bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation
Authors: Yang Yuan , Luo Ruizeng , Chao Shengyu , Xue Jiangtao , Jiang Dongjie , Feng Yun Hao , Guo Xin Dong , Luo Dan , Zhang Jiaping , Li Zhou , Wang Zhong Lin 
Published: November 2022

AbstractEpidermal growth factor is an excellent drug for promoting wound healing; however, its conventional administration strategies are associated with pharmacodynamic challenges, such as low transdermal permeability, reduction, and receptor desensitization. Here, we develop a microneedle-based self-powered transcutaneous electrical stimulation system (mn-STESS) by integrating a sliding free-standing triboelectric nanogenerator with a microneedle patch to achieve improved epidermal growth factor pharmacodynamics. We show that the mn-STESS facilitates drug penetration and utilization by using microneedles to pierce the stratum corneum. More importantly, we find that it converts the mechanical energy of finger sliding into electricity and mediates transcutaneous electrical stimulation through microneedles. We demonstrate that the electrical stimulation applied by mn-STESS acts as an “adjuvant” that suppresses the reduction of epidermal growth factor by glutathione and upregulates its receptor expression in keratinocyte cells, successfully compensating for receptor desensitization. Collectively, this work highlights the promise of self-powered electrical adjuvants in improving drug pharmacodynamics, creating combinatorial therapeutic strategies for traditional drugs.
Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment
Authors: Zelepukin Ivan V. , Griaznova Olga Yu. , Shevchenko Konstantin G. , Ivanov Andrey V. , Baidyuk Ekaterina V. , Serejnikova Natalia B. , Volovetskiy Artur B. , Deyev Sergey M. , Zvyagin Andrei V. 
Published: November 2022

AbstractTumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.
Valence-skipping and quasi-two-dimensionality of superconductivity in a van der Waals insulator
Authors: Zhang Caorong , Huang Junwei , Zhai Kun , Akhtari Keivan , Shen Zhiwei , Ao Lingyi , Li Zeya , Qin Feng , Chang Yukai , Zhou Ling , Tang Ming , Dai Xueting , Qiu Caiyu , Zhang Yi , Wang Lin , Liu Zhongyuan , Tian Yongjun , Bahramy Mohammad Saeed , Yuan Hongtao 
Published: November 2022

AbstractValence fluctuation of interacting electrons plays a crucial role in emergent quantum phenomena in correlated electron systems. The theoretical rationale is that this effect can drive a band insulator into a superconductor through charge redistribution around the Fermi level. However, the root cause of such a fluctuating leap in the ionic valency remains elusive. Here, we demonstrate a valence-skipping-driven insulator-to-superconductor transition and realize quasi-two-dimensional superconductivity in a van der Waals insulator GeP under pressure. This is shown to result from valence skipping of the Ge cation, altering its average valency from 3+ to 4+, turning GeP from a layered compound to a three-dimensional covalent system with superconducting critical temperature reaching its maximum of 10 K. Such a valence-skipping-induced superconductivity with a quasi-two-dimensional nature in thin samples, showing a Berezinskii-Kosterlitz-Thouless-like character, is further confirmed by angle-dependent upper-critical-field measurements. These findings provide a model system to examine competing order parameters in valence-skipping systems.
Engineering high quality graphene superlattices via ion milled ultra-thin etching masks
Authors: Barcons Ruiz David , Herzig Sheinfux Hanan , Hoffmann Rebecca , Torre Iacopo , Agarwal Hitesh , Kumar Roshan Krishna , Vistoli Lorenzo , Taniguchi Takashi , Watanabe Kenji , Bachtold Adrian , Koppens Frank H. L. 
Published: November 2022

AbstractNanofabrication research pursues the miniaturization of patterned feature size. In the current state of the art, micron scale areas can be patterned with features down to ~30 nm pitch using electron beam lithography. Here, we demonstrate a nanofabrication technique which allows patterning periodic structures with a pitch down to 16 nm. It is based on focused ion beam milling of suspended membranes, with minimal proximity effects typical to standard electron beam lithography. The membranes are then transferred and used as hard etching masks. We benchmark our technique by electrostatically inducing a superlattice potential in graphene and observe bandstructure modification in electronic transport. Our technique opens the path towards the realization of very short period superlattices in 2D materials, but with the ability to control lattice symmetries and strength. This can pave the way for a versatile solid-state quantum simulator platform and the study of correlated electron phases.
Theoretical insights into the Peierls plasticity in SrTiO3 ceramics via dislocation remodelling
Authors: Li Yi , Liu Xiangyang , Zhang Peng , Han Yi , Huang Muzhang , Wan Chunlei 
Published: November 2022

