Pancreatic cancer (PaCa) is one of the most fatal cancers in the world. Although great efforts have made to explore the mechanisms of PaCa oncogenesis, the prognosis of PaCa patients is still ...unsatisfactory. Thus, it is imperative to further understand the potential carcinogenesis of PaCa and reliable prognostic models.The gene expression profile and clinical information of GSE21501 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to explore the potent genes associated with the overall survival (OS) events of PaCa patients. Cox regression model was applied to selecting prognostic genes and establish prognostic model. The prognostic values of six-gene signature were validated in TCGA-PAAD cohort.According to the WGCNA analysis, a total of 19 modules were identified and 115 hub genes in the mostly associated module were reserved for next analysis. According to the univariate and multivariate Cox regression analysis, we established a six-gene signature (FTSJ3, STAT1, STX2, CDX2, RASSF4, MACF1) which could effectively evaluate the overall survival (OS) of PaCa patients. In validated patients' cohorts, the six-gene signature exhibited excellent prognostic value in TCGA-PAAD cohort as well.We developed a six-gene signature to exactly predict OS of PaCa patients and provide a novel personalized strategy for evaluating prognosis. The findings may be contributed to medical customization and therapeutic decision in clinical practice.
Light and brassinosteroid (BR) antagonistically regulate the developmental switch from etiolation in the dark to photomorphogenesis in the light in plants. Here, we identify GATA2 as a key ...transcriptional regulator that mediates the crosstalk between BR- and light-signaling pathways. Overexpression of GATA2 causes constitutive photomorphogenesis in the dark, whereas suppression of GATA2 reduces photomorphogenesis caused by light, BR deficiency, or the constitutive photomorphogenesis mutant
cop1. Genome profiling and chromatin immunoprecipitation experiments show that GATA2 directly regulates genes that respond to both light and BR. BR represses
GATA2 transcription through the BR-activated transcription factor BZR1, whereas light causes accumulation of GATA2 protein and feedback inhibition of GATA2 transcription. Dark-induced proteasomal degradation of GATA2 is dependent on the COP1 E3 ubiquitin ligase, and COP1 can ubiquitinate GATA2 in vitro. This study illustrates a molecular framework for antagonistic regulation of gene expression and seedling photomorphogenesis by BR and light.
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► GATA2 is a transcription factor that positively regulates photomorphogenesis ►
GATA2 transcription is repressed by the BR-activated transcription factor BZR1 ► GATA2 protein is stabilized by light and mutations of the COP1 E3 ligase ► GATA2 interacts with COP1 and is ubiquitinated by COP1 in vitro
In cruciferous plants, SI is determined by the S locus, which harbors genes encoding the stigma papilla cell‐specific S‐receptor kinase (SRK) and the pollen surface‐localized ligand of SRK, S‐locus ...cysteine‐rich protein/S‐locus protein 11 (SCR/SP11) (Schopfer et al., 1999; Suzuki et al., 1999). In B. rapa, the linear dominance hierarchy of class II S haplotype SCR alleles is controlled by SCR‐methylation‐inducing region 2 (Smi2) in the S locus; the Smi2 of the dominant S locus generates small interfering RNAs (siRNAs), which suppresses the expression of the recessive S‐locus SCR by siRNA‐mediated DNA methylation (e.g., BrS44 > BrS60 > BrS40 > BrS29, Yasuda et al., 2016). BoS15 and BrS60 are interspecific pairs between B. oleracea and B. rapa based on their high sequence similarity and incompatibility of B. oleracea BoS15 pollen with BrS60/BoS18 interspecific hybrid stigmas (Sato et al., 2006). ...BrS29 could be deduced to be recessive to BoS15.
