47 research outputs found
sj-pdf-1-ajs-10.1177_03635465221114412 – Supplemental material for A Slotted Decellularized Osteochondral Scaffold With Layer-Specific Release of Stem Cell Differentiation Stimulators Enhances Cartilage and Bone Regeneration in Osteochondral Defects in a Rabbit Model
Supplemental material, sj-pdf-1-ajs-10.1177_03635465221114412 for A Slotted Decellularized Osteochondral Scaffold With Layer-Specific Release of Stem Cell Differentiation Stimulators Enhances Cartilage and Bone Regeneration in Osteochondral Defects in a Rabbit Model by Zhenhan Deng, Weimin Zhu, Bangbao Lu, Muzhi Li and Daqi Xu in The American Journal of Sports Medicine</p
Integrative analyses with organoid modelling reveal the biology of kidney cancer
The genetic evolution of clear cell renal cell carcinoma (ccRCC) has been extensively characterised through observational studies; however, the corresponding molecular and cellular phenotypic adaptations along distinct evolutionary trajectories remain incompletely understood. This gap is largely due to the lack of representative experimental models and limited functional interrogation. In this thesis, I investigate the biology of ccRCC using patient-derived models and propose a conceptual framework outlining key molecular and cellular transitions across tumour initiation, progression, and metastasis.
To study initiation, I characterised the basal state of transformation-prone proximal tubular cells and identified a rare subpopulation harbouring chromosome 3p loss. I further evaluated the role of kidney injury in promoting tumour initiation, proposing a model in which injury expands a cell state permissive to transformation. Using patient-derived normal kidney organoids and CRISPR/Cas9 genome editing, I demonstrated that early tumour-initiating alterations, including 3p and VHL loss, do not confer immediate proliferative fitness advantages in vitro.
In the context of progression, I established a patient-derived organoid (PDO) biobank for ccRCC and characterised their genomic and transcriptomic landscape. Leveraging integrative analyses incorporating preclinical models and clinical datasets at bulk and single-cell levels, I delineated divergent genotype-to-phenotype relationships focusing on PBRM1- and BAP1-driven trajectories. Functional perturbation of these genes in both tumour and normal organoids confirmed key phenotypic differences related to proliferation, extracellular matrix remodelling, renal lineage commitment, inflammatory signalling, and chromosomal instability.
Finally, I demonstrated that CDKN2A is a target of 9p loss and frequently undergoes biallelic inactivation in metastatic ccRCC. Functional perturbation in organoid models revealed context-dependent effects, with CDKN2A-null tumour organoids exhibiting increased proliferation and growth factor independence
Poly[octaaquadi-μ-phosphato-trinickel(II)]. Corrigendum
A correction is made to the name of the first author in Shouwen, Wang, Gao, Wen & Zhou [Acta Cryst. (2008), E64, m259]
An inquiry into AI university curriculum and market demand: Facts, fits, and future trends
© 2019 Copyright is held by the owner/author(s). This study aims at exploring the fit/misfit between artificial intelligence (AI) curriculum objectives and AI-relevant job qualifications. In our preliminary analysis, we applied the data collected from a major employment website and multiple university programs to extricate dimensions and properties for academic curriculum design and job qualifications, respectively. After investigating AI career market demand and supply, we recommend aligning AI curriculum with current and future market demands. Envisioning our future research, further theoretical development with supportive evidence should be leveraged to interpret the fit/misfit between AI curriculum design and market needs
Dimension conversion and scaling of disordered protein chains
To extract protein dimension and energetics information from single-molecule fluorescence resonance energy transfer spectroscopy (smFRET) data, it is essential to establish the relationship between the distributions of the radius of gyration (R-g) and the end-to-end (donor-to-acceptor) distance (R-ee). Here, we performed a coarse-grained molecular dynamics simulation to obtain a conformational ensemble of denatured proteins and intrinsically disordered proteins. For any disordered chain with fixed length, there is an excellent linear correlation between the average values of R-g and R-ee under various solvent conditions, but the relationship deviates from the prediction of a Gaussian chain. A modified conversion formula was proposed to analyze smFRET data. The formula reduces the discrepancy between the results obtained from FRET and small-angle X-ray scattering (SAXS). The scaling law in a coil-globule transition process was examined where a significant finite-size effect was revealed, i.e., the scaling exponent may exceed the theoretical critical boundary [1/3, 3/5] and the prefactor changes notably during the transition. The Sanchez chain model was also tested and it was shown that the mean-field approximation works well for expanded chains.Ministry of Science and Technology of China [2015CB910300]SCI(E)[email protected]
How to remove the influence of trace water from the absorption spectra of SWNTs dispersed in ionic liquids
Single-walled carbon nanotubes (SWNTs) can be efficiently dispersed in the imidazolium-based ionic liquids (ILs), at relatively high concentration, with their intrinsic structure and properties retained. Due to the hygroscopicity of the ILs, water bands may be introduced in the absorption spectra of IL-dispersed SWNTs and cause problems in spectral deconvolution and further analysis. In order to remove this influence, a quantitative characterization of the trace water in [BMIM]+[PF6]− and [BMIM]+[BF4]− was carried out by means of UV–vis-NIR absorption spectroscopy. A simple yet effective method involving spectral subtraction of the water bands was utilized, and almost no difference was found between the spectra of the dry IL-dispersed SWNT samples treated under vacuum for 10 hours and the spectra of the untreated samples with subtraction of the pure water spectrum. This result makes it more convenient to characterize SWNTs with absorption spectra in the IL-dispersion system, even in the presence of trace amount of water
(n,m) Assignments of Metallic Single-Walled Carbon Nanotubes by Raman Spectroscopy: The Importance of Electronic Raman Scattering
In this work, we report an accurate and convenient method that can be used to assign the chirality of all metallic single-walled carbon * nanotubes (M-SWNTs). This method is designed based on the electronic Raman scattering (ERS) features, which are resonantly enhanced at the corresponding excitonic transition energies (M-ii(+) and M-ii(-)). Using this method, we are able to accurately determine the electronic property M-ii, with the resolution of a vibrational Raman spectroscopy (similar to 0.3 meV), which is significantly higher than that of the electronic spectroscopies (similar to 3 meV). We use the M-11 splitting value, which is found insensitive to environmental changes, as a universal criteria for (n,m) assignments in various environments. As an illustrative example, simply using a commercialized Raman spectrometer with two laser lines (1.959 and 2.330 eV), we are able to unambiguously assign 18 metallic chiralities with M-11 in the 1.6-2.3 eV range in our samples. This method provides an accurate database of M-ii's in a similar way as photoluminescence excitation spectroscopy does for S-ii's. It can facilitate further systematic studies on the properties of MSWNTs with defined chirality.Ministry of Science and Technology of China [2016YFA0201904]; National Natural Science Foundation of China [21631002, U1632119, 91333105]SCI(E)[email protected]; [email protected]
