Small sized EGFR1 and HER2 specific bifunctional antibody for targeted cancer therapy

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2014.07.10; Accepted: 2015.01.05; Published: 2015.01.21 Targeting tumors using miniature antibodies is a novel and attractive therapeutic approach, as these biomolecules exhibit low immunogenicity, rapid clearance, and high targeting specificity. However, most of the small-sized antibodies in existence do not exhibit marked anti-tumor ef-fects, which limit their use in targeted cancer immunotherapy. To overcome this difficulty in targeting multiple biomarkers by combination therapies, we designed a new bifunctional antibody, named MaAbNA (multivalent antibody comprised of nanobody and affibody moieties), capable of targeting EGFR1 and HER2, which are widely overexpressed in a variety of tumor types. The small-sized (29 kDa) MaAbNA, which was expressed in E.coli, consists of one anti-EGFR1 nano-body and two anti-HER2 affibodies, and possesses high affinity (KD) for EGFR1 (~4.1 nM) and HER2 (~4.7 nM). In order to enhance its anti-tumor activity, MaAbNA was conjugated with adriamycin (ADM) using a PEG2000 linker, forming a new complex anticancer drug, MaAbNA-PEG2000-ADM. MaAbNA exhibited high inhibitory effects on tumor cell

Pigments of aminophenoxazinones and viridomycins produced by termite-associated Streptomyces tanashiensis BYF-112

Termite-associated Streptomyces tanashiensis BYF-112 was found as a potential source for yellow and green pigments, which were stable under the tested temperature, light and metal ions. Eight metabolites (1–8), including four new natural yellow pigments aminophenoxazinones (1–4), and two rarely iron dependent green pigments viridomycin A and F (9–10) were isolated from BYF-112 cultured in YMS and YMS treated with FeSO4, respectively. The metabolites 2–4 displayed a significant safety performance on the normal liver cell line L-02, while the metabolite 1 showed weak cytotoxicity against the L-02 and several cancer cells. Especially, in the filter paper disc tests, the compound 1 possessed strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with the zone of inhibition (ZOI) of 15.3 mm, which was equal to that of referenced levofloxacin (ZOI = 15.2 mm). And the metabolite 1 also showed moderate antibacterial activities against Micrococcus teragenus and S. aureus, with the ZOI values of 15.3 and 17.2 mm. In addition, by the minimum inhibitory concentration (MIC) assay, the compound 1 displayed potential antibacterial activities against M. teragenus, S. aureus and MRSA, with the MIC values of 12.5, 12.5, and 25.0 μg/ml, respectively. The present results indicate that BYF-112 may be a promising source for safe and bioactive pigments, which can be used for further development and industrial applications

A multicenter cross-sectional survey of the knowledge, attitude, and behaviour of nurses regarding dysphagia after anterior cervical spine surgery: a prospective multicentre study

Abstract Background The incidence of dysphagia after anterior cervical spine surgery is high, which directly affects the quality of life of patients after surgery. The knowledge, attitude, and behavior of nurses can affect the identification and management of patients after anterior cervical spine surgery. Therefore, we need a survey to understand the current status of nurses’ knowledge, attitude, and behavior towards dysphagia after anterior cervical spine surgery. Objective To investigate the knowledge, attitude, and behaviour of orthopaedic nurses towards patients with dysphagia after anterior cervical spine surgery and provide recommendations for management and intervention. Method An online cross-sectional survey was conducted between March and June 2023, which among 894 orthopaedic nurses from 36 tertiary hospitals in Chongqing using a questionnaire. The questionnaire included general information and knowledge, attitudes, and behaviours related to the management of dysphagia after anterior cervical surgery. Results The orthopaedic nurses’ mean score for dysphagia-related knowledge was 16.1 ± 3.640 (out of a total score of 30). The orthopaedic nurses’ mean score for dysphagia-related attitude was 32.5 ± 4.623 (out of a total score of 40). The orthopaedic nurses’ mean score for dysphagia-related behaviour was 43.6 ± 11.513 (out of a total score of 60). The results of statistical analysis showed that the dysphagia after anterior cervical spine surgery -related knowledge scores differed significantly among the nurses according to, education level, and training (P < 0.05). Correlation analysis showed that there was a positive correlation between the knowledge, attitude, and behaviour scores of neurological nurses and swallowing disorders after anterior cervical surgery (P < 0.05). Conclusion Targeted knowledge and skills training should be carried out to improve the rules and regulations for dysphagia after anterior cervical spine surgery. Multidisciplinary team cooperation is needed, and dietary service processes and management standards should be improved to improve the management ability of orthopaedic nurses for dysphagia after anterior cervical spine surgery

Numerical and Field Investigations of Tremors Induced by Thick-Hard Strata Fracture

Large energy mining-induced tremors are generally caused by the rupture of thick-hard overlying strata, and the roadway is prone to rockburst danger under its dynamic load. Through numerical simulations, the laws and influencing factors of stress, deformation, fracture and energy caused by mining-induced tremors (red bed breaking) were revealed, and the results were verified by field observations. The main conclusions were obtained: (1) the tensile stress and the compressive stress were concentrated in the middle of the thick-hard rock and both sides of the goaf, which were prone to tensile and shear failure type caused by mining-induced tremors, respectively; (2) after the goaf was formed, the compressive stress around the roadway was transformed into tensile stress. When a strong mining-induced tremor occurred, the tensile stress increased further. Meanwhile, when it was close to the tensile strength of the coal around the roadway, a rockburst occurred; (3) the energy of the mining-induced tremor released by shear failure was larger than that of the tensile failure. With the increase in shear strength of the roof, the released energy also increased; (4) according to the frequency-spectrum of the mining-induced tremors located in the extremely thick-hard overlying strata above the working face in the Baodian coal mine, the dynamic load generated by the tremors was superimposed on the high static load around the roadway, which was very likely to induce the instability of the roadway. The research conclusions have certain guiding significance for rockburst prevention in coal mines with thick-hard strata roofs

