We report our studies to compare energy consumption of a CDI cell in constant voltage (CV) and constant current (CC) operations, with a focus on understanding the underlying physics of consumption ...patterns. The comparison is conducted under conditions that the CV and CC operations result in the same amounts of input charge and within identical charging phase durations. We present two electrical circuit models to simulate energy consumption in charging phase: one is a simple RC circuit model, and the other a transmission line circuit model. We built and tested a CDI cell to validate the transmission line model, and performed a series of experiments to compare CV versus CC operation under the condition of equal applied charge and charging duration. The experiments show that CC mode consumes energy at 33.8kJ per mole of ions removed, which is only 28% of CV mode energy consumption (120.6kJ/mol), but achieves similar level of salt removals. Together, the models and experiment support our major conclusion that CC is more energy efficient than CV for equal charge and charging duration. The models also suggest that the lower energy consumption of CC in charging is due to its lower resistive dissipation.
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•Two circuit models useful in elucidating constant current (CC) versus constant voltage (CV) CDI energy consumption dynamics.•CC mode consumes significantly less energy than CV mode for equal amounts of input charge and identical charging duration.•CC mode has approximately same salt removal as CV and avoids initial high-power resistive dissipation of CV mode.
Objective
To conduct multiparametric magnetic resonance imaging (MRI)-derived radiomics based on multi-scale tumor region for predicting disease-free survival (DFS) in early-stage squamous cervical ...cancer (ESSCC).
Methods
A total of 191 ESSCC patients (training cohort,
n
= 135; validation cohort,
n
= 56) from March 2016 to September 2019 were retrospectively recruited. Radiomics features were derived from the T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CET1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) map for each patient. DFS-related radiomics features were selected in 3 target tumor volumes (VOI
entire
, VOI
+5 mm
, and VOI
−5 mm
) to build 3 rad-scores using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Logistic regression was applied to build combined model incorporating rad-scores with clinical risk factors and compared with clinical model alone. Kaplan–Meier analysis was used to further validate prognostic value of selected clinical and radiomics characteristics.
Results
Three radiomics scores all showed favorable performances in DFS prediction. Rad-score (VOI
+5 mm
) performed best with a
C
-index of 0.750 in the training set and 0.839 in the validation set. Combined model was constructed by incorporating age categorized by 55, Federation of Gynecology and Obstetrics (Figo) stage, and lymphovascular space invasion with rad-score (VOI
+5 mm
). Combined model performed better than clinical model in DFS prediction in both the training set (
C
-index 0.815 vs 0.709;
p
= 0.024) and the validation set (
C
-index 0.866 vs 0.719;
p
= 0.001).
Conclusion
Multiparametric MRI-derived radiomics based on multi-scale tumor region can aid in the prediction of DFS for ESSCC patients, thereby facilitating clinical decision-making.
Key Points
•
Three radiomics scores based on multi-scale tumor region all showed favorable performances in DFS prediction. Rad-score (VOI
+5 mm
) performed best with favorable C-index values.
•
Combined model incorporating multiparametric MRI-based radiomics with clinical risk factors performed significantly better in DFS prediction than the clinical model.
•
Combined model presented as a nomogram can be easily used to predict survival, thereby facilitating clinical decision-making.
Mitochondrial pyruvate dehydrogenase complex (PDC) is crucial for glucose homeostasis in mammalian cells. The current understanding of PDC regulation involves inhibitory serine phosphorylation ...of pyruvate dehydrogenase (PDH) by PDH kinase (PDK), whereas dephosphorylation of PDH by PDH phosphatase (PDP) activates PDC. Here, we report that lysine acetylation of PDHA1 and PDP1 is common in epidermal growth factor (EGF)-stimulated cells and diverse human cancer cells. K321 acetylation inhibits PDHA1 by recruiting PDK1, and K202 acetylation inhibits PDP1 by dissociating its substrate PDHA1, both of which are important in promoting glycolysis in cancer cells and consequent tumor growth. Moreover, we identified mitochondrial ACAT1 and SIRT3 as the upstream acetyltransferase and deacetylase, respectively, of PDHA1 and PDP1, while knockdown of ACAT1 attenuates tumor growth. Furthermore, Y381 phosphorylation of PDP1 dissociates SIRT3 and recruits ACAT1 to PDC. Together, hierarchical, distinct posttranslational modifications act in concert to control molecular composition of PDC and contribute to the Warburg effect.
