An Overview of the Free Energy Principle and Related Research.

The free energy principle and its corollary, the active inference framework, serve as theoretical foundations in the domain of neuroscience, explaining the genesis of intelligent behavior. This principle states that the processes of perception, learning, and decision making-within an agent-are all driven by the objective of "minimizing free energy," evincing the following behaviors: learning and employing a generative model of the environment to interpret observations, thereby achieving perception, and selecting actions to maintain a stable preferred state and minimize the uncertainty about the environment, thereby achieving decision making. This fundamental principle can be used to explain how the brain processes perceptual information, learns about the environment, and selects actions. Two pivotal tenets are that the agent employs a generative model for perception and planning and that interaction with the world (and other agents) enhances the performance of the generative model and augments perception. With the evolution of control theory and deep learning tools, agents based on the FEP have been instantiated in various ways across different domains, guiding the design of a multitude of generative models and decision-making algorithms. This letter first introduces the basic concepts of the FEP, followed by its historical development and connections with other theories of intelligence, and then delves into the specific application of the FEP to perception and decision making, encompassing both low-dimensional simple situations and high-dimensional complex situations. It compares the FEP with model-based reinforcement learning to show that the FEP provides a better objective function. We illustrate this using numerical studies of Dreamer3 by adding expected information gain into the standard objective function. In a complementary fashion, existing reinforcement learning, and deep learning algorithms can also help implement the FEP-based agents. Finally, we discuss the various capabilities that agents need to possess in complex environments and state that the FEP can aid agents in acquiring these capabilities.

Genome-wide evolutionary characterization and expression analysis of SIAMESE-RELATED family genes in maize.

BACKGROUND: The SIAMESE (SIM) locus is a cell-cycle kinase inhibitor (CKI) gene that has to date been identified only in plants; it encodes a protein that promotes transformation from mitosis to endoreplication. Members of the SIAMESE-RELATED (SMR) family have similar functions, and some are related to cell-cycle responses and abiotic stresses. However, the functions of SMRs are poorly understood in maize (Zea mays L.). RESULTS: In the present study, 12 putative SMRs were identified throughout the entire genome of maize, and these were clustered into six groups together with the SMRs from seven other plant species. Members of the ZmSMR family were divided into four groups according to their protein sequences. Various cis-acting elements in the upstream sequences of ZmSMRs responded to abiotic stresses. Expression analyses revealed that all ZmSMRs were upregulated at 5, 20, 25, and 35 days after pollination. In addition, we found that ZmSMR9/11/12 may have regulated the initiation of endoreplication in endosperm central cells. Additionally, ZmSMR2/10 may have been primarily responsible for the endoreplication regulation of outer endosperm or aleurone cells. The relatively high expression levels of almost all ZmSMRs in the ears and tassels also implied that these genes may function in seed development. The effects of treatments with ABA, heat, cold, salt, and drought on maize seedlings and expression of ZmSMR genes suggested that ZmSMRs were strongly associated with response to abiotic stresses. CONCLUSION: The present study is the first to conduct a genome-wide analysis of members of the ZmSMR family by investigating their locations in chromosomes, identifying regulatory elements in their promoter regions, and examining motifs in their protein sequences. Expression analysis of different endosperm developmental periods, tissues, abiotic stresses, and hormonal treatments suggests that ZmSMR genes may function in endoreplication and regulate the development of reproductive organs. These results may provide valuable information for future studies of the functions of the SMR family in maize.

The distribution pattern of endopolyploidy in maize.

KEY MESSAGE: We discovered that endopolyploidization is common in various organs and tissues of maize at different development stages. Endopolyploidy is not specific in maize germplasm populations. Endopolyploidy is caused by DNA endoreplication, a special type of mitosis with normal DNA synthesis and a lack of cell division; it is a common phenomenon and plays an important role in plant development. To systematically study the distribution pattern of endopolyploidy in maize, flow cytometry was used to determine the ploidy by measuring the cycle (C) value in various organs at different developmental stages, in embryos and endosperm during grain development, in roots under stress conditions, and in the roots of 119 inbred lines from two heterotic groups, Shaan A and Shaan B. Endopolyploidy was observed in most organs at various developmental stages except in expanded leaves and filaments. The endosperm showed the highest C value among all organs. During tissue development, the ploidy increased in all organs except the leaves. In addition, the endopolyploidization of the roots was significantly affected by drought stress. Multiple comparisons of the C values of seven subgroups revealed that the distribution of endopolyploidization was not correlated with the population structure. A correlation analysis at the seedling stage showed a positive relationship between the C value and both the length of the whole plant and the length of main root. A genome-wide association study (GWAS) identified a total of 9 significant SNPs associated with endopolyploidy (C value) in maize, and 8 candidate genes that participate in cell cycle regulation and DNA replication were uncovered in 119 maize inbred lines.

