Dissecting the Role of the Hydroxyl Moiety at C14 in (+)-Opioid-Based TLR4 Antagonists via Wet-Lab Experiments and Molecular Dynamics Simulations.

Toll-like receptor 4 (TLR4) is pivotal as an innate immune receptor, playing a critical role in mediating neuropathic pain and drug addiction through its regulation of the neuroinflammatory response. The nonclassical (+)-opioid isomers represent a unique subset of TLR4 antagonists known for their effective blood-brain barrier permeability. Despite growing interest in the structure-activity relationship of these (+)-opioid-based TLR4 antagonists, the specific impact of heteroatoms on their TLR4 antagonistic activities has not been fully explored. This study investigated the influence of the hydroxyl group at C14 in six (+)-opioid TLR4 antagonists (1-6) using wet-lab experiments and in silico simulations. The corresponding C14-deoxy derivatives (7-12) were synthesized, and upon comparison with their corresponding counterparts (1-6), it was discovered that their TLR4 antagonistic activities were significantly diminished. Molecular dynamics simulations showed that the (+)-opioid TLR4 antagonists (1-6) possessed more negative binding free energies to the TLR4 coreceptor MD2, which was responsible for ligand recognition. This was primarily attributed to the formation of a hydrogen bond between the hydroxyl group at the C-14 position of the antagonists (1-6) and the R90 residue of MD2 during the binding process. Such an interaction facilitated the entry and subsequent binding of these molecules within the MD2 cavity. In contrast, the C14-deoxy derivatives (7-12), lacking the hydroxyl group at the C-14 position, missed this crucial hydrogen bond interaction with the R90 residue of MD2, leading to their egression from the MD2 cavity during simulations. This study underscores the significant role of the C14 hydroxyl moiety in enhancing the effectiveness of (+)-opioid TLR4 antagonists, which provides insightful guidance for designing future (+)-isomer opioid-derived TLR4 antagonists.

Hybrid mode for absorption enhancement in the Ga2O3 nanocavity photodetector with grating electrodes.

Gallium oxide (G a 2 O 3) photodetectors have drawn increased interest for their widespread applications ranging from military to civil. Due to the inherent oxygen vacancy defects, they seriously suffer from trade-offs that make them incompetent for high-responsivity, quick-response detection. Herein, a G a 2 O 3 nanocavity photodetector assisted with grating electrodes is designed to break the constraint. The proposed structure supports both the plasmonic mode and the Fabry-Perot (F-P) mode. Numerical calculations show that the absorption of 99.8% is realized for ultra-thin G a 2 O 3 (30 nm), corresponding to a responsivity of 12.35 A/W. Benefiting from optical mechanisms, the external quantum efficiency (EQE) reaches 6040%, which is 466 times higher than that of bare G a 2 O 3 film. Furthermore, the proposed photodetector achieves a polarization-dependent dichroism ratio of 9.1, enabling polarization photodetection. The grating electrodes also effectively reduce the transit time of the photo-generated carriers. Our work provides a sophisticated platform for developing high-performance G a 2 O 3 photodetectors with the advantages of simplified fabrication processes and multidimensional detection.

ZFHX3 acts as a tumor suppressor in prostate cancer by targeting FTO-mediated m6A demethylation.

Zinc-finger homeobox 3 (ZFHX3, also known as ATBF1) suppresses prostatic tumorigenesis. ZFHX3 is frequently found to have numerous deletions in human prostate cancer (PCa). However, the underlying molecular function of ZFHX3 during prostatic tumorigenesis is not well understood. N6-methyladenosine (m6A) modification in RNA plays a critical role in the development of cancers; however, the relationship between ZFHX3 and m6A modification is largely unknown in PCa. In this study, we found that ZFHX3 knockdown decreased total m6A levels through enhancing the transcriptional activity of FTO in PCa cells. Importantly, FTO inhibition suppressed cell proliferation and rescued the promoting function of ZFHX3 knockdown on cell proliferation. In vivo, we verified that FTO was upregulated and ZFHX3 was decreased in PCa patients and that a high level of ZFHX3 is indispensable for low FTO expression and is correlated with better patient survival. Through transcriptome sequencing and MeRIP sequencing, we revealed that E2F2 and CDKN2C were the direct targets of FTO-mediated m6A modification and ZFXH3 was required for the regulation of FTO on E2F2 and CDKN2C expression. Unexpectedly, we uncovered that ZFHX3 expression was in return regulated by FTO in an m6A-dependent way. These findings establish a novel crosstalk mechanism between ZFHX3 and FTO in prostatic tumorigenesis.

