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OBJECTIVE: To investigate the target delivery properties of RC48-ADC, a novel antibody drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-human epidermal growth factor receptor 2 (HER2) antibody tethered via valine-citrulline linker, in vitro and in vivo. MATERIALS AND METHODS: Dissociation rate of MMAE from RC48-ADC was used as an estimate of its stability in serum. Cytotoxicity of the antibody and RC48-ADC towards multiple cell lines was measured. Subcellular distribution of the drug was determined by fluorescence imaging. The mechanism of lysosome targeting was verified. Endocytic pathways of RC48-ADC were assessed by the cellular fluorescence intensity of fluorescently-labelled drugs. Intracellular and extracellular distribution of MMAE was analysed after RC48-ADC or MMAE administration to characterize MMAE release. The serum and tumour concentration of MMAE was compared after tail-vein injection of RC48-ADC into tumour-bearing mice. RESULTS: RC48-ADC was highly stable in human serum. HER2-overexpressed cell line SK-BR-3 proliferation was stronger when suppressed by RC48-ADC than by the naked antibody. Both RC48-ADC and naked antibody were internalized via caveolae-mediated and clathrin- mediated endocytosis and concentrated in lysosomes. Higher HER2 expression was associated with enhanced uptake and intracellular release of conjugated MMAE; free MMAE could kill tumour cells via the bystander effect. Although serum RC48-ADC concentration was higher than that in tumours, exposure of MMAE in tumours was ~200 times higher than in serum, which rationalized the reduced toxicity of RC48-ADC. CONCLUSIONS: In vitro and in vivo experiments confirmed the targeted transport and release of RC48-ADC; it could selectively deliver MMAE to the targeted HER2-positive cell or tumour tissue, which could reduce off-target toxicity and enhance anti-tumour potency in humans. [ABSTRACT FROM AUTHOR]

Chlorophytum capense var. medio-pictum is widely used as a houseplant with its central yellowish white stripe in green leaves. This study investigated chlorophyll biosynthesis, and epidermal characteristics in leaf stripes of different color. The results showed that yellowish white leaf stripes (YS) have a lower 5-aminolevulinic acid (ALA) content than that of green stripes. Meanwhile, YS had higher coproporphyrinogen III (Coprogen III) and Mg-protoporphyrin monomethyl ester (Mpe) contents, but the lower content of protoporphyrinogen IX (Proto IX) and protochlorophyllide (Pchlide) compared to green stripes, suggesting that the occurrence of yellowish white stripes may be attributed to the blocked ALA synthesis and the inhibited conversions from Coprogen III to Proto IX and Mpe to Pchlide. In addition, the upper and lower epidermal cells in YS were larger than those in green stripes. The chloroplasts developed normally in the guard cells of the YS epidermis, though almost no chloroplasts were detected in YS mesophyll cells. [ABSTRACT FROM AUTHOR]

Extracellular polymeric substances (EPS) are isolated from marineVibrio natriegens(V. natriegens) by a cation exchange resin method. The influences of EPS concentration and corrosion time on the corrosion of carbon steel in seawater are investigated. The results demonstrate that EPS are capable of forming a protective film on the surface of carbon steel in seawater, which retards the diffusion of dissolved oxygen and inhibits the reduction of oxygen on the cathode. In addition, the efficiency of corrosion inhibition increases with an increase in the amount of added EPS during the initial state (the first 3 days); however, excess EPS (exceeding 300 mg L−1) in seawater significantly accelerates the corrosion of carbon steel over the long term (10 days) due to the binding power of EPS with Fe ions. [ABSTRACT FROM PUBLISHER]

Importance: DNA-based detection and quantification of soil-borne pathogens, such as the Ralstonia solanacearum species complex (RSSC), plays a vital role in risk assessment, but meanwhile, precise quantification is difficult due to the poor purity and yield of the soil DNA retrieved. The internal sample process control (ISPC) strain RsPC we developed solved this problem and significantly improved the accuracy of quantification of RSSC in different soils. ISPC-based quantitative PCR detection is a method especially suitable for the quantitative detection of microbes in complex matrices (such as soil and sludge) containing various PCR inhibitors and for those not easy to lyse (like Gram-positive bacteria, fungi, and thick-wall cells like resting spores). In addition, the use of ISPC strains removes additional workload on the preparation of high-quality template DNA and facilitates the development of high-throughput quantitative detection techniques for soil microbes., Competing Interests: The authors declare no conflict of interest.