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•Lysine acetylation promotes PDHA and PDK binding but disrupts PDHA and PDP association•Lysine acetylation of PDHA1 and PDP1 promotes the Warburg effect•ACAT1 acetylates and SIRT3 deacetylates PDHA1 and PDP1•Tyrosine phosphorylation of PDP1 dissociates SIRT3 and recruits ACAT1 to PDC
Fan et al. report a mechanism where lysine acetylation of mitochondrial pyruvate dehydrogenase (PDH) A1 and PDH phosphatase (PDP) 1 contributes to inhibitory regulation of pyruvate dehydrogenase complex, providing complementary insight into the current understanding of PDHA1 regulation through the phosphorylation/dephosphorylation cycle.
It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in ...human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
► PGAM1 controls 3-PG and 2-PG levels to coordinate glycolysis and biosynthesis ► 3-PG binds to and inhibits 6PGD in the oxidative PPP ► 2-PG potentiates PHGDH to provide feedback control of 3-PG levels ► PGAM1 is a promising anticancer target
•A super-comprehensive proxy for the recognition of sedimentary rhythms is proposed.•This proxy can accurately identify alluvial rhythms and flood events.•The sedimentary rhythm and chronological ...framework of Kaifeng’s alluvial strata are established.•Kaifeng’s alluvial strata clearly recorded six flood events since the Warring States period.•These floods were mainly caused by prevailing climatic conditions and human activities.
In this paper we propose a new super-comprehensive proxy that integrates the sedimentary rhythm indicators of grain size, black carbon, anthropogenic elements, and pollen for the division of alluvial sedimentary rhythms suitable for use on sediments that have or have not been disturbed by past human activity. The new proxy was applied in the analysis of sedimentary records from two boreholes (identified as JM and SZ) in the Kaifeng area of the lower Yellow River, an area that has received less research attention in terms of flood events and sedimentary records compared to its middle and upper reaches. From this analysis, flood events that occurred in the lower Yellow River since the late Holocene were reconstructed. The results suggest there are 15 and 14 sedimentary rhythms in the cores of JM and SZ, respectively. Based on historical documents, archaeological excavation data from the vicinity of the core sites, and AMS14C dating, we established the chronological framework of sedimentary rhythms in both JM and SZ cores. Using this information, we then reconstructed six Yellow River flood events impacting Kaifeng that occurred after the Warring States period in the years 225 BCE, 1387 CE, 1399 CE, 1461 CE, 1642 CE and 1841 CE. Among the six flood events, except for the flood of 225 BCE which was directly caused by human factors, the rest were caused by natural factors, mainly from prevailing climatic conditions but superimposed by human activities. The research results, therefore, can provide a scientific basis for flood prediction, prevention and risk assessment in the Yellow River Basin under the background of global change, and also provide support for clarifying the relationship between regional climate background and human activities in abnormal flood events.
Summary
Raffinose is thought to play an important role in plant tolerance of abiotic stress. We report here that maize HEAT SHOCK FACTOR A2 (ZmHSFA2) and HEAT SHOCK BINDING PROTEIN 2 (ZmHSBP2) ...physically interact with each other and antagonistically modulate expression of GALACTINOL SYNTHASE2 (ZmGOLS2) and raffinose biosynthesis in transformed maize protoplasts and Arabidopsis plants. Overexpression of ZmHSFA2 in Arabidopsis increased the expression of Arabidopsis AtGOLS1, AtGOLS2 and AtRS5 (RAFFINOSE SYNTHASE), increased the raffinose content in leaves and enhanced plant heat stress tolerance. Contrary to ZmHSFA2, overexpression of ZmHSBP2 in Arabidopsis decreased expression of AtGOLS1, AtGOLS2 and AtRS5, decreased the raffinose content in leaves and reduced plant heat stress tolerance. ZmHSFA2 and ZmHSBP2 also interact with their Arabidopsis counterparts AtHSBP and AtHSFA2 as determined using bimolecular fluorescence complementation assays. Furthermore, endogenous ZmHSBP2 and Rluc, controlled by the ZmHSBP2 promoter, are transcriptionally activated by ZmHSFA2 and inhibited by ZmHSBP2 in maize protoplasts. These findings provide insights into the transcriptional regulation of raffinose biosynthetic genes, and the tolerance their product confers to plant heat stress.
