Nitrate recovery from groundwater and simultaneous upcycling into single-cell protein using a novel hybrid biological-inorganic system.

Nitrate pollution in groundwater is a serious problem worldwide, as its concentration in many areas exceeds the WHO-defined drinking water standard (50 mg/L). Hydrogen-oxidizing bacteria (HOB) are a group of microorganisms capable of producing single-cell protein (SCP) using hydrogen and oxygen. Furthermore, HOB can utilize various nitrogen sources, including nitrate. This study developed a novel hybrid biological-inorganic (HBI) system that coupled a new submersible water electrolysis system driven by renewable electricity with HOB fermentation for in-situ nitrate recovery from polluted groundwater and simultaneously upcycling it together with CO2 into single-cell protein. The performance of the novel HBI system was first evaluated in terms of bacterial growth and nitrate removal efficiency. With 5 V voltage applied and the initial nitrate concentration of 100 mg/L, the nitrate removal efficiency of 85.52 % and raw of 47.71 % (with a broad amino acid spectrum) were obtained. Besides, the HBI system was affected by the applied voltages and initial nitrogen concentrations. The water electrolysis with 3 and 4 V cannot provide sufficient H2 for HOB and the removal of nitrate was 57.12 % and 59.22 % at 180 h, while it reached 65.14 % and 65.42 % at 5 and 6 V, respectively. The nitrate removal efficiency reached 58.40 % and 50.72 % within 180 h with 200 and 300 mg/L initial nitrate concentrations, respectively. Moreover, a larger anion exchange membrane area promoted nitrate removal. The monitored of the determination of different forms of nitrogen indicated that around 60 % of the recovered nitrate was assimilated into cells, and 40 % was bio-converted to N2. The results demonstrate a potentially sustainable method for remediating nitrate contaminant in groundwater, upcycling waste nitrogen, CO2 sequestration and valorization of renewable electricity into food or feed.

Characteristics of acidic hydrothermal treatment for disintegration of spiramycin fermentation residue and degradation of residual antibiotics.

To recycle the nutrients in spiramycin (SPM) fermentation residue (SFR) through biological methods, acid hydrothermal treatment (AHT) was employed as pretreatment to enhance SFR biodegradability. The results showed that the degradation rate of residual SPM in SFR reached 100% after 120 min at 100℃ and 0.30 M acid with a 30.5% and 89.7% increase in proteins and polysaccharides, respectively. The SPM degradation was faster at higher acidity and temperature. However, elevated SPM concentration and the presence of protein, humic acid, and polysaccharide inhibited SPM degradation. The disintegration of SFR was evidenced by changes in its microstructure and could be predicted through the release of dissolved organic matter. Eight major SPM intermediates were identified with lower mutagenicity and antibacterial activity testing against Staphylococcus aureus. These results demonstrate that AHT not only disintegrates SFR but also degrades the residual SPM antibiotics, which implies the possibility for practical applications.

Management of infected bone defects of the femoral shaft by Masquelet technique: sequential internal fixation and nail with plate augmentation.

BACKGROUND: To evaluate the effectiveness of a sequential internal fixation strategy and intramedullary nailing with plate augmentation (IMN/PA) for bone reconstruction in the management of infected femoral shaft defects using the Masquelet technique. METHODS: We performed a retrospective descriptive cohort study of 21 patients (mean age, 36.4 years) with infected bone defects of the femoral shaft treated by the Masquelet technique with a minimum follow-up of 18 months after second stage. After aggressive debridement, temporary stabilisation (T1) was achieved by an antibiotic-loaded bone cement spacer and internal fixation with a bone cement-coated locking plate. At second stage (T2), the spacer and the locking plate were removed following re-debridement, and IMN/PA was used as definitive fixation together with bone grafting. We evaluated the following clinical outcomes: infection recurrence, bone union time, complications, and the affected limb's knee joint function. RESULTS: The median and quartiles of bone defect length was 7 (4.75-9.5) cm. Four patients required iterative debridement for infection recurrence after T1. The median of interval between T1 and T2 was 10 (9-19) weeks. At a median follow-up of 22 (20-27.5) months, none of the patients experienced recurrence of infection. Bone union was achieved at 7 (6-8.5) months in all patients, with one patient experiencing delayed union at the distal end of bone defect due to screws loosening. At the last follow-up, the median of flexion ROM of the knee joint was 120 (105-120.0)°. CONCLUSIONS: For infected femoral shaft bone defects treated by the Masquelet technique, sequential internal fixation and IMN/PA for the reconstruction can provide excellent mechanical stability, which is beneficial for early functional exercise and bone union, and does not increase the rate of infection recurrence.

