Dynamic Room Temperature Phosphorescence of Silane-Functionalized Carbon Dots Confining within Silica for Anti-Counterfeiting Applications.

Room temperature phosphorescent (RTP) materials with long-lived, excitation-dependent, and time-dependent phosphorescence are highly desirable but very hard to achieve. Herein, this work reports a rational strategy of multiple wavelength excitation and time-dependent dynamic RTP color by confining silane-functionalized carbon dots (CDs) in a silica matrix (Si-CDs@SiO2). The Si-CDs@SiO2 possesses unique green-light-excitation and a change in phosphorescence color from yellow to green. A slow-decaying phosphorescence at 500 nm with a lifetime of 1.28 s and a fast-decaying phosphorescence at 580 nm with a lifetime of 0.90 s are observed under 365 nm of irradiation, which originated from multiple surface triplet states of the Si-CDs@SiO2. Given the unique dynamic RTP properties, the Si-CDs@SiO2 are demonstrated for applications in fingerprint recognition and multidimensional dynamic information encryption. These findings will open an avenue to explore dynamic phosphorescent materials and significantly broaden their applications.

Influences of Fast Track Surgery Concept-based High-quality Medical Service on Postoperative Symptom Improvement and Safety among Patients with Lung Cancer.

Objective: To investigate the impacts of the fast track surgery (FTS) concept on postoperative symptom improvement and complication incidence among lung cancer patients. Methods: 100 patients diagnosed with lung cancer after the detection of pulmonary nodules in the hospital (January 2020 to December 2021) were included as research subjects. 50 patients in the control group received routine nursing, while 50 patients in the experimental group underwent FTS nursing based on routine nursing. Preoperative and postoperative stress reactions, operation-related information, degree of pain, nursing satisfaction, and complications among included patients were summarized. Results: According to the results, the heart rate in the experimental group 72 hours after the operation was superior to that in the control group (P < .05). Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in the experimental group were lower than those in the control group. The differences demonstrated statistical significance (P < .05). Mean arterial pressure (MAP) in the experimental group 12 hours after the operation was lower than that in the control group (P < .05). The length of hospital stays and chest drainage tube indwelling duration in the experimental group were shorter than those in the control group (P < .05). The degree of pain experienced by patients in the experimental group apparently reduced 3 days after operation (P < .05). The total incidence of complications in the experimental group was lower than that recorded for patients in the control group (P < .05). Nursing satisfaction in the experimental group was superior to that in the control group and the difference revealed statistical significance (P < .05). Conclusions: The study verified the safety and efficacy of FTS concept-based operation on patients with lung cancer.

Preparation of nitrogen-doped carbon dots and their enhancement on lettuce yield and quality.

Nanotechnology is an effective way to stimulate the yield potential of crops. Various nano-fertilizers and nano-carriers are gradually being developed to bring about a technological revolution in the agricultural industry. As a biocompatible water-soluble nanomaterial, carbon dots (CDs) have attracted the attention of researchers for applications in agriculture. In this study, we prepared nitrogen-doped CDs (N-CDs) as a type of water-soluble carbon nanofertilizer by a one-pot hydrothermal method, and investigated its effects on lettuce biomass and quality. 100 and 200 mg L-1 of N-CDs substantially promoted lettuce biomass accumulation (41.70%), elevated lettuce nutrient content, as well as promoted the accumulation of major nutrients. Moreover, 100 mg L-1 N-CDs increased the chlorophyll a content by 12.68%, significantly increased the electron transport rate (ETR) by 38.61%, significantly increased the light energy conversion efficiency (Y(II)) by 31.24% and increased the Rubisco activity by 60.61%, which are important reasons for its increase in actual photosynthesis rate. N-CDs also have a positive effect on plant nitrogen metabolism by promoting the activity of glutamine synthetase. The significant benefits of N-CDs on lettuce make them have great potential for agricultural yield increase and quality improvement.