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α-Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer.

BACKGROUND/AIMS: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. MATERIALS: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. RESULTS: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. CONCLUSION: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer.

BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in various cancers. However, the clinical significance of HMGB2 signaling in human breast cancer progression remains unknown. METHODS: We investigated HMGB2 expression in 185 cases of primary breast cancer and matched normal breast tissue specimens, and explored the underlying mechanisms of altered HMGB2 expression as well as the impact of this altered expression on breast cancer growth and on aerobic glycolysis using in vitro and animal models of breast cancer. RESULTS: HMGB2 was more highly expressed in tumor-cell nuclei of breast cancer cells than in the adjacent normal breast tissues (P < 0.05). Higher HMGB2 expression correlated with larger tumor size (P = 0.003) and advanced tumor stage (P = 0.033). A Cox proportional hazards model revealed that HMGB2 expression was an independent prognostic factor for breast cancer after radical resection (P < 0.05). Experimentally, knockdown of HMGB2 expression by stable transfected shRNA significantly decreased the growth and glycolysis of breast cancer cells both in vitro and in mouse models. Mechanically, promotion of breast cancer progression by HMGB2 directly and significantly correlated with activation of LDHB expression and inactivation of FBP1 expression. CONCLUSIONS: These results disclose a novel role for HMGB2 in reprogramming the metabolic process in breast cancer cells by targeting LDHB and FBP1 and provide potential prognostic predictors for breast cancer patients.

Genomic variation in weedy and cultivated broomcorn millet accessions uncovers the genetic architecture of agronomic traits.

Large-scale genomic variations are fundamental resources for crop genetics and breeding. Here we sequenced 1,904 genomes of broomcorn millet to an average of 40× sequencing depth and constructed a comprehensive variation map of weedy and cultivated accessions. Being one of the oldest cultivated crops, broomcorn millet has extremely low nucleotide diversity and remarkably rapid decay of linkage disequilibrium. Genome-wide association studies identified 186 loci for 12 agronomic traits. Many causative candidate genes, such as PmGW8 for grain size and PmLG1 for panicle shape, showed strong selection signatures during domestication. Weedy accessions contained many beneficial variations for the grain traits that are largely lost in cultivated accessions. Weedy and cultivated broomcorn millet have adopted different loci controlling flowering time for regional adaptation in parallel. Our study uncovers the unique population genomic features of broomcorn millet and provides an agronomically important resource for cereal crops.

Preparation, characterization, and evaluation of flaxseed oil liposomes coated with chitosan and pea protein isolate hydrolysates.

The effect of layer-by-layer coating of liposomes with chitosan and pea protein isolate hydrolysates (PPIH) was evaluated. Traditional flaxseed oil liposomes (FL Lipo) were used as a model for comparison to liposomes coated with chitosan and PPIH (FL LipoCP). The potential of PPIH as a coating material was evaluated. Additionally, the influence of chitosan and PPIH on vesicle size and zeta potential of liposomes was investigated. The chitosan layer of liposomes exhibited a loose structure. After the second layer of coating with PPIH, chitosan molecules were rearranged on the liposome surface, leading to a more compact and dense shell structure of liposomes. Electrostatic interactions, hydrogen bonds, and hydrophobic interactions favored the stability of FL LipoCP. Compared to FL Lipo, FL LipoCP displayed higher oxidation stability during storage and a slower release of flaxseed oil during in vitro digestion.

Geastrumsuae sp. nov. (Geastraceae, Basidiomycota) a new species from Yunnan Province, China.

