Study on efficiency and mechanism of ultrasonic controlling membrane fouling in ceramic membrane bioreactors.

In recent years, ceramic membranes have been increasingly used in membrane bioreactors (MBRs). However, membrane fouling was still the core issue restricting the large-scale engineering application of ceramic MBRs. As a novel and alternative technology, ultrasonic could be used to control membrane fouling. This research focused on the efficiency and mechanism of ultrasonic controlling membrane fouling in ceramic MBRs. The results showed that ultrasonic reduced the sludge concentration in MBR, and the average particle size of sludge was always in a high range. The sludge activity of the system was stable at 6-9 (mg O2·(g MLSS·h)-1), indicating that ultrasonic did not destroy the activity of microorganisms in the system. The extracellular polymer substance (EPS) of the ultrasonic group was slightly higher than that of the control group, while the soluble microbial product (SMP) content was relatively stable. The ceramic membrane of the ultrasonic group has a partial retention effect on the organic components. The application of ultrasonic slowed down the decrease of the hydrophilicity of the ceramic membrane. The main pollutants on the membrane surface exist in the form of aromatic and heteroaromatic rings, alkynes, and so forth. Ultrasonic removes the amide substances from the membrane surface. Membrane fouling resistance is mainly due to membrane pore blockage, accounting for 75.53%. PRACTITIONER POINTS: Enrich the research on the mechanism of ultrasonic technology in membrane fouling control. The MBR can still operate normally with ultrasonic applied. The time for the ceramic membrane to reach the fouling end point is 2.4 times that without ultrasonic. The main cause of membrane fouling was pore blocking, accounting for 75.53%.

Dual-Cation CuAgSe-Based Material: Rapid Mass Transfer in Synthesis and High Thermoelectric Performance Realization.

Understanding mass transfer mechanisms is vital for developing new material synthesis and densification technologies. Ion transport, serving both mass and charge transfer, is essential for the rapid preparation of high-performance fast ionic conductor thermoelectric materials like Zn4Sb3 and Cu2Q (Q = S, Se). In the case of dual-cation fast ion conductor materials like CuAgSe, exploring the relationship between cation transport becomes pertinent. In this study, copper (Cu) and selenium (Se) undergo a reaction in the presence of an electric field (∼15 A), resulting in the formation of the CuSe compound. Subsequent to this initial reaction, a subsequent thermal environment facilitates the interaction among Cu, CuSe, and Ag2Se, culminating in the rapid formation and densification of CuAgSe (with a relative density exceeding 99%) in just 30 s. Evidently, the diffusion of copper ions substantiates a pivotal role in facilitating mass transfer. As a result, CuAg1+xSe samples with different silver contents (x = 0.01, 0.02, 0.03, 0.04 and 0.05) can effectively inhibit cation vacancy, and introduce highly ordered Ag nanotwins to enhance the electrical transport performance. For CuAg1.04Se, a peak ZT value of 1.0 can be achieved at 673 K, which is comparable to the literatures. This work will guide the future electric field-assisted rapid mass transfer of materials.

The Failure Mechanism of Micro Thermoelectric Devices under the Action of the Temperature Field.

The micro thermoelectric device (m-TED) boasts features such as adjustable volume, straightforward structure, and precise, rapid temperature control, positioning it as the only current solution for managing the temperature of microelectronic systems. It is extensively utilized in 5G optical modules, laser lidars, and infrared detection. Nevertheless, as the size of the m-TED diminishes, the growing proportion of interface damages the device's operational reliability, constraining the advancement of the m-TED. In this study, we used commercially available bismuth telluride materials to construct the m-TED. The device's reliability was tested under various temperatures: -40, 85, 125, and 150 °C. By deconstructing and analyzing the devices that failed during the tests, we discovered that the primary cause of device failure was the degradation of the solder layer. Moreover, we demonstrated that encapsulating the device with polydimethylsiloxane (PDMS) could effectively delay the deterioration of its performance. This study sparks new insights into the service reliability of m-TEDs and paves the way for further optimizing device interface design and enhancing the device manufacturing process.

Generation of High-Quality African Swine Fever Virus Complete Genome from Field Samples by Next-Generation Sequencing.

