollution from the food system. Here, using Guangdong-Hong Kong-Macao Greater Bay Area of China as a case, we found a substantial decrease in N use efficiency of crop production from 45.2% to 29.3% during 1989-2007, along with a growing level of concentration of food N production in less-urbanized cities. From 1989 to 2018, 12.3% to 42.2% of total N pollution in food production became embedded in inter-city trade, leading to aggregation of N pollution in peripheral cities with relatively low levels of economic development. We suggest that protection and intensification of cropland from urban encroachment, as well as enhancing the economic and technical synergies among cities, can serve the sustainable transition of the food system with coordinated N pollution mitigation.

The comparison of contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI LI-RADS for nodules ≤2 cm in patients at high risk for HCC: a prospective study.

Objectives: To investigate the consistency of LI-RADS of CEUS and EOB-MRI in the categorization of liver nodules ≤2cm in patients at high risk for HCC. Methods: Patients at high risk for HCC with nodules ≤2cm who underwent CEUS and EOB-MRI in our hospital were prospectively enrolled. The CEUS images and EOB-MRI imaging of each liver nodule were observed to evaluate inter-observer consistency and category according to CEUS LI-RADS V2017 and CT/MRI LI-RADS V2017 criteria double blinded. Pathology and/or follow-up were used as reference standard. Results: A total of 127 nodules in 119 patients met the inclusion criteria. The inter-observer agreement was good on CEUS and EOB-MRI LI-RADS (kappa = 0.76, 0.76 p < 0.001). The inter-modality agreement was fair (kappa=0.21, p < 0.001). There was no statistical difference in PPV and specificity between CEUS and EOB-MRI LR-5 for HCC, while the difference in AUC was statistically significant. We used new criteria (CEUS LR-5 and EOB-MRI LR-4/5 or CEUS LR-4/5 and EOB-MRI LR-5) to diagnose HCC. The sensitivity, specificity, and AUC of this criteria was 63.4%, 95.6%, and 0.80. Conclusions: CEUS and EOB-MRI showed fair inter-modality agreement in LI-RADS categorization of nodules ≤2 cm. The inter-observer agreement of CEUS and EOB-MRI LI-RADS were substantial. CEUS and EOB-MRI LR-5 have equally good positive predictive value and specificity for HCC ≤ 2cm, and combining these two modalities may better diagnose HCC ≤ 2 cm. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04212286.

Ultrasensitive SERS aptasensor using Au@Ag bimetallic nanorod SERS tags for the selective detection of amantadine in foods.

Herein, a novel surface enhanced Raman spectroscopy (SERS) aptasensor was developed for amantadine (AMD) detection, based on magnetite nanoparticles coated with polyethylenimine, silver nanoclusters and aptamers (Fe3O4@PEI@AgNC-apt) as the capture probe and complementary DNA-modified gold nanorods (AuNRs@4-MPBA@Ag-c-DNA containing 4-mercaptophenylboric acid molecules) as the reporter probe. In the presence of AMD, the AMD and the reporter probe competed for the aptamer on the surface of the capture probe, resulting in the reporter probe detaching from the capture probe leading to a decrease in intensity of the SERS signal at 1067 cm-1 for 4-MPBA. Under optimal conditions, a good linear relationship was established between the SERS intensity at 1067 cm-1 and the logarithm of the AMD concentration over the range 10-6-102 mg L-1, with a LOD of 0.50 × 10-6 mg L-1. The AMD levels in spiked samples were evaluated using the SERS aptasensor, with good recoveries ranging from 90.57% to 113.49% being obtained.

Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study.

AIMS: To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression. METHODS: This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis. RESULTS: MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (P log-rank test =0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (P log-rank test=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor. CONCLUSION: Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.

Telephone follow-up based on artificial intelligence technology among hypertension patients: Reliability study.

