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World Journal of Hepatology Jun 2024The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its...
The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.
PubMed: 38948435
DOI: 10.4254/wjh.v16.i6.883 -
APL Bioengineering Jun 2024Monoclonal antibodies (mAbs) can undergo structural changes due to interaction with oil-water interfaces during storage. Such changes can lead to aggregation, resulting...
Monoclonal antibodies (mAbs) can undergo structural changes due to interaction with oil-water interfaces during storage. Such changes can lead to aggregation, resulting in a loss of therapeutic efficacy. Therefore, understanding the microscopic mechanism controlling mAb adsorption is crucial to developing strategies that can minimize the impact of interfaces on the therapeutic properties of mAbs. In this study, we used MARTINI coarse-grained molecular dynamics simulations to investigate the adsorption of the Fab and Fc domains of the monoclonal antibody COE3 at the oil-water interface. Our aim was to determine the regions on the protein surface that drive mAb adsorption. We also investigate the role of protein concentration on protein orientation and protrusion to the oil phase. While our structural analyses compare favorably with recent neutron reflectivity measurements, we observe some differences. Unlike the monolayer at the interface predicted by neutron reflectivity experiments, our simulations indicate the presence of a secondary diffused layer near the interface. We also find that under certain conditions, protein-oil interaction can lead to a considerable distortion in the protein structure, resulting in enhanced adsorption behavior.
PubMed: 38948350
DOI: 10.1063/5.0207959 -
Molecular Therapy. Nucleic Acids Jun 2024Infantile-onset Pompe disease (IOPD) results from pathogenic variants in the gene, which encodes acid α-glucosidase. The correction of pathogenic variants through...
Infantile-onset Pompe disease (IOPD) results from pathogenic variants in the gene, which encodes acid α-glucosidase. The correction of pathogenic variants through genome editing may be a valuable one-time therapy for PD and improve upon the current standard of care. We performed adenine base editing in human dermal fibroblasts harboring three transition nonsense variants, c.2227C>T (p.Q743∗; IOPD-1), c.2560C>T (p.R854∗; IOPD-2), and c.2608C>T (p.R870∗; IOPD-3). Up to 96% adenine deamination of target variants was observed, with minimal editing across >50 off-target sites. Post-base editing, expressed GAA protein was up to 0.66-fold normal (unaffected fibroblasts), an improvement over affected fibroblasts wherein GAA was undetectable. GAA enzyme activity was between 81.91 ± 13.51 and 129.98 ± 9.33 units/mg protein at 28 days post-transfection, which falls within the normal range (50-200 units/mg protein). LAMP2 protein was significantly decreased in the most robustly edited cell line, IOPD-3, indicating reduced lysosomal burden. Taken together, the findings reported herein demonstrate that base editing results in efficacious adenine deamination, restoration of GAA expression and activity, and reduction in lysosomal burden in the most robustly edited cells. Future work will assess base editing outcomes and the impact on Pompe pathology in two mouse models, and .
PubMed: 38948331
DOI: 10.1016/j.omtn.2024.102220 -
Frontiers in Molecular Biosciences 2024Human saliva was used to develop non-invasive liquid biopsy biomarkers to establish saliva as an alternate to blood and plasma in translational research. The present...
Human saliva was used to develop non-invasive liquid biopsy biomarkers to establish saliva as an alternate to blood and plasma in translational research. The present study focused on understanding the impact of sample storage conditions on the extraction of RNA from saliva and the RNA yield, to be applied in clinical diagnosis. In this study, genes related to asthma were used to test the method developed. Salivary RNA was extracted from three subjects using the Qiazol based method and quantified by both spectrophotometric (NanoDrop) and fluorometric (Qubit) methods. RNA integrity was measured using a bioanalyzer. Quantitative PCR was used to monitor the impact of storage conditions on the expression of housekeeping genes: and β-actin, and the asthma related genes: and . In addition, an independent cohort of 38 asthmatics and 10 healthy controls were used to validate the expression of and as mRNA salivary biomarkers. Approximately 2 µg of total RNA was obtained from the saliva stored at 40°C without any preservative for 2 weeks showing consistent gene expression with RNA stored at room temperature (RT) for 48 h with RNA. Although saliva stored with RNA showed a substantial increase in the yield (110 to 234 ng/μL), a similar Cq (15.6 ± 1.4) for the 18s rRNA gene from saliva without preservative showed that the RNA was stable enough. Gene expression analysis from the degraded RNA can be performed by designing the assay using a smaller fragment size spanning a single exon as described below in the case of the and genes in the asthma cohort. This study showed that samples stored at room temperature up to a temperature of 40°C without any preservative for 2 weeks yielded relatively stable RNA. The methodology developed can be employed to transport samples from the point of collection to the laboratory, under non-stringent storage conditions enabling the execution of gene expression studies in a cost effective and efficient manner.
