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[Introduction] Offshore wind power generation is gradually being widely applied in the global energy structure transformation due to its advantages of high annual power generation and stable power generation. However, due to the complex and ever-changing marine environment for offshore wind turbine construction, this poses significant obstacles to the construction process and technical solutions of offshore wind turbine foundations. [Method] In the context of the construction project of a certain offshore wind farm, this paper analyzed the type selection criteria and feasibility of pile driving construction ships, pile stabilizing platforms and hydraulic pile hammers. At the same time, in response to the construction requirements for wind turbine foundation pile driving, the preparation work before the operation, the construction plan for the pile stabilizing platform, and the wind turbine foundation pile driving operation with the cooperation of the main-auxiliary crane ships were emphasized. Furthermore, the control and correction measures for verticality in wind turbine foundation pile driving were analyzed. [Result] Steel pipe pile driving construction process can effectively ensure the project quality and expected progress, and has significant economic benefits, safety and reliability. During the pile driving process, it's necessary to complete preliminary and final adjustments to the verticality accural control. [Conclusion] Through the study of pile driving construction technology for offshore wind turbine foundations, it will provide useful reference and inspiration for similar offshore wind turbine projects.

This paper reports a strategy for more reliably obtaining sputtered thin yttrium–iron–garnet (YIG) films possessing both low magnetic damping (α) and a highly spin transparent surface, which represent two of the most important properties for YIG films applied in spintronic devices. The two key points of this strategy, concluded from our systematical studies, are as follows: oxygen reactive sputtering of a slight Y-rich YIG target to avoid the over-stoichiometry of the Fe component and at the same time minimize oxygen vacancy density; and employing phosphoric acid wet etching to remove the inevitable thin magnetic dead layer formed on the surface. The feasibility of this strategy was proved by the achievement of a high quality 30 nm-thick YIG film. It possesses a ferromagnetic resonance linewidth of only 3.4 Oe at 8 GHz, α of only 4.6 × 10−4, and a very spin-transparent surface, as proved by the measured extremely large spin pumping voltage of 650.1 µV after depositing a 3 nm Pt layer.

[Introduction] Under the background of "carbon peak and neutrality" target and "ocean power" strategy, the integration of ocean renewable energy represented by offshore wind power and ocean resources represented by marine ranch is the new direction, new situation and new opportunity for the future development and utilization of ocean resources. The article reviews and analyzes the integrated development mode and key technical problems of offshore wind power and marine pasture, in order to provide technical references to the relevant research and engineering projects in China. [Method] Taking the integration of China's marine resources development needs as the guide, the global development trend of offshore wind power and marine ranch integration was analyzed, and the current situation and shortcomings of China's wind-fishery integration development were clarified. On this basis, the integration mode, equipment design, engineering cases and key technical problems of the integration development of offshore wind power and ocean ranch were analyzed in detail. Finally, a future outlook on the integration development of offshore wind power and ocean ranch in China was discussed. [Result] Through the analysis of the integrated development mode and key technical problems of the integration of offshore wind power and marine ranch development, the bottlenecks and technical challenges are clarified, and the key breakthrough directions are pointed out, providing scientific guidance and reference basis for the comprehensive development and utilization of offshore resources in China. [Conclusion] The article illustrates the necessity and feasibility of integrating the development of offshore wind power and marine ranch, and proposes a feasible way to integrate offshore wind power and marine ranch in China.

Abstract Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease. Graphical Abstract

Abstract Background The underrepresentation of scholarly works from low- and middle-income countries (LMICs) in academic literature is a documented concern, attributed partly to editorial biases. This trend, prevalent across various disciplines, has been less explored in the context of medical ethics journals. This study aimed to examine the composition of editorial board members (EBM) in high-impact medical ethics journals and to evaluate the extent of international diversity within these editorial teams. Methods This study incorporated an analysis of 16 high-impact medical ethics journals. Information regarding the EBM of these journals was systematically gathered and categorized based on the World Bank’s country income classifications. An in-depth examination of the editorial board compositions was then conducted. Results The study identified 669 EBM across the selected journals. A predominant 89.84% (601) of these members were from high-income countries (HICs), with upper-middle-income countries contributing 7.47% (50) and lower-middle-income countries 2.69% (18). No EBM were associated with low-income countries. A regional breakdown indicated that North America was the most represented area, accounting for 48.88% (327), followed by Europe & Central Asia (27.50%, 184), East Asia & Pacific (13.45%, 90), Latin America & Caribbean (4.63%, 31), Sub-Saharan Africa (4.19%, 28), Middle East & North Africa (0.75%, 5), and South Asia (0.60%, 4). In total, these EBMs hailed from 46 different countries, with the United States representing the largest proportion (43.80%, 293), followed by the United Kingdom (13.15%, 88), Australia (7.92%, 53), Germany (6.73%, 45), and Canada (5.08%, 34). Conclusions There is a significant lack of international representation within the EBM of high-impact medical ethics journals. The majority of editors in this field are affiliated with HICs, leading to a severe underrepresentation of LMICs within the editorial boards.

Summary: Background: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC. Methods: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system. Findings: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression. Interpretation: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC. Funding: The funding details can be found in the Acknowledgements section.

