Effect of In Situ Polymerization of Super Absorbent Polymers on the Protection of Earthen Heritage Sites in Semi-Arid Regions.

As precious cultural heritage, earthen sites are susceptible to various natural factors, leading to diverse forms of degradation. To protect earthen sites, the effects of super absorbent polymers (SAPs) on soil water retention, physical properties, and color compatibility at different concentrations were studied. After applying SAP treatment to an earthen site with different degrees of weathering, we drew the following conclusions. SAP-2 improved soil water retention capacity, increased soil water content, and slowed down the precipitation of soluble salts. At the same time, SAP-2 had the least effect on soil color difference and reduced the development of cracks by filling soil pores and enhancing the cohesion between soil particles, thus giving the earthen sites better weathering resistance. Therefore, the results provide a useful reference for the surface cracking of earthen sites in semi-arid areas and the degradation caused by flaking and block spalling.

A perspective view of salt crystallization from solution in porous media: morphology, mechanism, and salt efflorescence.

Salt efflorescence is one of the major hazards to cultural heritages, masonries, and highways etc. It is now generally accepted that damages caused by salt efflorescence are mainly due to continuous cycles of salt crystallization/dissolution or hydration/dehydration in confined spaces. The position where salt efflorescence occurs and its type are closely related to the degree of damages caused by salt efflorescence. It is known that water is the key environmental factor determining the salt crystallization position. But influence of the correlation between water supply and evaporation on the position of salt crystallization is still not clearly understood. In this work, a set of experiments are designed to investigate salt efflorescence in porous matrix. It is found that the types and positions of salt efflorescence have little to do with nucleation, but are mainly governed by crystal growth, which is controlled by the rates of water evaporation, water and salt supply, capillary forces and surface properties of the porous matrices.

One Stone, Three Birds: Feasible Tuning of Barrier Heights Induced by Hybridized Interface in Free-Standing PEDOT@Bi2Te3 Thermoelectric Films.

Converting low-grade thermal energy into electrical energy is crucial for the development of modern smart wearable energy technologies. The free-standing films of PEDOT@Bi2Te3 prepared by tape-casting hold promise for flexible thermoelectric technology in self-powered sensing applications. Bi2Te3 nanosheets fabricated by the solvothermal method are tightly connected with flat-arranged PEODT molecules, forming an S-Bi bonded interface in the composite materials, and the bandgap is reduced to 1.63 eV. Compared with the PEDOT film, the mobility and carrier concentration of the composite are significantly increased at room temperature, and the conductivity reaches 684 S/cm. Meanwhile, the carrier concentration decreased sharply at 360 K indicating the creation of defect energy levels during the interfacial reaction of the composites, which increased the Seebeck coefficient. The power factor was improved by 68.9% compared to PEDOT. In addition, the introduction of Bi2Te3 nanosheets generated defects and multidimensional interfaces in the composite film, which resulted in weak phonon scattering in the conducting polymer with interfacial scattering. The thermal conductivity of the film is decreased and the ZT value reaches 0.1. The composite film undergoes 1500 bending cycles with a 14% decrease in conductivity and has good flexibility. This self-supporting flexible thermoelectric composite film has provided a research basis for low-grade thermal energy applications.

Piezo-photocatalytic reduction of nitrates to N2 over silver dispersed on BaTiO3@TiO2.

This communication first achieved piezo-photocatalytic reduction of nitrates to N2 through designing an Ag2O/BaTiO3@TiO2 core-shell catalyst. The built-in electric field induced by piezoelectric polarization suppresses photoexcited carrier recombination, and simultaneously causes energy band tilting, leading to the generation of electrons with higher reducibility to directly trigger the NO3- reduction to ˙NO32-, even without hole scavengers.

Effect of different lumbar-iliac fixation and sacral slope for Tile C1.3 pelvic fractures: a biomechanical study.

