The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.

Berberine Modulates Macrophage Activation by Inducing Glycolysis.

Classical activation of macrophage and monocyte differentiation induced by ß-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.

Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. RESULTS: In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. CONCLUSIONS: Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.

Enhanced π-π Stacking between Dipole-Bearing Single Molecules Revealed by Conductance Measurement.

Dipoles are widely involved in π-π interactions and are central to many chemical and biological functions, but their influence on the strength of π-π interactions remains unclear. Here, we report a study of π-π interaction between azulene-based, polar single molecules and between naphthalene-based, nonpolar single molecules. By performing scanning tunneling microscopy break junction measurements of single-molecule conductance, we show that the π-stacked dimers formed by the azulene-based, polar aromatic structures feature higher electrical conductivity and mechanical stability than those formed by the naphthalene-based, nonpolar molecules. Mechanical control of π-π interactions in both rotational and translational motion reveals a sensitive dependence of the stacking strength on relative alignment between the dipoles. The antiparallel alignment of the dipoles was found to be the optimal stacking configuration that underpins the observed enhancement of π-π stacking between azulene-based single molecules. Density functional theory calculations further explained the observed enhancement of stacking strength and the corresponding charge transport efficiency. Our experimental and theoretical results show that the antiparallel alignment of the dipole moments significantly enhances the electronic coupling and mechanical stability of π-π stacking. In addition, in the formation of single-molecule junctions, the azulene group was experimentally and theoretically proved to form a Au-π contact with electrodes with high charge transport efficiency. This paper provides evidence and interpretation of the role of dipoles in π-π interactions at the single-molecule level and offers new insights into potential applications in supramolecular devices.

Gram-Scale Room-Temperature Synthesis of Solid-State Fluorescent Carbon Nanodots for Bright Electroluminescent Light Emitting Diodes.

The reaction conditions of high temperature and high pressure will introduce structural defects, high energy consumption, and security risks, severely hindering the industrial application of organic carbon nanodots (CDs). Moreover, the aggregation caused quenching effect also fundamentally limits the CDs based electroluminescent light emitting diodes (LEDs). Herein, for the first time, a rapid one-step room temperature synthetic strategy is introduced to prepare highly emissive solid-state-fluorescent CDs (RT-CDs). A strong oxidizing agent, potassium periodate (KIO4 ), is adopted as a catalyst to facilitate the cyclization of o-phenylenediamine and 4-dimethylamino phenol in aqueous solution at room temperature for only 5 min. The resultant organic molecule, 2-(dimethylamino) phenazine, will self-assemble kinetically to generate supramolecular-structure CDs during crystallization. The elaborately arranged supramolecular structure (J aggregates) endows CDs with intense solid-state-fluorescence. Density functional theory (DFT) calculation shows that the excited state of RT-CDs exhibits charge transfer characteristic owing to the unique donor-Π-acceptor structure. A high-performance monochrome RT-CDs based electroluminescent LEDs (2967 cd m-2 and 1.38 cd A-1 ) were fabricated via systematic optimizations of device engineering. This work provides a concrete and feasible avenue for the rapid and massive preparation of CDs, advancing the commercialization of CDs based optoelectronic devices.

Room-temperature logic-in-memory operations in single-metallofullerene devices.

In-memory computing provides an opportunity to meet the growing demands of large data-driven applications such as machine learning, by colocating logic operations and data storage. Despite being regarded as the ultimate solution for high-density integration and low-power manipulation, the use of spin or electric dipole at the single-molecule level to realize in-memory logic functions has yet to be realized at room temperature, due to their random orientation. Here, we demonstrate logic-in-memory operations, based on single electric dipole flipping in a two-terminal single-metallofullerene (Sc2C2@Cs(hept)-C88) device at room temperature. By applying a low voltage of ±0.8 V to the single-metallofullerene junction, we found that the digital information recorded among the different dipole states could be reversibly encoded in situ and stored. As a consequence, 14 types of Boolean logic operation were shown from a single-metallofullerene device. Density functional theory calculations reveal that the non-volatile memory behaviour comes from dipole reorientation of the [Sc2C2] group in the fullerene cage. This proof-of-concept represents a major step towards room-temperature electrically manipulated, low-power, two-terminal in-memory logic devices and a direction for in-memory computing using nanoelectronic devices.

