Vacuolar degradation of plant organelles.

Plants continuously remodel and degrade their organelles due to damage from their metabolic activities and environmental stressors, as well as an integral part of their cell differentiation programs. Whereas certain organelles use local hydrolytic enzymes for limited remodeling, most of the pathways that control the partial or complete dismantling of organelles rely on vacuolar degradation. Specifically, selective autophagic pathways play a crucial role in recognizing and sorting plant organelle cargo for vacuolar clearance, especially under cellular stress conditions induced by factors like heat, drought, and damaging light. In these short reviews, we discuss the mechanisms that control the vacuolar degradation of chloroplasts, mitochondria, endoplasmic reticulum, Golgi, and peroxisomes, with an emphasis on autophagy, recently discovered selective autophagy receptors for plant organelles, and crosstalk with other catabolic pathways.

Quantum-limit Chern topological magnetism in TbMn6Sn6.

The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics1-15. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to their unusual lattice geometry and breaking of time-reversal symmetry14,15. However, quantum materials hosting ideal spin-orbit-coupled kagome lattices with strong out-of-plane magnetization are lacking16-21. Here, using scanning tunnelling microscopy, we identify a new topological kagome magnet, TbMn6Sn6, that is close to satisfying these criteria. We visualize its effectively defect-free, purely manganese-based ferromagnetic kagome lattice with atomic resolution. Remarkably, its electronic state shows distinct Landau quantization on application of a magnetic field, and the quantized Landau fan structure features spin-polarized Dirac dispersion with a large Chern gap. We further demonstrate the bulk-boundary correspondence between the Chern gap and the topological edge state, as well as the Berry curvature field correspondence of Chern gapped Dirac fermions. Our results point to the realization of a quantum-limit Chern phase in TbMn6Sn6, and may enable the observation of topological quantum phenomena in the RMn6Sn6 (where R is a rare earth element) family with a variety of magnetic structures. Our visualization of the magnetic bulk-boundary-Berry correspondence covering real space and momentum space demonstrates a proof-of-principle method for revealing topological magnets.

Cathodal bilateral transcranial direct-current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia-reperfusion injury.

Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.

A High-Voltage-Specialized Direct-Current Triboelectric Nanogenerator for Air Purification.

Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2. A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3, it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.

Age-Period-Cohort Analysis of Long-Term Trends in Ischemic Stroke Mortality in China Caused by Specific Risk Factors from 1990 to 2019.

OBJECTIVE: The objective of this study was to study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed joinpoint regression software and the age-period-cohort method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body mass index in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.

Association between C-reactive protein/albumin ratio and all-cause mortality in patients with stroke: Evidence from NHANES cohort study.

BACKGROUND AND AIMS: The inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. METHODS AND RESULTS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. CONCLUSION: Elevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.

Description of Nesterenkonia aerolata sp. nov., an actinobacterium isolated from air of manufacturing shop in a pharmaceutical factory.

During our studies on the microorganism diversity from air of manufacturing shop in a pharmaceutical factory in Shandong province, China, a Gram-stain-positive, aerobic, cocci-shaped bacterium, designated LY-0111T, was isolated from a settling dish. Strain LY-0111T grew at temperature of 10-42 °C (optimum 35 °C), pH of 5.0-10.0 (optimum pH 7.0) and NaCl concentration of 1-12% (optimum 0.5-3%, w/v). Based on the 16S rRNA gene sequence analysis, the strain shared the highest sequence similarities to Nesterenkonia halophila YIM 70179T (96.2%), and was placed within the radiation of Nesterenkonia species in the phylogenetic trees. The genome of the isolate was sequenced, which comprised 2,931,270 bp with G + C content of 66.5%. A supermatrix tree based on the gene set bac120 indicated that LY-0111T was close related to Nesterenkonia xinjiangensis YIM 70097T (16S rRNA gene sequence similarity 95.3%). Chemotaxonomic analysis indicated that the main respiratory quinones were MK-7, MK-8, and MK-9, the predominant cellular fatty acids were anteiso-C15:0 and iso-C15:0, and the major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. According to the phenotypic, chemotaxonomic and phylogenetic features, strain LY-0111T is considered to represent a novel species, for which the name Nesterenkonia aerolata sp. nov. is proposed. The type strain is LY-0111T (= JCM 36375T = GDMCC 1.3945T). In addition, Nesterenkonia jeotgali was proposed as a later synonym of Nesterenkonia sandarakina, according to the ANI (96.8%) and dDDH (72.9%) analysis between them.