African swine fever (ASF) is a lethal contagious viral disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV). The pandemic spread of ASF has caused severe effects on the global pig industry. Whole-genome sequencing provides crucial information for virus strain characterization, epidemiology analysis and vaccine development. Here, we evaluated the performance of next-generation sequencing (NGS) in generating ASFV genome sequences from clinical samples. Thirty-four ASFV-positive field samples including spleen, lymph node, lung, liver and blood with a range of Ct values from 14.73 to 25.95 were sequenced. For different tissue samples collected from the same sick pigs, the proportion of ASFV reads obtained from the spleen samples was 3.69-9.86 times higher than other tissues. For the high-viral-load spleen samples (Ct < 20), a minimum of a 99.8% breadth of ≥10× coverage was revealed for all the samples. For the spleen samples with Ct ≥ 20, 6/12 samples had a minimum of a 99.8% breadth of ≥10× coverage. A high average depth of sequencing coverage was also achieved from the blood samples. According to our results, high-quality ASFV whole-genome sequences could be obtained from the spleen or blood samples with Ct < 20. The high-quality ASFV genome sequence generated in this study was further used for the high-resolution phylogenetic analysis of the ASFV genomes in the early stage of the ASF epidemic in China. Our study demonstrates that NGS may act as a useful tool for efficient ASFV genome characterization, providing valuable information for disease control.

AnCMBR-AFB-integrated process for the treatment of high nitrogen and phosphorus wastewater.

Improving the nitrogen and phosphorus removal rates and efficiently controlling membrane fouling are the keys to fully exploiting the applicability of anaerobic membrane bioreactor (AnMBR) process in high-concentration wastewater treatment. To that purpose, an integrated reactor composed of an anaerobic ceramic membrane bioreactor and N anaerobic fluidized bed (AnCMBR-AFB) was built and pollutant removal efficiency, nitrogen and phosphorus recovery characteristics, and membrane pollution features of this integrated reactor were investigated. The results revealed that the integrated reactor had good pollutant removal efficiency, with turbidity, chromaticity, and UV254 average values of the effluent being 0.470 NTU, 0.011 A, and 0.057 cm-1, respectively, and the average CODCr removal rate was 80%. The nitrogen and phosphorus recoveries were significantly higher than the nitrogen and phosphorus removal rates of conventional AnMBR at 23.20 ± 1.17% and 43.34 ± 1.54%, respectively. Microscopic analysis revealed the formation of magnesium ammonium phosphate (MAP) crystals on the carrier's surface, and friction between the carrier and the membrane surface could delay membrane fouling while allowing the contaminated membrane surface to retain significant roughness. Membrane fouling was mostly brought on by amides and saturated hydrocarbons, and inorganic metal ions also played a role to some extent.

SNR enhancement of quasi-distributed weak acoustic signal detection by elastomers and MMF integrated Φ-OTDR.

We have proposed and demonstrated a weak acoustic signal detection technology based on phase-sensitive optical time-domain reflectometry (Φ-OTDR). Non-contact acoustic signals transmitting through air gap between the sound source and the receiver are difficult to detect due to fast attenuation. In order to improve the detection ability of non-contact weak acoustic signals, we demonstrate that multi-mode fiber (MMF) is a better solution than single-mode fiber (SMF) benefiting from its larger core and higher Rayleigh backscattering (RBS) capture coefficient. The frequency signal-to-noise ratio (SNR) has been enhanced by 9.26 dB. Then, with the help of 3D printing technology, elastomers have been designed to further enhance the detection ability due to the high-sensitive response to acoustic signals. Compared with the previous reported "I" type elastomer, the location and frequency SNR enhancement caused by our new proposed "n" type elastomer are 8.39 dB and 11.02 dB in SMF based system. The values are further improved to 10.51 dB and 13.38 dB in MMF and "n" type elastomer integrated system. And a phase-pressure sensitivity of -94.62 dB re rad/µPa has been achieved at 2.5 kHz. This non-contact weak acoustic signal detection technique has great application potential in the quasi-distributed partial discharge (PD) detection of smart grid.

Tunable Hydrogel Electronics for Diagnosis of Peripheral Neuropathy.