Cluster-Based Crystalline Materials for Iodine Capture.

The treatment of radioactive iodine in nuclear waste has always been a critical issue of social concern. The rational design of targeted and efficient capture materials is of great significance to the sustainable development of the ecological environment. In recent decades, crystalline materials have served as a molecular platform to study the binding process and capture mechanism of iodine molecules, enabling people to understand the interaction between radioactive iodine guests and pores intuitively. Cluster-based crystalline materials, including molecular clusters and cluster-based metal-organic frameworks, are emerging candidates for iodine capture due to their aggregative binding sites, precise structural information, tunable pores/packing patterns, and abundant modifications. Herein, recent progress of different types of cluster materials and cluster-dominated metal-organic porous materials for iodine capture is reviewed. Research prospects, design strategies to improve the affinity for iodine and possible capture mechanisms are discussed.

Selenite-Catalyzed Reaction between Benzoquinone and Acetylacetone Deciphered the Enhanced Inhibition on Microcystis aeruginosa Growth.

The coexistence of selenite (Se(IV)) and acetylacetone (AA) generated a synergistic effect on the growth inhibition of a bloom-forming cyanobacterium, Microcystis aeruginosa. The mechanism behind this phenomenon is of great significance in the control of harmful algal blooms. To elucidate the role of Se(IV) in this effect, the reactions in ternary solutions composed of Se(IV), AA (or two other similar hydrogen donors), and quinones, especially benzoquinone (BQ), were investigated. The transformation kinetic results demonstrate that Se(IV) played a catalytic role in the reactions between AA (or ascorbic acid) and quinones. By comparison with five other oxyanions (sulfite, sulfate, nitrite, nitrate, and phosphate) and two AA derivatives, the formation of an AA-Se(IV) complexation intermediate was confirmed as a key step in the accelerated reactions between BQ and AA. To our knowledge, this is the first report on Se(IV) as a catalyst for quinone-involved reactions. Since both quinones and Se are essential in cells and there are many other chemicals of similar electron-donating properties to that of AA, the finding here shed light on the regulation of electron transport chains in a variety of processes, especially the redox balances that are tuned by quinones and glutathione.

A Recyclable and Scalable High-Capacity Organic Battery.

Redox organic electrode materials (OEMs) have attracted extensive attention for batteries due to the possibility to be designed with high performance. However, the practical application of OEMs requires rigor criteria such as low cost, recyclability, scalability and high performance etc. and hence seems still far away. Here, we demonstrate an OEM for high performance aqueous organic batteries. Quantification of the charge storage confirmed the storage of protons with fast reaction kinetics, thereby enabling the high performance at high mass loading. As a result, the laminated pouch cells delivered Ampere-hour-scale capacity with excellent cycling performance. Benefited from the small molecular nature and the stable both charged and discharged states, the electrodes can be recycled at any states of charge with high yields (more than 90 %). This work provides a substantial step in the practical applications of OEMs for the future sustainable batteries.

Supracluster Assembly of Archimedean Cages with 72 Hydrogen Bonds for the Aldol Addition Reaction.

Clusters that can be experimentally precisely characterized and theoretically accurately calculated are essential to understanding the relationship between material structure and function. Here, we propose the concept of "supraclusters", which aim to connect "supramolecules" and "suprananoparticles" as well as reveal the unique assembly behavior of "supraclusters" with nanoparticle size at the molecular level. The implementation of supraclusters is full of challenges due to the difficulty in satisfying the ordered connectivity of clusters due to their abundant and dispersed hydrogen bonding sites. By solvothermal synthesis under a high catechol (H2 CATs) content, we successfully isolated a series of triangular {Al6 M3 } cluster compounds possessing brucite-like structural features. Interestingly, eight {Al6 M3 } clusters form 72-fold strong hydrogen bonding truncatedhexahedron Archimedean {Al6 M3 }8 supracluster cage (abbreviated as H-tcu). Surprisingly, the solution stability of the H-tcu was further proved by electrospray ionization mass spectrometry (ESI-MS) characterization. Therefore, it is not difficult to explain the reason for assembly of H-tcu into edge-directed and vertex-directed isomers. These porous supraclusters can be obtained by scale-up synthesis and exhibit a noticeable catalysis effect towards the condensation of acetone and p-nitrobenzaldehyde. As an intermediate state of supramolecule and suprananoparticle, the supracluster assembly can enrich the cluster chemistry and bring new structural types.