Numerical and Field Investigations of Tremors Induced by Thick-Hard Strata Fracture

Large energy mining-induced tremors are generally caused by the rupture of thick-hard overlying strata, and the roadway is prone to rockburst danger under its dynamic load. Through numerical simulations, the laws and influencing factors of stress, deformation, fracture and energy caused by mining-induced tremors (red bed breaking) were revealed, and the results were verified by field observations. The main conclusions were obtained: (1) the tensile stress and the compressive stress were concentrated in the middle of the thick-hard rock and both sides of the goaf, which were prone to tensile and shear failure type caused by mining-induced tremors, respectively; (2) after the goaf was formed, the compressive stress around the roadway was transformed into tensile stress. When a strong mining-induced tremor occurred, the tensile stress increased further. Meanwhile, when it was close to the tensile strength of the coal around the roadway, a rockburst occurred; (3) the energy of the mining-induced tremor released by shear failure was larger than that of the tensile failure. With the increase in shear strength of the roof, the released energy also increased; (4) according to the frequency-spectrum of the mining-induced tremors located in the extremely thick-hard overlying strata above the working face in the Baodian coal mine, the dynamic load generated by the tremors was superimposed on the high static load around the roadway, which was very likely to induce the instability of the roadway. The research conclusions have certain guiding significance for rockburst prevention in coal mines with thick-hard strata roofs

Effects of out-of-hospital continuing nursing on schizophrenia patients' rehabilitation and quality of life

This paper aims to explore specific effects of out-of-hospital continuing nursing on schizophrenia patients’ health rehabilitation and quality of life, and further improve application and popularization of out-of-hospital continuing nursing

Spatial Distribution Characteristics and Genetic Mechanism of the Metasilicate-Rich Groundwater in Ji’nan Rock Mass Area, Shandong Province, China

Metasilicate-rich groundwater could meet the high demand of the international community for high-quality water. In order to comprehensively analyze the genetic mechanism of metasilicate-rich groundwater, and help human communities effectively exploit and utilize high-quality water resources, taking the Ji’nan rock mass area as an example, this study carried out systematic research on the spatial distribution and genetic mechanism of the metasilicate-rich groundwater Based on the regional hydrogeological conditions, the influencing factors on the spatial distribution characteristics of the metasilicate-rich groundwater in the study area were systematically sorted out by means of petrogeochemistry, hydrochemistry, and chemical weathering index analysis, and the accumulation mechanism of the metasilicate-rich groundwater was discussed from the perspective of water-rock interaction. The results show that: (1) On the northwest side and part of the northeast side of Ji’nan rock mass, the metasilicate content of the groundwater samples exceeded 25 mg/L; the metasilicate content on the south, west, and east sides were relatively low; (2) Ji’nan rock mass is mainly composed of gabbro easily weathered, with high SiO2 content and high weathering degree showing obvious characteristics of desilication. FeS2 developing along the contact zones between the rock mass and surrounding rocks was easily oxidized to form H2SO4, which enhanced the solubility of silicate minerals in the groundwater. Ji’nan rock mass was located in the low-lying position of the monocline structure, which presented better water conservation and recharges conditions. The above factors resulted in the metasilicate-rich groundwater accumulating in the area of Ji’nan rock mass and showed different spatial distribution characteristics

Land Use and Land Cover Change in the Kailash Sacred Landscape of China

Land use and land cover change (LUCC) is an important driver of ecosystem function and services. Thus, LUCC analysis may lay foundation for landscape planning, conservation and management. It is especially true for alpine landscapes, which are more susceptible to climate changes and human activities. However, the information on LUCC in sacred landscape is limited, which will hinder the landscape conservation and development. We chose Kailash Sacred Landscape in China (KSL-China) to investigate the patterns and dynamics of LUCC and the driving forces using remote sensing data and meteorological data from 1990 to 2008. A supervised classification of land use and land cover was established based on field survey. Rangelands presented marked fluctuations due to climatic warming and its induced drought, for example, dramatic decreases were found in high- and medium-cover rangelands over the period 2000&#8211;2008. And recession of most glaciers was also observed in the study period. Instead, an increase of anthropogenic activities accelerated intensive alteration of land use, such as conversion of cropland to built-up land. We found that the change of vegetation cover was positively correlated with growing season precipitation (GSP). In addition, vegetation cover was substantially reduced along the pilgrimage routes particularly within 5 km of the routes. The findings of the study suggest that climatic warming and human disturbance are interacted to cause remarkable LUCC. Tourism development was responsible land use change in urban and pilgrimage routes. This study has important implications for landscape conservation and ecosystem management. The reduction of rangeland cover may decrease the rangeland quality and pose pressure for the carrying capacity of rangelands in the KSL-China. With the increasing risk of climate warming, rangeland conservation is imperative. The future development should shift from livestock-focus animal husbandry to service-based ecotourism in the sacred landscape