PVA enema ameliorates DSS-induced acute colitis in mice.

BACKGROUND: Ulcerative colitis (UC) represents a clinically challenging condition characterized by persistent damage to the colonic epithelial mucosa as the principal pathological feature. Polyvinyl alcohol (PVA) solution, primarily composed of glue, is a biodegradable polymer material that has found utility in the medical field. This research endeavors to investigate the therapeutic potential of PVA water solution in ameliorating UC in mice. METHODS: UC was induced in 48 C57BL/6 mice by administering 2.5% DSS in their diet for 6 days. Mice were treated with different concentrations of PVA (0.1 mg/ml PVA, 0.3 mg/ml PVA, 1 mg/ml PVA, 3 mg/ml PVA, 10 mg/ml PVA) enemas (n = 6). Disease Activity Index (DAI) and histologic score were evaluated for inflammation degree. Furthermore, mouse colon organoids were cultured, which were used to assess the effects of PVA on expansion in vitro. RESULTS: PVA aqueous solutions (1 mg/ml and 3 mg/ml) were able to alleviate the DAI in mice. By DAY 6, there was a significant 3/5-fold decrease in DAI within the 1 mg/ml PVA group (p = 0.02). Histopathology scores demonstrated improvements, while the levels of inflammatory factors in the intestinal mucosal tissue were reduced. Additionally, it was confirmed that PVA could promote the expansion of colonic organoids in vitro. CONCLUSIONS: In summary, our investigation has yielded findings indicating that PVA holds the potential to ameliorate symptoms associated with colitis in murine subjects afflicted by DSS-induced colitis, primarily through its facilitation of intestinal stem cell expansion. This study might provide a new candidate for the clinical treatment of ulcerative colitis.

Burden of ischemic stroke in mainland China and Taiwan province from 1990 to 2019: with forecast for the next 11 years.

Ischemic stroke is featured with high incidence, mortality, and disability. The aim of this study is to use Global Burden of Disease database to describe and compare the burden of ischemic stroke in mainland China and Taiwan province and to further predict the expected changes in the next 11 years using statistical modeling methods. Information on ischemic stroke incidence and mortality in China (mainland and Taiwan province) during 1990-2019 was obtained from the Global Burden of Disease database to analyze the effects of region, gender, and age on the incidence and mortality of ischemic stroke in China. The autoregressive integrated moving average model was used to predict the age-standardized incidence rate and age-standardized mortality rate of ischemic stroke in males and females in mainland China and Taiwan province in the next 11 years. The period from 1990 to 2019 witnessed an overall upward trend in the number of incidence and deaths in mainland China and Taiwan province. In 2019, there were nearly 2.87 million ischemic incidence cases with stroke in mainland China, with more female patients than male in the age group of over 60 years. Among the nearly 1.03 million deaths, the death toll of men under the age of 85 years was higher than that of women, while in Taiwan province, the number of incidence was 28 771, with more female patients of all ages than male. Among the 6788 deaths, the death toll of men under the age of 80 years was higher than that of women. In 2019, the age group with the highest number of patients in the two regions was 65-69 years, while the highest number of deaths was found in people aged 85 years and above. As our autoregressive integrated moving average model predicted, the age-standardized incidence rate value of ischemic stroke is expected to be 163.23/100 000 persons in mainland China by 2030, which would continue to increase, while the age-standardized mortality rate value of ischemic stroke is expected to be 16.41/100 000 persons in Taiwan province by 2030, which showed a decreasing trend. Disease burden of ischemic stroke is still increasing in mainland China and Taiwan province, and health resources should be deployed to implement effective prevention and control strategies, taking into account region, gender, and age.

DeepSATA: A Deep Learning-Based Sequence Analyzer Incorporating the Transcription Factor Binding Affinity to Dissect the Effects of Non-Coding Genetic Variants.

