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Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ2 = 9.007, P =.003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ2 = 56.523, P =.000; χ2 = 72.939, P =.000). From correlation analysis, there was a negative correlation between miR-133b and PKM2(r = −0.515, P <.001), a negative correlation between miR-133b and STAT3(r = −0.314, P =.007), and a positive correlation between PKM2 and STAT3(r = 0.771, P <.001). Conclusions: In ESCC, our study demonstrated that downregulation of miR-133b and upregulation of PKM2 and STAT3. We predict that miR-133b may inhibit the STAT3 pathway by downregulating PKM2. [ABSTRACT FROM AUTHOR]

A combined control strategy with an adaptive inverse control (AIC) and an inverse frequency response function (IFRF) equalization technique is proposed for the electrohydraulic shaking table (EST) system. The control purpose is to improve the accuracy of time waveform replication. In contrast to the iterative compensation through repetitive excitations control approach of industrial EST controllers, the proposed control strategy utilizes an IFRF of the EST system for extending the EST system frequency bandwidth and obtaining asymptotic reference tracking, and employs a variable tap-length filtered-x least-mean-squares algorithm to adaptively tune the time-domain drive signal and further improve the position and acceleration tracking performance of the EST system. Thus, the proposed combined control strategy is designed to combine the merits of IFRF and AIC. The procedures of the proposed control strategy are programmed in MATLAB/Simulink, and then compiled to a real-time PC with Microsoft Visual Studio.NET for implementation. The simulated and experimental results show that this control strategy achieves satisfactory position and acceleration waveform replication accuracy. [ABSTRACT FROM PUBLISHER]

To built pilot tracking control strategy model, the combination of sliding model control characteristic and optimal control characteristic is adopted to propose a sliding optimal control method, and the time-varying sliding surfaces are designed so that the system state is on the sliding surface from the beginning of the motion without reaching phase. The system is robust and stable. A parameter selected method of weighting matrix on H∞ control is improved, by which the weighting matrix of linear quadratic optimal control is calculated. To drive the system state variables to the acquisition control switching surface in minimum time, the acquisition control strategy is builed by sliding model control. The main error is regared as a judgement from acquisition control strategy to tracking control strategy. The simulation results show that the pilot variable strategy control is suitable to the real pilot control characteristic. [ABSTRACT FROM AUTHOR]

