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"Zeng, Zipeng"
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Generation of patterned kidney organoids that recapitulate the adult kidney collecting duct system from expandable ureteric bud progenitors
2021
Current kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of the adult kidney’s collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Applying an efficient gene editing strategy to remove RET activity, we demonstrate genetically modified UB organoids can model congenital anomalies of kidney and urinary tract. Taken together, these platforms will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting duct system.
Here, the authors model the collecting duct system in kidneys by taking ureteric bud (UB) progenitor cells from both mouse and human primary tissues, as well as from hESC and hiPSC to generate organoids, which can model congenital anomalies of the kidney and urinary tract.
Journal Article
Asymmetric Oxo‐Bridged ZnPb Bimetallic Electrocatalysis Boosting CO2‐to‐HCOOH Reduction
by
Wang, Yaobing
,
Zeng, Zipeng
,
Mohamed, Aya Gomaa Abdelkader
in
bimetallic electrocatalyst
,
Carbon dioxide
,
CO2 reduction
2022
Electrochemical CO2 reduction (ECR) is one of the promising CO2 recycling technologies sustaining the natural carbon cycle and offering more sustainable higher‐energy chemicals. Zn‐ and Pb‐based catalysts have improved formate selectivity, but they suffer from relatively low current activities considering the competitive CO selectivity on Zn. Here, lead‐doped zinc (Zn(Pb)) electrocatalyst is optimized to efficiently reduce CO2 to formate, while CO evolution selectivity is largely controlled. Selective formate is detected with Faradaic efficiency (FEHCOOH) of ≈95% at an outstanding partial current density of 47 mA cm–2 in a conventional H‐Cell. Zn(Pb) is further investigated in an electrolyte‐fed device achieving a superior conversion rate of ≈100 mA cm–2 representing a step closer to practical electrocatalysis. The in situ analysis demonstrates that the Pb incorporation plays a crucial role in CO suppression stem from the generation of the Pb–O–C–O–Zn structure rather than the CO‐boosted Pb–O–C–Zn. Density functional theory (DFT) calculations reveal that the alloying effect tunes the adsorption energetics and consequently modifies the electronic structure of the system for an optimized asymmetric oxo‐bridged intermediate. The alloying effect between Zn and Pb controls CO selectivity and achieves a superior activity for a selective CO2‐to‐formate reduction. This study reports a novel Zn(Pb) electrochemical CO2 reduction (ECR) electrocatalyst that shows >95% selectivity to formate production at an outstanding partial current density of 47 and ≈100 mA cm−2 in H‐Cell and flow cell, respectively, representing practical electrocatalysis. In situ and theoretical studies explain the local chemical environmental evolution and reveal the alloying effect of Zn(Pb) for ECR‐to‐HCOOH conversion.