PubMed: 38948078
DOI: 10.3389/fmolb.2024.1363897 -
PNAS Nexus Jul 2024Increased demands for sustainable water and energy resources in densely populated basins have led to the construction of dams, which impound waters in artificial...
Increased demands for sustainable water and energy resources in densely populated basins have led to the construction of dams, which impound waters in artificial reservoirs. In many cases, scarce field data led to the development of models that underestimated the seepage losses from reservoirs and ignored the role of extensive fault networks as preferred pathways for groundwater flow. We adopt an integrated approach (remote sensing, hydrologic modeling, and field observations) to assess the magnitude and nature of seepage from such systems using the Grand Ethiopian Renaissance Dam (GERD), Africa's largest hydropower project, as a test site. The dam was constructed on the Blue Nile within steep, highly fractured, and weathered terrain in the western Ethiopian Highlands. The GERD Gravity Recovery and Climate Experiment Terrestrial Water Storage (GRACE), seasonal peak difference product, reveals significant mass accumulation (43 ± 5 BCM) in the reservoir and seepage in its surroundings with progressive south-southwest mass migration along mapped structures between 2019 and 2022. Seepage, but not a decrease in inflow or increase in outflow, could explain, at least in part, the observed drop in the reservoir's water level and volume following each of the three fillings. Using mass balance calculations and GRACE observations, we estimate significant seepage (19.8 ± 6 BCM) comparable to the reservoir's impounded waters (19.9 ± 1.2 BCM). Investigating and addressing the seepage from the GERD will ensure sustainable development and promote regional cooperation; overlooking the seepage would compromise hydrological modeling efforts on the Nile Basin and misinform ongoing negotiations on the Nile water management.
PubMed: 38948018
DOI: 10.1093/pnasnexus/pgae219 -
Frontiers in Chemistry 2024Interfacial charge transfer reactions involving cations and electrons are fundamental to (photo/electro) catalysis, energy storage, and beyond. Lithium-coupled electron...
Interfacial charge transfer reactions involving cations and electrons are fundamental to (photo/electro) catalysis, energy storage, and beyond. Lithium-coupled electron transfer (LCET) at the electrode-electrolyte interfaces of lithium-ion batteries (LIBs) is a preeminent example to highlight the importance of charge transfer in modern-day society. The thermodynamics of LCET reactions define the minimal energy for charge/discharge of LIBs, and yet, these parameters are rarely available in the literature. Here, we demonstrate the successful incorporation of tungsten oxides (WO) within a chemically stable Zr-based metal-organic framework (MOF), MOF-808. Cyclic voltammograms (CVs) of the composite, WO@MOF-808, in Li-containing acetonitrile (MeCN)-based electrolytes showed an irreversible, cathodic Faradaic feature that shifted in a Nernstian fashion with respect to the Li concentration, i.e., ∼59 mV/log [(Li)]. The Nernstian dependence established 1:1 stoichiometry of Li and e. Using the standard redox potential of Li, the apparent free energy of lithiation of WO@MOF-808 (ΔG) was calculated to be -36 ± 1 kcal mol. ΔG is an parameter of WO@MOF-808, and thus by deriving the similar reaction free energies of other metal oxides, their direct comparisons can be achieved. Implications of the reported measurements will be further contrasted to proton-coupled electron transfer (PCET) reactions on metal oxides.
