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•The interplay between platinum(II) drugs and platinum(IV) prodrugs is summarized.•The oxidation reactions of platinum(II) drugs are reviewed.•The hydrolytic stability of platinum(IV) ...prodrugs is discussed.•Recent progress in the activation of platinum(IV) prodrugs is outlined.
Platinum-based anticancer drugs have been widely applied in clinical settings for more than 40 years. The remarkable breakthroughs that have come from the use of these complexes in cancer therapy have stimulated a continual search for new platinum anticancer drugs. The most promising result of these efforts is a prodrug strategy based on the use of platinum(IV) versions of the traditional platinum(II) anticancer drugs. Hence, the design of synthetic methods for platinum(IV) prodrugs and an understanding of their hydrolytic stability and intracellular activation processes are critical for the development of platinum(IV) prodrugs for cancer therapy. In this review, we summarize recent progress in this field from a comprehensive viewpoint, with an emphasis first on the oxidation processes in chemical environments where platinum(II) compounds are converted to their platinum(IV) species, followed by the reduction processes in biological environments where platinum(IV) species are converted back to platinum(II) forms. First, recent approaches that use new oxidizing reagents to synthesize platinum(IV) prodrugs are summarized, and the oxidation mechanisms and outer-sphere functionalization of platinum(IV) prodrugs are examined. Second, the hydrolysis of platinum(IV) complexes, which has sometimes been underexplored, is discussed, and the factors associated with the hydrolytic stability of platinum(IV) complexes are reviewed. Last, we focus on the reduction of platinum(IV) prodrugs, from the perspectives of reduction potential, rate of reduction, reducing agents, and reduction products. The need for new strategies to achieve controllable intracellular reduction of platinum(IV) prodrugs is emphasized. This review aims to help researchers to improve their understanding of platinum(IV) anticancer prodrugs and hopefully to generate new ideas, strategies, and applications in the area of metal-based drugs.
Cisplatin plays a pivotal role in the treatment of various malignant tumors, but its therapeutic effects are hampered by drug resistance. Pt(iv) prodrugs represent a promising class of ..."non-conventional" platinum-based anticancer agents to circumvent drug resistance, which can be easily functionalized with other bioactive ligands. One strategy is to build "dual-action" and "multi-action" Pt(iv) prodrugs that not only damage DNA but also perturb other pathways related to cisplatin resistance to achieve combinatorial therapeutic effects. Another way to overcome the shortcomings of cisplatin is to deliver Pt(iv) prodrugs via nanocarriers. Most studies in this area have focused on designing prodrugs based on the mechanism of cisplatin resistance within isolated cancer cells. Recent findings, however, reveal that the tumor microenvironment also plays important roles in the development of cisplatin resistance. This perspective focuses on various types of novel cisplatin-based Pt(iv) complexes, including Pt-loaded nanostructures, to overcome cisplatin resistance. Special attention will be devoted to complexes that target the tumor microenvironment, which is a new area for the development of effective Pt(iv) prodrugs. Our summary and outlook may have a hope to help researchers in the field generate new ideas and strategies to develop more potent Pt(iv) prodrugs to combat cisplatin resistance.
•1248 data series were collected to study response of soil microbes to N enrichment.•Thresholds effect of N enrichment on the response of MBC and MBN were observed.•Response of soil microbes depended ...on the biome types, N rates and types, etc.•The effect of N enrichment on soil microbes relate with changes in soil property.
Soil microbes play an important role in ecosystem processes, including carbon (C) and nutrient cycling. Nitrogen (N) enrichment is known to affect soil microbes, but whether other factors affect the impact of N enrichment on soil microbial biomass and composition and extracellular enzyme activities (EEAs) remains unclear. In this study, to evaluate the responses of soil microbial characteristics, including microbial biomass, microbial community composition and EEAs to N enrichment, we conducted a meta-analysis using 1248 global data series from 120 published papers at 125 sites that cover five types of biomes worldwide. The results showed that N enrichment significantly decreased microbial biomass carbon (MBC) and arbuscular mycorrhizal fungi (AMF) across all studies. In addition, the responses of soil microbes depended on the N enrichment rate, and different thresholds (the N rate at which the microbial response changes) of MBC (64.85 kg N ha−1 year−1), microbial biomass nitrogen (MBN, 57.00 kg N ha−1 year−1), bacterial biomass (106.75 kg N ha−1 year−1), fungal biomass (70.50 kg N ha−1 year−1), β-N-acetyl-glucosaminidase (NAG) (83.27 kg N ha−1 year−1) and peroxidase activity (19.75 kg N ha−1 year−1) were observed under N enrichment. Moreover, the responses of soil microbes to N enrichment were affected by biome type, N enrichment rate and type, experimental duration, precipitation and soil type. Furthermore, the results showed that N enrichment significantly altered soil physical and chemical properties, which may affect soil microbial biomass and composition under N enrichment. Our findings highlight that N enrichment decreased the soil microbial biomass and showed a significant effect on soil EEAs across all terrestrial ecosystems, with more pronounced effects observed with increasing N rate and duration.
