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Nature Communications Jun 2024Dynamic nuclear polarization (DNP) is one of the most powerful and versatile hyperpolarization methods to enhance nuclear magnetic resonance (NMR) signals. A major...
Dynamic nuclear polarization (DNP) is one of the most powerful and versatile hyperpolarization methods to enhance nuclear magnetic resonance (NMR) signals. A major drawback of DNP is the cost and complexity of the required microwave hardware, especially at high magnetic fields and low temperatures. To overcome this drawback and with the focus on the study of nanoliter and subnanoliter samples, this work demonstrates 200 GHz single chip DNP microsystems where the microwave excitation/detection are performed locally on chip without the need of external microwave generators and transmission lines. The single chip integrated microsystems consist of a single or an array of microwave oscillators operating at about 200 GHz for ESR excitation/detection and an RF receiver operating at about 300 MHz for NMR detection. This work demonstrates the possibility of using the single chip approach for the realization of probes for DNP studies at high frequency, high field, and low temperature.
PubMed: 38942752
DOI: 10.1038/s41467-024-49767-z -
Aging Jun 2024Blood transfusion is a common therapeutic procedure in hospitalized patients. Red blood cell (RBC) units undergo various biochemical and morphological changes during...
BACKGROUND AND OBJECTIVES
Blood transfusion is a common therapeutic procedure in hospitalized patients. Red blood cell (RBC) units undergo various biochemical and morphological changes during storage (storage lesion). miRNAs have been studied intensively regarding cellular metabolic processes, but the effect of miRNAs on blood storage is not well defined.
MATERIALS AND METHODS
We performed bioinformatics analysis on the public data set of miRNA expression of RBC based on R language, and performed the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis on the target genes of differentially expressed miRNA. The expression of miRNA differential genes in blood samples stored at different times was verified by qRT-PCR. Next, we used ELISA and qRT-PCR to verify the expression of IL-1β, IL-6, IL-12 and TNF-α in blood at day 1 and day 42. In addition, , we transfected macrophages with overexpressed miRNA, and the effects of overexpressed miRNA on macrophage polarization and the release of inflammatory factors were verified by flow cytometry and qRT-PCR and ELISA.
RESULTS
This study combined bioinformatics analysis and experiments to discover the differentially expressed miRNAs in long-term stored blood. The results showed that compared to fresh blood samples, the inflammatory factors were significantly doubled by ELISA, as well as the higher mRNA expression at 42 day. Experimentally verified that miR-33a-5p promoted the M1 type macrophage polarization and increased the release of related inflammatory factors through PPARα/ACC2/AMPK/CPT-1a axis regulation.
CONCLUSIONS
This study elucidates a potential mechanism of inflammatory factor accumulation in long-term stored blood, providing a theoretical basis and a potential target to prevent transfusion-related adverse reactions.
PubMed: 38942609
DOI: 10.18632/aging.205925 -
Clinics in Dermatology Jun 2024Melanoma is the deadliest skin cancer, presenting typically with changing pigmented areas and usually treated with surgical removal. As benign cutaneous pigmented...
Melanoma is the deadliest skin cancer, presenting typically with changing pigmented areas and usually treated with surgical removal. As benign cutaneous pigmented lesions are very common in all populations, it can be challenging to identify which areas should be cut out or left untreated. Delayed treatment in melanoma increases the risk of death, but it is not possible to remove all lesions. Dermatoscopy uses polarised light and can be used to help distinguish melanomas from benign lesions. Dermatoscopy images with a confirmed diagnosis can be utilized to develop artificial intelligence as a medical device (AIaMD) tool. This contribution discusses the utilization of artificial intelligence (AI) in melanoma management and describes an AIaMD tool that has been used in current UK clinical practice on over 80,000 patients. This is a springboard for discussing the scope, risks, and mitigations for future AI use by all clinicians involved in managing people with melanoma.
PubMed: 38942155
DOI: 10.1016/j.clindermatol.2024.06.015 -
Cell Reports. Medicine Jun 2024Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle...
Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after therapy exhibit high POSTN expression levels and high numbers of TTR macrophages. POSTN polarizes human macrophages toward a TTR phenotype and promotes resistance to targeted therapy in a melanoma mouse model, which is associated with a phenotype change in intratumoral macrophages. Finally, polarized TTR macrophages directly protect human melanoma cells from MEKi-induced killing via CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages may offer a strategy to overcome resistance to targeted therapy in melanoma.
PubMed: 38942020
DOI: 10.1016/j.xcrm.2024.101611 -
Biofabrication Jun 2024Human skin vasculature features a unique anatomy in close proximity to the skin appendages and acts as a gatekeeper for constitutive lymphocyte trafficking to the skin....
Human skin vasculature features a unique anatomy in close proximity to the skin appendages and acts as a gatekeeper for constitutive lymphocyte trafficking to the skin. Approximating such structural complexity and functionality in 3D skin models is an outstanding tissue engineering challenge. In this study, we leverage the capabilities of the digital-light-processing (DLP) bioprinting to generate an anatomically-relevant and miniaturized 3D skin-on-a-chip (3D-SoC) model in the size of a 6 mm punch biopsy. The 3D-SoC contains a perfusable vascular network resembling the superficial vascular plexus of the skin and closely surrounding bioengineered hair follicles. The perfusion capabilities of the 3D-SoC enables the circulation of immune cells, and high-resolution imaging of the immune cell-endothelial cell interactions, namely rolling, tethering and extravasation in real-time. Moreover, the vascular pattern in 3D-SoC captures the physiological range of shear rates found in cutaneous blood vessels and allows for studying the effect of shear rate on T cell trafficking. In 3D-SoC, as expected, in vitro-polarized T helper 1 (Th1) cells show a stronger attachment on the vasculature compared to naïve T cells. Both naïve and T cells exhibit higher retention in the low-shear zones in the early stages (< 5 min) of T cell attachment. Interestingly, at later stages T cell retention rate becomes independent of the shear rate. The attached Th1 cells further transmigrate from the vessel walls to the extracellular space and migrate toward the bioengineered hair follicles and interfollicular epidermis. When the epidermis is not present, Th1 cell migration toward the epidermis is significantly hindered, underscoring the role of epidermal signals on T cell infiltration. Our data validates the capabilities of 3D-SoC model to study the interactions between immune cells and skin vasculature in the context of epidermal signals. The biopsy-sized 3D-SoC model in this study represents a new level of anatomical and cellular complexity, and brings us a step closer to generating a truly functional human skin with its tissue-specific vasculature and appendages in the presence of circulating immune cells.
PubMed: 38941996
DOI: 10.1088/1758-5090/ad5d1a -
Journal of Physics. Condensed Matter :... Jun 2024The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus...
The application of half-metallic materials in single-molecule optoelectronic devices opens a promising way in advancing device performance and functionality, thus addressing a research question of significance. Here we propose a series of single-molecule devices with half-metallic FeN4-doped armchair graphene nanoribbon as electrodes and metalloporphyrin (MPr) molecules as photoresponsive materials for photon harvesting, which are driven by photogalvanic effects (PGEs). Through the quantum transport simulations, we systematically investigated the spin-polarized photocurrents under the linearly polarized light illumination in these devices. Since the exclusive opening only exists in the spin-up channel of the half-metallic nanoribbons, these devices can generate a large photocurrent in the spin-up direction whereas suppressing the spin-down photocurrent. Consequently, they exhibit an effective spin-filtering effect at numerous photon energies. Our study unveils the excellent spin-filtering effect achieved in single-molecule optoelectronic devices with half-metallic electrodes, showing instructive significance for the future design of new optoelectronic devices. .
PubMed: 38941993
DOI: 10.1088/1361-648X/ad5d37 -
Journal of Physics. Condensed Matter :... Jun 2024Quantum anomalous Hall insulators are topologically characterized by non-zero integer Chern numbers, the sign of which depends on the direction of the exchange field...
