Endoscopic submucosal dissection for the treatment of a large inflammatory fibroid polyp in the gastric antrum prolapsing into the duodenum: A case report.

RATIONALE: Inflammatory fibroid polyp (IFP), also known as Vanek tumor, is a rare, benign gastrointestinal lesion characterized by its inflammatory and fibroid histological features. IFP is often discovered incidentally during endoscopic examinations. It is exceedingly rare for an IFP to prolapse into the duodenum and results in incomplete obstruction of the pylorus. PATIENT CONCERNS: A 64-year-old male patient was admitted to the hospital with recurrent episodes of melena over a 6-month period, along with complaints of dizziness and fatigue in the past 10 days. DIAGNOSES: Gastroscopy showed a giant polypoid mass on the posterior wall of the gastric antrum, prolapsing into the duodenum. Abdominal computer tomography (CT) confirmed the tumor protruding into the duodenum. Pathologic examination of the resected specimen confirmed the IFP diagnosis. INTERVENTIONS: The giant tumor was completely and successfully excised using endoscopic submucosal dissection (ESD). After the surgery, the patient underwent acid suppression and fluid replenishment therapy. OUTCOMES: The patient responded well to ESD and was discharged in stable condition. As of the submission of the case report, there has been no recurrence of the tumor after a 5-month follow-up, and the patient is still under follow-up. LESSONS: While IFPs have traditionally been managed surgically, ESD demonstrates promising treatment outcomes, avoiding the need for surgical distal gastrectomy, and emerges as a safe and effective treatment option.

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Liraglutide Improves PCOS Symptoms in Rats by Targeting FDX1.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder characterized by ovulatory disorders, hyperandrogenemia, and polycystic changes in the ovaries. FDX1 is a ferredoxin-reducing protein on human mitochondria that plays an important role in steroid anabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has recently emerged as a potential therapeutic agent for PCOS. Recent studies have suggested that FDX1 may be associated with the development of PCOS. This study aims to explore the pivotal role of FDX1 in the amelioration of PCOS through liraglutide intervention. MATERIALS AND METHODS: A PCOS rat model was induced via subcutaneous DHEA injections. Following successful model establishment, the rats were treated with liraglutide combined with metformin, or with each drug individually, over a six-week period. After 6 weeks of treatment, we assessed changes in body weight, fasting blood glucose, sex hormone levels, estrous cycle regularity, ovarian morphology, FDX1 expression in ovarian tissue, and ovarian ROS levels. RESULTS: PCOS rats exhibited significant increases in body weight and fasting blood glucose levels, disrupted estrous cycles, and polycystic ovarian morphology. FDX1 expression was notably reduced in the ovarian tissues of PCOS rats. Treatment with liraglutide, both alone and in combination with metformin, led to improvements in body weight, fasting blood glucose, sex hormone balance, estrous cycle regularity, ovarian morphology, and ovarian ROS levels. Notably, FDX1 expression was significantly restored in all treatment groups, with the most substantial increase observed in the liraglutide-treated group. CONCLUSION: This study suggests that FDX1 could serve as a potential biomarker for elucidating the underlying mechanisms of liraglutide's therapeutic effects in PCOS management.

Deubiquitinase USP4 suppresses antitumor immunity by inhibiting IRF3 activation and tumor cell-intrinsic interferon response in colorectal cancer.

Despite the approval of immune checkpoint blockade (ICB) therapy for various tumor types, its effectiveness is limited to only approximately 15% of patients with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) colorectal cancer (CRC). Approximately 80%-85% of CRC patients have a microsatellite stability (MSS) phenotype, which features a rare T-cell infiltration. Thus, elucidating the mechanisms underlying resistance to ICB in patients with MSS CRC is imperative. In this study, we demonstrate that ubiquitin-specific peptidase 4 (USP4) is upregulated in MSS CRC tumors and negatively regulates the immune response against tumors in CRC. Additionally, USP4 represses the cellular interferon (IFN) response and antigen presentation and impairs PRR signaling-mediated cell death. Mechanistically, USP4 impedes the nuclear localization of interferon regulator Factor 3 (IRF3) by deubiquitinating the K63-polyubiquitin chain of TRAF6 and IRF3. Knockdown of USP4 enhances the infiltration of T cells in CRC tumors and overcomes ICB resistance in an MC38 syngeneic mouse model. Moreover, published datasets revealed that patients showing higher USP4 expression exhibited decreased responsiveness to anti-PD-L1 therapy. These findings highlight an essential role of USP4 in the suppression of antitumor immunity in CRC.

