Tuning the Chern number in quantum anomalous Hall insulators.

A quantum anomalous Hall (QAH) state is a two-dimensional topological insulating state that has a quantized Hall resistance of h/(Ce2) and vanishing longitudinal resistance under zero magnetic field (where h is the Planck constant, e is the elementary charge, and the Chern number C is an integer)1,2. The QAH effect has been realized in magnetic topological insulators3-9 and magic-angle twisted bilayer graphene10,11. However, the QAH effect at zero magnetic field has so far been realized only for C = 1. Here we realize a well quantized QAH effect with tunable Chern number (up to C = 5) in multilayer structures consisting of alternating magnetic and undoped topological insulator layers, fabricated using molecular beam epitaxy. The Chern number of these QAH insulators is determined by the number of undoped topological insulator layers in the multilayer structure. Moreover, we demonstrate that the Chern number of a given multilayer structure can be tuned by varying either the magnetic doping concentration in the magnetic topological insulator layers or the thickness of the interior magnetic topological insulator layer. We develop a theoretical model to explain our experimental observations and establish phase diagrams for QAH insulators with high, tunable Chern number. The realization of such insulators facilitates the application of dissipationless chiral edge currents in energy-efficient electronic devices, and opens up opportunities for developing multi-channel quantum computing and higher-capacity chiral circuit interconnects.

Direct visualization of electronic transport in a quantum anomalous Hall insulator.

A quantum anomalous Hall (QAH) insulator is characterized by quantized Hall and vanishing longitudinal resistances at zero magnetic field that are protected against local perturbations and independent of sample details. This insensitivity makes the microscopic details of the local current distribution inaccessible to global transport measurements. Accordingly, the current distributions that give rise to transport quantization are unknown. Here we use magnetic imaging to directly visualize the transport current in the QAH regime. As we tune through the QAH plateau by electrostatic gating, we clearly identify a regime in which the sample transports current primarily in the bulk rather than along the edges. Furthermore, we image the local response of equilibrium magnetization to electrostatic gating. Combined, these measurements suggest that the current flows through incompressible regions whose spatial structure can change throughout the QAH regime. Identification of the appropriate microscopic picture of electronic transport in QAH insulators and other topologically non-trivial states of matter is a crucial step towards realizing their potential in next-generation quantum devices.

Adipocyte CD1d Gene Transfer Induces T Cell Expansion and Adipocyte Inflammation in CD1d Knockout Mice.

CD1d, a lipid Ag-presenting molecule for invariant NKT (iNKT) cells, is abundantly expressed on adipocytes and regulates adipose homeostasis through iNKT cells. CD1d gene expression was restored in visceral adipose tissue adipocytes of CD1d knockout (KO) mice to investigate the interactions between adipocytes and immune cells within adipose tissue. We developed an adipocyte-specific targeting recombinant adeno-associated viral vector, with minimal off-target transgene expression in the liver, to rescue CD1d gene expression in visceral adipose tissue adipocytes of CD1d KO mice, followed by assessment of immune cell alternations in adipose tissue and elucidation of the underlying mechanisms of alteration. We report that adeno-associated virus-mediated gene transfer of CD1d to adipocytes in CD1d KO mice fails to rescue iNKT cells but leads to massive and selective expansion of T cells within adipose tissue, particularly CD8+ T effector cells, that is associated with adipocyte NLRP3 inflammasome activation, dysregulation of adipocyte functional genes, and upregulation of apoptotic pathway proteins. An NLRP3 inhibitor has no effect on T cell phenotypes whereas depletion of CD8+ T cells significantly attenuates inflammasome activation and abolishes the dysregulation of adipocyte functional genes induced by adipocyte CD1d. In contrast, adipocyte overexpression of CD1d fails to induce T cell activation in wild-type mice or in invariant TCR α-chain Jα18 KO mice that have a normal lymphocyte repertoire except for iNKT cells. Our studies uncover an adipocyte CD1d → CD8+ T cell → adipocyte inflammasome cascade, in which CD8+ T cells function as a key mediator of adipocyte inflammation likely induced by an allogeneic response against the CD1d molecule.

