Stress dependent gas-water relative permeability in gas hydrates: A theoretical model

        Research activities are currently being conducted to study multiphase flow in hydrate-bearing sediments (HBS). In this study, in view of the assumption that hydrates are evenly distributed in HBS with two major hydrate-growth patterns, i.e., pore filling hydrates (PF hydrates), wall coating hydrates (WC hydrates) and a combination of the two, a theoretical relative  permeability model is proposed for gas-water flow through HBS. Besides, in this proposed model, the change in pore structure (e.g., pore radius) of HBS due to effective stress is taken into account. Then, model validation is performed by comparing the predicted results from the derived model with that from the existing model and test data. By setting the value of hydrate saturation to zero, our derived model can be reducible to the existing model, which demonstrates that the existing model is a special case of our model. The results reveal that, under the same saturation, relative permeability to water Krw (or gas Krg) in PF hydrates is smaller than that in WC hydrates. Moreover, the morphological characteristics of relative permeability curve (relative permeability versus gas saturation) for WC hydrate and PF hydrate are different.Cited as: Lei, G., Liao, Q., Chen, W., Lin, Q., Zhang, L., Xue, L. Stress dependent gas-water relative permeability in gas hydrates: A theoretical model. Advances in Geo-Energy Research, 2020, 4(3): 326-338, doi: 10.46690/ager.2020.03.1

Upconverting nanorockers for intracellular viscosity measurements during chemotherapy

Funding: Ministerio de Economía y Competitividad de España (MAT2016-75362-C3-1-R and MAT2017-83111R); Instituto de Salud Carlos III (PI16/ 00812); Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM), and co-financed by the European Structural funds and also by COST action CM1403; Comunidad de Madrid predoctorate contracts and from the Spanish national project FIS2017-86007-C3-1-P (R.D-B and R.P.P).Chemicals capable of producing structural and chemical changes on cells are used to treat diseases (e.g., cancer). Further development and optimization of chemotherapies require thorough knowledge of the effect of the chemical on the cellular structure and dynamics. This involves studying, in a noninvasive way, the properties of individual cells after drug administration. Intracellular viscosity is affected by chemical treatments and it can be reliably used to monitor chemotherapies at the cellular level. Here, cancer cell monitoring during chemotherapeutic treatments is demonstrated using intracellular allocated upconverting nanorockers. A simple analysis of the polarized visible emission of a single particle provides a real-time readout of its rocking dynamics that are directly correlated to the cytoplasmic viscosity. Numerical simulations and immunodetection are used to correlate the measured intracellular viscosity alterations to the changes produced in the cytoskeleton of cancer cells by anticancer drugs (colchicine and Taxol). This study evidences the possibility of monitoring cellular properties under an external chemical stimulus for the study and development of new treatments. Moreover, it provides the biomedical community with new tools to study intracellular dynamics and cell functioning.PostprintPeer reviewe

Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain.

Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in distinct conformations. The domain organization reveals a unique "H"-shaped head-to-tail dimeric architecture. The capture of both aryl and peptidyl carrier protein-tethered substrates and intermediates inside the heterocyclization domain and L-cysteinyl adenylate in the adenylation domain illustrates the catalytic and recognition residues. The multilevel structural transitions guided by the adenylation C-terminal subdomain in combination with the inserted epimerase and the conformational changes of the heterocyclization tunnel are controlled by two residues. Moreover, we visualized the direct structural dynamics of the full catalytic cycle from thiolation to epimerization. This study establishes the catalytic trajectory of PchE and sheds light on the rational re-engineering of domain-inserted dimeric NRPSs for the production of novel pharmaceutical agents

Photon upconversion through triplet exciton-mediated energy relay.

Exploration of upconversion luminescence from lanthanide emitters through energy migration has profound implications for fundamental research and technology development. However, energy migration-mediated upconversion requires stringent experimental conditions, such as high power excitation and special migratory ions in the host lattice, imposing selection constraints on lanthanide emitters. Here we demonstrate photon upconversion of diverse lanthanide emitters by harnessing triplet exciton-mediated energy relay. Compared with gadolinium-based systems, this energy relay is less dependent on excitation power and enhances the emission intensity of Tb3+ by 158-fold. Mechanistic investigations reveal that emission enhancement is attributable to strong coupling between lanthanides and surface molecules, which enables fast triplet generation (<100 ps) and subsequent near-unity triplet transfer efficiency from surface ligands to lanthanides. Moreover, the energy relay approach supports long-distance energy transfer and allows upconversion modulation in microstructures. These findings enhance fundamental understanding of energy transfer at molecule-nanoparticle interfaces and open exciting avenues for developing hybrid, high-performance optical materials

