Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

Research Progress of Natural Products with the Activity of Anti-nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), a multi-target disease, is becoming a global epidemic. Although several anti-NASH drug candidates are being evaluated in late-stage clinical trials, none have been approved by the FDA to date. Given the global prevalence of the disease, the lack of effective drugs, and the very limited therapeutic efficacy of most of the existing synthetic drugs focusing on a single target, there is an urgent need to continue to develop new therapeutic agents. In contrast, many natural products, including pure compounds and crude extracts, possess hepatoprotective activities. Usually, these natural components are characterized by multi-targeting and low side effects. Therefore, natural products are important resources for the development of new anti- NASH drugs. In this paper, we focus on reviewing the anti-NASH potential, structure, and some of the side effects of natural products based on structural classification. We hope this mini-review will help researchers design and develop new anti-NASH drugs, especially based on the structure of natural products.

Clinical value of TAT, PIC and t-PAIC as predictive markers for severe sepsis in pediatric patients.

Objective: Sepsis in pediatric patients can progress to severe sepsis, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study aimed to investigate the ability of thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) to predict severe sepsis in pediatrics early. Methods: 148 eligible pediatric sepsis patients were enrolled in this study, and were then divided into those who progressed to severe sepsis (n = 50) or not (n = 98). Serum levels of TAT, PIC, and t-PAIC were analysed, and simplified pediatric critical illness score (PCIS) and DIC score were calculated on the day of pediatric sepsis diagnosis. Results: Compared with sepsis patients, severe sepsis patients had higher levels of TAT, PIC and t-PAIC. Correlation analysis revealed that TAT, PIC and t-PAIC were significantly correlated with simplified PCIS and DIC score. ROC curve analysis suggested that TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis with the AUC up to 0.862, 0.759 and 0.851, respectively. Stratified analysis demonstrated that the patients with increased levels of TAT, PIC and t-PAIC had worse illness severity and clinical outcome. Univariate logistic regression analysis revealed that TAT, PIC and t-PAIC were all risk factors for severe sepsis, yet only TAT and t-PAIC were independent risk factors in multivariate model. Conclusions: TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis, and correlated with illness severity in pediatrics, what's more, serum levels of TAT and t-PAIC may be independent risk factors for pediatric severe sepsis.

A selective Fibroblast Growth Factor Receptor 1/2 PROTAC degrader with antitumor activity.

The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no anti-proliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

Investigation on the Combined Effect of Hydroxypropyl Beta-Cyclodextrin (HPßCD) and Polysorbate in Monoclonal Antibody Formulation.

Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPßCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPßCD as excipients in protein formulations. The introduction of HPßCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPßCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPßCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPßCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10-3. Surface tension measurements illustrated that HPßCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Time-Frequency Aliased Signal Identification Based on Multimodal Feature Fusion.

The identification of multi-source signals with time-frequency aliasing is a complex problem in wideband signal reception. The traditional method of first separation and identification especially fails due to the significant separation error under underdetermined conditions when the degree of time-frequency aliasing is high. The single-mode recognition method does not need to be separated first. However, the single-mode features contain less signal information, making it challenging to identify time-frequency aliasing signals accurately. To solve the above problems, this article proposes a time-frequency aliasing signal recognition method based on multi-mode fusion (TRMM). This method uses the U-Net network to extract pixel-by-pixel features of the time-frequency and wave-frequency images and then performs weighted fusion. The multimodal feature scores are used as the classification basis to realize the recognition of the time-frequency aliasing signals. When the SNR is 0 dB, the recognition rate of the four-signal aliasing model can reach more than 97.3%.

Detection and Phylogenetic Analysis of Caprine Arthritis Encephalitis Virus Using TaqMan-based qPCR in Eastern China.