Unveiling the Enhancement of Electrocatalytic Oxygen Evolution Activity in Ru-Fe2O3/CoS Heterojunction Catalysts.

The development of highly efficient electrocatalysts for the sluggish anodic oxygen evolution reaction (OER) is crucial to meet the practical demand for water splitting. In this study, an effective approach is proposed that simultaneously enhances interfacial interaction and catalytic activity by modifying Fe2O3/CoS heterojunction using Ru doping strategy to construct an efficient electrocatalytic oxygen evolution catalyst. The unique morphology of Ru doped Fe2O3 (Ru-Fe2O3) nanoring decorated by CoS nanoparticles ensures a large active surface area and a high number of active sites. The designed Ru-Fe2O3/CoS catalyst achieves a low OER overpotential (264 mV) at 10 mA cm-2 and demonstrates exceptional stability even at high current density of 100 mA cm-2, maintaining its performance for an impressive duration of 90 h. The catalytic performance of this Ru-Fe2O3/CoS catalyst surpasses that of other iron-based oxide catalysts and even outperforms the state-of-the-art RuO2. Density functional theory (DFT) calculation as well as experimental in situ characterization confirm that the introduction of Ru atoms can enhance the interfacial electron interaction, accelerating the electron transfer, and serve as highly active sites reducing the energy barrier for rate determination step. This work provides an efficient strategy to reveal the enhancement of electrocatalytic oxygen evolution activity of heterojunction catalysts by doping engineering.

High-Performance Macroporous Free-Standing Microbial Fuel Cell Anode Derived from Grape for Efficient Power Generation and Brewery Wastewater Treatment.

Microbial fuel cells (MFCs) have the potential to directly convert the chemical energy in organic matter into electrical energy, making them a promising technology for achieving sustainable energy production alongside wastewater treatment. However, the low extracellular electron transfer (EET) rates and limited bacteria loading capacity of MFCs anode materials present challenges in achieving high power output. In this study, three-dimensionally heteroatom-doped carbonized grape (CG) monoliths with a macroporous structure were successfully fabricated using a facile and low-cost route and employed as independent anodes in MFCs for treating brewery wastewater. The CG obtained at 900 °C (CG-900) exhibited excellent biocompatibility. When integrated into MFCs, these units initiated electricity generation a mere 1.8 days after inoculation and swiftly reached a peak output voltage of 658 mV, demonstrating an exceptional areal power density of 3.71 W m-2. The porous structure of the CG-900 anode facilitated efficient ion transport and microbial community succession, ensuring sustained operational excellence. Remarkably, even when nutrition was interrupted for 30 days, the voltage swiftly returned to its original level. Moreover, the CG-900 anode exhibited a superior capacity for accommodating electricigens, boasting a notably higher abundance of Geobacter spp. (87.1%) compared to carbon cloth (CC, 63.0%). Most notably, when treating brewery wastewater, the CG-900 anode achieved a maximum power density of 3.52 W m-2, accompanied by remarkable treatment efficiency, with a COD removal rate of 85.5%. This study provides a facile and low-cost synthesis technique for fabricating high-performance MFC anodes for use in microbial energy harvesting.

Synthesis of Rhenium-Doped Copper Twin Boundary for High-Turnover-Frequency Electrochemical Nitrogen Reduction.

The precise design and synthesis of active sites to improve catalyst's performance has emerged as a promising tactic for electrochemistry. However, it is challenging to combine different types of active sites and manipulate them simultaneously at atomic resolution. Here, we present a strategy to synthesize Re atom-doped Cu twin boundaries (TBs), through pulsed electrodeposition and boundary segregation. The Re-doped Cu TBs demonstrate a highly efficient nitrogen reduction reaction (NRR) performance. Re-doped Cu TBs showed a turnover frequency of ∼5889 s-1, ∼800 times higher than the pure Cu TB active centers (∼7 s-1). In addition to the "acceptance-donation" activation of N2 molecules, theoretical calculations also reveal that the Re-Re dimer on TB can boost the NRR and impede the hydrogen evolution reaction synchronously, rendering Re-doped Cu TB catalysts with high NRR activity and selectivity.

