Nanoassembly-Mediated Exendin-4 Derivatives to Decrease Renal Retention.

An Exendin-4 analogue that was conjugated with 68Ga exhibited an excellent diagnostic effect on insulinoma in clinical practice. On account of its low molecular weight and short hydration radius, 68Ga-Exendin-4 showed high accumulation in kidney tissues. Nanoparticle-mediated strategies have attracted much attention due to polyvalent properties and the size amplification effect. In this study, Exendin-4 derivatives of radionuclide nanodevices were developed and evaluated. The Exendin-4 derivatives consisting of a ternary block recombinant protein were purified by an inverse transition cycle (ITC) and allowed to self-assemble into a nanodevice under physiological conditions. Our results showed that the nanoassemblies of Exendin-4 derivatives formed homogeneous spherical nanoparticles, exhibited outstanding affinity for insulinoma cells, and could be deposited in insulinoma tissues in vivo. The nanoassembly-mediated Exendin-4 derivatives showed fivefold reduced renal retention and exhibited an outstanding tumor-suppression effect.

Enhanced hydrodechlorination of 4-chlorophenol through carboxymethylcellulose-modified Pd/Fe nanosuspension synthesized by one-step methods.

Palladized iron (Pd/Fe) represents one of the most common modification strategies for nanoscale zero-valent iron (nZVI). Most studies prepared Pd/Fe by reducing iron salts and depositing Pd species on the surface of pre-synthesized nZVI, which can be called the two-step method. In this study, we proposed a one-step method to obtain Pd/Fe by the concurrent formation of Fe0 and Pd0 and investigated the effects of these two methods on 4-chlorophenol (4-CP) removal, with carboxymethylcellulose (CMC) coated as a surface modifier. Results indicated that the one-step method, not only streamlined the synthesis process, but also Pd/Fe-CMCone-step, synthesized by it, exhibited a higher 4-CP removal rate (97.9%) compared to the two-step method material Pd/Fe-CMCtwo-step (82.4%). Electrochemical analyses revealed that the enhanced activity of Pd/Fe-CMCone-step was attributed to its higher electron transfer efficiency and more available reactive species, active adsorbed hydrogen species (Hads*). Detection of intermediate products demonstrated that, under the influence of Pd/Fe-CMCone-step, the main route of 4-CP was through hydrodechlorination (HDC) to form phenol and H* was the main active specie, supported by EPR tests, quenching experiments and product analysis. Additionally, the effects of initial 4-CP concentration, initial pH, O2 concentration, anions such as Cl-, SO42-, HCO3-, and humic acid (HA) were also investigated. In conclusion, the results of this study suggest that Pd/Fe-CMCone-step, synthesized through the one-step method, is a convenient and efficient nZVI-modifying material suitable for the HDC of chlorinated organic compounds.

Selective abatement of electron-rich organic contaminants by trace complexed Mn(II)-catalyzed periodate via high-valent manganese-oxo species.

Mn(II) is among the most efficient catalysts for the periodate (PI)-based oxidation process. In-situ formed colloidal MnO2 simultaneously serves as the catalyst and oxidant during the degradation of organic contaminants by PI. Here, it is revealed that the complexation of Mn(II) by ethylene diamine tetraacetic acid (EDTA) further enhances the performance of PI-based oxidation in the selective degradation of organic contaminants. As evidenced by methyl phenyl sulfoxide probing, 18O-isotope labeling, and mass spectroscopy, EDTA complexation modulates the reaction pathway between Mn(II) and PI, triggering the generation of high-valent manganese-oxo (MnV-oxo) as the dominant reactive species. PI mediates the single-electron oxidation of Mn(II) to Mn(III), which is stabilized by EDTA complexation and then further oxidized by PI via the oxygen-atom transfer step, ultimately producing the MnV-oxo species. Ligands analogous to EDTA, namely, [S,S]-ethylenediaminedisuccinic acid and L-glutamic acid N,N-diacetic acid, also enhances the Mn(II)/PI process and favors MnV-oxo as the dominant species. This study demonstrates that functional ligands can tune the efficiency and reaction pathways of Mn(II)-catalyzed peroxide and peroxyacid-based oxidation processes.

