Study on the Influence of Surface Treatment Process on the Corrosion Resistance of Aluminum Alloy Profile Coating.

This work focuses on different surface treatment processes of the 6061 aluminum alloy profile coatings in the construction industry, mainly including the sand powder film coating, the flat powder coating, the hard anodized film, and the ordinary heat-sealing oxidized coating. The corrosion resistance of the coated aluminum alloy in a 3.5 wt.% NaCl solution (pH 6.5-7.5) and the influence of different surface treatment processes on the corrosion resistance of different samples were studied by scanning electron microscope (SEM) and electrochemical workstation. The result shows that with the increase in corrosion time, the corrosion inhibition performance of the four coated aluminum alloy materials decreased significantly, and the order of decline is: sand powder film coating > hard anodized film > flat powder coating > ordinary heat-sealing oxidized coating. When corroded in a 3.5 wt.% NaCl solution for 2 h, the corrosion inhibition performances of the flat powder coating and ordinary heat-sealing oxidized coating are poor, while the inhibition performances of the sand powder film coating and hard anodized film are good, and the inhibition performance follows the following sequence: the sand powder film coating > hard anodized film> the flat powder coating > ordinary heat-sealing oxidized coating. When corroded in a 3.5 wt.% NaCl solution for 200 h, the corrosion inhibition performances of the sand powder film coating and the flat powder coating are poor, while the inhibition performances of hard anodized film and ordinary heat-sealing oxidized coating are good, and the inhibition performance follows the following sequence: hard anodized film > ordinary heat-sealing oxidized coating > the sand powder film coating > the flat powder coating.

Genome editing mRNA nanotherapies inhibit cervical cancer progression and regulate the immunosuppressive microenvironment for adoptive T-cell therapy.

CRISPR/Cas9-based genome editing is promising for therapy of cervical cancer by precisely targeting human papillomavirus (HPV). To develop CRISPR/Cas9-based genome editing nanotherapies, a pH-responsive hybrid nonviral nanovector was constructed for co-delivering Cas9 mRNA and guide RNAs (gRNAs) targeting E6 or E7 oncogenes. The pH-responsive nanovector was fabricated using an acetalated cyclic oligosaccharide (ACD), in combination with low molecular weight polyethyleneimine. Thus obtained hybrid ACD nanoparticles (defined as ACD NP) showed efficient loading for both Cas9 mRNA and E6 or E7 gRNA, giving rise to two pH-responsive genome editing nanotherapies E6/ACD NP and E7/ACD NP, respectively. Cellularly, ACD NP exhibited high transfection but low cytotoxicity in HeLa cervical carcinoma cells. Also, efficient genome editing of target genes was achieved in HeLa cells, with minimal off-target effects. In mice bearing HeLa xenografts, treatment with E6/ACD NP or E7/ACD NP afforded effective editing of target oncogenes and considerable antitumor activities. More importantly, treatment with E6/ACD NP or E7/ACD NP notably promoted CD8+ T cell survival by reversing the immunosuppressive microenvironment, thereby leading to synergistic antitumor effects by combination therapy using the gene editing nanotherapies and adoptive T-cell transfer. Consequently, our pH-responsive genome editing nanotherapies deserve further development for the treatment of HPV-associated cervical cancer, and they can also serve as promising nanotherapies to improve efficacies of other immune therapies against different advanced cancers by regulating the immunosuppressive tumor microenvironment.

One-Pot Structure-Controlled Synthesis of Hyperbranched Polymers by a "Latent" Inimer Strategy Based on Diels-Alder Chemistry.

