Multi-therapeutic-activity selenium nanodot toward preventing brain injury and restoring neurobehavioral functions following hemorrhagic stroke.

Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases.

"Synergistic anticoagulant and endothelial regeneration strategy" based on mussel-inspired phospholipid copolymer coating and bioactive zeolitic imidazolate frameworks-90 to maintain the patency of CoCr stent.

Given the risks of poor patient compliance and bleeding associated with current dual antiplatelet therapies, it is urgent to develop the next generation of cardiovascular stents with anticoagulation and rapid endothelialization capabilities. Inspired by the prominent bioactivity and bioavailability of zeolitic imidazolate framework-90 (ZIF-90) in driving endothelial cell (EC) morphogenesis, this research proposes a "synergistic anticoagulant and endothelial regeneration strategy" depending on mussel-inspired phospholipid copolymer (MIPC) and ZIF-90. Depending on the copolymerization of the catechol with dopamine (Dopa) monomers, Dopa/MIPC coating was immobilized on the surface of CoCr via a one-pot process for resisting the initial thrombosis induced by platelets and fibrinogen. Meanwhile, ZIF-90 was loaded on the coating via coordination effect, aiming to accelerate the proliferation and migration of ECs. Compared with CoCr, the well-designed CoCr-Dopa/MIPC@ZIF-90 not only reduced fibrinogen adhesion by approximately 40 % and platelet adhesion by almost 55 %, but also promoted the proliferation and migration of ECs significantly in vitro. Furthermore, the blood flow velocity of CoCr-Dopa/MIPC@ZIF-90 stent was similar to natural aorta and ECs coverage on it was greatly strengthened after 30 days in a rat aorta vascular stent implantation model. Collectively, CoCr-Dopa/MIPC@ZIF-90 exhibited obvious superiority in reducing the formation of thrombus and promoting endothelial regeneration, which might meet the high requirement for the next generation of vascular stent.

Insights on the Contradiction between the Affinity and Capacity of Ferrihydrite toward As(III) and As(V): Surface Reaction Revisited.

Ferrihydrite is omnipresent in nature, and its adsorption of As(III/V) decides the migration of arsenic. Although As(III) is commonly recognized as the more mobile species of inorganic arsenic, it sometimes exhibits less mobility in ferrihydrite systems, which calls for further insights. In this study, we elucidated the adsorption behavior and mechanisms of As(III/V) on ferrihydrite under different loading levels (molar ratio As/Fe = 0-0.38), solution pH (3-10), and coexisting ions [P(V) and Ca(II)] based on batch adsorption experiments, surface complexation modeling, density functional theory calculations, and X-ray photoelectron spectroscopy. Our results show that As(III) exhibits weaker adsorption affinity but a larger capacity compared with that of As(V). On ferrihydrite, As(III) and As(V) are adsorbed mainly as bidentate mononuclear complexes at type-a sites [≡Fe(OH-0.5)2] and bidentate binuclear complexes at type-b sites (2≡FeOH-0.5), respectively. As the dosage increases, As(III) further forms mononuclear monodentate complexes at both surface sites, resulting in a higher site utilization efficiency, while As(V) does not due to repulsive electrostatic interaction. The difference in surface species of As(III/V) also leads to complex responses when coexisting with high concentrations of P(V) and Ca(II). This study helps us to understand environmental behavior of As(III/V) and develop remediation strategy in As(III/V) contaminated systems.

Nitrite facilitated transformation of halophenols in ice.

This study investigated the expediated transformation of halophenols in the presence of nitrite (NO2-) under slightly acidic conditions in ice, whereas such transformation was negligible in liquid water at 4 °C. We proposed that this phenomenon was attributed to the freeze-concentration effect, incurring a pH drop and the aggregation of NO2- and halophenols within the liquid-like grain boundary layer amid ice crystals. Within this micro-environment, NO2- underwent protonation to generate reactive nitrous acid (HNO2) and nitrosonium ions (NO+) that facilitate the nitration and oxidation of halophenols. When 10 µÐœ halophenol was treated by freezing in the presence of 5 µÐœ NO2-, the total yields of nitrated products reached 2.4 µÐœ and 1.4 µÐœ within 12 h for 2-chlorophenol (2CP) and 2-bromophenol (2BP), respectively. NO+ drove oxidative coupling reactions, generating hydroxyl polyhalogenated diphenyl ethers (OH-PBDEs) and hydroxyl polyhalogenated diphenyls via C-O or C-C coupling. These two pathways were intricately intertwined. The presence of natural organic matter (NOM) mitigated the formation of nitrated products and completely suppressed the coupling products. This study offers valuable insights into the fate of halophenols in ice and suggests potential pathways for the formation of nitrophenolic compounds and OH-PBDEs in natural cold environments. These findings also open up a new avenue in environmental chemistry research.

