A
bstract
After a review over past experiments and theoretical requirements from low-energy flavour physics, we argue that the possibility of low-mass leptoquarks (LQ) cannot be fully excluded due to ...the assumptions made in the measurements. Therefore we propose to search for the pair production of low-mass leptoquarks in Pb-Pb ultra-peripheral collisions with the least model dependence (assuming a small coupling constant ≲ 0
.
1). There are a couple of advantages: 1) high photon flux provides high production rate for low mass LQs; 2) the background contamination is much lower than that in
p
-
p
collisions. The analysis strategy permits a leptoquark to decay to all possible lepton-plus-quark modes. Taking the scalar LQ,
S
3
, with an electric charge
q
=
4
3
e
, as example, the mass point of 100 GeV can be excluded at the 95% confidence level using a dataset of 4 pb
−
1
Pb-Pb ultra-peripheral collisions at
s
= 5
.
02 TeV and the performance of the ATLAS detector in Run 2. The proposed method also applies to searching for high-mass LQs in
p
-
p
collisions as long as the LQ pair production mechanism dominates.
Mutation of Tar DNA‐binding protein 43 (TDP‐43) is linked to amyotrophic lateral sclerosis. Although astrocytes have important roles in neuron function and survival, their potential contribution to ...TDP‐43 pathogenesis is unclear. Here, we created novel lines of transgenic rats that express a mutant form of human TDP‐43 (M337V substitution) restricted to astrocytes. Selective expression of mutant TDP‐43 in astrocytes caused a progressive loss of motor neurons and the denervation atrophy of skeletal muscles, resulting in progressive paralysis. The spinal cord of transgenic rats also exhibited a progressive depletion of the astroglial glutamate transporters GLT‐1 and GLAST. Astrocytic expression of mutant TDP‐43 led to activation of astrocytes and microglia, with an induction of the neurotoxic factor Lcn2 in reactive astrocytes that was independent of TDP‐43 expression. These results indicate that mutant TDP‐43 in astrocytes is sufficient to cause non‐cell‐autonomous death of motor neurons. This motor neuron death likely involves deficiency in neuroprotective genes and induction of neurotoxic genes in astrocytes.
The debated role of astrocytes in amyotrophic lateral sclerosis (ALS) gains additional support from neurodegenerative phenotypes caused by astrocyte‐restricted expression of mutant TDP‐43 in transgenic rats.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate ...the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. It is reasonable to infer that an amplification of an as-yet undetermined hnRNPA1 function plays a pivotal role in the pathogenesis of familial ALS caused by pathogenic hnRNPA1 mutation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Thermal cloaks offer the potential to conceal internal objects from detection or to prevent thermal shock by controlling external heat flow. However, most conventional natural materials lack the ...desired flexibility and versatility required for on-demand thermal manipulation. We propose a solution in the form of homogeneous multilayer thermodynamic cloaks. Through an ingenious design, these cloaks achieve exceptional and extreme parameters, enabling the distribution of multiple materials in space. We first investigate the effects of important design parameters on the thermal shielding effectiveness of conventional thermal cloaks. Subsequently, we introduce an autonomous tuning function for the thermodynamic cloak, accomplished by leveraging two phase transition materials as thermal conductive layers. Remarkably, this tuning function does not require any energy input. Finite element analysis results demonstrate a significant reduction in the temperature gradient inside the thermal cloak compared to the surrounding background. This reduction indicates the cloak’s remarkable ability to manipulate the spatial thermal field. Furthermore, the utilization of materials undergoing phase transition leads to an increase in thermal conductivity, enabling the cloak to achieve the opposite variation of the temperature field between the object region and the background. This means that, while the temperature gradient within the cloak decreases, the temperature gradient in the background increases. This work addresses a compelling and crucial challenge in the realm of thermal metamaterials, i.e., autonomous tuning of the thermal field without energy input. Such an achievement is currently unattainable with existing natural materials. This study establishes the groundwork for the application of thermal metamaterials in thermodynamic cloaks, with potential extensions into thermal energy harvesting, thermal camouflage, and thermoelectric conversion devices. By harnessing phonons, our findings provide an unprecedented and practical approach to flexibly implementing thermal cloaks and manipulating heat flow.