Identification and Molecular Mapping of the Gene YrFL in Wheat Cultivar Flanders with Durable Resistance to Stripe Rust.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most severe diseases of wheat (Triticum aestivum L.) worldwide. Identification and characterization of resistance genes is advantageous to cultivating wheat varieties with durable resistance, which is the most economic and effective strategy to control stripe rust. Flanders, a common wheat cultivar released in France in 1986, confers effective resistance to stripe rust both at the seedling and adult plant stages. To elucidate the genetic basis of resistance in Flanders, F1, F2, and F2:3 generations derived from the cross Mingxian169 × Flanders were evaluated with the most prevalent Chinese Pst race CYR33 at the seedling stage. Inheritance analysis showed that the stripe rust resistance of Flanders was controlled by a single dominant gene, temporarily designated as YrFL. Bulked segregant analysis (BSA) combined with a wheat 660K single-nucleotide polymorphism (SNP) array indicated that polymorphic SNP markers were mainly located in the 0 to 150 Mb on wheat chromosome 5A. One hundred and eleven kompetitive allele-specific PCR (KASP) and 39 simple sequence repeat (SSR) markers on chromosome 5A were used to locate the YrFL. Linkage analysis mapped YrFL with 19 KASP and three SSR markers on wheat chromosome 5AS, and the genetic distances of the closest flanking markers AX108925494 and Xbarc56 to YrFL were 0.6 and 2.0 cM, respectively. Chromosome location, resistance characterization, and molecular marker positions indicated that YrFL is likely a novel stripe rust resistance gene on wheat chromosome 5AS and could be pyramided with other resistance genes to improve resistance in wheat breeding programs.

Correction: Wu et al. Homologous Drought-Induced 19 Proteins, PtDi19-2 and PtDi19-7, Enhance Drought Tolerance in Transgenic Plants. Int. J. Mol. Sci. 2022, 23, 3371.

The authors wish to make the following corrections to this paper [...].

Comparative transcriptome profiling of resistant and susceptible foxtail millet responses to Sclerospora graminicola infection.

BACKGROUND: Downy mildew of foxtail millet, which is caused by the biotrophic oomycete Sclerospora graminicola (Sacc.) Schroeter, is one of the most disruptive diseases. The foxtail millet-S. graminicola interaction is largely unexplored. Transcriptome sequencing technology can help to reveal the interaction mechanism between foxtail millet and its pathogens. RESULTS: Transmission electron microscopy observations of leaves infected with S. graminicola showed that the structures of organelles in the host cells gradually became deformed and damaged, or even disappeared from the 3- to 7-leaf stages. However, organelles in the leaves of resistant variety were rarely damaged. Moreover, the activities of seven cell wall degrading enzymes in resistant and susceptible varieties were also quite different after pathogen induction and most of enzymes activities were significantly higher in the susceptible variety JG21 than in the resistant variety G1 at all stages. Subsequently, we compared the transcriptional profiles between the G1 and JG21 in response to S. graminicola infection at 3-, 5-, and 7-leaf stages using RNA-Seq technology. A total of 473 and 1433 differentially expressed genes (DEGs) were identified in the resistant and susceptible varieties, respectively. The pathway analysis of the DEGs showed that the highly enriched categories were related to glutathione metabolism, plant hormone signalling, phenylalanine metabolism, and cutin, suberin and wax biosynthesis. Some defence-related genes were also revealed in the DEGs, including leucine-rich protein kinase, Ser/Thr protein kinase, peroxidase, cell wall degrading enzymes, laccases and auxin response genes. Our results also confirmed the linkage of transcriptomic data with qRT-PCR data. In particular, LRR protein kinase encoded by Seita.8G131800, Ser/Thr protein kinase encoded by Seita.2G024900 and Seita. 2G024800, which have played an essential resistant role during the infection by S. graminicola. CONCLUSIONS: Transcriptome sequencing revealed that host resistance to S. graminicola was likely due to the activation of defence-related genes, such as leucine-rich protein kinase and Ser/Thr protein kinase. Our study identified pathways and genes that contribute to the understanding of the interaction between foxtail millet and S. graminicola at the transcriptomic level. The results will help us better understand the resistance mechanism of foxtail millet against S. graminicola.

Effect of Risk-Focused Diversified Safety Management Mode in Patients with Major Artery Stent Implantation.