Field study on vibration characteristics of geocell-reinforced aeolian sand subgrades.

Constructing highways in deserts is expensive due to the difficulty of acquiring materials; utilizing aeolian sand effectively has become a problem, especially in the Xinjiang region, where the desert widely occurs. This paper aims to investigate the vibration response of a geocell-reinforced aeolian sand subgrade under traffic loading based on field tests of highways in deserts. The vibration acceleration response of geocell-reinforced aeolian sand and gravelly soil upper roadbed structures is tested. The field test results illustrate the effects of dynamic loading on geocell-reinforced aeolian sand roadbeds, and the thickness substitution ratio between geocell-reinforced aeolian sand roadbeds and conventional gravelly soil roadbeds is determined and verified based on the vibration acceleration monitoring values. The results show that the vibration response induced by the test vehicle is concentrated within the 30 Hz frequency band, and the higher the vibration frequency, the faster the vertical decay in the road. The vibration damping capacity of the reinforced aeolian sand roadbed is better than that of the gravelly soil roadbed; when replacing the gravelly soil roadbed with the reinforced aeolian sand roadbed, the substitution ratio is 0.31-0.42. It is verified that half thickness of gravel soil on roadbeds can be replaced by geocell-reinforced aeolian sand under different working conditions. The results of this study can provide reference data for the design of highway subgrades in deserts.

A Line-Search-Based Algorithm for Multiphase Flash Calculations with CO2-Hydrocarbon System.

Multiphase flash calculations are pivotal in compositional simulation, necessitating a robust and efficient computational algorithm. In this work, we have developed a line-search-based algorithm framework for stability analysis and multiphase flash calculations. This algorithm is rooted in the modified Newton step and line-search method. The modified Newton step, derived from modified Cholesky factorization, ensures a descent direction, while the line search determines the degree of decrease. This combination facilitates convergence even in challenging regions for phase stability analysis and multiphase flash calculations, exhibiting superlinear convergence speed. Unlike traditional approaches that rely on successive substitution iteration and may resort to Newton iteration only if the Hessian matrix is positive definite, our algorithm incorporates modification via modified Cholesky factorization upon encountering a nonpositive definite Hessian matrix. We tested our algorithm with several classical fluids, demonstrating its efficiency and robustness. Furthermore, we assessed the algorithm's performance by computing the pressure-composition diagram for the CO2-hydrocarbon system, where all calculations achieved rapid convergence without failure. This newly developed algorithm for phase stability analysis and multiphase flash calculations represents a significant advancement for compositional or chemical process simulations.

Self-control and bed procrastination as mediators between mindfulness and sleep quality among college students during the COVID-19 pandemic.

In recent years, sleep problems among college students have become increasingly prominent, especially in the context of the COVID-19 pandemic, and their sleep quality has deteriorated dramatically, severely affecting their physical and mental health. Numerous research studies have investigated the relationship between mindfulness and sleep quality; however, it is still unclear what psychological process underlies this relationship. In the current study, college students' bed procrastination and self-control as mediating factors in the association between mindfulness and sleep quality were investigated. Using the convenience sampling method, 763 Chinese college students (mean age = 19.48 years, SD = 2.06) were recruited to complete self-reported questionnaires that included the Mindful Attention Awareness Scale, Self-Control Scale, Bed Procrastination Scale, and Sleep Quality Scale. All statistical analyses were performed using SPSS 23.0 software. Results showed that (a) mindfulness was positively associated with sleep quality; (b) both self-control and bed procrastination mediated the relationship between mindfulness and sleep quality, and (c) self-control and bed procrastination sequentially mediated the relationship between mindfulness and sleep quality. These findings collectively suggest a potential mechanism for how mindfulness influences sleep quality, providing a therapeutic target for mindfulness-based interventions aimed at helping college students improve sleep quality.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Molecular Structural Characteristics and 3D Model Reconstruction of Organic Matter in Longmaxi Formation Shale.