Symmetry-Like Relation of Relative Entropy Measure of Quantum Coherence.

Quantum coherence is an important physical resource in quantum information science, and also as one of the most fundamental and striking features in quantum physics. To quantify coherence, two proper measures were introduced in the literature, the one is the relative entropy of coherence C r ( ρ ) = S ( ρ diag ) - S ( ρ ) and the other is the ℓ 1 -norm of coherence C ℓ 1 ( ρ ) = ∑ i ≠ j | ρ i j | . In this paper, we obtain a symmetry-like relation of relative entropy measure C r ( ρ A 1 A 2 ⋯ A n ) of coherence for an n-partite quantum states ρ A 1 A 2 ⋯ A n , which gives lower and upper bounds for C r ( ρ ) . As application of our inequalities, we conclude that when each reduced states ρ A i is pure, ρ A 1 ⋯ A n is incoherent if and only if the reduced states ρ A i and tr A i ρ A 1 ⋯ A n ( i = 1 , 2 , … , n ) are all incoherent. Meanwhile, we discuss the conjecture that C r ( ρ ) ≤ C ℓ 1 ( ρ ) for any state ρ , which was proved to be valid for any mixed qubit state and any pure state, and open for a general state. We observe that every mixture η of a state ρ satisfying the conjecture with any incoherent state σ also satisfies the conjecture. We also observe that when the von Neumann entropy is defined by the natural logarithm ln instead of log 2 , the reduced relative entropy measure of coherence C ¯ r ( ρ ) = - ρ diag ln ρ diag + ρ ln ρ satisfies the inequality C ¯ r ( ρ ) ≤ C ℓ 1 ( ρ ) for any state ρ .

Identification of Differentially Expressed miRNAs between a Wheat K-type Cytoplasmic Male Sterility Line and Its Near-Isogenic Restorer Line.

K-type cytoplasmic male sterility (KCMS) lines were ideal material for three-line hybrid wheat system due to the major role in hybrid wheat production. In this study, the morphology of developing microspore and mature pollen was compared between a KCMS line and its near-isogenic restorer line (KCMS-NIL). The most striking difference is that the microspore was unable to develop into tricellular pollen in the KCMS line. MicroRNA plays vital roles in flowering and gametophyte development. Small RNA sequencing identified a total of 274 known and 401 novel miRNAs differentially expressed between two lines or two developmental stages. Most of miRNAs with high abundance were differentially expressed at the uninucleate stage, and their expression level recovered or remained at the binucleate stage. Further degradome sequencing identified target genes which were mainly enriched in transcription regulation, phytohormone signaling and RNA degradation pathways. Combining with the transcriptome data, a correlation was found between the abnormal anther development, such as postmeiotic mitosis cessation, deformative pollen wall and the chromosome condensation of the vegetative cell, and the alterations in the related miRNA and their targets expression profiles. According to the correlation and pathway analysis, we propose a hypothetic miRNA-mediated network for the control of KCMS restoration.

Approximating Ground States by Neural Network Quantum States.

Motivated by the Carleo's work (Science, 2017, 355: 602), we focus on finding the neural network quantum statesapproximation of the unknown ground state of a given Hamiltonian H in terms of the best relative error and explore the influences of sum, tensor product, local unitary of Hamiltonians on the best relative error. Besides, we illustrate our method with some examples.

Organic peroxyl radicals from biacetyl accelerated the visible-light degradation of steroid estrogens in aqueous solution.