Utilizing large-scale epigenomics data, deep learning tools can predict the regulatory activity of genomic sequences, annotate non-coding genetic variants, and uncover mechanisms behind complex traits. However, these tools primarily rely on human or mouse data for training, limiting their performance when applied to other species. Furthermore, the limited exploration of many species, particularly in the case of livestock, has led to a scarcity of comprehensive and high-quality epigenetic data, posing challenges in developing reliable deep learning models for decoding their non-coding genomes. The cross-species prediction of the regulatory genome can be achieved by leveraging publicly available data from extensively studied organisms and making use of the conserved DNA binding preferences of transcription factors within the same tissue. In this study, we introduced DeepSATA, a novel deep learning-based sequence analyzer that incorporates the transcription factor binding affinity for the cross-species prediction of chromatin accessibility. By applying DeepSATA to analyze the genomes of pigs, chickens, cattle, humans, and mice, we demonstrated its ability to improve the prediction accuracy of chromatin accessibility and achieve reliable cross-species predictions in animals. Additionally, we showcased its effectiveness in analyzing pig genetic variants associated with economic traits and in increasing the accuracy of genomic predictions. Overall, our study presents a valuable tool to explore the epigenomic landscape of various species and pinpoint regulatory deoxyribonucleic acid (DNA) variants associated with complex traits.

CAFU: a Galaxy framework for exploring unmapped RNA-Seq data.

A widely used approach in transcriptome analysis is the alignment of short reads to a reference genome. However, owing to the deficiencies of specially designed analytical systems, short reads unmapped to the genome sequence are usually ignored, resulting in the loss of significant biological information and insights. To fill this gap, we present Comprehensive Assembly and Functional annotation of Unmapped RNA-Seq data (CAFU), a Galaxy-based framework that can facilitate the large-scale analysis of unmapped RNA sequencing (RNA-Seq) reads from single- and mixed-species samples. By taking advantage of machine learning techniques, CAFU addresses the issue of accurately identifying the species origin of transcripts assembled using unmapped reads from mixed-species samples. CAFU also represents an innovation in that it provides a comprehensive collection of functions required for transcript confidence evaluation, coding potential calculation, sequence and expression characterization and function annotation. These functions and their dependencies have been integrated into a Galaxy framework that provides access to CAFU via a user-friendly interface, dramatically simplifying complex exploration tasks involving unmapped RNA-Seq reads. CAFU has been validated with RNA-Seq data sets from wheat and Zea mays (maize) samples. CAFU is freely available via GitHub: https://github.com/cma2015/CAFU.

Rare Earth Engineering in RMn_{6}Sn_{6} (R=Gd-Tm, Lu) Topological Kagome Magnets.

Exploration of the topological quantum materials with electron correlation is at the frontier of physics, as the strong interaction may give rise to new topological phases and transitions. Here we report that a family of kagome magnets RMn_{6}Sn_{6} manifest the quantum transport properties analogical to those in the quantum-limit Chern magnet TbMn_{6}Sn_{6}. The topological transport in the family, including quantum oscillations with nontrivial Berry phase and large anomalous Hall effect arising from Berry curvature field, points to the existence of Chern gapped Dirac fermions. Our observation demonstrates a close relationship between rare-earth magnetism and topological electron structure, indicating the rare-earth elements can effectively engineer the Chern quantum phase in kagome magnets.

Evaluation of relationship between KEAP1 gene and genetic susceptibility of deep vein thrombosis after orthopedic surgery in Han Chinese population.