Journal Article
Epigenetic regulation of kidney progenitor cells
2020
The reciprocal interactions among the different embryonic kidney progenitor populations lay the basis for proper kidney organogenesis. During kidney development, three types of progenitor cells, including nephron progenitor cells, ureteric bud progenitor cells, and interstitial progenitor cells, generate the three major kidney structures—the nephrons, the collecting duct network, and the stroma, respectively. Epigenetic mechanisms are well recognized for playing important roles in organism development, in fine‐tuned control of physiological activities, and in responses to environment stimuli. Recently, evidence supporting the importance of epigenetic mechanisms underlying kidney organogenesis has emerged. In this perspective, we summarize the research progress and discuss the potential contribution of novel stem cell, organoid, and next‐generation sequencing tools in advancing this field in the future. Representative scheme of epigenetic regulation of kidney progenitors within a nephrogenic niche during kidney development. Epigenetic mechanisms involved in kidney organogenesis include DNA methylation, histone acetylation, chromatin remodeling complexes, and versatile noncoding RNAs. These mechanisms are mediated by special epigenetic modifiers and play important roles in the regulation of self‐renewal maintenance and differentiation of three types of kidney progenitors during kidney development
Journal Article
The Mechanism and Diagnosis of Insulation Deterioration Caused by Moisture Ingress into Oil-Impregnated Paper Bushing
2018
The healthy state of insulation in oil-impregnated bushings is traditionally evaluated by tanδ and capacitance at power frequency and mostly at 10 kV in the test standard. However, there has frequently been insulation accidents induced by moisture ingress (MI) for bushings that have passed the standard. The mechanism and new diagnostic features for MI into bushings were not distinct enough and an accurate test method is urgently needed research. To address this technical gap, a bushing model with a transparent sheath was designed and an ultrasonic humidifier device was adopted to simulate the environment of MI in bushings and recorded by digital camera. The parameters of dielectric dissipation factor, capacitance, partial discharge (PD), frequency domain response, and moisture content in oil were measured at room temperature with time. The results presented that both the increment dissipation factor at low frequency of 0.001 Hz and the increment dissipation factor of 1.2 Um could be used for detecting the earlier insulation defect of oil-impregnated paper (OIP) bushings. The phase resolved partial discharge (PRPD) can serve as the diagnostic basis of the severe state (S3) of insulation deterioration caused by MI into bushings around the phases of 0–117°, 151–303°, and 325–360°. The research findings would provide a useful reference for the condition diagnosis and maintenance of OIP bushings. Especially, the increment detection of Frequency Domain Spectroscopy (FDS) at the frequency of 1 mHz and 10 kHz was recommended firstly for the operative bushings in real sites.
Journal Article
Approaches to kidney replacement therapies—opportunities and challenges
by
Li, Zhongwei
,
Zeng, Zipeng
,
Schreiber, Megan E.
in
bioartificial kidney
,
Blood
,
Cell and Developmental Biology
2022
One out of seven people develop chronic kidney disease (CKD). When kidney function continues to decline, CKD patients may develop end-stage renal disease (ESRD, or kidney failure). More than 2 out of 1,000 adults develop ESRD and these patients must live on dialysis or get a kidney transplant to survive. Each year, more than $51 billion is spent to treat patients with ESRD in the United States. In addition, ESRD greatly reduces longevity and quality of life for patients. Compared to dialysis, kidney transplant offers the best chance of survival, but few donor organs are available. Thus, there is an urgent need for innovative solutions that address the shortage of kidneys available for transplantation. Here we summarize the status of current approaches that are being developed to solve the shortage of donor kidneys. These include the bioartificial kidney approach which aims to make a portable dialysis device, the recellularization approach which utilizes native kidney scaffold to make an engineered kidney, the stem cell-based approach which aims to generate a kidney de novo by recapitulating normal kidney organogenesis, the xenotransplantation approach which has the goal to make immunocompatible pig kidneys for transplantation, and the interspecies chimera approach which has potential to generate a human kidney in a host animal. We also discuss the interconnections among the different approaches, and the remaining challenges of translating these approaches into novel therapies.
Journal Article
Asymmetric Oxo‐Bridged ZnPb Bimetallic Electrocatalysis Boosting CO 2 ‐to‐HCOOH Reduction
2022
Electrochemical CO 2 reduction (ECR) is one of the promising CO 2 recycling technologies sustaining the natural carbon cycle and offering more sustainable higher‐energy chemicals. Zn‐ and Pb‐based catalysts have improved formate selectivity, but they suffer from relatively low current activities considering the competitive CO selectivity on Zn. Here, lead‐doped zinc (Zn(Pb)) electrocatalyst is optimized to efficiently reduce CO 2 to formate, while CO evolution selectivity is largely controlled. Selective formate is detected with Faradaic efficiency (FE HCOOH ) of ≈95% at an outstanding partial current density of 47 mA cm –2 in a conventional H‐Cell. Zn(Pb) is further investigated in an electrolyte‐fed device achieving a superior conversion rate of ≈100 mA cm –2 representing a step closer to practical electrocatalysis. The in situ analysis demonstrates that the Pb incorporation plays a crucial role in CO suppression stem from the generation of the Pb–O–C–O–Zn structure rather than the CO‐boosted Pb–O–C–Zn. Density functional theory (DFT) calculations reveal that the alloying effect tunes the adsorption energetics and consequently modifies the electronic structure of the system for an optimized asymmetric oxo‐bridged intermediate. The alloying effect between Zn and Pb controls CO selectivity and achieves a superior activity for a selective CO 2 ‐to‐formate reduction.