Distinct global brain connectivity alterations in depressed adolescents with subthreshold mania and the relationship with processing speed: Evidence from sBEAD Cohort.

BACKGROUND: Bipolar disorder (BD) is a progressive condition. Investigating the neuroimaging mechanisms in depressed adolescents with subthreshold mania (SubMD) facilitates the early identification of BD. However, the global brain connectivity (GBC) patterns in SubMD patients, as well as the relationship with processing speed before the onset of full-blown BD, remain unclear. METHODS: The study involved 72 SubMD, 77 depressed adolescents without subthreshold mania (nSubMD), and 69 gender- and age-matched healthy adolescents (HCs). All patients underwent a clinical follow-up ranging from six to twelve months. We calculated the voxel-based graph theory analysis of the GBC map and conducted the TMT-A test to measure the processing speed. RESULTS: Compared to HCs and nSubMD, SubMD patients displayed distinctive GBC index patterns: GBC index decreased in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) while increased in the right Precuneus and left Postcentral Gyrus. Both patient groups showed increased GBC index in the right Inferior Temporal Gyrus. An increased GBC value in the right Supplementary Motor Area was exclusively observed in the nSubMD-group. There were opposite changes in the GBC index in SFGmed.R/SFG between two patient groups, with an AUC of 0.727. Additionally, GBC values in SFGmed.R/SFG exhibited a positive correlation with TMT-A scores in SubMD-group. LIMITATIONS: Relatively shorter follow-up duration, medications confounding, and modest sample size. CONCLUSION: These findings suggest that adolescents with subthreshold BD have specific impairments patterns at the whole brain connectivity level associated with processing speed impairments, providing insights into early identification and intervention strategies for BD.

Aging increases the particulate- and leachate-induced toxicity of tire wear particles to microalgae.

The toxic effects of tire wear particles (TWPs) on organisms have attracted widespread concerns over the past decade. However, the underlying toxicity mechanism of TWPs, especially aged TWPs to marine microalgae remains poorly understood. This study investigated the physiological and metabolic responses of Phaeodactylum tricornutum to different concentrations of TWPs (Experiment 1), virgin and differently aged TWPs (Experiment 2) as well as their leachates and leached particles (Experiment 3). Results demonstrated that TWPs promoted the growth of microalgae at low concentrations (0.6 and 3 mg L-1) and inhibited their growth at high concentrations (15 and 75 mg L-1). Moreover, aged TWPs induced more profound physiological effects on microalgae than virgin TWPs, including inhibiting microalgae growth, decreasing the content of Chla, promoting photosynthetic efficiency, and causing oxidative damage to algal cells. Untargeted metabolomics analysis confirmed that aged TWPs induced more pronounced metabolic changes than virgin TWPs. This study represented the first to demonstrate that both particulate- and leachate-induced toxicity of TWPs was increased after aging processes, which was confirmed by the changes in the surface morphology of TWPs and enhanced release of additives. Through the significant correlations between the additives and the microalgal metabolites, key additives responsible for the shift of microalgal metabolites were identified. These results broaden the understanding of the toxicity mechanism of aged TWPs to microalgae at the physiological and metabolic levels and appeal for considering the effects of long-term aging on TWP toxicity in risk assessment of TWPs.

Strong suppression of silver nanoparticles on antibiotic resistome in anammox process.

This study comprehensively deciphered the effect of silver nanoparticles (AgNPs) on anammox flocculent sludge, including nitrogen removal performance, microbial community structure, functional enzyme abundance, antibiotic resistance gene (ARGs) dissemination, and horizontal gene transfer (HGT) mechanisms. After long-term exposure to 0-2.5 mg/L AgNPs for 200 cycles, anammox performance significantly decreased (P < 0.05), while the relative abundances of dominant Ca. Kuenenia and anammox-related enzymes (hzsA, nirK) increased compared to the control (P < 0.05). For antibiotic resistome, ARG abundance hardly changed with 0-0.5 mg/L AgNPs but decreased by approximately 90% with 1.5-2.5 mg/L AgNPs. More importantly, AgNPs effectively inhibited MGE-mediated HGT of ARGs. Additionally, structural equation model (SEM) disclosed the underlying relationship between AgNPs, the antibiotic resistome, and the microbial community. Overall, AgNPs suppressed the anammox-driven nitrogen cycle, regulated the microbial community, and prevented the spread of ARGs in anammox flocs. This study provides a theoretical baseline for an advanced understanding of the ecological roles of nanoparticles and resistance elements in engineered ecosystems.

