Europium-Doped 3D Dimensional Porous Calcium Phosphate Scaffolds as a Strategy for Facilitating the Comprehensive Regeneration of Bone Tissue: In Vitro and In Vivo.

In response to the challenges faced by clinicians treating bone defects caused by various factors, various bone repair materials have been investigated, but the efficiency of bone healing still needs to be improved due to the acting of scaffolds only in a single stage of bone tissue regeneration. We investigated the potential of a novel 3D scaffold to support different stages of bone tissue regeneration, including initial inflammation, proliferation, and remodeling. Eu (0, 0.5, 2, 3.5, 5, and 6.5%) was added to calcium polyphosphate to obtain 3D porous network-doped Eu calcium polyphosphate (EuCPP) scaffolds with ideal mechanical strength and pore size. Both in vitro and in vivo experiments proved that Eu3+ released from 5% EuCPP scaffolds could significantly promote the migration and proliferation of bone marrow stromal cells which effectively promote angiogenesis; 5% EuCPP could significantly upregulate the ratio of OPG/RANKL in MC3T3-E1 and promote the secretion of osteogenic-related growth factors (ALP and OPN) from MC3T3-E1, indicating the potential of the scaffold to inhibit bone resorption and promote bone formation. In conclusion, 5% EuCPP possesses the biological properties of pro-angiogenesis, anti-inflammation, pro-osteogenesis, and inhibiting bone resorption, which may provide a sustained positive effect throughout the process of bone tissue repair.

Gallic Acid Alleviates Psoriasis Keratinization and Inflammation by Regulating BRD4 Expression.

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

Copper-based carbon dots modified hydrogel with osteoimmunomodulatory and osteogenesis for bone regeneration.

Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared copper-based carbon dots (CuCDs) and doped them into oxychondroitin sulfate/poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factors from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo, which is beneficial for anti-inflammatory action and presents good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair and is a promising bone filling and repair material.

Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis.

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Double crosslinking decellularized bovine pericardium of dialdehyde chondroitin sulfate and zwitterionic copolymer for bioprosthetic heart valves with enhanced antithrombogenic, anti-inflammatory and anti-calcification properties.

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, the zwitterion radical copolymerization system was introduced in situ to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance due to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVEC-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simple cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, and HUVEC-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification properties. It might be a promising alternative to GA-fixed BP and exhibited good prospects in clinical applications.

Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression.

Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma.

Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/ß signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.

Cancer Development in Hepatocytes by Long-Term Induction of Hypoxic Hepatocellular Carcinoma Cell (HCC)-Derived Exosomes In Vivo and In Vitro.

Hypoxic tumor cell-derived exosomes play a key role in the occurrence, development, and metastasis of tumors. However, the mechanism of hypoxia-mediated metastasis remains unclear. In this study, hypoxic hepatocellular carcinoma cell (HCC-LM3)-derived exosomes (H-LM3-exos) were used to induce hepatocytes (HL-7702) over a long term (40 passages in 120 days). A nude mouse experiment further verified the effect of H-LM3-exos on tumor growth and metastasis. The process of cancer development in hepatocytes induced by H-LM3-exos was analyzed using both biological and physical techniques, and the results showed that the proliferation and soft agar growth abilities of the transformed cells were enhanced. The concentration of tumor markers secreted by transformed cells was increased, the cytoskeleton was disordered, and the migration ability was enhanced and was accompanied by epithelial-mesenchymal transition (EMT). Transcriptome results showed that differentially expressed genes between transformed cells and hepatocytes were enriched in cancer-related signaling pathways. The degree of cancer development in transformed cells was enhanced by an increase in H-LM3-exos-induced passages. Nude mice treated with different concentrations of H-LM3-exos showed different degrees of tumor growth and liver lesions. The physical properties of the cells were characterized by atomic force microscopy. Compared with the hepatocytes, the height and roughness of the transformed cells were increased, while the adhesion and elastic modulus were decreased. The changes in physical properties of primary tumor cells and hepatocytes in nude mice were consistent with this trend. Our study linking omics with the physical properties of cells provides a new direction for studying the mechanisms of cancer development and metastasis.

Effects of targeted lung cancer drugs on cardiomyocytes studied by atomic force microscopy.

