Immunotoxins are Ab‐cytotoxin chimeric molecules with mighty cytotoxicity. Programmed cell death 1‐ligand 1 (PD‐L1), is a transmembrane protein expressed mainly in inflammatory tumor tissues and ...plays a pivotal role in immune escape and tumor progression. Although PD‐L1 immune checkpoint therapy has been successful in some cases, many patients have not benefited enough due to primary/secondary resistance. In order to optimize the therapeutic efficacy of anti‐PD‐L1 mAb, we used durvalumab as the payload and CUS245C, a type I ribosome‐inactivating protein isolated from Cucurbita moschata, as the toxin moiety, to construct PD‐L1‐specific immunotoxin (named D‐CUS245C) through the engineered cysteine residue. In vitro, D‐CUS245C selectively killed PD‐L1+ tumor cells. In vivo studies also showed that D‐CUS245C had obvious antitumor effect on PD‐L1+ human xenograft tumors in nude mice. In conclusion, in the combination of the toxin with mAb, this study developed a new immunotoxin targeting PD‐L1, emphasizing a novel and promising treatment strategy and providing a valuable way to optimize cancer immunotherapy.
Programmed cell death 1‐ligand 1 is a potential target for immunotoxins. Synthesis and purification of a chemically conjugated immunotoxin D‐CUS245C kills the cells mediated by the apoptosis pathway and shows potent antitumor activity both in vitro and in vivo.
Human embryonic stem cells (hES cells) have unlimited self-renewal capacity and can differentiate into most, if not all, possible cell types. This unique property makes them valuable not only for ...investigation of early developmental processes, but also for regenerative medicine. Mesoderm-derived cardiac cells and hematopoietic cells both have the potential for various therapeutic applications. However, efficient induction of hES cell differentiation into mesoderm remains a challenge. Here, we showed that treatment of hES cells with bone morphogenetic protein-4 (BMP-4) exhibited differential effects: long-term treatment results in trophoblast and extra-embryonic endoderm differentiation, whereas short-term treatment can promote early mesoderm induction. The induction of mesoderm in hES cells occurs at a high efficiency as measured using several markers, such as Brachyury, WNT3, and MIXL1 expression. Moreover, these mesoderm progenitor cells can differentiate into cardiac and hematopoietic lineages in vitro. Further analysis showed that the mesoderm-inducing capacity of BMP-4 requires endogenous FGF and TGF-β/Nodal/activin signaling activities. Thus, our results uncover a novel role for BMP-4 in regulation of hES cell differentiation and should provide insights into the mechanism of mesoderm induction in hES cells.
Neurite orientation dispersion and density imaging (NODDI) is a diffusion model specifically designed for brain magnetic resonance imaging. Despite recent studies suggesting that NODDI modeling might ...be more sensitive to brain development than diffusion tensor imaging (DTI), these studies were limited to a relatively small age range and mainly based on the manually operated region of interest analysis. Therefore, this study applied NODDI to investigate brain development in a large sample size of 214 subjects ranging in ages from 0 to 14. The whole brain was automatically segmented into 122 regions. The maturation trajectory of each region was characterized by the time course of diffusion metrics and further quantified using nonlinear regression. The NODDI-derived metrics, neurite density index (NDI) and orientation dispersion index (ODI), increased with age. And these two metrics were superior to the DTI-derived metrics in SVM regression models of age. The NDI in white matter exhibited a more rapid growth than that in gray matter (including the cortex and deep nucleus). These diffusion indicators experienced conspicuous increases during early childhood and the growth speed slowed down in adolescence. Region-specific maturation patterns were described throughout the brain, including white matter, cortical and deep gray matter. These development patterns were evaluated and discussed on the basis of NODDI's model assumptions. To summarize, this study verified the high sensitivity of NODDI to age over a crucial developmental period from newborn to adolescence. Moreover, the existing knowledge of brain development has been complemented, suggesting that NODDI has a potential capability in the investigation of brain development.
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► Nitric acid pressure leaching was used to treat Fe (II)-rich limonitic laterite ores. ► Ni, Co and Fe can be extracted selectively under milder pressure leaching conditions. ► Major ...parameters affecting extractions of target elements were determined. ► Behavior of iron as well as nickel and cobalt in the leaching process was clarified. ► A certain amount of acid can be saved and low residual acid is needed in the process.
