The idea that tumor initiation and progression are driven by a subset of cells endowed with stem-like properties was first described by Rudolf Virchow in 1855. 'Cancer stem cells', as they were ...termed more than a century later, represent a subset of tumor cells that are able to generate all tumorigenic and nontumorigenic cell types within the malignancy. Although their existence was hypothesized >150 years ago, it was only recently that stem-like cells started to be isolated from different neoplastic malignancies. Interestingly, Virchow, in suggesting a correlation between cancer and the inflammatory microenvironment, also paved the way for the 'Seed and Soil' theory proposed by Paget a few years later. Despite the time that has passed since these two important concepts were suggested, the relationships between Virchow's 'stem-like cells' and Paget's 'soil' are far from being fully understood. One emerging topic is the importance of a stem-like niche in modulating the biological properties of stem-like cancer cells and thus in affecting the response of the tumor to drugs. This review aims to summarize the recent molecular data concerning the multilayered relationship between cancer stem cells and tumor-associated macrophages that form a key component of the tumor microenvironment. We also discuss the therapeutic implications of targeting this synergistic interplay.
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Microalgal lipids are precursors to the production of biodiesel, as well as a source of valuable dietary components in the biotechnological industries. So, this study aimed to assess the effects of ...nutritional (nitrogen, and phosphorus) starvations and salinity stress (NaCl) on the biomass, lipid content, fatty acids profile, and predicted biodiesel properties of green microalga Monoraphidium braunii. The results showed that biomass, biomass productivity, and photosynthetic pigment contents (Chl. a, b, and carotenoids) of M. braunii were markedly decreased by nitrogen and phosphorus depletion and recorded the maximum values in cultures treated with full of N and P concentrations (control, 100%). These parameters were considerably increased at the low salinity level (up to 150 mM NaCl), while an increasing salinity level (up to 250 mM NaCl) reduces the biomass, its productivity, and pigment contents. Nutritional limitations and salt stress (NaCl) resulted in significantly enhanced accumulation of lipid and productivity of M. braunii, which represented more than twofold of the control. Furthermore, these conditions have enhanced the profile of fatty acid and biodiesel quality-related parameters. The current study exposed strategies to improve M. braunii lipid productivity for biodiesel production on a small scale in vitro in terms of fuel quality under low nutrients and salinity stress.
Hybrid-reinforced metals are novel composite materials in which nano-phases including nanoparticles and nanotubes/nanosheets are used simultaneously to reinforce metals or alloys to enhance physical, ...mechanical, wear and other properties. In this research, Cu/(CNT-SiC) hybrid nanocomposite was synthesized using flake powder metallurgy and spark plasma sintering method and the effects of hybrid reinforcements on microstructural, wear and corrosion properties of the developed material were investigated and compared with those of copper. Microstructural characterization showed reduction of average grain size from 419 to 307 nm and increase of low angle grain boundaries with the introduction and homogeneous dispersion of hybrid reinforcements. Mechanical tests indicated that the addition of hybrid SiC and CNT reinforcements substantially increased microhardness and reduced wear rate and friction coefficient of the Cu. Also, polarization and EIS tests revealed the suppressing of the anodic dissolution of the matrix, hindering the oxygen reduction reaction and 62.5% improvement of corrosion rate for the composite material. The effects of hybrid nano-reinforcements are presented and discussed.