Caprine arthritis encephalitis is an infectious disease caused by the caprine arthritis encephalitis virus that infects goats, sheep, and other small ruminants. An outbreak of CAEV could be extremely harmful to the goat farming industry and could cause severe economic losses. We designed specific primers and probes for the gag gene and established a TaqMan real-time quantitative polymerase chain reaction assay. This method's correlation coefficient (R2) was >0.999, and the sensitivity of the assay to the plasmid-carried partial gag gene was approximately 10 copies/µL, 1000 times higher than that of conventional PCR. No specific fluorescence was detected for other sheep viruses. Using this method, we tested 776 asymptomatic sheep blood samples and 4 neurodegenerative sheep brain samples from six farms in eastern China, and the positivity rate was 0.77% (6/780). The gag gene was partially sequenced in the three positive samples and compared with the sequences from other representative strains in GenBank. The results revealed that all three strains belonged to the B1 subtype and were most closely related to the strains from Shanxi and Gansu, previously isolated in China, with their homology ranging from 97.7% to 98.9%. These results suggest that the designed RT-qPCR assay can be used to detect subclinical CAEV in sheep and that the virus is still present in eastern China.

Enhancement of Broadband Reverse Saturable Absorption of Red/Black Phosphorus Heterojunction.

Although laser technology brings convenience to production and daily life, it also causes high-energy damage. Therefore, there is an urgent need to develop optical limiting materials for laser protection. In this study, a novel nonlinear optical material, red/black phosphorus lateral heterojunction, is successfully prepared through solvothermal and ultrasonic treatment. Using the Z-scan method, the nonlinear optical properties of the red/black phosphorus heterojunction are determined at wavelengths of 532 and 1064 nm. These results indicate that the red/black phosphorus heterojunction exhibits reverse saturable absorption properties in 1.2.3-glycerol. Interestingly, the red/black phosphorus heterojunction shows an enhanced performance over red phosphorus by introducing the black phosphorus phase. Moreover, the red/black phosphorus heterojunction is doped into organically modified silicate gel glass with excellent broadband optical limiting performance. This study highlights the promising prospect of the red/black phosphorus heterojunction in the nonlinear optical and optical limiting fields.

Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Satellite observations of suspended particulate matter concentration in Lake Gaoyou in the past four decades.

Suspended Particulate Matter (SPM) concentration stands as a pivotal determinant of water quality within lake ecosystems. However, comprehension of the enduring dynamics of SPM within lakes is severely hindered due to a shortage of long-term records. Our research has developed a robust remote sensing algorithm to retrieve the SPM concentration in Lake Gaoyou, situated in the lower reaches of the Huai River basin in China. The algorithm demonstrates commendable performance, with an uncertainty of 28.68 %. Leveraging Landsat series sensors imagery, our investigation yields high spatial resolution SPM concentration maps, which first provide a four-decades record of the SPM distribution within Lake Gaoyou. Our findings unveil a significant annual reduction of 1.35 mg L-1 in SPM concentration over the past four decades. This notable decline is probably attributable to a series of ecological initiatives to enhancing the management of the eco-friendly within the basin. Furthermore, our research delineated the influence of environmental factors on the intra-annual SPM dynamics across distinct spatial domains, encompassing the natural inlet region, semi-obstructed inlet region and outlet areas within the lake The SPM concentration in the natural inlet region exhibits a conspicuous correlation with precipitation. Increased precipitation induces runoff within the basin, facilitating the transport of suspended solids and sediment into the lake, consequently augmenting SPM levels. Conversely, the semi-obstructed inlet and outlet areas are predominantly influenced by the wind field, with variations in SPM attributed to sediment resuspension caused by water mixing driven by wind forcing. Our research can be considered an important reference to the evaluation of the management of the lake over long periods.

Desquamative interstitial pneumonia: A case report.

Diffuse cystic lung diseases (DCLDs) are a group of heterogeneous lung diseases that are characterized by inflated spaces or cysts within the lung parenchyma. They also exhibit similar imaging characteristics and clinical manifestations compared with those of cystic lesions, such as pulmonary cavities, emphysema, bronchiectasis and honeycomb lung. The most common DCLDs encountered in the clinic include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, Langerhans cell histiocytosis and lymphocytic interstitial pneumonia. In particular, accurate diagnosis of DCLDs in terms of the different lesions found is important, because their clinical courses, prognoses and treatment strategies vary widely. However, because DCLDs usually have overlapping clinical presentations, diagnosis typically requires a combination of clinical considerations that take into account characteristics of the cyst, its distribution, organ of origin and background parenchymal findings. The present report documents the case of a 73-year-old man diagnosed with desquamative interstitial pneumonia (DIP). The patient was admitted to the hospital due to chest tightness, shortness of breath and intermittent fever. The patient had been a smoker for >60 years and had stopped smoking for 6 months before being admitted. A transbronchial lung biopsy, bronchoscopy and alveolar lavage cytopathogen culture were performed to confirm the diagnosis of desquamative interstitial pneumonia (DIP). The patient was treated with hormonal therapy and advised to abstain from smoking. The diagnosis of DIP in comparison with other DCLDs was summarized for the purpose of providing a clinical basis for the accurate clinical diagnosis of DIP and the development of evidence-based practice guidelines.