Deep vein thrombosis (DVT) is the blood clot formed in a vein deep in body, mostly occurred in the lower leg or thigh. Early studies indicate that DVT is a complex disorder affected by both environmental and genetic factors. Previous biological evidence have indicated that KEAP1 gene may play an important role in the pathogenesis of DVT. In the present study, we aimed to investigate the genetic association between genetic polymorphisms of KEAP1 gene and the risk of DVT in Han Chinese population. A total of 2558 study subjects comprised of 660 DVT following orthopedics surgery cases and 1898 controls were recruited as discovery sample. In addition, we have also recruited another independent sample sets including 704 DVT following orthopedics surgery cases and 1056 controls for replication. Ten tag SNPs located on KEAP1 gene were selected for genotyping. Single marker based association analyses were conducted at both allelic and genotypic levels. SNPs that passed the Bonferroni correction in the discovery stage were genotyped in the replication dataset. Bioinformatics tools including PolymiRTS, GTEx, STRING and Gene Ontology database were utilized to investigate the functional consequences of the significant SNPs. SNP rs3177696 was identified to be significantly associated with risk of DVT in the study subjects. The G allele of SNP rs3177696 was significantly related to decreased risk of DVT. Functional consequences of SNP rs3177696 were obtained based on bioinformatics analyses. The G allele of SNP rs3177696 was related to the increased gene expression level of KEAP1. In summary, we have identified KEAP1 gene to be a potential susceptible locus for DVT in Han Chinese population. Further bioinformatics analyses have provided supportive evidence for the functional consequence of the significant SNP.

Path-Independent Quantum Gates with Noisy Ancilla.

Ancilla systems are often indispensable to universal control of a nearly isolated quantum system. However, ancilla systems are typically more vulnerable to environmental noise, which limits the performance of such ancilla-assisted quantum control. To address this challenge of ancilla-induced decoherence, we propose a general framework that integrates quantum control and quantum error correction, so that we can achieve robust quantum gates resilient to ancilla noise. We introduce the path independence criterion for fault-tolerant quantum gates against ancilla errors. As an example, a path-independent gate is provided for superconducting circuits with a hardware-efficient design.

Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells.

Polyphyllin I (PPI), an extract from Paris polyphylla, has been demonstrated to possess antitumor activity against multiple cancers. However, whether PPI can inhibit bladder cancer (BCa) and the underlying mechanisms have never been researched. In this study, we initially found that PPI could induce BCa cell apoptosis and cell cycle arrest, as well as inhibit cell proliferation in vitro. Additionally, PPI could effectively suppress the in vivo growth of BCa in the xenograft mice model. Furthermore, we found that forkhead box O3 (FOXO3) and its targets including BIM or NOXA were significantly upregulated in BCa cells following PPI treatment. Interestingly, we observed that FOXO3 knockdown partly reversed the effects of PPI on BCa cells. Taken together, our findings suggested that PPI exerted a cytotoxic effect in vitro and an antitumor activity in vivo against BCa partly by activating FOXO3 signaling pathway. Therefore, PPI may serve as a promising chemotherapy agent for BCa treatment.

Combinatorial pathway enzyme engineering and host engineering overcomes pyruvate overflow and enhances overproduction of N-acetylglucosamine in Bacillus subtilis.

BACKGROUND: Glucosamine-6-phosphate N-acetyltransferase (GNA1) is the key enzyme that causes overproduction of N-acetylglucosamine in Bacillus subtilis. Previously, we increased GlcNAc production by promoting the expression of GNA1 from Caenorhabditis elegans (CeGNA1) in an engineered B. subtilis strain BSGN12. In this strain overflow metabolism to by-products acetoin and acetate had been blocked by mutations, however pyruvate accumulated as an overflow metabolite. Although overexpression of CeGNA1 drove carbon flux from pyruvate to the GlcNAc synthesis pathway and decreased pyruvate accumulation, the residual pyruvate reduced the intracellular pH, resulting in inhibited CeGNA1 activity and limited GlcNAc production. RESULTS: In this study, we attempted to further overcome pyruvate overflow by enzyme engineering and host engineering for enhanced GlcNAc production. To this end, the key enzyme CeGNA1 was evolved through error-prone PCR under pyruvate stress to enhance its catalytic activity. Then, the urease from Bacillus paralicheniformis was expressed intracellularly to neutralize the intracellular pH, making it more robust in growth and more efficient in GlcNAc production. It was found that the activity of mutant CeGNA1 increased by 11.5% at pH 6.5-7.5, with the catalytic efficiency increasing by 27.5% to 1.25 s-1 µM-1. Modulated expression of urease increased the intracellular pH from 6.0 to 6.8. The final engineered strain BSGN13 overcame pyruvate overflow, produced 25.6 g/L GlcNAc with a yield of 0.43 g GlcNAc/g glucose in a shake flask fermentation and produced 82.5 g/L GlcNAc with a yield of 0.39 g GlcNAc/g glucose by fed-batch fermentation, which was 1.7- and 1.2-times, respectively, of the yield achieved previously. CONCLUSIONS: This study highlights a strategy that combines pathway enzyme engineering and host engineering to resolve overflow metabolism in B. subtilis for the overproduction of GlcNAc. By means of modulated expression of urease reduced pyruvate burden, conferred bacterial survival fitness, and enhanced GlcNAc production, all of which improved our understanding of co-regulation of cell growth and metabolism to construct more efficient B. subtilis cell factories.