PubMed: 38947957
DOI: 10.3389/fchem.2024.1427536 -
Frontiers in Plant Science 2024Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun')...
Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO and the decrease in O gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes , , , cellulose synthase , and related transcription factors , and were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.
PubMed: 38947949
DOI: 10.3389/fpls.2024.1431097 -
ArXiv Jun 2024We introduce ProteinWorkshop, a comprehensive benchmark suite for representation learning on protein structures with Geometric Graph Neural Networks. We consider...
We introduce ProteinWorkshop, a comprehensive benchmark suite for representation learning on protein structures with Geometric Graph Neural Networks. We consider large-scale pre-training and downstream tasks on both experimental and predicted structures to enable the systematic evaluation of the quality of the learned structural representation and their usefulness in capturing functional relationships for downstream tasks. We find that: (1) large-scale pretraining on AlphaFold structures and auxiliary tasks consistently improve the performance of both rotation-invariant and equivariant GNNs, and (2) more expressive equivariant GNNs benefit from pretraining to a greater extent compared to invariant models. We aim to establish a common ground for the machine learning and computational biology communities to rigorously compare and advance protein structure representation learning. Our open-source codebase reduces the barrier to entry for working with large protein structure datasets by providing: (1) storage-efficient dataloaders for large-scale structural databases including AlphaFoldDB and ESM Atlas, as well as (2) utilities for constructing new tasks from the entire PDB. ProteinWorkshop is available at: github.com/a-r-j/ProteinWorkshop.
PubMed: 38947934
DOI: No ID Found -
ACS Omega Jun 2024The combustion of lithium-ion batteries is characterized by fast ignition, prolonged duration, high combustion temperature, release of significant energy, and generation...
The combustion of lithium-ion batteries is characterized by fast ignition, prolonged duration, high combustion temperature, release of significant energy, and generation of a large number of toxic gases. Fine water mist has characteristics such as a high fire extinguishing efficiency and environmental friendliness. In order to thoroughly investigate the temperature control effect of fine water mist on lithium-ion battery fires. This study employs numerical simulation methods, utilizing PyroSim software to simulate the fire process in lithium-ion battery energy storage compartments. First, we focus on the variation patterns of flame, changes in combustion temperature, and heat release rate over time at environmental temperatures of 10, 25, and 35 °C. Subsequently, the suppression of flame, reduction in temperature, and changes in heat release rate are simulated for water mist in lithium-ion battery fires. The simulation results indicate that the environmental temperature has a considerable impact on the flame but a lesser effect on the heat release rate. Fine water mist effectively impedes the spread of thermal runaway between internal battery core cells, leading to a reduction in the flame size and a significant decrease in the maximum temperature and heat release rate. The numerical simulation results can provide scientific guidance for the prevention and control of fires in lithium-ion battery energy storage compartments.
PubMed: 38947830
DOI: 10.1021/acsomega.4c00921 -
ACS Omega Jun 2024As gas reservoir pressure decreases, edge and bottom water irregularly flow into the reservoir through storage and permeability spaces. Water influx poses a significant...
As gas reservoir pressure decreases, edge and bottom water irregularly flow into the reservoir through storage and permeability spaces. Water influx poses a significant challenge for the development of gas reservoirs, impacting development efficiency and the ultimate recovery rate. Therefore, exploring rational optimization methods for gas well allocation is essential. This study utilizes the vertical well productivity equation considering two-phase flow and employs the net present value (NPV) to evaluate the economic benefits of gas well production. A parallel-structured genetic algorithm (GA) is developed to account for dynamic reservoir inflow, wellbore conditions, and surface facilities engineering. The new model is applied to investigate the optimal allocation of the B-21 well in the Amu Darya right bank gas reservoirs in Turkmenistan. Results indicate a match of over 90% between the cumulative gas production and water/gas ratio calculated by the proposed method and those calculated by a numerical simulation model. Compared with the traditional genetic algorithm, the new approach reduces the number of iterations to approximately 2100 (a 72.4% decrease) and significantly improves the convergence rate.
PubMed: 38947819
DOI: 10.1021/acsomega.4c01877