Spatio-temporal differentiation characteristics and the influencing factors of PM2.5 emissions from coal consumption in Central Plains Urban Agglomeration.

Central Plains urban agglomeration (CPUA) had developed rapidly, but its air pollution was also serious. Despite advances in study on China's PM2.5 emissions from coal consumption (CC), the differentiation characteristics and the affecting variables of PM2.5 in CPUA required further investigation. This paper computed the PM2.5 emissions of each city from 2000 to 2020 using CC data from CPUA, evaluated its spatio-temporal fluctuation characteristics using the spatial autocorrelation and analyzed its influencing factors by combining various indicators through the spatial Durbin model (SDM). The results verified that: (1) There was a trend of rapid increase of PM2.5 emissions from CC; (2) The Moran's I of the PM2.5 emissions from CC showed a significant agglomeration effect; (3) PM2.5 emissions from CC had a strong spillover effect. The recommendations were in this following: (1) The urban pollution regulation and the pace of industrial green transformation should be Strengthened; (2) Close linkages between cities should be established and attention should be paid to pollution management; (3) The spillover of PM2.5 emissions from CC should be lessened and development of environmental governance technology should be enhanced.

Association of the American Heart Association's new "Life's Essential 8" with all-cause mortality in patients with chronic kidney disease: a cohort study from the NHANES 2009-2016.

BACKGROUND: People with chronic kidney disease (CKD) are more likely to die prematurely, and this increased risk of death is primarily attributable to deaths from cardiovascular disease (CVD). We aim to investigate the relationship between Life's Essential 8 (LE8), a newly proposed cardiovascular health (CVH) measurement system, and all-cause mortality of CKD patients among US adults. METHODS: A total of 3,169 CKD patients aged 20 and older from the National Health and Nutritional Examination Survey in 2009-2016 were involved in this study. Participants were divided into low (0-49), moderate (50-79) and high (80-100) CVH groups according to LE8 score (range 0-100). The mortality was ascertained from the National Death Index. Cox proportional hazards regression and restricted cubic spline were used to investigate the relationship. RESULTS: Among the 3,169 CKD patients, the median age was 66.0 (25.0) years and 1,671 (52.7%) were female, and the median follow-up time was 6.00 years. The median LE8 score of the study cohort was 57.5 (19.4). CKD patients with low CVH, health behavior (HB) and health factors (HF) scores presented with higher all-cause mortality (both log-rank P-values < 0.001). After adjusted for multiple confounders, patients in higher CVH group had a lower risk of all-cause mortality, with a HR (95%CI) of 0.32 (0.19-0.55). Similar results were observed in high HB group [HR 0.36 (0.25-0.50)]. The restricted cubic spline showed a significant inverse relationship between LE8, HB and HF scores with CKD all-cause mortality, while the protective effect seemed weaker for HF score. Above results remained robust in the sensitivity analysis. Stronger inverse associations were revealed in middle-aged patients and patients with higher education levels. CONCLUSIONS: LE8 and its subscales scores were inversely associated with all-cause mortality in patients with CKD. Promoting CVH in CKD patients is a potential way to improve their long-term survival rate.

Fe/Mn (oxyhydr)oxides reductive dissolution promoted by cyanobacterial algal bloom-derived dissolved organic matter caused sediment W release during an algal bloom in Taihu Lake.