Indirect photodegradation is an important pathway for the reduction of steroid estrogens in sunlit surface waters. Nevertheless, the kinetics and mechanisms governing the interaction between coexisting carbonyl compounds and estrogens under visible light (Vis) remain unexplored. This study systematically investigates the Vis-induced photodegradation of 17ß-estradiol (E2) in the presence of five specific carbonyl compounds-biacetyl (BD), acetone, glyoxal, pyruvic acid, and benzoquinone. The results demonstrate that, among these compounds, only BD significantly enhanced the photodegradation of E2 under Vis irradiation (λ > 400 nm). The pseudo-first order photodegradation rate constants (k1) of E2 in the Vis/BD system were 0.025 min-1 and 0.076 min-1 in ultrapure water and river water, respectively. The enhancing effect of BD was found to be pH-dependent, increasing the pH from 3.0 to 11.0 resulted in a 76% reduction in the k1 value of E2 in the Vis/BD system. Furthermore, the presence of humic acid, NO3-, or HCO3- led to an increase of more than 35% in the k1 value of E2, while NO2- exerted a pronounced inhibitory effect, resulting in a 92% decrease. Peroxyacetyl and peroxymethyl radicals, derived from BD in a yield ratio of 9, played a crucial role in the degradation of E2. These peroxyl radicals primarily targeted electron-rich hydroxyl sites of E2, initiating hydroxylation and ring-opening reactions that culminated in the formation of acidic byproducts. Notably, toxicity evaluation indicates that these hydroxylated and acidic products exhibited lower toxicity than the parent compound E2. This study highlights the important role of peroxyl radicals in estrogen degradation within aquatic environment, and also helps to design efficient visible light-responsive photo-activators for the treatment of estrogen-contaminated waters.

One-Step Extrusion Preparation for Low-Cost Multicolored Carbon Dot Fluorescent Films.

Carbon dots (CDs), an emerging class of environmentally friendly luminescent materials, have been extensively applied in full-color display of light-emitting diodes (LEDs). However, the synthesis of CDs usually requires high pressure, and the conventional preparation of CD-based LED films involves intricate manufacturing techniques. The resulting security risk and high cost restrict the further application of CD-based LEDs. Here, we present a cost-effective method to obtain CD-based LED films via in situ extrusion in a twin-screw extruder. By fine-tuning the extrusion temperature, we created blue-emitting LEDs. The resulting fluorescent films exhibited remarkable stability, retaining 94% fluorescence intensity after 180 days of storage. We also prepared yellow, pure white, and cool white LEDs with malleable shapes, validating the versatility of the in situ extrusion method. More importantly, the manufacturing cost for CD-based films amounts to only about 0.8 RMB/g, which is substantially lower than that of the reported preparation methods. This work offers a cost-effective, safe, and massive approach to preparing photoluminescent LEDs, paving the way for the development of more sustainable and efficient CD-based LEDs.

Cardioprotective role of oleanolic acid in patients with type 2 diabetes mellitus.

Background: Patients with type 2 diabetes mellitus (T2DM) experience a decline in cardiac function, resulting in poor prognosis. Therefore, restoration of cardiac function and improvement of myocardial fibrosis is an important treatment goal for patients with T2DM. Material and methods: The chemical structure of oleanolic acid(OA) was downloaded from PubChem and uploaded to PharmMapper. GeneCards and OMIM databases were searched for genes related to OA and disease and plotted into a Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. Then, a mouse model of diabetes mellitus was established, and ELISA, echocardiographic analysis of cardiac function, TUNEL assay, and reactive oxygen species assay were performed. Results: Network pharmacology analysis identified the related targets and potential molecular mechanisms underlying the effects of OA in T2DM. ELISA, echocardiographic analysis of cardiac function, and TUNEL assay results showed that OA inhibits apoptosis and improves apoptotic indexes in mice with T2DM-induced myocardial injury. Conclusion: The results demonstrate the myocardial protective effect of OA in this mouse model.

Metagenomic and Antibiotic Resistance Analysis of the Gut Microbiota in Larus relictus and Anatidae Species Inhabiting the Honghaizi Wetland of Ordos, Inner Mongolia, from 2021 to 2023.

