Rechargeable alkali metal-chlorine batteries: advances, challenges, and future perspectives.

The emergence of Li-SOCl2 batteries in the 1970s as a high-energy-density battery system sparked considerable interest among researchers. However, limitations in the primary cell characteristics have restricted their potential for widespread adoption in today's sustainable society. Encouragingly, recent developments in alkali/alkaline-earth metal-Cl2 (AM-Cl2) batteries have shown impressive reversibility with high specific capacity and cycle performance, revitalizing the potential of SOCl2 batteries and becoming a promising technology surpassing current lithium-ion batteries. In this review, the emerging AM-Cl2 batteries are comprehensively summarized for the first time. The development history and advantages of Li-SOCl2 batteries are traced, followed by the critical working mechanisms for achieving high rechargeability. The design concepts of electrodes and electrolytes for AM-Cl2 batteries as well as key characterization techniques are also demonstrated. Furthermore, the current challenges and corresponding strategies, as well as future directions regarding the battery are systematically discussed. This review aims to deepen the understanding of the state-of-the-art AM-Cl2 battery technology and accelerate the development of practical AM-Cl2 batteries for next-generation high-energy storage systems.

Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis.

BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

TFE3-SLC36A1 axis promotes resistance to glucose starvation in kidney cancer cells.

Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms shall shed insight into cancer progression and benefit cancer therapy. TFE3 is a transcription factor known to activate autophagic genes. Physiological TFE3 activity is regulated by phosphorylation-triggered translocation responsive to nutrient status. We recently reported TFE3 constitutively localizes to the cell nucleus and promotes cell proliferation in kidney cancer even under nutrient replete condition. It remains unclear whether and how TFE3 responds to glucose starvation. In this study, we show TFE3 promotes kidney cancer cell resistance to glucose starvation by exposing cells to physiologically relevant glucose concentration. We find glucose starvation triggers TFE3 protein stabilization through increasing its O-GlcNAcylation. Furthermore, through an unbiased functional genomic study, we identify SLC36A1, a lysosomal amino acid transporter, as a TFE3 target gene sensitive to TFE3 protein level. We find SLC36A1 is overexpressed in kidney cancer, which promotes mTOR activity and kidney cancer cell proliferation. Importantly, SLC36A1 level is induced by glucose starvation through TFE3, which enhances cellular resistance to glucose starvation. Suppressing TFE3 or SLC36A1 significantly increases cellular sensitivity to GLUT1 inhibitor in kidney cancer cells. Collectively, we uncover a functional TFE3-SLC36A1 axis that responds to glucose starvation and enhances starvation tolerance in kidney cancer.

Superwetting Capillary Tubes: Surface Science under Confined Space.

Capillarity is a crucial and pervasive phenomenon in nature and has found important applications in wearable electronics, medical devices, and miniature energy systems. Capillary tubes are the transport vessels in which the surface wettability plays an essential role in efficient and accurate liquid delivery. However, it remains a challenging issue to tailor and measure the surface wettability inside the tubes in view of the confined space. Herein, recent progress on the surface science under confined space is discussed, with a particular focus on surface modification, wettability evaluation, and advanced applications of the superwetting capillary tubes. This Perspective aims to highlight the emerging opportunities in surface science with spatial confinement toward flexible and portable devices.

TiO2 Nanotube Arrays Inside Ultrafine Ti Tubes with an Aspect Ratio of 2500 for Sensing Needles: The Bubble Effect in a Confined Space.

Capillary metal tubes have attracted considerable interest for flexible electronics, portable devices, trace sampling, and detection. Tailoring the microstructure and wettability inside the capillary tubes is of paramount importance, yet it presents great difficulty because of the spatial confinement. Here, the coupling effect is revealed between the fluidic and electric field induced by bubble motion in a confined space during anodic oxidation. By controlling the bubble regeneration and flow rate, uniform and superhydrophilic TiO2 nanotube arrays are developed throughout the inner surface of an ultrafine Ti tube with a diameter of 0.4 mm and length of 1000 mm, equivalent to an aspect ratio of 2500 that is the largest value being ever reported. The inner surface of a capillary tube is further coated with a polytetrafluoroethylene layer and explored as a sensing needle for liquid detection in terms of concentration and species. This study provides an innovative approach to tailor the microstructure and wettability in a confined space for functional capillary tubes.

[Effect of Spatholobi Caulis extract from ethyl acetate on immune killing function of NK cells].