Defect and Donor Manipulated Highly Efficient Electron-Hole Separation in a 3D Nanoporous Schottky Heterojunction.

Given the rapid recombination of photogenerated charge carriers and photocorrosion, transition metal sulfide photocatalysts usually suffer from modest photocatalytic performance. Herein, S-vacancy-rich ZnIn2S4 (VS-ZIS) nanosheets are integrated on 3D bicontinuous nitrogen-doped nanoporous graphene (N-npG), forming 3D heterostructures with well-fitted geometric configuration (VS-ZIS/N-npG) for highly efficient photocatalytic hydrogen production. The VS-ZIS/N-npG presents ultrafast interfacial photogenerated electrons captured by the S vacancies in VS-ZIS and holes neutralization behaviors by the extra free electrons in N-npG during photocatalysis, which are demonstrated by in situ XPS, femtosecond transient absorption (fs-TA) spectroscopy, and transient-state surface photovoltage (TS-SPV) spectra. The simulated interfacial charge rearrangement behaviors from DFT calculations also verify the separation tendency of photogenerated charge carriers. Thus, the optimized VS-ZIS/N-npG 3D hierarchical heterojunction with 1.0 wt % N-npG exhibits a comparably high hydrogen generation rate of 4222.4 µmol g-1 h-1, which is 5.6-fold higher than the bare VS-ZIS and 12.7-fold higher than the ZIS without S vacancies. This work sheds light on the rational design of photogenerated carrier transfer paths to facilitate charge separation and provides further hints for the design of hierarchical heterostructure photocatalysts.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

Objective: To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods: From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results: A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions: The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Enhanced disintegration mechanism of surplus activated sludge to improve dewatering by thermally activated persulfate oxidation under mild temperature.

The dewatering treatment is an essential process for the treatment and disposal of surplus activated sludge (SAS), and improving sludge dewatering performance is still a challenge and has become a research hotspot in recent years. The oxidation and disintegration of bacterial cells and extracellular polymeric substances (EPS) by active radicals produced by advanced oxidation processes (AOPs) were extremely promising to achieve deep sludge dewatering. This paper systematically studied the efficiency and mechanism of thermally activated persulfate (TAP) oxidation technology to the improvement of SAS dewatering performance. The results showed that the relative filterability (CST0/CST) was increased 2.52 times with 2.0 mmol/g VSS potassium peroxydisulfate (PDS) at 80 °C in 90 min. Under this condition, the Zeta potential of SAS significantly decreased from - 14.8 to - 1.44 mV, while the average particle size (dp50) decreased from 52.981 to 48.259 µm. Thermal treatment disrupted the sludge structure to release large amounts of EPS including polysaccharides and protein. Meanwhile, the results of three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectra showed that the TAP treatment could expedite the disintegration of sludge, facilitating the decrease of total EPS content and conversion of tightly bound EPS (TB-EPS) to loosely bound EPS (LB-EPS) and soluble EPS (S-EPS). The mechanism of TAP process to improve SAS dewatering performance was revealed, which could contribute to breaking the bottleneck of sludge depth dewatering and provide a theoretical and technical basis for its practical application.

MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention.

Nonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed male mice. The focus of this work is to investigate whether and how MKP1 is involved in the development of NASH. Under NASH conditions increased oxidative stress, induces MKP1 expression leading to nuclear p38 MAPK dephosphorylation and decreases liver kinase B1 (LKB1) phosphorylation at a site required to promote LKB1 nuclear exit. Hepatic deletion of MKP1 in NASH diet fed male mice releases nuclear LKB1 into the cytoplasm to activate AMPKα and prevents hepatocellular death, inflammation and NASH. Hence, nuclear-localized MKP1-p38 MAPK-LKB1 signaling is required to suppress AMPKα which triggers hepatocyte death and the development of NASH.

Constructing Hollow Multishelled Microreactors with a Nanoconfined Microenvironment for Ofloxacin Degradation through Peroxymonosulfate Activation: Evolution of High-Valence Cobalt-Oxo Species.