An efficient "one-pot" strategy for the structure-controlled synthesis of hyperbranched polymers (HBPs) based on a "latent" inimer (LI-Br), containing a furan-protected maleimide monomer and a haloalkane initiator, is presented. At high temperatures, the "latent" inimer is converted to a "real" inimer after releasing maleimide (MI) via a retro-Diels-Alder (r-DA) reaction and then copolymerized with methyl methacrylate by self-condensing vinyl copolymerization. Due to the dynamic characteristic of the r-DA reaction, the release of naked MI and the subsequent copolymerization can be regulated by the temperature or stereochemistry of Diels-Alder (DA) adducts. Thus, the "one-pot" structure-controlled synthesis of HBPs with various degrees of branching was achieved. By further implementation of a programmable temperature change, some valuable hyperbranched topologies such as star-shaped and long-chain hyperbranched polymers can be constructed avoiding sophisticated synthetic routes.

Research Value of Intensity Modulated Radiation Therapy in Alleviating Parotid Gland Function Injury in Patients with Stage N0 Nasopharyngeal Carcinoma from Physical and Dosimetric Aspects.

Objective: To study the feasibility of intensity modulated radiation therapy (IMRT) for stage N0 nasopharyngeal carcinoma (NPC) and its parotid gland (PG) function preservation from physical and dosimetric aspects. Methods: All the clinical data of 77 patients with pathologically confirmed T1-4N0M0 NPC who received radiotherapy between July 2017 and October 2019 in the Radiotherapy Center of Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University were analyzed retrospectively. Three-dimensional conformal radiotherapy (3D-CRT) and IMRT were used in 35 and 42 cases, respectively. The treatment efficiency and the dosimetry differences of the PG in the intensity modulation plan were compared between groups. Quantitative monitoring of 99mTc radionuclide imaging of PG was performed before, at the end of, and 3, 6, and 12 months after radiotherapy. The degree of PG function injury and xerostomia was compared between groups at the end of radiotherapy and 12 months later. Results: Higher minimal, maximal, and average irradiation doses of PG were determined in 3D-CRT-treated patients compared with IMRT-treated cases (P < 0.05). Compared with before radiotherapy, the PG uptake index (UI) and excretion index (EI) of both cohorts of patients decreased to varying degrees at the end of radiotherapy, with PG function injury and xerostomia symptoms observed in all cases but with no obvious difference between groups (P > 0.05). To a certain extent, the PG function recovered and the xerostomia symptoms relieved in both groups 12 months after radiotherapy, with better improvements in IMRT group versus 3D-CRT group. Conclusion: IMRT has similar short-term efficacy to 3D-CRT in treating patients with stage N0 NPC, but it can effectively reduce the dose of PG radiotherapy and protect the PG function on the premise of ensuring sufficient tumor coverage and dose, showing certain dosimetry advantages.

Postoperative Examination of Laryngeal Malignant Tumor Based on Narrowband Imaging Resolution Enhancement Technology.

The application of endoscopic imaging in the biopsy of malignant laryngeal lesions is one of the current research hotspots in the medical field. Based on the narrowband imaging resolution enhancement technology, a model for postoperative examination of laryngeal malignant tumor was constructed in this paper. The article calculated the biopsy detection rate of malignant lesions and the correct biopsy detection rate of the two groups and made a statistical comparison. In the NBI mode group, the mucosal morphology and superficial mucosal microvascular morphology of the same lesion under two different modes of white light and NBI were compared, which solved the problem of data processing of cases. During the case comparison process, patients who needed biopsies to be sent for pathology were selected for inclusion in the study and were randomly divided into two groups. The coincidence rate of EUS combined with NBI diagnosis was significantly higher than that of ordinary white light gastroscopy (47.92%), and the difference was statistically significant (P=0.000 < 0.05). The experimental results compared the accuracy of the normal white light mode and the NBI mode to diagnose the nature of the lesions: according to the Kudo classification criteria, 23 cases of tumor lesions were to be diagnosed in the normal white light mode, with an accuracy rate of 69.70%, and the NBI mode was to be used to diagnose tumors. There were 81 cases of sexual lesions, with an accuracy rate of 93.94%. The NBI mode was more accurate in diagnosing the nature of the lesions under the Kudo classification standard (P < 0.05). In 64 cases, the accuracy rate was 63.63%. Under the NBI mode, 29 cases of tumor lesions were proposed to be diagnosed, and the accuracy rate was 87.88% to promote the application of NBI endoscopy in the biopsy of malignant laryngeal lesions.

