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2.
Nature ; 569(7755): 222-228, 2019 05.
Article in English | MEDLINE | ID: mdl-30971824

ABSTRACT

The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single-cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands. Our studies demonstrate a considerable transcriptional remodelling of niche elements under stress conditions, including an adipocytic skewing of perivascular cells. Among the stress-induced changes, we observed that vascular Notch delta-like ligands (encoded by Dll1 and Dll4) were downregulated. In the absence of vascular Dll4, haematopoietic stem cells prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the bone marrow niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress and illustrate the utility of single-cell transcriptomic data in evaluating the regulation of haematopoiesis by discrete niche populations.


Subject(s)
Bone Marrow/blood supply , Cellular Microenvironment , Hematopoiesis , Hematopoietic Stem Cells , Single-Cell Analysis , Stem Cell Niche , Adaptor Proteins, Signal Transducing/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Animals , Calcium-Binding Proteins/metabolism , Cell Differentiation , Cell Lineage , Endothelium, Vascular/cytology , Female , Gene Expression Regulation , Hematopoiesis/genetics , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Male , Mice , Myeloid Cells/cytology , Myeloid Cells/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , RNA-Seq , Receptors, Notch/metabolism , Stem Cell Niche/genetics , Stress, Physiological/genetics , Transcriptome/genetics
3.
Cereb Cortex ; 34(2)2024 01 31.
Article in English | MEDLINE | ID: mdl-38342690

ABSTRACT

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.


Subject(s)
Gyrus Cinguli , Migraine without Aura , Humans , Gyrus Cinguli/diagnostic imaging , Migraine without Aura/diagnostic imaging , Cerebral Cortex , Pain/diagnostic imaging , Emotions , Magnetic Resonance Imaging/methods
4.
Mol Cell Proteomics ; 22(7): 100583, 2023 07.
Article in English | MEDLINE | ID: mdl-37236439

ABSTRACT

Single-cell proteomics as an emerging field has exhibited potential in revealing cellular heterogeneity at the functional level. However, accurate interpretation of single-cell proteomics data suffers from challenges such as measurement noise, internal heterogeneity, and the limited sample size of label-free quantitative mass spectrometry. Herein, the author describes peptide-level differential expression analysis for single-cell proteomic (pepDESC), a method for detecting differentially expressed proteins using peptide-level information designed for label-free quantitative mass spectrometry-based single-cell proteomics. While, in this study, the author focuses on the heterogeneity among the limited number of samples, pepDESC is also applicable to regular-size proteomics data. By balancing proteome coverage and quantification accuracy using peptide quantification, pepDESC is demonstrated to be effective in real-world single-cell and spike-in benchmark datasets. By applying pepDESC to published single-mouse macrophage data, the author found a large fraction of differentially expressed proteins among three types of cells, which remarkably revealed distinct dynamics of different cellular functions responding to lipopolysaccharide stimulation.


Subject(s)
Peptides , Proteomics , Animals , Mice , Proteomics/methods , Peptides/analysis , Mass Spectrometry/methods , Proteome/metabolism
5.
Nano Lett ; 24(29): 9058-9064, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39007901

ABSTRACT

PdSe2 is a puckered transition metal dichalcogenide that has been reported to undergo a two-dimensional to three-dimensional structural transition under pressure. Here, we investigated the electronic and phononic evolution of PdSe2 under high pressure using pump-probe spectroscopy. We observed the electronic intraband and interband transitions occurring in the d orbitals of Pd, revealing the disappearance of the Jahn-Teller effect under high pressure. Furthermore, we found that the decay rates of interband recombination and intraband relaxation lifetimes change at 3 and 7 GPa, respectively. First-principles calculations suggest that the bandgap closure slows the decay rate of interband recombination after 3 GPa, while the saturation of phonon-phonon scattering is the main reason for the relatively constant intraband relaxation lifetime. Our work provides a novel perspective for understanding the evolution of the electron and modulation of the carrier dynamics by phonons under pressure.