This study constructed hollow multishelled microreactors with a nanoconfined microenvironment for degrading ofloxacin (OFX) through peroxymonosulfate (PMS) activation in Fenton-like advanced oxidation processes (AOPs), resulting in adequate contaminant mineralization. Among the microreactors, a triple-shelled Co-based hollow microsphere (TS-Co/HM) exhibited optimal performance; its OFX degradation rate was 0.598 min-1, which was higher than that of Co3O4 nanoparticles by 8.97-fold. The structural tuning of Co/HM promoted the formation of oxygen vacancies (VO), which then facilitated the evolution of high-valence cobalt-oxo (Co(IV)═O) and shifted the entire t2g orbital of the Co atom upward, promoting catalytic reactions. Co(IV)═O was identified using a phenylmethyl sulfoxide (PMSO) probe and in situ Raman spectroscopy, and theoretical calculations were conducted to identify the lower energy barrier for Co(IV)═O formation on the defect-rich catalyst. Furthermore, the TS-Co/HM catalyst exhibited remarkable stability in inorganic (Cl-, H2PO4-, and NO3-), organic (humic acid), real water samples (tap water, river water, and hospital water), and in a continuous flow system in a microreactor. The nanoconfined microenvironment could enrich reactants in the catalyst cavities, prolong the residence time of molecules, and increase the utilization efficiency of Co(IV)═O. This work describes an activation process involving Co(IV)═O for organic contaminants elimination. Our results may encourage the use of multishelled structures and inform the design of nanoconfined catalysts in AOPs.

Regulation of insulin secretion by the post-translational modifications.

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic ß cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in ß cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in ß cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

DNMT1-mediated DNA methylation in toll-like receptor 4 (TLR4) inactivates NF-κB signal pathway-triggered pyroptotic cell death and cellular inflammation to ameliorate lipopolysaccharides (LPS)-induced osteomyelitis.

Toll-like receptor 4 (TLR4) plays a critical role in various human diseases, and was associated with pyroptotic cell death and inflammatory responses. DNA methylation, which has stable and reversible properties, has been reported to alter the expression of target genes, including TLR4. However, the role of methylated TLR4 in osteomyelitis (OM) and the underlying molecular mechanisms remain unclear. RNA sequencing was used to identify differentially expressed genes and associated signaling pathways. RT-qPCR, Western blot, emzyme-linked immunosorbent assay (ELISA), cell counting kit-8 (CCK-8) and LDH assay kit were used to detect mRNA and protein expression of relevant genes, cell viability and the LDH activity, respectively. TLR4 methylation was detected by methylation-specific PCR (MSP) and verified by Chromatin immunoprecipitation (ChIP). Here, we found that DNA methyltransferase-1 (DNMT1)-mediated TLR4 demethylation significantly suppressed lipopolysaccharides (LPS)-induced pyroptosis and inflammatory response by inhibiting the TLR4/nuclear transcription factor-kappa B (NF-κB) axis. First, we confirmed TLR4 as the study target by mRNA transcriptome sequencing analysis, and TLR4 was observably high-expressed in both OM patients and LPS-treated osteoblastic MC3T3-E1. Then, we found that downregulation of DNMT1 blocked TLR4 promoter methylation modification, resulting in upregulation of TLR4. Simultaneously, functional experiments indicated that suppression of TLR4 or overexpression of DNMT1 promoted cell proliferation and inhibited cell pyroptosis and inflammation in LPS-induced MC3T3-E1, while upregulation of TLR4 restored the effects of DNMT1 silencing on OM progression. In addition, TLR4 elevated phosphorylation of IκB-α and NF-κB p65 in the NF-κB signal pathway, and inhibition of TLR4 or the NF-κB inhibitor PDTC reversed the influence of inhibition of DNMT1. In conclusion, our study demonstrated that DNMT1-mediated TLR4 DNA methylation alleviated LPS-induced OM by inhibiting the NF-κB signaling pathway.

MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention.

Nonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed mice. The focus of this work was to investigate whether and how MKP1 is involved in the development of NASH. Under NASH conditions increased oxidative stress, induces MKP1 expression leading to nuclear p38 MAPK dephosphorylation and decreased liver kinase B1 (LKB1) phosphorylation at a site required to promote LKB1 nuclear exit. Hepatic deletion of MKP1 in NASH diet fed mice released nuclear LKB1 into the cytoplasm to activate AMPKα and prevent hepatocellular death, inflammation and NASH. Hence, nuclear-localized MKP1-p38 MAPK-LKB1 signaling is required to suppress AMPKα which triggers hepatocyte death and the development of NASH.