ObjectiveTo explore the relationship between plasma lactoferrin (Lf) and glaucoma, assessing the clinical utility of Lf in glaucoma.MethodsA cross-sectional study involved 161 glaucoma patients and 115 healthy controls, with a follow-up of 14 subjects after approximately 2 years. Plasma Lf markers were quantified using ELISA, comparing levels between glaucoma patients and healthy controls, and analyzing plasma Lf across different glaucoma severity grades.ResultsGlaucoma patients had significantly elevated plasma Lf levels compared to healthy controls (p

The prediction of traffic flow has emerged as a pivotal element within the domain of intelligent transport systems, garnering considerable interest and attention from various quarters. SpatioTemporal Graph Neural Networks (STGNNS) have been extensively employed to develop traffic representations. However, the extant research is constrained by several limitations: 1) The majority of STGNNs fail to account for the spatial heterogeneity of traffic data, with the distribution of traffic flows in different regions potentially being biased. This makes it challenging to capture comprehensive traffic flow data features. 2) In the case of complex spatial relationships, the loss of spatial correlation makes it challenging to accurately capture the dynamically variable spatial dependence of traffic flow data. In order to address these challenges, this paper proposes a new coordinate attention enhanced adaptive spatiotemporal convolutional network prediction model (CAAS), which introduces coordinate attention with the objective of modelling spatial heterogeneity and capturing complex spatiotemporal correlations. Moreover, a novel spatial multi-head attention mechanism is introduced with the objective of capturing the intricate interdependencies of multi-scale dynamic spatiotemporal data. This is accomplished by augmenting the input matrix of the softmax function in the attention mechanism, which enhances the differentiation of attention weights and facilitates the capture of spatial relationships at a finer granularity. Ultimately, the prediction of traffic flow is accomplished through the adaptive fusion of temporal and spatial features via a gated fusion mechanism.Experiments conducted on the publicly available PEMS04 and PEMS08 datasets show that the proposed CAAS model significantly surpasses existing cutting-edge methods.

BackgroundHuman tumors pose significant challenges, with targeted therapy against specific molecular targets or signaling pathways being a mainstay alongside surgical resection. Previous studies have implicated KHDRBS1 in the oncogenesis of certain human tumors such as colorectal and prostate cancers, underscoring its potential as a therapeutic target. However, the comprehensive expression pattern of KHDRBS1 in hepatocellular carcinoma (HCC) warrants further exploration.MethodsIntegrating and analyzing multi-omics, multi-cohort data from public databases, coupled with clinical samples and molecular biology validation, we elucidate the oncogenic role of KHDRBS1 in HCC progression. Additionally, leveraging HCC single-cell sequencing data, we segregate malignant cells into KHDRBS1-positive and negative subsets, uncovering significant differences in their expression profiles and functional roles.ResultsOur study identifies KHDRBS1 as a tumor-promoting factor in HCC, with its positivity correlating with tumor progression. Furthermore, we highlight the clinical significance of KHDRBS1-positive malignant cells, aiming to further propel its clinical utility.ConclusionKHDRBS1 plays a key role in HCC development. This study provides crucial insights for further investigation into KHDRBS1 as a therapeutic target in HCC.

Background: The widespread absence of papers originating in low and middle income economies (LAMIE) across various scholarly disciplines has been widely acknowledged. One potential reason for this could be editorial biases against submissions from LAMIE. Although this bias has been observed in different academic areas, its extent in spinal research remains largely uninvestigated. This research endeavored to investigate the composition of editorial staff members (ESM) within major spinal journals and scrutinize the degree of international diversity represented among the ESM. Methods: We pinpointed ten major spinal journals by referencing their presence in the Journal Citation Reports of 2021. Countries of the ESM affiliated with these journals were categorized according to World Bank classifications. Following this, we conducted a thorough analysis of the ESM compositions. Results: A total of 982 ESM from 50 countries were identified. The United States exhibited the highest representation among ESM (395, 40.22%), followed by South Korea (57, 5.80%), Switzerland (53, 5.40%). When segmented by geographical regions, North America emerged with the highest representation, constituting 43.38% of ESM at 426, trailed by Europe & Central Asia at 31.16% (306), East Asia & Pacific at 17.92% (175). The majority of ESM, amounting to 87.98%, hailed from high income economies (HIE). There was an absence of ESM representation of low income economies. The relationship regarding the quantity of ESM in each country and its population failed to demonstrate significance (p = 0.274, r = 0.281). However, a notable positive correlation emerged when exploring the connection between ESM numbers and gross domestic product (p = 0.033, r = 0.517). Conclusions: Major spinal journals exhibit a notable absence of international representation within their editorial boards, predominantly comprising members from HIE. This underscores a substantial underrepresentation of ESM originating from LAMIE within the sphere of spinal investigation.

Abstract Background Although low- and middle-income countries (LMIC) have great disease burden, but the lack of studies from LMIC have been shown in several fields. Multiple researchers from LMIC perceive editorial bias against their studies. Editorial board members (EBMs) from LMIC are under-represented across many medical journals. It is still unclear whether this phenomenon exists in the field of hand research. The purpose of this study was to investigate the composition of EBMs in leading subspecialty hand journals, and to reveal the international representation of EBMs in the field of hand research. Methods This cross-sectional study included seven leading subspecialty hand journals. The EBMs were obtained from the journals’ websites. The country affiliations of EBMs were categorized based on their locations and economy status. The composition of EBMs was investigated. Results There were 211 EBMs in the seven journals. A total of 185 EBMs (87.7%) were affiliated with high-income countries (HIC), 18 (8.5%) with upper middle-income countries, and 8 (3.8%) with lower middle-income countries. None EBMs were affiliated with low income countries. The EBMs were affiliated with 30 countries. The biggest number of EBMs were affiliated with the USA 74 (35.07%), followed by the United Kingdom (45, 21.33%), and France (13, 6.16%). Most of EBMs were based in Europe and Central Asia (86, 40.8%) and North America (81, 38.4%). Conclusions The EBMs of leading subspecialty hand journals are dominated by HIC with a very low representation of LMIC. There is a need to make the editorial boards more international in the field of hand research.