The selective extraction of nickel and cobalt over iron from an Indonesian limonitic laterite was investigated using nitric acid pressure leaching (NAPL). The mineralogical analysis showed that the major minerals were goethite and magnetite, and the content of the divalent iron was as high as 7.06%. Nickel and cobalt were mainly distributed in these two minerals; however, the distribution was non-uniform. A series experiments were conducted to examine the basic parameters and propose the optimal conditions for the extraction. When the ore was treated via HPAL under the optimal condition, the extracted nickel and cobalt were less than 75%, and the iron concentration in the leach liquor was over 12.5g/L. By contrast, over 85% of nickel and cobalt were extracted and about 1.8g/L iron was achieved using NAPL. The loss of nickel and cobalt can be mainly attributed to the undissolved magnetite and manganese minerals. The leaching process of NAPL is a dissolution–oxidation–precipitation mechanism, and in this process nitric acid acts as both a lixiviant and an oxidant. The formation of hematite results in a low iron concentration in the leach liquor without oxygen injected. Meanwhile, the oxidation and the precipitation of dissolved divalent iron results in a calculated savings in acid consumption of about 120kg nitric acid per ton of ore can be obtained, which is equal to over 93kg of sulfuric acid per ton of ore. Moreover, lower residual acid (20g/L nitric acid) is a significant advantage of NAPL. The iron residues had a high iron content (>56wt%) with no sulfur, making it suitable as raw materials for ironmaking.
The chloridization and reduction roasting of high-magnesium, low-nickel oxide ore containing 0.82 pct Ni and 31.49 pct MgO were investigated in this study. Mineralogical investigation indicated that ...84.6 pct of nickel was associated with silicates, and nickel was well distributed in mineral in the form of isomorphism. A series of chloridization tests with different added proportions of sodium chloride and coal along with different roasting temperatures and times was conducted. The results indicate that for a ferronickel content of 7.09 pct Ni, a nickel recovery of 98.31 pct could be obtained by chloridizing the laterite ore at 1473 K (1200 °C) for 20 minutes with the addition of 10 wt pct sodium chloride and 8 wt pct coal followed by the application of a 150-mT magnetic field. X-ray diffraction indicated that the nickel is mainly present in the form of ferronickel, which can also be detected by SEM-EDS. Compared with the roasted ore with no added chlorinating agent, the ore roasted in the presence of sodium chloride exhibited enhanced ferronickel particle growth.
To improve the sinterability, a new LATP-x wt% LiBiO
3
composite solid electrolyte was fabricated by adding LiBiO
3
to a NASICON-type Li
1.5
Al
0.5
Ti
1.5
(PO
4
)
3
(LATP) solid electrolyte ...synthesized by the sol–gel method. The results showed that the liquid phase formed by the LiBiO
3
additive promoted grain growth during the sintering process, which led to structural stability and an increased relative density of LATP. When the LiBiO
3
addition amount was 2 wt%, the relative density was 94%, and the bulk ionic conductivity was 2.91 × 10
−4
S cm
−1
. In addition, to improve the interfacial instability between the solid electrolyte and lithium metal, we prepared a PPS/LATP-LiBiO
3
/PPS composite solid electrolyte with a sandwich structure using a polymer PVDF-HFP-PEO-SN (PPS) cladding method to construct an LFP/SSCEs/Li all-solid-state battery. The electrical property test results showed that the all-solid-state battery still had 92% discharging capacity and nearly 100% coulombic efficiency after 50 cycles at 25 °C and 0.1 C.
The use of laterite ore as a major nickel source is gradually increasing because of the depletion of sulphide ores. However, in contrast to high-grade nickel sulphide ore, low-grade nickel laterite ...ore cannot be as easily upgraded by current technologies due to its complicated mineral structure and nickel distribution. This study investigated the mineralogical characteristics, occurrence state and dissemination characteristics of nickel within Yunnan nickel laterite ore in China. Nickel laterite ore had a complex internal structure and mainly consisted of limonite (10wt.%) and serpentine (87wt.%). Sulphides were not a significant part of this laterite ore and were rarely observed. Furthermore, the nickel was mainly hosted in serpentine by substitution for Mg or by adsorption. Serpentine had a mean grade of approximately 0.77wt.% Ni and represented approximately 81.49wt.% of the total laterite resource. A portion of the laterite ore had a pore structure that was formed by destruction of the original protolith during and after its formation, with a specific surface area of 70.042m2/g. The actual temperature for the reduction of metal oxides within the ore was analysed by H2-TPR (temperature-programmed reduction), which indicated that it was higher than the reduction temperature of the pure metal oxides. Finally, based on the above analyses, a non-melting reduction treatment process was proposed for efficient and reasonable utilization of Yunnan laterite ore.
•Mineralogical characteristics of Yunnan laterite ore have been made a detailed investigation.•Thermal properties and reduction characteristic of laterite ore are also studied.•A non-melting reduction treatment process has been designed to utilize Yunnan laterite ore reasonably.