Peripheral neuropathy characterized by rapidly increasing numbers of patients is commonly diagnosed via analyzing electromyography signals obtained from stimulation-recording devices. However, existing commercial electrodes have difficulty in implementing conformal contact with skin and gentle detachment, dramatically impairing stimulation/recording performances. Here, this work develops on-skin patches with polyaspartic acid-modified dopamine/ethyl-based ionic liquid hydrogel (PDEH) as stimulation/recording devices to capture electromyography signals for the diagnosis of peripheral neuropathy. Triggered by a one-step electric field treatment, the hydrogel achieves rapid and wide-range regulation of adhesion and substantially strengthened mechanical performances. Moreover, hydrogel patches assembled with a silver-liquid metal (SLM) layer exhibit superior charge injection and low contact impedance, capable of capturing high-fidelity electromyography. This work further verifies the feasibility of hydrogel devices for accurate diagnoses of peripheral neuropathy in sensory, motor, and mixed nerves. For various body parts, such as fingers, the elderly's loose skin, hairy skin, and children's fragile skin, this work regulates the adhesion of PDEH-SLM devices to establish intimate device/skin interfaces or ensure benign removal. Noticeably, hydrogel patches achieve precise diagnoses of nerve injuries in these clinical cases while providing extra advantages of more effective stimulation/recording performances. These patches offer a promising alternative for the diagnosis and rehabilitation of neuropathy in future.

Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis.

BACKGROUND: Senescent adipose-derived stem cells (ASCs) exhibit reduced therapeutic efficacy during wound healing. Transcriptional regulation factors including long noncoding RNAs (lncRNAs) reportedly have essential roles in stem cell aging. However, the mechanisms of which lncRNAs influence mesenchymal stem cell aging and how it works need further investigation. METHODS: The expression patterns of lncRNA senescence-associated noncoding RNA (SAN) and miR-143-3p in ASCs obtained from old and young volunteer donors were detected by quantitative polymerase chain reaction. ASCs with overexpression or knockdown of SAN and γ-adducin (ADD3) were constructed by lentiviral transduction. Mimic and inhibitor were used to manipulate the cellular level of miR-143-3p in ASCs. The effects of these RNAs on ASCs proliferation, migration and cellular senescence were examined by EdU, transwell and senescence-activated ß-galactosidase (SA-ß-gal) staining assays. Wound scratch and tube formation assays were conducted to evaluate the capacities of ASCs in promoting fibroblasts migration and endothelial cells angiogenesis. Furthermore, dual-luciferase assays and rescue experiments were performed to identify the RNA interactions. Finally, the therapeutic effects of SAN-depleted aged ASCs were evaluated in a skin injury model. RESULTS: The lncRNA SAN (NONHSAT035482.2) was upregulated in aged ASCs; it controlled cellular senescence in ASCs. lncRNA SAN knockdown in ASCs led to ASC functional enhancement and the inhibition of cellular senescence; it also promoted the effects of conditioned medium (CM) on endothelial cell tube formation and fibroblast migration. Mechanistic analysis showed that SAN serves as a sponge for miR-143-3p, thereby regulating the expression of ADD3. The application of SAN-depleted aged ASCs increased re-epithelialization, collagen deposition, neovascularization and led to accelerated skin wound closure, compared with transplantation of aged ASCs. CONCLUSION: The lncRNA SAN mediates ASC senescence by regulating the miR-143-3p/ADD3 pathway, providing a potential target for rejuvenation of senescent ASCs and enhancement of wound repair.

Impairment of bile acid metabolism and altered composition by lead and copper in Bufo gargarizans tadpoles.

Lead (Pb) and copper (Cu) are two common heavy metal contaminants in environments, and liver is recognized as one of the main target organs for toxicity of Pb and Cu in animal organisms. Bile acids play a critical role in regulating hepatic metabolic homeostasis by activating farnesoid X receptor (Fxr). However, there were few studies on the interactions between bile acids and liver pathology caused by heavy metals. In this work, the histopathological changes, targeted metabolome and transcriptome responses in the liver of Bufo gargarizans tadpoles to Pb and/or Cu were examined. We found that exposure to Pb and/or Cu altered the hepatic bile acid profile, resulting in increased hydrophobicity and toxicity of the bile acid pool. And the expression of genes involved in bile acid metabolism and their downstream signaling pathways in the liver were significantly altered by Pb and/or Cu exposure. The alteration of bile acid profiles and the expression of genes related to bile acid metabolism might induce oxidative stress and inflammation, ultimately inducing hepatocyte injury observed in the histological sections. To our knowledge, this is the first study to provide histological, biochemical, and molecular evidence for establishing the link between Pb and Cu exposure, disturbances in hepatic bile acid metabolism, and liver injury.

