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Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. Methods A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. Results After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. Conclusion Collectively, these findings suggest that domperidone serves as an effective “multi-target” inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

The study examined the impact of adding cattle manure to the composting process of Agaricus bisporus mushroom substrate on compost humification. A control group CK comprised entirely of Agaricus bisporus mushroom substrate, while the experimental group CD (70 percent Agaricus bisporus mushroom substrate and 30 percent cattle manure) comprised the two composting treatments that were established. The study determined that the addition of cow dung has promoted the formation of humus components. Particularly, humic substance (HS-C) and humic acid (HA) increased by 41.3 and 74.7%, respectively, and the ratio of humic acid to fulvic acid (HA/FA) also increased by 2.78. It showed that the addition of cow dung accelerated the synthesis and decomposition of precursors, such as polysaccharides, polyphenols, and reducing sugars. Thereby promoting the formation of humic acid. Network analysis revealed that adding cow dung promoted microbial interactions increased the complexity and stability of the bacterial and fungal symbiotic network, enhanced cooperation and reciprocity among microbes, and assisted in transforming fulvic acid (FA) components. Structural equation modeling (SEM) is a multivariate data analysis method for analyzing complex relationships among constructs and core indicators. SEM illustrated that introducing cattle manure into the composting process resulted in alterations to the correlation between physicochemical parameters and the microbial community, in addition to humus formation. Polysaccharides are the primary precursors for polymerization to form HA, which is an essential prerequisite for the conversion of fulvic acid to humic acid. Additionally, microbes affected the formation of humus, with bacteria substantially more influential than fungi. These findings provide new ideas for regulating the degree of humification in the composting process and have important practical implications for optimizing mushroom cultivation and composting techniques today.

ABSTRACTEsophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC. Here, we developed a humanized and Fc-engineered anti-B7H3 mAb 24F-Hu-mut2 and systematically evaluated its anti-tumor activity in vitro and in vivo. The 24F-Hu-mut2 was humanized and modified in Fc fragment to obtain stronger antibody-dependent cell-mediated cytotoxicity(ADCC) activity and nanomolar affinity. Furthermore, both of ESCC cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models indicated that 24F-Hu-mut2 displayed potent in vivo anti-tumor activity. In addition, a computational docking model showed that the mAb bound to IgC1 and IgC2 domain of B7-H3, which is closer to the cell membrane. Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo, and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors.

Abstract T-LAK-originated protein kinase (TOPK), a dual specificity serine/threonine kinase, is up-regulated and related to poor prognosis in many types of cancers. Y-box binding protein 1 (YB1) is a DNA/RNA binding protein and serves important roles in multiple cellular processes. Here, we reported that TOPK and YB1 were both highly expressed in esophageal cancer (EC) and correlated with poor prognosis. TOPK knockout effectively suppressed EC cell proliferation and these effects were reversible by rescuing YB1 expression. Notably, TOPK phosphorylated YB1 at Thr 89 (T89) and Ser 209 (S209) amino acid residues, then the phosphorylated YB1 bound with the promoter of the eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) to activate its transcription. Consequently, the AKT/mTOR signal pathway was activated by up-regulated eEF1A1 protein. Importantly, TOPK inhibitor HI-TOPK-032 suppressed the EC cell proliferation and tumor growth by TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo. Taken together, our study reveals that TOPK and YB1 are essential for the growth of EC, and TOPK inhibitors may be applied to retard cell proliferation in EC. This study highlights the promising therapeutic potential of TOPK as a target for treatment of EC.