Background: Geastrum is the largest genus of Geastraceae and is widely distributed all over the world. Four specimens which belong to Geastrum were collected during our scientific expedition to Cangshan Mountain, Yunnan, China. Based on morphological characteristics and phylogenetic analysis, a new species was introduced. New information: Geastrumsuae is characterised by its large basidiomata (height 35-70 mm, diameter 18-37 mm) with long stipe (height 10-45 mm), smooth pink exoperidium and sessile globose endoperidial body. Phylogenetic analysis has been carried out, based on the internal transcribed spacer (ITS) and large subunit ribosomal ribonucleic acid (nrLSU) sequence data. The illustration and description for the new taxa are provided.

Genomic analyses of rice bean landraces reveal adaptation and yield related loci to accelerate breeding.

Rice bean (Vigna umbellata) is an underexploited domesticated legume crop consumed for dietary protein in Asia, yet little is known about the genetic diversity of this species. Here, we present a high-quality reference genome for a rice bean landrace (FF25) built using PacBio long-read data and a Hi-C chromatin interaction map, and assess the phylogenetic position and speciation time of rice bean within the Vigna genus. We sequence 440 landraces (two core collections), and GWAS based on data for growth sites at three widely divergent latitudes reveal loci associated with flowering and yield. Loci harboring orthologs of FUL (FRUITFULL), FT (FLOWERING LOCUS T), and PRR3 (PSEUDO-RESPONSE REGULATOR 3) contribute to the adaptation of rice bean from its low latitude center of origin towards higher latitudes, and the landraces which pyramid early-flowering alleles for these loci display maximally short flowering times. We also demonstrate that copy-number-variation for VumCYP78A6 can regulate seed-yield traits. Intriguingly, 32 landraces collected from a mountainous region in South-Central China harbor a recently acquired InDel in TFL1 (TERMINAL FLOWER1) affecting stem determinacy; these materials also have exceptionally high values for multiple human-desired traits and could therefore substantially advance breeding efforts to improve rice bean.

Population-scale peach genome analyses unravel selection patterns and biochemical basis underlying fruit flavor.

A narrow genetic basis in modern cultivars and strong linkage disequilibrium in peach (Prunus persica) has restricted resolution power for association studies in this model fruit species, thereby limiting our understanding of economically important quality traits including fruit flavor. Here, we present a high-quality genome assembly for a Chinese landrace, Longhua Shui Mi (LHSM), a representative of the Chinese Cling peaches that have been central in global peach genetic improvement. We also map the resequencing data for 564 peach accessions to this LHSM assembly at an average depth of 26.34× per accession. Population genomic analyses reveal a fascinating history of convergent selection for sweetness yet divergent selection for acidity in eastern vs. western modern cultivars. Molecular-genetics and biochemical analyses establish that PpALMT1 (aluminum-activated malate transporter 1) contributes to their difference of malate content and that increases fructose content accounts for the increased sweetness of modern peach fruits, as regulated by PpERDL16 (early response to dehydration 6-like 16). Our study illustrates the strong utility of the genomics resources for both basic and applied efforts to understand and exploit the genetic basis of fruit quality in peach.

Development of a five-stage solid-state linear transformer driver.

In this paper, the development of a five-stage solid-state linear transformer driver (LTD) is described. Each stage consists of eight compact pulse generating modules and a magnetic core. The pulse generating modules contain a multilayer-ceramic-capacitor-based pulse-forming network (PFN) and an insulated-gate bipolar transistor (IGBT) switch array, as well as magnetic switches, which are used to speed up the pulse front. To prevent damage from the reverse voltage to the IGBT switch, a reverse voltage absorption circuit was added to the PFN. For this study, a larger cross-sectional core with improved output characteristics was adopted. The developed five-stage LTD has the advantages of long life, low jitter, fast rising edge, and so on. The device can provide a 35 kV, 119 ns, 4.3 kA square pulse train with a maximum frequency of 50 Hz. On this basis, a 50-stage LTD of output 500 kV, which would serve as a high-power microwave driver source, is under development.

A solid-state pulse generator based on multilayer ceramic capacitors and insulated gate bipolar transistors.