Realization of exceptional points along a synthetic orbital angular momentum dimension.

Exceptional points (EPs), at which more than one eigenvalue and eigenvector coalesce, are unique spectral features of non-Hermiticity (NH) systems. They exist widely in open systems with complex energy spectra. We experimentally demonstrate the appearance of paired EPs in a periodical-driven degenerate optical cavity along the synthetic orbital angular momentum dimension with a tunable parameter. The complex-energy band structures and the key features of EPs, i.e., their bulk Fermi arcs, parity-time symmetry breaking transition, energy swapping, and half-integer band windings, are directly observed by detecting the wavefront angle-resolved transmission spectrum. Our results demonstrate the flexibility of using the photonic synthetic dimensions to implement NH systems beyond their geometric dimension and EP-based sensing.

Natural Killer Cells: A Promising Kit in the Adoptive Cell Therapy Toolbox.

As an important component of the innate immune system, natural killer (NK) cells have gained increasing attention in adoptive cell therapy for their safety and efficacious tumor-killing effect. Unlike T cells which rely on the interaction between TCRs and specific peptide-MHC complexes, NK cells are more prone to be served as "off-the-shelf" cell therapy products due to their rapid recognition and killing of tumor cells without MHC restriction. In recent years, constantly emerging sources of therapeutic NK cells have provided flexible options for cancer immunotherapy. Advanced genetic engineering techniques, especially chimeric antigen receptor (CAR) modification, have yielded exciting effectiveness in enhancing NK cell specificity and cytotoxicity, improving in vivo persistence, and overcoming immunosuppressive factors derived from tumors. In this review, we highlight current advances in NK-based adoptive cell therapy, including alternative sources of NK cells for adoptive infusion, various CAR modifications that confer different targeting specificity to NK cells, multiple genetic engineering strategies to enhance NK cell function, as well as the latest clinical research on adoptive NK cell therapy.

TWIST1 induces proteasomal degradation of ß-catenin during the differentiation of ovarian cancer stem-like cells.

Ovarian cancer (OC) is one of the leading gynecologic cancers worldwide. Cancer stem-like cells are correlated with relapse and resistance to chemotherapy. Twist1, which is involved in ovarian cancer stem-like cell differentiation, is positively correlated with CTNNB1 in different differentiation stages of ovarian cancer cells: primary epithelial ovarian cancer cells (primary EOC cells), mesenchymal spheroid-forming cells (MSFCs) and secondary epithelial ovarian cancer cells (sEOC cells). However, the expression of ß-catenin is inversed compared to CTNNB1 in these 3 cell states. We further demonstrated that ß-catenin is regulated by the protein degradation system in MSFCs and secondary EOC but not in primary EOC cells. The differentiation process from primary EOC cells to MSFCs and sEOC cells might be due to the downregulation of ß-catenin protein levels. Finally, we found that TWIST1 can enhance ß-catenin degradation by upregulating Axin2.

Chemical Exchange Saturation Transfer for Pancreatic Ductal Adenocarcinoma Evaluation.