Accurate estimation of fractional vegetation cover (FVC) is essential for crop growth monitoring. Currently, satellite remote sensing monitoring remains one of the most effective methods for the ...estimation of crop FVC. However, due to the significant difference in scale between the coarse resolution of satellite images and the scale of measurable data on the ground, there are significant uncertainties and errors in estimating crop FVC. Here, we adopt a Strategy of Upscaling-Downscaling operations for unmanned aerial systems (UAS) and satellite data collected during 2 growing seasons of winter wheat, respectively, using backpropagation neural networks (BPNN) as support to fully bridge this scale gap using highly accurate the UAS-derived FVC (FVC
UAS
) to obtain wheat accurate FVC. Through validation with an independent dataset, the BPNN model predicted FVC with an RMSE of 0.059, which is 11.9% to 25.3% lower than commonly used Long Short-Term Memory (LSTM), Random Forest Regression (RFR), and traditional Normalized Difference Vegetation Index-based method (NDVI-based) models. Moreover, all those models achieved improved estimation accuracy with the Strategy of Upscaling-Downscaling, as compared to only upscaling UAS data. Our results demonstrate that: (1) establishing a nonlinear relationship between FVC
UAS
and satellite data enables accurate estimation of FVC over larger regions, with the strong support of machine learning capabilities. (2) Employing the Strategy of Upscaling-Downscaling is an effective strategy that can improve the accuracy of FVC estimation, in the collaborative use of UAS and satellite data, especially in the boundary area of the wheat field. This has significant implications for accurate FVC estimation for winter wheat, providing a reference for the estimation of other surface parameters and the collaborative application of multisource data.
In this paper, an integrated system based on low-concentrated photovoltaic/thermal (LCPV/T) technology and efficient vacuum membrane distillation (VMD) seawater desalination utilizing the energy of ...solar is established. Through a theoretical analysis and a series of experiments, this paper explores the temperature change of a single VMD process, and the variation trend of single-day membrane flux with solar irradiation and temperature parameters. In addition, the changes in solar irradiation, temperatures of the integrated system, membrane flux, and thermoelectric properties in different seasons are also analyzed. A mathematical model was established to calculate the relationship between membrane flux and temperature difference. The experimental results show that the membrane flux of VMD is 2.73 L/(m2·h); the simulated seawater can achieve a desalination rate of 99.9%. After economic analysis, the operating incomes of the system under sunny weather conditions in different seasons were all positive.
In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness.
To investigate, in older adults undergoing surgical ...repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia.
A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018.
Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474).
Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications.
Among 950 randomized patients (mean age, 76.5 years; 247 26.8% male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference RD, 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk RR, 1.2 95% CI, 0.7 to 2.0; P = .57). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 95% CI, 0.7 to 3.5). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 95% CI, 0.8 to 6.3). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 95% CI, 0.6 to 6.5). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 44.3% vs 34 33.3%) and postoperative hypotension (13 12.3% vs 10 9.8%).
In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia.
ClinicalTrials.gov Identifier: NCT02213380.
Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages in the tumor immune-microenvironment are closely related to GR. Uncovering ...the macrophage-induced GR mechanism could help devise a novel strategy to improve gemcitabine treatment outcomes in PAAD. Therefore, preclinical models accurately replicating patient tumor properties are essential for cancer research and drug development. Patient-derived organoids (PDOs) represent a promising in vitro model for investigating tumor targets, accelerating drug development, and enabling personalized treatment strategies to improve patient outcomes.
To investigate the effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. To identify signaling factors between macrophages and pancreatic cancer cells (PCCs), a 97-target cytokine array and the TCGA-GTEx database were utilized. The analysis revealed CCL5 and AREG as potential candidates. The role of CCL5 in inducing GR was further investigated using clinical data and tumor sections obtained from 48 PAAD patients over three years, inhibitors, and short hairpin RNA (shRNA). Furthermore, single-cell sequencing data from the GEO database were analyzed to explore the crosstalk between PCCs and macrophages. To overcome GR, inhibitors targeting the macrophage-CCL5-Sp1-AREG feedback loop were evaluated in cell lines, PDOs, and orthotopic mouse models of pancreatic carcinoma.
The macrophage-CCL5-Sp1-AREG feedback loop between macrophages and PCCs is responsible for GR. Macrophage-derived CCL5 activates the CCR5/AKT/Sp1/CD44 axis to confer stemness and chemoresistance to PCCs. PCC-derived AREG promotes CCL5 secretion in macrophages through the Hippo-YAP pathway. By targeting the feedback loop, mithramycin improves the outcome of gemcitabine treatment in PAAD. The results from the PDO model were corroborated with cell lines, mouse models, and clinical data.