Cardioembolic stroke, characterized by severe illness, poor prognosis, and high recurrence rate, is one of the important causes of ischemic stroke. In the field of genetic research, numerous genes associated with cardioembolic stroke have been identified, and their potential in predicting disease risk and evaluating risk factors has been progressively explored. Here, we provide an overview of the latest advancements in genetics for cardioembolic stroke, including genome-wide association studies, copy number variation studies, whole-genome sequencing studies. Furthermore, we also summarize the application of genetic datasets in polygenic risk score and Mendelian randomization. The aim of this overview is to provide insights and references from multiple perspectives for future investigations on the genetic information for cardioembolic stroke.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal tumor type, but studies on the ESCC tumor microenvironment are limited. We found that cystatin SN (CST1) plays an important role in the ESCC tumor microenvironment. CST1 has been reported to act as an oncogene in multiple human cancers, but its clinical significance and underlying mechanism in ESCC remain elusive., Methods: We performed ESCC gene expression profiling with data from RNA-sequencing and public databases and found CST1 upregulation in ESCC. Then, we assessed CST1 expression in ESCC by RT‒qPCR and Western blot analysis. In addition, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to estimate the expression of CST1 in ESCC tissue and serum. Moreover, further functional experiments were conducted to verify that the gain and loss of CST1 in ESCC cell lines significantly influenced the proliferation and metastasis of ESCC. Mass spectrometry, coimmunoprecipitation, and gelatin zymography experiments were used to validate the interaction between CST1 and matrix metalloproteinase 2 (MMP2) and the mechanism of CST1 influence on metastasis in ESCC., Results: Here, we found that CST1 expression was significantly elevated in ESCC tissues and serum. Moreover, compared with patients with low CST1 expression, patients with high CST1 expression had a worse prognosis. Overall survival (OS) and disease-free survival (DFS) were significantly unfavorable in the high CST1 expression subgroup. Likewise, the CST1 level was significantly increased in ESCC serum compared with healthy control serum, indicating that CST1 may be a potential serum biomarker for diagnosis, with an area under the curve (AUC) = 0.9702 and p < 0.0001 by receiver operating curve (ROC) analysis. Furthermore, upregulated CST1 can promote the motility and metastatic capacity of ESCC in vitro and in vivo by influencing epithelial mesenchymal transition (EMT) and interacting with MMP2 in the tumor microenvironment (TME)., Conclusions: Collectively, the results of this study indicated that high CST1 expression mediated by SPI1 in ESCC may serve as a potentially prognostic and diagnostic predictor and as an oncogene to promote motility and metastatic capacity of ESCC by influencing EMT and interacting with MMP2 in the TME., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Objective: To investigate the role of p38α mitogen-activated protein kinases (MAPK) in human esophageal squamous cell carcinoma cell line Eca109., Methods: Specific short hairpin (shRNA) vector as well as eukaryotic expression vector harbouring full length cDNA of human p38α MAPK were transfected into Eca109 cells. Cell proliferation after transfection was detected by MTT, cell cycle and apoptosis were assayed by flow cytometry. The variation of migration and invasion after transfection was determined using wound healing assay and Transwell assay, respectively., Results: The proliferation of Eca109 cells after knock-down for 48 h (0.951 ± 0.086) was significantly increased (t = 3.20, P < 0.05) compared with control (0.811 ± 0.012), Sphase was increased but not significantly. Cell apoptosis rate after knock down for 48 h (17.400 ± 5.495) was significantly increased (t = 40.06, P < 0.01) compared with control(1.000 ± 0.721) . Migration after knock down for 72 h (0.034 ± 0.031) were enhanced pronouncedly (t = -5.79, P < 0.01) compared with control (0.278 ± 0.021) and invasive ability also increased; whereas the proliferation of Eca109 cells after over-expression for 48 h (0.472 ± 0.089) was inhibited significantly (t = -7.50, P < 0.01) compared with control(0.811 ± 0.012), cells arrested at G1 phase (t = 4.80, P < 0.01). Cell apoptosis rate (32.233 ± 1.457) were decreased significantly (t = 17.20, P < 0.01) compared with control (1.000 ± 0.721) mm, migration after overexpression for 72 h ((0.770 ± 0.054) mm) was suppressed pronouncedly compared with control groups of (0.278 ± 0.021) mm(t = 11.00, P < 0.01).Invasion after overexpression was inhibited., Conclusions: p38α MAPK plays an anti-oncogenic role in the pathogenesis of esophageal squamous cell carcinoma cell line Eca109.

Objective: To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients., Methods: The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas., Results: ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05)., Conclusions: ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.

Aim: To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC)., Methods: A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects. Genotypes of 69 single nucleotide polymorphisms (SNPs) of metabolic enzyme (aldehyde dehydrogenase-2, ALDH2; alcohol dehydrogenase-1 B, ADHB1; Cytochrome P450 2A6, CYP2A6) and DNA repair capacity genes (excision repair cross complementing group 1, ERCC1; O(6)-methylguanine DNA methyltransferase, MGMT; xeroderma pigmentosum group A, XPA; xeroderma pigmentosum group A, XPD) were determined by the Sequenom MassARRAY system, and results were analyzed using unconditional logistic regression adjusted for age, gender., Results: There was no association between the variation in the ERCC1, XPA, ADHB1 genes and ESCC risk. Increased risk of ESCC was suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626 (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A allele [Rs11016897: 1.666 (1.245-2.228)]. Five variants of MGMT were associated with a protective effect on ESCC carcinogenesis, including C allele [Rs7069143: 0.698 (0.518-0.939)], C allele [Rs3793909: 0.653 (0.429-0.995)], A allele [Rs12771882: 0.719 (0.524-0.986)], C allele [Rs551491: 0.707 (0.529-0.945)], and A allele [Rs7071825: 0.618 (0.506-0.910)]. At the genotype level, increased risk of ESCC carcinogenesis was found in homozygous carriers of the ALDH2 Rs886205 [CC vs TT, odds ratios (OR): 3.116, 95% CI: 1.179-8.234], MGMT Rs11016879 (AA vs GG, OR: 3.112, 95% CI: 1.565-6.181), Rs12771882 (AA vs GG, OR: 2.442, 95% CI: 1.204-4.595), and heterozygotes carriers of the ALDH2 Rs886205 (CT vs TT, OR: 3.930, 95% CI: 1.470-10.504), MGMT Rs11016879 (AG vs GG, OR: 3.933, 95% CI: 2.216-6.982) and Rs7075748 (CT vs CC, OR: 1.949, 95% CI: 1.134-3.350), respectively. Three variants were associated with a protective effect on ESCC carcinogenesis, carriers of the MGMT Rs11016878 (AG vs AA, OR: 0.388, 95% CI: 0.180-0.836), Rs7069143(CT vs CC, OR: 0.478, 95% CI: 0.303-0.754) and Rs7071825 (GG vs AA, OR: 0.493, 95% CI: 0.266-0.915). Increased risk of ESCC metastasis was indicated in MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251-3.791)]. Two variants in frequency of presence C allele of CYP2A6 [Rs8192720: 0.290 (0.099-0.855)] and A allele of MGMT [Rs2053139: 0.511 (0.289-0.903)] were associated with a protective effect on ESCC progression. Increased risk of ESCC metastasis was found in heterozygote carriers of the MGMT Rs7068306 (CG vs CC, OR: 4.706, 95% CI: 1.872-11.833)., Conclusion: Polymorphic variation in ALDH2, XPD and MGMT genes may be of importance for ESCC susceptibility. Polymorphic variation in CYP2A6 and MGMT are associated with ESCC metastasis.