Journal Article
Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids
2023
Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron in vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identifying novel genes associated with kidney development and disease. A rapid, efficient, and scalable organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron in vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identifying novel genes associated with kidney development and disease. A rapid, efficient, and scalable organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.
Journal Article
Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis
2020
Kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from pluripotent human stem cells. UB organoids differentiate into CD organoids in vitro, with differentiated cell types adopting spatial assemblies reflective of the adult kidney collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Combining efficient gene editing with the UB organoid model will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting system.
Collecting duct organoids derived from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells provide an in vitro platform for genetic dissection of development, regeneration and diseases of the mammalian collecting system.
Variational learning algorithms for quantum query complexity
2024
Quantum query complexity is pivotal in the analysis of quantum algorithms, encompassing well-known examples like search and period-finding algorithms. These algorithms typically involve a sequence of unitary operations and oracle calls dependent on an input variable. In this study, we introduce a variational learning approach to explore quantum query complexity. Our method employs an efficient parameterization of the unitary operations and utilizes a loss function derived from the algorithm’s error probability. We apply this technique to various quantum query complexities, notably devising a new algorithm that resolves the 5-bit Hamming modulo problem with four queries, addressing an open question from Cornelissen et al (2021 arXiv: 2112.14682 ). This finding is corroborated by a semidefinite programming (SDP) approach. Our numerical method exhibits superior memory efficiency compared to SDP and can identify quantum query algorithms (QQAs) that require a smaller workspace register dimension, an aspect not optimized by SDP. These advancements present a significant step forward in the practical application and understanding of QQAs.
Journal Article
Prostate Cancer Radiomic Features: Limited Cross‐Scanner Reproducibility Despite High Reader Reliability
2026
Purpose To quantify the agreement of prostate cancer radiomic features within a reader, between readers, and across scanners for T2‐weighted imaging (T2WI), diffusion‐weighted imaging (DWI; b = 1500 s/mm2), and apparent diffusion coefficient (ADC). Materials and Methods Seventeen men with biopsy‐proven prostate cancer underwent 3.0 T magnetic resonance imaging on two platforms. Two radiologists contoured the dominant lesion. Reader 1 repeated the segmentation approximately 4 weeks later on the same examination. For each sequence and prespecified comparison, feature‐wise agreement across patients was quantified using the concordance correlation coefficient (CCC). CCCs were summarized as median (interquartile range) and categorized as poor (< 0.40), moderate (0.40–0.69), good (0.70–0.89), or excellent (≥ 0.90). Results Within a given scanner, prostate cancer radiomic features showed consistently high agreement for both Reader 1 repeat segmentation and Reader 1 versus Reader 2, with most features in the good and excellent ranges across T2WI, DWI, and ADC. In contrast, the cross‐scanner agreement was low, even for the same reader and session, and the majority of features were categorized as poor. Sequence‐wise, as shown in Figure 2, adjusted T2WI outperformed DWI and ADC for cross‐scanner comparisons, yet still fell short of within‐scanner performance. Conclusion Prostate cancer radiomic features demonstrated good reproducibility on a single scanner but poor cross‐scanner reproducibility. For future radiomic research, researchers should incorporate scanner type into model analyses and perform data harmonization before integrating data from different manufacturers.
Journal Article