Our study highlights that the PDO model is a superior choice for preclinical research and precision medicine. The macrophage-CCL5-Sp1-AREG feedback loop confers stemness to PCCs to facilitate gemcitabine resistance by activating the CCR5/AKT/SP1/CD44 pathway. The combination of gemcitabine and mithramycin shows potential as a therapeutic strategy for treating PAAD in cell lines, PDOs, and mouse models.
This study aimed to investigate whether self-rated health status (SRH) and subjective health complaints (SHC) of urban Chinese women are associated with their health-promoting lifestyles (HPL).
We ...conducted a cross-sectional study on 8142 eligible Chinese participants between 2012 and 2013. Demographic and SHC data were collected. Each subject completed the SRH questionnaire and the Chinese version of the Health-Promoting Lifestyle Profile-II (HPLP-II). Correlation and binary regression analyses were performed to examine the associations of SRH and SHC with HPL.
Both SRH and HPL of urban Chinese women were moderate. The most common complaints were fatigue (1972, 24.2%), eye discomfort (1571, 19.3%), and insomnia (1542, 18.9%). Teachers, highly educated subjects and elderly women had lower SRH scores, while college students and married women had better HPL. All items of HPLP-II were positively correlated with SRH (r = 0.127-0.533, P = 0.000) and negatively correlated with SHC to a significant extent (odds ratio OR = 1.40-11.37).
Aspects of HPL, particularly stress management and spiritual growth, are associated with higher SRH and lower SHC ratings among urban Chinese women. Physical activity and health responsibility are additionally related to reduced fatigue and nervousness. We believe that these findings will be instrumental in encouraging researchers and urban women to adopt better health-promoting lifestyles with different priorities in their daily lives.
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•A simple molecular model for electric double layer (EDL) with Faradaic reactions is developed.•The oxygen functional groups increase the Faradaic capacitance but have relatively ...little influence on the EDL capacitance.•The theoretical predictions agree quantitatively with experimental observations.
Oxygen-containing functional groups have strong effect on the electrochemical capacitive behavior of carbon electrodes and have been subjected to many experimental investigations. However, there are relatively few theoretical reports on the relation between the oxygen-containing functional groups and the capacitance of carbon supercapacitors. In this study, we present a simple molecular model to describe electric double layer (EDL) in the presence of Faradaic reactions. We find that electrodes modified with oxygen functional groups increase the Faradaic capacitance but have relatively little influence on the EDL capacitance. The theoretical predictions agree quantitatively with experimental observations. We hope that this joint model by combining quantum DFT and classical DFT could provide a theoretical routine to study pseudocapacitors.
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•The thin Al2O3 ALD-PE porous separator possesses good electrolyte wettability, high ionic conductivity and low interface impedance.•The 4.5 V high voltage LiCoO2 cell using PE-75 ...separator exhibits excellent cycling performance and rate capability.•The pouch cell using PE-75 separator has superior safety.
Lithium-ion batteries that utilize polyethylene (PE) separators still require improvement. To improve the electrochemical properties and thermal stability of the PE separators, an-ultrathin Al2O3 layer (∼10 nm) was precisely coated onto the surface of a 7 μm thick PE separator via atomic layer deposition. The resulting ultrathin Al2O3 ALD-PE separators exhibited the excellent thermal dimensional stability and flexibility, and the tensile strength was considerably improved. Moreover, the ultrathin Al2O3 ALD-PE separator demonstrated better electrolyte wettability, higher ionic conductivity, and lower interface impedance. The 4.5 V high-voltage LiCoO2/Li coin-cells with the PE-75 separator exhibited better initial specific discharge capacity (184.3 mAh/g) and capacity retention rate (96 % after 300 cycles at 0.5C) compared to the PE separator (176.8 mAh/g; 87.7 % after 300 cycles at 0.5C). Furthermore, the Li/PE-75/Li symmetric cell had stably cycled for 1000 h without significant dendrites generation. Finally, the pouch-cell using the PE-75 separator was less prone to thermal runaway at high temperatures, indicating its improved safety.
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