The establishment of molecular structure modeling is an important means to study the pore characteristics of shale organic matter and is significant for molecular-level simulations of gas storage and diffusion. Using 13C NMR, FTIR, and XPS combined with the split-peak fitting technique, the structural characteristics of the aromatic structure, aliphatic structure, and oxygen functional groups of kerogen from the shale of the Longmaxi Formation, Wuxi County, Chongqing Municipality, were quantitatively characterized. A macromolecular structure model of the kerogen was also constructed by using the 2D macromolecular structure model construction method in combination with elemental analysis experiments. The results showed that the 2D single-molecule structural model of the sample consisted of 2 benzenes, 2 naphthalenes, 1 anthracene, 5 pyrenes, 1 pyridine, and 1 pyrrole. The C skeleton types were 93 protonated arylons, 39 bridged arylons, 6 carboxylons, 5 alkyl-substituted carbons, 2 oxygen-substituted carbons, 4 methylene carbons, and 3 methylons. The established 2D molecular structure formula was C152H82O12N2. The final 3D macromolecular structure model consisted of 14 2D molecular structures (structural formula C2128H1148O168N28), with the density set to 1.77 cm3/g, compressed in a cubic cell with an edge length of 3.05 nm. Finally, the adsorption results showed that the experimental adsorption of CO2 adsorption was less than the simulated adsorption, completing the validation of the model. The above study provides a method for determining the molecular structure of kerogen in the Longmaxi Formation shale, which can guide the study of the pore structure characteristics of the Longmaxi Formation shale.

Spin-Charge-Lattice Coupling across the Charge Density Wave Transition in a Kagome Lattice Antiferromagnet.

Understanding spin and lattice excitations in a metallic magnetic ordered system forms the basis to unveil the magnetic and lattice exchange couplings and their interactions with itinerant electrons. Kagome lattice antiferromagnet FeGe is interesting because it displays a rare charge density wave (CDW) deep inside the antiferromagnetic ordered phase that interacts with the magnetic order. We use neutron scattering to study the evolution of spin and lattice excitations across the CDW transition T_{CDW} in FeGe. While spin excitations below ∼100 meV can be well described by spin waves of a spin-1 Heisenberg Hamiltonian, spin excitations at higher energies are centered around the Brillouin zone boundary and extend up to ∼180 meV consistent with quasiparticle excitations across spin-polarized electron-hole Fermi surfaces. Furthermore, c-axis spin wave dispersion and Fe-Ge optical phonon modes show a clear hardening below T_{CDW} due to spin-charge-lattice coupling but with no evidence of a phonon Kohn anomaly. By comparing our experimental results with density functional theory calculations in absolute units, we conclude that FeGe is a Hund's metal in the intermediate correlated regime where magnetism has contributions from both itinerant and localized electrons arising from spin polarized electronic bands near the Fermi level.

Reclaiming Selenium from Water Using Aluminum-Modified Biochar: Adsorption Behaviors, Mechanisms, and Effects on Growth of Wheat Seedlings.

Although selenium is an essential nutrient, its contamination in water poses serious risks to human health and ecosystems. In this study, aluminum-modified bamboo biochar (Al-BC) was developed to reclaim Se(VI) from water. Compared to pristine biochar (BC), Al-BC had a larger specific surface area (176 m2/g) and pore volume (0.180 cm³/g). The modification, achieved by loading AlOOH and Al2O3 particles onto the surface, enabled Al-BC to achieve a maximum adsorption capacity of 37.6 mg/g for Se(VI) within 2 hours and remove 99.6% of Se(VI) across a pH range of 3-10. The main adsorption mechanism of Se(VI) involved electrostatic attraction, forming outer-sphere complexes between Se(VI) and AlOOH sites on the biochar. The bioavailability of Se sorbed on the spent biochar (Al-BC-Se) was thus evaluated. It was discovered that Al-BC-Se successfully released Se(VI), which impacted the growth of wheat seedlings. The Se content reached 134 µg/g dry weight (DW) in wheat shoots and 638 µg/g DW in roots, significantly exceeding normal selenium content (<40 µg/g DW). By successfully applying the modified biochar to capture selenium from water through adsorption and then reusing it as an essential nutrient in soil, this study suggests the promising feasibility of the "removal-collection-reuse" approach for the circular economy of selenium in wastewater.