Background: Intracranial atherosclerotic stenosis (ICAS) causes a series of neurological symptoms, such as vertigo, impaired consciousness, limb weakness, ataxia, dysphagia, ocular motility disorders, and visual impairment. With the improvement of people's living standards, there are higher requirements for nursing care. Nursing, as an indispensable part of medical care, is closely related to achieving the goal of patient's safety and the overall quality of nurses, quality of care, and nursing management methods. Objective: To explore the effect of risk-centered diversified safety management in patients undergoing aortic stenting. Methods: Eighty patients with cerebral infarction were selected and treated with percutaneous transluminal angioplasty and stent implantation (PTAS). Then they were divided into a control group (40 cases) with routine monitoring and an experimental group (40 cases) with risk-focused intervention of a diversified safety management model according to the mode of care. Patient satisfaction and blood index test results were compared after the intervention. Results: Patients in the experimental group had 6 falls, 3 bed falls, 3 phlebitis, 4 tube slips, and 10 deep vein thrombosis, all significantly fewer than those in the control group. Thirty-eight patients in the experimental group expressed satisfaction with safe management, which was substantially better than the control group (P < 0.05). The levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PA1-1), and von Willebrand factor (vWF) in the experimental group were (13.5 ± 1.3) ng/mL, (60.1 ± 9.9) ng/mL, and (2.1 ± 0.2), respectively, which were substantially lower than those in the control group ((14.6 ± 2.4) ng/mL, (64.2 ± 10.7) ng/mL, and (2.8 ± 0.3)), respectively (P < 0.05). Conclusion: The risk-centered diversified safety management model can effectively reduce the probability of adverse events in patients, improve patient satisfaction with nursing services, and promote faster postoperative recovery, which has clinical application value.

SAUR8, a small auxin-up RNA gene in poplar, confers drought tolerance to transgenic Arabidopsis plants.

SAUR (small auxin-up RNA) is an early auxin-responsive gene. In this study, a novel SAUR gene PtSAUR8 was cloned from poplar (Populus trichocarpa), and subcellular location analysis showed that it is targeted to the nuclear membrane. In addition, PtSAUR8 overexpression in Arabidopsis improved the plant resistance to drought stress. Meanwhile, the loss of function mutant saur53 showed more drought sensitivity compared to the WT. PtSAUR8 conferred drought tolerance in transgenic Arabidopsis, as determined through phenotypic and stress-associated physiological indicator analyses, namely, root length, germination rate, relative water content, proline content, CAT content, POD content, malondialdehyde content, hydrogen peroxide content, and relative conductivity. In addition, after the 1 µM abscisic acid (ABA) treatment, the PtSAUR8-OE lines promoted stomata closure. Quantitative fluorescence analysis of related genes induced by drought mutant stress further confirmed that overexpression of PtSAUR8 can improve drought resistance in transgenic Arabidopsis lines. Therefore, PtSAUR8 may play a role in plant drought resistance through ABA-mediated pathways; thus, providing new research materials for molecular breeding of poplar resistance.

Homologous Drought-Induced 19 Proteins, PtDi19-2 and PtDi19-7, Enhance Drought Tolerance in Transgenic Plants.

Drought-induced 19 (Di19) proteins play important roles in abiotic stress responses. Thus far, there are no reports about Di19 family in woody plants. Here, eight Di19 genes were identified in poplar. We analyzed phylogenetic tree, conserved protein domain, and gene structure of Di19 gene members in seven species. The results showed the Di19 gene family was very conservative in both dicotyledonous and monocotyledonous forms. On the basis of transcriptome data, the expression patterns of Di19s in poplar under abiotic stress and ABA treatment were further studied. Subsequently, homologous genes PtDi19-2 and PtDi19-7 with strong response to drought stress were identified. PtDi19-2 functions as a nuclear transcriptional activator with a transactivation domain at the C-terminus. PtDi19-7 is a nuclear and membrane localization protein. Additionally, PtDi19-2 and PtDi19-7 were able to interact with each other in yeast two-hybrid system. Overexpression of PtDi19-2 and PtDi19-7 in Arabidopsis was found. Phenotype identification and physiological parameter analysis showed that transgenic Arabidopsis increased ABA sensitivity and drought tolerance. PtDi19-7 was overexpressed in hybrid poplar 84K (Populus alba × Populus glandulosa). Under drought treatment, the phenotype and physiological parameters of transgenic poplar were consistent with those of transgenic Arabidopsis. In addition, exogenous ABA treatment induced lateral bud dormancy of transgenic poplar and stomatal closure of transgenic Arabidopsis. The expression of ABA/drought-related marker genes was upregulated under drought treatment. These results indicated that PtDi19-2 and PtDi19-7 might play a similar role in improving the drought tolerance of transgenic plants through ABA-dependent signaling pathways.

