Creatine kinase mitochondrial 2 promotes the growth and progression of colorectal cancer via enhancing Warburg effect through lactate dehydrogenase B.

Background: Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive. Methods: We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of CKMT2 in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation. Results: We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of CKMT2 expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB). Conclusion: In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism via amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.

Rational Design of Dual-Functionalized Gd@C82 Nanoparticles to Relieve Neuronal Cytotoxicity in Alzheimer's Disease via Inhibition of Aß Aggregation.

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.

Quantifying the Length of Stay and Economic Impact of Albuterol and Levalbuterol in Hospitalized Patients With Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.

Introduction Chronic obstructive pulmonary disease (COPD) affects millions in China and imposes a considerable economic burden on hospitalized patients who experience exacerbations. Nebulized short-acting beta-2 agonists (SABA) are recommended as initial therapy for exacerbation patients, but the optimal SABA remains uncertain. This study aimed to evaluate the impact of different SABAs, such as albuterol and levalbuterol, on the length of stay (LOS) and direct medical costs among hospitalized patients diagnosed with COPD. Methods This retrospective cohort study uses linked hospital administrative data from three hospitals in Chongqing. Patients with COPD, aged 40 years and older, who had been continuously treated with nebulized albuterol or levalbuterol during hospitalization, were eligible for the study. Patients were matched 1:1 by sex, age, and severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. Patients were grouped according to the different SABA treatments they received. Demographic, economic, and clinical data were retrieved. LOS and direct healthcare costs were assessed. Results A total of 158 COPD patients were included, with 79 in each treatment group. Patients treated with levalbuterol had a significantly shorter median LOS (7.0 days vs. 8.0 days, P=0.003) and fewer direct healthcare median costs (total cost: ¥8,868.3 vs. ¥10,290.7, P=0.014; COPD-related western medicine fees: ¥383.8 vs. ¥505.3). Patients aged 60 or older were more likely to experience longer LOS and higher direct costs. Conclusion This retrospective cohort analysis supports that albuterol was associated with longer LOS and higher costs than levalbuterol.

Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response.

Subunit vaccines are becoming increasingly important because of their safety and effectiveness. However, subunit vaccines often exhibit limited immunogenicity, necessitating the use of suitable adjuvants to elicit robust immune responses. In this study, we demonstrated for the first time that pathogenic bacteria can be prepared into a purified peptidoglycan skeleton without nucleic acids and proteins, presenting bacterium-like particles (pBLP). Our results showed that the peptidoglycan skeletons screened from four pathogens could activate Toll-like receptor1/2 receptors better than bacterium-like particles from Lactococcus lactis in macrophages. We observed that pBLP was safe in mouse models of multiple ages. Furthermore, pBLP improved the performance of two commercial vaccines in vivo. We confirmed that pBLP successfully loaded antigens onto the surface and proved to be an effective antigen delivery platform with enhanced antibody titers, antibody avidity, balanced subclass distribution, and mucosal immunity. These results indicate that the peptidoglycan skeleton of pathogenic bacteria represents a new strategy for developing subunit vaccine delivery systems.

Extrahepatic conditions of primary biliary cholangitis: A systematic review and meta-analysis of prevalence and risk.

BACKGROUND AND AIM: Many studies reported the prevalence of extrahepatic conditions (EHC) of primary biliary cholangitis (PBC), but the great heterogeneity existed across different studies. Therefore, we conducted the systematic review and meta-analyses to determine EHC prevalence and association with PBC. METHODS: We searched PUBMED and included observational, cross-sectional and case-controlled studies. A random or fixed effects model was used to estimate the pooled prevalence and odd ratio (OR) as appropriate. RESULTS: Of 5370 identified publications, 129 publications with 133 studies met the inclusion criteria. Sjögren's syndrome had the highest prevalence (21.4 % vs. 3 % in non-PBC individuals), followed by Raynaud's syndrome (12.3 % vs. 1 %), rheumatoid arthritis-like arthritis (5 % vs. 3 %), systemic sclerosis (3.7 % vs. 0 %) and systemic lupus erythematosus (2 % vs. 0 %). The prevalence of overall thyroid diseases (11.3 %), autoimmune thyroid diseases (9.9 %), osteoporosis (21.1 %), celiac disease (1 %) and chronic bronchitis (4.6 %) was also increased among PBC patients. CONCLUSION: This is the first exhaustive study on the old theme about EHC of PBC. Given increased prevalence of many EHCs in PBC patients, promptly recognizing these EHCs are of great importance for timely and precise diagnosis of PBC.