AbstractAn in-depth understanding of the dislocations motion process in non-metallic materials becomes increasingly important, stimulated by the recent emergence of ceramics and semiconductors with unexpected room temperature dislocation-mediated plasticity. In this work, local misfit energy is put forward to accurately derive the Peierls stress and model the dislocation process in SrTiO3 ceramics instead of the generalized stacking fault (GSF) approach, which considers the in-plane freedom degrees of the atoms near the shear plane and describes the breaking and re-bonding processes of the complex chemical bonds. Particularly, we discover an abnormal shear-dependence of local misfit energy, which originates from the re-bonding process of the Ti-O bonds and the reversal of lattice dipoles. In addition, this approach predicts that oxygen vacancies in the SrTiO3 can facilitate the nucleation and activation of dislocations with improvement of fracture toughness, owing to the reduction of average misfit energy and Peierls stress due to the disappearance of lattice dipole reversal. This work provides undiscovered insights into the dislocation process in non-metallic materials, which may bring implications to tune the plasticity and explore unknown ductile compositions.
Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b
Authors: Shibata Kensuke , Motozono Chihiro , Nagae Masamichi , Shimizu Takashi , Ishikawa Eri , Motooka Daisuke , Okuzaki Daisuke , Izumi Yoshihiro , Takahashi Masatomo , Fujimori Nao , Wing James B. , Hayano Takahide , Asai Yoshiyuki , Bamba Takeshi , Ogawa Yoshihiro , Furutani-Seiki Makoto , Shirai Mutsunori , Yamasaki Sho 
Published: November 2022

AbstractMHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.
Zinc- and magnesium-doped hydroxyapatite-urea nanohybrids enhance wheat growth and nitrogen uptake
Authors: Sharma Bhaskar , Afonso Luis O. B. , Singh Manoj Pratap , Soni Udit , Cahill David M. 
Published: November 2022

AbstractThe ongoing and unrestrained application of nitrogen fertilizer to agricultural lands has been directly linked to climate change and reductions in biodiversity. The agricultural sector needs a technological upgrade to adopt sustainable methods for maintaining high yield. We report synthesis of zinc and magnesium doped and undoped hydroxyapatite nanoparticles, and their urea nanohybrids, to sustainably deliver nitrogen to wheat. The urea nanohybrids loaded with up to 42% nitrogen were used as a new source of nitrogen and compared with a conventional urea-based fertilizer for efficient and sufficient nitrogen delivery to pot-grown wheat. Doping with zinc and magnesium manipulated the hydroxyapatite crystallinity for smaller size and higher nitrogen loading capacity. Interestingly, 50% and 25% doses of urea nanohybrids significantly boosted the wheat growth and yield compared with 100% doses of urea fertilizer. In addition, the nutritional elements uptake and grain protein and phospholipid levels were significantly enhanced in wheat treated with nanohybrids. These results demonstrate the potential of the multi-nutrient complexes, the zinc and magnesium doped and undoped hydroxyapatite-urea nanoparticles, as nitrogen delivery agents that reduce nitrogen inputs by at least 50% while maintaining wheat plant growth and nitrogen uptake to the same level as full-dose urea treatments.
Chromosome painting and phylogenetic analysis suggest that the genus Lophostoma (Chiroptera, Phyllostomidae) is paraphyletic
Authors: da Silva Natalia Karina Nascimento , Nagamachi Cleusa Yoshiko , Rodrigues Luis Reginaldo Ribeiro , O’Brien Patricia Caroline Mary , Yang Fengtang , Ferguson-Smith Malcolm Andrew , Pieczarka Julio Cesar 
Published: November 2022