Significance Statement
Supraoptimal temperature is a major threat to plant productivity and survival. We found that maize HEAT SHOCK FACTOR A2 (HSFA2) and HEAT SHOCK BINDING PROTEIN 2 (HSBP2) antagonistically modulate expression of the GALACTINOL SYNTHASE gene in maize protoplast cells, and regulate both raffinose biosynthesis and plant heat stress tolerance in Arabidopsis. In addition, ZmHSBP2 is transcriptionally activated by ZmHSFA2 and inhibited by its own protein ZmHSBP2, elucidating control of protective oligosaccharide production in response to this abiotic stress.
The cohesin complex participates in the organization of 3D genome through generating and maintaining DNA loops. Stromal antigen 2 (STAG2), a core subunit of the cohesin complex, is frequently mutated ...in various cancers. However, the impact of STAG2 inactivation on 3D genome organization, especially the long-range enhancer-promoter contacts and subsequent gene expression control in cancer, remains poorly understood. Here we show that depletion of STAG2 in melanoma cells leads to expansion of topologically associating domains (TADs) and enhances the formation of acetylated histone H3 lysine 27 (H3K27ac)-associated DNA loops at sites where binding of STAG2 is switched to its paralog STAG1. We further identify Interferon Regulatory Factor 9 (IRF9) as a major direct target of STAG2 in melanoma cells via integrated RNA-seq, STAG2 ChIP-seq and H3K27ac HiChIP analyses. We demonstrate that loss of STAG2 activates IRF9 through modulating the 3D genome organization, which in turn enhances type I interferon signaling and increases the expression of PD-L1. Our findings not only establish a previously unknown role of the STAG2 to STAG1 switch in 3D genome organization, but also reveal a functional link between STAG2 and interferon signaling in cancer cells, which may enhance the immune evasion potential in STAG2-mutant cancer.
Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and ...predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRα and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.
The pollen grains of 38 species and one variety of 17 genera in the family Solanaceae were studied using light microscopy (LM) and scanning electron microscopy (SEM). Among them, the pollen ...morphology of 13 species was described for the first time. Our results suggested that the exine ornamentation of pollen grains could be divided into 11 types, made up of three types (cerebroid, granulate-perforate-punctate and rugulate-perforate) which were observed for the first time in Solanaceae, and other normal types (granulate, granulate-perforate, punctate, reticulate, rugulate, rugulate-striate, spinulose-perforate, striate). In addition, the studied species have pollen grains that differ in size, shape, equatorial view, polar view, aperture features and exine ornamentation, confirming that Solanaceae is a eurypalynous family. Furthermore, the intergeneric and intrageneric relationships of Solanaceae were explored. These results could provide a palynological basis for classification and systematic study of Solanaceae.
To present the experience on prenatal features of 17q12 microdeletion and microduplication syndromes.
Prenatal chromosomal microarray analysis (CMA) were conducted between January 2015 and December ...2018 at a single Chinese tertiary medical centre. Information of cases identified with 17q12 microdeletion or microduplication syndromes were retrospectively collected. Foetal ultrasonographic findings were reviewed, and other information about the gestation week at diagnosis, inheritance and pregnancy outcomes were also included.
Ten pregnancies with 17q12 microdeletion and 4 with 17q12 microduplication were identified. The copy number variation (CNV) sizes were 1.39–1.94 Mb in the deleted cases and 1.42–1.48 Mb in the duplicated cases, respectively. All the duplicated and deleted regions included HNF1B and LHX1 genes. Most individuals with 17q12 deletion presented kidney anomalies (9/10), with renal hyperechogenicity being the most common finding (7/10). Fetuses with 17q12 duplication presented a wide phenotypic spectrum, including “double bubble” sign, structural anomalies of the heart and growth anomalies.
Our experience further demonstrated the high correlation between 17q12 microdeletion and renal anomalies especially hyperechogenic kidneys. Structural anomalies of the heart were newly identified phenotypes of 17q12 duplication during prenatal period. Besides, growth anomalies and duodenal atresia might be associated with the duplication.
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