Azoramide ameliorates cadmium-induced cytotoxicity by inhibiting endoplasmic reticulum stress and suppressing oxidative stress.

Background: Cadmium (Cd) is hazardous to human health because of its cytotoxicity and long biological half-life. Azoramide is a small molecular agent that targets the endoplasmic reticulum (ER) and moderates the unfolded protein response. However, its role in Cd-induced cytotoxicity remains unclear. This study was performed to investigate the protective effect of azoramide against Cd-induced cytotoxicity and elucidate its underlying mechanisms. Methods: Inductively coupled plasma‒mass spectrometry was used to measure Cd concentrations in each tissue of ICR male mice. The human proximal tubule epithelial cell line HK-2 and the human retinal pigment epithelial cell line ARPE-19 were used in the in vitro study. Cell apoptosis was determined by DAPI staining, JC-1 staining, and annexin V/propidium iodide double staining. Intracellular oxidative stress was detected by MitoSOX red staining, western blot, and quantitative real-time PCR. Moreover, ER stress signaling, MAPK cascades, and autophagy signaling were analyzed by western blot. Results: The present data showed that Cd accumulated in various organs of ICR mice, and the concentrations of Cd in the studied organs, from high to low, were as follows: liver > kidney > testis > lung > spleen > eye. Our study demonstrated that azoramide inhibited ER stress by promoting BiP expression and suppressing the PERK-eIF2α-CHOP pathway. Additionally, we also found that azoramide significantly decreased ER stress-associated radical oxidative species production, attenuated p38 MAPK and JNK signaling, and inhibited autophagy, thus suppressing apoptosis in HK-2 and ARPE-19 cells. Conclusion: Our study investigated the effect of azoramide on Cd-induced cytotoxicity and revealed that azoramide may be a therapeutic drug for Cd poisoning.

Biogenic Selenium Nanoparticles Synthesized by L. brevis 23017 Enhance Aluminum Adjuvanticity and Make Up for its Disadvantage in Mice.

The most popular vaccine adjuvants are aluminum ones, which have significantly reduced the incidence and mortality of many diseases. However, aluminum-adjuvanted vaccines are constrained by their limited capacity to elicit cellular and mucosal immune responses, thus constraining their broader utilization. Biogenic selenium nanoparticles are a low-cost, environmentally friendly, low-toxicity, and highly bioactive form of selenium supplementation. Here, we purified selenium nanoparticles synthesized by Levilactobacillus brevis 23017 (L-SeNP) and characterized them using Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and transmission electron microscopy. The results indicate that the L-SeNP has a particle size ranging from 30 to 200 nm and is coated with proteins and polysaccharides. Subsequently, we assessed the immune-enhancing properties of L-SeNP in combination with an adjuvant-inactivated Clostridium perfringens type A vaccine using a mouse model. The findings demonstrate that L-SeNP can elevate the IgG and SIgA titers in immunized mice and modulate the Th1/Th2 immune response, thereby enhancing the protective effect of aluminum-adjuvanted vaccines. Furthermore, we observed that L-SeNP increases selenoprotein expression and regulates oxidative stress in immunized mice, which may be how L-SeNP regulates immunity. In conclusion, L-SeNP has the potential to augment the immune response of aluminum adjuvant vaccines and compensate for their limitations in eliciting Th1 and mucosal immune responses.

Toward Smart, Flexible, and Omnidirectional Self-Powered Photodetection by an All-Solution-Processed In2O3/Pbl2 Heterojunction.