We propose a photonic quasi-crystal fiber which has five ring-shaped cores in the cross section. It realizes the multiplexing of 6 vortex modes. The fiber is based on SiO2 and has an octuple photonic quasi-crystal structure. It achieves four independent dual-core coupling pairs with the optimization of geometric parameters. By adjusting the thickness of five ring-shaped cores, the fundamental mode (HE11) in the small side ring-shaped fiber cores couple to different higher order vector modes (TE01, HE21, TM01, HE31) in the large center ring-shaped fiber core, which makes the light field transfer from small side cores to large center core and realizes the multiplexing of 6 vortex modes (TE01, $\text{OAM}_{ \pm 1,1}^ \pm $, TM01, $\text{OAM}_{ \pm 2,1}^ \pm $). The transmission characteristics are analyzed with supermode theory. The $\Delta {n}_{\text{eff}}$ of adjacent vector modes is larger than ${10}^{ - 4}$ due to the thin center ring core. The coupling length (${L}_c$) keeps in the order of ${10}^{ - 2}$ m between 1500--1600 nm and the coupling efficiency is larger than 90% in 1550 nm for four dual-core coupling pairs. We believe this design will have great potential in the field of all-fiber vortex mode division multiplexing.

Target alignment technology is one of the most critical technologies in laser fusion experiments and is an important technology related to the success of laser fusion experiments. In this study, by combining the open-loop and closed-loop errors of the target alignment, the Kalman state observer is used to estimate the position of the target, which improves the observation precision of the target alignment. Then the optimized result is used to guide the alignment of the target. This method can greatly optimize the target alignment error and reduce uncertainty. With the improvement of the target alignment precision, it will greatly improve the reliability and repeatability of the experiments’ results, thereby improving the success rate of the experiments.

We propose a ring-core photonic quasi-crystal fiber (RC-PQCF) featuring a ring-shaped fiber core and two symmetrical SiO2 stress-applying parts (SAPs). By optimizing the mole percentage of GeO2 and geometrical parameters of the fiber, the design supports 34 full vector polarization modes (FV-PMs). The effective refractive index difference ($\Delta {n_{eff}}$) of adjacent FV-PMs is larger than $1.07 \times {10^{ - 4}}$ at 1550 nm. The confinement loss (${\mathrm{\alpha }}$) of FV-PMs is less than ${10^{ - 6}}$, which is sufficient to confine the light field in the ring-core. Through numerical analysis, broadband performance is investigated subsequently in the 1500–1600 nm. The dispersion (${D_\lambda }$) of FV-PMs is less than $138.14{\mathrm{\ ps}} \cdot {\mathrm{n}}{{\mathrm{m}}^{ - 1}} \cdot {\mathrm{k}}{{\mathrm{m}}^{ - 1}}$ and maintains a flat trend. The mode field area (${A_{eff}}$) of FV-PMs is larger compared to single mode fibers and the nonlinear coefficient (${\mathrm{\gamma }}$) of FV-PMs is within ($6.97 \times {10^{ - 4}}$, $1.54 \times {10^{ - 3}}$) ${{\mathrm{m}}^{ - 1}} \cdot {{\mathrm{W}}^{ - 1}}{\mathrm{\ }}$ in the 1500–1600 nm. The fiber is a promising design for mode division multiplexing (MDM) that supports the MIMO-free processing and improves the transmission capacity and spectral efficiency.

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase β (Polβ), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polβ is related to the occurrence of esophageal cancer, but the role of Polβ deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polβ-knockout mice were used to explore the relationship of Polβ deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polβ-KO mice were more serious than those in Polβ-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polβ increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polβ-KO mice. We also found that deletion of Polβ promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polβ knockout promotes the occurrence of esophageal precancerous lesions.

Abstract Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation.