Morphology-related foot function analysis:implications for jumping and running

Barefoot and shod running has received increased attention in recent years, however, the influence of morphology-related foot function has not been explored. This study aimed to investigate morphology-related jumping and running biomechanical functions in habitually barefoot and shod males. A total of 90 barefoot males (Indians) and 130 shod males (Chinese), with significant forefoot and toe morphology differences, participated in a vertical jump and running test to enable the collection of kinematic and kinetic data. The difference of pressure distribution in the hallux and forefoot was shown while jumping and running. The unrestricted forefoot and toes of the barefoot group presented flexible movement and leverage functions to expand the forefoot loading area during performance of the two tasks. Findings related to morphology functions, especially in the forefoot and toe may provide useful information for footwear design

The burden of heatwave-related preterm births and associated human capital losses in China

Frequent heatwaves under global warming can increase the risk of preterm birth (PTB), which in turn will affect physical health and human potential over the life course. However, what remains unknown is the extent to which anthropogenic climate change has contributed to such burdens. We combine health impact and economic assessment methods to comprehensively evaluate the entire heatwave-related PTB burden in dimensions of health, human capital and economic costs. Here, we show that during 2010-2020, an average of 13,262 (95%CI 6,962-18,802) PTBs occurred annually due to heatwave exposure in China. In simulated scenarios, 25.8% (95%CI 17.1%-34.5%) of heatwave-related PTBs per year on average can be attributed to anthropogenic climate change, which further result in substantial human capital losses, estimated at over $1 billion costs. Our findings will provide additional impetus for introducing more stringent climate mitigation policies and also call for more sufficient adaptations to reduce heatwave detriments to newborn

The unique immune ecosystems in pediatric brain tumors: integrating single-cell and bulk RNA-sequencing

BackgroundThe significant progress of immune therapy in non-central nervous system tumors has sparked interest in employing the same strategy for adult brain tumors. However, the advancement of immunotherapy in pediatric central nervous system (CNS) tumors is not yet on par. Currently, there is a lack of comprehensive comparative studies investigating the immune ecosystem in pediatric and adult CNS tumors at a high-resolution single-cell level.MethodsIn this study, we comprehensively analyzed over 0.3 million cells from 171 samples, encompassing adult gliomas (IDH wild type and IDH mutation) as well as four major types of pediatric brain tumors (medulloblastoma (MB), ependymoma (EPN), H3K27M-mutation (DIPG), and pediatric IDH-mutation glioma (P-IDH-M)). Our approach involved integrating publicly available and newly generated single-cell datasets. We compared the immune landscapes in different brain tumors, as well as the detailed functional phenotypes of T-cell and myeloid subpopulations. Through single-cell analysis, we identified gene sets associated with major cell types in the tumor microenvironment (gene features from single-cell data, scFes) and compared them with existing gene sets such as GSEA and xCell. The CBTTC and external GEO cohort was used to analyze and validate the immune-stromal-tumor patterns in pediatric brain tumors which might potentially respond to the immunotherapy.ResultsFrom the perspective of single-cell analysis, it was observed that major pediatric brain tumors (MB, EPN, P-IDH-M, DIPG) exhibited lower immune contents compared with adult gliomas. Additionally, these pediatric brain tumors displayed diverse immunophenotypes, particularly in regard to myeloid cells. Notably, the presence of HLA-enriched myeloid cells in MB was found to be independently associated with prognosis. Moreover, the scFes, when compared with commonly used gene features, demonstrated superior performance in independent single-cell datasets across various tumor types. Furthermore, our study revealed the existence of heterogeneous immune ecosystems at the bulk-RNA sequencing level among different brain tumor types. In addition, we identified several immune-stromal-tumor patterns that could potentially exhibit significant responses to conventional immune checkpoint inhibitors.ConclusionThe single-cell technique provides a rational path to deeply understand the unique immune ecosystem of pediatric brain tumors. In spite of the traditional attitudes of “cold” tumor towards pediatric brain tumor, the immune-stroma-tumor patterns identified in this study suggest the feasibility of immune checkpoint inhibitors and pave the way for the upcoming tide of immunotherapy in pediatric brain tumors