This study aims to investigate the regulatory effect of the Spatholobi Caulis extract from ethyl acetate(SEA) on natural killer(NK) cells under physiological conditions and elucidate the underlying mechanism. The C57BL/6 mice were randomized into NC and SEA groups, and NK-92 cells were respectively treated with 0, 25, 50, and 100 µg·mL~(-1) SEA. The body weight and immune organ index of the mice were compared between groups. The lactate dehydrogenase(LDH) assay was employed to examine the cytotoxicity of NK-92 cells treated with SEA and the killing activity of mouse NK cells against YAC-1 cells. The cell-counting kit-8(CCK-8) was used to examine the impact of SEA on the proliferation of NK-92 cells. Flow cytometry was employed to measure the number of NK cells in the peripheral blood as well as the expression levels of natural killer group 2 member A(NKG2A) and natural killer group 2 member D(NKG2D). The enzyme-linked immunosorbent assay(ELISA) was performed to determine the interferon(IFN)-γ secretion in the serum. Semi-quantitative PCR was conducted to determine the mRNA levels of NKG2A, NKG2D, and IFN-γ in spleen cells. Western blot was employed to investigate the involvement of phosphoinositide 3-kinase(PI3K)/extracellular regulated protein kinase 1(ERK1) signaling pathway. The results showed that SEA exhibited no adverse effects on the body, while significantly enhance the number of NK cells and augment the cytotoxicity of NK-92 cells against YAC-1 cells. Moreover, it suppressed the expression of NKG2A, enhanced the expression of NKG2D, promoted IFN-γ secretion, and upregulated the protein levels of PI3K and ERK. The findings suggest that SEA has the potential to enhance the immune recognition and effector function of NK cells by increasing the cell number, modulating the expression of functional receptors, and promoting IFN-γ secretion via the PI3K/ERK signaling pathway.

Ethyl-acetate extract of Spatholobi Caulis blocked the pro-metastatic support from the hemato-microenvironment of colon cancer by specific disruption of tumor-platelet adhesion.

BACKGROUND: Within the pro-metastatic hemato-microenvironment, interaction between platelets and tumor cells provides essential support for tumor cells by inducing Epithelial-Mesenchymal Transition (EMT), which greatly increases the stemness of colon cancer cells. Pharmacologically, although platelet deactivation has proved to be benefit against metastasis, its wide application is severely restricted due to the bleeding risk. Spatholobi Caulis, a traditional Chinese herb with circulatory promotion and blood stasis removal activity, has been proved to be clinically effective in malignant medication, leaving its mechanistic relevance to tumor-platelet interaction largely unknown. METHODS: Firstly, MC38-Luc cells were injected into tail-vein in C57BL/6 mice to establish hematogenous metastasis model and the anti-metastasis effects of SEA were evaluated by using a small-animal imaging system. Then, we evaluated the anti-tumor-platelet interaction efficacy of SEA using a tumor-specific induced platelet aggregation model. Platelet aggregation was specifically induced by tumor cells in vitro. Furthermore, to clarify the anti-metastatic effects of SEA is mainly attributed to its blockage on tumor-platelet interaction, after co-culture with tumor cells and platelets (with or without SEA), MC38-Luc cells were injected into the tail-vein and finally count the total of photons quantitatively. Besides, to clarify the blocking pattern of SEA within the tumor-platelet complex, the dependence of SEA on different fractions from activated platelets was tested. Lastly, molecular docking screening were performed to screen potential effective compounds and we used ß-catenin blockers to verify the pathways involved in SEA blocking tumor-platelet interaction. RESULTS: Our study showed that SEA was effective in blocking tumor-platelet specific interaction: (1) Through CCK-8 and LDH assays, SEA showed no cytotoxic effects on tumor cells and platelets. On this basis, by the tail vein injection model, the photon counts in the SEA group was significantly lower than model group, indicating that SEA effectively reduced metastasis. (2) In the "tumor-platelet" co-culture model, SEA effectively inhibited the progression of EMT and cancer stemness signatures of MC38 cells in the model group. (3) In mechanism study, by using the specific inhibitors for galectin-3 (GB1107) andWNT (IWR) respectively, we proved that SEA inhibits the activation of the galectin-3-mediated ß-catenin activation. CONCLUSION: By highlighting the pro-metastatic effects of galectin-3-mediated tumor-platelet adhesion, our study provided indicative evidence for Spatholobi Caulis as the representative candidate for anti-metastatic therapy.

YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation.