Modern agricultural industrial parks are based on the large-scale development of traditional agriculture, which are a new carrier as agricultural modernization promotion, rural revitalization and supply-side structural reform, also are vital to the "three rural" work. The construction of modern agricultural industrial park involves a lot of contents, requires a large amount of funds and a long period. Since the country proposed the construction of modern agricultural industrial parks, governments at all levels have attached great importance to organizing financial investment, leveraging social capital, and initiating the construction of industrial parks at all levels. Guangdong has taken the lead in utilizing financial investment to implement the construction of provincial-level modern agricultural industrial parks, with the overall goal of building high standard industrial parks, combined with local natural endowments and market demands, scientifically designed and systematically planned various industrial parks at the provincial, municipal, county and town levels, initially forming a tiered development layout, and making industrial park construction as one of the main contents of implementing the rural revitalization strategy. Through multiple rounds of industrial park construction, Guangdong has built and innovated the system of project approval review, fund management, supervision and acceptance in the industrial parks, which provide institutional guarantees for the efficient use of financial funds. Through financial investment, Guangdong Province has built modern agricultural industrial parks, enhanced the attraction of agricultural industry, levered social capital, and injected inexhaustible impetus into agricultural modernization. The special investment of financial funds has played a huge supporting role in the construction of the industrial park, effectively ensuring the smooth implementation of the industrial park project, and accumulating certain experience in the use and management of financial funds. The rational and effective use of financial funds is also the core of industrial park construction. Guangdong has formulated a series of management measures for the use of funds, clearly defining the scope and plan of fund use, improving the safety and efficiency of financial fund use, and ensuring the supporting role of financial funds in the construction of industrial parks. Based on the current situation of agricultural industry and industrial park construction in Guangdong, this paper analyzes the problems existing in the process of financial support for industrial park construction, and puts forward corresponding countermeasures and suggestions, in order to provide reference for the high-level construction of modern agricultural industrial park in Guangdong.

Abstract Objective To establish the risk scoring model for HIV-negative neurosyphilis (NS) patients and to optimize the lumbar puncture strategy. Methods From 2016 to 2021, clinical information on 319 syphilis patients was gathered. Multivariate logistic regression was used to examine the independent risk factors in NS patients who tested negative for human immunodeficiency virus (HIV). Receiver operating characteristic curves (ROC) were used to assess the risk scoring model’s capacity for identification. According to scoring model, the timing of lumbar puncture was suggested. Results There were statistically significant differences between HIV-negative NS and non-neurosyphilis (NNS) patients in the following factors. These included age, gender, neuropsychiatric symptoms (including visual abnormalities, hearing abnormalities, memory abnormalities, mental abnormalities, paresthesia, seizures, headache, dizziness), serum toluidine red unheated serum test (TRUST), cerebrospinal fluid Treponema pallidum particle agglutination test (CSF-TPPA), cerebrospinal fluid white blood cell count (CSF-WBC), and cerebrospinal fluid protein quantification (CSF-Pro) (P

Objectives. Osteochondral defects (OCDs) are localized areas of damaged cartilage and underlying subchondral bone that can produce pain and seriously impair joint function. Literature reports indicated that icariin (ICA) has the effect of promoting cartilage repair. However, its mechanism remains unclear. Here, we explored the effects of icariin and extracellular vesicles (EVs) from rabbit synovial-derived mesenchymal stem cells (rSMSCs) on repairing of OCDs. Materials and Methods. Rabbit primary genicular chondrocytes (rPGCs), knee skeletal muscle cells (rSMCKs), and rSMSCs, and extracellular vesicles derived from the latter two cells (rSMCK-EVs and rSMSC-EVs) were isolated and identified. The rPGCs were stimulated with ICA, rSMSC-EVs either separately or in combination. The rSMCK-EVs were used as a control. After stimulation, chondrogenic-related markers were analyzed by quantitative RT-PCR and western blotting. Cell proliferation was determined by the CCK-8 assay. The preventative effects of ICA and SMSC-EVs in vivo were determined by H&E and toluidine blue staining. Immunohistochemical analyses were performed to evaluate the levels of COL2A1 and β-catenin in vivo. Results. In vitro, the proliferation of rPGCs was markedly increased by ICA treatment in a dose-dependent manner. When compared with ICA or rSMSC-EVs treatment alone, combined treatment with ICA and SMSC-EVs produced stronger stimulative effects on cell proliferation. Moreover, combined treatment with ICA and rSMSC-EVs promoted the expression of chondrogenic-related gene, including COL2A1, SOX-9, and RUNX2, which may be via the activation of the Wnt/β-catenin pathway. In vivo, combined treatment with rSMSC-EVs and ICA promoted cartilage repair in joint bone defects. Results also showed that ICA or rSMSC-EVs both promoted the COL2A1 and β-catenin protein accumulation in articular cartilage, and that was further enhanced by combined treatment with rSMSC-EVs and ICA. Conclusion. Our findings highlight the promising potential of using combined treatment with ICA and rSMSC-EVs for promoting osteochondral repair.

Comparatively little attention has been given to a contemporary examination on the gender disparities in publishing within the Communication field. The major goal of the research was to examine female scholars’ publishing performance and determine whether gender disparity exists in the publication rate of each gender. This study utilized bibliometric methods to conduct a gendered analysis of the publication rates among female and male lead authors in the top five Chinese Journalism and Communication journals from 2011 to 2020. The results confirmed the presence of consistent gender differences in the percentage of articles published by female and male authors. Data analysis also revealed an ongoing tendency towards decline due to female’s increasing educational background, improved academic collaboration and intensified government interventions. The findings of this study contribute to a better understanding of the current status of female scholars and may be used to promote discussion and actions related to gender and equity.