The poplar VQ1 gene confers salt tolerance and pathogen resistance in transgenic Arabidopsis plants via changes in hormonal signaling.

The VQ protein family is plant-specific, and is involved in growth, development, and biotic and abiotic stress responses. In this study, we found that the gene expression of poplar VQ1(Potri.001G029700) from Populus trichocarpa varied remarkably under salt stress and hormones associated with disease. A subcellular localization experiment showed that VQ1 was localized in the nucleus and cytomembrane in tobacco. The overexpression of VQ1 in Arabidopsis thaliana enhanced its resistance to salt stress and disease, and was also responsive to it through abscisic acid. Compared with wild-type, transgenic Arabidopsis lines had significantly increased levels of abscisic acid and salicylic acid. The expression of some stress-related genes, such as MPK6, NPR1, and PDF1.2, was significantly up-regulated by salt in transgenic plants, while WRKY70, ABI1, KUP6, and NCED2 were significantly down-regulated by Pseudomonas syringae pv. tomato DC3000 in transgenic plants. Together, these results demonstrate that VQ1 modulates hormonal signaling to confer multiple biotic and abiotic stress responses in transgenic Arabidopsis plants.

GEPSdb: The Gene Expression Database of Poplar under Stress.

As a model tree species, poplar (Populus L.) has important economic and ecological value. Here, we constructed the GEPSdb (Gene Expression Database of Poplar under Stress; http://gepsdb.ahau-edu.cn/), which is an integrated database of poplar gene expression profiles derived from RNA-seq and microarray library data. This database provides a comprehensive collection of gene expression data from poplar exposed to 14 types of environmental stress from 11 high-quality RNA-seq experiments and 51 microarray libraries. The GEPSdb includes 56 genes from previous literature that have been examined in poplar and functionally verified. By incorporating data from numerous expression analyses, GEPSdb provides a user-friendly web interface for querying, browsing, and visualizing the expression profiles of related genes. Consequently, GEPSdb can be used to link transcription data with phenotypes and can enhance our understanding of important biological processes and mechanisms underlying complex agronomic traits in poplar.

Relationship between Lp-PLA2 and in-stent restenosis after coronary stenting: a 3-year follow-up study.

BACKGROUND AND AIMS: Coronary in-stent restenosis (ISR) is an important complication of percutaneous coronary intervention (PCI). However, the relationship between lipoprotein associated phospholipase A2 (Lp-PLA2) level and ISR after PCI is rarely reported. This study aims to explore the relationship between Lp-PLA2 and the occurrence of ISR at post-PCI and its predictive value for ISR. METHODS AND RESULTS: Plasma Lp-PLA2 mass were measured in 847 patients planting 1262 stents and evaluated along with known risk indicators. One-year angiographic follow-up showed that baseline elevated Lp-PLA2 mass was strongly associated with early restenosis (95% CI = 1.062-3.050, P < 0.05). Beyond the first year, the occurrence of late restenosis (95% CI = 1.043-3.214, P < 0.05) was significantly larger in the elevated Lp-PLA2 group. Kaplan-Meier analysis after three-year clinical follow up suggested that Lp-PLA2 mass did add the positive effect on the occurrence of major adverse cardiovascular events (MACEs). CONCLUSION: In conclusion, increased baseline plasma Lp-PLA2 predicts increased risks of re-stenosis and MACEs, which may be a novel biomarker for predicting ISR and MACEs.

Calcitonin gene­related peptide regulates FOSL2 expression and cell proliferation of BMSCs via mmu_circRNA_003795.