Tungsten (W) can be toxic to aquatic organisms. However, the spatiotemporal characteristics and controlling factors of W mobility during harmful algal blooms (HABs) have rarely been investigated. In this study, simultaneous changes in soluble W, iron (Fe), manganese (Mn), and ultraviolet absorbance (UV254) in the sediment-water interface (SWI) were measured monthly using high-resolution peeper (HR-Peeper) devices. Laboratory experiments were conducted to verify the effects of environmental factors on W release. From May 2021 to October 2021, the concentration and flux of soluble W were higher than in other months. In addition, from May to October, DMAX (the depth at which the maximum concentration occurs on each profile) was 30-50 mm below the SWI, rather than the maximum depth. Principal component analysis (PCA) also divided the year into two periods, designated W-stable (December 2020, January, March, April and November 2021 with low soluble W concentration) and W-active periods (from May 2021 to October 2021 with high soluble W concentration). Laboratory experiments showed that both warming and anoxic conditions caused simultaneous release of soluble W, Fe(II), Mn, and dissolved organic matter (DOM), with strong correlations among soluble W, Fe(II), Mn. Partial least squares path modeling (PLS-PM) and random forest model showed that DOM directly affected W release or indirectly affected W release through promoting ferromanganese (oxyhydr)oxides reduction under warming and anaerobic conditions. The results of the field investigation showed that, in the W-stable period with low T, high DO, and an oxic SWI, the concentrations of soluble W, Fe, Mn, and DOM were low. The redundancy analysis (RDA) showed that these months were mainly affected by water DO. The significant and strong positive correlation among soluble W, Fe and Mn indicated that soluble W was probably scavenged by Fe/Mn (oxyhydr)oxides in the oxic water during the W-stable period. The W-active period corresponded to the cyanobacterial HABs (cyanoHABs) outbreak, with higher T, lower DO, and a more anoxic SWI. During this period, the concentrations of soluble W, Fe, Mn, and DOM were high and their correlations were stronger. RDA showed that these months were mainly affected by T, UV254, soluble Fe and Mn. These results indicated that reductive dissolution of Fe/Mn (oxyhydr)oxides driven by DOM generated in W-active period, especially cyanoHAB-derived DOM, mainly caused soluble W release. These results reveal the coupling relationship between cyanoHABs and W release and emphasize the need for prevention and control of heavy metal release in eutrophic lakes.

Network pharmacology combined with metabolomics to reveal the anti-fibrotic mechanism of Polygoni Orientalis Fructus in CCl4-induced hepatic fibrosis rats.

Polygoni Orientalis Fructus (POF), a dried ripe fruit of Polygonum orientale L., is commonly used in China for liver disease treatment. However, its therapeutic mechanism remains unclear. The aim of this study was to elucidate the effects of POF on the regulation of endogenous metabolites and identify its key therapeutic targets in hepatic fibrosis (HF) rats by integrating network pharmacology and metabolomics approaches. First, serum liver indices and histopathological analyses were used to evaluate the therapeutic effects of POF on carbon tetrachloride (CCl4)-induced HF. Subsequently, differential metabolites and potential therapeutic targets of POF were screened using plasma metabolomics and network pharmacology, respectively. The key targets of POF were identified by overlapping differential metabolite-associated targets with the potential targets and validated by molecular docking and ELISA experiments. The results showed that POF effectively alleviated HF in rats. A total of 51 metabolites related to HF were screened, and 24 were associated with POF. 232 potential therapeutic targets were identified by network pharmacology analysis. Finally, six key targets were identified through a combined analysis. Furthermore, molecular docking and ELISA validation revealed that AGXT, PAH, and NOS3 are targets of POF action, while CBS, ALDH2, and ARG1 were identified as potential targets. SIGNIFICANCE: POF is now commonly used in the treatment of liver disease, but its mechanism of action remains unclear. Current studies on metabolomics of liver disease primarily focuse on the interpretation of differential metabolites and related metabolic pathways. This research delves into the intricate details of metabolomics findings via network pharmacology to uncover the targets and pathways of drug action.

O-glycosylation in viruses: A sweet tango.

O-glycosylation is an ancient yet underappreciated protein posttranslational modification, on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseases or even cancer. But due to the innate complexity of O-glycosylation, research techniques have been limited to study its exact role in viral attachment and entry, assembly and exit, spreading in the host cells, and the innate and adaptive immunity of the host. Recently, the advent of many newly developed methodologies (e.g., mass spectrometry, chemical biology tools, and molecular dynamics simulations) has renewed and rekindled the interest in viral-related O-glycosylation in both viral proteins and host cells, which is further fueled by the COVID-19 pandemic. In this review, we summarize recent advances in viral-related O-glycosylation, with a particular emphasis on the mucin-type O-linked α-N-acetylgalactosamine (O-GalNAc) on viral proteins and the intracellular O-linked ß-N-acetylglucosamine (O-GlcNAc) modifications on host proteins. We hope to provide valuable insights into the development of antiviral reagents or vaccines for better prevention or treatment of infectious diseases.