A solid-state pulse-forming network (PFN) module was designed using multilayer ceramic capacitors (MLCCs). In addition, an all-solid-state pulse generator was fabricated with a Blumlein line that consisted of two PFN single lines and an insulated gate bipolar transistor (IGBT) switch array. This generator was integrated on printed circuit boards (PCBs). The stage capacitors of the PFN were composed of MLCCs connected in series and parallel. To obtain a compact structure, folded, copper-clad wires were used as interstage inductors. The copper-clad wires were structurally optimized to reduce coupling between adjacent interstage inductors. A relatively fast rising waveform edge was obtained using an IGBT gate-boosting circuit and magnetic switch technology. A square-wave pulse with a rise time of 27 ns, a voltage of 5 kV, a width of 120 ns, a maximum repetition rate of 100 Hz, and an evaluated lifetime of 109 pulses was obtained on a load of 6.6 Ω. With its compact size, fast rise time, and long lifetime, the fabricated pulse generator can be used as a component in linear transformer drivers or Marx generators.

ZmSMR4, a novel cyclin-dependent kinase inhibitor (CKI) gene in maize (Zea mays L.), functions as a key player in plant growth, development and tolerance to abiotic stress.

Endoreduplication is a key cell cycle variant in the developing maize endosperm and has been associated with cell enlargement and dry matter accumulation. Therefore, identification of the key genes associated with endosperm development and endoreduplication would not only lay the groundwork for understanding the biological process of endoreduplication but also be important for maize breeding. Here, we identified 12 putative endoreduplication-related candidate genes as members of the Zea mays L. SIAMESE-RELATED (ZmSMR) gene family and denoted them ZmSMR1-ZmSMR12. Sequence analysis indicated that all the ZmSMR protein sequences exhibited modest sequence similarity to the SIAMESE gene from Arabidopsis. Further analyses suggested that most ZmSMR genes might be associated with the transition from mitosis to endoreduplication because the expression levels of most ZmSMR genes were upregulated in endosperm cells during the phase of switching to an endoreduplication cell cycle. Additionally, the ZmSMRs responded to various abiotic stresses at the transcriptional level. One member of the ZmSMR gene family, the ZmSMR4 (KY946768) gene, was isolated as the first maize endoreduplication-related gene and has been used to develop transgenic Arabidopsis plants. ZmSMR4 was localized to the nucleus and could interact with ZmCDKA and ZmCDKB. Moreover, ZmSMR4 was able to rescue the multicellular trichome phenotype of Arabidopsis sim mutants and enhanced the endoreduplication levels of transgenic Arabidopsis plants. Arabidopsis plants overexpressing ZmSMR4 not only displayed enhanced leaf margin serrations but also showed several interesting breeding phenotypes, such as early blossoming and fuller seeds. Taken together, our data suggest that the ZmSMR4 gene is plant-specific and functions as a key player in the signalling network that controls plant growth, development and responses to abiotic stress by regulating the transition between the mitotic cycle and endoreduplication.

Evolutionary, structural and expression analysis of core genes involved in starch synthesis.

Starch is the main storage carbohydrate in plants and an important natural resource for food, feed and industrial raw materials. However, the details regarding the pathway for starch biosynthesis and the diversity of biosynthetic enzymes involved in this process are poorly understood. This study uses a comprehensive phylogenetic analysis of 74 sequenced plant genomes to revisit the evolutionary history of the genes encoding ADP-glucose pyrophosphorylase (AGPase), starch synthase (SS), starch branching enzyme (SBE) and starch de-branching enzyme (DBE). Additionally, the protein structures and expression patterns of these four core genes in starch biosynthesis were studied to determine their functional differences. The results showed that AGPase, SS, SBE and DBE have undergone complicated evolutionary processes in plants and that gene/genome duplications are responsible for the observed differences in isoform numbers. A structure analysis of these proteins suggested that the deletion/mutation of amino acids in some active sites resulted in not only structural variation but also sub-functionalization or neo-functionalization. Expression profiling indicated that AGPase-, SS-, SBE- and DBE-encoding genes exhibit spatio-temporally divergent expression patterns related to the composition of functional complexes in starch biosynthesis. This study provides a comprehensive atlas of the starch biosynthetic pathway, and these data should support future studies aimed at increasing understanding of starch biosynthesis and the functional evolutionary divergence of AGPase, SS, SBE, and DBE in plants.

High expression of PLA2G16 is associated with a better prognosis in HER2-positive breast cancer.