Induction of chemokine (C-C motif) ligand 5 by Epstein-Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection and is known to be highly vascularized. Previous studies have suggested that EBV oncoproteins contribute to NPC angiogenesis. However, the regulatory network of EBV in angiogenesis still remains elusive. Herein, we reveal a novel mechanism of EBV-induced angiogenesis in NPC. First, we showed that EBV-infected NPC cell lines generated larger tumors with more microvessels in mouse xenograft models. Subsequent proteomic analysis revealed that EBV infection increased the expression of a series of angiogenic factors, including chemokine (C-C motif) ligand 5 (CCL5). We then proved that CCL5 was a target of EBV in inducing tumor angiogenesis and growth. Further investigation through transcriptome analysis indicated that the pro-angiogenic function of CCL5 might be mediated by the PI3K/AKT pathway. Furthermore, we confirmed that activation of the PI3K/AKT and hypoxia-inducible factor-1α pathways was essential for CCL5-promoted angiogenesis. Finally, the immunohistochemical analysis of human NPC specimens also showed that CCL5 was correlated with angiogenesis. Taken together, our study identifies CCL5 as a key EBV-regulated molecular driver that promotes NPC angiogenesis, suggesting it as a potential therapeutic target.

A deep convolutional neural network approach for predicting phenotypes from genotypes.

MAIN CONCLUSION: Deep learning is a promising technology to accurately select individuals with high phenotypic values based on genotypic data. Genomic selection (GS) is a promising breeding strategy by which the phenotypes of plant individuals are usually predicted based on genome-wide markers of genotypes. In this study, we present a deep learning method, named DeepGS, to predict phenotypes from genotypes. Using a deep convolutional neural network, DeepGS uses hidden variables that jointly represent features in genotypes when making predictions; it also employs convolution, sampling and dropout strategies to reduce the complexity of high-dimensional genotypic data. We used a large GS dataset to train DeepGS and compared its performance with other methods. The experimental results indicate that DeepGS can be used as a complement to the commonly used RR-BLUP in the prediction of phenotypes from genotypes. The complementarity between DeepGS and RR-BLUP can be utilized using an ensemble learning approach for more accurately selecting individuals with high phenotypic values, even for the absence of outlier individuals and subsets of genotypic markers. The source codes of DeepGS and the ensemble learning approach have been packaged into Docker images for facilitating their applications in different GS programs.

Kuwanon G attenuates atherosclerosis by upregulation of LXRα-ABCA1/ABCG1 and inhibition of NFκB activity in macrophages.

BACKGROUND: Atherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored. AIMS: To explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo. METHODS: RAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG. Foam cell formation was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines mRNA levels were tested by Real-time PCR method. Further molecular mechanism was investigated using Western blot. In vivo, ApoE-/- mice were fed with high-fat diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry and Sirius Red staining. Serum lipid profile and inflammatory cytokines were evaluated by enzymatic method and ELISA. RESULTS: KWG significantly decreased intracellular lipid accumulation and inflammatory cytokines mRNA levels in macrophages through enhancing LXRα-ABCA1/ABCG1 pathway and inhibiting NFκB activation. Administrated with KWG remarkably reduced the atherosclerotic lesion areas and macrophage content in the plaque of high-fat diet fed ApoE-/- mice. KWG also reduced hyperlipidemia and serum inflammatory cytokines in vivo. CONCLUSION: Taken together, these data highlight that KWG can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response.