AbstractThe subfamily Phyllostominae (Chiroptera, Phyllostomidae) comprises 10 genera of Microchiroptera bats from the Neotropics. The taxonomy of this group is controversial due to incongruities in the phylogenetic relationships evident from different datasets. The genus Lophostoma currently includes eight species whose phylogenetic relationships have not been resolved. Integrative analyzes including morphological, molecular and chromosomal data are powerful tools to investigate the phylogenetics of organisms, particularly if obtained by chromosomal painting. In the present work we performed comparative genomic mapping of three species of Lophostoma (L. brasiliense 2n = 30, L. carrikeri 2n = 26 and L. schulzi 2n = 26), by chromosome painting using whole chromosome probes from Phyllostomus hastatus and Carollia brevicauda; this included mapping interstitial telomeric sites. The karyotype of L. schulzi (LSC) is a new cytotype. The species L. brasiliense and L. carrikeri showed interstitial telomeric sequences that probably resulted from expansions of repetitive sequences near pericentromeric regions. The addition of chromosomal painting data from other species of Phyllostominae allowed phylogeny construction by maximum parsimony, and the determination that the genera of this subfamily are monophyletic, and that the genus Lophostoma is paraphyletic. Additionally, a review of the taxonomic status of LSC is suggested to determine if this species should be reclassified as part of the genus Tonatia.
Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease
Authors: Thomas Alyssa L. , Lehn Maria A. , Janssen Edith M. , Hildeman David A. , Chougnet Claire A. 
Published: November 2022

AbstractAge-associated microglial dysfunction contributes to the accumulation of amyloid-β (Aβ) plaques in Alzheimer’s disease. Although several studies have shown age-related declines in the phagocytic capacity of myeloid cells, relatively few have examined phagocytosis of normally aged microglia. Furthermore, much of the existing data on aging microglial function have been generated in accelerated genetic models of Alzheimer’s disease. Here we found that naturally aged microglia phagocytosed less Aβ over time. To gain a better understanding of such dysfunction, we assessed differences in gene expression between young and old microglia that either did or did not phagocytose Aβ. Young microglia had both phagocytic and neuronal maintenance signatures indicative of normal microglial responses, whereas, old microglia, regardless of phagocytic status, exhibit signs of broad dysfunction reflective of underlying neurologic disease states. We also found downregulation of many phagocytic receptors on old microglia, including TREM2, an Aβ phagocytic receptor. TREM2 protein expression was diminished in old microglia and loss of TREM2+ microglia was correlated with impaired Aβ uptake, suggesting a mechanism for phagocytic dysfunction in old microglia. Combined, our work reveals that normally aged microglia have broad changes in gene expression, including defects in Aβ phagocytosis that likely underlies the progression to neurologic disease.
Peripheral arterial elasticity changes derived by volume-oscillometry in reaction to hyperemia as a possible assessment of flow-mediated vasodilatation
Authors: Yamakoshi Takehiro , Rolfe Peter , Yamakoshi Ken-ichi 
Published: November 2022

AbstractThe flow-mediated dilation (FMD) test is commonly utilized and is the only technique for the assessment of vascular endothelial cell function. With this test, the augmentation of a brachial artery diameter following reactive hyperemia is measured precisely using ultrasonography by a skilled operator. This is a hospital-only test, and would be more useful if conveniently performed at home. This paper describes a first approach for studying the impact of changes in peripheral arterial elasticity, with prospects towards possible assessment of functional reactivity. A recently developed smartphone-based instrument was used to measure elastic properties of finger and radial arteries, related to stiffness and vasodilatation, as a function of distending pressure derived by photo-plethysmographic volume-oscillometry. Elasticity changes in both arteries before and after a 5-min supra-systolic upper-arm cuff occlusion were successfully obtained in 15 normal volunteers. The index-values of stiffness and vasodilatation showed, respectively, a significant decrease and increase (p < 0.01), demonstrating clearly the expected elasticity changes with hyperemia, which could be consistent with the clinically-stated reaction in an FMD test. The results suggest that this method could easily provide important information of both elasticity and vasodilatation. It appears promising as a convenient assessment method to contribute to arteriosclerotic cardiovascular screening.
Tumor suppressor DEAR1 regulates mammary epithelial cell fate and predicts early onset and metastasis in triple negative breast cancer
Authors: Le Uyen Q. , Chen Nanyue , Balasenthil Seetharaman , Lurie Eugene , Yang Fei , Liu Suyu , Rubin Laura , Solis Soto Luisa Maren , Raso Maria Gabriela , Batra Harsh , Sahin Aysegul A. , Wistuba Ignacio I. , Killary Ann McNeill 
Published: November 2022