Glial reaction is a common feature of neurodegenerative diseases. Recent studies have suggested that reactive astrocytes gain neurotoxic properties, but exactly how reactive astrocytes contribute to ...neurotoxicity remains to be determined. Here, we identify lipocalin 2 (lcn2) as an inducible factor that is secreted by reactive astrocytes and that is selectively toxic to neurons. We show that lcn2 is induced in reactive astrocytes in transgenic rats with neuronal expression of mutant human TAR DNA-binding protein 43 (TDP-43) or RNA-binding protein fused in sarcoma (FUS). Therefore, lcn2 is induced in activated astrocytes in response to neurodegeneration, but its induction is independent of TDP-43 or FUS expression in astrocytes. We found that synthetic lcn2 is cytotoxic to primary neurons in a dose-dependent manner, but is innocuous to astrocytes, microglia, and oligodendrocytes. Lcn2 toxicity is increased in neurons that express a disease gene, such as mutant FUS or TDP-43. Conditioned medium from rat brain slice cultures with neuronal expression of mutant TDP-43 contains abundant lcn2 and is toxic to primary neurons as well as neurons in cultured brain slice from WT rats. Partial depletion of lcn2 by immunoprecipitation reduced conditioned medium-mediated neurotoxicity. Our data indicate that reactive astrocytes secrete lcn2, which is a potent neurotoxic mediator.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Pathogenic mutation of ubiquilin 2 (UBQLN2) causes neurodegeneration in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. How UBQLN2 mutations cause the diseases is not clear. ...While over‐expression of UBQLN2 with pathogenic mutation causes neuron death in rodent models, deletion of the Ubqln2 in rats has no effect on neuronal function. Previous findings in animal models suggest that UBQLN2 mutations cause the diseases mainly through a gain rather than a loss of functions. To examine whether the toxic gain in UBQLN2 mutation is related to the enhancement of UBQLN2 functions, we created new transgenic rats over‐expressing wild‐type human UBQLN2. Considering that human UBQLN2 may not function properly in the rat genome, we also created transgenic rats over‐expressing rat's own Ubqln2. When over‐expressed in rats, both human and rat wild‐type Ubqln2 caused neuronal death and spatial learning deficits, the pathologies that were indistinguishable from those observed in mutant UBQLN2 transgenic rats. Over‐expressed wild‐type UBQLN2 formed protein inclusions attracting the autophagy substrate sequestosome‐1 and the proteasome component 26S proteasome regulatory subunit 7. These findings suggest that excess UBQLN2 is toxic rather than protective to neurons and that the enhancement of UBQLN2 functions is involved in UBQLN2 pathogenesis.
Pathogenic mutation in ubiquilin 2 (UBQLN2) causes neurodegeneration in ALS and FTLD. Studies in rodent models suggest a gain of toxic function in mutant UBQLN2. We created new transgenic rats as a relevant model and examined whether enhancing wild‐type UBQLN2 expression is implicated in the pathogenesis of mutant UBQLN2. We observed that over‐expression of human or rat wild‐type Ubqln2 caused protein aggregation and neuronal death in transgenic rats. Our findings suggest that excess UBQLN2 is toxic rather than protective to neurons and that uncontrolled enhancement of UBQLN2 function is involved in UBQLN2 pathogenesis.
Read the Editorial Highlight for this article on page 159.
Pathogenic mutation in ubiquilin 2 (UBQLN2) causes neurodegeneration in ALS and FTLD. Studies in rodent models suggest a gain of toxic function in mutant UBQLN2. We created new transgenic rats as a relevant model and examined whether enhancing wild‐type UBQLN2 expression is implicated in the pathogenesis of mutant UBQLN2. We observed that over‐expression of human or rat wild‐type Ubqln2 caused protein aggregation and neuronal death in transgenic rats. Our findings suggest that excess UBQLN2 is toxic rather than protective to neurons and that uncontrolled enhancement of UBQLN2 function is involved in UBQLN2 pathogenesis.