BACKGROUND: Lumbar-iliac fixation (LIF) is a common treatment for Tile C1.3 pelvic fractures, but different techniques, including L4-L5/L5 unilateral LIF (L4-L5/L5 ULIF), bilateral LIF (BLIF), and L4-L5/L5 triangular osteosynthesis (L4-L5/L5 TOS), still lack biomechanical evaluation. The sacral slope (SS) is key to the vertical shear of the sacrum but has not been investigated for its biomechanical role in lumbar-iliac fixation. The aim of this study is to evaluate the biomechanical effects of different LIF and SS on Tile C1.3 pelvic fracture under two-legged standing load in human cadavers. METHODS: Eight male fresh-frozen human lumbar-pelvic specimens were used in this study. Compressive force of 500 N was applied to the L4 vertebrae in the two-legged standing position of the pelvis. The Tile C1.3 pelvic fracture was prepared, and the posterior pelvic ring was fixed with L5 ULIF, L4-L5 ULIF, L5 TOS, L4-L5 TOS, and L4-L5 BLIF, respectively. Displacement and rotation of the anterior S1 foramen at 30° and 40° sacral slope (SS) were analyzed. RESULTS: The displacement of L4-L5/L5 TOS in the left-right and vertical direction, total displacement, and rotation in lateral bending decreased significantly, which is more pronounced at 40° SS. The difference in stability between L4-L5 and L5 ULIF was not significant. BLIF significantly limited left-right displacement. The ULIF vertical displacement at 40° SS was significantly higher than that at 30° SS. CONCLUSIONS: This study developed an in vitro two-legged standing pelvic model and demonstrated that TOS enhanced pelvic stability in the coronal plane and cephalad-caudal direction, and BLIF enhanced stability in the left-right direction. L4-L5 ULIF did not further improve the immediate stability, whereas TOS is required to increase the vertical stability at greater SS.

Low-Cytotoxic Core-Sheath ZnO NWs@TiO2-xNy Triggered Piezo-photocatalytic Antibacterial Activity.

Sonophotodynamic antimicrobial therapy (SPDAT) is recognized as a highly efficient biomedical treatment option, known for its versatility and remarkable healing outcomes. Nevertheless, there is a scarcity of sonophotosensitizers that demonstrate both low cytotoxicity and exceptional antibacterial effectiveness in clinical applications. In this paper, a novel ZnO nanowires (NWs)@TiO2-xNy core-sheath composite was developed, which integrates the piezoelectric effect and heterojunction to build dual built-in electric fields. Remarkably, it showed superb antibacterial effectiveness (achieving 95% within 60 min against S. aureus and ∼100% within 40 min against E. coli, respectively) when exposed to visible light and ultrasound. Due to the continuous interference caused by light and ultrasound, the material's electrostatic equilibrium gets disrupted. The modification in electrical properties facilitates the composite's ability to attract bacterial cells through electrostatic forces. Moreover, Zn-O-Ti and Zn-N-Ti bonds formed at the interface of ZnO NWs@TiO2-xNy, further enhancing the dual internal electric fields to accelerate the excited carrier separation to generate more reactive oxygen species (ROS), and thereby boosting the antimicrobial performance. In addition, the TiO2 layer limited Zn2+ dissolution into solution, leading to good biocompatibility and low cytotoxicity. Lastly, we suggest a mechanistic model to offer practical direction for the future development of antibacterial agents that are both low in toxicity and high in efficacy. In comparison to the traditional photodynamic therapy systems, ZnO NWs@TiO2-xNy composites exhibit super piezo-photocatalytic antibacterial activity with low toxicity, which shows great potential for clinical application as an antibacterial nanomaterial.

Endoplasmic reticulum stress and death receptor-mediated apoptosis in the neuronal differentiation of adult adipose-derived stromal cells.

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using ß-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

Effects of Dietary Fish Meal Replaced by Fish Steak Meal on Growth Performance, Antioxidant Capacity, Intestinal Health and Microflora, Inflammatory Response, and Protein Metabolism of Large Yellow Croaker Larimichthys crocea.