OBJECTIVES: The aims of the study are to evaluate the feasibility of using pH-sensitive magnetic resonance imaging, chemical exchange saturation transfer (CEST) in pancreatic imaging and to differentiate pancreatic ductal adenocarcinoma (PDAC) with the nontumor pancreas (upstream and downstream) and normal control pancreas. METHODS: Sixteen CEST images with PDAC and 12 CEST images with normal volunteers were acquired and magnetization transfer ratio with asymmetric analysis were measured in areas of PDAC, upstream, downstream, and normal control pancreas. One-way analysis of variance and receiver operating characteristic curve were used to differentiate tumor from nontumor pancreas. RESULTS: Areas with PDAC showed higher signal intensity than upstream and downstream on CEST images. The mean (standard deviation) values of magnetization transfer ratio with asymmetric analysis were 0.015 (0.034), -0.044 (0.030), -0.019 (0.027), and -0.037 (0.031), respectively, in PDAC area, upstream, downstream, and nontumor area in patient group and -0.008 (0.024) in normal pancreas. Significant differences were found between PDAC and upstream ( P < 0.001), between upstream and normal pancreas ( P = 0.04). Area under curve is 0.857 in differentiating PDAC with nontumor pancreas. CONCLUSIONS: pH-sensitive CEST MRI is feasible in pancreatic imaging and can be used to differentiate PDAC from nontumor pancreas. This provides a novel metabolic imaging method in PDAC.

Biology and Clinical Relevance of HCMV-Associated Adaptive NK Cells.

Natural killer (NK) cells are an important component of the innate immune system due to their strong ability to kill virally infected or transformed cells without prior exposure to the antigen (Ag). However, the biology of human NK (hNK) cells has largely remained elusive. Recent advances have characterized several novel hNK subsets. Among them, adaptive NK cells demonstrate an intriguing specialized antibody (Ab)-dependent response and several adaptive immune features. Most adaptive NK cells express a higher level of NKG2C but lack an intracellular signaling adaptor, FcϵRIγ (hereafter abbreviated as FcRγ). The specific expression pattern of these genes, with other signature genes, is the result of a specific epigenetic modification. The expansion of adaptive NK cells in vivo has been documented in various viral infections, while the frequency of adaptive NK cells among peripheral blood mononuclear cells correlates with improved prognosis of monoclonal Ab treatment against leukemia. This review summarizes the discovery and signature phenotype of adaptive NK cells. We also discuss the reported association between adaptive NK cells and pathological conditions. Finally, we briefly highlight the application of adaptive NK cells in adoptive cell therapy against cancer.

Hotair promotes the migration and proliferation in ovarian cancer by miR-222-3p/CDK19 axis.

Previous studies in our laboratory have reported that miR-222-3p was a tumor-suppressive miRNA in OC. This study aims to further understand the regulatory role of miR-222-3p in OC and provide a new mechanism for its prevention and treatment. We first found that miR-222-3p inhibited the migration and proliferation of OC cells. Then, we observed CDK19 was highly expressed in OC and inversely correlated with miR-222-3p. Besides, we observed that miR-222-3p directly binds to the 3'-UTR of CDK19 and inhibits CDK19 translation, thus inhibiting OC cell migration and proliferation in vitro and repressed tumor growth in vivo. We also observed the inhibitory effect of Hotair on miR-222-3p in OC. In addition, Hotair could promote the proliferation and migration of OC cells in vitro and facilitate the growth and metastasis of tumors in vivo. Moreover, Hotair was positively correlated with CDK19 expression. These results suggest Hotair indirectly up-regulates CDK19 through sponging miR-222-3p, which enhances the malignant behavior of OC. This provides a further understanding of the mechanism of the occurrence and development of OC.

Topological band structure via twisted photons in a degenerate cavity.

Synthetic dimensions based on particles' internal degrees of freedom, such as frequency, spatial modes and arrival time, have attracted significant attention. They offer ideal large-scale lattices to simulate nontrivial topological phenomena. Exploring more synthetic dimensions is one of the paths toward higher dimensional physics. In this work, we design and experimentally control the coupling among synthetic dimensions consisting of the intrinsic photonic orbital angular momentum and spin angular momentum degrees of freedom in a degenerate optical resonant cavity, which generates a periodically driven spin-orbital coupling system. We directly characterize the system's properties, including the density of states, energy band structures and topological windings, through the transmission intensity measurements. Our work demonstrates a mechanism for exploring the spatial modes of twisted photons as the synthetic dimension, which paves the way to design rich topological physics in a highly compact platform.

Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer.

Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.

Simulating electrical fields in the orbital angular momentum space of light.

We study a system of coupled degenerate cavities with a switchable beam rotator embedded in the optical path of the main cavity. By exploiting the phase shift of the beam rotator dependent on the orbital angular momentum of the optical modes, and modulating the phase imbalance in the auxiliary cavity, it is shown that the system dynamics is equivalent to that of a charged particle in a 1D lattice subject to both static and time-dependent electrical fields. We investigate interesting physics and phenomena such as Bloch oscillations that arise due to the simulated electrical fields, and discuss how they can be used for practical purposes such as storing optical signals in a quantum memory. We also present a powerful measurement scheme to detect the system dynamics that is non-intrusive and technically easy to perform.

Wnt/ß-catenin signalling: function, biological mechanisms, and therapeutic opportunities.

The Wnt/ß-catenin pathway comprises a family of proteins that play critical roles in embryonic development and adult tissue homeostasis. The deregulation of Wnt/ß-catenin signalling often leads to various serious diseases, including cancer and non-cancer diseases. Although many articles have reviewed Wnt/ß-catenin from various aspects, a systematic review encompassing the origin, composition, function, and clinical trials of the Wnt/ß-catenin signalling pathway in tumour and diseases is lacking. In this article, we comprehensively review the Wnt/ß-catenin pathway from the above five aspects in combination with the latest research. Finally, we propose challenges and opportunities for the development of small-molecular compounds targeting the Wnt signalling pathway in disease treatment.

Nonenhanced Chemical Exchange Saturation Transfer Cardiac Magnetic Resonance Imaging in Patients With Amyloid Light-Chain Amyloidosis.

BACKGROUND: Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. PURPOSE: To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. STUDY TYPE: Prospective. POPULATION: Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. ASSESSMENT: The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. STATISTICAL TESTS: Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P < 0.05. RESULTS: Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). DATA CONCLUSIONS: This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes.

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.

Whole-brain steady-state CEST at 3 T using MR Multitasking.

PURPOSE: To perform fast 3D steady-state CEST (ss-CEST) imaging using MR Multitasking. METHODS: A continuous acquisition sequence with repetitive ss-CEST modules was developed. Each ss-CEST module contains a single-lobe Gaussian saturation pulse, followed by a spoiler gradient and eight FLASH readouts (one "training line" + seven "imaging lines"). Three-dimensional Cartesian encoding was used for k-space acquisition. Reconstructed CEST images were quantified with four-pool Lorentzian fitting. RESULTS: Steady-state CEST with whole-brain coverage was performed in 5.6 s per saturation frequency offset at the spatial resolution of 1.7 × 1.7 × 3.0 mm3 . The total scan time was 5.5 min for 55 different frequency offsets. Quantitative CEST maps from multipool fitting showed consistent image quality across the volume. CONCLUSION: Three-dimensional ss-CEST with whole-brain coverage can be done at 3 T within 5.5 min using MR Multitasking.

Design of Inhibitors of the Intrinsically Disordered Protein NUPR1: Balance between Drug Affinity and Target Function.

Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their physiological ubiquity and their prevalence in various diseases, including cancer. NUPR1 is an IDP that localizes throughout the whole cell, and is involved in the development and progression of several tumors. We have previously repurposed trifluoperazine (TFP) as a drug targeting NUPR1 and, by using a ligand-based approach, designed the drug ZZW-115 starting from the TFP scaffold. Such derivative compound hinders the development of pancreatic ductal adenocarcinoma (PDAC) in mice, by hampering nuclear translocation of NUPR1. Aiming to further improve the activity of ZZW-115, here we have used an indirect drug design approach to modify its chemical features, by changing the substituent attached to the piperazine ring. As a result, we have synthesized a series of compounds based on the same chemical scaffold. Isothermal titration calorimetry (ITC) showed that, with the exception of the compound preserving the same chemical moiety at the end of the alkyl chain as ZZW-115, an increase of the length by a single methylene group (i.e., ethyl to propyl) significantly decreased the affinity towards NUPR1 measured in vitro, whereas maintaining the same length of the alkyl chain and adding heterocycles favored the binding affinity. However, small improvements of the compound affinity towards NUPR1, as measured by ITC, did not result in a corresponding improvement in their inhibitory properties and in cellulo functions, as proved by measuring three different biological effects: hindrance of the nuclear translocation of the protein, sensitization of cells against DNA damage mediated by NUPR1, and prevention of cancer cell growth. Our findings suggest that a delicate compromise between favoring ligand affinity and controlling protein function may be required to successfully design drugs against NUPR1, and likely other IDPs.