The application of rainwater harvesting and mulching planting (RHMP) methods has effectively improved the productivity in dryland farming. However, different RHMP methods lead to differences in soil water availability, which must be matched with appropriate amounts of fertilizer to obtain further improvements in farmland productivity. In this study, we conducted a long-term (2014–2019) in situ experiment by using a split-plot design with four planting methods (control treatment, NN, no film mulching and no ridge; RHMP, HS, half-film mulching and single ridge; HN, half-film mulching and no ridge; FD, full-film mulching and double ridge) as main treatments and four fertilizer application levels (N, no fertilizer; L, low fertilizer; M, medium fertilizer; and H, high fertilizer, with N:P2O5 rates of 0:0, 150:75, 300:150, and 450:225 kg ha–1, respectively) as sub-treatments. We studied the long-term soil water dynamics, crop growth responses, and economic benefits under the interactive effects of RHMP and fertilization. The results showed that RHMP changed the pattern of soil water consumption and recovery, thereby making it more compatible with the water demand of spring maize, and improving the water availability. Compared with NN, HS, HN, and FD increased the evapotranspiration by 8.7, 12.5, and 20.7 mm, respectively, the yield by 19.8%, 21.1%, and 69.4%, and the water use efficiency by 17.5%, 17.8%, and 61.8%. Under the same RHMP method, fertilization increased the consumption of soil water by crops but improved the water use efficiency. Compared with N, L, M, and H increased the evapotranspiration by 13.1 mm, 14.1 mm, and 15.4 mm, respectively, the yield by 198.7%, 228.5%, and 243.7%, and the water use efficiency increased significantly by 190.0%, 218.2%, and 231.9%. Due to the high variability of inter-annual rainfall (differences up to 419.1 mm during 2014–2019), the soil water availability varied significantly in different years, thereby affecting the yield and economic benefits. We also analyzed the responses in terms of the grain yield and net income to fertilizer application, as well as the soil water storage in the 0–200 cm soil layer before sowing under different RHMP methods. The amount of fertilizer that obtains the best yield and maximum economic benefit in the current year can be evaluated according to the soil water conditions before sowing in order to maximize the production of spring maize in the current season. The results obtained in this study provide a simple method for determining the amount of fertilizer based on water availability to improve and stabilize the crop production efficiency in arid regions.

[Introduction] The spudcan foundation is the key structure of the mobile jack-up platform, which displaces surrounding soil during its penetrating installation. In order to ensure the safety in the application of mobile jack-up platform to the offshore wind power installation works, it is particularly important to research the evolution of surrounding soil flow mechanism during spudcan penetration, and to evaluate the penetration resistance of spudcan reliably. [Method] The coupling Euler-Lagrange (CEL) method was used in this research to simualte the process of spudcan penetration under several typical seabed geological conditions (homogeneous and heterogeneous clay, sand, "clay-sand-clay" and "clay (hard)-sand (soft) and clay (hard)"), and to analyze the differences of penetration mechanisms. [Result] The simulation results show that in the process of spudcan penetration, the soil flow mechanism and penetration resistance of spudcan are closely related to the strength characteristics of seabed soil, while the friction coefficient of the interface between spudcan and seabed soil has little effect on the penetration mechanism and resistance. [Conclusion] From comparision with the results calculated in accordance current design specifications, the method combining large deformation finite element analysis and industry code design should be recommended to be applied in engineering design practice, as to provide a better basis for the assessment of punch-through risk and the prediction of penetrating depth in the process of spudcan penetration.

[Introduction] This paper adoptes the methods based on parametric study and CPT in-situ test for analysis and calculation, the preliminary analysis is carried out according to the actual construction data. By doing this, the self-weight penetration of monopiles can be better and faster predicted and the risks in monopile installation are significantly reduced. [Method] Modified the design input parameters by API recommended pile capacity theory, combined with error analysis, the predicted self-weight penetration was compared to the real data on site. [Result] The analysis results show that there is a great difference in prediction of self-weight penetration due to the different reduction strength coefficient \begin{document}$ {S}_{\mathrm{r}} $\end{document} in the process of calculating clay self-weight penetration and pile running analysis. At the same time, the selection of reduction strength coefficient is different between the self-weight penetration and pile running process. [Conclusion] Through comparative analysis, the value range of clay strength reduction coefficient \begin{document}$ {S}_{\mathrm{r}} $\end{document} of Guangdong sea area is obtained, which can provide a design reference for the following offshore pile penetration operations. It's also proved that the CPT can be used to better predict self-weight penetration and pile running phenomenon.

Context Morinda officinalis F.C. How. (MO) (Rubiaceae) can strengthen bone function.Objective To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP).Materials and methods Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [n = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for in vitro studies.Results MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%, p

The ridge-furrow rainfall harvesting system (RFRH) improved the water shortages, and reasonable fertilization can promote nutrient uptake and utilization of crops, leading to better yield in semi-arid regions. This holds significant practical significance for improving fertilization strategies and reducing the application of chemical fertilizers in semi-arid areas. This field study was conducted to investigate the effects of different fertilization rates on maize growth, fertilizer use efficiency, and grain yield under the ridge-furrow rainfall harvesting system during 2013-2016 in semiarid region of China. Therefore, a four-year localization field experiment was conducted with four fertilizer treatments: RN (N 0 kg hm-2, P2O5 0 kg hm-2), RL (N 150 kg hm-2, P2O5 75 kg hm-2), RM (N 300 kg hm-2, P2O5 150 kg hm-2), and RH (N 450 kg hm-2, P2O5 225 kg hm-2). The results showed that the total dry matter accumulation of maize increased with the fertilizer application rate. The nitrogen accumulation was highest under the RM treatment after harvest, average increase by 1.41% and 22.02% (P

Abstract Background The link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer. Methods This study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy. Results There were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I–III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ 2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141–16.000, P = 0.031) was an independent variable associated with neutropenia. Conclusions The findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.