Quantum anomalous Hall insulators are topologically characterized by non-zero integer Chern numbers, the sign of which depends on the direction of the exchange field that breaks time-reversal symmetry. This feature allows the manipulation of the conducting chiral edge states present at the interface of two magnetic domains with opposite magnetization and opposite Chern numbers. Motivated by this broad understanding, the present study investigates the quantum transport properties of a magnetized $Bi_2Se_3$ topological insulator nanoribbon with a domain wall oriented either parallel or perpendicular to the transport direction. Employing an atomistic tight-binding model and a non-equilibrium Green's function formalism, we calculate the quantum conductance and explore the nature of the edge states. We elucidate the conditions leading to exact conductance quantization and identify the origin of deviations from this behavior. Our analysis shows that although the conductance is quantized in the presence of the horizontal domain wall, the quantization is absent in the perpendicular domain wall case. Furthermore, the investigation of the spin character of the edge modes confirms that the conductance in the horizontal domain wall configuration is spin polarized. This finding underscores the potential of our system as a simple three dimensional spin-filter device.
PubMed: 38941992
DOI: 10.1088/1361-648X/ad5d34 -
Emerging Infectious Diseases Jun 2024We report a natural infection with a Eurasian highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in a free-ranging juvenile polar bear (Ursus maritimus)...
We report a natural infection with a Eurasian highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in a free-ranging juvenile polar bear (Ursus maritimus) found dead in North Slope Borough, Alaska, USA. Continued community and hunter-based participation in wildlife health surveillance is key to detecting emerging pathogens in the Arctic.
PubMed: 38941966
DOI: 10.3201/eid3008.240481 -
Journal of Environmental Management Jun 2024Alpine grasslands are distributed widely on high-elevated ranges and plateaus from the wet tropics to polar regions, accounting for approximately 3% of the world's land...
Alpine grasslands are distributed widely on high-elevated ranges and plateaus from the wet tropics to polar regions, accounting for approximately 3% of the world's land area. The Qinghai-Tibetan Plateau (QTP) is the highest and largest plateau in the world, and approximately 60% of the plateau consists of alpine grassland, which is used mainly for grazing animals. Livestock structure was determined in Guinan (GN), Yushu (YS) and Maqu counties (MQ) on the QTP by interviewing 235 local pastoralists. Based on data collected from GN, the livestock carrying capacity was calculated using herbage dry matter biomass intake (LCC) by the livestock, and the metabolizable energy yield (LCC) and digestible crude protein (LCC) available in pasture. The pasture area per household differed among the regions of the QTP, which was the main reason for the difference in livestock stocking rate. The householders raised the appropriate proportion of breeding females and young yaks and sheep in GN and MQ, but not in YS, to maintain a constant turnover. Most pasture in YS was used at the community level, especially in summer. The calculated carrying capacities based on metabolizable energy yield (LCC) of the pasture and dry matter biomass (LCC) were similar in most months except for August, when the value of LCC was higher than LCC. Based on the digestible protein of the pasture, the calculated livestock carrying capacity overestimated the actual carrying capacity during the herbage growing season from May to September. Appropriate practices should be taken in different regions of QTP, such as providing supplementary feed, especially protein, during the forage non-growing season. Livestock carrying capacity should be adjusted dynamically, and calculated by a number of parameters. The stocking rate should be controlled to optimize livestock production and curb or minimize grassland degradation to generate a sustainable system. This study examined the grasslands and LCC on the QTP, but the results could be applied to grasslands worldwide.
PubMed: 38941853
DOI: 10.1016/j.jenvman.2024.121586 -
Biochemical and Biophysical Research... Jun 2024Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the...
Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins. In this study, we enhanced the previous scyllatoxin-based synthetic peptide by substituting natural amino acids and successfully expressed it in E. coli. The peptide was optimized by mutating the C-terminal amidated valine to valine and glutamine, and by reducing the disulfide bonds from three to two. Circular dichroism confirmed proper secondary structure formation, and fluorescence polarization analysis revealed specific, concentration-dependent binding to HIV gp120, supported by molecular dynamics simulations. These findings indicate the potential for scalable microbial production of effective antiviral peptides, with significant applications in pharmaceutical development for HIV treatment.
PubMed: 38941793
DOI: 10.1016/j.bbrc.2024.150310