Role of differentiated embryo-chondrocyte expressed gene 2 in immunity.

Differentiated embryo-chondrocyte expressed gene 2 (DEC2) is a member of the basic helix-loop-helix (bHLH) subfamily of transcription factors. DEC2 is implicated in tumor immunotherapy, immune system function regulation, and autoimmune diseases. DEC2 enhances Th2 cell differentiation by regulating the IL-2 and IL-4 signaling pathways and mediates the growth of B-1a cells, thereby promoting the occurrence and development of inflammatory responses. In this study, we review the reported roles of DEC2, including the regulation of immune cell differentiation and cytokine production in various cells in humans, and discuss its potential in treating autoimmune diseases and tumors.

Microplastics enhance the invasion of exotic submerged macrophytes by mediating plant functional traits, sediment properties, and microbial communities.

Plant invasions and microplastics (MPs) have significantly altered the structure and function of aquatic habitats worldwide, resulting in severe damage to aquatic ecosystem health. However, the effects of MPs on plant invasion and the underlying mechanisms remain largely unknown. In this study, we conducted mesocosm experiments over a 90-day period to assess the effects of polystyrene microplastics on the invasion of exotic submerged macrophytes, sediment physicochemical properties, and sediment bacterial communities. Our results showed that PS-MPs significantly promoted the performance of functional traits and the invasive ability of exotic submerged macrophytes, while native plants remained unaffected. Moreover, PS-MPs addition significantly decreased sediment pH while increasing sediment carbon and nitrogen content. Additionally, MPs increased the diversity of sediment bacterial community but inhibited its structural stability, thereby impacting sediment bacterial multifunctionality to varying degrees. Importantly, we identified sediment properties, bacterial composition, and bacterial multifunctionality as key mediators that greatly enhance the invasion of exotic submerged macrophytes. These findings provide compelling evidence that the increase in MPs may exacerbate the invasion risk of exotic submerged macrophytes through multiple pathways. Overall, this study enhances our understanding of the ecological impacts of MPs on aquatic plant invasion and the health of aquatic ecosystems.

Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans.

Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues. Besides the diverse ageing-regulated miRNA expression across tissues, we discover numerous miRNAs in the tissues without their transcription. We further profile miRNAs in the extracellular vesicles and find that worm miRNAs undergo inter-tissue trafficking via these vesicles in an age-dependent manner. Using these datasets, we uncover the interaction between body wall muscle-derived mir-1 and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, we systematically investigate worm miRNAs in the somatic tissues and extracellular vesicles during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing.

Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice.

OBJECTIVE: Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism. METHODS: Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot. RESULTS: The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1ß, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae. CONCLUSIONS: Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.

Comparison of ultrasound features and lesion sites in dysfunctional arteriovenous fistula.