Influence of Magnetic and Electric Fields on Universal Conductance Fluctuations in Thin Films of the Dirac Semimetal Cd3As2.

Time-reversal invariance (TRS) and inversion symmetry (IS) are responsible for the topological band structure in Dirac semimetals (DSMs). These symmetries can be broken by applying an external magnetic or electric field, resulting in fundamental changes to the ground state Hamiltonian and a topological phase transition. We probe these changes using universal conductance fluctuations (UCF) in the prototypical DSM, Cd3As2. With increasing magnetic field, the magnitude of the UCF decreases by a factor of 2, in agreement with numerical calculations of the effect of broken TRS. In contrast, the magnitude of the UCF increases monotonically when the chemical potential is gated away from the charge neutrality point. We attribute this to Fermi surface anisotropy rather than broken IS. The concurrence between experimental data and theory provides unequivocal evidence that UCF are the dominant source of fluctuations and offers a general methodology for probing broken-symmetry effects in topological quantum materials.

Crossover from Ising- to Rashba-type superconductivity in epitaxial Bi2Se3/monolayer NbSe2 heterostructures.

A topological insulator (TI) interfaced with an s-wave superconductor has been predicted to host topological superconductivity. Although the growth of epitaxial TI films on s-wave superconductors has been achieved by molecular-beam epitaxy, it remains an outstanding challenge for synthesizing atomically thin TI/superconductor heterostructures, which are critical for engineering the topological superconducting phase. Here we used molecular-beam epitaxy to grow Bi2Se3 films with a controlled thickness on monolayer NbSe2 and performed in situ angle-resolved photoemission spectroscopy and ex situ magnetotransport measurements on these heterostructures. We found that the emergence of Rashba-type bulk quantum-well bands and spin-non-degenerate surface states coincides with a marked suppression of the in-plane upper critical magnetic field of the superconductivity in Bi2Se3/monolayer NbSe2 heterostructures. This is a signature of a crossover from Ising- to Rashba-type superconducting pairings, induced by altering the Bi2Se3 film thickness. Our work opens a route for exploring a robust topological superconducting phase in TI/Ising superconductor heterostructures.

Enriched environment enhances NK cell maturation through hypothalamic BDNF in male mice.

Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti-obesity and anti-cancer phenotypes that are associated with enhanced adaptive immunity and are mediated by brain-derived neurotrophic factor (BDNF). Natural killer (NK) cells have anti-cancer and anti-viral properties, and their absence or depletion is associated with inferior clinical outcomes. In this study, we investigated the effects of EE on NK cell maturation following their depletion. Mice living in EE displayed a higher proportion of NK cells in the spleen, bone marrow, and blood, compared to those living in the standard environment (SE). EE enhanced NK cell maturation in the spleen and was associated with upregulation of BDNF expression in the hypothalamus. Hypothalamic BDNF overexpression reproduced the EE effects on NK cell maturation in secondary lymphoid tissues. Conversely, hypothalamic BDNF knockdown blocked the EE modulation on NK cell maturation. Our results demonstrate that a bio-behavior intervention enhanced NK cell maturation and was mediated at least in part by hypothalamic BDNF.

Concurrence of quantum anomalous Hall and topological Hall effects in magnetic topological insulator sandwich heterostructures.

The quantum anomalous Hall (QAH) effect is a consequence of non-zero Berry curvature in momentum space. The QAH insulator harbours dissipation-free chiral edge states in the absence of an external magnetic field. However, the topological Hall (TH) effect, a hallmark of chiral spin textures, is a consequence of real-space Berry curvature. Here, by inserting a topological insulator (TI) layer between two magnetic TI layers, we realized the concurrence of the TH effect and the QAH effect through electric-field gating. The TH effect is probed by bulk carriers, whereas the QAH effect is characterized by chiral edge states. The appearance of the TH effect in the QAH insulating regime is a consequence of chiral magnetic domain walls that result from the gate-induced Dzyaloshinskii-Moriya interaction and occurs during the magnetization reversal process in the magnetic TI sandwich samples. The coexistence of chiral edge states and chiral spin textures provides a platform for proof-of-concept dissipationless spin-textured spintronic applications.