Stem cell therapy has been increasingly investigated as a promising strategy for intervertebral disc degeneration (IDD). However, no international analysis of stem cell research has yet been conducted. This study aimed to analyze the major characteristics of published reports of stem cell use for IDD and to present a global insight into stem cell research. The study period spanned from the inception of the Web of Science database to 2021. A search strategy using specific keywords was implemented to retrieve relevant publications. The numbers of documents, citations, countries, journals, article types, and stem cell types were evaluated. A total of 1170 papers were retrieved. The analysis showed a significant increase in the number of papers over time (p

Abstract Background Acetaminophen (APAP) overdose is a major cause of the morbidity of acute liver failure. The current clinically approved treatment for APAP poisoning, N-acetylcysteine (NAC), has a limited therapeutic window, and prolonged treatment with NAC delays liver regeneration. Mesenchymal stem cells (MSCs) also have therapeutic effects on APAP-induced mouse liver failure, but whether the effects are comparable to those of NAC has not been determined, and the mechanism still needs further exploration. Methods Fasted C57BL/6 mice that received 500 mg/kg APAP were treated intravenously with 300 mg/kg NAC or different amounts of MSCs at 2 h after APAP to investigate survival, hepatocyte necrosis and neutrophil/macrophage recruitment. In vitro co-culture was performed to study the anti-necrotic effects of MSCs on the APAP-injured hepatocyte cell line L-O2. Results MSCs dose-dependently rescued the C57BL/6J mice from APAP-induced liver failure, with 87.5% of MSCs (1 × 106) surviving similar to that of NAC (90%). MSC has similar effects on reduced hepatocyte necrosis and granulocytic myeloid-derived suppressor cells (MDSC) infiltration but enhanced the proportion of regenerative monocytic MDSC when compared to NAC. Mechanistically, MSCs attenuate hepatocyte necrosis by secreting hepatocyte growth factor (HGF). When HGF was knocked down, the protective effects of MSCs were reduced on APAP-induced hepatocyte necrosis and mouse liver failure. Conclusions MSCs are comparable to NAC against APAP-induced liver failure by secreting HGF with less regenerative retardation concerns, thus facilitating the application of MSCs in clinical therapy for APAP liver failure.

Abstract Background Macrophages are the first line of defense against Talaromyces marneffei. CD86 is a surface molecule expressed on antigen‐presenting cells, such as macrophages, that provide costimulatory signals necessary for T cell activation and survival. In a prior study, it was shown that as infection progressed, CD86 expression levels in macrophages considerably declined while CD86 concentrations in the supernatant significantly increased. Additionally, M1 macrophage polarization was insufficient and switched to M2 macrophage polarization. Besides costimulation, however, additional roles of CD86 are not known or well‐studies. Therefore, we hypothesized that upregulating CD86 on macrophages might promote T. marneffei defense. Methods A lentivirus vector, called Lenti‐CD86, was used to infect THP‐1 cells to overexpress secretory CD86. Through killing assay, nitric oxide detection, and cytokine detection, the capacity of THP‐1 macrophages to phagocytose and kill T. marneffei was examined. Results In the current study, Lenti‐CD86 transfection of THP‐1 cells resulted in a signifant expression of CD86. Additionally, the THP‐1 macrophages stably transfected with Lenti‐CD86 showed higher nitric oxide and IL‐1β production, faster polarization, and stronger phagocytosis and killing capabilities than the non‐transfected or control virus transfected cells. Conclusion Our study shows that lentivirus‐mediated CD86 overexpression improves THP‐1 macrophages' capacity to phagocytose and eliminate T. marneffei.

Abstract Androgen receptor splice variant‐7 (AR‐V7), one of the major driving factors, is the most attractive drug target in castration‐resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR‐V7 in clinical practice. The DNA binding domain (DBD) is indispensable for the transcriptional activity of AR full length and AR splice variants, including AR‐V7. Based on the homodimerization structure of the AR DBD, a novel peptide‐based proteolysis‐targeting chimera (PROTAC) drug is designed to induce AR and AR‐V7 degradation in a DBD and MDM2‐dependent manner, without showing any activity on other hormone receptors. To overcome the short half‐life and poor cell penetrability of peptide PROTAC drugs, an ultrasmall gold (Au)‐peptide complex platform to deliver the AR DBD PROTAC in vivo is developed. The obtained Au‐AR pep‐PROTAC effectively degrades AR and AR‐V7 in prostate cancer cell lines, particularly in CWR22Rv1 cells with DC50 values 48.8 and 79.2 nM, respectively. Au‐AR pep‐PROTAC results in suppression of AR levels and induces tumor regression in both enzalutamide sensitive and resistant prostate cancer animal models. Further optimization of the Au‐AR pep‐PROTAC can ultimately lead to a new therapy for AR‐V7‐positive CRPC.

ObjectiveThe purpose of this study was to identify potential therapeutic targets by examining the hub genes contributing to progression of intracranial aneurysm (IA) in patients with hypertension.MethodsThe bulk RNA sequencing (RNA-seq) datasets of hypertension and IA were obtained from the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo) database. These data were then used to calculate disease-related differentially expressed genes (DEGs) at the individual level. An scRNA-seq dataset of patients with abdominal aortic aneurysms (AAA) was used to analyze monocyte/macrophage-related DEGs. On the basis of the DEG data related to monocytes and macrophages, a TF-genes network has been developed. Hub genes and core sub-networks have also been identified. Furthermore, the key genes have been validated in an external cohort.ResultsFrom combined monocyte and macrophage-derived DEGs from abdominal aortic aneurysms, five hub DEGs were detected, including IFI30, SERPINE1, HMOX1, IL24, and RUNX1. A total of 57 genes were found in the IA bulk RNA-seq dataset. A support vector machine-recursive feature elimination algorithm (SVM-RFE) was applied to further screen the seven genes (RPS4Y1, DDX3Y, RUNX1, CLEC10A, PLAC8, SLA, and LILRB3). RUNX1 was the hub gene that regulated NFKB1 in the monocyte/macrophage-related network. And RUNX1 is implicated in IA progression by regulating hematopoietic stem cell differentiation and abnormal platelet production, according to gene set enrichment analysis.ConclusionAmong patients with hypertension, RUNX1 in monocytes and macrophages was associated with a higher risk of IA through its regulation of NFKB1.