Amorphous In2O3 film is emerging as a promising oxide semiconductor for next-generation electronics and optoelectronics owing to high mobility and wide band gap. However, the persistent photocurrent phenomenon and high carrier concentration in amorphous In2O3 film are challenging the photodetection performances, resulting in a long response time and low Ilight/Idark ratio. In this work, the In2O3/PbI2 heterojunction is constructed by an all-solution synthesis process to inhibit the persistent photocurrent phenomenon and large dark current. Benefiting from the built-in electric field at the heterojunction interface, the In2O3/PbI2 heterojunction photodetector exhibits excellent self-powered photodetection performances with an ultralow dark current of 10-12 A, a high Ilight/Idark ratio of 104, and fast response times of 0.6/0.6 ms. Furthermore, the entire solution synthesis process and amorphous characteristics enable the fabrication of an In2O3/PbI2 heterojunction photodetector on arbitrary substrates to realize specific functions. When configured onto the polyimide substrate, the In2O3/PbI2 heterojunction photodetector shows excellent mechanical flexibility, bending endurance, and photoresponse stability. When implanted onto the transparent substrate, the In2O3/PbI2 heterojunction photodetector exhibits an outstanding omnidirectional self-powdered photodetection performance and imaging capability. All results pave the way for an all-solution-processed amorphous In2O3 film in advanced high-performance photodetectors.

Tunable Contacts of Bi2 O2 Se Nanosheets MSM Photodetectors by Metal-Assisted Transfer Approach for Self-Powered Near-Infrared Photodetection.

Owing to the Fermi pinning effect arose in the metal electrodes deposition process, metal-semiconductor contact is always independent on the work function, which challenges the next-generation optoelectronic devices. In this work, a metal-assisted transfer approach is developed to transfer Bi2 O2 Se nanosheets onto the pre-deposited metal electrodes, benefiting to the tunable metal-semiconductor contact. The success in Bi2 O2 Se nanosheets transfer is contributed to the stronger van der Waals adhesion of metal electrodes than that of growth substrates. With the pre-deposited asymmetric electrodes, the self-powered near-infrared photodetectors are realized, demonstrating low dark current of 0.04 pA, high Ilight /Idark ratio of 380, fast rise and decay times of 4 and 6 ms, respectively, under the illumination of 1310 nm laser. By pre-depositing the metal electrodes on polyimide and glass, high-performance flexible and omnidirectional self-powered near-infrared photodetectors are achieved successfully. This study opens up new opportunities for low-dimensional semiconductors in next-generation high-performance optoelectronic devices.

Ovatodiolide induces autophagy-mediated cell death through the p62-Keap1-Nrf2 signaling pathway in chronic myeloid leukemia cells.

Ovatodiolide is a macrocyclic diterpenoid compound with various biological activities that displays considerable anticancer potential in different tumor models. However, the underlying mechanism for this antineoplastic activity remains unclear. The aim of the present study was to investigate the anticancer effect and possible molecular mechanism of ovatodiolide in human chronic myeloid leukemia (CML). Ovatodiolide suppressed cell colony formation and induced apoptosis in the K562 and KU812 cells. We also observed that ovatodiolide enhanced the production of reactive oxygen species (ROS), activated Nrf2 signaling, and inhibited mTOR phosphorylation. Autophagic flux was shown to be enhanced after treatment with ovatodiolide in K562 cells. Furthermore, autophagy inhibition alleviated ovatodiolide-induced cell apoptosis, whereas autophagy promotion aggravated apoptosis in CML cells. These results demonstrated that ovatodiolide activates autophagy-mediated cell death in CML cells. Additionally, ovatodiolide transcriptionally activated the expression of p62, and the p62 levels were negatively regulated by autophagy. Moreover, p62-Keap1-Nrf2 signaling was confirmed to be involved in ovatodiolide-induced cell death. Accordingly, LC3B knockdown augmented the ovatodiolide-induced p62 expression, increased the p62-Keap1 interaction, and enhanced the translocation of Nrf2 into the nucleus. In contrast, p62 inhibition abolished the effects that were induced through ovatodiolide treatment. Nrf2 inhibition with ML385 diminished the protective effect of autophagy inhibition in CML cells. Collectively, our results indicate that ovatodiolide induces oxidative stress and provokes autophagy, which effectively decreases the expression of p62 and weakens the protective effect of Nrf2 signaling activation, thus contributing to apoptosis in CML cells.

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium.

Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against Enterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, an anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons, and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against Enterococcus. Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant Enterococcus infections.

Lattice-mismatch-free construction of III-V/chalcogenide core-shell heterostructure nanowires.

