Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The ...tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8
+
exhausted T cells and Tregs highly expressed
PDCD1
,
CTLA4
and
TIGIT
. Thus,
PDCD1
,
CTLA4
and
TIGIT
were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention
via
tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.
Oligocene and Miocene Himalayan anatexis is generally thought to have been induced by intracrustal heating or processes without the involvement of mantle-derived heat and materials, suggesting that ...the Himalayan leucogranites are typical examples of purely crustal melts. This study focuses on a Miocene leucogranite at Langkazi within the Himalayan orogen, an intrusion that contains a large number of dioritic enclaves. These enclaves have typical igneous textures, contain acicular apatites, and have back-veining structures, quenched margins, and crystallization ages identical to the hosting two-mica granites, indicating that these enclaves are magmatic. Although the enclaves are evolved, the most primitive samples contain high concentrations of MgO (up to 4.3wt.%), Cr (up to 159ppm), and Ni (up to 102ppm), are strongly enriched in large-ion lithophile elements, are depleted in high-field-strength elements, have negative εNd(t) values (–8.6 to –6.1), and have relatively high 87Sr/86Sr(i) values (0.7085–0.7137), suggesting that they were derived from a relatively enriched region of the lithospheric mantle source. Whole-rock geochemical data indicate that the hosting Langkazi leucogranite formed from magmas generated by the partial melting of metapelite material within the High Himalaya crystalline sequence, and these magmas subsequently mixed with mantle-derived melts that are now represented by the Langkazi dioritic enclaves. This indicates that mantle-derived material played an important role in the generation of the Langkazi intrusions. The whole-rock geochemical compositions of samples from the study area also indicate that the primary melts that formed the Langkazi enclaves were significantly contaminated by the relatively juvenile Himalayan lower crustal material, suggesting in turn that these mantle-derived magmas underwent MASH (crustal melting, melt assimilation, magma storage, and homogenization) processes at the base of crust, introducing heat to the lower crust. This mantle-derived heat may have induced partial melting of the Himalayan lower crust, forming adakite-like magmas. Although the small volumes of these dioritic enclaves suggest that this heat may have assisted the genesis of the north Himalayan granites and the High Himalayan leucogranites, whereas in situ crustal radiogenic heating, shear heating, and decompression melting dominated the melting processes in this region.
•The Miocene Langkazi leucogranite contains a large number of dioritic enclaves.•The Langkazi dioritic enclaves are derived from an enriched lithospheric mantle source.•A large amount of mantle-derived melts were added into the Langkazi leucogranites.•Anatexis of the Himalayan crust should be facilitated by addition of mantle heat.
Background: Osteoporosis is a systemic skeletal disease with the high incidence, serious complications, financial burden, and heavily decrease in living quality. Methods: Proliferation of osteoblast ...was tested by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, alkaline phosphatase (ALP) activity of osteoblasts was tested by ALP REAGENT, Calcium level was determined by a colorimetric assay, mRNA expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1 (PDK1), Akt, Caspase-3, Caspase-7, Caspase-9, osteocalcin (OCN), Osterix and Runx2 of osteoblasts was tested by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR), and protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt was measured by Western Blot analysis. Results: In osteoporosis model rats, it found that mRNA expression of PI3K, PDK1 and Akt showed no changes while protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt in bone tissue was decreased dramatically. To further characterize the molecular mechanisms that regulate osteoporosis, we examined the contribution of the PI3K/Akt cell signaling pathway in cultured osteoblasts. It suggested that, the blockade of PI3K activation by LY294002, a specific inhibitor of the PI3K/Akt signaling pathway in osteoblasts, heavily inhibited cell proliferation, ALP activity, calcium accumulation, and mRNA expression of OCN, Osterix and Runx2. However, mRNA expression of Caspase-3 and Caspase-9 was promoted accordingly. Conclusion: The in vivo and in vitro studies indicated that the PI3K/Akt cell signaling pathway is involved in the inhibition of osteoporosis through promoting osteoblast proliferation, differentiation and bone formation.