A new organocatalytic transfer hydrogenation strategy for the asymmetric synthesis of 1,1-diarylethanes is described. Under mild conditions, a range of 1,1-diarylethanes substituted with an ...o-hydroxyphenyl or indole unit could be obtained with excellent efficiency and enantioselectivity. We also extended the protocol to an unprecedented asymmetric hydroarylation of 1,1-diarylalkenes with indoles for the synthesis of a range of highly enantioenriched 1,1,1-triarylethanes bearing acyclic all-carbon quaternary stereocenters. These diaryl- and triarylethanes exhibit impressive cytotoxicity against a number of human cancer cell lines. Preliminary mechanistic studies combined with DFT calculations provided important insight into the reaction mechanism.
•The influencing factors of C and N sequestration and nutrient loss are discussed.•C and N sequestration of artificial vegetation is affected by soil particles and BD.•Natural vegetation C and N are ...affected by MWD and soil C: N ratio.•The average soil and nutrient loss of artificial vegetation is relatively high.•To reduce the nutrient loss of crops, we propose four management measures.
The “Grain for Green” programme has had a significant impact on land use change and carbon and nitrogen balance. However, it is unlear how vegetation restoration affects soil organic carbon (SOC), nitrogen (N) and their losses based on the grid measured data of regional scale. In this study, at the watershed scale, the SOC, N, nutrient losses, sequestration rates, sequestration potential, and influencing factors of croplands, orchards, grasslands, forests and human settlements were assessed through 113 sampling points. Results showed that natural vegetation soil exhibited the highest SOC storage (38.9 Mg·ha−1) and N storage (0.86 Mg·ha−1), and grasslands had the highest SOC sequestration rate (19.2 kg·hm−2·yr−1) and N sequestration potential (5.7 kg·yr−1). Additionally, forests had the highest SOC sequestration rate (0.43 Mg·hm−2·yr−1), and orchards had the highest SOC sequestration potential (161.2 Mg·yr−1). The SOC storage, N storage, and sequestration potential of artificial vegetation were mainly affected by the soil particles and bulk density, however, the SOC storage, N storage, and sequestration potential of natural vegetation were mainly affected by the soil aggregate stability and soil C: N. In addition, the heaviest losses of SOC and N occurred in grasslands, with the highest average amounts in orchards, and the lowest average amounts in forests. We put forward general management suggestions for different vegetation types and focus on four measures for the management of orchards, with a view toward reducing SOC and N losses in different land use types.
As one of the most pervasive methods of individual identification and document authentication, signatures present convincing evidence and provide an important form of indexing for effective document ...image processing and retrieval in a broad range of applications. However, detection and segmentation of free-form objects such as signatures from clustered background is currently an open document analysis problem. In this paper, we focus on two fundamental problems in signature-based document image retrieval. First, we propose a novel multiscale approach to jointly detecting and segmenting signatures from document images. Rather than focusing on local features that typically have large variations, our approach captures the structural saliency using a signature production model and computes the dynamic curvature of 2D contour fragments over multiple scales. This detection framework is general and computationally tractable. Second, we treat the problem of signature retrieval in the unconstrained setting of translation, scale, and rotation invariant nonrigid shape matching. We propose two novel measures of shape dissimilarity based on anisotropic scaling and registration residual error and present a supervised learning framework for combining complementary shape information from different dissimilarity metrics using LDA. We quantitatively study state-of-the-art shape representations, shape matching algorithms, measures of dissimilarity, and the use of multiple instances as query in document image retrieval. We further demonstrate our matching techniques in offline signature verification. Extensive experiments using large real-world collections of English and Arabic machine-printed and handwritten documents demonstrate the excellent performance of our approaches.
Upconversion nanoparticles (UCNPs) have been extensively explored for photodynamic therapy (PDT) and imaging due to their representative large anti-Stokes shifts, deep penetration into biological ...tissues, narrow emission bands, and high spatial-temporal resolution. Conventional UCNP-based PDT system, however, utilizes exitation at 980 nm, at which water has significant absorption, leading to a huge concern that the cell killing effect is from the irradiation due to overheating effect. Here we report an efficient nanoplatform using 808-nm excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles loaded with Chlorin e6 and folic acid for simultaneous imaging and PDT. At this wavelength, the absorption of water is minimized. High energy transfer efficiency is achieved to generate cytotoxic singlet oxygen. Our nanoplatform effectively kills cancer cells in concentration-, time-, and receptor-dependent manners. More importantly, our nanoplatform is still able to efficiently generate singlet oxygen beneath 15-mm thickness of muscle tissue but 980 nm excitation cannot, showing that a higher penetration depth is achieved by our system. These results imply that our nanoplatform has the ability to effectively kill intrinsic tumor or the center of large tumors through PDT, which significantly improves the anticancer efficacy using UCNP-based PDT system and broadens the types of tumors that could be cured.