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has become one of the important targeted drugs for the treatment of non-small cell lung cancer (NSCLC). But the cardiac adverse events (AEs) related to the EGFR-TKI treatment occur frequently. And the cases of TKI-associated cardiac AEs remain poorly understood. In order to study the effects of EGFR-TKIs on cardiomyocytes, atomic force microscopy (AFM) was used to measure and analyze the physical properties of cardiomyocytes under the actions of three drugs (gefitinib, afatinib and osimertinib) with different concentrations. By comparing the height, adhesion, Young's modulus, the amplitude and the time of the contraction and relaxation process, it was found that the changes of the mechanical properties of cells were well correlated with the symptoms of AEs, such as cardiomyocyte hypertrophy, QT prolongation, atrial fibrillation, ejection fraction reductions, and cardiac failure. In addition, osimertinib has the most obvious effect on cardiomyocytes at a low concentration, and gefitinib has the greatest effect with the increase of concentration, while afatinib has the least effect on cardiomyocytes. This provides a new method for screening drugs and exploring the principle of action in the process of cancer treatment at the cellular level.

MCP-1-Loaded Poly(l-lactide-co-caprolactone) Fibrous Films Modulate Macrophage Polarization toward an Anti-inflammatory Phenotype and Improve Angiogenesis.

Tissue engineering approaches such as the electrospinning technique can fabricate nanofibrous scaffolds which are widely used for small-diameter vascular grafting. However, foreign body reaction (FBR) and lack of endothelial coverage are still the main cause of graft failure after the implantation of nanofibrous scaffolds. Macrophage-targeting therapeutic strategies have the potential to address these issues. Here, we fabricate a monocyte chemotactic protein-1 (MCP-1)-loaded coaxial fibrous film with poly(l-lactide-co-ε-caprolactone) (PLCL/MCP-1). The PLCL/MCP-1 fibrous film can polarize macrophages toward anti-inflammatory M2 macrophages through the sustained release of MCP-1. Meanwhile, these specific functional polarization macrophages can mitigate FBR and promote angiogenesis during the remodeling of implanted fibrous films. These studies indicate that MCP-1-loaded PLCL fibers have a higher potential to modulate macrophage polarity, which provides a new strategy for small-diameter vascular graft designing.

CO2 sequestration and CaCO3 recovery with steel slag by a novel two-step leaching and carbonation method.

The steel smelting process produces extensive CO2 and Ca-containing steel slag (SS). Meanwhile, the low value utilization of steel slag results in the loss of Ca resources. CO2 sequestration utilizing SS can reduce carbon emissions while achieving Ca circulation. However, conventional SS carbon sequestration methods suffer from slow reaction rates, finite Ca usage efficiency, and difficulty separating the CaCO3 product from SS. Herein, an innovative two-step leaching (TSL) and carbonation method was presented based on the variations in leaching efficiency of activated Ca under different conditions, aiming at efficient leaching, carbon sequestration, and high-value reuse of SS. This method employed two NH4Cl solutions in sequence for two leaching operations on SS, allowing the Ca leaching rate to be effectively increased. According to the findings, TSL could increase the activated Ca leaching rate by 26.9 % and achieve 223.15 kg CO2/t SS sequestration compared to the conventional one-step leaching (CSL) method. If part of the CaCO3 is recovered as a slagging agent, about 34.1 % of the exogenous Ca introduction could be saved. In addition, the CO2 sequestration of TSL did not significantly decrease after 8 cycles. This work proposes a strategy that has the potential for recycling SS and reducing carbon emissions.

Design and Application Strategies of Natural Polymer Biomaterials in Artificial Ovaries.

For certain types of cancer patients, ovarian transplantation has a risk of malignant cancer cell infection. However, the autologous transplantation of an artificial ovary is safe and effective, guarantees the normal development of isolated follicles, regular oocyte maturation, and ovulation, partially restores endocrine function, and enables the patient to regain reproductive ability. Despite the complexity of the natural ovary, some progress has been made in the repair or replacement of reproductive tissues with the use of various biomaterials. This article reviews the physical structure, biomechanical properties, design elements, preparation routes, construction and practical use of natural polymer materials, usually hydrogel scaffolds, such as alginate, fibrin, gelatin, collagen, agarose, and acellular ovarian matrix in the preparation of artificial ovaries. We summarize how these materials can be made into artificial ovaries to achieve the conditions for fertility through follicle and oocyte development and identify several major issues to overcome for the future development of artificial ovaries, including how to establish blood recirculation, and how to establish hormone synthesis and release channels. This review is intended to provide a reference for the use of natural polymer biomaterials in reproductive clinics.

A Smart "Energy NanoLock" Selectively Blocks Oral Cancer Energy Metabolism through Synergistic Inhibition of Exogenous Nutrient Supply and Endogenous Energy Production.