AbstractTriple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are enriched for ALDH1A1 and CK5 expression, EpCAM−/CD49f+ and CD44high/24low basal-like epithelial cells, indicating that DEAR1 regulates stem/progenitor cell properties and luminal-basal progenitor transition. We show that DEAR1 maintains luminal differentiation as a novel ubiquitin ligase for SNAI2/SLUG, a master regulator driving stemness and generation of basal-like progenitor populations. We also identify a significant inverse correlation between DEAR1 and SNAI2 expression in a 103 TNBC case cohort and show that low DEAR1 expression significantly correlates with young age of onset and shorter time to metastasis, suggesting DEAR1 could serve as a biomarker to stratify early onset TNBCs for targeted stem cell therapies.
Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia
Authors: Okoi Catherine , Anderson Suzanne T. , Mulwa Sarah , Worwui Archibald , Antonio Martin , Gehre Florian , Adetifa Ifedayo 
Published: November 2022

AbstractThe clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease.
Extraction and mapping of downpour impact and their Cumulonimbus origin, 20 May 2020, Vâlcea (Romania) via Sentinnel-1 SAR dual polarization
Authors: Hachemi Kamel , Grecu Florina , Constantin Dana Maria , Ioana-Toroimac Gabriela 
Published: November 2022

AbstractThe aim of this work is to study the impact and characteristics of the meteorological phenomenon that occurred on May 20, 2020 in Vâlcea County, Romania. For this purpose, we used SAR radar images from the Sentinel-1 series at different dates, before, during and after the event. The methodology consists in exploiting and combining the two polarisations, VV and VH, of the recorded radar wave. The results obtained can be summarised as the extraction of areas completely covered by water and areas characterised by high roughness and very high humidity. The latter (roughness/humidity) can have two different origins. The first one corresponds to an area affected by downpours, giving a high roughness due to the interaction of water drops with the ground and also to the presence of hail, amplified by the wind factor. On the other hand, the second one coincides, quite simply, with the presence of a thundercloud, precisely a Cumulonimbus, which formed in that particular place as a result of the favourable geomorphological characteristics and meteorological conditions, giving a high humidity due to the high water content. We also determined the total impacted area of about 96.71 km2, whose 60.17 km2 of water covered area, which is 2.45% of the study area. The remaining 36.54 km2 (1.49%) represents the affected rough surface, located in the plain, or the humid surface corresponding to the area of the Cumulonimbus head covering the plain.
Gut bacteriome and metabolome of Ascaris lumbricoides in patients
Authors: Klomkliew Pavit , Sawaswong Vorthon , Chanchaem Prangwalai , Nimsamer Pattaraporn , Adisakwattana Poom , Phuphisut Orawan , Tipthara Phornpimon , Tarning Joel , Payungporn Sunchai , Reamtong Onrapak 
Published: November 2022

AbstractThe most frequent intestinal helminth infections in humans are attributed to Ascaris lumbricoides, and there are concerns over the anthelminthic resistance of this species. The gut microbiota has essential roles in host physiology. Therefore, discovering host-parasite–microbiota interactions could help develop alternative helminthiasis treatments. Additionally, these interactions are modulated by functional metabolites that can reveal the mechanisms of infection and disease progression. Thus, we aimed to investigate bacteriomes in the gut of helminths and fecal samples of patients via next-generation sequencing. Our results showed that infection intensity was associated with the bacterial composition of helminth guts but not with the intestinal bacteriome of human hosts. Moreover, the metabolomes of A. lumbricoides in the heavy and light ascariasis cases were characterized using ultra-high performance liquid chromatography/time-of-flight mass spectrometry. Increased levels of essential biomolecules, such as amino acids, lipids, and nucleotide precursors, were found in the guts of helminths isolated from heavily infected patients, implying that these metabolites are related to egg production and ascariasis pathogenicity. These findings are the first step towards a more complete understanding of the mechanisms by which the bacteriome of helminth guts affect their colonization and may reveal novel and more effective approaches to parasitic disease therapy.