Aim: This research investigated the therapeutic effect of an allogeneic mouse brain microvascular endothelial cell vaccine on lung cancer and further elucidated its potential anti-angiogenic mechanism. Materials & methods: The immune effect of the allogeneic bEnd.3 vaccine and DC vaccine loaded with bEnd.3 antigen on the subcutaneous transplantation of Lewis lung cancer (LLC) was assessed by ELISA, the CCK test and the CTL killing test. The mechanism was preliminarily revealed by immunohistochemistry and immunoblot analysis. Results: This study revealed that tumor volume was decreased (p .05). Importantly, tumor volume and survival of the T lymphocyte therapeutic group were decreased and prolonged (p

The unified analytical model is proposed for SOI LDMOS (Silicon On Insulator Lateral Double-diffused Metal Oxide Semiconductor) based on the electric field modulation in this paper for the first time. The analytical solutions of the surface electric field distributions and potential distributions are derived on the basis of the 2-D Poisson equation. The variation of the buried layer parameters modulates the surface electric field by the electric field modulation effect to optimize the surface electric field distribution of the device. Also, the simulation results obtained through the simulation software ISE are consistent with the expected results of the analytical model. This not only proves the feasibility of the electric field modulation theory, but also shows that the accurate analytical model will be of great guiding significance for designing and optimizing the same LDMOS based on SOI structures.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear. Methods Tissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings. Results The enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin. Conclusion The findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.

Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2.

Background: Our preclinical data showed that the leukotriene A4 hydrolase (LTA4H) pathway plays a role in colorectal cancer (CRC). High expression of LTA4H and leukotriene B4 receptor type 1 (BLT1) were also associated with CRC survival probability. Clinical samples were evaluated to determine whether LTA4H could serve as a therapeutic target and whether leukotriene B4 (LTB4) could be used as a biomarker for evaluating the efficacy of bestatin in CRC. Methods: Patients with Stage I-III CRC did or did not receive bestatin prior to surgery. Evaluable pairwise CRC patient blood samples were collected to evaluate LTB4 concentration. Tissues were processed by immunohistochemistry to detect the LTA4H pathway and Ki-67 expression. We also determined whether LTA4H or BLT1 was associated with CRC survival probability and explored the mechanism of bestatin action in CRC. Findings: Samples from 13 CRC patients showed a significant decrease in LTB4, the LTA4H signaling pathway, and Ki-67 in the bestatin-treated group compared with the untreated group. LTA4H and BLT1 are overexpressed in CRC and associated with CRC survival probability. Bestatin effectively inhibited LTB4 and tumorigenesis in the ApcMin/+ and CRC patient-derived xenograft mouse model. Interpretation: These results demonstrate that LTB4 could serve as a biomarker for evaluating bestatin efficacy in CRC and the antitumor effects of bestatin through its targeting of LTA4H and support further studies focusing on LTA4H inhibition in CRC. Keywords: Bestatin, LTA4H, LTB4, BLT1, Colorectal cancer

Abstract Background We and others have previously shown that the STAT3 signaling pathway is activated in some esophageal squamous cell carcinoma (ESCC) cells and is required for the survival and growth of these primary ESCC-derived xenografts. It has also been shown that the natural polyphenol curcumin is an effective anti-tumor agent. Methods Luciferase assay and immunoblotting were performed to examine whether curcumin suppressed STAT3 signaling. CCK-8 assay and xenografts were utilized for analyzing ESCC cell growth in culture and mice. Soft agar assay was carried out to determine the colony formation ability of ESCC cells in the presence or absence of curcumin. Cell death and cell cycle were assessed by In CELL Analyzer 2000. Immunohistochemistry and TUNEL assay were used for detecting apoptosis in ESCC tisuses. Molecular docking was performed to evaluate the interaction of curcumin with JAK2. JAK2 activity was assessed using an in vitro cell-free system. HE staining was used to evaluate the ESCC tissues. Results The natural polyphenol curcumin inhibited STAT3 phosphorylation rapidly and blocked STAT3-mediated signaling in ESCC cells. It also induced growth arrest and apoptosis in cultured ESCC cells, which were attenuated by enforced expression of STAT3. Furthermore, curcumin preferentially blocked the growth of primary ESCC-derived xenografts that harbored activated STAT3. Conclusions Curcumin is able to exert anti-tumor action through inhibiting the STAT3 signaling pathway. Giving its wide use in traditional medicines with low toxicity and few adverse reactions, it is conceivable that curcumin might be further explored as a unique STAT3 inhibitor for anti-cancer therapies.

Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6KT389 and p70S6KT421/S424. Furthermore, the levels of mTORS2448, p70S6KT389, p70S6KT421/S424 and RPS6S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTORS2448 by binding to AKT1 and p70S6K kinases. In vivo, DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC.

High recurrence rates and poor survival of patients with esophageal squamous cell carcinoma (ESCC) after treatment make ongoing research on chemoprevention drugs for ESCC particularly important. In this study, we screened a large number of FDA-approved drugs and found levodopa, a drug used to treat Parkinson’s disease, had an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms involved, we applied quantitative proteomics to investigate the anti-tumor activity of levodopa on ESCC. The results suggest that levodopa could down-regulate oxidative phosphorylation, non-alcoholic fatty liver disease, and Parkinson’s disease pathways. Major mitochondrial respiratory compounds were involved in the pathways, including succinate dehydrogenase subunit D, NADH-ubiquinone oxidoreductase Fe-S protein 4, and mitochondrial cytochrome c oxidase subunit 3. Down-regulation of these proteins was associated with mitochondrial dysfunction. Western blotting and immunofluorescence results confirmed the proteomics findings. Cell viability assays indicated mitochondrial activity was suppressed after levodopa treatment. Reduced mitochondrial membrane potential was detected using JC-1 staining and TMRE assays. Transmission electron microscopy revealed changes in the morphology of mitochondria. Taken together, these results indicate that levodopa inhibited the growth of ESCC through restraining mitochondria function.

Abstract Background Burnout is a health problem in nurses. Individuals with a certain personality are more susceptible to job-related burnout. General self-efficacy (GSE) is an important predictor of job-related burnout. The relationships between general self-efficacy, job-related burnout and different personality types are still not clear. This study aims to analyze the relationships of job-related burnout, stress, general self-efficacy and personality types, as well as their interactions in job-related burnout. Method A cross-sectional survey of 860 nurses was conducted between June and July 2015 in China. We measured their job-related burnout using the scale of the Maslach Occupational Burnout Scale, and personality, stress, and GSE. Machine learning of generalized linear model were performed. Results Maslach Burnout Inventory (MBI) professional efficacy was significantly associated with gender, marital status, age, job title and length of service. A machine learning algorithm showed that stress was the most important factor in job-related burnout, followed by GSE, personality type (introvert unstable), and job title. Individuals with low GSE and either introversion or unstable (high neuroticism) personality seemed to have stronger burnout when they faced stress (regardless of stress intensity) compared to others. Conclusion Stress, GSE and introvert unstable personality are the top three factors of job-related burnout. GSE moderates the effect of stress on burnout in nurses with extroversion or neuroticism personality. Reducing stress, increasing GSE, and more social support may alleviate job-related burnout in nurses. Nurses with introvert unstable personality should be given more social support in reducing stress and enhancing their GSE.

Background: The mouse brain microvascular endothelial cell line bEnd.3 was used to develop a vaccine and its anti-tumor effect on lung metastases was observed in immunized mice. Methods: Mouse bEnd.3 cells cultured in-vitro and then fixed with glutaraldehyde was used to immunize mice; mice were challenged with the metastatic cancer cell line U14, and changes in metastatic cancer tissues were observed through hematoxylin and eosin staining. Carboxyfluorescein succinimidyl amino ester (CSFE) and propidium iodide (PI) were used to detect cytotoxic activity of spleen T lymphocytes; the ratio of CD3+ and CD8+ T-cell sub-sets was determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and immunoblot were used to examine the specific response of the antisera of immunized mice. Results: The number of metastatic nodules in bEnd.3 and human umbilical vein endothelial cell (HUVEC) vaccine groups was less than NIH3T3 vaccine group and phosphate buffered saline (PBS) control group. The bEnd.3-induced and HUVEC-induced cytotoxic T-lymphocytes (CTLs) showed significant lytic activity against bEnd.3 and HUVEC target cells, while the antisera of mice in bEnd.3 and HUVEC vaccine groups showed specific immune responses to membrane proteins and inhibited target cell proliferation in-vitro. Immunoblot results showed specific bands at 180KD and 220KD in bEnd.3 and at 130 kD and 220 kD in HUVEC lysates. Conclusions: Allogeneic bEnd.3 vaccine induced an active and specific immune response to tumor vascular endothelial cells that resulted in production of antibodies against the proliferation antigens VEGF-R II, integrin, Endog etc. Immunization with this vaccine inhibited lung metastasis of cervical cancer U14 cells and prolonged the survival of these mice.