How can the recycling of power batteries for EVs be promoted in China? A multiparty cooperative game analysis.

While electric vehicles (EVs) are developing at a high speed in China, the power battery market is facing a decommissioning peak. The problem is that the recycling situation of domestic power batteries is not ideal, partly due to neglect by consumers. By considering the recycling system, mode, and policy of China's EV power batteries, we construct a tripartite evolutionary game model of the government, consumers and EV manufacturers; analyse the stable strategy adjustment mechanisms of tripartite participation in this recycling cooperation game; and simulate the tripartite evolutionary game. The results show that when the initial willingness of the government, consumers and EV manufacturers to recycle power batteries is not strong, the government takes the lead, driving EV manufacturers and consumers to participate in power battery recycling. When the government, consumers and EV manufacturers have medium or high levels of initial willingness, the government evolves and chooses a nonregulation strategy. In addition, by simulating the impact of changes in consumer-related influencing factors on this tripartite evolutionary game, we find that subsidies for recycling power batteries are a key factor affecting consumers' strategy choices and that boosting recycling compensation for consumers can improve their enthusiasm to participate in such recycling. Therefore, to improve the recycling of power batteries for EVs, in terms of both efficiency and percentage of deployment, the Chinese government should strengthen public education on power battery recycling, further integrate informal recycling channels, and balance the distribution of profits among consumers for recycling compensation.

Deep decarbonization potential and implementation path under provincial differences in China's fleet electrification.

Fleet electrification is considered to be an important measure for reducing carbon emissions in the road transport industry. Considering the heterogeneity of the NEV market penetration and the vehicle types in different provinces, how to design targeted and time-sequenced road transport decarbonisation reduction strategies has become a key issue that needs to be discussed urgently. In this study, the NEVs ownership in China's 31 provinces is used as an intermediate variable. Considering the process of energy transition and changes in vehicle structure, a two-layer scenario framework that combines Shared Socioeconomic Pathways scenarios and model structure was developed to predict carbon emissions. This study firstly analyzes the electrification process and carbon emission reduction potential of provincial road transport industry by region, vehicle type and stage. The potential for reducing carbon emissions was determined under benchmark, transition, and electrification scenarios. The results indicate that the Pearson Correlation Coefficient-Discrete Wavelet Transform-Bidirectional Long Short-term Memory prediction model has an mean absolute percentage error of 8.583 and an R-squared of 0.975. China's road transportation industry total carbon emissions will reach its peak as early as 2027, due to the rapid implementation of renewable energy and fleet electrification. Shanghai, Jiangsu, Shandong, Henan, and Guangdong have set carbon peak targets that can be achieved faster with the transition plan for new energy vehicles to replace fossil fuel vehicles. This paper proposes a timing-responsive deep decarbonization path and policy recommendations for China's road transport industry in sub provincial and time-series settings.

Effect of sacubitril-valsartan on left ventricular remodeling and NT-proBNP in patients with heart failure complicated with hypertension and reduced ejection fraction.