Environmental activation of a hypothalamic BDNF-adipocyte IL-15 axis regulates adipose-natural killer cells.

Physical and social environments influence immune homeostasis within adipose tissue, yet the mechanisms remain poorly defined. We report that an enriched environment (EE) housing modulates the immune cell population in white adipose tissue of mice including an increase in the abundance of natural killer (NK) cells. EE upregulates the expression of IL-15 and its receptor IL-15Rα specifically within mature adipocytes. Mechanistically, we show that hypothalamic brain-derived neurotrophic factor (BDNF) upregulates IL-15 production in adipocytes via sympathetic ß-adrenergic signaling. Overexpressing BDNF mediated by recombinant adeno-associated virus (rAAV) vector in the hypothalamus expands adipose NK cells. Conversely, inhibition of hypothalamic BDNF signaling via gene transfer of a dominant negative TrkB receptor suppresses adipose NK cells. In white adipose tissue, overexpression of IL-15 using an adipocyte-specific rAAV vector stimulates adipose NK cells and inhibits the progression of subcutaneous melanoma, whereas local IL-15 knockdown blocks the EE effect. These results suggest that bio-behavioral factors regulate adipose NK cells via a hypothalamic BDNF-sympathoneural-adipocyte IL-15 axis. Targeting this pathway may have therapeutic significance for cancer.

Dopamine receptor D2 on CD4+ T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4+ T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5. However, roles of DRs particularly DRD2 expressed on CD4+ T cells in PD remain elucidated. Global Drd1- or Drd2-knockout (Drd1-/- or Drd2-/-) mice or CD4+ T cell-specific Drd2-knockout (Drd2fl/fl/CD4Cre) mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD with the different mutants. On the 7th day following MPTP injection, mice were assessed for dopaminergic neurodegeneration, locomotor impairments, microglial activation, as well as CD4+ T-cell differentiation and function. Furthermore, in vitro CD4+ T cells were exposed to DRD2 agonist and antagonist and then differentiation and function of the cells were determined. MPTP induced dopaminergic neuronal loss in the nigrostriatal system, motor coordinative and behavioral impairments, microglial activation, and CD4+ T-cell polarization to pro-inflammatory T-helper (Th)1 and Th17 phenotypes. Importantly, either Drd2-/- or Drd2fl/fl/CD4Cre mice manifested more severe dopaminergic neurodegeneration, motor deficits, microglial activation, and CD4+ T-cell bias towards Th1 and Th17 phenotypes in response to MPTP, but Drd1-/- did not further alter MPTP intoxication. DRD2 agonist sumanirole inhibited shift of CD4+ T cells obtained from MPTP-intoxicated mice to Th1 and Th17 phenotypes and DRD2 antagonist L-741,626 reversed sumanirole effects. These findings suggest that DRD2 expressed on CD4+ T cells is protective against neuroinflammation and neurodegeneration in PD. Thus, developing a therapeutic strategy of stimulating DRD2 may be promising for mitigation of PD.

Experimental demonstration of hidden nonlocality with local filters.

The violation of the Bell inequalities implies that quantum mechanics cannot be interpreted using any local hidden variable theory. However, particular quantum states that can originally be described using a local hidden variable model surprisingly exhibit nonlocality by employing local filters before a standard Bell test is performed. This is referred to as hidden nonlocality. In this study, we provide the experimental demonstration of hidden nonlocality through linear optics towards the local states which are put forword by Hirsch et al., PRL 111, 160402 (2013). A class of local states is generated through a spontaneous parametric down-conversion process, and the violation of the Clauser-Horne-Shimony-Holt (CHSH)-Bell inequality is observed by applying local filters. Our experimental results confirm the superiority of local filters, and throw light on deep understanding the intriguing phenomena of hidden nonlocality and local states.

Adipocytes: A Novel Target for IL-15/IL-15Rα Cancer Gene Therapy.

