Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls

Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells

Gene expression analysis of human microvascular endothelial cells exposed to diesel exhaust particles and oxidized phospholipids revealed several upregulated gene modules, including genes involved in vascular inflammatory processes such as atherosclerosis

Functional connectivity of the anterior cingulate cortex in depression and in health

The first voxel-level resting-state functional connectivity (FC) neuroimaging analysis of depression of the anterior cingulate cortex (ACC) showed in 282 patients with major depressive disorder compared with 254 controls, some higher, and some lower FCs. However, in 125 unmedicated patients, primarily increases of FC were found: of the subcallosal anterior cingulate with the lateral orbitofrontal cortex, of the pregenual/supracallosal anterior cingulate with the medial orbitofrontal cortex, and of parts of the anterior cingulate with the inferior frontal gyrus, superior parietal lobule, and with early cortical visual areas. In the 157 medicated patients, these and other FCs were lower than in the unmedicated group. Parcellation was performed based on the FC of individual ACC voxels in healthy controls. A pregenual subdivision had high FC with medial orbitofrontal cortex areas, and a supracallosal subdivision had high FC with lateral orbitofrontal cortex and inferior frontal gyrus. The high FC in depression between the lateral orbitofrontal cortex and the subcallosal parts of the ACC provides a mechanism for more non-reward information transmission to the ACC, contributing to depression. The high FC between the medial orbitofrontal cortex and supracallosal ACC in depression may also contribute to depressive symptoms

Research progress in surface plasmon resonance technology in exosome characterization and identification

Exosomes are lipid bilayer membrane vesicles that are widely distributed in peripheral blood， saliva， urine， ascites and other fluids. A variety of tumor-related genes in exosomes are involved in the information exchange between cancer cells and normal cells， as well as the process of tumor cell proliferation and metastasis， play an important role in tumor development， and are potential biomarkers for tumor liquid biopsy. In recent years， surface plasmon resonance （SPR） is considered to have great application potential in the characterization of exosomes due to its high sensitivity， small sample size required for testing， short detection time and low background interference， etc. In this article， the basic principle of SPR and the application prospect of SPR-based biosensing platform in exosomes characterization were mainly illustrated

Super-resolution microscopy and its applications in neuroscience

Optical microscopy promises researchers to see most tiny substances directly. However, the resolution of conventional microscopy is restricted by the diffraction limit. This makes it a challenge to observe subcellular processes happened in nanoscale. The development of super-resolution microscopy provides a solution to this challenge. Here, we briefly review several commonly used super-resolution techniques, explicating their basic principles and applications in biological science, especially in neuroscience. In addition, characteristics and limitations of each technique are compared to provide a guidance for biologists to choose the most suitable tool

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion

AIM: To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy (DR) or retinal vein occlusion (RVO). METHODS: This is a retrospective case control study. The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor (VEGF) for patients diagnosed with macular edema secondary to DR (DME) or RVO (RVO-ME) at Xijing Hospital from August 2021 to July 2022. Meanwhile, aqueous humor samples during vitrectomy from patients with idiopathic macular hole (IMH) were also collected and served as controls. The aqueous humor concentrations of VEGF, platelet-derived factor (PDGF), interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured with Human Premixed Multi-Analyte Kit (Luminex). The difference of the aqueous cytokines and the correlation between the two diseases were analyzed. RESULTS: A total of 40 eyes of 38 patients were enrolled in the study, including 13 eyes of 11 DME patients (DME group), 16 eyes of 16 RVO-ME patients (RVO-ME group) and 11 eyes of 11 IMH patients (control group). The VEGF, PDGF, IL-6, IL-8, and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group (all P<0.05), the levels of TNF-α was higher in the DME group than in the control group (P<0.05). The VEGF, IL-6, MCP-1, and TNF-α levels in the aqueous humor were significantly higher in the DR group than those in the RVO group (all P<0.05). Correlation analyses revealed that there were complex positive correlations between IL-6, IL-8, IL-18, MCP-1, and TNF-α levels in the aqueous humor of eyes with two diseases. CONCLUSION: Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME, the roles of these factors are more significant or more likely to be activated in DR patients, suggesting different treatment strategies should be considered for the two diseases

Constraints on holographic dark energy from X-ray gas mass fraction of galaxy clusters

We use the Chandra measurements of the X-ray gas mass fraction of 26 rich clusters released by Allen et al. to perform constraints on the holographic dark energy model. The constraints are consistent with those from other cosmological tests, especially with the results of a joint analysis of supernovae, cosmic microwave background, and large scale structure data. From this test, the holographic dark energy also tends to behave as a quintom-type dark energy.Comment: 5 pages, 3 figures; to appear in Phys. Lett.

Evaluation of the learning curve for conformal sphincter preservation operation in the treatment of ultralow rectal cancer

BACKGROUND: To investigate the learning curve of conformal sphincter preservation operation (CSPO) in the treatment of ultralow rectal cancer and to further explore the influencing factors of operation time. METHODS: From August 2011 to April 2020, 108 consecutive patients with ultralow rectal cancer underwent CSPO by the same surgeon in the Department of Colorectal Surgery of Changhai Hospital. The moving average and cumulative sum control chart (CUSUM) curve were used to analyze the learning curve. The preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data were compared before and after the completion of learning curve. The influencing factors of CSPO operation time were analyzed by univariate and multivariate analysis. RESULTS: According to the results of moving average and CUSUM method, CSPO learning curve was divided into learning period (1–45 cases) and learning completion period (46–108 cases). There was no significant difference in preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data between the two stages. Compared with the learning period, the operation time (P < 0.05), blood loss (P < 0.05), postoperative flatus and defecation time (P < 0.05), liquid diet time (P < 0.05), and postoperative hospital stay (P < 0.05) in the learning completion period were significantly reduced, and the difference was statistically significant. Univariate and multivariate analysis showed that distance of tumor from anal verge (≥ 4cm vs. < 4cm, P = 0.039) and T stage (T3 vs. T1-2, P = 0.022) was independent risk factors for prolonging the operation time of CSPO. CONCLUSIONS: For surgeons with laparoscopic surgery experience, about 45 cases of CSPO are needed to cross the learning curve. At the initial stage of CSPO, beginners are recommended to select patients with ultralow rectal cancer whose distance of tumor from anal verge is less than 4 cm and tumor stage is less than T3 for practice, which can enable beginners to reduce the operation time, accumulate experience, build self-confidence, and shorten the learning curve on the premise of safety

Tumor Suppressor Spred2 Interaction with LC3 Promotes Autophagosome Maturation and Induces Autophagy-Dependent Cell Death

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner