Effect of the Laser Cladding Parameters on Microstructure and Elevated Temperature Wear of FeCrNiTiZr Coatings.

In order to prepare coating with good friction and wear resistance at elevated temperature on the surface of hot-working tool steel, by using a CO2 laser, FeCrNiTiZr high-entropy alloy coating with different laser scanning speeds (360, 480 and 600 mm/min, respectively) was successfully fabricated by using laser cladding technology on the surface of H13 steel in this paper. Phase constitutions, microhardness, microstructure, and wear characteristics of FeCrNiTiZr coatings under different laser scanning speeds were analyzed. It was determined that 480 mm/min was the optimal laser scanning speed. The results showed that the coating at the scanning speed of 480 mm/min consists of a BCC phase with significant lattice distortion and high dislocation density; the crystal structure is cellular crystal and dendrite crystal. The coating demonstrates the highest microhardness (842 HV0.2), which is 4.2 times that of the substrate (200 HV0.2). Its average friction coefficients at room temperature and 823 K are approximately one-seventh and one-third of the substrate's, respectively, and its wear volume is reduced by about 98% and 81% under these conditions. Compared to the substrate, the coating underwent slight abrasive wear, adhesive wear, and oxidative wear at both room temperature and 823 K. In contrast, the substrate underwent severe abrasive wear, adhesive wear, oxidative wear, and even fatigue wear.

Development of semicircular canal occlusion.

Surgical treatment of vertigo is performed with in-depth study of inner ear diseases. Achieving an effective control of vertigo symptoms while reducing damage to hearing and reducing surgical complications is the principle followed by scholars studying surgical modalities. Semicircular canal occlusion is aimed at treatment of partial peripheral vertigo disease and has attracted the attention of scholars because of the above advantages. This article provides a review of the origins of semicircular canal occlusion, related basic research, clinical applications, and the effects of surgery on vestibular and hearing function.

Fully automated magnetically controlled capsule endoscopy for examination of the stomach and small bowel: a prospective, feasibility, two-centre study.

BACKGROUND: The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. METHODS: We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18-80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. FINDINGS: Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0-55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3-100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45-99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00-20·00), compared with 5·21 min (2·00; 5·18, 3·68-6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. INTERPRETATION: The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. FUNDING: Chinese National Key Research and Development Program.

Microfluidics sorting enables the isolation of an intact cellular pair complex of CD8+ T cells and antigen-presenting cells in a cognate antigen recognition-dependent manner.

Adaptive immune responses begin with cognate antigen presentation-dependent specific interaction between T cells and antigen-presenting cells. However, there have been limited reports on the isolation and analysis of these cellular complexes of T cell-antigen-presenting cell (T/APC). In this study, we successfully isolated intact antigen-specific cellular complexes of CD8+ T/APC by utilizing a microfluidics cell sorter. Using ovalbumin (OVA) model antigen and OT-I-derived OVA-specific CD8+ T cells, we analyzed the formation of antigen-specific and antigen-non-specific T/APC cellular complexes and revealed that the antigen-specific T/APC cellular complex was highly stable than the non-specific one, and that the intact antigen-specific T/APC complex can be retrieved as well as enriched using a microfluidics sorter, but not a conventional cell sorter. The single T/APC cellular complex obtained can be further analyzed for the sequences of T cell receptor Vα and Vß genes as well as cognate antigen information simultaneously. These results suggested that this approach can be applied for other antigen and CD8+ T cells of mice and possibly those of humans. We believe that this microfluidics sorting method of the T/APC complex will provide useful information for future T cell immunology research.

Diverse regulatory manners of human telomerase reverse transcriptase.

Human telomerase reverse transcriptase (hTERT) is the core subunit of human telomerase and plays important roles in human cancers. Aberrant expression of hTERT is closely associated with tumorigenesis, cancer cell stemness maintaining, cell proliferation, apoptosis inhibition, senescence evasion and metastasis. The molecular basis of hTERT regulation is highly complicated and consists of various layers. A deep and full-scale comprehension of the regulatory mechanisms of hTERT is pivotal in understanding the pathogenesis and searching for therapeutic approaches. In this review, we summarize the recent advances regarding the diverse regulatory mechanisms of hTERT, including the transcriptional (promoter mutation, promoter region methylation and histone acetylation), post-transcriptional (mRNA alternative splicing and non-coding RNAs) and post-translational levels (phosphorylation and ubiquitination), which may provide novel perspectives for further translational diagnosis or therapeutic strategies targeting hTERT.

Circular incision and cutting, a novel treatment for patients with esophageal cancer with anastomotic stricture after esophagectomy.