Prostate cancer is a leading cause of cancer-related mortality in males. Dysregulation of RNA adenine N-6 methylation (m6A) contributes to cancer malignancy. m6A on mRNA may affect mRNA splicing, turnover, transportation, and translation. m6A exerts these effects, at least partly, through dedicated m6A reader proteins, including YTH domain-containing family protein 2 (YTHDF2). YTHDF2 is necessary for development while its dysregulation is seen in various cancers, including prostate cancer. However, the mechanism underlying the dysregulation and function of YTHDF2 in cancer remains elusive. Here, we find that the deubiquitinase OUT domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) increases YTHDF2 protein stability by inhibiting its ubiquitination. With in vivo and in vitro ubiquitination assays, OTUB1 is shown to block ubiquitin transfer to YTHDF2 independent of its deubiquitinase activity. Furthermore, analysis of functional transcriptomic data and m6A-sequencing data identifies PRSS8 as a potential tumor suppressor gene. OTUB1 and YTHDF2 decrease mRNA and protein levels of PRSS8, which is a trypsin-like serine protease. Mechanistically, YTHDF2 binds PRSS8 mRNA and promotes its degradation in an m6A-dependent manner. Further functional study on cellular and mouse models reveals PRSS8 is a critical downstream effector of the OTUB1-YTHDF2 axis in prostate cancer. We find in prostate cancer cells, PRSS8 decreases nuclear ß-catenin level through E-cadherin, which is independent of its protease activity. Collectively, our study uncovers a key regulator of YTHDF2 protein stability and establishes a functional OTUB1-YTHDF2-PRSS8 axis in prostate cancer.

The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1.

Liver cancer is notoriously refractory to conventional therapeutics. Tumor progression is governed by the interplay between tumor-promoting genes and tumor-suppressor genes. BRD4, an acetyl lysine-binding protein, is overexpressed in many cancer types, which promotes activation of a pro-tumor gene network. But the underlying mechanism for BRD4 overexpression remains incompletely understood. In addition, understanding the regulatory mechanism of BRD4 protein level will shed insight into BRD4-targeting therapeutics. In this study, we investigated the potential relation between BRD4 protein level and P53, the most frequently dysregulated tumor suppressor. By analyzing the TCGA datasets, we first identify a strong negative correlation between protein levels of P53 and BRD4 in liver cancer. Further investigation shows that P53 promotes BRD4 protein degradation. Mechanistically, P53 indirectly represses the transcription of USP1, a deubiquitinase, through the P21-RB1 axis. USP1 itself is also overexpressed in liver cancer and we show USP1 deubiquitinates BRD4 in vivo and in vitro, which increases BRD4 stability. With cell proliferation assays and xenograft model, we show the pro-tumor role of USP1 is partially mediated by BRD4. With functional transcriptomic analysis, we find the USP1-BRD4 axis upholds expression of a group of cancer-related genes. In summary, we identify a functional P53-P21-RB1-USP1-BRD4 axis in liver cancer.

Organocatalytic Lithium Chloride Oxidation by Covalent Organic Frameworks for Rechargeable Lithium-Chlorine Batteries.

Rechargeable Li-Cl2 battery is a promising high energy density battery system. However, reasonable cycle life could only be achieved under low specific capacities due to the sluggish oxidation of LiCl to Cl2 . Herein, we propose an amine-functionalized covalent organic framework (COF) with catalytic activity, namely COF-NH2 , that significantly decreases the oxidation barrier of LiCl and accelerates the oxidation kinetics of LiCl in Li-Cl2 cell. The resulting Li-Cl2 cell using COF-NH2 (Li-Cl2 @COF-NH2 ) simultaneously exhibits low overpotential, ultrahigh discharge capacity up to 3500 mAh/g and a promoted utilization ratio of deposited LiCl at the first cycle (UR-LiCl) of 81.4 %, which is one of the highest reported values to date. Furthermore, the Li-Cl2 @COF-NH2 cell could be stably cycled for over 200 cycles when operating at a capacity of 2000 mAh/g at -20 °C with a Coulombic efficiency (CE) of ≈100 % and a discharge plateau of 3.5 V. Our superior Li-Cl2 batteries enabled by organocatalyst enlighten an arena towards high-energy storage applications.

Enrichment of Chlorine in Porous Organic Nanocages for High-Performance Rechargeable Lithium-Chlorine Batteries.

