Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.

Superaerophilic/Superaerophobic NiFe-LDHs Electrode for Enhancing Overall Water Splitting in Alkaline Media.

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

Revolutionizing CO2 Electrolysis: Fluent Gas Transportation within Hydrophobic Porous Cu2O.

The success of electrochemical CO2 reduction at high current densities hinges on precise interfacial transportation and the local concentration of gaseous CO2. However, the creation of efficient CO2 transportation channels remains an unexplored frontier. In this study, we design and synthesize hydrophobic porous Cu2O spheres with varying pore sizes to unveil the nanoporous channel's impact on gas transfer and triple-phase interfaces. The hydrophobic channels not only facilitate rapid CO2 transportation but also trap compressed CO2 bubbles to form abundant and stable triple-phase interfaces, which are crucial for high-current-density electrocatalysis. In CO2 electrolysis, in situ spectroscopy and density functional theory results reveal that atomic edges of concave surfaces promote C-C coupling via an energetically favorable OC-COH pathway, leading to overwhelming CO2-to-C2+ conversion. Leveraging optimal gas transportation and active site exposure, the hydrophobic porous Cu2O with a 240 nm pore size (P-Cu2O-240) stands out among all the samples and exhibits the best CO2-to-C2+ productivity with remarkable Faradaic efficiency and formation rate up to 75.3 ± 3.1% and 2518.2 ± 8.1 µmol h-1 cm-2, respectively. This study introduces a novel paradigm for efficient electrocatalysts that concurrently addresses active site design and gas-transfer challenges.

Ligand-Receptor Interaction-Induced Intracellular Phase Separation: A Global Disruption Strategy for Resistance-Free Lethality of Pathogenic Bacteria.

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.

Enhancing the performance of mode-pairing quantum key distribution by wavelength division multiplexing.

Mode-pairing quantum key distribution (MP-QKD) holds great promise for the practical implementation of QKD in the near future. It combines the security advantages of measurement device independence while still being capable of breaking the Pirandola-Laurenza-Ottaviani-Banchi bound without the need for highly demanding phase-locking and phase-tracking technologies for deployment. In this work, we explore optimization strategies for MP-QKD in a wavelength-division multiplexing scenario. The simulation results reveal that incorporation of multiple wavelengths not only leads to a direct increase in key rate but also enhances the pairing efficiency by employing our novel pairing strategies among different wavelengths. As a result, our work provides a new avenue for the future application and development of MP-QKD.

Losses of low-germinating, slow-growing species prevent grassland composition recovery from nutrient amendment.

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication.

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

SRSF2 is required for mRNA splicing during spermatogenesis.

BACKGROUND: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. RESULTS: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. CONCLUSIONS: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

Chemical Biology Approach to Reveal the Importance of Precise Subcellular Targeting for Intracellular Staphylococcus aureus Eradication.

Intracellular bacterial pathogens, such as Staphylococcus aureus, that may hide in intracellular vacuoles represent the most significant manifestation of bacterial persistence. They are critically associated with chronic infections and antibiotic resistance, as conventional antibiotics are ineffective against such intracellular persisters due to permeability issues and mechanistic reasons. Direct subcellular targeting of S. aureus vacuoles suggests an explicit opportunity for the eradication of these persisters, but a comprehensive understanding of the chemical biology nature and significance of precise S. aureus vacuole targeting remains limited. Here, we report an oligoguanidine-based peptidomimetic that effectively targets and eradicates intracellular S. aureus persisters in the phagolysosome lumen, and this oligomer was utilized to reveal the mechanistic insights linking precise targeting to intracellular antimicrobial efficacy. The oligomer has high cellular uptake via a receptor-mediated endocytosis pathway and colocalizes with S. aureus persisters in phagolysosomes as a result of endosome-lysosome interconversion and lysosome-phagosome fusion. Moreover, the observation of a bacterium's altered susceptibility to the oligomer following a modification in its intracellular localization offers direct evidence of the critical importance of precise intracellular targeting. In addition, eradication of intracellular S. aureus persisters was achieved by the oligomer's membrane/DNA dual-targeting mechanism of action; therefore, its effectiveness is not hampered by the hibernation state of the persisters. Such precise subcellular targeting of S. aureus vacuoles also increases the agent's biocompatibility by minimizing its interaction with other organelles, endowing excellent in vivo bacterial targeting and therapeutic efficacy in animal models.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Vincristine exposure impairs mouse oocyte quality by inducing spindle defects and early apoptosis.

Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.

LI-RADS Morphological Type Predicts Prognosis of Patients with Hepatocellular Carcinoma After Radical Resection.