OBJECTIVE: Endoscopic balloon dilation (EBD) is still considered the standard treatment for patients with anastomotic strictures after esophagectomy. However, repeated dilation sessions are often required to maintain the lumen patency. We therefore developed a novel method called circular incision and cutting (CIC) and compared the efficacy of CIC and EBD among patients with anastomotic strictures after esophagectomy or gastrectomy. METHODS: In this retrospective study, 71 consecutive patients with esophageal cancer with anastomotic strictures after esophagectomy or gastrectomy between January 2011 and December 2016 were included. Among them, 22 patients received CIC therapy and 49 were treated with EBD. RESULTS: The dysphagia in all patients immediately ameliorated and no serious adverse events requiring further intervention were observed after CIC therapy. Compared with EBD, CIC exhibited a greater score in the difference of dysphagia before and after treatment (1.73 vs 1.16, P = 0.03). Moreover, the interval of restenosis and 6-month lumen patency in CIC had a better effect than that in EBD (88.07 days vs 62.76 days, P = 0.001; dysphagia score 0.63 vs 1.44, P = 0.007). CONCLUSION: The CIC method may be an effective and safe option for patients with esophageal cancer with anastomotic strictures after esophagectomy.

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy.

Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.

Magnetic Gold Nanoparticle-Labeled Heparanase Monoclonal Antibody and its Subsequent Application for Tumor Magnetic Resonance Imaging.

Heparanase (HPA) is ubiquitously expressed in various metastatic malignant tumors; previous studies have demonstrated that HPA was a potential tumor-associated antigen (TAA) for tumor immunotherapy. We sought to evaluate the feasibility of HPA as a common TAA for magnetic resonance imaging (MRI) of tumor metastasis and its potential application in tumor molecular imaging. We prepared a targeted probe based on magnetic gold nanoparticles coupled with an anti-HPA antibody for the specific detection of HPA by MRI. The specificity of the targeted probe was validated in vitro by incubation of the probe with various tumor cells, and the probe was able to selectively detect HPA (+) cells. We found the probes displayed significantly reduced signal intensity in several tumor cells, and the signal intensity decreased significantly after the targeted probe was injected in tumor-bearing nude mice. In the study, we demonstrated that the HPA&GoldMag probe had excellent physical and chemical properties and immune activities and could specifically target many tumor cell tissues both in vitro and in vivo. This may provide an experimental base for molecular imaging of tumor highly expressing heparanase using HPA mAbs.

hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation.

BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) plays an important role in cancer invasion, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. DESIGN: Proteomics analysis, qPCR and western blotting were used to screen for hTERT-regulated candidate molecules in gastric cancer invasion. Chromatin immunoprecipitation (ChIP) qPCR was performed to identify the binding sites of hTERT at the regulatory region of the integrin ß1 (ITGB1) gene. ChIP assays were further applied to elucidate the transcription factors that bound to the regulatory region. The interactions between hTERT and the transcription factors were tested by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down experiments. Moreover, the revealed pathway was verified in tumour-bearing nude mice and human gastric cancer tissues. RESULTS: ITGB1 was identified as a downstream gene of hTERT, and there were two hTERT-binding regions within this gene. hTERT alleviated the binding of forkhead box O3 (FOXO3a) to FOXO3a binding element (+9972∼+9978), but it enhanced the binding of forkhead box M1 (FOXM1) to FOXM1 binding element (-1104∼-1109) in ITGB1 gene. Importantly, FOXO3a played a major role in hTERT-induced ITGB1 expression, and the hTERT/murine double minute 2 (MDM2) complex promoted the ubiquitin-mediated degradation of FOXO3a. Moreover, hTERT increased ITGB1 expression in xenograft gastric cancer, and the level of hTERT was positively correlated with that of ITGB1 in human gastric cancer tissues. CONCLUSIONS: The hTERT/MDM2-FOXO3a-ITGB1 pathway markedly contributes to hTERT-promoted gastric cancer invasion, suggesting that this pathway might be a novel target for the prevention and treatment of gastric cancer metastasis.

Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression.

Gastric cancer is one of the leading causes of tumor-related deaths in the world. Current treatment options do not satisfy doctors and patients, and new therapies are therefore needed. Cerium oxide nanoparticles (CNPs) have been studied as a potential therapeutic approach for treating many diseases. However, their effects on human gastric cancer are currently unknown. Therefore, in this study, we aimed to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and BGC823). Gastric cancer cells were cocultured with different concentrations of CNPs, and proliferation and migration were measured both in vitro and in vivo. We found that CNPs inhibited the migration of gastric cancer cells when applied at different concentrations, but only a relatively high concentration (10 µg/mL) of CNPs suppressed proliferation. Furthermore, we found that CNPs increased the expression of DHX15 and its downstream signaling pathways. We therefore provide evidence showing that CNPs may be a promising approach to suppress malignant activity of gastric cancer by increasing the expression of DHX15.