The utilization of laterite sulfuric acid leach residue has always been a challenge in the metallurgical industry. The current treatment involves deep-sea landfills, which leads to considerable ...environmental pollution and resource wastage. In this work, an effective method is proposed to recover iron and chromium from sulfuric acid leach residue. The effects of roasting temperature, reducing agent dosage, and reaction duration on the recovery of iron and chromium were investigated. The optimum conditions were as follows: roasting temperature of 1200 °C, reducing agent dosage of 30%, and reaction duration of 60 min. Results show that the concentrate contains 87% Fe and that only 0.7% S can be obtained with an iron recovery of 82%, indicating suitability for ironmaking. Meanwhile, 85% of chromium can be beneficiated in tailings at a chromium content of 3.5%. The microstructure and composition of reduction products were analyzed by XRD, SEM, and EDS to understand the phase transformation and the aggregation of the reduction products. Hematite in the leach residue is first reduced to FeS and Fe3O4 at low temperature and then reduced to metallic iron with increased temperature. Sulfur is combined with alunite to form FeS at a low temperature, and the decomposition of chromite at high temperature leads to the formation of chromium oxide. In a high temperature and reducing atmosphere, Cr2O3 reacts with FeS to transform Fe and CrS. Through the reduction roasting–magnetic separation process, most of the iron is beneficiated in the concentrate, and nonmagnetic minerals such as FeS and CrS remain in the tailings. Consequently, the separation and beneficiation of iron and chromium occur. The process is economically feasible and environmentally friendly and thus has great potential for the industrial-scale recycling of laterite sulfuric acid leach residue.
Producing iron concentrate in nickel–cobalt extraction form a limonitic laterite by reduction roasting–ammonia leaching. Display omitted
•Laterite screened to remove silicates and subjected to ...roasting and ammonia leaching.•High-grade iron concentrates (Fe>60%) can be directly produced for ironmaking.•Extractions of Ni and Co can be improved under the identical optimal conditions.•Thermodynamic analysis of the reduction roasting process was discussed.•Phase transformation of the improved reduction roasting process was clarified.
This study focuses on the comprehensive utilization of a limonitic laterite from the Philippines. The ore was screened to remove some silicate minerals and then treated via reduction roasting-ammonia leaching. The optimal conditions of reduction roasting of screened ore (Ore I) were determined through a series of tests. Compared with the extractions of nickel and cobalt from the initial ore, those from Ore I increased from 84.0% to 87.9% and from 35.5% to 47.4%, respectively. The iron in leach residue increased from 56.2% to 60.7% without any further treatment, and the final recovery of iron was up to 85.2%. The improved reduction roasting process was analyzed to illustrate the phase transformations of iron, nickel, and cobalt, as well as the effects of such behaviors on the recoveries of these metals.
To evaluate the effect of resolution on iron content using quantitative susceptibility mapping (QSM); to verify the consistency of QSM across field strengths and manufacturers in evaluating the iron ...content of deep gray matter (DGM) of the human brain using subjects from multiple sites; and to establish a susceptibility baseline as a function of age for each DGM structure using both a global and regional iron analysis.
Data from 623 healthy adults, ranging from 20 to 90 years old, were collected across 3 sites using gradient echo imaging on one 1.5 Tesla and two 3.0 Tesla MR scanners. Eight subcortical gray matter nuclei were semi-automatically segmented using a full-width half maximum threshold-based analysis of the QSM data. Mean susceptibility, volume and total iron content with age correlations were evaluated for each measured structure for both the whole-region and RII (high iron content regions) analysis. For the purpose of studying the effect of resolution on QSM, a digitized model of the brain was applied.
The mean susceptibilities of the caudate nucleus (CN), globus pallidus (GP) and putamen (PUT) were not significantly affected by changing the slice thickness from 0.5 to 3 mm. But for small structures, the susceptibility was reduced by 10% for 2 mm thick slices. For global analysis, the mean susceptibility correlated positively with age for the CN, PUT, red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). There was a negative correlation with age in the thalamus (THA). The volumes of most nuclei were negatively correlated with age. Apart from the GP, THA, and pulvinar thalamus (PT), all the other structures showed an increasing total iron content despite the reductions in volume with age. For the RII regional high iron content analysis, mean susceptibility in most of the structures was moderately to strongly correlated with age. Similar to the global analysis, apart from the GP, THA, and PT, all structures showed an increasing total iron content.
A reasonable estimate for age-related iron behavior can be obtained from a large cross site, cross manufacturer set of data when high enough resolutions are used. These estimates can be used for correcting for age related iron changes when studying diseases like Parkinson's disease, Alzheimer's disease, and other iron related neurodegenerative diseases.
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