Evaluation of the Effect of Nutritional Intervention on Patients with Nasopharyngeal Carcinoma.

Aim: The paper aims to combine mathematical statistics to assess the effect of nutritional intervention in the population of nasopharyngeal cancer patients. Methodology. After following the inclusion and exclusion criteria, a total of 120 patients with nasopharyngeal carcinoma were selected. All patients are treated with intensity-modulated radiotherapy (IMRT). The nurse collects relevant clinical treatment data during the radiotherapy of the patient. After the patient's radiotherapy, the nurse remeasures the patient's nutritional status indicators. Three months after the completion of radiotherapy, the patient will be reexamined by MRI, and the radiotherapist will assess the patient's radiosensitivity based on the results of the MRI examination. All the blood biochemical indicators and body measurement indicators were also assessed and coordinated with nasopharyngeal carcinoma patients. This study performs multiple linear regression analysis on treatment-related factors that affect nutritional status during radiotherapy. Results: The experimental results showed that the side effects of radiotherapy are independent influencing factors of nutritional status. Radiotherapy damages the DNA of cells, so that cells cannot continue to divide and grow, and all cells in the treatment area were affected by radiation. The standard radiotherapy treatment is quite long, and the oral cavity, throat, and parotid gland, are all within the irradiation range. In addition to killing the tumor cells, the radiation can also cause certain damage to the surrounding tissues of the tumor. This article takes radiosensitivity as the dependent variable (insensitivity = 0; sensitivity = 1) and takes the nutritional index NI, age, gender, education level, marriage, smoking, chronic disease history, TNM staging, whether the chemotherapy steps are the same or not, GTVnx prescription dose, and the number of radiotherapies as independent variables. AMC, albumin, hemoglobin, serum prealbumin, and transferrin are all correlated with radiosensitivity, which is consistent with the results of most studies. The results of multivariate logistic regression analysis showed that nutritional index (NI) was correlated with the radiosensitivity of nasopharyngeal carcinoma. Conclusion: Finally, this paper concludes that nutritional intervention has a certain effect on the treatment of patients with nasopharyngeal carcinoma.

Evaluating the efficacy of endoscopic sphincterotomy on biliary-type sphincter of Oddi dysfunction: A retrospective clinical trial.

BACKGROUND: Although endoscopic sphincterotomy (EST) has a positive therapeutic effect on biliary-type sphincter of Oddi dysfunction (SOD), some patients still have little relief after EST, which implies that other functional abdominal pain may also be present with biliary-type SOD and interfere with the diagnosis and treatment of it. AIM: To retrospectively assess EST as a treatment for biliary-type SOD and analyze the importance of functional gastrointestinal disorder (FGID) in guiding endoscopic treatment of SOD. METHODS: Clinical data of 79 patients with biliary-type SOD (type I and type II) treated with EST at Affiliated Hospital of Guizhou Medical University from January 2014 to January 2019 were retrospectively collected to evaluate the clinical therapeutic effect of EST. The significance of relationship between FGID and biliary-type SOD was analyzed. RESULTS: Seventy-nine patients with biliary-type SOD received EST, including 29 type 1 patients and 50 type 2 patients. The verbal rating scale-5 (VRS-5) scores before EST were all 3 or 4 points, and the scores decreased after EST; the difference was statistically significant (P < 0.05). After EST, the serum indexes of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin in biliary-type SOD were significantly lower than before (P < 0.05). After EST, 67 (84.8%) and 8 (10.1%) of the 79 patients with biliary-type SOD had obviously effective (VRS-5 = 0 points) and effective treatment (VRS-5 = 1-2 points), with an overall effectiveness rate of 94.9% (75/79). There was no difference in VRS-5 scores between biliary-type SOD patients with or without FGID before EST (P > 0.05). Of 12 biliary-type SOD (with FGID) patients, 11 had abdominal pain after EST; of 67 biliary-type SOD (without FGID) patients, 0 had abdominal pain after EST. The difference was statistically significant (P <0.05). The 11 biliary-type SOD (with FGID) patients with recurrence of symptoms, the recurrence time was about half a year after the EST, and the symptoms were significantly relieved after regular medical treatment. There were 4 cases of post-endoscopic retrograde cholangiopancreatography pancreatitis (5.1%), and no cholangitis, bleeding or perforation occurred. Patients were followed up for 1 year to 5 years after EST, with an average follow-up time of 2.34 years, and there were no long-term adverse events such as sphincter of Oddi restenosis or cholangitis caused by intestinal bile reflux during the follow-up. CONCLUSION: EST is a safe and effective treatment for SOD. For patients with type I and II SOD combined with FGID, single EST or medical treatment has limited efficacy. It is recommended that EST and medicine be combined to improve the cure rate of such patients.

Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer.

Given the heterogeneity of solid tumors, single-target CAR-T cell therapy often leads to recurrence, especially in ovarian cancer (OV). Here, we constructed a Tandem-CAR targeting two antigens with secretory activity (IL-12) to improve the effects of CAR-T cell therapy. Twenty coexpressed upregulated genes were identified from the GEO database, and we found FOLR1 (folate receptor 1) and MSLN (mesothelin) were specifically and highly expressed in cancer tissues and only 11.25% of samples were negative for both antigens. We observed an increased proliferation rate for these three CAR-T cells, and Tandem CAR-T cells could efficiently lyse antigen-positive OV cells in vitro and secrete higher levels of cytokines than single-target CAR-T cells. More importantly, in vivo experiments indicated that Tandem CAR-T cells markedly decreased tumor volume, exhibited enhanced antitumor activity, and prolonged mouse survival. Furthermore, the infiltration and persistence of T cells in the Tandem-CAR group were higher than those in the MSLN-CAR and Control-T groups but comparable to those in the FOLR1-CAR group. Collectively, this study demonstrated that Tandem CAR-T cells secreting IL-12 could enhance immunotherapeutic effects by reducing tumor antigen escape and increasing T cell functionality, which could be a promising therapeutic strategy for OV and other solid tumors.

Short-term ambient nitrogen dioxide exposure is associated with increased risk of spontaneous abortion: A hospital-based study.

There are increasing concerns with regard to spontaneous abortion (SAB), the loss of pregnancy without external intervention before 20 weeks of gestation, among reproductive-aged women. To date, limited evidence is available concerning the association between SAB and air pollutants, especially in developing countries. Daily baseline outpatient data for SAB from January 1, 2014, to December 31, 2018 (1826 days) were obtained in Chongqing, a metropolis of southwest China. The over-dispersed Poisson generalized additive model with control of meteorological conditions and day of week was used to estimate the short-term effects of ambient air pollution on the daily number of SAB outpatients. A total of 42,334 SAB outpatient visits for SAB were recorded. No statistically significant association was observed between SAB and CO, PM2.5, PM10, O3, and SO2. The positive association only appeared for NO2: positive associations between SAB and NO2 were observed in both single-day models (lag 0, lag 1, lag 3, and lag 4) and cumulative exposure models (lag 01, lag 03, and lag 05) and the most significant effects were observed at lag 05 (3.289%; 95% CI: 1.568%, 5.011%). Moreover, the women with higher ages (30-39 and > 39) were more sensitive than those with lower ages (18-29), and the effect estimates were more evident in cool seasons. Collectively, our results suggested that short-term NO2 exposure was associated with higher risk of SAB, especially in elder women and cool seasons, which may contribute to further understand the role of air pollution on SAB and other adverse obstetric outcomes.

Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis.

Leukemia stem cells (LSCs) and therapy-resistant acute myeloid leukemia (AML) blasts contribute to the reinitiation of leukemia after remission, necessitating therapeutic interventions that target these populations. Autophagy is a prosurvival process that allows for cells to adapt to a variety of stressors. Blocking autophagy pharmacologically by using mechanistically distinct inhibitors induced apoptosis and prevented colony formation in primary human AML cells. The most effective inhibitor, bafilomycin A1 (Baf A1), also prevented the in vivo maintenance of AML LSCs in NSG mice. To understand why Baf A1 exerted the most dramatic effects on LSC survival, we evaluated mitochondrial function. Baf A1 reduced mitochondrial respiration and stabilized PTEN-induced kinase-1 (PINK-1), which initiates autophagy of mitochondria (mitophagy). Interestingly, with the autophagy inhibitor chloroquine, levels of enhanced cell death and reduced mitochondrial respiration phenocopied the effects of Baf A1 only when cultured in hypoxic conditions that mimic the marrow microenvironment (1% O2). This indicates that increased efficacy of autophagy inhibitors in inducing AML cell death can be achieved by concurrently inducing mitochondrial damage and mitophagy (pharmacologically or by hypoxic induction) and blocking mitochondrial degradation. In addition, prolonged exposure of AML cells to hypoxia induced autophagic flux and reduced chemosensitivity to cytarabine (Ara-C), which was reversed by autophagy inhibition. The combination of Ara-C with Baf A1 also decreased tumor burden in vivo. These findings demonstrate that autophagy is critical for mitochondrial homeostasis and survival of AML cells in hypoxia and support the development of autophagy inhibitors as novel therapeutic agents for AML.

Optimized design to adverse transportation conditions for railway freight system.

This study proposed a method for transportation agencies to efficiently and accurately formulate or revise rules for the movement of railway transport while ensuring safety under adverse conditions. Determining such a method in general requires trial-and-error experimentation, which consumes large amounts of time and money. We used the uniform experiment (UE) and generalized linear autoregression (GLAR) to establish our method. Based on it, a series of numerical models were proposed to examine the association between the operational indices of safety (derailment coefficient and rate of wheel unloading) and such factors as the type of wagon, cargo weight, partial loading (covering longitudinal and lateral offset), line condition, and operating speed. The models were used to determine the worst transportation conditions. The results of analysis showed the following: 1) the effect of the speed of operation on the safety indices followed a parabolic law, those of cargo weight and part loading followed a linear law, the type of wagon and line condition exhibited no clear regularity, and some of these factors have an interactive influence. 2) A combination of the UE and GLAR helped deal with the complex multivariate process using the fewest multilevel experiments to accurately determine the most adverse conditions for railway freight transportation. The proposed method provided reference schemes for governmental agencies to study and revise freight management regulations.

Novel biallelic variants in COL7A1 cause recessive dystrophic epidermolysis bullosa.

BACKGROUND: Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is an incurable and severe inherited skin disorder characterized by recurrent blistering at the sublamina densa beneath the cutaneous basement membrane. It is caused by biallelic loss-of-function mutation in the gene encoding type VII collagen (COL7A1). This study aimed to identify the causative variants of a Chinese RDEB patient and further provide prenatal diagnosis for the ongoing risk pregnancy of the proband's mother. METHODS: Clinical exome sequencing (CES) has been performed and an in-house pipeline was used to conduct a phenotype-driven data analysis. A minigene assay was used to verify the pathogenicity of a novel splice site variant in the COL7A1. RESULTS: Here we report two compound heterozygous variants in COL7A1, c.3867delT (p.G1290Efs*35) and c.5532+4_5532+5delAG, identified in a RDEB patient by CES. The minigene assay confirmed that thec.5532+4_5532+5delAGchange was a noncanonic splice site variant leading to in an in-frame deletion of exon 64. Prenatal diagnosis indicated that the present pregnancy of the patient's mother was not affected. CONCLUSION: Our study expands the mutation spectrum of COL7A1 and demonstrated that CES and minigene assays were efficient tools for RDEB molecular diagnoses.