High-efficiency cleaning technology and lifespan prediction for the ceramic membrane treating secondary treated effluent.

Chemical cleaning is one of the key technical means to control membrane fouling, restore membrane flux and ensure the stable operation of membrane systems. In the experiment, the six most representative chemical cleaning agents for ceramic membranes, such as sulfuric acid (H2SO4), sodium hydroxide (NaOH), sodium hypochlorite (NaClO), ethylenediaminetetraacetic acid disodium salt (EDTA-Na2), sodium dodecyl sulfate (SDS) and nonylphenol polyoxyethylene ether (OP-10), were used as research objects. The cleaning effect of the two-step combined cleaning of chemical cleaning agents on the fouled membrane was systematically investigated. Results showed that the order of the chemical cleaning agent had a significant effect on the cleaning effect. The best chemical cleaning program was determined to be NaClO first and then SDS: the fouled ceramic membrane was soaked in NaClO solution at 0.15% for 2.5 h and further soaked in SDS solution at five times its own critical micelle concentration for 2.5 h. The predicted long-term lifespan of the ceramic membranes was 4.91 years. Scanning electron microscopy-energy spectrum analysis showed that the surface roughness of the cleaned ceramic membrane was slightly higher than that of the new membrane. The contact angle was slightly lower than that of the new membrane.

Picky eating is associated with lower life satisfaction and elevated psychological distress and psychosocial impairment in Chinese pregnant women.

OBJECTIVE: This study assessed picky eating in pregnant women by exploring whether picky eating is associated with pregnant women's well-being, including life satisfaction, psychological distress, and psychosocial impairment. METHOD: Data collected were from 345 Chinese pregnant women ( M age = 29.95 years, SD = 5.58). Pearson correlation analyses were conducted to examine zero-order correlations between picky eating and well-being variables (i.e., life satisfaction, psychological distress, and psychosocial impairment). Hierarchical multiple regressions were conducted to examine the unique associations of picky eating with well-being variables, adjusting for demographic and pregnancy-related characteristics and thinness-oriented disordered eating. RESULTS: Picky eating was significantly and negatively correlated with life satisfaction (r = -.24, p < .001) and positively correlated with psychological distress (r = .37, p < .001) and psychosocial impairment (r = .50, p < .001). When adjusting for covariates and thinness-oriented disordered eating, picky eating was still significantly associated with lower life satisfaction, higher psychological distress, and higher psychosocial impairment. DISCUSSION: The findings suggest that picky eating may be a significant correlate of pregnant women's poorer well-being. Future research with longitudinal designs is warranted to further examine the temporal associations between picky eating and pregnant women's well-being. PUBLIC SIGNIFICANCE: Picky eating behaviors are poorly understood in pregnant women. Our results revealed that higher picky eating behaviors were associated with lower life satisfaction and higher psychological distress and psychosocial impairment in Chinese pregnant women. Researchers and clinicians may consider picky eating in the assessment and treatment of mental health and disordered eating in pregnant women.

On-skin biosensors for noninvasive monitoring of postoperative free flaps and replanted digits.