6.
Nano Lett ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753313

ABSTRACT

Carrier multiplication (CM) in semiconductors, the process of absorbing a single high-energy photon to form two or more electron-hole pairs, offers great potential for the high-response detection of high-energy photons in the ultraviolet spectrum. However, compared to two-dimensional semiconductors, conventional bulk semiconductors not only face integration and flexibility bottlenecks but also exhibit inferior CM performance. To attain efficient CM for ultraviolet detection, we designed a two-terminal photodetector featuring a unilateral Schottky junction based on a two-dimensional γ-InSe/graphene heterostructure. Benefiting from a strong built-in electric field, the photogenerated high-energy electrons in γ-InSe, an ideal ultraviolet light-absorbing layer, can efficiently transfer to graphene without cooling. It results in efficient CM within the graphene, yielding an ultrahigh responsivity of 468 mA/W and a record-high external quantum efficiency of 161.2% when it is exposed to 360 nm light at zero bias. This work provides valuable insights into developing next-generation ultraviolet photodetectors with high performance and low-power consumption.

7.
Small ; 20(24): e2308863, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38287727

ABSTRACT

Ternary organic solar cells (T-OSCs) have attracted significant attention as high-performance devices. In recent years, T-OSCs have achieved remarkable progress with power conversion efficiency (PCE) exceeding 19%. However, the introduction of the third component complicates the intermolecular interaction compared to the binary blend, resulting in poor controllability of active layer and limiting performance improvement. To address these issues, dual-functional third components have been developed that not only broaden the spectral range but also optimize morphology. In this review, the effect of the third component on expanding the absorption range of T-OSCs is first discussed. Second, the extra functions of the third component are introduced, including adjusting the crystallinity and molecular stack in active layer, regulating phase separation and purity, altering molecular orientation of the donor or acceptor. Finally, a summary of the current research progress is provided, followed by a discussion of future research directions.

8.
Opt Express ; 32(8): 14200-14210, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859372

ABSTRACT

A four-wavelength passive demodulation algorithm is proposed and experimentally demonstrated for the interrogation of the one cavity in a dual-cavity extrinsic Fabry-Perot interferometric (EFPI) sensor. The lengths of two cavities are adjusted to generate four quadrature signals for each individual cavity. Both simulation and experimental results are presented to validate the performance of this technique. The experimental results demonstrate that dynamic signals at frequencies of 100 Hz, 200 Hz, and 300 Hz with varying amplitude are successfully extracted from a dual-cavity EFPI sensor with initial lengths of 93.4803 µm and 94.0091 µm. The technique shows the potential application to measure dynamic signals in dual-cavity fiber-optic EFPI sensors.

9.
Opt Express ; 32(8): 14826-14836, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859418

ABSTRACT

An all-sapphire fiber-optic extrinsic Fabry-Perot interferometric (EFPI) sensor for the simultaneous measurement of ultra-high temperature and high pressure is proposed and experimentally demonstrated. The sensor is fabricated based on all-sapphire, including a sapphire fiber, a sapphire capillary and a sapphire wafer. A femtosecond (fs) laser is employed to drill a through hole at the side wall of the sapphire capillary to allow gas flow. The sapphire fiber is inserted from one side of the sapphire capillary. The sapphire wafer is fixed at the other side of the sapphire capillary. The first Fabry-Perot (FP) cavity, composed of the end face of the sapphire fiber and the front surface of the sapphire wafer, is used for measuring pressure, while the second FP cavity, composed of the two surfaces of the sapphire wafer, is used for measuring temperature. Experimental results show that the sensor can simultaneously measure ultra-high temperature and gas pressure within the temperature range of 20 - 1400 °C and the pressure range of 0 - 5 MPa. The temperature sensitivity is 0.0033 µm/°C, and the pressure sensitivity decreases as the temperature increases, reaching 1.8016 µm/MPa and 0.3253 µm/MPa at temperatures of 20 °C and 1400 °C, respectively.

10.
Pediatr Blood Cancer ; : e31288, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189644

ABSTRACT

BACKGROUND: Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS). METHODS: Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively. RESULTS: The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p < .05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p < .05). CONCLUSIONS: CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies.

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