Wernekinck commissure syndrome is a rare midbrain infarction, it consists of several symptoms including bilateral cerebellar ataxia, ophthalmoplegia, and palatal tremor. Holmes tremor is a rare clinical syndrome characterized by a combination of resting, postural, and action tremors. We describe two cases of Wernekinck commissure syndrome with Holmes tremor. To the best of our knowledge, it has been rarely reported in the literature to date. Both of the cases were presented with acute onset of bilateral cerebellar ataxia, dysarthria, and Holmes tremor. In the treatment, one patient was given "clonazepam and benheisol," the other was received acupuncture therapy, both of them showed a marked improvement in ataxia and tremor., Competing Interests: None

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion: The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

Objective: To analyze the clinical features, treatment and outcomes of primary lymphoma of bone (PLB) . Methods: The clinical data of 11 PLB patients were retrospectively analyzed. Results: 11 patients were enrolled in our study including 7 females and 4 males. The median age of the patients was 45 years old. The main histologic type was diffuse large B cell lymphoma and anaplastic large cell lymphoma. Of the 11 PLB cases, 3 cases were at stage ⅠE, 2 at stage ⅡE, 6 at stage ⅣE respectively. 6 cases were treated with chemotherapy and radiotherapy, 2 cases with total joint arthroplasty and chemotherapy, and 3 cases chemotherapy alone respectively. 5 cases got complete remission, 4 cases partial remission and 2 cases stable disease respectively. The median progression free survival was 17 (5-58) months after a median follow up of 21 (6-58) months. Conclusions: Most of PLB patients were clinically in late stage lacking of clinical and imagine features. The optimal treatment for PLB was radiotherapy combined with chemotherapy, and its prognosis was relatively good.

The novel interpenetrating (HA+β-TCP)/MgCa composites were fabricated by infiltrating MgCa alloy into porous HA+β-TCP using suction casting technique. The microstructure, mechanical properties and corrosion behaviors of the composites have been evaluated by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), mechanical testing, electrochemical and immersion tests. It was shown that the composites had compact structure and the interfacial bonding between MgCa alloy and HA+β-TCP scaffolds was very well. The ultimate compressive strength of the composites was about 500-1000 fold higher than that of the original porous scaffolds, and it still retained quarter-half of the strength of the bulk MgCa alloy. The electrochemical and immersion tests indicated that the corrosion resistance of the composites was better than that of the MgCa matrix alloy, and the corrosion products of the composite surface were mainly Mg(OH)2, HA and Ca3(PO4)2. Meanwhile, the mechanical and corrosive properties of the (HA+β-TCP)/MgCa composites were adjustable by the choice of HA content., (© 2013.)

A novel interpenetrating C/Mg-Zn-Mn composite was fabricated by infiltrating Mg-Zn-Mn alloy into porous carbon using suction casting technique. The microstructure, mechanical properties and corrosion behaviors of the composite have been evaluated by means of SEM, XRD, mechanical testing and immersion test. It was shown that the composite had a compact structure and the interfacial bonding between Mg-Zn-Mn alloy and carbon scaffold was very well. The composite had an ultimate compressive strength of (195 ± 15) MPa, which is near with the natural bone (2-180 MPa) and about 150-fold higher than that of the original porous carbon scaffold, and it still retained half of the strength of the bulk Mg-Zn-Mn alloy. The corrosion test indicated that the mass loss percentage of the composite was 52.9% after 30 days' immersion in simulated body fluid (SBF) at 37 ± 0.5 °C, and the corrosion rates were 0.043 mg/cm(2)h and 0.028 mg/cm(2)h after 3 and 7 days' immersion, respectively. The corrosion products on the composite surface were mainly Mg(OH)2 and hydroxyapatite (HA)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is gene-radiotherapy, i.e. a combination of radiation therapy and gene therapy. It is to choose certain exogenous radiation-inducible regulatory genes, for example, early growth response-1 (Egr-1), and transcript its downstream tumor-therapeutic genes under ionizing radiation so as to kill the tumor cells synergistically by the expressed gene products together after transfection and irradiation exposure. In this study, we engineered a plasmid encoding both TRAIL and endostatin under the control of the radiation-inducible Egr-1 promoter, and evaluated its anti-tumor efficacy in combination with radiotherapy. Our plasmid showed significant efficacy in up-regulating the levels of TRAIL and endostatin proteins after transfected into breast cancer cells and exposed to X-ray irradiation. The detected cellular effects in vitro manifested that TRAIL-endostatin-based gene therapy could enhance radiosensitizing effects in breast cancer cells in terms of tumor cell growth inhibition, promoting apoptosis and the induction of cell cycle arrest. In summary, our results suggest that TRAIL-endostain-targeting approach might be a promising method to sensitize solid tumors to radiation therapy.

Receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 54 progesterone receptor (PR) inhibitors. The established CoMFA model from the training set gives statistically significant results with the cross-validated q (2) of 0.534 and non-cross-validated [Formula: see text] of 0.947. The best CoMSIA model was derived by the combination of steric field and hydrophobic field with a q (2) of 0.615 and [Formula: see text] of 0.954. A test set of 18 compounds was used to validate the predictive ability of the two models. The predicted correlation coefficients [Formula: see text] are 0.681 and 0.677 for CoMFA and CoMSIA models, respectively. Based on the CoMFA maps, the key structural characters of progesterone receptor inhibitors are identified. Moreover, the binding modes of oxindoles and benzimidazol-2-ones are also given by the quantum mechanical/molecular mechanical (QM/MM) calculations. This may provide useful information for drug design.