Severe soft tissue defects and amputated digits are clinically common injuries. Primary treatments include surgical free flap transfer and digit replantation, but these can fail because of vascular compromise. Postoperative monitoring is therefore crucial for timely detection of vessel obstruction and survival of replanted digits and free flaps. However, current postoperative clinical monitoring methods are labor intensive and highly dependent on the experience of nurses and surgeons. Here, we developed on-skin biosensors for noninvasive and wireless postoperative monitoring based on pulse oximetry. The on-skin biosensor was made of polydimethylsiloxane with gradient cross-linking to create a self-adhesive and mechanically robust substrate that interfaces with skin. The substrate was shown to exhibit appropriate adhesion on one side for both high-fidelity measurements of the sensor and low risk of peeling injury to delicate tissues. The other side demonstrated mechanical integrity to facilitate flexible hybrid integration of the sensor. Validation studies using a model of vascular obstruction in rats demonstrated the effectiveness of the sensor in vivo. Clinical studies indicated that the on-skin biosensor was accurate and more responsive than current clinical monitoring methods in identifying microvascular conditions. Comparisons with existing monitoring techniques, including laser Doppler flowmetry and micro-lightguide spectrophotometry, further verified the sensor's accuracy and ability to identify both arterial and venous insufficiency. These findings suggest that this on-skin biosensor may improve postoperative outcomes in free flap and replanted digit surgeries by providing sensitive and unbiased data directly from the surgical site that can be remotely monitored.

Associations among retrospective parenting styles, retrospective food parenting, and current eating behaviors in Chinese adults.

The current study explored the relationships between retrospective parenting styles and food parenting in childhood (≤ 12 years old) and Chinese adults' current maladaptive and adaptive eating behaviors. We recruited 501 Chinese adults (50.30% men, aged 19-46 years). A set of questionnaires were used to measure retrospective parenting styles (i.e., emotional warmth, rejection, and overprotection), food parenting (i.e., parental concern, monitoring, pressure to eat, and restriction), and current maladaptive (i.e., disordered eating) and adaptive (i.e., intuitive eating) eating behaviors. Correlation and mediation analyses were employed to analyze these data. Results revealed that retrospective parenting styles and food parenting were significantly related to current maladaptive and adaptive eating behaviors in both Chinese men and women. Mediation analyses showed that higher retrospective parental warmth was related to higher retrospective parental concern which, in turn, was related to higher current disordered eating in men (indirect effect = 0.14, 95% CI 0.08, 0.24). Furthermore, higher retrospective parental overprotection was related to higher retrospective parental pressure to eat which, in turn, was related to higher current disordered eating in men (indirect effect = 0.06, 95% CI 0.01, 0.14). For women, higher retrospective parental warmth was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.04, 95% CI = -0.10, -0.01). Furthermore, higher retrospective parental overprotection was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.03, 95% CI = -0.08, -0.004). The findings indicate the importance of including childhood parenting styles and food parenting in future research and intervention of adults' current maladaptive and adaptive eating behaviors.

[Automatic modeling of the knee joint based on artificial intelligence].

Objective: To investigate an artificial intelligence (AI) automatic segmentation and modeling method for knee joints, aiming to improve the efficiency of knee joint modeling. Methods: Knee CT images of 3 volunteers were randomly selected. AI automatic segmentation and manual segmentation of images and modeling were performed in Mimics software. The AI-automated modeling time was recorded. The anatomical landmarks of the distal femur and proximal tibia were selected with reference to previous literature, and the indexes related to the surgical design were calculated. Pearson correlation coefficient ( r) was used to judge the correlation of the modeling results of the two methods; the consistency of the modeling results of the two methods were analyzed by DICE coefficient. Results: The three-dimensional model of the knee joint was successfully constructed by both automatic modeling and manual modeling. The time required for AI to reconstruct each knee model was 10.45, 9.50, and 10.20 minutes, respectively, which was shorter than the manual modeling [(64.73±17.07) minutes] in the previous literature. Pearson correlation analysis showed that there was a strong correlation between the models generated by manual and automatic segmentation ( r=0.999, P<0.001). The DICE coefficients of the 3 knee models were 0.990, 0.996, and 0.944 for the femur and 0.943, 0.978, and 0.981 for the tibia, respectively, verifying a high degree of consistency between automatic modeling and manual modeling. Conclusion: The AI segmentation method in Mimics software can be used to quickly reconstruct a valid knee model.

Lead and copper influenced bile acid metabolism by changing intestinal microbiota and activating farnesoid X receptor in Bufo gargarizans.