Growing high-quality core-shell heterostructure nanowires is still challenging due to the lattice mismatch issue at the radial interface. Herein, a versatile strategy is exploited for the lattice-mismatch-free construction of III-V/chalcogenide core-shell heterostructure nanowires by simply utilizing the surfactant and amorphous natures of chalcogenide semiconductors. Specifically, a variety of III-V/chalcogenide core-shell heterostructure nanowires are successfully constructed with controlled shell thicknesses, compositions, and smooth surfaces. Due to the conformal properties of obtained heterostructure nanowires, the wavelength-dependent bi-directional photoresponse and visible light-assisted infrared photodetection are realized in the type-I GaSb/GeS core-shell heterostructure nanowires. Also, the enhanced infrared photodetection is found in the type-II InGaAs/GeS core-shell heterostructure nanowires compared with the pristine InGaAs nanowires, in which both responsivity and detectivity are improved by more than 2 orders of magnitude. Evidently, this work paves the way for the lattice-mismatch-free construction of core-shell heterostructure nanowires by chemical vapor deposition for next-generation high-performance nanowire optoelectronics.

Fabrication of ß-Ga2O3 Nanotubes via Sacrificial GaSb-Nanowire Templates.

ß-Ga2O3 nanostructures are attractive wide-band-gap semiconductor materials as they exhibit promising photoelectric properties and potential applications. Despite the extensive efforts on ß-Ga2O3 nanowires, investigations into ß-Ga2O3 nanotubes are rare since the tubular structures are hard to synthesize. In this paper, we report a facile method for fabricating ß-Ga2O3 nanotubes using pre-synthesized GaSb nanowires as sacrificial templates. Through a two-step heating-treatment strategy, the GaSb nanowires are partially oxidized to form ß-Ga2O3 shells, and then, the residual inner parts are removed subsequently in vacuum conditions, yielding delicate hollow ß-Ga2O3 nanotubes. The length, diameter, and thickness of the nanotubes can be customized by using different GaSb nanowires and heating parameters. In situ transmission electron microscopic heating experiments are performed to reveal the transformation dynamics of the ß-Ga2O3 nanotubes, while the Kirkendall effect and the sublimation process are found to be critical. Moreover, photoelectric tests are carried out on the obtained ß-Ga2O3 nanotubes. A photoresponsivity of ~25.9 A/W and a detectivity of ~5.6 × 1011 Jones have been achieved with a single-ß-Ga2O3-nanotube device under an excitation wavelength of 254 nm.

C3N nanodots inhibits Aß peptides aggregation pathogenic path in Alzheimer's disease.

Despite the accumulating evidence linking the development of Alzheimer's disease (AD) to the aggregation of Aß peptides and the emergence of Aß oligomers, the FDA has approved very few anti-aggregation-based therapies over the past several decades. Here, we report the discovery of an Aß peptide aggregation inhibitor: an ultra-small nanodot called C3N. C3N nanodots alleviate aggregation-induced neuron cytotoxicity, rescue neuronal death, and prevent neurite damage in vitro. Importantly, they reduce the global cerebral Aß peptides levels, particularly in fibrillar amyloid plaques, and restore synaptic loss in AD mice. Consequently, these C3N nanodots significantly ameliorate behavioral deficits of APP/PS1 double transgenic male AD mice. Moreover, analysis of critical tissues (e.g., heart, liver, spleen, lung, and kidney) display no obvious pathological damage, suggesting C3N nanodots are biologically safe. Finally, molecular dynamics simulations also reveal the inhibitory mechanisms of C3N nanodots in Aß peptides aggregation and its potential application against AD.

An Amorphous Native Oxide Shell for High Bias-Stress Stability Nanowire Synaptic Transistor.

The inhomogeneous native oxide shells on the surfaces of III-V group semiconductors typically yield inferior and unstable electrical properties metrics, challenging the development of next-generation integrated circuits. Herein, the native GaOx shells are profitably utilized by a simple in-situ thermal annealing process to achieve high-performance GaSb nanowires (NWs) field-effect-transistors (FETs) with excellent bias-stress stability and synaptic behaviors. By an optimal annealing time of 5 min, the as-constructed GaSb NW FET demonstrates excellent stability with a minimal shift of transfer curve (ΔVth ≈ 0.54 V) under a 60 min gate bias, which is far more stable than that of pristine GaSb NW FET (ΔVth ≈ 8.2 V). When the high bias-stress stability NW FET is used as the chargeable-dielectric free synaptic transistor, the typical synaptic behaviors, such as short-term plasticity, long-term plasticity, spike-time-dependent plasticity, and reliable learning stability are demonstrated successfully through the voltage tests. The mobile oxygen ion in the native GaOx shell strongly offsets the trapping states and leads to enhanced bias-stress stability and charge retention capability for synaptic behaviors. This work provides a new way of utilizing the native oxide shell to realize stable FET for chargeable-dielectric free neuromorphic computing systems.