Although fish steak meal (FSM) is a potentially available protein source, its efficiency as a fish meal (FM) substitute remains unclear to date. To this end, this study was carried out to determine the effects of dietary FM replaced by FSM on growth performance, antioxidant capacity, intestinal health and microflora, inflammatory response, and protein metabolism of large yellow croaker. Five isolipidic and isonitrogenous diets were formulated by substituting FM with FSM at levels of 0% (FSM0, control diet), 25% (FSM25), 50% (FSM50), 75% (FSM75), and 100% (FSM100), and were fed to juvenile large yellow croaker for 8 weeks. Compared with the control diet, the replacement of 25% dietary FM with FSM did not markedly alter the weight gain (WG) and specific growth rate (SGR). When the FM substitution level was over 25%, WG and SGR markedly reduced. The intestinal structure observation found that the FSM75 and FSM100 diets markedly decreased villus height, villus width, and muscle thickness of the anterior intestine. The FSM75 and FSM100 diets significantly decreased enzyme activities of amylase (AMS), lipase (LPS), trypsin, catalase (CAT), and total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), and increased the malondialdehyde (MDA) content in the liver of large yellow croaker. The mRNA expression levels of intestinal barrier and inflammatory response-related genes suggested that the FSM50, FSM75, and FSM100 diets significantly decreased the mRNA abundances of intestinal barrier-related genes and anti-inflammatory response-related genes, and increased the mRNA abundances of proinflammatory gene il-6 in the anterior intestine. The compositions of intestinal microflora displayed that the FSM50, FSM75, and FSM100 diets decreased relative abundances of Firmicutes phylum and increased relative abundances of Proteobacteria phylum. In addition, the results of protein expression levels showed that the phosphorylation level of mammalian target of rapamycin (mTOR) and 4E-binding protein 1 (4E-BP1) in FSM75 and FSM100 groups were markedly reduced. In conclusion, FSM can replace up to 25% dietary FM without compromising the growth performance, intestinal health, and protein metabolism of the large yellow croaker.

Metabolic Profile of Alzheimer's Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Alzheimer's disease (AD) represents a significant public health concern in modern society. Metabolic syndrome (MetS), which includes diabetes mellitus (DM) and obesity, represents a modifiable risk factor for AD. MetS and AD are interconnected through various mechanisms, such as mitochondrial dysfunction, oxidative stress, insulin resistance (IR), vascular impairment, inflammation, and endoplasmic reticulum (ER) stress. Therefore, it is necessary to seek a multi-targeted and safer approach to intervention. Thus, 10-hydroxy-2-decenoic acid (10-HDA), a unique hydroxy fatty acid in royal jelly, has shown promising anti-neuroinflammatory, blood-brain barrier (BBB)-preserving, and neurogenesis-promoting properties. In this paper, we provide a summary of the relationship between MetS and AD, together with an introduction to 10-HDA as a potential intervention nutrient. In addition, molecular docking is performed to explore the metabolic tuning properties of 10-HDA with associated macromolecules such as GLP-1R, PPARs, GSK-3, and TREM2. In conclusion, there is a close relationship between AD and MetS, and 10-HDA shows potential as a beneficial nutritional intervention for both AD and MetS.

Rheological studies of cellulose nanocrystal/dimethyl sulfoxide organogels.

Cellulose nanocrystals (CNCs)/H2O gels have received significant interest in various applications for the past decades. And yet CNCs organogels, which are important to their wider application, are less explored. In this work, CNCs/Dimethyl sulfoxide (DMSO) organogels are carefully investigated by rheological methods. It is found that metal ions also can facilitate the organogel formation as in hydrogel. Charge screening and coordination effects play vital roles in the organogel formation and their mechanical strength. CNCs/DMSO gels with different cations display similar mechanical strength, while CNCs/H2O gels show increasing mechanical strength with the increasing valence of cations. It seems that the coordination between cations and DMSO alleviate the influence of valence on gel mechanical strength. Due to weak, fast and reversible electrostatic interactions among CNCs particles, both CNCs/DMSO and CNCs/H2O gels show instant thixotropic behavior, which may find some interesting applications in the field of drug delivery. The morphological changes observed in polarized optical microscope appear to be consistent with rheological results.

Correction to "Research on MgSO4 Whiskers Grown on the Surface of Porous Materials".

[This corrects the article DOI: 10.1021/acsomega.2c06533.].

Partial Substitution of Fish Meal with Soy Protein Concentrate on Growth, Liver Health, Intestinal Morphology, and Microbiota in Juvenile Large Yellow Croaker (Larimichthys crocea).