Circular RNAs (circRNAs) are a class of non­coding RNAs that may have important regulatory potency in various biological processes. However, the role of circRNAs and their potential functions in bone marrow mesenchymal stem cells of mice (BMSCs) are still ambiguous. The current study aims to examine the expression of circRNAs and to investigate their effects on FOS like 2 AP­1 transcription factor subunit (FOSL2) expression following stimulation of BMSCs with calcitonin gene­related peptide (CGRP). RNA generated from BMSCs stimulated with or without CGRP was used in a microarray to detect expression of circRNAs. There were 58 significantly differentially expressed circRNAs following CGRP treatment, with 44 circRNAs downregulated and 14 upregulated. Bioinformatics analysis and regulatory networks were used to identify the potential interactions between circRNAs and microRNAs (miRs). mmu_circRNA_003795 was significantly increased in the CGRP­stimulated BMSCs compared with the blank control. Silencing of mmu_circRNA_003795, significantly increased the expression of mmu_miR­504­3p, whereas FOSL2 expression and cell proliferation were decreased. Furthermore, silencing of mmu_mir­504­3p using an miR inhibitor led to increased FOSL2 expression. Additionally, silencing of mmu_circRNA_003795 using small interfering RNA induced marked alterations in the cell cycle of BMSCs. The results demonstrated that mmu_circRNA_003795 can indirectly regulate FOSL2 expression via sponging of miR­504­3p, resulting in alterations in BMSC proliferation.

3D printing mesoporous bioactive glass/sodium alginate/gelatin sustained release scaffolds for bone repair.

Drug delivery and release are a major challenge fabricating bone tissue engineering. In this study, we fabricated new sustained release hydrogel scaffolds composited of mesoporous bioactive glass, sodium alginate and gelatin by a three-dimensional printing technique. Naringin and calcitonin gene-related peptide were used as drugs to prepare drug-loaded scaffolds by direct printing or surface absorption. The physicochemical properties of the scaffolds and the drug release profiles of the two drug-loading models were investigated. We also examined the biocompatibility of the scaffolds, as well as the effect of the released medium on the proliferation and osteogenic differentiation of human osteoblast-like MG-63 cell. The results showed that the scaffolds had a high porosity (approximately 80%) with an interconnected cubic pore structure, rough surface morphology, bioactivity and strong biocompatibility. Furthermore, the naringin or calcitonin gene-related peptide co-printed into the scaffold displayed a steady sustained release behaviour for up to 21 days without an initial burst release, while both naringin and calcitonin gene-related peptide absorbed onto the surface of the scaffold were completely released within two days. MG-63 cells cultured with the extraction containing released drugs displayed promoted cell proliferation and the expression of osteogenesis-related genes more effectively compared with the drug-free extractions. Therefore, these results demonstrate that the developed mesoporous bioactive glass/sodium alginate/gelatin sustained release scaffolds provide a potential application for bone tissue engineering.

Mm9_circ_009056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22-3p.

Circular RNAs (circRNAs) are noncoding RNAs that can function as miRNA sponges, post-transcriptionally regulating the expression of genes. Here, we report a novel positive function of mm9_circ_009056 during osteogenesis in regulating bone morphogenetic protein 7 (BMP7) through miR-22-3p. First, we found that calcitonin gene-related peptide (CGRP) had great osteogenesis function on MC3T3 cells. Then aberrant expression of mm9_circ_009056 were confirmed in CGRP-induced cells. Furthermore, the expression of mm9_circ_009056 was up-regulated in the CGRP-induced cells, whereas miR-22-3p was obviously decreased. Silencing of mm9_circ_009056 increased the expression of miR-22-3p and decreased the gene and protein levels of BMP7, RUNX2. Cells proliferation and growth were also inhibited following silengcing. The protein levels of BMP7 and RUNX2 decreased after mimics transfection and increased after inhibitors transfection. In summary, mm9_circ_009056 may function as a sponge for miR-22-3p to regulate osteogenesis in CGRP-induced cells.

Bio-Oss® modified by calcitonin gene-related peptide promotes osteogenesis in vitro.

