ABSTRACT
The newly established luminosity functions (LFs) of high-
z
galaxies at 4 ≲
z
≲ 10 can provide a stringent check on dark matter models that aim to explain the core properties of dwarf ...galaxies. The cores of dwarf spheroidal galaxies are understood to be too large to be accounted for by free streaming of warm dark matter without overly suppressing the formation of such galaxies. Here we demonstrate with cosmological simulations that wave dark matter,
, appropriate for light bosons such as axions, does not suffer from this problem, given a boson mass of
(2
σ
). In this case, the halo mass function is suppressed below
at a level that is consistent with the high-
z
LFs, while simultaneously generating the kiloparsec-scale cores in dwarf galaxies arising from the solitonic ground state in
. We demonstrate that the reionization history in this scenario is consistent with the Thomson optical depth recently reported by
Planck
, assuming a reasonable ionizing photon production rate. We predict that the LF should turn over slowly around an intrinsic ultraviolet luminosity of
at
. We also show that for galaxies magnified
in the Hubble Frontier Fields,
predicts an order of magnitude fewer detections than cold dark matter at
down to
, allowing us to distinguish between these very different interpretations for the observed coldness of dark matter.
Due to its versatile applications in biotechnology, ion current rectification (ICR), which arises from the asymmetric nature of the ion transport in a nanochannel, has drawn much attention, recently. ...Here, the ICR behavior of a pH‐regulated nanochannel comprising two series connected cylindrical nanochannels of different radii is examined theoretically, focusing on the influences of the radii ratio, the length ratio, the bulk concentration, and the solution pH. The results of numerical simulation reveal that the rectification factor exhibits a local maximum with respect to both the radii ratio and the length ratio. The values of the radii ratio and the length ratio at which the local maximum in the rectification factor occur depend upon the level of the bulk salt concentration. The rectification factor also shows a local maximum as the solution pH varies. Among the factors examined, the solution pH influences the ICR behavior of the nanochannel most significantly.
Germanium phosphide is a potential anode material because of its high theoretical capacity and incredible rate capability on lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). However, the ...huge volume change that occurs while germanium phosphide is converted to Na3P or Li3P directly leads to poor cyclability and limits further applications. Herein, mesoporous germanium phosphide (MGeP x ) microspheres with diameter size ranging from 0.5 to 1.5 μm were first prepared by a one-step and template-free approach. MGeP x microspheres were composed of nanoparticles of around 10 nm with a narrow distribution of pore sizes of around 4 nm. The MGeP x possessed superior features in LIBs/SIBs since it shortens the diffusion path of the energy carrier and provides the buffer space for the transport of Li/Na ions. MGeP x showed attractive electrochemical properties as a potential anode candidate, such as a high first-cycle Coulombic efficiency of 82.63%, high reversible capacity (1400 mA h g–1 after 150 cycles at 0.2 C), excellent ultrahigh rate capacity (370 mA h g–1 at 72 A g–1, 40 C), and stable cycling performance (450 cycles at 1 C) in the LIBs and high reversible capacity (704 mA h g–1 after 100 cycles at 0.2 C) and stable cycling performance (200 cycles at 0.6 C) in SIBs.
Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100–200 nm, exosomes) are intensely ...investigated, the properties and functions of medium and large EVs (big EVs (bEVs); >200 nm, microvesicles) are less well explored. Here, bEVs and sEVs are identified as distinct EV populations, and it is determined that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple‐negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence‐resonance‐energy‐transfer (BRET)‐based EV reporter, reveals dose‐dependent EV biodistribution at nonlethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, yet individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass‐spectrometry‐identified tumor‐progression‐associated EV surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, and Cd44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.
Big and small extracellular vesicles circulate differentially and confer tumorigenic function modulatable by extracellular vesicle (EV) membrane proteins. Malignant breast cancers release more big EVs, in addition to small EVs, than normal cells to target organs and individually promote tumor growth via tumor‐progression‐associated EV surface membrane proteins.