Abstract Objective To evaluate the analgesic effect of vertebral cancellous bone infiltration anaesthesia during percutaneous vertebroplasty (PVP). Methods Patients treated with vertebral cancellous bone infiltration anaesthesia (intervention group) or local anaesthesia alone (control group) during PVP at our institution during 2016–2018 were reviewed. The visual analogue scale (VAS) score before the operation, during establishment of the puncture channel, during pressure changes in the vertebral body (e.g., when removing or inserting pushers or needle cores), during bone cement injection, immediately after the operation, and at 2 h and 1 day postoperatively were compared between the groups. The patient’s satisfaction with the operation was recorded and compared between groups. Results A total of 112 patients were enrolled (59 cases in the intervention group and 53 cases in the control group). There was no difference in the VAS score between the groups before the operation or during establishment of the intraoperative puncture channel (P > 0.05). The VAS score in the intervention group was significantly lower than that in the control group during pressure changes in the vertebral body (removal or insertion of puncture needle cores or pushers) and bone cement injection (P < 0.05). Immediately after the operation and at 2 h postoperatively, the pain in the intervention group was also significantly lower than that in the control group (P < 0.05), but there was no significant difference between the groups at 1 day postoperatively (P > 0.05). The patient satisfaction rate was 88% (52/59) in the intervention group and 67% (35/53) in the control group (P < 0.05). Conclusions Vertebral cancellous bone infiltration anaesthesia may effectively relieve intraoperative pain and improve the surgical experience of patients without affecting the clinical effect of surgery.

Adoptive allogeneic natural killer (NK) cell therapy has shown promise in treating castration-resistant prostate cancer (CRPC), which is the terminal stage of prostate cancer (PCa) and incurable. Thus, we employed an efficient manufacturing method for the large-scale ex vivo expansion of high-quality NK cells from peripheral blood of healthy donors. In the present study, we evaluated the in vitro cytotoxicity of NK cells against human PCa cell lines and in vivo antitumor activity in a preclinical mouse model of CRPC. CCK-8 results demonstrated that the NK cells exerted potent cytotoxicity against all PCa cell lines in vitro. The NK cells were activated when cocultured with PCa C4-2 cells, evidenced by upregulation of the degranulation marker CD107a and secretion of cytokines (TNF-α and IFN-γ). In a xenograft mouse model of CRPC, the caliper, CT, and ultrasonography examination results showed that the size of tumors treated with NK cells was significantly smaller than that in the control group. Moreover, ultrasonography examination also indicated that the NK cell treatment evidently reduced the blood supply of the tumors and HE staining results demonstrated that the NK treatment increased the proportion of necrosis in the tumor specimen compared to PBS treatment. Meanwhile, the NK cell treatment did not cause significant serum IL-6 elevation. Therefore, our study suggested that the expanded NK cells exhibited significant cytotoxicity against PCa cell lines in vitro and excellent therapeutic efficacy against CRPC in a xenograft mouse model, which was of great value for the clinical treatment of CRPC.

Abstract Objective To evaluate the clinical effect of the second puncture and injection technique during a percutaneous vertebroplasty (PVP) procedure. Methods Patients treated with a second puncture and injection (group A) or a single puncture and injection (group B) during PVP at our institution during 2010–2017 were reviewed. Vertebral height loss, visual analogue scale (VAS) score, Oswestry disability index (ODI), adjacent vertebral fractures, and cement leakage were compared between the groups. Results A total of 193 patients were enrolled (86 cases in group A, 107 cases in group B). The follow-up period was 15.64 (12–20) months. The loss of anterior (group A 0.01 ± 0.03; group B 0.14 ± 0.17) and middle (group A 0.13 ± 0.12; group B 0.16 ± 0.11) vertebral height in group B was significantly higher than that in group A (P < 0.05). The VAS score and ODI were also significantly higher in group B than in group A at the final follow-up; the VAS score and ODI in group B were 1.65 ± 0.70 and 14.50 ± 4.16, respectively, and those in group A were 1.00 ± 0.74 and 12.81 ± 4.02, respectively (P < 0.05). Three patients in group A and two in group B experienced adjacent vertebral fractures. Regarding mild, moderate, and severe cement leakage, there were 25 (29%), 5 (5%), and 0 cases, respectively, in group A and 28 (26%), 3 (2.8%), and 1 (0.009%) case, respectively, in group B (P > 0.05). Conclusions The second puncture and injection technique may effectively increase the dispersion of cement, thus preventing recompression of the cemented vertebral body, and it does not increase the risk of cement leakage or adjacent vertebral fracture.

Background Breast invasive carcinoma (BRCA) is a commonly occurring malignant tumor. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and play a mechanistic role in many cancers’ development. The prognostic value of ZNFs has yet to be approached systematically for BRCA. Methods We analyzed the data of a training set from The Cancer Genome Atlas (TCGA) database and two validation cohort from GSE20685 and METABRIC datasets, composed of 3,231 BRCA patients. After screening the differentially expressed ZNFs, univariate Cox regression, LASSO, and multiple Cox regression analysis were performed to construct a risk-based predictive model. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and gene set enrichment analyses (GSEA) were utilized to assess the potential relations among the tumor immune microenvironment and ZNFs in BRCA. Results In this study, we profiled ZNF expression in TCGA based BRCA cohort and developed a novel prognostic model based on 14 genes with ZNF relations. This model was composed of high and low-score groups for BRCA classification. Based upon Kaplan-Meier survival curves, risk-status-based prognosis illustrated significant differences. We integrated the 14 ZNF-gene signature with patient clinicopathological data for nomogram construction with accurate 1-, 3-, and 5-overall survival predictive capabilities. We then accessed the Genomics of Drug Sensitivity in Cancer database for therapeutic drug response prediction of signature-defined BRCA patient groupings for our selected TCGA population. The signature also predicts sensitivity to chemotherapeutic and molecular-targeted agents in high- and low-risk patients afflicted with BRCA. Functional analysis suggested JAK STAT, VEGF, MAPK, NOTCH TOLL-like receptor, NOD-like receptor signaling pathways, apoptosis, and cancer-based pathways could be key for ZNF-related BRCA development. Interestingly, based on the results of ESTIMATE, ssGSEA, and GSEA analysis, we elucidated that our ZNF-gene signature had pivotal regulatory effects on the tumor immune microenvironment for BRCA. Conclusion Our findings shed light on the potential contribution of ZNFs to the pathogenesis of BRCA and may inform clinical practice to guide individualized treatment.