IL-15 is a proinflammatory cytokine that plays an essential role in the development and activation of natural killer (NK) cells. Adipose tissue acts as an endocrine organ that secretes cytokines and is an important reservoir for lymphocytes. We hypothesized that activation of the IL-15 signaling in adipose tissue will activate and expand the NK cell population and control tumor growth. We recently developed an adipocyte-targeting recombinant adeno-associated viral (rAAV) vector with minimal off-target transgene expression in the liver. Here, we used this rAAV system to deliver an IL-15/IL-15Rα complex to the abdominal fat by intraperitoneal (i.p.) injection. Adipose IL-15/IL-15Rα complex gene transfer led to the expansion of NK cells in the adipose tissue and spleen in normal mice without notable side effects. The i.p. injection of rAAV-IL-15/IL-15Rα complex significantly suppressed the growth of Lewis lung carcinoma implanted subcutaneously and exerted a significant survival advantage in a B16-F10 melanoma metastasis model. The antitumor effects were associated with the expansion of the NK cells in the blood, spleen, abdominal fat, and tumor, as well as the enhancement of NK cell maturity. Our proof-of-concept preclinical studies demonstrate the safety and efficacy of the adipocyte-specific IL-15/IL-15Rα complex vector as a novel cancer immune gene therapy.

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice.

Environmental and social factors have profound impacts on immune homeostasis. Our work on environmental enrichment (EE) has revealed a novel anti-obesity and anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues. Here we investigated how an EE modulated thymus and thymocyte development. EE decreased thymus mass and cellularity, decreased the double positive thymocyte population, increased the proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69 expression in T cells. In a model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord inflammation through regulation of type 1 T-helper cells mediated by glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance. Our mechanistic studies demonstrated that hypothalamic BDNF activated a hypothalamic-pituitary-adrenal axis mediating the EE's thymic effects. Our results indicate that a lifestyle intervention links the nervous, endocrine, and adaptive immune system, allowing the body to adapt to internal and external environments.

Vibsanin B preferentially targets HSP90ß, inhibits interstitial leukocyte migration, and ameliorates experimental autoimmune encephalomyelitis.

Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.

Anaerobic ammonium oxidation in sediments of surface flow constructed wetlands treating swine wastewater.

Anaerobic ammonium oxidation (anammox) was suggested to be involved in the nitrogen (N) removal process in constructed wetlands (CWs). Nevertheless, its occurrence and role in CWs treating swine wastewater have not been well evaluated yet. In this study, we investigated the diversity, activity, and role of anammox bacteria in sediments of mesoscale surface flow CWs (SFCWs) subjected to different N loads of swine wastewater. We found that anammox bacteria were abundant in SFCW sediments, as indicated by 7.5 × 105 to 3.5 × 106 copies of the marker hzsB gene per gram of dry soil. Based on stable isotope tracing, potential anammox rates ranged from 1.03 to 12.5 nmol N g-1 dry soil h-1, accounting for 8.63-57.1% of total N2 production. We estimated that a total N removal rate of 0.83-2.68 kg N year-1 was linked to the anammox process, representing ca. 10% of the N load. Phylogenetic analyses of 16S ribosomal RNA (rRNA) revealed the presence of multiple co-occurring anammox genera, including "Candidatus Brocadia" as the most common one, "Ca. Kuenenia," "Ca. Scalindua," and four novel unidentified clusters. Correlation analyses suggested that the activity and abundance of anammox bacteria were strongly related to sediments pH, NH4+-N, and NO2--N. In conclusion, our results confirmed the presence of diverse anammox bacteria and indicated that the anammox process could serve as a promising N removal pathway in the treatment of swine wastewater by SFCWs.

[Induction of rat hepatic CYP2E1 expression by arecoline in vivo].

The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.

Structural framework of c-Src activation by integrin ß3.