The present study investigated the growth performance, feed utilization, intestinal morphology, and microbiota communities of juvenile large yellow croaker (Larimichthys crocea) fed diets containing different proportions of soy protein concentrate (SPC) (0, 15%, 30%, and 45%, namely FM, SPC15, SPC30, and SPC45) as a substitute for fish meal (FM) for 8 weeks. The weight gain (WG) and specific growth rate (SGR) in fish fed SPC45 were significantly lower than those fed FM and SPC15 but not differ with these fed SPC30. The feed efficiency (FE) and protein efficiency ratio (PER) decreased sharply when the dietary SPC inclusion level was higher than 15%. The activity of alanine aminotransferase (ALT) and expression of alt and aspartate aminotransferase (ast) were significantly higher in fish fed SPC45 than those fed FM. The activity and mRNA expression of acid phosphatase were opposite. The villi height (VH) in distal intestine (DI) showed a significant quadratic response to increasing dietary SPC inclusion levels and was highest in SPC15. The VH in proximal intestine, middle intestine decreased significantly with increasing dietary SPC levels. The 16S rRNA sequences in intestine revealed that fish fed SPC15 had higher bacterial diversity and abundance of Phylum Firmicutes such as order Lactobacillales and order Rhizobiaceae than those fed other diets. Genus vibrio, family Vibrionaceae and order Vibrionales within phylum Proteobacteria were enriched in fish fed FM and SPC30 diets. Tyzzerella and Shewanella that belongs to phylum Firmicutes and Proteobacteria, respectively, were enriched in fish fed SPC45 diet. Our results indicated that SPC replacing more than 30% FM could lead to lower quality diet, retard growth performance, ill health, disordered intestine structure, and microbiota communities. Tyzzerella could be the bacteria indicator of intestinal in large yellow croaker fed low quality diet due to high SPC content. Based on the quadratic regression analysis of WG, the best growth performance could be observed when the replacement of FM with SPC was 9.75%.

Research on MgSO4 Whiskers Grown on the Surface of Porous Materials.

The wooden sluice site of the Nanyue Kingdom in Guangzhou, China, is covered with white magnesium sulfate salt whiskers continuously growing from the surface. In this paper, polarizing microscopy, scanning electron microscopy, infrared thermography, Fourier transform infrared spectrometry, and surface tension analysis were utilized to comprehensively analyze the micromorphology of whiskers grown on the surfaces of porous materials collected at the site of Nanyue Kingdom, as well as the change laws of magnesium sulfate solution droplets on the porous hydrophilic matrix, and the migration and crystallization of magnesium sulfate solution in the capillary tube. The diameters of magnesium sulfate salt whiskers grown on the surfaces of porous samples range from 30 to 110 µm. For the first time, it is clear to see that the whisker's structure is hollow and nodular. There are solid crystalline salts in hollow tubes, and some of them are aqueous. The top sections of whiskers are approximately circular and are composed of particles with a size of about 0.4-4.0 µm. Their growth conditions are mainly characterized by the high humidity environment where the porous material is located or locally located, the formation of an annular whisker base, and the pressure difference generated during the formation progress of water-bearing crystals in the capillary of the whisker. The research results expound on the circumstances and mechanism of magnesium sulfate solution-induced whisker development on the surface of porous materials, providing a reference for the study of the whisker growth mechanism.

Thermal vacuum de-oxygen fabrication of new catalytic pigments: SiO2@TiO2-x amorphous photonic crystals for formaldehyde removal.

Eliminating benzene and formaldehyde pollution is indispensable after the popularity of colorful home decoration in current society. The possibility and advantages of vividly colorful amorphous photonic crystals (APCs) as catalytic pigments were established. Biomimetic synthesis of APCs is an effective approach to obtaining angle-independent structural colors. Herein, we introduce oxygen vacancies through thermal vacuum de-oxygenation to synthesize SiO2@TiO2-x APCs for angle-independent structural colors and enhanced photocatalytic performance in one step. Core-shell nanospheres with controllable particle size were synthesized using a mixed-solvent method as the structural unit of APCs to prepare seven structural colors: red, orange, yellow, green, cyan, blue, and purple. The photocatalytic activity of in situ fabricated SiO2@TiO2-x APCs was conspicuously enhanced by thermal vacuum deoxidation. An amorphous layer formed on the TiO2 nanocrystals provides TiO2-x with excellent spectral response to visible light, transient photocurrent, and surface photovoltage up to 38.44 µA cm-2 and 28.8 mV, respectively. Black TiO2-x absorbs incoherent scattering, causing APCs to generate vividly angle-independent structural colors. The existence of oxygen vacancies in TiO2-x promotes electron activation and a synergistic effect with the photonic local effect of APCs in improving the degradation of formaldehyde by catalytic pigments, effectively protecting the beautiful living environment of human beings.

HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.

YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCFß-TrCP . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to ß-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer.

Effect of Mg Powder's Particle Size on Structure and Mechanical Properties of Ti Foam Synthesized by Space Holder Technique.