BACKGROUND: PLA2G16 functions as a phosphatase in metabolism and its abnormal expression is closely associated with tumor progression. The aim of this study is to investigate the prognosis value of PLA2G16 in breast cancer. METHODS: A tissue microarray including 200 invasive ductal carcinoma specimens was constructed. Immunohistochemistry was performed to determine the PLA2G16 expression status. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of PLA2G16. The Multivariate Cox regression analysis was performed to identify whether PLA2G16 was an independent prognostic factor. RESULTS: In our retrospective study, Kaplan-Meier analysis showed that elevated PLA2G16 expression was correlated with improved DFS (P=0.032) in the whole breast cancer patients. In further subgroup analysis, PLA2G16 overexpression was found to be associated with prolonged DFS (P=0.018) in HER2-positive breast cancer patients. More importantly, Multivariate analysis suggested that PLA2G16 was a significant independent prognostic factor in HER2-enriched patients [hazard ratio (HR) =0.151; 95% confidence interval (CI) =0.034-0.672; P=0.013]. CONCLUSIONS: Our study evaluated the prognostic significance of PLA2G16 in patients with HER2-positive breast cancer and confirmed the relevance of this metabolism-related gene in patient outcome.

Novel colon-specific microspheres with highly dispersed hydroxycamptothecin cores: their preparation, release behavior, and therapeutic efficiency against colonic cancer.

To increase therapeutic efficiency of hydroxycamptothecin (HCPT) against colonic cancer and decrease its side-effects, highly dispersed HCPT was first incorporated in fast release microspheres. HCPT in the microspheres showed a solubility two times larger, and its cumulative release rate for 24 h in simulated colonic juice 140 times higher than that of free HCPT. The microspheres were then coated with a layer of Eudragit S100 by air suspension spray-drying method with a self-designed device to obtain colon-specific microspheres (HCPT-CSMS). The mean particle size of the microspheres was 200 microm before coating and 230 microm after coating. The in vitro cumulative release results for HCPT-CSMS in simulated gastric juice for 2 h, in simulated enteric juice for 4 h, and in simulated colonic juice for 18 h showed that over 60% of total HCPT released in simulated colonic juice in the initial 5 h. Animal tests with per os (po) administration showed that free HCPT was mainly absorbed in stomach and small intestine, while the HCPT in HCPT-CSMS was mainly delivered and absorbed in colon. po administration of HCPT-CSMS to nude mice with colonic cancer showed a cancer inhibition rate of 61.4% compared to 39.8% for free HCPT.

Influence of a municipal solid waste incinerator on ambient air PCDD/F levels: a comparison of running and non-running periods.

The concentration of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the ambient air of a municipal solid waste incinerator (MSWI) during its running and non-running periods was monitored in this study to investigate the contribution of the MSWI to PCDD/F pollution in the vicinal environment. Results show that the PCDD/F levels for the normal MSWI running period and after shut-down ranged 0.156-1.44 pg I-TEQ/m(3) (0.514 pg I-TEQ/m(3)) and 0.158-0.648 pg I-TEQ/m(3) (0.345 pg I-TEQ/m(3)), respectively. Significant differences were found between the results of the two surveys in 2011 and 2012. High PCDD/F levels were observed in two of the seven study sites in 2011, and these levels directly declined in 2012. A dramatic increase in PCDD/F concentrations was observed in two sites in 2012. Comparison of congener and homologue fingerprint characteristics in the two surveys, together with principal component analysis, revealed that the PCDD/F levels in all of the samples collected in 2012 and in three of the samples collected in 2011 are mainly influenced by heavy traffic. MSWI is the primary PCDD/F emission sources of the PCDD/Fs detected in the remaining samples collected in 2011.

Multiterawatt laser system based on optical parametric chirped pulse amplification.

A compact multiterawatt laser system based on optical parametric chirped pulse amplification is demonstrated. Chirped pulses are amplified from 20 pJ to 900 mJ by two lithium triborate optical parametric preamplifiers and a final KDP optical parametric power amplifier with a pump energy of 5 J at 532 nm from Nd:YAG-Nd:glass hybrid amplifiers. After compression, we obtained a final output of 570-mJ-155-fs pulses with a peak power of 3.67 TW, which is the highest output power from an optical parametric chirped pulse amplification laser, to the best of our knowledge.