Read the Editorial Highlight for this article on page 159.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bismuth(III)‐based complexes have garnered increasing attention in fluorescence sensing due to their environmentally friendly and sustainable characteristics. A Bismuth(III) coordination polymer ...(CP),1‐Cl based on a naphthalene diimides(NDI)‐pyridinium is synthesized by an in situ reaction method. Notable for its sensitivity to visible light, 1‐Cl shows excellent photochromic properties, and the integration of NDI and pyridinium in one ligand makes photogenerated radicals more stable. Structural analysis and theoretical calculations are employed to investigate the potential pathway of photoinduced electron transfer (ET) during the photochromic process. Notably, in aqueous solutions, 1‐Cl displays an extraordinary fluorescence enhancement response to bromide ion (Br‐), resulting in a distinct transition from yellow to orange in color. The potential mechanism of fluorescence sensing has been revealed through single‐crystal X‐ray diffraction analysis. This insight highlights a continuous substitution process where the Cl− ions are successively replaced by Br− ions. Consequently, a single‐crystal‐to‐single‐crystal transformation (SCSC) occurs, yielding the intermediate species, 1‐Cl‐Br, which ultimately transforms into the final product, 1‐Br. Finally, the photochromic film is successfully prepared and applied to practical applications such as ink‐free printing, information anti‐counterfeiting, and the visual detection of Br− ions. This work combines photochromism with fluorescence sensing, broadening the research field and practical application of photochromic materials.
The integration of pyridinium group into the NDI core makes the photogenerated radicals in Bi(III) complex (1‐Cl) more stable. 1‐Cl has selective dynamic detection for bromide ions in aqueous media with Cl− ions in 1‐Cl continuously replaced by Br− ions. The 1‐Cl photochromic film is applied to ink‐free printing, anti‐counterfeiting, and visual detection of Br− ions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Due to green and environment‐friendly characteristics, ultra‐high‐performance supercritical fluid chromatography has been widely used in analytical fields in recent years, but until now few reports ...are available for monosaccharide compositional analysis of macromolecule polysaccharides. In this study, an ultra‐high‐performance supercritical fluid chromatography technology with an unusual binary modifier is used to determine the monosaccharide compositions of natural polysaccharides. Each carbohydrate herein is simultaneously labeled as 1‐pheny‐3‐methyl‐5‐pyrazolone and acetyl‐derivative via pre‐column derivatizations aiming to increase UV absorption sensitivity and decrease water solubility. Ten common monosaccharides are fully separated and detected on ultra‐high‐performance supercritical fluid chromatography combined with a photo‐diode array detector by systematic optimization of multiple relevant parameters, for example, column stationary phases, organic modifiers, additives, flow rates, and so on. Compared with carbon dioxide as a mobile phase, the addition of a binary modifier increases the resolution of analytes. Additionally, this method has the advantages of small consumption of organic solvent, safety, and being environmental‐friendly. It has been successfully applied for full monosaccharide compositional analysis of heteropolysaccharides from Schisandra chinensis fruits. To sum up, a new alternative approach is provided for monosaccharide compositional analysis of natural polysaccharides.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA ...mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund’s adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
An unprecedent glucuronoxylogalactoglucomannan (GXG′G″M), ME-2 (Mw, 2.60 × 105 g/mol; O-acetyl % = 16.7 %), was isolated and purified from water extracts of Auricularia auricula-judae (black woody ...ear). Firstly, due to much higher O-acetyl contents, we prepared its fully deacetylated products (dME-2; Mw, 2.13 × 105 g/mol) for convenient structure survey. The repeating structure-unit of dME-2 was readily proposed based on Mw determination, monosaccharide compositions, methylation analysis, free-radical degradation and 1/2D NMR spectroscopy. The dME-2 was identified as a highly branched polysaccharide with an average of 10 branches per 10 sugar backbone units. The backbone was only repeating →3)-α-Manp-(1→ residues, substituted at the C-2, C-6 and C-2,6 positions. The side chains included β-GlcAp-(1→, β-Xylp-(1→, α-Manp-(1→, α-Galp-(1→ and β-Glcp-(1→. Secondly, the complex substituted positions of O-acetyl groups in ME-2 were determined to be at C-2, C-4, C-6 and C-4,6 in the backbone and at C-2 and C-2,3 in some side chains. Finally, the anti-inflammatory activity of ME-2 was preliminarily explored on LPS-stimulated THP-1 cells. The above date not only provided the first example for structural studies of GXG′G″M type polysaccharides, but also facilitated development and application of black woody ear polysaccharides as medicinal agents or functional dietary supplements.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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