Gender Differences in the Longitudinal Linkages between Fear of COVID-19 and Internet Game Addiction: A Moderated Multiple Mediation Model.

BACKGROUND: The COVID-19 outbreak has profoundly affected the psychological well-being of university students globally. Previous studies have found a positive longitudinal link between fear of COVID-19 (FoC-19) and internet addiction. However, there is a notable gap in the literature regarding COVID-19-specific predictors and underlying mechanisms of internet gaming addiction (IGA). METHODS: Integrating the compensatory internet use theory and social role theory as frameworks, a three-wave longitudinal approach was used in this study to test the hypothesized model. Data spanning a duration of one year were gathered from undergraduate students in China. From 2021 to 2022, we conducted online self-report surveys in the midst of the COVID-19 pandemic to obtain participants' levels of FoC-19, loneliness, depressive symptoms, and IGA. RESULTS: FoC-19 showed a longitudinal positive relationship with IGA. The longitudinal link between FoC-19 and IGA was mediated by loneliness and depression. Gender moderated the direct effect of FoC-19 on IGA, with this effect being significant only among male students and not among their female counterparts. CONCLUSION: These findings advance our comprehension of the mechanisms and gender differences underlying the link between FoC-19 and IGA, and provide a novel perspective for interventions to reduce IGA.

White matter microstructure alterations of the posterior limb of internal capsule in first-episode drug naive schizophrenia patients.

OBJECTIVES: Previous studies have shown that microstructural alterations in white matter (WM) could contribute to the symptom manifestation and support the dysconnectivity hypothesis in schizophrenia patients. These alterations were pervasive, non-specific, and reported inconsistently across the literature. This study aimed to specifically investigate the microstructure alterations of the posterior limb of the internal capsule (PLIC) in first-episode, drug-naive schizophrenia patients. Utilizing a multicompartmental biophysical model, we further explored the correlation between these alterations and syndrome scale scores. METHODS: Thirty-two individuals with first-episode, drug-naive schizophrenia (FES) and thirty demographically matched healthy controls were enrolled. High-resolution multi-shell diffusion MRI data were collected, followed by the application of a three-compartment Neurite Orientation Dispersion and Density Imaging (NODDI) model to scrutinize the alterations in white matter microstructure. Changes in sensory and motor fibers within the PLIC were specifically focused on. Additionally, the correlation between these pathological changes and scores on the Positive and Negative Syndrome Scale (PANSS) was investigated. RESULTS: The Neurite density index (NDI) in the left PLIC was significantly lower in FES patients compared to healthy individuals, and positively correlated with PANSS positive syndrome scores (r = 0.0379, p = 0.046). In the sensory component (left superior thalamic radiation within PLIC, STR_P), the NDI was significantly elevated (p < 0.0001). Conversely, the NDI in the motor component (left corticospinal tract within PLIC, CST_P) was reduced (p = 0.007) in FES patients compared to healthy individuals, and strongly correlated with PANSS positive syndrome scores (p < 0.020) and PANSS total scores (p < 0.045). Moreover, the NDI deviation of STR from total PLIC (fSTR_P) and NDI deviation in STR_P and CST_P compared to PLIC region (fPLIC) were significantly higher in FES patients than in healthy controls (p < 0.00001), with an area under the curve (AUC) of fPLIC reaching 0.872. CONCLUSION: The study's findings provided new insights into the discrepancy of white matter microstructure changes associated with the sensory and motor fibers in the PLIC region in FES patients. These results contribute to the growing body of evidence suggesting that WM microstructural alterations play a critical role in schizophrenia pathophysiology.

A bimetallic MOF-derived MnCo spinel oxide catalyst to enhance toluene catalytic degradation.

MnCo spinel oxide catalysts were successfully synthesized by the calcination of bimetallic Mn/Co-MOFs as sacrificial templates. The derived catalysts exhibited optimal catalytic activity, reusability and thermal stability for toluene oxidation, which was ascribed to their large specific surface area, higher number of octahedral metal ions and the weakest metal-oxygen bonds.

Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration.

