How to Retain Rural Preschool Teachers?

As a result of the accelerated urbanization and the improved remunerations of urban teachers, a large number of rural teachers have been pursuing employment in urban areas, resulting in a severe shortage of rural teaching staff. This phenomenon is particularly pronounced in developing countries. Disadvantages in rural school working and living situations such as low pay, poor living conditions, heavy workloads, limited professional development has made teacher recruitment and retention extremely challenging tasks. The unbalanced urban-rural distribution of teachers, especially high-quality teachers, have become barriers to rural education development and further exacerbated the disadvantaged situations of rural students

Numerical Modeling of Mineralizing Processes During the Formation of the Yangzhuang Kiruna-Type Iron Deposit, Middle and Lower Yangtze River Metallogenic Belt, China: Implications for the Genesis and Longevity of Kiruna-Type Iron Oxide-Apatite Systems

The Yangzhuang iron deposit is a Kiruna-type iron oxide-apatite (IOA) deposit within the Ningwu mining district of the Middle and Lower Yangtze River Metallogenic Belt (MLYRMB), China. This study applies a numerical modeling approach to identify the key processes associated with the formation of the deposit that cannot be easily identified using traditional analytical approaches, including the duration of the mineralizing process and the genesis of iron orebodies within intrusions associated with the deposit. This approach highlights the practical value of numerical modeling in quantitatively analyzing mineralizing processes during the formation of mineral deposits and assesses how these methods can be used in future geological research. Our numerical model links heat transfer, pressure, fluid flow, chemical reactions, and the movement of ore-forming material. Results show that temperature anomaly and structure (occurrence of the contact of intrusion and the Triassic Xujiashan group) are two key factors controlling the formation of the Yangzhuang deposit. This modeling also indicates that the formation of the Yangzhuang deposit only took some 8000 years, a reaction that is likely to be controlled by temperature and diffusion rates within the system. The dynamic changes of temperature and the distribution of mineralization also indicate that the orebodies located inside the intrusions most likely formed after magma ascent rather than representing blocks of existing mineralization that descended into the magma as a result of stoping or other similar processes. All these data form the basis for future research into the forming processes of Kiruna-type IOA systems as well as magmatic–hydrothermal systems more broadly, including providing useful insights for future exploration for these systems. The simulation approach used in this study has several limitations, such as oversimplified chemical reactions, uncertainty of pre-metallogenic conditions and limitation of 2D model. Future development into both theories and methods will definitely improve the practical significance of numerical simulation of ore-forming processes and provide quantitative results for more geological issues

Study on the impact of social capital on the rural residents’ conscious interpersonal waste separation behavior: evidence from Jiangxi province, China

Guiding rural residents to implement interpersonal waste separation in their daily lives consciously is crucial for controlling solid waste pollution in developing countries. This paper utilizes survey data from Jiangxi Province which is one of the national pilot zones for ecological conservation in China to analyze the impact of the social capital that includes social networks, social trust, and social norms on the rural residents’ conscious interpersonal waste separation behavior. The empirical results indicate that social capital has a positive effect on the rural residents’ conscious interpersonal waste separation behavior, wherein the effects of social networks and social trust are significant. Among the three dimensions of social capital, social networks and social norms are substitutable, while social trust and social norms have a complementary effect on each other. Moreover, the ecological cognition and subjective norm play a significant mediating role in the relationship between social network, social trust, and social norms and the rural residents’ conscious interpersonal waste separation behavior, while the government policies plays a significant moderating effect

Turning an antiviral into an anticancer drug: Nanoparticle delivery of acyclovir monophosphate

Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~69%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (p<0.05~0.005) of A-LCP NPs, suggests excellent in vivo efficacy. Whereas, two free drugs (ACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug

Theranostic etoposide phosphate/indium nanoparticles for cancer therapy and imaging

Etoposide phosphate, a water-soluble anti-cancer prodrug, was successfully encapsulated together with indium in nanoparticles. We have used indium both as a carrier to deliver etoposide phosphate and as a SPECT imaging agent through incorporation of 111 In

Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

<p>Abstract</p> <p>Background</p> <p>c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells <it>in vitro </it>and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer <it>in vivo </it>is currently unknown.</p> <p>Methods</p> <p>To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both <it>in vitro </it>and in nude mice.</p> <p>Results</p> <p>Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection.</p> <p>Conclusion</p> <p>The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and <it>in vivo </it>liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy.</p

Protective Effect of Anthocyanin on Neurovascular Unit in Cerebral Ischemia/Reperfusion Injury in Rats

Treating cerebral ischemia continues to be a clinical challenge. Studies have shown that the neurovascular unit (NVU), as the central structural basis, plays a key role in cerebral ischemia. Here, we report that anthocyanin, a safe and natural antioxidant, could inhibit apoptosis and inflammation to protect NVU in rats impaired by middle cerebral artery occlusion/reperfusion (MCAO/R). Administration of anthocyanin significantly reduced infarct volume and neurological scores in MCAO/R rats. Anthocyanin could also markedly ameliorate cerebral edema and reduce the concentration of Evans blue (EB) by inhibiting MMP-9. Moreover, anthocyanin alleviated apoptotic injury resulting from MCAO/R through the regulation of Bcl-2 family proteins. The levels of inflammation-related molecules including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which were over-expressed with MCAO/R, were decreased by anthocyanin. In addition, Nuclear factor-kappa B (NF-κB) and the NLRP3 inflammasome pathway might be involved in the anti-inflammatory effect of anthocyanin. In conclusion, anthocyanin could protect the NVU through multiple pathways, and play a protective role in cerebral ischemia/reperfusion injury

Lipid-Coated Cisplatin Nanoparticles Induce Neighboring Effect and Exhibit Enhanced Anticancer Efficacy

Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP’s poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8wt%). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent anti-tumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via IV without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anti-cancer effectiveness

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Introductions: Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. Objectives: To identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. Methods: Chondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. Results: Human cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. Conclusions: Our findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment

Identification of CD8+ T-cell epitope from multiple myeloma-specific antigen AKAP4

Multiple myeloma (MM) is a malignant plasma cell disorder affecting mainly the elderly population. Revolutionary progress in immunotherapy has been made recently, including monoclonal antibodies and chimeric antigen receptor T cell (CAR-T) therapies; however, the high relapse rate remains problematic. Therefore, combination therapies against different targets would be a reasonable strategy. In this study, we present a new X-chromosome encoded testis-cancer antigen (CTA) AKAP4 as a potential target for MM. AKAP4 is expressed in MM cell lines and MM primary malignant plasma cells. HLA-A*0201-restricted cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transduced with an adenovirus vector encoding the full-length AKAP4 gene were demonstrated to lyse AKAP4+ myeloma cells. Seven of the 12 candidate epitopes predicated by the BIMAS and SYFPEITH algorithms were able to bind HLA-A*0201 in the T2 binding assay, of which only two peptides were able to induce CTL cytotoxicity in the co-culture of peptide-loaded human mature dendritic cells and the autologous peripheral blood mononuclear cells (PBMCs) from the same HLA-A*0201 donor. The AKAP4 630–638 VLMLIQKLL was identified as the strongest CTL epitope by the human IFN-γ ELISPOT assay. Finally, the VLMLIQKLL-specific CTLs can lyse the HLA-A*0201+AKAP4+ myeloma cell line U266 in vitro, and inhibit tumor growth in the mice bearing U266 tumors in vivo. These results suggest that the VLMLIQKLL epitope could be used to develop cancer vaccine or T-cell receptor transgenic T cells (TCR-T) to kill myeloma cells