Lead (Pb) and copper (Cu) are ubiquitous metal contaminants and can pose a threat to ecosystem and human health. Bile acids have recently received considerable attention for their role in the maintenance of health. However, there were few studies on whether Pb and Cu affect bile acid metabolism in amphibians. In this study, a combination approach of histological analysis, targeted metabolomics, 16S rDNA sequencing and qPCR was used to explore the impacts of Pb, Cu and their mixture (Mix) on bile acid in Bufo gargarizans tadpoles. The results showed that Pb, Cu, and Mix resulted in intestinal damage and altered the bile acid profiles. Specifically, Pb and Mix exposure decreased total bile acid concentrations while increased toxic bile acid levels; in contrast, Cu exposure increased total bile acid levels. And hydrophilic bile acids were reduced in all treated tadpoles. Moreover, Pb and/or Cu changed the composition of intestinal microbiota, especially Clostridia, Bacteroides and Eubacterium involved in bile acid biotransformation. qPCR revealed that the decreased total bile acid concentrations in Pb- and Mix-treated tadpoles were most likely attributed to the activation of intestinal farnesoid X receptor (Fxr), which suppressed bile acid synthesis and reabsorption. While activated fxr in the Cu treatment group may be a regulatory mechanism in response to increased bile excretion, which is a detoxification route of tadpoles under Cu stress. Collectively, Pb, Cu and Mix changed bile acid profiles by affecting intestinal microbial composition and activating Fxr signaling. This study provided insight into the impacts of Pb and Cu on bile acid metabolism and contributed to the assessment of the potential ecotoxicity of heavy metals on amphibians.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy.

Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy. However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy. Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Hybrid Reinforcement Learning for Power Transmission Network Self-Healing Considering Wind Power.

Transmission network self-healing considering uncertain wind power becomes crucial with increasing penetration of wind power. A hybrid reinforcement learning (HRL) method combining offline self-learning with online Monte Carlo tree search (MCTS) is designed to deal with the strong uncertainty induced by wind power restoration. The HRL method trains a policy network with offline self-learning based on historical wind and transmission system data. It then applies the policy network to guide MCTS to realize step-by-step transmission network self-healing based on real-time and forecast data in different wind power scenarios. Besides, a model predictive control method for active power dispatch is proposed to improve wind power generation credibility during self-healing. Simulation results of both test and real-life power systems demonstrate that the proposed method can realize online transmission system self-healing reliably. Comparisons among different reinforcement learning methods indicate that the number of scenarios dominated by HRL is more than twice that dominated by MCTS and a dozen times that dominated by deep Q-network. Meanwhile, the online method is more flexible in uncertain wind power scenarios than optimization methods.

Lead and copper led to the dysregulation of bile acid homeostasis by impairing intestinal absorption in Bufo gargarizans larvae: An integrated metabolomics and transcriptomics approach.

Bile acids, as metabolic regulators and signaling molecules, play key roles in the regulation of host metabolism and immune responses. Heavy metals such as lead (Pb) and copper (Cu) are widespread environmental pollutants that threaten public health. However, the effects of heavy metals on bile acid metabolism and the underlying molecular mechanisms remain unclear, particularly for ecologically important amphibian species. In the present research, the effects of exposure to environmentally-relevant concentrations of Pb (250 µg/L), Cu (50 µg/L), and a mixture of both (Mix) on bile acid metabolism and the underlying molecular mechanisms in the intestines of Bufo gargarizans larvae were comprehensively investigated using histopathology, metabolomics and transcriptomics analysis. Our results suggested that Pb and/or Cu caused histopathological damage to the intestine and liver, such as decreased intestinal epithelial cell height and dilated hepatic sinusoid. The total bile acid level was decreased in the Pb and Mix exposure groups but elevated in the Cu treatment. A significant decrease in the ratio of conjugated to unconjugated bile acids was present in all treatment groups. Also, the level of GCA was increased while TCA and TCDCA were decreased in all exposure groups. In addition, exposure to Pb and Cu altered the expression levels of genes related to intestinal absorption. For example, mrp2, mrp3 and aqp4 had higher expression in the Pb and Mix treatment groups, and aqp1 and mrp4 were increased in the Cu treatment group. Overall, we speculated that the dysregulation of bile acid homeostasis induced by Pb and Cu exposure may be due to impaired intestinal absorption. These findings raise further concerns about the hazards of Pb and/or Cu in influencing bile acid metabolism that might lead to the development of metabolic diseases and inflammatory disorders.