Peptide-Based Treatment: A Promising Cancer Therapy.

Many new therapies are currently being used to treat cancer. Among these new methods, chemotherapy based on peptides has been of great interest due to the unique advantages of peptides, such as a low molecular weight, the ability to specifically target tumor cells, and low toxicity in normal tissues. In treating cancer, peptide-based chemotherapy can be mainly divided into three types, peptide-alone therapy, peptide vaccines, and peptide-conjugated nanomaterials. Peptide-alone therapy may specifically enhance the immune system's response to kill tumor cells. Peptide-based vaccines have been used in advanced cancers to improve patients' overall survival. Additionally, the combination of peptides with nanomaterials expands the therapeutic ability of peptides to treat cancer by enhancing drug delivery and sensitivity. In this review, we mainly focus on the new advances in the application of peptides in treating cancer in recent years, including diagnosis, treatment, and prognosis.

Preparation of Stabilizer-Free Silver Nanoparticle-Coated Micropipettes as Surface-Enhanced Raman Scattering Substrate for Single Cell Detection.

In this work, we established a convenient while reproduceable method for stabilizer-free silver nanoparticle (AgNP)-coated micropipettes by the combination of magnetron sputtering and surface coupling agent. The clear surfaces of the AgNPs are beneficial for absorbing biological or functional molecules on their surfaces. By optimizing the operating parameters, such as sputtering current and sputtering time, the tip of micropipettes coated with AgNPs exhibits excellent surface-enhanced Raman scattering (SERS) performance. Finally, the Raman spectra of a single A549 lung adenocarcinoma cell are successfully acquired by these advanced SERS-active micropipettes.

Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.

Antifatigue properties of dragonfly Pantala flavescens wings.

The wing of a dragonfly is thin and light, but can bear high frequent alternating stress and present excellent antifatigue properties. The surface morphology and microstructure of the wings of dragonfly Pantala flavescens were observed using SEM in this study. Based on the biological analysis method, the configuration, morphology, and structure of the vein were studied, and the antifatigue properties of the wings were investigated. The analytical results indicated that the longitudinal veins, cross veins, and membrane of dragonfly wing form a optimized network morphology and spacially truss-like structure which can restrain the formation and propagation of the fatigue cracks. The veins with multilayer structure present high strength, flexibility, and toughness, which are beneficial to bear alternating load during the flight of dragonfly. Through tensile-tensile fatigue failure tests, the results were verified and indicate that the wings of dragonfly P. flavescens have excellent antifatigue properties which are the results of the biological coupling and synergistic effect of morphological and structural factors.

[Akt involved in diazoxide preconditioning against rat hippocampal neuronal apoptosis induced by anoxia-reoxygenation injury].

OBJECTIVE: Investigate whether preconditioning with diazoxide (DZ), a mitochondrial ATP-sensitive potassium channel opener, could enhance Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis. METHODS: Cultured for 9 - 10 d in vitro, the hippocampal neurons of Sprague-Dawley rats were assigned to the following 5 groups randomly: Control (Group A), Anoxia (Group B), Anoxia + DZ100 micromol/L (Group C), Anoxia + DZ100 micromol/L + 5-hydroxydecanoate (Group D), Anoxia + DZ100 micromol/L + LY294002 50 micromol/L (Group E). Prior to oxygen deprivation, the hippocampal neurons were treated with DZ for 1 h per day and this treatment was persisted for 3 d. Each experiment was repeated for three times and each group contained 16 wells or 2 dishes of neurons for each time. Thereafter, neurons were derived of oxygen for 4 h. At 48 h of reoxygenation the neuronal optical density (A) were measured by MTT method, while the apoptotic rates were assayed by annexin V-FITC staining. The expressions of Akt, Bcl-2 and Bax proteins were detected and evaluated by Western blot. RESULTS: Compared with other pretreatment, DZ 100 micromol/L led to the elevation of A, whereas promoted the decrease of apoptotic rate (P < 0.05). Compared with those in other anoxic groups, the expressions of Akt protein and Bcl-2 protein in Group C were increased significantly (P < 0.05), whereas the Bax density were reduced significantly (P < 0.05). Preceding administration of 100 micromol/L DZ took protective effects on the neurons induced by anoxia-reoxygenation. CONCLUSIONS: DZ 100 micromol/L increased Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis induced by anoxia-reoxygenation.

