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LTBP1 is closely related to TGF-β1 function as an essential component, which was unclear in gastric cancer (GC). Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined to form a training cohort to calculate the connection between LTBP1 mRNA expression, prognosis and clinicopathological features. The training cohort was also used to verify the biological function of LTBP1 and its relationship with immune microenvironment and chemosensitivity. In the tissue microarrays (TMAs), immunohistochemical (IHC) staining was performed to observe LTBP1 protein expression. The correlation between LTBP1 protein expression level and prognosis was also analyzed, and a nomogram model was constructed. Western blotting (WB) was used in cell lines to assess LTBP1 expression. Transwell assays and CCK-8 were employed to assess LTBP1's biological roles. In compared to normal gastric tissues, LTBP1 expression was upregulated in GC tissues, and high expression was linked to a bad prognosis for GC patients. Based on a gene enrichment analysis, LTBP1 was primarily enriched in the TGF-β and EMT signaling pathways. Furthermore, high expression of LTBP1 in the tumor microenvironment was positively correlated with an immunosuppressive response. We also found that LTBP1 expression (p = 0.006) and metastatic lymph node ratio (p = 0.044) were independent prognostic risk factors for GC patients. The prognostic model combining LTBP1 expression and lymph node metastasis ratio reliably predicted the prognosis of GC patients. In vitro proliferation and invasion of MKN-45 GC cells were inhibited and their viability was decreased by LTBP1 knockout. LTBP1 plays an essential role in the development and progression of GC, and is a potential prognostic biomarker and therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Background: Long-term outcome of patients with locally advanced gastric cancer (LAGC) who achieved a pathological complete response (pCR) was scarcely discussed, and never had the factors affecting the prognosis of pCR patients been investigated. Methods: We retrospectively reviewed all patients who achieved a pCR to neoadjuvant chemotherapy (NAC) in Jinling Hospital. The 3- and 5-year overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan–Meier method. Meanwhile, univariate and multivariate COX regression analysis was applied to identify prognostic factors affecting patients' survival. Results: A total of 37 consecutive LAGC patients with pCR were included. The 3- and 5-year OS rates were 88.8% and 78.6%, and the 3- and 5-year PFS rates were 86.5% and 75.8%. In the multivariate COX model, NAC duration of more than 3 cycles (HR 0.11 [0.02–0.62], P = 0.013) and poorly differentiated tumor at diagnosis (HR 0.17 [0.03–0.95], P = 0.043) were detected as protective factors for patients OS. Whereas for PFS, NAC duration (HR 0.12 [0.02–0.67], P = 0.015) was the only protective factor confirmed, with tumor differentiation at diagnosis exhibiting marginal significance (HR 0.21 [0.04–1.09], P = 0.063). Conclusions: Patients with LAGC who achieved a pCR displayed favorable long-term survival outcome, especially those with adequate cycles (≥ 3) of NAC. Besides, poor differentiation at diagnosis might also predict the better OS when pCR achieved. [ABSTRACT FROM AUTHOR]

Edge detection is a widely popular data processing tool in magnetic and gravity exploration which plays an important role in defining shapes and horizontal locations of underground geological structures such as faults, rock boundaries, and minor lineaments. Conventional edge detectors, which are mostly derived from the total field anomaly, have long been applied in field exploration. However, the development of full gradient tensor measurement, which improves detection resolution and provides greater geophysical detail for researchers, has given greater importance to edge detection for full gradient tensors. We propose the use of multiple combinations of gradient tensor components and their eigenvalues to construct balanced boundary recognition filters, taking full advantage of information from the gradient tensor matrix. Different synthetic tests demonstrated that model boundaries were definitely detected, and our methods demonstrated great robustness to noise and oblique magnetization. Field processing of magnetic and gravity data using our methods also yielded clear lineaments and structure locations. Compared with other edge detectors derived from gradient tensors, boundary detection accuracy was considerably improved and false edges were nearly eliminated. [ABSTRACT FROM AUTHOR]

Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread. Therefore, the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial. Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) infection, we found that U18666A, a specific inhibitor of Niemann-Pick C1 (NPC1), is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma membrane, thereby inhibiting the dynamics of clathrin-coated pits (CCPs), which are indispensable for clathrin-mediated endocytosis. Significantly, exogenous cholesterol can complement the dynamics of CCPs, leading to efficient viral entry and infectivity. Administration of U18666A improves the survival and pathology of PRV- and influenza A virus-infected mice. Thus, our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity, indicating a potential new therapeutic strategy against SARS-CoV-2, as well as other emerging viruses. [ABSTRACT FROM AUTHOR]

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4+ T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naïve and memory CD4+ T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection. [ABSTRACT FROM AUTHOR]

The incidence of gastric cancer cachexia is high and the clinical management is poor, so the study aimed to clarify the mechanism of muscle wasting to better screen patients with gastric cancer cachexia. Gastric cancer patients undergoing radical gastrectomy were divided into cachexia with sarcopenia (CS, n = 13) and normal (N, n = 10) two groups. The possible mechanism of skeletal muscle reduction was explored through Tandem Mass Tag (TMT) technique, Perls staining, Western blot analysis and measurement of oxidative stress indicators. The preoperative weight, weight loss, body mass index, calorie intake and skeletal muscle index values of the CS group were significantly lower than those of the N group (P < 0.05). We identified 114 differentially expressed proteins (DEP) in the muscles of two groups using TMT analysis. Bioinformatics analysis of DEP revealed that ferritin, iron and oxidative stress may be related to skeletal muscle consumption. Following Perls staining and measurement iron concentration in skeletal muscles, we found that the iron in the muscles of the CS group was significantly increased, and at the same time, western blot analysis showed that the expression of ferritin in the CS group was significantly increased and regulated by hepcidin-ferroportin axis. Finally, the CS group showed increased oxidative stress and weakened antioxidant stress systems in the muscles compared with the N group when oxidative stress indicators were analyzed. In conclusion, iron overload may be related to muscle loss in patients with gastric cancer cachexia. Gastric cancer patients with elevated ferritin are more likely to have muscle wasting. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine. [ABSTRACT FROM AUTHOR]

Due to the backscattered parasitic current from the barriers, the current gain of the widely used amplifier is far from ideal. In this work, we demonstrate a vertical Au/Al2O3/BP/MoS2 tunneling hot-electron transfer amplifier with a hot-electron emitter-base junction and a p-n junction as the base-collector barrier. Fairly monoenergetic electrons traverse through the ultrathin Al2O3 dielectric via tunneling, which are accelerated and shifted to the collector region. The devices exhibit a high current on-off ratio of > 105 and a high current density (JC) of ∼ 1,000 A/cm2 at the same time. Notably, this work demonstrates a common-emitter current gain (β) value of 1,384 with a nanowatt power consumption at room temperature, which is a record high value among the all 2D based hot-electron transistors. Furthermore, the temperature dependent performance is investigated, and the β value of 1,613 is obtained at 150 K. Therefore, this work presents the potential of 2D based transistors for high-performance applications. [ABSTRACT FROM AUTHOR]

Purpose: BRCA1 and BRCA2 ( BRCA1/2) are two major high-penetrance breast cancer predisposition genes, mutations in which can lead to high risks and early onset of breast cancer. This study was performed to comprehensively investigate the spectrum and prevalence of BRCA1/2 mutations in unselected Chinese breast cancer patients and evaluate the associations of BRCA1/2 mutations with related clinicopathological characteristics of the tumors. Methods: By integrating microfluidic PCR-based target enrichment and next-generation sequencing, paired tumor and normal tissues from 313 unselected breast cancer patients were analyzed for both germline and somatic mutations of BRCA1/2 genes in Chinese Han population. Results: Total 5 BRCA1 and 8 BRCA2 deleterious germline mutations were detected in 5 (1.60%) and 12 (3.83%) of the 313 patients, respectively. The entire frequency of deleterious germline mutations of BRCA1/2 was 5.43%. Among them, c.1069A > T and c.3418_3419insTGACTACT in BRCA1, c.8474_8487delCATACCCTATACAG and c.6547delG in BRCA2 were novel. In addition, 32 germline variants of unknown significance in 31 (9.90%) of the 313 patients were identified. We also detected 13 somatic mutations in ten patients (3.19%), including 4 (1.28%) deleterious mutations (c.1575delT, c.2677C > T, c.7024C > T, and c.7672G > T in BRCA2) and 5 novel mutations (c.4728A > G and c.4820T > C in BRCA1; c.2527G > A, c.4069C > G and c.7672G > T in BRCA2). Notably, BRCA1 mutation carriers were significantly younger, and more likely to be ER negative and basal-like breast cancers. Conclusions: Our study provided a reliable and effective platform for BRCA1/2 genetic testing, and suggested that there was a relatively high prevalence and special spectrum of BRCA1/2 mutations in unselected Chinese breast cancer patients. [ABSTRACT FROM AUTHOR]

Multi-model switching controllers can handle the complexity of process plants and other engineered systems, based on the switched system model. In this paper, a switched Nonlinear Auto Regressive Moving Average eXogenous (NARMAX) model for a continuously mechatronic servo turntable system is proposed to make a better description than the single structure model. Then the identification issue is converted into a constrained multiobjective optimization problem (CMOP). Further, a kind of multi-objective particle swarm optimization algorithm is developed on the basis of Pareto optimality. The selection of global best location for each particle and the maintenance of the external archive are ensured in the same procedure in this algorithm. Finally, our theoretical findings are supported by simulation and experimental results. [ABSTRACT FROM AUTHOR]

Purpose: Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance.Methods: The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed.Results: The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors.Conclusions: Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

Aspergillus niger is an effective secretor of glycoside hydrolases that facilitate the saprophytic lifestyle of the fungus by degrading plant cell wall polysaccharides. In the present study, a series of dynamic zymography assays were applied to quantify the secreted glycoside hydrolases of A. niger cultured in media containing different carbon sources. Differences in the diversity and concentrations of polysaccharide hydrolysates dynamically regulated the secretion of glycoside hydrolases. The secretion of β-1,4-endoglucanase isozymes was observed to lag at least 24 h behind, rather than coincide with, the secretion of xylanase isozymes. Low concentrations of xylose could induce many endoxylanases (such as Xyn1/XynA, Xyn2, and Xyn3/XynB). High concentrations of xylose could sustain the induction of Xyn2 and Xyn3/XynB but repress Xyn1/XynA (GH10 endoxylanase), which has a broad substrate specificity, and also triggers the low-level secretion of Egl3/EglA, which also has a broad substrate specificity. Mixed polysaccharide hydrolysates sustained the induction of Egl1, whereas the other β-1,4-endoglucanases were sustainably induced by the specific polysaccharide hydrolysates released during the hydrolysis process (such as Egl2 and Egl4). These results indicate that the secretion of glycoside hydrolases may be specifically regulated by the production of polysaccharide hydrolysates released during the process of biomass degradation. [ABSTRACT FROM AUTHOR]

Purpose: To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer. Methods: A total of forty cases with advanced gastric cancer of T3-4N1-2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed. Results: The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent ( P = 0.033, P = 0.025) and pathologic remission extent ( P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better. Conclusions: From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the antitumor effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on human Bel7402 hepatocarcinoma in vitro and in vivo, with preliminary exploration of its antitumor mechanism.Methods: MTT was used to observe the anticarcinogenic effects of YSL on human hepatocarcinoma Bel7402 cells in vitro. The ultrastructure of tumor cells was observed by electron microscopy. Nude mice bearing xenografts of human hepatocarcinoma Bel7402 were given daily i.p. injections of YSL or saline and an admixture of amino acids as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. The effects of YSL on the cell cycle and apoptosis of Bel7402 cells were determined by flow cytometry, and the effects on the ultrastructure of the cells by electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and proliferating-cell nuclear antigen (PCNA) immunohistochemical staining were used to investigate apoptosis in tumor tissue in nude mice.Results: In vitro YSL inhibited the proliferation of human Bel7402 tumor cells and changed their ultrastructure, resulting in the necrosis and apoptosis of the tumor cells. YSL at 80, 160, or 320 microg/kg/d inhibited tumor growth in nude mice by 40.26, 64.17, and 59.19%, respectively, which are significantly lower than the inhibition exerted by saline and an admixture of YSL amino acids (P<0.05). The ultrastructure and cell cycle of human hepatocarcinoma Bel7402 cells were changed by treatment with YSL, with a rate of apoptosis higher than that of the control group. TUNEL and PCNA analysis showed that YSL inhibited the proliferation of tumor cells and induced apoptosis at the level of the cell.Conclusions: YSL significantly inhibited human hepatocarcinoma Bel7402 growth in vitro and in vivo. The growth inhibition of the tumor may involve necrosis and apoptosis of the tumor induced by YSL. [ABSTRACT FROM AUTHOR]

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg-kg-1 · d-1, 160 μg·kg-1 ·d-1 and 320 μg · kg-1 · d-1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h ( P< 0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model. [ABSTRACT FROM AUTHOR]

Immune response and protective efficacy for the combination of four tuberculosis DNA vaccines were evaluated in this study. We obtained 1: 200 antibody titers against Ag85B 21d after mice were vaccinated for the first time by four recombinant eukaryotic expression vectors containing coding sequences for Ag85B, MPT-64, MPT-63 and ESAT-6. The titers of Ag85B were elevated to 1: 102400 after the second injection and decreased to 1: 12800 after the third injection. Antibody titers for MPT-64 and MPT-63 reached 1: 25600 21 d after the first vaccination, and were then decreased following the second and third injections. No antigen-specific antibody titer against ESAT-6 was detected in sera harvested from immunized mice at any time. These DNA vaccines evoked specific IFN-γ responses in the spleens of vaccinated mice as well. When challenged with M. tuberculosis H37Rv, we found that the lungs of the vaccinated mice produced 99.8% less bacterial counts than that of the empty-vector control group and the bacterial counts were also significantly less than that of the BCG group. Histopathological analyses showed that the lungs of vaccinated mice produced no obvious caseation while over 50%-70% of the pulmonary parenchyma tissue produced central caseation in the vector control group. Our results indicated that the combination of four tuberculosis DNA vaccines may generate high levels of immune responses and result in better animal protection. [ABSTRACT FROM AUTHOR]

Reports the cloning of coding regions of Ag85B MPT-64, and ESAT-6 secreted proteins. Insertion into the eukaryotic expression vector pJW4303, then transformed to E. coli Top 10 strain for plasmid DNA extraction; Sequencing of plasmids containing the right insertion to confirm their identity; Indication COS7 cells were transfected with a mixture containing serially diluted plasmid DNA encoding three secreted proteins and Lipofectin (Gibco); Preparation of the supernatants and pellets from various cell lines that ran on SDS-PAGE gel; The expression of these proteins in COS7 cells shown by immunoblot using polyclonal or monoclonal antiserum of M.TBH37Rv. 21 days after first vaccination of C57BL-6 mice; The antibody titer for Ag85B 21 days after second vaccination; Assertion that the highest antibody levels induced by multivalent vaccines after the second injection are equal to or greater than the highest levels of single DNA vaccine after third injections; Antibody titer of MPT-64 after the first and second injections; Finding of no antigen-specific antibody against ESAT-6 in sera harvested from immunized mice 21 days after both injections; Antigen-specific IFN-γ level of Ag85B; Detection of no antigen-specific IFN-γ level of ESAT-6 and MPT-64 even after third injections; Idea that this is the first time studies of polyvalent recombinant DNA vaccines against TB were carried out in C57BL-6 mice; Implication for multiple DNA vaccines to enhance protective responses against M.TB.

The affiliation numbers of the authors were unfortunately misplaced on the first page and the first page of the ESM. Instead of Xu Zhao1,§ (✉), Peng Chen1,2,§, Xingqiang Liu2 (✉), Guoli Li2, Xuming Zou2, Yuan Liu2, Qilong Wu2, Yufang Liu1 (✉), Woo Jong Yu3, and Lei Liao21Key Laboratory for Micro/Nano Optoelectronic Devices of Ministry of Education & Hunan Provincial Key Laboratory of Low-Dimensional Structural Physics and Devices, School of Physics and Electronics, Changsha 410082, China 2Henan Normal University, School of Physics, Xinxiang 453007, China 3Department of Electronic and Electrical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea §Xu Zhao and Peng Chen contributed equally to this work. It should read Xu Zhao1,2,§ (✉), Peng Chen1,2,§, Xingqiang Liu1 (✉), Guoli Li1, Xuming Zou1, Yuan Liu1, Qilong Wu1, Yufang Liu2 (✉), Woo Jong Yu3, and Lei Liao11Key Laboratory for Micro/Nano Optoelectronic Devices of Ministry of Education & Hunan Provincial Key Laboratory of Low-Dimensional Structural Physics and Devices, School of Physics and Electronics, Changsha 410082, China 2Henan Normal University, School of Physics, Xinxiang 453007, China 3Department of Electronic and Electrical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea §Xu Zhao and Peng Chen and contributed equally to this work. [ABSTRACT FROM AUTHOR]