Abstract
Heavy metal pollution of agricultural and urban soils limits economic progress in the rapidly developing society. Terahertz technology is applied to detect heavy metal pollutants under ...existence of multiple pathways of their dissemination. In this study, terahertz time-domain spectroscopy (THz-TDS) is employed as an advanced probing technique in combination with traditional detecting methods to measure the adsorption ability of trivalent chromium ions on bentonite. The concentration of chromium ions and the weight of bentonite are known to influence on the adsorption capacity of the latter. It is tested here by both qualitative and quantitative measurements of two mentioned parameters. The adsorption process of chromium ions by bentonite is monitored using THz-TDS. The adsorptions signal from samples at 0.5 THz gradually increases with the increase of bentonite weight or chromium ion concentration. It would appear to indicate that terahertz could be used for quantitative detection of metal ions. Secondly, the ratios of results obtained by inductively coupled plasma mass spectrometry (ICP-MS) and the THz-TDS ones are stabilized at 0.105 ± 0.014 as the bentonite weight or chromium ion concentration increase. Such finding confirms that terahertz technology can be used for the quantitative detection of metal ions. Using the relationship between the ICP-MS test results and the THz-TDS ones, the amplitude value of bentonite is obtained to be 13.925 at the concentration of chromium ions of 0.05 mol/L, the mass of bentonite sample involved in adsorption of 1.5 g, and the detection frequency in THz-TDS measurements of 0.5 THz. The adsorption coefficient of bentonite is calculated to be 1.44%. Increase of the chromium ion concentration to 0.2 mol/L, and the mass of bentonite involved in adsorption to 3 g leads to the increase of the amplitude corresponding to adsorbed chromium ions to about 19.463, and the adsorption coefficient to about 2.1%. Obtained results demonstrate that terahertz technology is promising to meet the ever-increasing requirements in mineral analyses for rapid detection of chemical contaminants and measurement of the adsorption efficiencies of materials.
Objective
Leucocyte esterase (LE) strip test is the most rapid, convenient, and cheap method to diagnose chronic periprosthesis joint infection (PJI). However, the determination of LE strip mainly ...relies on colorimetric method with strong subjectivity, which leads to low diagnostic accuracy. Therefore, we try to convert LE strip images into digital data through the RGB photometric system to achieve objective diagnosis. This method will greatly improve the accuracy of LE strip detection and diagnosis of PJI.
Methods
From January 2021 to September 2021, 46 patients with suspected PJI after total hip and knee arthroplasty underwent diagnostic joint puncture. After effective joint fluid samples were harvested, they were divided into original fluid and centrifuged fluid for LE strip detection. Real‐time images of LE strip were taken at 90 s, 3 min, 5 min, 10 min, and 15 min after sampling, and their brightness (Y) was obtained after they were input into an RGB photometric system. Grouping was based on centrifugation, infection, and time points, and then the differences in brightness among groups were compared. The correlation between LE strip image brightness and WBC count was evaluated. Student t‐test was used for the parametric data and chi‐square test for qualitative data. Simple linear regression was utilized to analyze the correlation between brightness and WBC count in each group.
Results
Included were 19 cases of PJI and 27 Non‐PJI subjects diagnosed against ICM2018 diagnostic criteria. The brightness was lower in the PJI group than in Non‐PJI group (p < 0.05). The brightness of the uncentrifuged group was lower than that of the centrifuged group (p < 0.05). Irrespective of centrifugation or infection, the brightness of LE strip decreased with the exposure time after sampling. The brightness of LE strip was correlated with WBC count at different time points, with the correlation being strongest 5 min after sampling (R2 (5 min) = 0.86, p < 0.0001). The correlation between LE strip brightness and WBC count was also found in the centrifugation group, with the correlation being most robust 15 min after sampling (R2 (15 min) = 0.73, p < 0.0001).
Conclusion
A remarkable correlation was found between LE strip brightness and the WBC count. It is feasible to directly quantify LE strip image on a RGB photometer to achieve quantitative detection of LE strip to diagnose PJI.
As shown in the Graphical Image, our study confirmed that there was a good correlation between the WBC count and the brightness value of the leucocyte esterase strips at the time points of 90 s, 3 min, 5 min, 10 min, and 15 min, and the correlation was the best at the time point of 5 min. It may be possible to provide a reliable method for the quantitative detection of leucocyte esterase strips by using RGB photometric system and to establish the correlation between leucocyte esterase strips brightness and WBC count, thus improving the accuracy of rapid diagnosis of PJI.
The permeability modeling of self-healing due to calcium carbonate precipitation in cement-based materials with mineral additives was studied in this work. The parameters of calcium carbonate ...precipitation during self-healing were simulated. A permeability modeling of self-healing, combined with numerical simulation of calcium carbonate formation, was proposed based on the modified Poiseuille flow model. Moreover, the percentage of calcium carbonate in healing products was measured by TG-DTA. The simulated results show that self-healing can be dramatically promoted with the increase of pH and Ca
2+
concentration. The calculated result of permeability is consistent with that measured for cracks appearing in middle or later stages of self-healing, it indicates that this model can be used to predict the self-healing rate to some extent. In addition, TG-DTA results show that the percentage of calcium carbonate in healing products is higher for mortar with only chemical expansion additives or cracks appearing in the later stage, which can more accurately predict the self-healing rate for the model.
Innate immune dysfunction contributes to the development and progression of nonalcoholic fatty liver disease (NAFLD), however, its pathogenesis is still incompletely understood. Identifying the key ...innate immune component responsible for the pathogenesis of NAFLD and clarifying the underlying mechanisms may provide therapeutic targets for NAFLD. Recently, F-box- and WD repeat domain-containing 7 (FBXW7) exhibits a regulatory role in hepatic glucose and lipid metabolism. This study aims to investigate whether FBXW7 controls high-mobility group box 1 protein (HMGB1)-mediated innate immune signaling to improve NAFLD and the mechanism underlying this action.