OBJECTIVE: To analyze the effect of sacubitril-valsartan on left ventricular remodeling and NT-proBNP in heart failure patients with hypertension and reduced ejection fraction. METHOD: A retrospective analysis was conducted on 112 heart failure patients with reduced ejection fraction (HFrEF) and concomitant hypertension who were treated in Baoji Central Hospital from May 2019 to October 2021. Standard heart failure treatment was applied in both groups. Besides, the observation group (n=60) was additionally treated with sacubitril/valsartan (initial dose of 50 mg twice daily, adjusted every 2-4 weeks by doubling the dose to a maximum of 200 mg twice daily based on the patients' actual conditions and tolerance), and the control group (n=52) received valsartan (80 mg once daily). The treatment duration for both groups was 6 months. Therapeutic efficacy, blood pressure, echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left ventricular remodeling before and after treatment were recorded and compared between the two groups, as well as the adverse drug reactions during the treatment and life quality after treatment. Finally, multifactor regression analysis was performed to screen the independent risk factors affecting patient prognosis. RESULTS: Compared with the CG, the overall response rate in the OG was evidently higher (P < 0.001); the improvements in blood pressure, NT-proBNP, interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular mass index (LVMI) were more significant in the OG (all P < 0.001). Both groups showed marked improvements in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and (left ventricular end-systolic diameter) LVESD compared to baseline, with more significant improvement in the OG compared with the CG (all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups. However, post-treatment quality of life was much higher in the OG compared to the CG (P < 0.001). Comorbid diabetes and treatment regimen were identified as independent risk factors affecting patient prognosis. CONCLUSION: Sacubitril-valsartan can effectively improve blood pressure, cardiac function and ventricular remodeling in patients with HFrEF and hypertension without increasing adverse reactions. It is highly safe and worthy of clinical promotion.

Development and Application of a Selective Analytical Method for Indole Metabolites in Urine: Dietary Exposure Biomarkers for Broccoli Consumption.

The identification of dietary exposure biomarkers is crucial for advancing our understanding of the health benefits of specific foods. Broccoli, a vegetable with well-known anticancer properties, contains active ingredients, such as isothiocyanates with indole side chains. Hence, indole metabolites related to broccoli consumption have the potential to serve as biomarkers of dietary exposure. In this work, we developed a new analytical method for indole metabolites in urine using a poly(deep eutectic solvents)-molecularly imprinted polymer/vinyl-functionalized graphene oxide (PDESs-MIP/VGO) in miniaturized centrifugal pipet-tip solid-phase extraction (CPT-SPE) coupled with liquid chromatography. This method integrates the strengths of PDESs-MIP/VGO, including rich adsorption interactions, high adsorption capacity, and excellent selectivity, with the simplicity and cost-effectiveness of CPT-SPE. The proposed method demonstrated low limits of quantification (1.2-2.5 ng mL-1), high accuracy (91.7-104.8%), and good precision (relative standard deviation ≤4.4%). By applying this method to analyze indole metabolites in urine, our results suggested that indole-3-carbinol and indole-3-acetonitrile have the potential to emerge as reliable dietary exposure biomarkers for broccoli intake. Furthermore, highly selective analytical methods based on molecular imprinting technology are advantageous for precise screening and analysis of dietary exposure biomarkers associated with food consumption.

Enhancing post-harvest quality of tomato fruits with chitosan oligosaccharide-zinc oxide nanocomposites: A study on biocompatibility, quality improvement, and carotenoid enhancement.

In this study, a new composite with combination of chitosan oligosaccharide (COS) and zinc oxide nanoparticles (ZnO NPs), termed Chitosan Oligosaccharide-Zinc Oxide Nanocomposites (COS-ZnO NC), was designed to enhance the quality of tomato fruits during postharvest storage. SEM analysis showed a uniform distribution of COS-ZnO NC films on tomato surfaces, indicating high biocompatibility, while the FTIR spectrum confirmed the interaction of COS and ZnO NPs via hydrogen bonds. The COS-ZnO NC exerts positive effects on post-harvest quality of tomato fruits, including significantly reduced water loss, fewer skin wrinkles, increased sugar-acid ratio, and enhanced vitamin C and carotenoids accumulation. Furthermore, COS-ZnO NC induces transcription of carotenoid biosynthesis genes and promotes carotenoids storage in the chromoplast. These results suggest that the COS-ZnO NC film can significantly improve the quality traits of tomato fruits, and therefore is potential in post-harvest storage of tomato fruits.

Chaperone-mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3ß/ß-catenin pathway.

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.

Positive role of plateau pika (Ochotona coronae) on environmental quality at low and moderate density on the Tibetan plateau: Evidence from a meta-analysis.