ABSTRACT
We report the result of searching for globular clusters (GCs) around 55 Milky Way (MW) satellite dwarf galaxies within the distance of 450 kpc from the Galactic Centre except for the Large ...and Small Magellanic Clouds and the Sagittarius dwarf. For each dwarf, we analyse the stellar distribution of sources in Gaia DR2, selected by magnitude, proper motion, and source morphology. Using the kernel density estimation of stellar number counts, we identify 11 possible GC candidates. Cross-matched with existing imaging data, all 11 objects are known either GCs or galaxies and only Fornax GC 1–6 among them are associated with the targeted dwarf galaxy. Using simulated GCs, we calculate the GC detection limit $M_{\rm V}^{\rm lim}$ that spans the range from $M_{\rm V}^{\rm lim}\sim -7$ for distant dwarfs to $M_{\rm V}^{\rm lim}\sim 0$ for nearby systems. Assuming a Gaussian GC luminosity function, we compute that the completeness of the GC search is above 90 per cent for most dwarf galaxies. We construct the 90 per cent credible intervals/upper limits on the GC specific frequency SN of the MW dwarf galaxies: 12 < SN < 47 for Fornax, SN < 20 for the dwarfs with −12 < MV < −10, SN < 30 for the dwarfs with −10 < MV < −7, and SN < 90 for the dwarfs with MV > −7. Based on SN, we derive the probability of galaxies hosting GCs given their luminosity, finding that the probability of galaxies fainter than MV = −9 to host GCs is lower than 0.1.
We have developed a colorimetric assay for the highly sensitive and selective detection of Pb
2+ by narrowing the size distribution of gallic acid–capped gold nanoparticles (GA–AuNPs) and minimizing ...electrostatic repulsion between each GA–AuNP. We unveil that the particle size and size distribution of GA–AuNPs could be controlled by varying the pH of HAuCl
4 with fixed concentrations of HAuCl
4 and GA. When the pH of the precursor solution (i.e., HAuCl
4) was adjusted from 2.2 to 11.1, the average diameter of GA–AuNPs was decreased from 75.1
nm to 9.3
nm and their size distribution was reduced from 56.6−93.6
nm to 9.0−9.6
nm. The colorimetric sensitivity of the Pb
2+-induced aggregation of GA–AuNPs could be improved using narrow size distribution of GA–AuNPs. Moreover, further enhancement of the colorimetric sensitivity of GA–AuNPs toward Pb
2+ could be achieved by adding NaClO
4 to minimize electrostatic repulsion between GA–AuNPs, which provide a small energy barrier for Pb
2+ to overcome. Under the optimum conditions (1.0
mM NaClO
4 and 20
mM formic acid at pH 4.5), the selectivity of 9.3
nm GA–AuNPs for Pb
2+ over other metal ions in aqueous solutions is remarkably high, and its minimum detectable concentration for Pb
2+ is 10
nM. We demonstrate the practicality of 9.3
nm GA–AuNPs for the determination of Pb
2+ in drinking water. This approach offers several advantages, including simplicity (without temperature control), low cost (no enzyme or DNA), high sensitivity, high selectivity, and a large linear range (10.0–1000.0
nM).
The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While ...CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.
Background
In the house dust mite (HDM) Dermatophagoides pteronyssinus, Der p 1, 2, 5, 7, 21, and 23 have been identified as the most important allergens. The aim of this study was to define ...hypoallergenic peptides derived from the sequences of the six allergens and to use the peptides and the complete allergens to study antibody, T cell, and cytokine responses in sensitized and nonsensitized subjects.
Methods
IgE reactivity of HDM‐allergic and non‐HDM‐sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirty‐three peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP, respectively. Allergenic activity was determined by basophil activation. CD4+ T cell and cytokine responses were determined in PBMC cultures by CFSE dilution and Luminex technology, respectively.
Results
House dust mite allergics showed IgE reactivity only to complete allergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity. IgG antibodies of HDM‐allergic and nonsensitized subjects were directed against peptide epitopes and higher allergen‐specific IgG levels were found in HDM allergics. PBMC from HDM‐allergics produced higher levels of IL‐5 whereas non‐HDM‐sensitized individuals mounted higher levels of IFN‐gamma, IL‐17, pro‐inflammatory cytokines, and IL‐10.
Conclusion
IgG antibodies in HDM‐allergic patients recognize peptide epitopes which are different from the epitopes recognized by IgE. This may explain why naturally occurring allergen‐specific IgG antibodies do not protect against IgE‐mediated allergic inflammation. A mix of hypoallergenic peptides containing T cell epitopes of the most important HDM allergens was identified.
A mix of thirty‐one hypoallergenic peptides containing T cell epitopes of the six most important house dust mite (HDM) allergens was identified. Natural IgG antibodies of HDM‐allergic patients recognize different epitopes than IgE antibodies. Hypoallergenic T cell epitope‐containing peptides comprising the important HDM allergens may be used for therapy and prevention of HDM allergy.
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer ...immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8
T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
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