Abstract Background The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. Methods 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines. Tumor growth measurements, histological and immunohistochemistry analysis, Western blotting, EGFR and K-RAS mutation detection and gefitinib sensitive assay were performed to evaluate the characteristic of established PDX models. Immunofluorescence analysis, anchorage-independent cell growth, Western blotting and gefitinib sensitive assay were performed to assay the characteristic of established primary cell lines. The whole-exome sequencing was used to compare the characteristic of the patient’s tumor tissue, established PDX and primary cell line. Results Twenty-one lung cancer PDX models (67.74%, 21/31) and ten primary cell lines (32.25%, 10/31) were established from patients’ tumor tissues. The histology and pathological immunohistochemistry of PDX xenografts are consistent with the patients’ tumor samples. Various signal pathways were activated in different PDX models (n = 5) and primary cell lines (n = 2). EGFR mutation PDX model and primary cell line (LG1) were sensitive to gefitinib treatment. The expression of CK8/18, TTF1 and NapsinA in LG1 and LG50 primary cells were also positive. And the activated signal pathways were activated in LG1 and LG50 primary cell lines. Furthermore, the gene mutation in PDX tumor tissues and primary cell line (LG50) was consistent with the mutation in LG50 patient’s tumor tissues. Conclusion These data suggested that established lung cancer PDX models and primary cell lines reserved mostly molecular characteristics of primary lung cancer and could provide a new tool to further understand the mechanisms and explore new therapeutic strategies.

To improve the beam pointing accuracy of PW laser facility and reduce the optical axis deviation caused by the deflection amplitude response deviation of the confocal lens of spatial filter for microvibration action, an Optomechanical coupling vibration active control theory is proposed to make the peak value of output optical angle response lower than the pointing threshold value by 0.2 μrad. To establish an Optomechanical coupling vibration active control system, the active control parameters are introduced into the beam transmission matrix of the Optomechanical coupling system. The active control parameters and the peak value of the output light angle response are linked point to point. The algorithm flow of the active control system is designed, the control rules are established, and the control effect is verified. The results show that the peak value of the output optical angle response of the spatial filter decreases by 98.13%, and the attenuation is nearly two orders of magnitude after the active control, which effectively improves the convergence accuracy of the beam pointing of the spatial filter of the PW laser facility, and realizes the beam pointing control under the broadband excitation, and the control result is consistent with the expectation.

Following publication of the original article [1], the authors reported the errors in Fig. 1C and D, Fig. 2, Fig. 4B and C and Fig. 6D and E.