Plasma-enhanced chemical vapour deposition (PECVD) is an industrially compatible microelectronics technology. Here, the authors use PECVD to obtain low-temperature, catalyst-free growth of poly-crystalline two-dimensional hexagonal-boron nitride, thus enabling superior thermal dissipation in WSe2 field-effect transistors with mobility up to 121 cm2 V−1 s−1.

In order to design a water-saving and high-yield maize planting model suitable for semiarid areas, we conducted trials by combining supplementary irrigation with different planting densities. Three planting densities (L: 52,500, M: 75,000, and H: 97,500 plants ha–1) and four supplementary irrigation modes (NI: no irrigation; IV: 375 m3 ha–1 during the 11-leaf stage; IS: 375 m3 ha–1 in the silking stage; and IVS: 375 m3 ha–1 during both stages) were tested. The irrigation treatments significantly increased the leaf relative water content, but the high planting density significantly decreased the relative water content during the silking and filling stages. After supplementary irrigation during the 11-leaf stage, IV and IVS significantly increased the photosynthetic capacity, but decreased the leaf water use efficiency. IS and IVS significantly increased the photosynthetic capacity after supplementary irrigation in the silking stage over two years. During the filling stage, IV, IS, and IVS increased the two-year average net photosynthetic rate by 17.0%, 27.2%, and 30.3%, respectively. The intercellular CO2 concentration increased as the density increased, whereas the stomatal conductance, transpiration rate, net photosynthetic rate, and leaf water use efficiency decreased, and the high planting density significantly reduced the leaf photosynthetic capacity. The highest grain yield was obtained using the IVS treatment under the medium planting density, but it did not differ significantly from that with the IS treatment. Furthermore, the IVS treatment used two times more water than the IS treatment. Thus, the medium planting density combined with supplementary irrigation during the silking stage was identified as a suitable water-saving planting model to improve the photosynthetic capacity and grain yield, and to cope with drought and water shortages in semiarid regions.

Surface-enhanced Raman spectroscopy (SERS) is a promising technology for sensitive optical sensors, generally using rough metal films. Here, Liu et al. synthesize high-quality graphene quantum dot films which offer a large SERS enhancement due to a strong light-matter interaction with Van Hove singularities.

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 μmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.

In vivo implants that are composed of titanium and titanium alloys as raw materials are widely used in the fields of biology and medicine. In the field of dental medicine, titanium is considered to be an ideal dental implant material. Good osseointegration and soft tissue closure are the foundation for the success of dental implants. Therefore, the enhancement of the osseointegration and antibacterial abilities of titanium and its alloys has been the focus of much research. With its many advantages, layer-by-layer (LbL) assembly is a self-assembly technique that is used to develop multilayer films based on complementary interactions between differently charged polyelectrolytes. The LbL approach provides new methods and applications for the surface modification of dental titanium implant. In this review, the application of the LbL technique to surface modification of titanium including promoting osteogenesis and osseointegration, promoting the formation and healing of soft tissues, improving the antibacterial properties of titanium implant, achieving local drug delivery and sustained release is summarized.

Background Hordeum vulgare is an economically important crop that is consumed in large quantities in the world. In a previous investigation, we found that cadmium (Cd) could induce some nucleolar materials containing the argyrophilic proteins scattered in the nuclei and located in the cytoplasm in the root tip cells of H. vulgare. However, what kinds of nucleolar proteins are affected has not been reported. In order to further confirm the cytological effects of Cd on nucleolus and nucleolar proteins, alterations in the cellular localization and expression of two major nucleolar proteins: fibrillarin and nucleolin in the root tips of H. vulgare were studied in the present investigation. Methods Cytological effects of Cd on nucleolus were observed by silver-staining method and two nucleolarproteins: nucleolin and fibrillarin were observed and analyzed by means of indirect immunofluorescent microscopy and western blotting. Results Results from the present investigation demonstrated that under Cd stress (cadmium chloride at 50 and 100 ?M), Cd could disturb the nucleolar cycle with the extrusion of silver-stained materials containing argyrophilic proteins from the nucleolus into the cytoplasm. Nucleolar material containing nucleolin and fibrillarin and their movement into the cytoplasm following Cd stress was detected with indirect immunofluorescence techniques. Western blotting revealed higher expression of these two major nucleoproteins in Cd-treated roots, which was consistent with the results obtained by indirect immunofluorescence. Conclusion The findings of the present study confirm that Cd can have toxic effects on nucleolus and affect the expression of nucleolar proteins, nucleolin and fibrillarin. The data obtained here can provide valuable information for monitoring and forecast early effects of exposure to Cd in polluted environments.