The prevalence, genetic diversity and evolutionary analysis of cachavirus firstly detected in northeastern China.

Canine cachavirus is a novel parvovirus belonging to the genus Chaphamaparvovirus that was first detected in dogs in the United States. However, our knowledge of the prevalence and genetic characteristics of cachavirus is relatively limited. In this study, 325 canine fecal specimens collected from healthy and diarrheic dogs in northeastern China were screened with PCR. Twenty-two of the 325 (6.8%) samples were positive for cachavirus. The diarrhea samples showed high viral coinfection rates, and we detected coinfections with canine astrovirus (CaAstV) and cachavirus for the first time. A sequence analysis revealed that the Chinese cachavirus strains have point mutations in four consecutive amino acid codons relative to the original American strain. A codon usage analysis of the VP1 gene showed that most preferred codons in cachavirus were A- or T-ending codons, as in traditional canine parvovirus 2. A co-evolutionary analysis showed that cachavirus has undergone cospeciation with its hosts and has been transmitted among different host species. Our findings extend the limited cachavirus sequences available, and provide detailed molecular characterization of the strains in northeastern China. Further epidemiological surveillance is required to determine the significance and evolution of cachavirus.

d-Band Center of Rare Earth Oxides Determines Biotransformation-Induced Cell Membrane Damage.

Biotransformation of rare earth oxide (REO) nanoparticles on biological membranes may trigger a series of adverse health effects in biosystems. However, the physicochemical mechanism of the complicated biotransformation behavior remains elusive. By investigating the distinctly different biotransformation behavior of two typical REOs (Gd2O3 and CeO2) on erythrocyte membranes, we demonstrate that dephosphorylation by stripping phosphate from phospholipids correlates highly with the membrane destructive effects of REOs. Density functional theory calculations decode the decisive role of the d-band center in dephosphorylation. Furthermore, using the d-band center as an electronic descriptor, we unravel a universal structure-activity relationship of the membrane-damaging capability of 13 REOs (R2 = 0.82). The effect of ion release on dephosphorylation and physical damage to cell membranes by Gd2O3 are largely excluded. Our findings depict a clear physicochemical microscopic picture of the biotransformation of REOs on the nano-bio interface, providing a theoretical basis for safe application of REOs.

Increasing autophagy ameliorates all-trans-retinal-activated NLRP3 inflammasomes in human THP-1 macrophages.

OBJECTIVE: Severe inflammation, mediated by innate immune sensors, can be observed in the retina and is considered to play an important role in the pathogenesis of retinal degeneration caused by all-trans-retinal (atRAL). However, the underlying mechanism thereof remains elusive. This study investigated the effects of atRAL on the macrophage cell line THP-1 and determined the underlying signaling pathway through pharmacological and genetical manipulation. METHODS: The cytotoxicity of atRAL in THP-1 macrophage cells was assessed using the cell counting kit-8 (CCK-8) assay, and mature IL-1ß was detected by enzyme-linked immunosorbent assay (ELISA). We measured levels of NLRP3 and cleaved caspase-1 by western blotting to evaluate the activation of NLRP3 inflammasomes. Oxidative stress was validated by measuring mitochondria-associated reactive oxygen species (ROS) with MitoSOXTM Red staining. Autophagy was assessed with the LC3BII turnover assay and tandem mCherry-eGFP-LC3B fluorescence microscopy. RESULTS: The maturation and release of IL-1ß were regulated by the activation of the NLRP3 inflammasome. Mitochondria-associated ROS were involved in the regulation of NLRP3 inflammasome activation and caspase-1 cleavage. In addition, atRAL functionally activated autophagy in THP-1 cells, and atRAL-induced NLRP3 inflammasome activation was suppressed by autophagy. CONCLUSIONS: atRAL activates both the NLRP3 inflammasome and autophagy in THP-1 cells, and the increasing level of autophagy leads to the inhibition of excessive NLRP3 inflammasome activation. These findings shed new light on the pathogenesis of age-related retinal degeneration.