Rechargeable Li-Cl2 batteries are recognized as promising candidates for energy storage due to their ultrahigh energy densities and superior safety features. However, Li-Cl2 batteries suffer from a short cycle life and low Coulombic efficiency (CE) at a high specific cycling capacity due to a sluggish and insufficient Cl2 supply during the redox reaction. To achieve Li-Cl2 batteries with high discharge capacity and CE, herein, we propose and design an imine-functionalized porous organic nanocage (POC) to enrich Cl2 molecules. Based on density functional theory (DFT) calculations, the imine group sites in host cages strongly interact with Cl2 molecules, facilitating the rapid capture of Cl2. As a result, the output capacity of the Li-Cl2 battery using POC (Li-Cl2@POC) is significantly boosted, achieving an ultrahigh discharge capacity of 4000 mAh/g at ∼100% CE. Benefiting from the designed POC, the highest utilization ratio of deposited LiCl at the first cycle in the Li-Cl2@POC battery reaches as high as 85%, superior to all reported values. The Li-Cl2@POC battery exhibits excellent electrochemical performance even at low temperatures, delivering stable cycling over 200 cycles under a capacity of 2000 mAh/g at -20 °C with a voltage plateau of 3.5 V and an average CE of 99.7%. We also demonstrate that the Li-Cl2@POC cells can be assembled and well-operated in a dry room, showing advantages for mass production. Our designed POC promotes the practical deployment of rechargeable Li-Cl2 batteries.

Monitoring Autophagy with GFP-LC3 Reporter.

Autophagy is a key process that maintains cellular homeostasis. Autophagy contributes to various physiological and pathophysiological processes. Development of methodologies for autophagy detection has greatly facilitated the research on autophagy. Among these methodologies, GFP-LC3 reporter has been popularly used in the literature. In this chapter, we will detail step-by-step the GFP-LC3 reporter protocol we have adapted in our lab. This protocol begins with the generation of lentivirus expressing GFP-LC3. Then, the cells are transduced with titrated virus. After selecting the positive cells, single colonies are isolated, characterized, validated, and used in further study.

Excitons Enabled Topological Phase Singularity in a Single Atomic Layer.

The nontrivial and rigorous Heaviside phase jump behavior of phase singularities (PSs) empowers exotic topological modes and widely divergent nature compared to neighboring points, which has attracted great attention in condensed matter physics as well as applications in photonics and ultrasensitive sensors. Here we demonstrate the universal existence of a family of topologically protected PSs generated from exciton resonances of single-atom layers. We obtain the PSs by coating the transition metal dichalcogenide (TMDC) monolayers on a nonabsorptive semi-infinite substrate without surface plasmon effect or other assisted resonators, which exploits the benefits of both exciton-dominated enhancement and peculiarities of the singular phase. We show that a refractive indices matched transparent substrate enables TMDC monolayers to exhibit topologically protected zero reflection accompanied by a perfect Heaviside π-phase jump at strong light adsorptions, which can be utilized to radically reduce the thickness of PS-based devices to a single atomic layer. By using the TMDC monolayer-based PSs for refractive index biosensors, we demonstrate its superior phase sensitivity at a level of 104 degrees per refractive index unit and detection of bioactive bacteria, respectively, which is comparable to the cutting-edge surface plasmon and Fabry-Perot resonance sensors. Our proof-of-concept results offer experimental and theoretical insights into a single atomic playground for flat singular optics and label-free biosensing technologies.

TRIM28 represses renal cell carcinoma cell proliferation by inhibiting TFE3/KDM6A-regulated autophagy.

Autophagy plays a pivotal role in physiology and pathophysiology, including cancer. Mechanisms of autophagy dysregulation in cancer remain elusive. Loss of function of TRIM28, a multifunction protein, is seen in familial kidney malignancy, but the mechanism by which TRIM28 contributes to the etiology of kidney malignancy is unclear. In this study, we show TRIM28 retards kidney cancer cell proliferation through inhibiting autophagy. Mechanistically, we find TRIM28 promotes ubiquitination and proteasome-mediated degradation of transcription factor TFE3, which is critical for autophagic gene expression. Genetic activation of TFE3 due to gene fusion is known to cause human kidney malignancy, but whether and how transcription activation by TFE3 involves chromatin changes is unclear. Here, we find another mode of TFE3 activation in human renal carcinoma. We find that TFE3 is constitutively localized to the cell nucleus in human and mouse kidney cancer, where it increases autophagic gene expression and promotes cell autophagy as well as proliferation. We further uncover that TFE3 interacts with and recruits histone H3K27 demethylase KDM6A for autophagic gene upregulation. We reveal that KDM6A contributes to expression of TFE3 target genes through increasing H3K4me3 rather than demethylating H3K27. Collectively, in this study, we identify a functional TRIM28-TFE3-KDM6A signal axis, which plays a critical role in kidney cancer cell autophagy and proliferation.

[Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling].

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Metal Fluoride Cathode Materials for Lithium Rechargeable Batteries: Focus on Iron Fluorides.