PURPOSE: This study aimed to explore the association of preoperative magnetic resonance imaging (MRI) tumor morphological classification with early recurrence (ER) and overall survival (OS) after radical surgery of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis of 296 patients with HCC who underwent radical resection was performed. On the basis of LI-RADS, tumor imaging morphology was classified into three types. The clinical imaging features, ER, and survival rates of three types were compared. Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors associated with OS and ER after hepatectomy for HCC. RESULTS: There were 167 tumors of type 1, 95 of type 2, and 34 of type 3. In patients with type 3 HCC, postoperative mortality and ER were significantly higher than in patients with type 1 and type 2 (55.9% versus 32.6% versus 27.5% and 52.9% versus 33.7% versus 28.7%). In multivariate analysis, the LI-RADS morphological type was a stronger risk factor for predicting poor OS [hazard ratio (HR) 2.77, 95% confidence interval (CI) 1.59-4.85, P < 0.001] and ER (HR 2.14, 95% CI 1.24-3.70, P = 0.007). A subgroup analysis revealed that type 3 was associated with poor OS and ER in > 5 cm cases but not in < 5 cm cases. CONCLUSIONS: ER and OS of patients with HCC undergoing radical surgery can be predicted using the preoperative tumor LI-RADS morphological type, which could help to select personalized treatment plans for patients with HCC in the future.

Boosting the performance of loss-tolerant measurement-device-independent quantum key distribution.

Measurement-device-independent quantum key distribution can remove all possible detector side channels, and is robust against state preparation flaws when further combined with the loss-tolerant method. However, the secure key rate in this scenario is relatively low, thus hindering its practical application. Here, we first present a four-intensity decoy-state protocol where the signal intensity is modulated only in Z basis for key generation while the decoy intensities are modulated in both Z and X bases for parameter estimation. Moreover, we adopt collective constraint and joint-study strategy in statistical fluctuation analysis. We have also experimentally demonstrated this protocol and the result indicates high performance and good security for practical applications.

Combination of Backbone Rigidity and Richness in Aryl Structures Enables Direct Membrane Translocation of Polymer Scaffolds for Efficient Gene Delivery.

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.

The importance of supercooled stability for food during supercooling preservation: a review of mechanisms, influencing factors, and control methods.

Supercooling can preserve food in its original fresh state below its ice point temperature without freezing. However, the supercooled state is unstable in thermodynamics, state breakdown can occur at any moment, resulting in irregular and larger ice crystals formation, leading to food tissue damage, and loss of quality and nutrients. While the effectiveness of supercooling preservation has been verified in the lab and pilot scale tests, the stability of the supercooled state of food remains an open question, posing a limitation for larger industrial-scale application of supercooling preservation. Based on this background, this review presents the instability mechanisms of supercooling preservation and summarizes the factors such as food properties (e.g., material size, food components, specific surface area, and surface roughness) and preservation circumstances (e.g., cooling rate, temperature variation, and mechanical disturbance) that influence the stability of the supercooled state of food. The review also discusses novel techniques for enhancing the supercooling capacity and their limitations (e.g., precise temperature control and magnetic field). Further studies are necessary to comprehensively evaluate the effects of influence factors and supercooling technologies on supercooling, realizing the true sense of 'no-crystal' food products under subzero temperature preservation conditions in commercial applications.

Supercooling can maximize the potential of low temperature in food preservation.Supercooled state of food is unstable, with many factors affecting its stability.The quality of foodstuffs with supercooled failure is unacceptable.Instability of supercooling limits its large application in food industry.Novel technologies are developed to enhance the state stability of food supercooling.

Contribution of mitochondria to postmortem muscle tenderization: a review.

Postmortem meat tenderization is a process mediated by a series of biochemical reactions related to muscle cell death. Cell death is considered a sign that muscle has started to transform into meat. Mitochondria play a significant role in regulating and executing cell death, as they are an aggregation point for many cell death signals and are also the primary target organelle damaged by tissue anoxia. Mitochondrial damage is likely to have an expanded role in postmortem meat tenderization. This review presents current findings on mitochondrial damage induced by the accumulation of reactive oxygen species during postmortem anaerobic metabolism and on the impact of mitochondrial damage on proteolysis and discusses how this leads to improved tenderness during aging. The underlying mechanisms of mitochondrial regulation of postmortem muscle tenderization likely focus on the mitochondria's role in postmortem cell death and energy metabolism. The death process of postmortem skeletal muscle cells may exhibit multiple types, possibly involving transformation from autophagy to apoptosis and, ultimately, necroptosis or necrosis. Mitochondrial characteristics, especially membrane integrity and ATP-related compound levels, are closely related to the transformation of multiple types of dead postmortem muscle cells. Finally, a possible biochemical regulatory network in postmortem muscle tenderization is proposed.

Characterization and evaluation of substratum material selection for microalgal biofilm cultivation.