The liver has the great ability to regenerate after partial resection or injury, and the mechanisms underlying liver regeneration have been extensively investigated. Interestingly, acute liver injuries triggered by various etiologies are associated with the formation of necrotic lesions, and such necrotic lesions are also rapidly resolved. However, how necrotic liver lesions are repaired has not been carefully investigated until recently. In this review, we briefly summarize the spatiotemporal process of necrotic liver lesion resolution in several liver injury models including immune-mediated liver injury and drug-induced liver injury. The roles of liver nonparenchymal cells and infiltrating immune cells in controlling necrotic liver lesion resolution are discussed, which may help identify potential therapies for acute liver injury and failure.

Spodoptera frugiperda Salivary Glucose Oxidase Reduces the Release of Green Leaf Volatiles and Increases Terpene Emission from Maize.

The intricate relationships between plants and insects are essential for understanding ecological dynamics. Among these interactions, HIPVs serve as a pivotal defense mechanism. Our findings reveal the highly conserved nature of the GOX gene within the Lepidoptera order, highly expressed in the salivary glands of S. frugiperda, and its role in mediating maize's defense responses. Notably, salivary GOX activity expression significantly decreases subsequent gene knockout. The presence of GOX in the saliva of S. frugiperda significantly modulates the emission of HIPVs during maize consumption. This research delineates that GOX selectively inhibits the emission of certain green leaf volatiles (GLVs) while concurrently enhancing the release of terpene volatiles. This study unveils a novel mechanism whereby S. frugiperda utilizes GOX proteins in OS to modulate volatile emissions from maize, offering fresh perspectives on the adaptive evolution of phytophagous insects and their interactions with their preferred host plants.

Effect of extracellular matrix stiffness on efficacy of Dapagliflozin for diabetic cardiomyopathy.

BACKGROUND: Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. MATERIALS AND METHODS: This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. RESULTS: The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin ß1, but without significant impact on piezo 1. CONCLUSIONS: Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Seasonal dynamics, tidal influences, and anthropogenic impacts on microplastic distribution in the Yangtze River estuary: A comprehensive characterization and comparative analysis.

Microplastics (MPs) are emerging contaminants with significant ecological and human health implications. This study examines the abundance, characteristics, and distribution of MPs in the Yangtze River estuary, focusing on seasonal variations, tidal cycles, and anthropogenic influences. Surface samples were collected using the Manta trawl method to ensure consistency with previous marine MP research. The study found an average MP concentration of 1.01 (± 0.65) n m-3, predominantly comprising low-density polymers such as polystyrene (38 %), polypropylene (33 %), and polyethylene (29 %). MPs were mainly fragments (34.9 %) and foam (30.7 %), with a prevalence of white particles. Seasonal analysis indicated significantly higher MP concentrations during flood seasons (1.32 ± 1.09 n m-3), nearly 1.9 times higher than during non-flood seasons (0.70 ± 0.28 n m-3). Tidal cycles also impacted MP distribution, with ebb tides showing increased concentrations (2.44 ± 1.30 n m-3) compared to flood tides (1.48 ± 2.07 n m-3). Furthermore, MP abundance showed a decreasing trend with increasing distance from urban centers, with significant correlations (0.52 < R2 < 0.65, P < 0.001). These findings underscore the necessity for seasonally adjusted monitoring and robust management strategies to combat MP pollution. The study advocates for the integration of diverse sampling methods and the consideration of environmental factors in future MP assessments, laying the groundwork for understanding the MP transport mechanism in the Yangtze River estuary and similar estuarine systems worldwide.

Coordinated action of a gut-liver pathway drives alcohol detoxification and consumption.

Alcohol use disorder (AUD) affects millions of people worldwide, causing extensive morbidity and mortality with limited pharmacological treatments. The liver is considered as the principal site for the detoxification of ethanol metabolite, acetaldehyde (AcH), by aldehyde dehydrogenase 2 (ALDH2) and as a target for AUD treatment, however, our recent data indicate that the liver only plays a partial role in clearing systemic AcH. Here we show that a liver-gut axis, rather than liver alone, synergistically drives systemic AcH clearance and voluntary alcohol drinking. Mechanistically, we find that after ethanol intake, a substantial proportion of AcH generated in the liver is excreted via the bile into the gastrointestinal tract where AcH is further metabolized by gut ALDH2. Modulating bile flow significantly affects serum AcH level and drinking behaviour. Thus, combined targeting of liver and gut ALDH2, and manipulation of bile flow and secretion are potential therapeutic strategies to treat AUD.