The roles of plateau pika (Ochotona coronae) in the Tibetan Plateau are often controversial, because it is often regarded as a destructive pest or an ecosystem engineer. Here a meta-analysis using 72 paired observations was conducted to examine whether the impacts of plateau pika on environmental quality (i.e., plant and soil properties) depend on population density in the Tibetan Plateau. Pika population density was used as a proxy for disturbance intensity. The pika disturbance intensity was divided into five groups based on the number of burrows, including low disturbance intensity (LD) (9-30 burrows per ha), medium disturbance intensity (MD) (31-100 burrows per ha), high disturbance intensity (HD) (101-170 burrows per ha), extreme disturbance intensity (ED) (171-240 burrows per ha) and uncontrolled (or excessive) disturbance intensity (UD) (>241 burrows per ha). Given that sample sizes in some of the groups are small (especially for the HD), we further pooled the disturbance groups including the LD-MD and HD-UD. Overall, relative to control (i.e., no disturbing), there was a great increase (80.3%) in aboveground biomass under the LD-MD, whereas a decrease of 41.1% occurred under the HD-UD. At the same time, plant coverage, species richness, height, and belowground biomass greatly decreased only in the HD-UD. Furthermore, the effect size of plant coverage, species richness, and aboveground biomass also declined with pika burrow density significantly. With regard to soil properties, there was a significant increase in soil organic carbon, ammonium nitrogen, and soil organic carbon stock under the LD-MD, whereas a decrease under the HD-UD. In addition, soil total nitrogen, total potassium, and nitrate nitrogen increased at the LD-MD and HD-UD. Nevertheless, the effect size of these soil properties (with >20 observations) was not related to pika burrow density. In summary, there is an implication that the low and moderate disturbance of pikas is beneficial to maintain and promote ecosystem functioning in the Tibetan grasslands. In the future pikas' eradication policy should be reconsidered in alpine grassland management.

A new multi-attribute group decision-making method based on Einstein Bonferroni operators under interval-valued Fermatean hesitant fuzzy environment.

Faced with the increasing complexity and uncertainty of decision-making information, interval-valued Fermatean hesitant fuzzy sets (IVFHFSs) were presented as a novel mathematical model that handled uncertain data more effectively. However, existing multi-attribute group decision-making (MAGDM) methods based on IVFHFSs do not thoroughly investigate the operational laws. Also, these existing MAGDM methods do not take into account the connections between attributes and are less flexible. To address these issues, this paper proposes a new MAGDM method based on Einstein Bonferroni operators under IVFHFSs. First, we thoroughly examine the operational laws of Einstein t-norms under the IVFHFSs to further extend the study of the operational laws. Then, we introduce the interval-valued Fermatean hesitant fuzzy Einstein Bonferroni mean operator and the interval-valued Fermatean hesitant fuzzy Einstein weighted Bonferroni mean operator under Einstein t-norms. Our suggested aggregation operators consider the relationship between attributes and are far more flexible in comparison to the current approaches. Later, a novel MAGDM method based on Einstein Bonferroni operators under the IVFHFSs is given. Finally, the practicality and validity of the proposed method are demonstrated by a cardiovascular disease diagnosis application.

Co-expression network analysis and identification of core genes in the interaction between wheat and Puccinia striiformis f. sp. tritici.

The epidemic of stripe rust, caused by the pathogen Puccinia striiformis f. sp. tritici (Pst), would reduce wheat (Triticum aestivum) yields seriously. Traditional experimental methods are difficult to discover the interaction between wheat and Pst. Multi-omics data analysis provides a new idea for efficiently mining the interactions between host and pathogen. We used 140 wheat-Pst RNA-Seq data to screen for differentially expressed genes (DEGs) between low susceptibility and high susceptibility samples, and carried out Gene Ontology (GO) enrichment analysis. Based on this, we constructed a gene co-expression network, identified the core genes and interacted gene pairs from the conservative modules. Finally, we checked the distribution of Nucleotide-binding and leucine-rich repeat (NLR) genes in the co-expression network and drew the wheat NLR gene co-expression network. In order to provide accessible information for related researchers, we built a web-based visualization platform to display the data. Based on the analysis, we found that resistance-related genes such as TaPR1, TaWRKY18 and HSP70 were highly expressed in the network. They were likely to be involved in the biological processes of Pst infecting wheat. This study can assist scholars in conducting studies on the pathogenesis and help to advance the investigation of wheat-Pst interaction patterns.

High-Temperature-Induced Differential Expression of miRNA Mediates Liver Inflammatory Response in Tsinling Lenok Trout (Brachymystax lenok tsinlingensis).