Biofilm cultivation is considered a promising method to achieve higher microalgae biomass productivity with less water consumption and easier harvest compared to conventional suspended cultivation. However, studies focusing on the selection of substratum material and optimization of the growth of certain microalgae species on specific substratum are limited. This study investigated the selection of membranous and fabric fiber substrata for the attachment of unicellular microalgae Scenedesmus dimorphus and filamentous microalgae Tribonema minus in biofilm cultivation. The results indicated that both algal species preferred hydrophilic membranous substrata and nitrate cellulose/cellulose acetate membrane (CN-CA) was selected as a suitable candidate on which the obtained biomass yields were up to 10.24 and 7.81 g m-2 day-1 for S. dimorphus and T. minus, respectively. Furthermore, high-thread cotton fiber (HCF) and low-thread polyester fiber (LPEF) were verified as the potential fabric fiber substrata for S. dimorphus (5.42 g m-2 day-1) and T. minus (5.49 g m-2 day-1) attachment, respectively. The regrowth of microalgae biofilm cultivation strategy was applied to optimize the algae growth on the fabric fiber substrata, with higher biomass density and shear resistibility achieved for both algal species. The present data highlight the importance to establish the standards for selection the suitable substratum materials in ensuring the high efficiency and sustainability of the attached microalgal biomass production. KEY POINTS: • CN-CA was suitable membranous substratum candidate for algal biofilm cultivation. • HCF and LPEF were potential fabric fiber substrata for S. dimorphus and T. minus. • Regrowth biofilm cultivation was effective in improving algal biomass and attachment.

Dynamic nomogram prediction model for diabetic retinopathy in patients with type 2 diabetes mellitus.

BACKGROUND: To develop a dynamic prediction model for diabetic retinopathy (DR) using systemic risk factors. METHODS: This retrospective study included type 2 diabetes mellitus (T2DM) patients discharged from the Second Affiliated Hospital of Kunming Medical University between May 2020 and February 2022. The early patients (80%) were used for the training set and the late ones (20%) for the validation set. RESULTS: Finally, 1257 patients (1049 [80%] in the training set and 208 [20%] in the validation set) were included; 360 (28.6%) of them had DR. The areas under the curves (AUCs) for the multivariate regression (MR), least absolute shrinkage and selection operator regression (LASSO), and backward elimination stepwise regression (BESR) models were 0.719, 0.727, and 0.728, respectively. The Delong test showed that the BESR model had a better predictive value than the MR (p = 0.04899) and LASSO (P = 0.04999) models. The DR nomogram risk model was established according to the BESR model, and it included disease duration, age at onset, treatment method, total cholesterol, urinary albumin to creatinine ratio (UACR), and urine sugar. The AUC, kappa coefficient, sensitivity, specificity, and compliance of the nomogram risk model in the validation set were 0.79, 0.48, 71.2%, 78.9%, and 76.4%, respectively. CONCLUSIONS: A relatively reliable DR nomogram risk model was established based on the BESR model.

Atrazine induces phagocytotic dysfunction of microglia depends on nucleocytoplasmic translocation of acetylated HMGB1.

Atrazine (ATR) is a widely applied herbicide which was named an environmental endocrine disrupting chemical (EDC). Increasing evidence indicates ATR causes neurotoxic effects resulting in central nervous system (CNS) disease. As the primary immunocytes in the CNS, microglia cells carry out their phagocytosis to maintain the CNS microenvironment by preventing damage from healthy cells. However, the mechanism in which ATR affects the phagocytic function of microglia remains unclear. The present study was designed to investigate the effect of ATR on the phagocytosis of microglia. BV-2 cells and primary microglia selected as microglial models in which BV-2 cells were administrated by ATR at different concentrations (0, 4, 8, 16 µM) for 24 h. Results demonstrated ATR dose-dependently increased the expression of ionized calcium binding adapter molecule 1 (Iba-1), indicating that microglia were activated. Microglial phagocytotic activity induced by ATR fluctuated at the different time points, accompanied by fluctuations in membrane receptor MERTK and cytoplasmic lysosomal marker LAMP1 (two markers related to cell phagocytosis). In this period, the expression of iNOS gradually increased. A mechanistic study further demonstrated that the translocation of High Mobility Group Protein-B1 (HMGB1) from nucleus to cytoplasm in the BV-2 and primary microglial cells induced by ATR, and the process showed a positive correlation with phagocytosis activity of BV-2 cells induced by ATR (r = 0.8030, P = 0.05; α = 0.1). ATR was also shown to spur the acetylation of HMGB1 by breaking the balance between acetylase P300 and deacetylase SIRT1. Unexpectedly, the inhibition of acetylating HMGB1 by resveratrol (Res) was effectively retained by HMGB1 in the nucleus, reversed the SIRT1 and MERTK expression, and enhanced the phagocytosis activity in BV-2 cells. Our results suggested that ATR exposure influenced microglial phagocytosis by acetylating HMGB1 further translocated it in the nucleoplasm.