Titanium foam has been the focus of special attention for its specific structure and potential applications in purification, catalyst substrate, heat exchanger, biomaterial, aerospace and naval industries. However, the liquid-state foaming techniques are difficult to use in fabricating Ti foam because of its high melting temperature and strong chemical reactivity with atmospheric gases. Here, the fabrication of Ti foams via the powder metallurgy route was carried out by utilizing both magnesium powders and magnesium particles as spacer holders, and Ti powders as matrix metal. The green compacts containing Ti powder, Mg powder and Mg particles were heated to a certain temperature to remove the magnesium and obtain the Ti foam. The results show that the porosities of the obtained Ti foam are about 35-65%, and Young's modulus and yield strength are found to be in the ranges of 22-126 MPa and 0.063-1.18 GPa, respectively. It is found that the magnesium powders play a more important role than the magnesium particles in the deformation and the densification of the green compact during the pressing, and the pore structure of Ti foam depends on the amount and the size of the magnesium spacer holders after sintering.

Effects of an Isobutylene-Maleic Anhydride Copolymer on the Rheological Behavior and Early Hydration of Natural Hydraulic Lime.

Natural hydraulic lime (NHL) is a cementitious material widely used in the restoration of stone cultural relics and maintenance of historic buildings, the practical use of which is mainly hindered by its poor fluidity. Due to the multilayer (double-layer) adsorption that isobutylene-maleic anhydride (IBMA) has on the surface of NHL, the effects that IBMA copolymer have on the fluidity and hydration of NHL were thus investigated. Moreover, the yield stress and plastic viscosity of NHL pastes were found to be reduced significantly by the incorporation of IBMA. Combined with the effects of electrostatic repulsion and steric hindrance, the flocculated structures in NHL pastes were gradually dismantled, releasing the trapped water and leading to a significant enhancement in the fluidity of NHL. IBMA was found to postpone the early hydration of NHL. In particular, it showed that adding specific content of IBMA can significantly improve the early strength of NHL.

The Aptamer Ob2, a novel AChE inhibitor, restores cognitive deficits and alleviates amyloidogenesis in 5×FAD transgenic mice.

Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5×FAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5×FAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5×FAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Aß by lowering the expression of ß-secretase (BACE1), and activation of astrocytes in the brains of 5×FAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.

The Development of New Catalytic Pigments Based on SiO2 Amorphous Photonic Crystals via Adding of Dual-Functional Black TiO2-x Nanoparticles.

Biomimetic synthesis of amorphous photonic crystals (APCs) is an effective approach to obtaining non-iridescent structural colors. However, the structural colors of artificially prepared APCs are dim or even white due to the influence of incoherent scattering. In this paper, we present a novel method to combine APCs with black TiO2-x to construct a noniridescent structural color pigments with high visibility and photocatalytic activity. Due to the absorption of incoherently scattered light by black TiO2-x , the color saturation of structural colors has been significantly increased. In addition, the utilization rate of photogenic carriers was effectively enhanced by the slow light effect generated from the pseudoband gap of SiO2 APCs with TiO2-x absorbed full spectrum. The tone and color saturation of catalytic pigments is controlled by the diameter of SiO2 nanospheres and the ratio of TiO2-x nanoparticles, which provides a controllable application study in color-related fields as artwork, environmental coatings, and textiles.

AMBRA1 Promotes TGFß Signaling via Nonproteolytic Polyubiquitylation of Smad4.

Transforming growth factor ß (TGFß) is prometastatic in advanced cancers and its biological activities are mainly mediated by the Smad family of proteins. Smad4 is the central signal transducer and transcription factor in the TGFß pathway, yet the underlying mechanisms that govern transcriptional activities of Smad4 are not fully understood. Here, we show that AMBRA1, a member of the DDB1 and CUL4-associated factor (DCAF) family of proteins, serves as the substrate receptor for Smad4 in the CUL4-RING (CRL4) ubiquitin ligase complex. The CRL4-AMBRA1 ubiquitin ligase mediates nonproteolytic polyubiquitylation of Smad4 to enhance its transcriptional functions. Consequently, AMBRA1 potentiated TGFß signaling and critically promoted TGFß-induced epithelial-to-mesenchymal transition, migration, and invasion of breast cancer cells. Mouse models of breast cancer demonstrated that AMBRA1 promotes metastasis. Collectively, these results show that CRL4-AMBRA1 facilitates TGFß-driven metastasis by increasing Smad4 polyubiquitylation, suggesting AMBRA1 may serve as a new therapeutic target in metastatic breast cancer. SIGNIFICANCE: This study identifies AMBRA1 as a novel regulator of TGFß signaling and breast cancer metastasis, supporting further exploration of AMBRA1 as a target for cancer therapy.