High-temperature stress poses a significant environmental challenge for aquatic organisms, including tsinling lenok trout (Brachymystax lenok tsinlingensis). This study aimed to investigate the role of microRNAs (miRNAs) in inducing liver inflammation in tsinling lenok trout under high-temperature stress. Tsinling lenok trout were exposed to high-temperature conditions (24 °C) for 8 h, and liver samples were collected for analysis. Through small RNA sequencing, we identified differentially expressed miRNAs in the liver of high-temperature-stressed tsinling lenok trout compared to the control group (maintained at 16 °C). Several miRNAs, including novel-m0105-5p and miR-8159-x, showed significant changes in expression levels. Additionally, we conducted bioinformatics analysis to explore the potential target genes of these differentially expressed miRNAs. Our findings revealed that these miRNA target genes are involved in inflammatory response pathways, such as NFKB1 and MAP3K5. The downregulation of novel-m0105-5p and miR-8159-x in the liver of high-temperature-stressed tsinling lenok trout suggests their role in regulating liver inflammatory responses. To validate this, we performed a dual-luciferase reporter assay to confirm the regulatory relationship between miRNAs and target genes. Our results demonstrated that novel-m0105-5p and miR-8159-x enhance the inflammatory response of hepatocytes by promoting the expression of NFKB1 and MAP3K5, respectively. In conclusion, our study provides evidence that high-temperature stress induces liver inflammation in tsinling lenok trout through dysregulation of miRNAs. Understanding the molecular mechanisms underlying the inflammatory response in tsinling lenok trout under high-temperature stress is crucial for developing strategies to mitigate the negative impacts of environmental stressors on fish health and aquaculture production.

DeepSeeded: Volumetric Segmentation of Dense Cell Populations with a Cascade of Deep Neural Networks in Bacterial Biofilm Applications.

Accurate and automatic segmentation of individual cell instances in microscopy images is a vital step for quantifying the cellular attributes, which can subsequently lead to new discoveries in biomedical research. In recent years, data-driven deep learning techniques have shown promising results in this task. Despite the success of these techniques, many fail to accurately segment cells in microscopy images with high cell density and low signal-to-noise ratio. In this paper, we propose a novel 3D cell segmentation approach DeepSeeded, a cascaded deep learning architecture that estimates seeds for a classical seeded watershed segmentation. The cascaded architecture enhances the cell interior and border information using Euclidean distance transforms and detects the cell seeds by performing voxel-wise classification. The data-driven seed estimation process proposed here allows segmenting touching cell instances from a dense, intensity-inhomogeneous microscopy image volume. We demonstrate the performance of the proposed method in segmenting 3D microscopy images of a particularly dense cell population called bacterial biofilms. Experimental results on synthetic and two real biofilm datasets suggest that the proposed method leads to superior segmentation results when compared to state-of-the-art deep learning methods and a classical method.

Polymer Engineering Enables High Linear Capacity Fiber Electrodes by Microenvironment Regulation.

Unlike bulky and rigid traditional power systems, 1D fiber batteries possess appealing features such as flexibility and adaptability, which are promising for use in wearable electronic devices. However, the performance and energy density fiber batteries are limited by the contradiction between ionic transfer and robust structure of fiber electrodes. Herein, these problems are addressed via polymer engineering to regulate the microenvironment in electrodes, realizing high-linear-capacity thick fiber electrodes with excellent cycling performance. The porosity of the electrodes is regulated using polymer crosslink networks designed with various components, and lithium-ion transfer is optimized through ether-abundant polymer chains. Furthermore, reinforced covalent bonding with carbon nanotube networks is established based on the modified functional groups of polymer networks. The multiscale optimizations of the porous structure, ionic transportation, and covalent bonding network enhance the lithium-ion dynamics property and structural stability. Therefore, ultrahigh linear-capacity fiber electrodes (17.8 mAh m-1) can be fabricated on a large scale and exhibit excellent stability (92.8% after 800 cycles), demonstrating obvious superiority among the reported fiber electrodes. Moreover, this study highlights the high effectiveness of polymer regulation in fiber electrodes and offers new avenues for designing next-generation wearable energy-storage systems.