Gene Targeting of HPV18 E6 and E7 Synchronously by Nonviral Transfection of CRISPR/Cas9 System in Cervical Cancer.

High-risk human papillomavirus (HPV) E6 and E7 genes display vital oncogenic properties in cervical cancer. Eliminating HPV driver gene or loss of function by the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is a promising treatment for the HPV-associated cancer. Thus, this study designed a CRISPR/Cas9 system to target the E6 and E7 genes at once, to detect whether it have efficacy in vitro and in vivo. Meanwhile, CRISPR/Cas9 system was measured after transfection with liposomes but virus. Cervical cancer lines (HeLa and SiHa) were used in this study. Sanger sequencing confirmed that the single CRISPR/Cas9 vector [termed E6E7-knockout (KO)] containing guide RNAs could targeting both HPV18 E6 and E7 genes in vitro. In addition, double-targeting E6 and E7 increased p53 protein expression significantly while compared with E6 or E7 targeting, respectively. Mice with xenografts were divided into four groups: three doses of experimental groups (20, 40, and 60 µg) and one control group. The E6E7-KO through liposome delivery was injected into tumors. Tumor growth was measured and protein expression was observed through immunohistochemistry. The toxic side effects in vivo were also evaluated. E6E7-KO induced cell apoptosis and inhibited cell proliferation markedly in vitro. E6E7-KO downregulated the messenger RNA and protein expression of E6 and E7, whereas p53 and p21 protein levels were upregulated accordingly. Notably, E6E7-KO delivery by liposome exhibited an effect in vivo. Tumor growth was inhibited in the E6E7-KO groups, which was accompanied by decreased E6/E7 protein expression and increased p53/p21 protein expression, especially the level of p53 protein expression. Therefore, E6E7-KO could have synergy efficient by p53 pathway. Furthermore, local injection with CRISPR/Cas9 by nonviral delivery may be regarded as a potential therapy for cervical cancer in the future.

Angelicin inhibits the malignant behaviours of human cervical cancer potentially via inhibiting autophagy.

Angelicin is an active compound isolated from the Chinese herb Angelica archangelica, which has been reported to exert antitumor effects by inhibiting malignant behaviors in several types of tumor, including proliferation, colony formation, migration and invasion. However, the effects of angelicin on human cervical cancer cells is yet to be elucidated. The present study evaluated the antitumor effects of angelicin on cervical cancer cells. The results demonstrated that cervical cancer cells were more sensitive to angelicin than cervical epithelial cells. At its IC30, angelicin inhibited the proliferation of HeLa and SiHa cells by blocking the cell cycle at the G1/G0 phase and inhibiting other malignant behaviors, including colony formation, tumor formation in soft agar, migration and invasion. At the IC50, angelicin induced cell death potentially by promoting apoptosis. By identifying the hallmarks of autophagy, it was observed that angelicin treatment caused the accumulation of microtubule associated protein 1 light chain 3-ß (LC3B) in the cytoplasm of HeLa and SiHa cells. Western blotting results demonstrated that cleaved LC3B-II and autophagy related proteins (Atg)3, Atg7 and Atg12-5 were upregulated following angelicin treatment. It was also determined that the phosphorylation of mTOR was induced by angelicin treatment. Furthermore, the inhibition of angelicin-induced mTOR phosphorylation did not disrupt its inhibitory effect on autophagy, indicating that angelicin inhibited autophagy in an mTOR-independent manner. Taken together, the present results suggested that angelicin regulated malignant behaviors in cervical cancer cells by inhibiting autophagy in an mTOR-independent manner. Findings suggested that autophagy might be a potential therapeutic target for cervical cancer.

Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway.

Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with high prevalence in humans. Carnosic acid (CA) has been reported to possess antioxidative properties; however, its role in IBDs has not been determined. In the present study, we found that CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS). Pronounced infiltration of immune cells and a loss of crypt architecture and goblet cells were ameliorated by CA. CA significantly decreased the activity of MPO and infiltration of F4/80+ macrophages in the colon. DSS-induced pro-inflammatory cytokine mRNA and protein levels in the colon were also attenuated by CA. CA decreased the activation of p65 and c-Jun signalling. CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity. In addition, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1, which resulted in the decrease of Nrf2 target genes. Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced. Taken together, our data showed that CA may be useful as a potential therapeutic candidate for IBDs.

Photoelectrochemical oxidation of ibuprofen via Cu2O-doped TiO2 nanotube arrays.

A p-n junction based Cu2O-doped TiO2 nanotube arrays (Cu2O-TNAs) were synthesized and used as a working anode in a photoelectrochemical (PEC) system. The results revealed that the Cu2O-TNAs were dominated by the anatase phase and responded significantly to visible light. XPS analyses indicated that with an amount of 24.79% Cu doping into the structure, the band gap of Cu2O-TNAs was greatly reduced. SEM images revealed that the supported TiO2 nanotubes had diameters of approximately 80nm and lengths of about 2.63µm. Upon doping with Cu2O, the TiO2 nanotubes maintained their structural integrity, exhibiting no significant morphological change, favoring PEC applications. Under illumination, the photocurrent from Cu2O/TNAs was 2.4 times larger than that from TNAs, implying that doping with Cu2O significantly improved electron mobility by reducing the rate of recombination of electron-hole pairs. The EIS and Bode plot revealed that the estimated electron lifetimes, τel, of TNAs and Cu2O/TNAs were 6.91 and 26.26ms, respectively. The efficiencies of degradation of Ibuprofen by photoelectrochemical, photocatalytic (PC), electrochemical (EC) and photolytic (P) methods were measured.

Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.

Recent successes in immunotherapeutic strategies are being investigated to combat cancers that have less than ideal responses to standard of care treatment, such as non-small-cell lung cancer. In this paper, we summarize concepts and the current status of immunotherapy for non-small cell lung cancer, including salient features of the major categories of immunotherapy-monoclonal antibody therapy, immune checkpoint blockade, immunotoxins, anticancer vaccines, and adoptive cell therapy.

A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene.

The plant protein trichosanthin (Tk) and its derived peptide tetramer Tk-tPN have been shown to stimulate the type 2 immune responses for treating autoimmune disease. This work explores the possibility of using Tk-tPN as a non-toxic immunosuppressant to induce transplantation tolerance using the mechanisms by which T-cell-mediated immune responses are transferred from type 1 to type 2 through innate immunity-related pathways. Immunocytes and cytokine secretions involved in the mouse cardiac allografting model with Tk-tPN treatment were characterized. Identification of critical genes and analysis of their functions through Toll-like receptor (TLR) -initiated signalling and the possible epigenetic changes were performed. Mean survival times of the cardiac allografts were delayed from 7.7 ± 0.3 days (control) to 22.7 ± 3.9 days (P < 0.01) or 79.1 ± 19.2 days (P < 0.0001) when Tk-tPN was introduced into the recipients alone or together with rapamycin, respectively. The grafting tolerance was donor-specific. The secretion pattern of the type 1 cytokine/transcription factor (IL-2(+) IFN-γ(+) T-bet(+)), which is responsible for the acute graft rejection, was shifted to the type 2 factor (IL-4(+) IL-10(+) Gata3+), together with a selective expansion of the IL-4/IL-10-producing CD8+ CD28- regulatory T-cell subset. A TLR2-initiated high expression of chemokine gene MCP1 was detectable simultaneously. Epigenetically Tk/Tk-tPN could also acetylate the histone H3K9 of MCP1 promoter to skew the immunity towards T helper type 2 responses. Tk/Tk-tPN is therefore capable of down-regulating the type 1 response-dominant rejection of cardiac allografts by evoking type 2 immunity through the activation of a TLR2-initiated signalling pathway and MCP1 gene to expand the IL-4/IL-10-secreting CD8+ CD28- regulatory T cells. Tk-tPN could be a promising novel immunosuppressant to induce tolerance in allotransplantation.

Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G2/M cell cycle arrest and DNA damage.

AIM: Cathepsin L is a lysosomal cysteine protease that plays important roles in cancer tumorigenesis, proliferation and chemotherapy resistance. The aim of this study was to determine how cathepsin L regulated the radiosensitivity of human glioma cells in vitro. METHODS: Human glioma U251 cells (harboring the mutant type p53 gene) and U87 cells (harboring the wide type p53 gene) were irradiated with X-rays. The expression of cathepsin L was analyzed using Western blot and immunofluorescence assays. Cell survival and DNA damage were evaluated using clonogenic and comet assays, respectively. Flow cytometry was used to detect the cell cycle distribution. Apoptotic cells were observed using Hoechst 33258 staining and fluorescence microscopy. RESULTS: Irradiation significantly increased the cytoplasmic and nuclear levels of cathepsin L in U251 cells but not in U87 cells. Treatment with the specific cathepsin L inhibitor Z-FY-CHO (10 µmol/L) or transfection with cathepsin L shRNA significantly increased the radiosensitivity of U251 cells. Both suppression and knockdown of cathepsin L in U251 cells increased irradiation-induced DNA damage and G2/M phase cell cycle arrest. Both suppression and knockdown of cathepsin L in U251 cells also increased irradiation-induced apoptosis, as shown by the increased levels of Bax and decreased levels of Bcl-2. CONCLUSION: Cathepsin L is involved in modulation of radiosensitivity in human glioma U251 cells (harboring the mutant type p53 gene) in vitro.

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway.

AIM: Cathepsin L, a lysosomal cysteine proteinase, is exclusively elevated in a variety of malignancies, including gliomas. In this study we investigated the relationship between cathepsin L and NF-κB, two radiation-responsive elements, in regulating the sensitivity of human glioma cells ionizing radiation (IR) in vitro. METHODS: Human glioma U251 cells were exposed to IR (10 Gy), and the expression of cathepsin L and NF-κB was measured using Western blotting. The nuclear translocation of NF-κB p65 and p50 was analyzed with immunofluorescence assays. Cell apoptosis was examined with clonogenic assays. NF-κB transcription and NF-κB-dependent cyclin D1 and ATM transactivation were monitored using luciferase reporter and ChIP assays, respectively. DNA damage repair was investigated using the comet assay. RESULTS: IR significantly increased expression of cathepsin L and NF-κB p65 and p50 in the cells. Furthermore, IR significantly increased the nuclear translocation of NF-κB, and NF-κB-dependent cyclin D1 and ATM transactivation in the cells. Knockdown of p65 did not change the expression of cathepsin L in IR-treated cells. Pretreatment with Z-FY-CHO (a selective cathepsin L inhibitor), or knockdown of cathepsin L significantly attenuated IR-induced nuclear translocation of NF-κB and cyclin D1 and ATM transactivation, and sensitized the cells to IR. Pretreatment with Z-FY-CHO, or knockdown of p65 also decreased IR-induced DNA damage repair and clonogenic cell survival, and sensitized the cells to IR. CONCLUSION: Cathepsin L acts as an upstream regulator of NF-κB activation in human glioma cells and contributes to their sensitivity to IR in vitro. Inhibition of cathepsin L can sensitize the cells to IR.