The major challenge in oral cancer is the lack of state-of-the-art treatment modality that effectively cures cancer while preserving oral functions. Recent insights into tumor metabolic dependency provide a therapeutic opportunity for exploring optimal treatment approaches. Herein, a smart responsive "Energy NanoLock" is developed to improve cancer metabolic intervention by simultaneously inhibiting nutrient supply and energy production. NanoLock is a pomegranate-like nanocomplex of cyclicRGD-modified carboxymethyl chitosan (CyclicRC, pI = 6.7) encapsulating indocyanine green and apoptotic peptides functionalized gold nanoparticles (IK-AuNPs), which together form a dual pH- and photoresponsive therapeutic platform. NanoLock exhibits good stability under physiological conditions, but releases small-size CyclicRC and IK-AuNPs in response to the tumor acidic microenvironment, leading to deep tumor penetration. CyclicRC targets integrins to inhibit tumor angiogenesis, and consequently blocks tumor nutrient supply. Meanwhile, IK-AuNPs specifically induce apoptotic peptides and photothermally mediated mitochondrial collapse, and consequently inhibits endogenous energy production, thereby facilitating cell death. Importantly, in both xenograft and orthotopic oral cancer models, NanoLock selectively eliminates tumors with little cross-reactivity with normal tissues, especially oral functions, resulting in prolonged survival of mice. Therefore, NanoLock provides a novel metabolic therapy to exploit synergistic inhibition of exogenous nutrient supply and endogenous energy production, which potentially advances oral cancer treatment.

Sulfonated, oxidized pectin-based double crosslinked bioprosthetic valve leaflets for synergistically enhancing hemocompatibility and cytocompatibility and reducing calcification.

Clinically frequently-used glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) are still curbed by acute thrombosis, malignant immunoreaction, calcification, and poor durability. In this study, an anticoagulant heparin-like biomacromolecule, sulfonated, oxidized pectin (SAP) with a dialdehyde structure was first obtained by modifying citrus pectin with sulfonation of 3-amino-1-propane sulfonic acid and then oxidating with periodate. Notably, a novel crosslinking approach was established by doubly crosslinking BVLs with SAP and the nature-derived crosslinking agent quercetin (Que), which play a synergistic role in both crosslinking and bioactivity. The double crosslinked BVLs also presented enhanced mechanical properties and enzymatic degradation resistance owing to the double crosslinking networks formed via CN bonds and hydrogen bonds, respectively, and good HUVEC-cytocompatibility. The in vitro and ex vivo assay manifested that the double-crosslinked BVLs had excellent anticoagulant and antithrombotic properties, owing to the introduction of SAP. The subcutaneous implantation also demonstrated that the obtained BVLs showed a reduced inflammatory response and great resistance to calcification, which is attributed to quercetin with multiple physiological activities and depletion of aldehyde groups by hydroxyl aldehyde reaction. With excellent stability, hemocompatibility, anti-inflammatory, anti-calcification, and pro-endothelialization properties, the obtained double-crosslinked BVLs, SAP + Que-PP, would have great potential to substitute the current clinical GA-crosslinked BVLs.

Well-designed two-fold crosslinked biological valve leaflets with heparin-loaded hydrogel coating for enhancing anticoagulation, endothelialization, and anticalcification.

Commercial biological valve leaflets (BVLs) crosslinked with glutaraldehyde (GA) are at risk of accelerating damage and even failure, owing to the high cell toxicity of GA, acute thrombosis, and calcification in clinical applications. In this study, a novel joint strategy of double crosslinking agents (dialdehyde pectin (AP) and carbodiimide) and heparin-loaded hydrogel coating was developed, endowing BVLs with excellent mechanical properties and multiple performances. Herein, AP played two essential roles, the crosslinking agent and the main component of the hydrogel coating. Both experimental and theoretical results indicated that the mechanical properties and stability of double-crosslinked BVLs were comparable to those of GA, and heparin loaded in hydrogel coating could improve the hemocompatibility of AP + EDC/NHS-PP. Further, cytocompatibility and in vivo tests showed that compared with GA-PP, AP + EDC/NHS + CS + Hep-PP has exhibited good endothelialization ability, mild immune response and anti-calcification performance and therefore prompts it to be an extremely valuable candidate for more durable and multifunctional BVLs.

An agar-polyvinyl alcohol hydrogel loaded with tannic acid with efficient hemostatic and antibacterial capacity for wound dressing.

Rapid hemostasis, antibacterial effect and promotion of wound healing are the most important functions that wound dressings need to have. In this work, we designed and prepared a hydrogel with antibacterial effect, hemostatic ability and wound healing promotion using agar, polyvinyl alcohol (PVA) and tannic acid (TA). We performed a series of tests to characterize the structure and properties of AGAR@PVA-TA hydrogels. The results showed that the AGAR@PVA-TA hydrogels had good mechanical properties and excellent antibacterial ability as well as good hemocompatibility. The cytotoxicity results showed that the AGAR@PVA-TA hydrogels had good cytocompatibility. And the TA loaded hydrogels also presented some good performances in animal studies. In the liver hemostasis model, the AGAR@PVA-TA hydrogel showed good hemostatic ability. Also, the AGAR@PVA-TA hydrogel was able to promote wound healing in an S. aureus-infected rat wound model. More importantly, our research results demonstrated that compared to other polyphenols (such as proanthocyanidins), TA could better improve the mechanical properties, antibacterial ability and rapid hemostasis of hydrogels, which illustrated the uniqueness of TA. Therefore, the TA loaded hydrogel (AGAR@PVA-TA hydrogel) has the potential to be applied as a wound dressing.

Design of a DT neutron source based PGNAA facility for element determination in aqueous solution.

A DT neutron source-based prompt gamma ray neutron activation (PGNAA) facility for bulk sample analysis was designed and developed in this research. The aqueous samples containing chlorine and boron with known concentration were determined for the calibration curve by the facility. The neutron self-shielding effect was corrected by internal standard method. The minimum detectable concentration of boron and chlorine are 1.37 ± 0.42 and 12.51 ± 3.80 mg/L, respectively. Finally, five mixture aqueous solution samples were measured for the facility performance test. The maximum relative deviation of boron and chlorine are 4.49% and 5.32% respectively.

Buffer effect of MgO on Na2SO3 to stabilize S(IV) for the enhancement in simultaneous absorption of NOx and SO2 from non-ferrous smelting gas.

Oxidation-reduction-absorption based on sulfite is a promising process for simultaneous removal of NOx and SO2. However, excessive oxidation of sulfite and competitive absorption between NOx and SO2 limit its application. A matching strategy between antioxidants and alkaline agents has been proposed to solve these problems and enhance the absorption process. The comparison results of inhibitors showed that hydroquinone exhibited long-term high-efficiency inhibition of S(IV) (SO32-/HSO3-) oxidation. The comparison of alkaline agents showed that the Na2SO3 solution with heterogeneous mixture of MgO and hydroquinone exhibited better absorption performance than that with other combinations. The absorption amounts of NOx in 0.15 mol/L Na2SO3 50 mL solution added 0.1% hydroquinone (HQ) with 0.09 mol/L MgO were 2.24 mmol, which improved 5 times than that without additives. In addition, studies on the influence of pH showed that the pH of MgO mixture could be stabilized at 9-10 for a long time, while the pH of Na2CO3 mixture decreased faster. Further studies suggested that the hydration of MgO resulted in the solution with MgO keeping high pH. This is also the main reason why the combination of MgO and hydroquinone is superior to the combination of Na2CO3 and hydroquinone in desulfurization and denitration performance.

Acyl-CoA synthetase long-chain 3-mediated fatty acid oxidation is required for TGFß1-induced epithelial-mesenchymal transition and metastasis of colorectal carcinoma.

Cancer cells frequently undergo metabolic reprogramming to support tumorigenicity and malignancy, which is recognized as a hallmark of cancer. In addition to glycolysis and glutaminolysis, alterations in fatty acid (FA) metabolism have received increasing concerns in the past few years. Recently, accumulating evidence has shown that fatty acid ß-oxidation (FAO) is abnormally activated in various tumors, which is associated with the machinery of proliferation, stemness, metastasis, and radiochemotherapeutic resistance of cancer cells. Acyl-CoA synthetases 3 (ACSL3) belongs to a family of enzymes responsible for converting free long-chain FAs into fatty acyl-CoA esters, which act as substrates both for lipid synthesis and FAO. Here, we demonstrate that transforming growth factor beta 1 (TGFß1) induces the up-regulation of ACSL3 through sterol regulatory element-binding protein 1 (SREBP1) signaling to promote energy metabolic reprogramming in colorectal carcinoma (CRC) cells. ACSL3 mediates the epithelial mesenchymal transition (EMT) and metastasis of CRC cells by activation of FAO pathway to produce ATP and reduced nicotinamide adenine dinucleotide phosphate (NADPH), which sustain redox homeostasis and fuel cancer cells for invasion and distal metastasis. Thus, targeting ACSL3 and FAO metabolic pathways might be exploited for therapeutic gain for CRC and other FAs- addicted cancers.