The integrin ß3-mediated c-Src priming and activation, via the SH3 domain, is consistently associated with diseases, such as the formation of thrombosis and the migration of tumor cells. Conventionally, activation of c-Src is often induced by the binding of proline-rich sequences to its SH3 domain. Instead, integrin ß3 uses R(760)GT(762) for priming and activation. Because of the lack of structural information, it is not clear where RGT will bind to SH3, and under what mechanism this interaction can prime/activate c-Src. In this study, we present a 2.0-Å x-ray crystal structure in which SH3 is complexed with the RGT peptide. The binding site lies in the "N"-Src loop of the SH3 domain. Structure-based site-directed mutagenesis showed that perturbation on the "N"-Src loop disrupts the interaction between the SH3 domain and the RGT peptide. Furthermore, the simulated c-Src:ß3 complex based on the crystal structure of SH3:RGT suggests that the binding of the RGT peptide might disrupt the intramolecular interaction between the SH3 and linker domains, leading to the disengagement of Trp260:"C"-helix and further activation of c-Src.

Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice.

Activation of the hypothalamus-adipocyte axis is associated with an antiobesity and anticancer phenotype in animal models of melanoma and colon cancer. Brain-derived neurotrophic factor (BDNF) is a key mediator in the hypothalamus leading to preferential sympathoneural activation of adipose tissue and the ensuing resistance to obesity and cancer. Here, we generated middle age obese mice by high fat diet feeding for a year and investigated the effects of hypothalamic gene transfer of BDNF on a hormone receptor-positive mammary tumor model. The recombinant adeno-associated viral vector-mediated overexpression of BDNF led to marked weight loss and decrease of adiposity without change of food intake. BDNF gene therapy improved glucose tolerance, alleviated steatosis, reduced leptin level, inhibited mouse breast cancer EO771 growth, and prevented the metastasis. The reduced tumor growth in BDNF-treated mice was associated with reduced angiogenesis, decreased proliferation, increased apoptosis, and reduced adipocyte recruitment and lipid accumulation. Moreover, BDNF gene therapy reduced inflammation markers in the hypothalamus, the mammary gland, the subcutaneous fat, and the mammary tumor. Our results suggest that manipulating a single gene in the brain may influence multiple mechanisms implicated in obesity-cancer association and provide a target for the prevention and treatment of both obesity and cancer.

Interface-induced superconductivity in magnetic topological insulators.

The interface between two different materials can show unexpected quantum phenomena. In this study, we used molecular beam epitaxy to synthesize heterostructures formed by stacking together two magnetic materials, a ferromagnetic topological insulator (TI) and an antiferromagnetic iron chalcogenide (FeTe). We observed emergent interface-induced superconductivity in these heterostructures and demonstrated the co-occurrence of superconductivity, ferromagnetism, and topological band structure in the magnetic TI layer-the three essential ingredients of chiral topological superconductivity (TSC). The unusual coexistence of ferromagnetism and superconductivity is accompanied by a high upper critical magnetic field that exceeds the Pauli paramagnetic limit for conventional superconductors at low temperatures. These magnetic TI/FeTe heterostructures with robust superconductivity and atomically sharp interfaces provide an ideal wafer-scale platform for the exploration of chiral TSC and Majorana physics.

Social isolation exacerbates diet-induced obesity and peripheral inflammation in young male mice under thermoneutrality.

Social isolation (SI) is associated with an increased risk of mortality and various chronic diseases-including obesity-in humans. Murine studies probing SI metabolic outcomes remain inconsistent, due in part to a lack of consideration for housing temperature. Such experiments typically occur at room temperature, subjecting mice to chronic cold stress. Single housing prevents social thermoregulation, further exacerbating cold stress and obscuring psychosocial influences on metabolism at room temperature. In this study, C57BL/6 and BALB/c male mice were group- and single-housed under thermoneutral conditions to determine whether SI affects the development of high-fat diet-induced obesity. We report SI promotes weight gain, increases food intake, increases adiposity, worsens glycemic control, reduces insulin signaling, exacerbates systemic and adipose inflammatory responses, and induces a molecular signature within the hypothalamus. This study establishes a murine model that recapitulates the SI-induced propensity for obesity, which may further our understanding of SI's influence on health and disease.

Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.