This study aimed to investigate ultrasound features of arteriovenous fistula stenosis and their relationship with primary patency after percutaneous transluminal angioplasty (post-intervention primary patency) and compare this classification with that using lesion location. Hemodialysis patients who underwent ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis from July 2020 to December 2021 were retrospectively evaluated. Lesions (excluding inflow arteries) were categorized into five groups based on ultrasound features, and the clinical characteristics and risk factors affecting the post-intervention primary patency of the arteriovenous fistula were analyzed. Among 185 patients, 100 (54.05%), 36 (19.46%), 22 (11.89%), 11 (5.95%), and 16 (8.65%) were classified into the intima-dominant, non-intima-dominant, valve obstruction, vascular calcification, and mixed groups, respectively. The dialysis duration and arteriovenous fistula use time were the highest in the vascular calcification group at 86 (interquartile range: 49-140) and 77 (interquartile range: 49-110) months, respectively. Diabetes mellitus was most common in the intima-dominant group (42.0%). In Kaplan-Meier and univariate Cox analysis, type III lesion location (stenosis in the venous confluence site) was associated with the lower post-intervention primary patency. In the multivariate Cox analysis, percutaneous transluminal angioplasty times (the number of times patients were treated with percutaneous transluminal angioplasty for arteriovenous fistula stenosis dysfunction), vascular calcification, calcification at the lesion site requiring percutaneous transluminal angioplasty, and serum parathyroid hormone levels were independent risk factors for post-intervention primary patency. Ultrasound features showed that calcification of the arteriovenous fistula was detrimental to the post-intervention primary patency of arteriovenous fistula.

Molecular Basis and Genome Editing Applications of a Compact Eubacterium ventriosum CRISPR-Cas9 System.

CRISPR-Cas9 systems have been widely harnessed for diverse genome editing applications because of their ease of use and high efficiency. However, the large molecular sizes and strict PAM requirements of commonly used CRISPR-Cas9 systems restrict their broad applications in therapeutics. Here, we report the molecular basis and genome editing applications of a novel compact type II-A Eubacterium ventriosum CRISPR-Cas9 system (EvCas9) with 1107 residues and distinct 5'-NNGDGN-3' (where D represents A, T, or G) PAM specificity. We determine the cryo-EM structure of EvCas9 in a complex with an sgRNA and a target DNA, revealing the detailed PAM recognition and sgRNA and target DNA association mechanisms. Additionally, we demonstrate the robust genome editing capacity of EvCas9 in bacteria and human cells with superior fidelity compared to SaCas9 and SpCas9, and we engineer it to be efficient base editors by fusing a cytidine or adenosine deaminase. Collectively, our results facilitate further understanding of CRISPR-Cas9 working mechanisms and expand the compact CRISPR-Cas9 toolbox.

Molecular basis and engineering of miniature Cas12f with C-rich PAM specificity.

CRISPR-Cas12f nucleases are currently one of the smallest genome editors, exhibiting advantages for efficient delivery via cargo-size-limited adeno-associated virus delivery vehicles. Most characterized Cas12f nucleases recognize similar T-rich protospacer adjacent motifs (PAMs) for DNA targeting, substantially restricting their targeting scope. Here we report the cryogenic electron microscopy structure and engineering of a miniature Clostridium novyi Cas12f1 nuclease (CnCas12f1, 497 amino acids) with rare C-rich PAM specificity. Structural characterizations revealed detailed PAM recognition, asymmetric homodimer formation and single guide RNA (sgRNA) association mechanisms. sgRNA engineering transformed CRISPR-CnCas12f1, which initially was incapable of genome targeting in bacteria, into an effective genome editor in human cells. Our results facilitate further understanding of CRISPR-Cas12f1 working mechanism and expand the mini-CRISPR toolbox.

Comparison and development of scanning electron microscope techniques for delicate plant tissues.

Cell deformation often occurs during sample preparation and imaging with scanning electron microscope (SEM), especially with delicate samples, which influences the accuracy of the results. Here we investigate the influence of several preparation methods on cell deformation, using water content and tissue hardness as indicators to classify "delicate" samples of plant species. The degree of deformation in samples resulting from five preparation methods was measured at the tissue and single-cell levels, revealing that a cryo- and methanol-fixation produced lower degrees of tissue dimension deformation and better preservation of cell shape for delicate samples, while for harder tissues, other preparation methods for a dehydrated specimen are also suitable. Stability and image quality of delicate samples could be improved with the application of a cryo-protectant combined with a lower cryo-stage temperature, e.g. - 30 °C. We show that the sample stability under the beam was improved by combining larger sample size and cryo-stage application. Furthermore, the influence of adaxial and abaxial tissue surfaces, the accelerating voltage, and sputter coating time on sample stability and image quality was evaluated. Our study is valuable for artifact reduction and easy application of SEM.

pH-Responsive doxorubicin-loaded magnetosomes for magnetic resonance-guided focused ultrasound real-time monitoring and ablation of breast cancer.

MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.

Study on Low Thermal-Conductivity of PVDF@SiAG/PET Membranes for Direct Contact Membrane Distillation Application.

In order to enhance the separation performance and reduce the heat loss of transmembrane for membrane distillation, the thermal efficiency and hydrophobicity of the membrane distillation need to be simultaneously enhanced. In this work, a polyvinylidene difluoride/polyethylene glycol terephthalate (PVDF/PET) hydrophobic/hydrophilic membrane has been prepared by non-solvent phase induction method. Nanosized silica aerogel (SiAG) with high porosity has been added to the composite membranes. The modifying effects and operating conditions on permeate flux and thermal efficiency in direct contact membrane distillation (DCMD) are investigated. Furthermore, the latent heat of vaporization and the heat transfer across the membranes have been compared for SiAG addition, which indicates that the composite PVDF@SiAG/PET membranes demonstrate a great potential for distillation-separation application due to their high heat efficiency.

Molecularly imprinted composite membranes with interleaved imprinted network structure for highly selective separation of acteoside.

Acteoside (ACT) is one of the phenylethanoid glycosides in Cistanche tubulosa. The ACT molecules have high medicinal value, but the content of ACT is scarce. Therefore, it is imperative to develop the ACT-based molecularly imprinted composite membranes (A-MICMs) with highly selective separation of ACT. In this study, the amine-polyhedral oligomeric sesquisiloxanes (NH2-POSS) were uniformly introduced into polydopamine modified polyvinylidene fluoride (pDA@PVDF) membranes to fabricate NH2-POSS-pDA@PVDF. Then, the ACT-imprinted layers were synthesized on the surface of NH2-POSS-pDA@PVDF to obtain A-MICMs. The results showed that the optimal conditions were 180 mg DA, 12 h DA self-polymerization time, 400 mg NH2-POSS and 10 h washing time for the synthesis of A-MICMs. The results of adsorption isotherm experiments showed that there was a single layer adsorbate analyte on the A-MICMs. The results of adsorption kinetic experiments showed that chemisorption mechanism played a major function in the adsorption process of A-MICMs for ACT. The A-MICMs exhibited the maximum rebinding capacity of 98.37 mg⋅g-1, an excellent rebinding selectivity of 4.63, and the permselectivity of 7.02. The same A-MICMs kept 95.99% of the maximum rebinding capacity for ACT after 5 adsorption-desorption cycles. The designed A-MICMs with the interleaved imprinted network structure have a potential to be applied to the highly selective separation of bioactive components from natural products.

Poly(ionic liquid)/OPBI Composite Membrane with Excellent Chemical Stability for High-Temperature Proton Exchange Membrane.

Despite the outstanding proton conductivity of phosphoric acid (PA)-doped polybenzimidazole (PBI) membranes as high-temperature proton exchange membranes (HT-PEMs), chemical stability is a critical issue for the operation life of PEM fuel cells (PEMFCs). Herein, we introduced polymerized [HVIM]H2PO4 ionic liquids (PIL) into an OPBI membrane to accelerate proton transfer and enhance the chemical stability of the membrane. Based on the regulation of the intrinsic viscosity of PIL, the entanglement between PIL chains and OPBI chains is enhanced to prevent the loss of PIL and the oxidative degradation of membrane materials. The PIL/OPBI membrane with the intrinsic viscosity of 2.34 dL·g-1 (2.34-PIL/OPBI) exhibited the highest proton conductivity of 113.9 mS·cm-1 at 180 °C, which is 3.5 times that of the original OPBI membrane. The 2.34-PIL/OPBI membrane exhibited the highest remaining weight of 92.1% under harsh conditions (3 wt% H2O2; 4 ppm Fe2+ at 80 °C) for 96 h, and a much lower attenuation amplitude than the OPBI did in mechanical strength and proton conductivity performance. Our present work demonstrates a simple and effective method for blending PIL with OPBI to enhance the chemical durability of the PA-PBI membranes as HT-PEMs.