C dots (CDs) have shown great potential in bioimaging and phototherapy. However, it is challenging to manipulate their fluorescent properties and therapeutic efficacy to satisfy the requirements for ...clinic applications. In this study, we prepared S, Se-codoped CDs via a hydrothermal method and demonstrated that the doping resulted in excitation wavelength-independent near-infrared (NIR) emissions of the CDs, with peaks at 731 and 820 nm. Significantly, the CDs exhibited a photothermal conversion efficiency of ~58.2%, which is the highest reported value for C nanostructures and is comparable to that of Au nanostructures. Moreover, the CDs had a large two-photon absorption cross section (~30,045 GM), which allowed NIR emissions and the photothermal conversion of the CDs through the two-photon excitation (TPE) mechanism.
In vitro
and
in vivo
tests suggested that CDs can function as new multifunctional phototheranostic agents for the TPE fluorescence imaging and photothermal therapy of cancer cells.
Maintaining permanent forest canopy cover and eventually harvesting timber by predetermined target diameter are often considered as a prototype for future management of the oak natural forest. ...However, target diameters and harvest age based on average forest growth rates from wide geographical areas often hamper improved management of oak forests. In this study, based on the sampling of 129 target trees from 51 oak natural secondary forest plots in Hunan Province, China, an individual-tree DBH (diameter at breast height) growth model of oak target trees was developed, and the site type (41 levels) was related to the model as random effects by a nonlinear mixed-effects approach. Moreover, the 41 site types were clustered into four site type groups (STG1, STG2, STG3, and STG4) by the K-means clustering algorithm to improve the model performance and practicality. With the help of the model, the five target diameters (including 24, 30, 40, 50, and 60 cm) were simulated in each of the four STGs, and the minimum target diameter was determined for each STG based on the theory of quantitative maturity. In the four STGs, the harvest age of the 24 cm diameter target ranged from 30 to 51 years; the harvest age of the 60 cm target diameter ranged from 131 to 220 years, with the oaks failing to reach 60 cm in the lowest-quality STG4; the minimum target diameter ranged from 21 cm to 29 cm. Results showed that lower-quality sites exclude higher target diameters from optimal harvesting strategies, in contrast to the higher target diameter as a more reasonable strategy in higher quality sites, and that the minimum target diameter is significantly influenced by site conditions. Therefore, it is necessary to develop a diverse target-diameter-harvesting strategy adapted for the complex site conditions of oak forests in Hunan Province towards site-specific timber management to improve the sustainability of timber production in oak forests.
Changes in land use caused by natural vegetation succession can enhance the soil organic carbon (SOC) and carbon (C) stock of terrestrial ecosystems, as reported in many studies throughout the world. ...However, the dynamics of SOC and soil C stocks and their changes in each succession stage are not clearly following restoration age. Additionally, whether litter and fine roots have positive effects on SOC and soil C sequestration is unclear. We simultaneously studied litter and fine root production and SOC and C stocks along a natural vegetation succession – abandoned farmland, grassland, shrubland, pioneer woodland to natural climax forest – in 2005 and 2015 on the Loess Plateau of China. This allowed a better understanding of the variations of SOC and soil C stock in different land use stages in relation to soil layers and effects of litter and fine roots following vegetation restoration. The land use stages and soil layers significantly affected the rates of SOC and soil C sequestration change. The SOC and soil C stocks in the 0–60 cm soil profile rapidly increased over the course of the long-term natural vegetation succession. During 2005 to 2015, the topsoils (0–20 and 20–40 cm) had higher rates of SOC change (from 0.06 to 0.55 and from 0.23 to 0.51 g kg−1 yr−1, respectively) and soil C sequestration rates (from 0.37 to 1.09 and from 0.40 to 1.16 Mg ha−1 yr−1, respectively) than subsoils (40–60 cm, from 0.04 to 0.36 and from 0.05 to 1.16 Mg ha−1 yr−1). The litter and fine root production increased with age of the natural vegetation succession, and had significant positive effects on changes in SOC and soil C sequestration. Therefore, long-term natural vegetation restoration improved the SOC accumulation, and increased litter and fine root inputs were probably the main factors contributing to soil C sequestration.
•Land use and soil depth had significant effect on SOC.•Litter and fine root are the primary contributors to soil carbon sequestration.•Topsoils had higher rates of soil carbon changes than subsoils.
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