Artificial intelligence (AI) telephone is reliable for the follow-up and management of hypertensives. It takes less time and is equivalent to manual follow-up to a high degree. We conducted a reliability study to evaluate the efficiency of AI telephone follow-up in the management of hypertension. During May 18 and June 30, 2020, 350 hypertensives managed by the Pengpu Community Health Service Center in Shanghai were recruited for follow-up, once by AI and once by a human. The second follow-up was conducted within 3-7 days (mean 5.5 days). The mean length time of two calls were compared by paired t-test, and Cohen's Kappa coefficient was used to evaluate the reliability of the results between the two follow-up visits. The mean length time of AI calls was shorter (4.15 min) than that of manual calls (5.24 min, P < .001). The answers related to the symptoms showed moderate to substantial consistency (κ:.465-.624, P < .001), and those related to the complications showed fair consistency (κ:.349, P < .001). In terms of lifestyle, the answer related to smoking showed a very high consistency (κ:.915, P < .001), while those addressing salt consumption, alcohol consumption, and exercise showed moderate to substantial consistency (κ:.402-.645, P < .001). There was moderate consistency in regular usage of medication (κ:.484, P < .001).

Platelet-mediated circulating tumor cell evasion from natural killer cell killing via immune checkpoint CD155-TIGIT.

BACKGROUND AIMS: Circulating tumor cells (CTCs) are precursors of cancer metastasis. However, how CTCs evade immunosurveillance during hematogenous dissemination remains unclear. APPROACH RESULTS: We identified CTC-platelet adhesions by single-cell RNA sequencing and multiplex immunofluorescence of blood samples from multiple cancer types. Clinically, CTC-platelet aggregates were associated with significantly shorter progression-free survival and overall survival in hepatocellular carcinoma patients. In vitro, ex vivo, and in vivo assays demonstrated direct platelet adhesions gifted cancer cells with an evasive ability from natural killer (NK) cell killing by upregulating inhibitory checkpoint CD155, therefore facilitating distant metastasis. Mechanistically, CD155 was transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact-dependent manner. Further competition assays and cytotoxicity experiments revealed that CD155 on CTCs inhibited NK cell cytotoxicity only by engaging with immune receptor TIGIT, but not CD96 and DNAM1, another two receptors for CD155. Interrupting the CD155-TIGIT interactions with a TIGIT antibody restored NK cell immunosurveillance on CTCs and markedly attenuated tumor metastasis. CONCLUSIONS: Our results demonstrated CTC evasion from NK cell-mediated innate immunosurveillance mainly via immune checkpoint CD155-TIGIT, potentially offering an immunotherapeutic strategy for eradicating CTCs.

N-doped Ti3C2-reinforced porous g-C3N4 for photocatalytic contaminants degradation and nitrogen reduction.

Herein, a series of N-doped Ti3C2/porous g-C3N4 composites are ultrasonically prepared from N-doped Ti3C2 and porous g-C3N4 under N2 atmosphere. The structure, morphology, and optical characteristics of the as-prepared composites are characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, etc. Moreover, photocatalytic measurements show that N-doped Ti3C2 is an excellent modifier for porous g-C3N4 to heighten its photocatalytic activity. Only 44.1% of rhodamine B can be degraded by the photocatalysis of pristine porous g-C3N4, while the photocatalytic degradation ratio of rhodamine B can reach up to 97.5% for the optimal N-doped Ti3C2 loading composites under visible light for 15 min. Moreover, the photocatalytic tests of N2 fixation confirm that the optimal composites show the highest production yield of NH4+ (11.8 µmol gcat-1 h-1), which is 2.11-folds more than that of porous g-C3N4 (5.6 µmol gcat-1 h-1). The reinforced photocatalytic properties are revealed to profit from the more photogenerated electrons and holes' separation, higher ability for light response, and more abundant active sites. This work develops the route for boosting the photocatalytic properties of porous g-C3N4 with N-doped Ti3C2.

PSEENet: A pseudo-siamese neural network incorporating electroencephalography and electrooculography characteristics for heterogeneous sleep staging.