Bio-Oss® and α-calcitonin gene-related peptide (CGRP) are involved in osteogenesis. However, it has remained to be assessed how α-CGRP affects the effect of Bio-Oss. In the present study, primary osteoblasts were incubated with α-CGRP, Bio-Oss, α-GGRP-Bio-Oss or mimic-α-CGRP. The proliferation rate, mineralization nodules, alkaline phosphatase (ALP) activity and the expression of osteogenic genes were measured by a Cell Counting Kit-8 assay, Alizarin Red-S staining, ALP activity detection and reverse-transcription quantitative PCR as well as western blot analysis, respectively. The proliferation rate, ALP activity and the number of mineralization nodules were significantly increased in the α-CGRP-modified Bio-Oss group compared to that in the Bio-Oss group. The mRNA and protein levels of osteocalcin, Runt-related transcription factor-2 and ALP were significantly upregulated in the α-CGRP-Bio-Oss group compared with those in the Bio-Oss group. Furthermore, the effect of mimic-α-CGRP on osteogenesis was reduced as it carried a mutation. In conclusion, the present study was the first to demonstrate that Bio-Oss modified with CGRP contributed to osteogenesis and may provide a novel formulation applied in the clinic for restoration of large bone defects.

Calcitonin gene­related peptide induces IL­6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893.

Several circular RNAs (circRNAs) may have role important roles in biological processes, however, there is limited knowledge of circRNAs and their potential functions in RAW264.7 macrophages. The present study aimed to examine the expression of circRNAs and explore their effects on interleukin­6 (IL­6) expression induced by calcitonin gene­related peptide (CGRP) in RAW264.7 macrophages. To identify circRNAs, the circRNA expression was measured in macrophages with or without CGRP stimulation. The interaction between circRNAs and microRNAs (miRs) were then identified using bioinformatic software and networks. In the current study, it was demonstrated that CGRP increased the expression of IL­6 mRNA in a dose­ and time­dependent manner. Furthermore, mmu_circRNA_007893 was significantly increased in the CGRP­stimulated macrophages. Silencing of mmu_circRNA_007893, IL­6 mRNA expression was significantly decreased, whereas mmu­miR­485­5p expression was markedly increased. Furthermore, when overexpression of mmu­miR­485­5p, IL­6 mRNA was markedly decreased. The results demonstrated that CGRP­induced IL­6 mRNA expression was mediated by mmu_circRNA_007893, and mmu_circRNA_007893 functioned as an endogenous mmu­miR­485­5p sponge as part of induction of IL­6 mRNA expression.

Preparation of natural alpha-tocopherol from non-alpha-tocopherols.

Non-alpha-tocopherols are hydroxymethylated and hydrogenated to produce alpha-tocopherol in one pot process by simultaneously reacting with paraformaldehyde and hydrogen in the presence of catalysts of benzenesulfonic acid and 5% Pd/C in an autoclave. Effects of various operation conditions have been studied. The preferable reaction conditions are: temperature 180 degrees C to 200 degrees C, pressure 5.0 MPa, acid concentration 0.5 g/100 ml ethanol, mass ratio of Pd/C to tocopherols 7.1 g/100 g, and reaction time 5.0 h. A product with alpha-tocopherol content of 80% was obtained by using a raw material with a total tocopherols content of 80.54%. The conversion of non-alpha-tocopherols is almost 100%, and the mole yield of alpha-tocopherol is more than 90%.

[Extra-thermodynamic properties of 2-arylpropionic acids on a chiral-AGP column by high performance liquid chromatography].

The effect of temperature (274-313 K) on the chromatographic behavior of naproxen and ibuprofen on a Chiral-AGP column was investigated with a mobile phase consisting of 50 mmol/L phosphate buffer (pH 6.41) and 0.5% (or 1.0%, v/v) 1-propanol. Higher temperature was found disadvantageous to the enantiomeric separation. With temperature increased, the retention time, resolution and selectivity of the chiral separation were decreased. The resolution of naproxen was larger than that of ibuprofen in all cases. When naproxen and ibuprofen enantiomers were entirely separated by the mobile phase containing 1.0% 1-propanol, the maximum temperatures allowed were 298 K and 288 K, respectively. All of the Van' t Hoff plots of the In k vsrsus 1/T were found to have good linearity, with the correlation coefficients better than 0.99 in all cases. The thermodynamic parameters (changes of enthalpy, i. e., deltaH0, for the transfer of enantiomers from the mobile phase to the stationary phase and differences of enthalpy and entropy changes, i. e., deltaS,R deltaH0 and deltaS,R deltaS0) were calculated. In general, in the temperature range examined the enthalpic contribution to the overall enantiomer transfer energy was found to be more significant than the entropic one.