Exploring prospective rechargeable batteries with high energy densities is urgently needed on a worldwide scale to address the needs of the large-scale electric vehicle market. Conversion-type metal fluorides (MFs) are attractive cathodes for next-generation rechargeable batteries because of their high theoretical potential and capacities and provide new perspectives for developing novel battery systems that satisfy energy density requirements. However, some critical issues, such as high voltage hysteresis and poor cycling stability must be solved to further enhance MF cathode materials. In this review, the recent advances in mechanisms focused on FeF3 cathodes under lithiation/delithiation processes are discussed in detail. Then, the classifications and advantages of various synthesis methods to prepare MF-based materials are first minutely discussed. Moreover, the performance attenuation mechanisms of MFs and the effort in the development of mitigation strategies are comprehensively reviewed. Finally, prospects for the current obstacles and possible research directions, with the aim to provide some inspiration for the development of MF cathode-based batteries are presented.

OTUB1-mediated inhibition of ubiquitination: a growing list of effectors, multiplex mechanisms, and versatile functions.

Protein ubiquitination plays a pivotal role in protein homeostasis. Ubiquitination may regulate the stability, activity, protein-protein interaction, and localization of a protein. Ubiquitination is subject to regulation by two groups of counteracting enzymes, the E3 ubiquitin ligases and deubiquitinases. Consistently, deubiquitinases are involved in essentially all biological processes. OTUB1, an OTU-family deubiquitinase, is a critical regulator of development, cancer, DNA damage response, and immune response. OTUB1 antagonizes the ubiquitination of a wide-spectrum of proteins through at least two different mechanisms. Besides direct deubiquitination, OTUB1 can also inhibit ubiquitination by non-canonically blocking ubiquitin transfer from certain ubiquitin-conjugases (E2). In this review, we start with a general background of protein ubiquitination and deubiquitination. Next, we introduce the basic characteristics of OTUB1 and then elaborate on the updated biological functions of OTUB1. Afterwards, we discuss potential mechanisms underlying the versatility and specificity of OTUB1 functions. In the end, we discuss the perspective that OTUB1 can be a potential therapeutic target for cancer.

Efficient and reversible Cas13d-mediated knockdown with an all-in-one lentivirus-vector.

Type VI CRISPR effector Cas13d from Ruminococcus flavefaciens XPD3002 (RfxCas13d) is an RNA-guided RNA endonuclease. RfxCas13d has been harnessed to knockdown gene expression with high specificity in various systems including mammalian cells. While inducible knockdown is advantageous over constitutive knockdown in many scenarios, current inducible systems of RfxCas13d express CRISPR RNA and Cas13d separately. Such systems could be cumbersome to handle and may hamper the application of RfxCas13d in some scenarios. Here, we design an all-in-one Cas13d lentivirus vector which renders efficient and inducible knockdown in a doxycycline dosage-dependent manner. Furthermore, we find that Cas13d has a short half-life in mammalian cells. As a result, knockdown can be promptly reversed after doxycycline withdrawal. This vector is particularly useful for applications involving indispensable genes and/or in cells hard to transduce.

Lysine demethylase KDM1A promotes cell growth via FKBP8-BCL2 axis in hepatocellular carcinoma.

Advanced hepatocellular carcinoma (HCC) has a dismal prognosis. KDM1A (lysine demethylase 1A), overexpressed in multiple cancer types, is a lysine demethylase that targets both histone and nonhistone proteins. However, it is unclear how KDM1A expression affects HCC etiology. Here, we show that KDM1A can interact with and demethylate FKBP8 (FKBP prolyl isomerase 8), a cytoplasmic protein that regulates cell survival through the antiapoptotic protein BCL2 (B-cell lymphoma-2). We show that demethylation of FKBP8 enhances its ability to stabilize BCL2. Consistently, we observed positive correlation between KDM1A and BCL2 protein levels in liver cancer patients. Functionally, we reveal that FKBP8 demethylation by KDM1A is critical for liver cancer cell growth in vitro and in vivo. We went on to explore the mechanisms that might regulate KDM1A cytoplasmic localization. We found that the cytoplasmic localization and protein stability of KDM1A were promoted by acetylation at lysine-117 by the acetyl transferase KAT8 (lysine acetyltransferase 8). In agreement with this, we show that KDM1A-K117 (lysine 117) acetylation promotes demethylation of FKBP8 and level of BCL2. Finally, it has been shown that the efficacy of sorafenib, a first-line treatment for advanced HCC, is limited by clinical resistance. We show that KDM1A and BCL2 protein levels are increased during acquired sorafenib resistance, whereas inhibiting KDM1A can antagonize sorafenib resistance. Collectively, these results define a functional KDM1A-FKBP8-BCL2 axis in HCC.