Nitric oxide (NO) is a well-accepted signaling molecule that has regulatory effects on plants under various stresses. Salinity is a major issue that adversely affects plant growth and productivity. ...The current study was carried out to investigate changes in the growth, biochemical parameters, and yield of wheat plants in response to NO donors, namely sodium nitroprusside (SNP) (2.5 and 5.0 mM) and arginine (10 and 20 mM), under two salinity levels (1.2 mM and 85.5 mM NaCl). Salinity stress significantly decreased the lengths and weights of plant parts (shoot, tiller, and root) and reduced the flag leaf area, photosynthetic pigments, indole acetic acid (IAA), and yield and its components. Moreover, salt stress induced a significant accumulation of some osmoprotectants (total soluble sugars (TSS) and amino acids, especially proline) and triggered the accumulation of hydrogen peroxide (H2O2) and lipid peroxidation in wheat leaves. In contrast, arginine and SNP treatments significantly mitigated the negative impacts of salinity on growth and productivity via enhancing photosynthetic pigments, nitrate reductase, phenolic compounds, IAA, TSS, free amino acids, and proline. In addition, SNP and arginine potentially reduced oxidative damage by decreasing H2O2 and lipid peroxidation through the induction of antioxidant enzymes. The individual amino acid composition of wheat grains under the interactive effect of salinity and NO sources has been scarcely documented until now. In this study, the NO sources restrained the reduction in essential amino acids (isoleucine and lysine) of wheat grains under salinity stress and further stimulated the contents of non-essential and total aromatic amino acids. Interestingly, the applied protectants recovered the decrease in arginine and serine induced by salinity stress. Thus, SNP or arginine at the levels of 5.0 and 20 mM, respectively, had a profound effect on modulating the salt stress of wheat throughout the life cycle.
In this study, ultra-fine grained Cu and Cu + carbon nanotube (CNT) nanocomposites were prepared through a processes combining flake powder metallurgy, hot pressing, and high-pressure torsion (HPT). ...The effects of grain refinement and CNT reinforcement on the microstructure, hardness, wear resistance, and corrosion behavior of the newly developed nanocomposites were investigated. The results indicated that the HPT process decreased the grain size of Cu and Cu + CNT by 67.7% and 68.1%, respectively, and increased their microhardness by 151% and 132%. The addition of CNTs substantially improved the tribological behavior of Cu by generating a mechanically mixed carbon- and oxide-rich layer. Moreover, polarization and electrochemical impedance spectroscopy tests revealed that the CNTs have a negligible adverse effect on the corrosion resistance of the Cu + CNT nanocomposites. The influences of the processing route and CNTs are discussed.
Graphic Abstract
The microstructure and characterization of Sn–Zn–Cu–Ni (SZCN) solder alloy reinforced with TiO
2
and ZrO
2
nanoparticles (NPs) synthesized by powder metallurgy were investigated. Sn, Zn, Cu and Ni ...metallic powders were mixed mechanical by 10:1 ball to powder ratio with 300 rpm speed for 2 h. Then 0.5 wt% from nano ZrO
2
or TiO
2
was mixed by the same parameters with the mixed metal powder. The morphologies and microstructures development during the fabrication process was investigated by X-ray diffractometer (XRD), optical microscope (OM), and scanning electron microscope (SEM) with energy dispersive X-ray spectrometry (EDX). The results reveal an improved distribution of TiO
2
or ZrO
2
NPs in the SZCN matrix solder, which resulted in an improvement in its density. The analyses of microstructural demonstrated that the addition of TiO
2
or ZrO
2
NPs to SZCN solder results in the grain refinement of the β-Sn phase, besides the formation of Ni
3
Sn IMC with small size and uniform distribution. The microhardness was enhanced as a result of the addition of TiO
2
or ZrO
2
NPs. The experimental results showed that the SZCN-ZrO
2
composite solder had the greatest hardness and stress exponent values due to its effectiveness in suppressing the growth of β-Sn grains and the pile-up of dislocations. Both the electrical and thermal conductivities were improved by incorporating TiO
2
NPs compared to other solders.
Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a ...study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE
100
C or endocrine therapy: letrozole 2.5 mg, daily for 18–23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95 % CI 57–81) were randomised. 12 (54.5, 95 % CI 32.2–75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95 % CI 36.4–79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2–4 and at surgery fold change: 0.24 (95 % CI 0.12–0.51) and 0.24; (95 % CI 0.15–0.37), respectively. Plasma total cfDNA levels rose from baseline to week 8 fold change: chemotherapy 2.10 (95 % CI 1.47–3.00), letrozole 1.47(95 % CI 0.98–2.20), and were maintained at surgery in the chemotherapy group chemotherapy 2.63; 95 % CI 1.56–4.41), letrozole 0.95 (95 % CI 0.71–1.26). An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.
Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of ...infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m
. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.
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