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PKA signaling is important for the post-translational modification of proteins, especially those in cardiomyocytes involved in cardiac excitation-contraction coupling. PKA activity is spatially and temporally regulated through compartmentalization by protein kinase A anchoring proteins. Cypher/ZASP, a member of PDZ-LIM domain protein family, is a cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines. It has been demonstrated that Cypher/ZASP plays a pivotal structural role in the structural integrity of sarcomeres, and several of its mutations are associated with myopathies including dilated cardiomyopathy. Here we show that Cypher/ZASP, interacting specifically with the type II regulatory subunit RIIα of PKA, acted as a typical protein kinase A anchoring protein in cardiomyocytes. In addition, we show that Cypher/ZASP itself was phosphorylated at Ser(265) and Ser(296) by PKA. Furthermore, the PDZ domain of Cypher/ZASP interacted with the L-type calcium channel through its C-terminal PDZ binding motif. Expression of Cypher/ZASP facilitated PKA-mediated phosphorylation of the L-type calcium channel in vitro. Additionally, the phosphorylation of the L-type calcium channel at Ser(1928) induced by isoproterenol was impaired in neonatal Cypher/ZASP-null cardiomyocytes. Moreover, Cypher/ZASP interacted with the Ser/Thr phosphatase calcineurin, which is a phosphatase for the L-type calcium channel. Taken together, our data strongly suggest that Cypher/ZASP not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins.

In the present study, sixteen novel RNA mycoviruses co-infecting a single strain of Rhizoctonia zeae (strain D40) were identified and molecularly characterized using metatranscriptome sequencing combined with a method for rapid amplification of cDNA ends. The fungal strain was isolated from diseased seedlings of sugar beet with damping-off symptoms. Based on genome analysis and phylogenetic analysis of amino acid sequences of RNA-dependent RNA polymerase, the sixteen mycoviruses associated with strain D40 contained three genome types with nine distinct lineages, including positive single-stranded RNA (Hypoviridae, Yadokariviridae, Botourmiaviridae, and Gammaflexiviridae), double-stranded RNA (Phlegiviridae, Megabirnaviridae, Megatotiviridae, and Yadonushiviridae), and negative single-stranded RNA (Tulasviridae), suggesting a complex composition of a mycoviral community in this single strain of R. zeae (strain D40). Full genome sequences of six novel mycoviruses and the nearly full-length sequences of the remaining ten novel mycoviruses were obtained. Furthermore, seven of these sixteen mycoviruses were confirmed to assemble virus particles present in the R. zeae strain D40. To the best of our knowledge, this is the first detailed study of mycoviruses infecting R. zeae. [ABSTRACT FROM AUTHOR]

In the present study, sixteen novel RNA mycoviruses co-infecting a single strain of Rhizoctonia zeae (strain D40) were identified and molecularly characterized using metatranscriptome sequencing combined with a method for rapid amplification of cDNA ends. The fungal strain was isolated from diseased seedlings of sugar beet with damping-off symptoms. Based on genome analysis and phylogenetic analysis of amino acid sequences of RNA-dependent RNA polymerase, the sixteen mycoviruses associated with strain D40 contained three genome types with nine distinct lineages, including positive single-stranded RNA ( Hypoviridae , Yadokariviridae , Botourmiaviridae , and Gammaflexiviridae ), double-stranded RNA (Phlegiviridae, Megabirnaviridae , Megatotiviridae, and Yadonushiviridae), and negative single-stranded RNA ( Tulasviridae ), suggesting a complex composition of a mycoviral community in this single strain of R. zeae (strain D40). Full genome sequences of six novel mycoviruses and the nearly full-length sequences of the remaining ten novel mycoviruses were obtained. Furthermore, seven of these sixteen mycoviruses were confirmed to assemble virus particles present in the R. zeae strain D40. To the best of our knowledge, this is the first detailed study of mycoviruses infecting R. zeae .

Objective: The extent of tumor regression varies widely among patients who receive neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision (TME) surgery. We evaluated the tumor regression grade (TRG) classification of patients and analyzed factors related to TRG and its value in predicting prognosis in locally advanced rectal cancer (LARC)., Methods: This study retrospectively analyzed the clinicopathologic data of 269 consecutive patients with LARC treated from February 2002 to October 2014. The grade of TRG was based on the extent of primary tumor replaced by fibrosis. Clinical characteristics and relative survival were retrospectively analyzed., Results: There were 269 patients, among whom 67 patients (24.9%) achieved TRG0, whereas 46 patients (17.1%) showed TRG3. TRG1 and TRG2 were both found in 78 patients (29.0%). Clinicopathologic factors that were related to TRG included post-NACRT carcinoembryonic antigen (CEA) level (P=0.002), clinical T stage (P=0.022), pathologic T stage (P<0.001) and pathologic lymph node status (P=0.003). The 5-year overall survival (OS) was 74.6%, 55.1%, 47.4%, 28.3% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). The 5-year disease-free survival (DFS) was 64.2%, 47.4%, 37.2%, 23.9% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). Based on multivariate analysis, TRG was a significant predictor for both OS (P=0.039) and DFS (P=0.043)., Conclusion: Clinicopathologic factors such as post-NACRT CEA level, clinical T stage, pathological T stage and pathological lymph node status are significantly associated with TRG. TRG is an independent predictor of survival. Therefore, it is reasonable to include the TRG for clinicopathologic assessment., Competing Interests: None., (IJCEP Copyright © 2023.)

Matrix metalloproteinase 7 (MMP-7) was speculated to have a key role in the development and progression of human cancer. Considerable studies investigated the relationship between its expression and survival in colorectal cancer (CRC), but inconsistent results were obtained. The clinical significance of MMP-7 overexpression in CRC remains controversial. Therefore, in this article, we conducted a meta-analysis to analyze the prognostic value of MMP-7 in CRC. We searched studies in PubMed, Medline, and Web of Science databases until August 2014 to find relevant studies. A total of six high-quality studies met the inclusion criteria and 1631 patients were included in our study. Combined hazard ratios (HRs) suggested that MMP-7 overexpression had an unfavorable impact on overall survival (HR = 1.83, 95% CI: 1.24-2.71). Subgroup and sensitivity analyses further validated the role of MMP-7 as a predictor for prognosis. In conclusion, MMP-7 overexpression detected by immunohistochemistry indicated worse prognosis in CRC and may help to guide clinical therapy.