An Advanced Intrahepatic Cholangiocarcinoma Patient Benefits from Personalized Immunotherapy.

Advanced intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by limited response to standard therapeutic modalities, such as radiotherapy, chemotherapy, and targeted therapy. The prognosis for patients with advanced ICC is exceedingly bleak, with an overall survival of less than 1 year. In recent years, personalized neoantigen vaccines have emerged as a promising approach to augment the immune response against tumors. Clinical investigations are currently underway to evaluate the efficacy of neoantigen-based peptide, DNA, and dendritic cell vaccines. Herein, we present a noteworthy case of advanced ICC patients who experienced disease progression following relapse and subsequently received immunotherapy with a personalized neoantigen nanovaccine. This innovative treatment strategy involved the administration of a custom-designed neoantigen-based peptide nanovaccine tailored to the patient's specific gene mutation profile subsequent to failure of first-line therapy. The clinical efficacy and anti-tumor immune responses were evaluated using various methods, including imaging, interferon-γ ELISPOT assay, and intracellular cytokine staining. Notably, the neoantigen nanovaccine elicited a robust and specific tumor-killing effect mediated by T cells, resulting in a durable response lasting up to 25 months. These findings highlight the potential of neoantigen-based immunotherapy as a novel therapeutic avenue for the management of advanced ICC.

Wide-field color imaging through multimode fiber with single wavelength illumination: plug-and-play approach.

Multimode fiber (MMF) is extensively studied for its ability to transmit light modes in parallel, potentially minimizing optical fiber size in imaging. However, current research predominantly focuses on grayscale imaging, with limited attention to color studies. Existing colorization methods often involve costly white light lasers or multiple light sources, increasing optical system expenses and space. To achieve wide-field color images with typical monochromatic illumination MMF imaging system, we proposed a data-driven "colorization" approach and a neural network called SpeckleColorNet, merging U-Net and conditional GAN (cGAN) architectures, trained by a combined loss function. This approach, demonstrated on a 2-meter MMF system with single-wavelength illumination and the Peripheral Blood Cell (PBC) dataset, outperforms grayscale imaging and alternative colorization methods in readability, definition, detail, and accuracy. Our method aims to integrate MMF into clinical medicine and industrial monitoring, offering cost-effective high-fidelity color imaging. It serves as a plug-and-play replacement for conventional grayscale algorithms in MMF systems, eliminating the need for additional hardware.

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

HDAC9-mediated calmodulin deacetylation induces memory impairment in Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. METHODS: The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. RESULTS: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. CONCLUSIONS: HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.

Peripheral serotonergic neurons regulate gut motility and anxiety-like behavior.

Serotonergic circuits in the central nervous system play important roles in regulating mood and behavior, yet the functions of peripheral serotonergic neurons are less understood. Here, we engineered mice lacking the serotonin-producing enzyme Tph2 in peripheral neurons but with intact Tph2 in central neurons. In contrast to mice lacking Tph2 in all neurons, mice lacking Tph2 in peripheral serotonergic neurons did not exhibit increased territorial aggression. However, similar to the total body Tph2 knockout (KO) mice, the conditional KO animals exhibited reduced gut motility and decreased anxiety-like behavior. These observations reveal that peripheral serotonergic neurons contribute to control of intestinal motility and anxiety-like behavior and suggest that therapeutics targeting this subset of peripheral neurons could be beneficial.

N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.

N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers.

Constructing and Evaluating a Mitophagy-Related Gene Prognostic Model: Implications for Immune Landscape and Tumor Biology in Lung Adenocarcinoma.

Mitophagy, a conserved cellular mechanism, is crucial for cellular homeostasis through the selective clearance of impaired mitochondria. Its emerging role in cancer development has sparked interest, particularly in lung adenocarcinoma (LUAD). Our study aimed to construct a risk model based on mitophagy-related genes (MRGs) to predict survival outcomes, immune response, and chemotherapy sensitivity in LUAD patients. We mined the GeneCards database to identify MRGs and applied LASSO/Cox regression to formulate a prognostic model. Validation was performed using two independent Gene Expression Omnibus (GEO) cohorts. Patients were divided into high- and low-risk categories according to the median risk score. The high-risk group demonstrated significantly reduced survival. Multivariate Cox analysis confirmed the risk score as an independent predictor of prognosis, and a corresponding nomogram was developed to facilitate clinical assessments. Intriguingly, the risk score correlated with immune infiltration levels, oncogenic expression profiles, and sensitivity to anticancer agents. Enrichment analyses linked the risk score with key oncological pathways and biological processes. Within the model, MTERF3 emerged as a critical regulator of lung cancer progression. Functional studies indicated that the MTERF3 knockdown suppressed the lung cancer cell proliferation and migration, enhanced mitophagy, and increased the mitochondrial superoxide production. Our novel prognostic model, grounded in MRGs, promises to refine therapeutic strategies and prognostication in lung cancer management.

Estimating four-decadal variations of seagrass distribution using satellite data and deep learning methods in a marine lagoon.

Seagrasses are marine flowering plants that inhabit shallow coastal and estuarine waters and serve vital ecological functions in marine ecosystems. However, seagrass ecosystems face the looming threat of degradation, necessitating effective monitoring. Remote-sensing technology offers significant advantages in terms of spatial coverage and temporal accessibility. Although some remote sensing approaches, such as water column correction, spectral index-based, and machine learning-based methods, have been proposed for seagrass detection, their performances are not always satisfactory. Deep learning models, known for their powerful learning and vast data processing capabilities, have been widely employed in automatic target detection. In this study, a typical seagrass habitat (Swan Lake) in northern China was used to propose a deep learning-based model for seagrass detection from Landsat satellite data. The performances of UNet and SegNet at different patch scales for seagrass detection were compared. The results showed that the SegNet model at a patch scale of 16 × 16 pixels worked well, with validation accuracy and loss of 96.3 % and 0.15, respectively, during training. Evaluations based on the test dataset also indicated good performance of this model, with an overall accuracy >95 %. Subsequently, the deep learning model was applied for seagrass detection in Swan Lake between 1984 and 2022. We observed a noticeable seasonal variation in germination, growth, maturation, and shrinkage from spring to winter. The seagrass area decreased over the past four decades, punctuated by intermittent fluctuations likely attributed to anthropogenic activities, such as aquaculture and construction development. Additionally, changes in landscape ecology indicators have demonstrated that seagrass experiences severe patchiness. However, these problems have weakened recently. Overall, by combining remote sensing big data with deep learning technology, our study provides a valuable approach for the highly precise monitoring of seagrass. These findings on seagrass area variation in Swan Lake offer significant information for seagrass restoration and management.

Growth performance, lipid metabolism, and systemic immunity of weaned piglets were altered by buckwheat protein through the modulation of gut microbiota.

Tartary buckwheat protein (BWP) is well known for the wide-spectrum antibacterial activity and the lipid metabolism- regulating property; therefore, BWP can be applied as feed additives to improve the animal's nutritional supply. With the aim to investigate the bioactive actions of the BWP, growth performance, lipid metabolism and systemic immunity of the weaned piglets were measured, and the alterations of pig gut microbiota were also analyzed. According to the results, the growth performances of the weaned piglets which were calculated as the average daily gain (ADG) and the average daily feed intake (ADFI) were significantly increased when compared to the control group. Simultaneously, the serum levels of the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, while the levels of high-density lipoprotein cholesterol (HDL-C) were increased in the BWP group. Moreover, the relative abundances of Lactobacillus, Prevotella_9, Subdoligranulum, Blautia, and other potential probiotics in the gut microbiota of weaned piglets were obviously increased in the BWP group. However, the relative abundances of Escherichia-Shigella, Campylobacter, Rikenellaceae_RC9_gut_group and other opportunistic pathogens were obviously decreased in the BWP group. In all, BWP was proved to be able to significantly improve the growth performance, lipid metabolism, and systemic immunity of the weaned piglets, and the specific mechanism might relate to the alterations of the gut microbiota. Therefore, BWP could be explored as a prospective antibiotic alternative for pig feed additives.