Sleep staging plays a critical role in evaluating the quality of sleep. Currently, most studies are either suffering from dramatic performance drops when coping with varying input modalities or unable to handle heterogeneous signals. To handle heterogeneous signals and guarantee favorable sleep staging performance when a single modality is available, a pseudo-siamese neural network (PSN) to incorporate electroencephalography (EEG), electrooculography (EOG) characteristics is proposed (PSEENet). PSEENet consists of two parts, spatial mapping modules (SMMs) and a weight-shared classifier. SMMs are used to extract high-dimensional features. Meanwhile, joint linkages among multi-modalities are provided by quantifying the similarity of features. Finally, with the cooperation of heterogeneous characteristics, associations within various sleep stages can be established by the classifier. The evaluation of the model is validated on two public datasets, namely, Montreal Archive of Sleep Studies (MASS) and SleepEDFX, and one clinical dataset from Huashan Hospital of Fudan University (HSFU). Experimental results show that the model can handle heterogeneous signals, provide superior results under multimodal signals and show good performance with single modality. PSEENet obtains accuracy of 79.1%, 82.1% with EEG, EEG and EOG on Sleep-EDFX, and significantly improves the accuracy with EOG from 73.7% to 76% by introducing similarity information.

Associations between socioeconomic status and rates of blood pressure changes among Chinese older adults: a longitudinal community-based cohort study.

OBJECTIVES: The relationships between socioeconomic status (SES) and blood pressure changes among older adults in China remain unclear. This study aimed to examine the associations between SES and rates of blood pressure changes among Chinese older adults. STUDY DESIGN: Community-based, prospective, longitudinal cohort study. METHODS: This study included 13,541 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey between 2002 and 2018. SES was assessed by educational level, occupation, household yearly per capita income, and financial support. The estimated annual changes (EACs) of blood pressure were computed as the difference in blood pressure levels between any two adjacent surveys divided by the time interval. Associations between SES and EACs of blood pressure were evaluated using generalised estimating equations. RESULTS: Lower SES was significantly associated with greater annual increases of blood pressure among Chinese older adults. The effect of SES on EACs of blood pressure was more pronounced among non-hypertensive participants. Compared to EACs among non-hypertensive participants with high SES, multivariable-adjusted EACs among those with low SES increased by 0.57 mmHg (95% confidence interval [CI]: 0.16, 0.99), 0.32 mmHg (95% CI: 0.07, 0.57), and 0.40 mmHg (95% CI: 0.13, 0.66) for systolic blood pressure, diastolic blood pressure, and mean arterial pressure, respectively. CONCLUSIONS: This study revealed strong associations between SES and EACs of blood pressure among Chinese older adults, especially in the non-hypertensive population. Findings suggest that prevention strategies for hypertension should pay more attention to the older population with low SES.

miR-101a-3p/ROCK2 axis regulates neuronal injury in Parkinson's disease models.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). This study focuses on deciphering the role of microRNA (miR)-101a-3p in the neuronal injury of PD and its regulatory mechanism. METHODS: We constructed a mouse model of PD by intraperitoneal injection of 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP), and used 1-methyl-4-phenylpyridinium (MPP+) to treat Neuro-2a cells to construct an in-vitro PD model. Neurological dysfunction in mice was evaluated by swimming test and traction test. qRT-PCR was utilized to examine miR-101a-3p expression and ROCK2 expression in mouse brain tissues and Neuro-2a cells. Western blot was conducted to detect the expression of α-synuclein protein and ROCK2 in mouse brain tissues and Neuro-2a cells. The targeting relationship between miR-101a-3p and ROCK2 was determined by dual-luciferase reporter gene assay. The apoptosis of neuro-2a cells was assessed by flow cytometry. RESULTS: Low miR-101a-3p expression and high ROCK2 expression were found in the brain tissues of PD mice and MPP+-treated Neuro-2a cells; PD mice showed decreased neurological disorders, and apoptosis of Neuro-2a cells was increased after MPP+ treatment, both of which were accompanied by increased accumulation of α-synuclein protein. After miR-101a-3p was overexpressed, the neurological function of PD mice was improved, and the apoptosis of Neuro-2a cells induced by MPP+ was alleviated, and the accumulation of α-synuclein protein was reduced; ROCK2 overexpression counteracted the protective effect of miR-101a-3p. Additionally, ROCK2 was identified as the direct target of miR-101a-3p. CONCLUSION: MiR-101a-3p can reduce neuronal apoptosis and neurological deficit in PD mice by inhibiting ROCK2 expression, suggesting that miR-101a-3p is a promising therapeutic target for PD.