HMGB1: A new marker for estimation of the postmortem interval.

Estimation of the postmortem interval (PMI) is one of the most important tasks in forensic medicine. Numerous methods have been proposed for the determination of the time since death by chemical means. High mobility group box-1 (HMGB1), a nonhistone DNA-binding protein is released by eukaryotic cells upon necrosis. Postmortem serum levels of HMGB1 of 90 male Wistar rats stored at 4, 14 and 24°C since death were measured by enzyme-linked immunosorbent assay. The serum HMGB1 level showed a time-dependent increase up to seven days at 4°C. At 14°C, the HMGB1 level peaked at day 3, decreased at day 4, and then plateaued. At 24°C, the HMGB1 level peaked at day 2, decreased at day 3, and then plateaued. Our findings suggest that HMGB1 is related to the PMI in rats.

C-reactive protein induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells.

BACKGROUND: C-reactive protein (CRP) is widely used as a sensitive biomarker for inflammation. Increasing evidence suggests that CRP plays a role in inflammation. High-mobility group box-1 (HMGB1), a primarily nuclear protein, is passively released into the extracellular milieu by necrotic or damaged cells and is actively secreted by monocytes/macrophages. Extracellular HMGB1 as a potent inflammatory mediator has stimulated immense curiosity in the field of inflammation research. However, the molecular dialogue implicated between CRP and HMGB1 in delayed inflammatory processes remains to be explored. METHODS AND RESULTS: The levels of HMGB1 in culture supernatants were determined by Western blot analysis and enzyme-linked immunosorbent assay in macrophage RAW264.7 cells. Purified CRP induced the release of HMGB1 in a dose- and time-dependent fashion. Immunofluorescence analysis revealed nuclear translocation of HMGB1 in response to CRP. The binding of CRP to the Fc gamma receptor in RAW264.7 cells was confirmed by fluorescence-activated cell sorter analysis. Pretreatment of cells with IgG-Fc fragment, but not IgG-Fab fragment, efficiently blocked this binding. CRP triggered the activation of p38MAPK and ERK1/2, but not Jun N-terminal kinase. Moreover, both p38MAPK inhibitor SB203580 and small interfering RNA significantly suppressed the release of HMGB1, but not the MEK1/2 inhibitor U-0126. CONCLUSION: We demonstrated for the first time that CRP, a prominent risk marker for inflammation including atherosclerosis, could induce the active release of HMGB1 by RAW264.7 cells through Fc gamma receptor/p38MAPK signaling pathways, thus implying that CRP plays a crucial role in the induction, amplification, and prolongation of inflammatory processes, including atherosclerotic lesions.

Pharmacological activity of cardiovascular agents from herbal medicine.

Some of the active phytochemicals in herbal medicine are finding therapeutic use. For example, patients with heart disease are reported to benefit from treatment with herbal medicine with fewer side effects. Previous studies showed the inhibitory effects of tetramethylpyrazine, an active component of medicinal herb, on phosphodiesterase that is associated with heart disease and the cardio-protective effects of other herbal medicine that was used to protect ischemia-reperfusion injury of rat hearts. Individual herbal medicines show antipyretic, analgesic and anti-inflammatory and anti-cancer effects. In addition to sharing many therapeutic activities, the active components of herbal medicine are also used in nutrient supplement for cardiovascular disease. Numerous in vitro studies of herbal medicine on different cell lines and in vivo study of herbal medicine have been reported. However, the mechanism of actions remains unclear. The present review aims to give an overview of the recent development of herbal medicine in treatment of cardiovascular disease, and covers the possible mechanism of action of some of active principles. The study will provide insights into drug action and demonstrate the therapeutic benefits of herbal medicine for the treatment of cardiovascular disease.

Effect of transgenic expression of porcine interleukin-6 gene and CpG sequences on immune responses of newborn piglets inoculated with Pseudorabies attenuated vaccine.

Porcine interleukin-6 gene and CpG sequences were used as immunoadjuvants to enhance the immune responses of newborn piglets to Pseudorabies attenuated vaccine (PAV). The titer of specific antibodies to PAV, the proliferation of lymphocytes and induced IL-2 activities were all examined to identify the immune response of the piglets. The results showed that the immune responses with CpG ODN and porcine interleukin-6 gene were significantly stronger than routine immunities. The data suggests that porcine IL-6 and CpG motifs could be employed as effective immunoadjuvants to raise the humoral and cellular responses of newborn piglets to Pseudorabies attenuated vaccine.