To study the toxic mechanisms of lead (Pb) in plants, the effects of Pb on the morphology and structure of the nucleolus in root tip meristematic cells of Allium cepa var. agrogarum L. were investigated. Fluorescence labeling, silver-stained indirect immunofluorescent microscopy and western blotting were used. Fluorescence labeling showed that Pb ions were localized in the meristematic cells and the uptake and accumulation of Pb increased with treatment time. At low concentrations of Pb (1–10 μM) there were persistent nucleoli in some cells during mitosis, and at high concentration (100 μM) many of the nucleolar organizing regions were localized on sticky chromosomes in metaphase and anaphase cells. Pb induced the release of particles containing argyrophilic proteins to be released from the nucleus into the cytoplasm. These proteins contained nucleophosmin and nucleolin. Pb also caused the extrusion of fibrillarin from the nucleus into the cytoplasm. Western blotting demonstrated the increased expression of these three major nucleolar proteins under Pb stress.

In this work, novel docetaxel (DTX) -loaded Tween 80-free Pluronic P123 (P123) micelles with improved therapeutic effect were developed. The freeze-dried DTX-loaded P123 micelles (DTX-micelles) were analyzed by HPLC, TEM and DLS to determine the DTX loading, micelle morphology, size, respectively. The in vitro cytotoxic activity of DTX-micelles in HepG2, A549 and malignant melanoma B16 cells were evaluated by MTT assay. The corresponding in vivo antitumor efficacy was assessed in Kunming mice bearing B16 tumor after intravenous administration. The DTX-loading and efficiency into the micelles were 2.12 ± 0.09% and 86.34 ± 3.32%, respectively. The DTX-micelles were spherical with a mean particle size of 50.7 nm and size distribution from 22 to 84 nm, which suggested that they should be able to selectively accumulate in solid tumors by means of EPR effect, with a zeta potential of −12.45 ± 3.24 mV. The in vitro release behavior of DTX from DTX-micelles followed the Weibull equation. Compared with Duopafei®, DTX-micelles showed higher cytotoxicity against HepG2 (P < 0.01), A549 (P < 0.05) and B16 (P < 0.01) cells. In addition, DTX-micelles exhibited remarkable antitumor activity and reduced toxicity on B16 tumor in vivo. The tumor inhibition rates (TIR) of DTX-micelles was 91.6% versus 76.3% of Duopafei® (P < 0.01). These results suggested that P123 micelles might be considered as an effective DTX delivery system.

Human penicilliosis marneffei is an emerging infectious disease caused by the fungus Penicillium marneffei. High prevalence of infection among bamboo rats of the genera Rhizomys and Cannomys suggest that these rodents are a key facet of the P. marneffei life cycle. We trapped bamboo rats during June 2004–July 2005 across Guangxi Province, China, and demonstrated 100% prevalence of infection. Multilocus genotypes show that P. marneffei isolates from humans are similar to those infecting rats and are in some cases identical. Comparison of our dataset with genotypes recovered from sites across Southeast Asia shows that the overriding component of genetic structure in P. marneffei is spatial, with humans containing a greater diversity of genotypes than rodents. Humans and bamboo rats are sampling an as-yet undiscovered common reservoir of infection, or bamboo rats are a vector for human infections by acting as amplifiers of infectious dispersal stages.

Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(L-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH2-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ε-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.

Different aluminum concentrations (5, 50, and 100 ?M), as well as different exposure times (24, 48, and 72 h), were applied to investigate cytogenetical alterations in sunflower (Helianthus annuus L.) meristem cells. Nucleolin was also examined under aluminum stress using silver-staining method and indirect immunofluorescent method. Results showed that the mitotic index decreased progressively when either aluminum concentration or exposure time increased. C-mitosis, anaphase bridges, and chromosome stickiness were observed in the aluminum treated root tip cells. Some particulates containing the argyrophilic NOR-associated proteins were distributed in the nucleus of the root-tip cells, and the amount of this particulate material progressively increased with increasing exposure time. Finally, the nucleolar material was extruded from the nucleus into the cytoplasm. The result also indicated the nucleolar protein nucleolin was translocated from nucleolus to nucleoplasm and cytoplasm, that presence of 50 ?M of aluminum for 48 h, suggesting that aluminum disturbed rRNA synthesis and induced the abnormal cellular location of nucleolar protein. The strongly toxic effect of aluminum on the nucleolus can inhibit or stop mitosis, and consequently inhibit root growth.

This paper presents a 500 V high voltage NLDMOS with breakdown voltage (VBD) improved by field plate technology. Effect of metal field plate (MFP) and polysilicon field plate (PFP) on breakdown voltage improvement of high voltage NLDMOS is studied. The coeffect of MFP and PFP on drain side has also been investigated. A 500 V NLDMOS is demonstrated with a 37 μm drift length and optimized MFP and PFP design. Finally the breakdown voltage 590 V and excellent on-resistance performance (Rsp = 7.88 ohm * mm2) are achieved.

The fungal pathogen Penicillium marneffei produces melanin-like pigment in vitro. The synthetic pathway of melanin and its possible influence in the protective yeast cells surviving within macrophage cells are not known. In this work, P. marneffei produced brown black pigment in the presence of L-DOPA and black particles were extracted from yeast cells treated with proteolytic enzymes, denaturant and concentrated hot acid. Kojic acid inhibited the brown-black pigment production of P. marneffei yeast grown on brain heart infusion agar. Transmitting electron microscopy showed spherical granular electron-dense particles with an average diameter of 100 nm in a beaded arrangement in the innermost cell wall. Electron-paramagnetic resonance revealed that the black particles contain a stable free radical compound. The UV-visible and Fourier transform infrared spectra of particles extracted from P. marneffei and synthetic DOPA-melanin showed a high degree of similarity. Melanized yeast cells decreased phagocytosis by macrophage cells and increased resistance to intracellular digestion in vitro. These results indicate that P. marneffei can synthesize DOPA-melanin or melanin-like compounds in vitro and suggest that the DOPA-melanin pathway is associated with cell wall structure and enhances the resistance to phagocytosis by macrophages.