Abstract Background Human DNA polymerase β (polβ) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. Methods We evaluated the mutation of polβ in a larger cohort of esophageal cancer (EC) patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by CCK-8, in vivo tumor growth, and flow cytometry assays. Results There are 229 patients with the polβ mutation, 18 patients with A613T mutation, 12 patients with G462T mutation among 538 ECs. Analysis results of survival time showed that EC patients with A613T, G462T mutation had a shorter survival than the others (P

Background: Esophageal cancer (EC) is one of the most common malignant tumors in the world. Due to difficulties with performing the operation, most patients choose to have palliative treatment instead. Radiotherapy is one of the main palliative treatments of EC. However, the clinical efficacy of radiotherapy is not satisfactory α-Solanine is a bioactive component of steroidal glycoalkaloids which has been demonstrated to exhibit anti-metastasis activity in different cancers. In the present study, we determined the effect of α-solanine on the radiosensitivity of EC cells and priliminarily explored the underlying molecular mechanisms. Methods: Cell Counting Kit-8 (CCK-8) assay was conducted to found the cytotoxic effect of α-solanine on EC cells. CCK-8 assay and colony-forming survival assays were performed to explore the effect of α-solanine on cell viability and proliferation of EC cells after irradiation. Immunofluorescence and comet assays were used to detect the effect of α-solanine on DNA repair capacity of EC cells after irradiation. The flow cytometry (FCM) and Hoechst/PI staining were conductd to study the effect of α-solanine on apoptosis of EC cells after irradiation. Results: The cytotoxic effect of α-solanine to EC cells was dose-dependent. The results of CCK-8, colony-forming survival assay, immunofluorescence, comet assay, FCM and Hoechst/PI staining showed that α-solanine could enhance the radiosensitivity of EC cells. α-Solanine could downregulate Survivin expression level by upregulating miR-138 expression in EC cells. Upregulation of miR-138 and knock down Survivin both enhanced the radiosensitivity of EC cells. Moreover, Survivin could restore the effect of α-solanine and miR-138 on radiosensitivity of EC cells. Conclusions: α-solanine could enhance the radiosensitivity of esophageal cancer cells by inducing microRNA-138 expression, and probably be an effective radiosensitizer in treating EC.

The Editor-in-Chief has retracted this article [1] because Figure 3a overlaps with Figure 2 in [2]. An investigation by Zhengzhou University has confirmed this. The data reported in this article are therefore unreliable. There is also considerable text overlap with a previously published article [3]. Guoqiang Zhao does not agree with this retraction. The other authors have not responded to correspondence from the editor about this retraction.

Background: Human DNA polymerase β (DNA polymerase β, polβ) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. Methods: Luciferase reporter and western blot assays were used to determine whether polβ is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR-499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. Results: polβ was pinpointed as a target gene of miR-499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. Conclusions: We first investigated whether miR-499 modulates polβ, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future.

Angiogenesis is essential for the development, growth, and metastasis of solid tumors. Vaccination with viable human umbilical vein endothelial cells (HUVECs) has been used for antitumor angiogenesis. However, the limited immune response induced by HUVECs hinders their clinical application. In the present study, we found that HUVECs induced by a tumor microenvironment using the supernatant of murine CT26 colorectal cancer cells exerted a better antiangiogenic effect than HUVECs themselves. The inhibitory effect on tumor growth in the induced HUVEC group was significantly better than that of the HUVEC group, and the induced HUVEC group showed a strong inhibition in CD31-positive microvessel density in the tumor tissues. Moreover, the level of anti-induced HUVEC membrane protein antibody in mouse serum was profoundly higher in the induced HUVEC group than in the HUVEC group. Based on this, the antitumor effect of a vaccine with a combination of induced HUVECs and dendritic cell-loading CT26 antigen (DC-CT26) was evaluated. Notably, the microvessel density of tumor specimens was significantly lower in the combined vaccine group than in the control groups. Furthermore, the spleen index, the killing effect of cytotoxic T lymphocytes (CTLs), and the concentration of interferon-γ in the serum were enhanced in the combined vaccine group. Based on these results, the combined vaccine targeting both tumor angiogenesis and tumor cells may be an attractive and effective cancer immunotherapy strategy.

The Editor-in-Chief has retracted this article [1] because Figure 6a and 6b show overlap with Figure 4b in [2]. An investigation by Zhengzhou University has confirmed that these figures overlap. The data reported in this article are therefore unreliable.