Mice were fed a high-fat diet (HFD) for 12 or 20 weeks to establish NAFLD model. Hepatic overexpression or knockdown of FBXW7 was induced by tail-vein injection of recombinant adenovirus. Some Ad-FBXW7-injected mice fed a HFD were injected intraperitoneally with recombinant mouse HMGB1 to confirm the protective role of FBXW7 in NAFLD via inhibition of HMGB1.
FBXW7 improves NAFLD and related metabolic parameters without remarkable influence of body weight and food intake. Moreover, FBXW7 markedly ameliorated hepatic inflammation and insulin resistance in the HFD-fed mice. Furthermore, FBXW7 dramatically attenuated the expression and release of HMGB1 in the livers of HFD-fed mice, which is associated with inhibition of protein kinase R (PKR) signaling. Thereby, FBXW7 restrains Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) signaling in HFD-fed mouse livers. In addition, exogenous HMGB1 treatment abolished FBXW7-mediated inhibition of hepatic inflammation and insulin resistance in HFD-fed mouse livers.
Our results demonstrate a protective role of FBXW7 in NAFLD by abating HMGB1-mediated innate immune signaling to suppress inflammation and consequent insulin resistance, suggesting that FBXW7 is a potential target for therapeutic intervention in NAFLD development.
Here we disclose a fast (ON time ∼50 μs and OFF time ∼25 μs at 55
°C), high‐contrast, continuous phase modulator without fringe field effect (FFE). The phase modulator uses the Kerr effect of ...vertically aligned deformed helix ferroelectric liquid crystals (VADHFLCs). Specifically, FFE is a long‐term problem for nematic liquid crystals (NLCs). In this article, we are disclosing, for the first‐time found, that no FFE exists for VADHFLCs, even for phase modulator with 1‐μm pixel pitch. It is an attractive feature for ultra‐high‐resolution display and photonic applications. Moreover, the Kerr constant is 88
nm/V2, and the contrast ratio is larger than 1000:1. It is a promising candidate for high‐PPI augmented reality (AR)/virtual reality (VR) displays, wavelength selective switch (WSS), hologram, adaptive optics, and LiDARs.
Here we disclose a fast (ON+OFF = 50 μs + 25 μs at 55°C), high‐contrast, continuous phase modulator without fringe‐field‐effect (FFE) based on the Kerr effect of vertical aligned deformed helix ferroelectric liquid crystals (VADHFLC). No FFE exists, even for 1μm pixel pitch, which solves the long‐term problems in NLCs. It shows Kerr constant 88 nm/V2, and contrast ratio 1000:1.
The measurable supply of 232Th to the ocean can be used to derive the supply of other elements, which is more difficult to quantify directly. The measured inventory of an element divided by the ...derived supply yields a replacement time estimate, which in special circumstances is related to a residence time. As a proof of concept, Th‐based supply rates imply a range in the replacement times of the rare earth elements in the North Atlantic that is consistent with the chemical reactivity of rare earth elements related to their ionic charge density. Similar estimates of replacement times for the bioactive trace elements (Fe, Mn, Zn, Cd, Cu, and Co), ranging from <5 years to >50,000 years, demonstrate the broad range of elemental reactivity in the ocean. Here we discuss how variations in source composition, fractional solubility ratios, or noncontinental sources, such as hydrothermal vents, lead to uncertainties in Th‐based replacement time estimates. We show that the constraints on oceanic replacement time provided by the Th‐based calculations are broadly applicable in predicting how elements are distributed in the ocean and for some elements, such as Fe, may inform us on how the carbon cycle may be impacted by trace element supply and removal.
Key Points
Thorium‐232 supply rates produce reasonable ocean replacement times for the rare earth elements
Iron residence time in the North Atlantic may be less than 6 years
Thorium‐232 supply rates may provide an accurate basis for the supply of many other elements for constraining biogeochemical models
Abstract
Based on AUTODYN-3D finite element analysis platform, the SPH algorithm is used to simulate the forming characteristics of Al/PTFE reactive Explosively Formed Projectile (EFP). The evolution ...behaviors and distribution of morphology, velocity, density, and temperature field during the reactive EFP were analyzed. Numerical simulation results show that Al/PTFE reactive shaped charge can form stable reactive EFP, and the overall density of reactive EFP decreases with the extension of the forming time, and the density of reactive EFP is much lower than the initial density of reactive liner. When the reactive EFP is in the state of freely flying, the high temperature region mainly concentrates on the tail of the reactive EFP, the bottom of the reactive liner and the fracture flying zone, and the high temperature region proportion is significantly affected by the explosive type, the curvature radius of the reactive liner and the wall thickness of the reactive liner.
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