Preparation, Air Filtration Performance of a Fluorinated Polyimide/Polyacrylonitrile Nanofibrous Membrane by Electrospinning.

This paper reports the successful fabrication of a new nanofibrous membrane, F-PI/PAN, through electrospinning of polyacrylonitrile (PAN) and fluorinated polyimide (F-PI). The nanofibrous membrane exhibits comprehensive properties for high-temperature filtration and robust PM2.5 (particulate matter with an aerodynamic equivalent diameter of 2.5 microns or less) removal. The introduction of F enhances the hydrophobicity of the PI. The relationship between the hydrophobic performance and the filtration performance of particles is investigated. The chemical group of the composite membrane was demonstrated using FITR, while the surface morphology was investigated using field emission scanning electron microscopy. The TGA results indicated good thermal stability at 300 °C. Various ratios of F-PI membranes were prepared to characterize the change in properties, with the optimal mass ratio of F-PI being 20 wt%. As the proportion of F-PI increases, its mechanical and filtration efficiency properties and hydrophobicity become stronger. The contact angle reaches its maximum of 128 ± 5.2° when PAN:F-PI = 6:4. Meanwhile, when PAN:F-PI = 8:2, the filtration efficiency reaches 99.4 ± 0.3%, and the elongation at break can reach 76%. The fracture strength can also reach 7.1 MPa, 1.63 times that of the pure PAN membrane.

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

Two-dimensional materials and their applications in fuel cells.

In recent years, two-dimensional (2D) materials have been extensively studied and applied in the field of catalysis on account of their high specific surface areas, high exposure of metal active sites, and readily tunable structures. This article introduces various 2D materials (including materials composed of a few atomic layers) and the related synthesis methods and discusses their catalytic performances for hydrogen fuel cells, in particular, for oxygen reduction reaction and hydrogen oxidation reaction. At the end of this review, the advantages and current challenges of 2D materials are summarized, and the prospects of 2D electrocatalytic materials are proposed.

Berbamine ameliorates DSS-induced colitis by inhibiting peptidyl-arginine deiminase 4-dependent neutrophil extracellular traps formation.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with immune dysregulation affecting colon inflammatory response. Recent studies have highlighted that neutrophil extracellular traps (NETs) play an important role in the pathogenesis of UC. Berbamine (BBM), one of the bioactive ingredients extracted from Chinese herbal medicine Berberis vulgaris L, has attracted intensive attentions due to its significant anti-inflammatory activity and a marketing drug for treating leukemia in China. However, the exact role and potential molecular mechanism of BBM against UC remains elusive. In the present study, our results showed that BBM could markedly improve the pathological phenotype and the colon inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. Then, comprehensive approaches combining network pharmacology and molecular docking analyses were employed to predict the therapeutic potential of BBM in treating UC by peptidyl-arginine deiminase 4 (PAD4), a crucial molecule involved in NETs formation. The molecular docking results showed BBM had a high affinity for PAD4 with a binding energy of -9.3 kcal/mol Moreover, PAD4 expression and NETs productions, including citrullination of histone H3 (Cit-H3), neutrophil elastase (NE), myeloperoxidase (MPO) in both neutrophils and colonic tissue were reduced after BBM administration. However, in the mice with DSS-induced colitis pretreated with GSK484, a PAD4-specific inhibitor, BBM could not further reduce disease related indexes, expression of PAD4 and NETs productions. Above all, the identification of PAD4 as a potential target for BBM to inhibit NETs formation in colitis provides novel insights into the development of BBM-derived drugs for the clinical management of UC.