Intradiscal quantitative chemical exchange saturation transfer MRI signal correlates with discogenic pain in human patients.

Low back pain (LBP) is often a result of a degenerative process in the intervertebral disc. The precise origin of discogenic pain is diagnosed by the invasive procedure of provocative discography (PD). Previously, we developed quantitative chemical exchange saturation transfer (qCEST) magnetic resonance imaging (MRI) to detect pH as a biomarker for discogenic pain. Based on these findings we initiated a clinical study with the goal to evaluate the correlation between qCEST values and PD results in LBP patients. Twenty five volunteers with chronic low back pain were subjected to T2-weighted (T2w) and qCEST MRI scans followed by PD. A total of 72 discs were analyzed. The average qCEST signal value of painful discs was significantly higher than non-painful discs (p = 0.012). The ratio between qCEST and normalized T2w was found to be significantly higher in painful discs compared to non-painful discs (p = 0.0022). A receiver operating characteristics (ROC) analysis indicated that qCEST/T2w ratio could be used to differentiate between painful and non-painful discs with 78% sensitivity and 81% specificity. The results of the study suggest that qCEST could be used for the diagnosis of discogenic pain, in conjunction with the commonly used T2w scan.

Identification of a Gene Set Correlated With Immune Status in Ovarian Cancer by Transcriptome-Wide Data Mining.

Immune checkpoint blocking (ICB) immunotherapy has achieved great success in the treatment of various malignancies. Although not have been approved for the treatment of ovarian cancer (OC), it has been actively tested for the treatment of OC. However, biomarkers that could indicate the immune status of OC and predict the response to ICB are rare. We downloaded RNAseq and clinical data of OC from The Cancer Genome Atlas (TCGA). Data analysis revealed both TMBhigh and immunityhigh were significantly related to better survival of OC. Up-regulated differentially expressed genes (Up-DEGs) were identified by analyzing the gene expression levels. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the "GSVA" and "limma" package in R software. The correlation of genes with overall survival was also analyzed by conducted Kaplan-Meier survival analysis. Four genes, CXCL13, FCRLA, MS4A1, and PLA2G2D were found positively correlated with better prognosis of OC and mainly involved in immune response-related pathways. Finally, TIMER and TIDE were used to predict gene immune function and its association with immunotherapy. We found that these four genes were positively correlated with better response to immune checkpoint blockade-based immunotherapy. Altogether, CXCL13, FCRLA, MS4A1, and PLA2G2D may be used as potential therapeutic genes for reflecting OC immune status and predicting response to immunotherapy.

DBA/1 mice display equivalent cardiac function to C57BL/6J mice.

NEW FINDINGS: What is the central question of this study? Do normal adult DBA/1 mice have cardiac function and performance equal to those of C57BL/6J mice? What is the main finding and its importance? Male adult DBA/1 mice show equivalent cardiac function to C57BL/6J mice up to 8 months old. Therefore, cardiac dysfunction could be investigated in an autoimmune diseases model established with DBA/1 mice. ABSTRACT: Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitation-contraction coupling-related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin-eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac ß-adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca2+ /calmodulin-dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease-induced heart dysfunction and exploring potential interventions.