Aim: To prepare the mouse antibody against Cecropin-XJ, identify its specificity and use it in cellular localization of Cecropin-XJ in vitro., Methods: The cDNA sequence of Cecropin-XJ with signal peptide sequence was subcloned into the eukaryotic expression vector pcDNA3. The recombinant plasmid was named pcDNA3-Cecropin-XJ, which was used as an antigen to immune the Kunming white mouse. Meanwhile, the cDNA sequence was subcloned into the fusion expression vector and the fusion protein was expressed as a test antigen., Results: Indirect ELISA showed that the fifth immunity's titer was highest. The immune gold-conjugated experiment showed that the prepared antibody was clearly and efficiently localized in prokaryotic cells where the Cecropin-XJ worked., Conclusion: The antibody against Cecropin-XJ has high immune reactivity and specificity, which is beneficial to further study on Cecropin-XJ function and antibody preparation of small peptides.

Nowadays many of antimicrobial peptides have been extensively studied in order to elucidate their antimicrobial mode of action. Much of the research focused on mechanisms of cytoplasmic membrane disruption has been proposed for antimicrobial peptides, but it is not known whether their antimicrobial mode of action is due to their effects on bacterial chromosome. To obtain more information about the possible mechanisms, Cecropin-XJ, a kind of antimicrobial peptide from Xinjiang silkworm, was used as subject and prepared by purification of Pichia yeast fermentation containing cecropin-XJ gene expression product. Subsequently, ultraviolet absorption spectra were employed to investigate whether this antibacterial function is due to Cecropin-XJ works on S. aureus DNA in vitro. The increase in absorbance of DNA samples at 260nm due to the addition of Cecropin-XJ was measured. It is called hyperchromicity of DNA, which can provide a direct measure of the degree of base-pair unstacking. The unstacking results in the loss of duplex helix, and then leads to the duplex helix becoming relaxing. At the same time, the interaction mode was studied by using ethidium bromide (EB) as an extrinsic fluorescence probe. With the addition of Cecropin-XJ, the intensity of intrinsic fluorescence absorbance of DNA at 307 nm increases greatly. It is suggested that the addition of Cecropin-XJ may unstack base-paire of DNA exposing the fluorescent amino acide, leading to the enhancing of DNA fluorescence intensity. Subsequently the competition between Cecropin-XJ and EB to combine with DNA was found. It is suggested that the style was groove binding and intercalation in the interaction of Cecropin-XJ and double helix DNA. Furthermore, in this study, the binding constant and binding number of Cecropin-XJ complex with DNA were determined. There were different binding constant and number of EB complex with DNA because of the the addition of Cecropin-XJ. It is showed that the interaction of Cecropin-XJ and DNA was based on intercalation or non-intercalation. Meanwhile, these results help explain the molecule mechanism of antimicrobial peptide from the interaction style and structure characteristic of Cecropin-XJ and S. aureus DNA. These findings could contribute to further investigation on the mechanism of action of Cecropin-XJ.