Recurrent syncope due to central venous occlusion in a patient undergoing hemodialysis.

A 66-year-old male patient receiving maintenance hemodialysis with arteriovenous fistula of the right upper limb was admitted to the hospital because of intermittent syncope, dizziness, and distension. Central venography indicated occlusion of the right brachiocephalic vein (RBV), and the contrast agent flowed from the right internal jugular vein into the intracranial vein, then into the contralateral internal jugular vein, and finally returned into the superior vena cava. Percutaneous transluminal angioplasty was performed to dilate the RBV. Postoperatively, the contrast agent flowed smoothly into the right atrium through the RBV and the superior vena cava. Craniocerebral magnetic resonance angiography and magnetic resonance venography indicated that the intracranial venous reflux disappeared. The patient did not experience syncope again; moreover, dizziness and distention improved, as well as right facial swelling and right eye congestion, and he was discharged 2 days later. Two months later, the patient complained of dizziness. Venography under digital subtraction angiography showed severe stenosis at the RBV and percutaneous transluminal angioplasty was performed; moreover, stent placement was performed. The contrast agent flowed smoothly into the right atrium through the RBV and the superior vena cava again. Ultimately, the headaches and dizziness improved significantly postoperatively. Hence, if hemodialysis patients present with neurological symptoms, intracranial venous congestion should be monitored; nonetheless, most patients have a good prognosis when treated appropriately.

High-efficiency targeted transgene integration via primed micro-homologues.

Due to the difficulties in precisely manipulating DNA repair pathways, high-fidelity targeted integration of large transgenes triggered by double-strand breaks is inherently inefficient. Here, we exploit prime editors to devise a robust knock-in (KI) strategy named primed micro-homologues-assisted integration (PAINT), which utilizes reverse-transcribed single-stranded micro-homologues to boost targeted KIs in different types of cells. The improved version of PAINT, designated PAINT 3.0, maximizes editing efficiency and minimizes off-target integration, especially in dealing with scarless in-frame KIs. Using PAINT 3.0, we target a reporter transgene into housekeeping genes with editing efficiencies up to 80%, more than 10-fold higher than the traditional homology-directed repair method. Moreover, the use of PAINT 3.0 to insert a 2.5-kb transgene achieves up to 85% KI frequency at several therapeutically relevant genomic loci, suggesting its potential for clinical applications. Finally, PAINT 3.0 enables high-efficiency non-viral genome targeting in primary T cells and produces functional CAR-T cells with specific tumor-killing ability. Thus, we establish that the PAINT method is a powerful gene editing tool for large transgene integrations and may open new avenues for cell and gene therapies and genome writing technologies.

Primary cilia support cartilage regeneration after injury.

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.

FOXK2 regulates PFKFB3 in promoting glycolysis and tumorigenesis in multiple myeloma.

Forkhead box K2 (FOXK2) is a transcription factor involved in regulating the pathophysiological processes in many types of cancers. Functioning as either an oncogene or tumor suppressor, FOXK2 is involved in cell proliferation, metastasis, DNA damage, metabolism, and autophagy. However, the functions of FOXK2 in multiple myeloma (MM) are still unexplored. Here we show that FOXK2 silencing by small interfering RNA (siRNA) prevented the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) via dephosphorylation of an AMP-activated protein kinase (AMPK). Consistently, suppression of FOXK2 inhibited glycolysis and cell proliferation in MM cells. Furthermore, the correlation between FOXK2 expression and disease progression in MM was evaluated using the TCGA (The Cancer Genome Atlas) database. Taken together, we identified a novel FOXK2-dependent signaling pathway involved in the regulation of PFKFB3 expression in response to glycolysis, which might serve as a potential therapeutic target in MM.