Gut microbes thrive by utilising host energy and, in return, provide valuable benefits, akin to a symbiotic relationship. Here, metagenomic sequencing was performed to characterise and compare the community composition, diversity and antibiotic resistance of the gut microbiota of Relict gull (Larus relictus) and Anatidae species. Alpha diversity analysis revealed that the intestinal microbial richness of L. relictus was significantly lower than that of Anatidae, with distinct differences observed in microbial composition. Notably, the intestines of L. relictus harboured more pathogenic bacteria such as clostridium, which may contribute to the decline in their population and endangered status. A total of 117 strains of Escherichia coli were isolated, with 90.60% exhibiting full susceptibility to 21 antibiotics, while 25.3% exhibited significant biofilm formation. Comprehensive Antibiotic Resistance Database data indicated that glycopeptide resistance genes were the most prevalent type carried by migratory birds, alongside quinolone, tetracycline and lincosamide resistance genes. The abundance of resistance genes carried by migratory birds decreased over time. This metagenomic analysis provides valuable insights into the intestinal microbial composition of these wild bird species, offering important guidance for their conservation efforts, particularly for L. relictus, and contributing to our understanding of pathogen spread and antibiotic-resistant bacteria.

Bright Blue Emission Lead-Free Halides with Narrow Bandwidth Enabled by Oversaturated Europium Doping.

Eu2+-based lead-free metal halide nanocrystals (LFMH NCs), including CsEuCl3 NCs and CsX:Eu2+ NCs (X = Cl or Br), exhibit highly efficient narrow-band blue photoluminescence, making them competitive candidates for next-generation lighting and displays. However, the growing mechanism of the aforementioned NCs lacks in-depth study, which hinders the development of Eu2+-based nanomaterials. Herein, we demonstrate the colloidal synthesis of CsBr:Eu2+ NCs based on an air-stable europium source. The NCs show deep blue photoluminescence centered at 444 nm, with a maximum photoluminescence quantum yield (PLQY) reaching 53.4% and a fwhm of 30 nm. We further reveal the mechanism that determines CsBr host growth and Eu2+ doping in CsBr:Eu2+ nanocrystals, especially dopant trapping and self-purification, that determine the PLQY level. Pure white, warm white, and cold white LEDs are fabricated based on CsBr:Eu2+ NCs, red and green phosphors, and their performance suits the needs of high-quality lighting.

Difference-Deformable Convolution with Pseudo Scale Instance Map for Cell Localization.

Cell localization still faces two unresolved challenges: 1) the dramatic variations in cell morphology, coupled with the heterogeneous intensity distribution of lightly stained cells; 2) existing cell location maps lack scale information, resulting in insufficient supervision for point maps and inaccurate supervision for density maps. 1) To address the first challenges, we introduce a novel gradient-aware and shape-adaptive Difference-Deformable Convolution (DDConv), which enhances the model's robustness to color by leveraging gradient information while adaptively adjusting the shape of the convolutional kernel to tackle the substantial variability in cell morphology. 2) To overcome the issue of unreasonable location maps, we propose the Pseudo-Scale Instance (PSI) map, which can adaptively provide the corresponding scale information for each cell to realize accurate supervision. We analyze and evaluate DDConv and the PSI map in three challenging cell localization tasks. In comparison to existing methods, our proposed approach significantly enhances localization performance, setting a new benchmark for the cell localization task. Our code is available at https://github.com/ChyaZhang/DDConv-PSI.

Development and Optimization of A Human Hepatocellular Carcinoma Patient-Derived Organoid Model for Potential Target Identification and Drug Discovery.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents necessitate further research into its pathogenesis and treatment. Organoids, a novel model that closely resembles native tumor tissue and can be cultured in vitro, have garnered significant interest in recent years, with numerous reports on the development of organoid models for liver cancer. In this study, we have successfully optimized the procedure and established a culture protocol that enables the formation of larger-sized HCC organoids with stable passaging and culture conditions. We have comprehensively outlined each step of the procedure, covering the entire process of HCC tissue dissociation, organoid plating, culture, passaging, cryopreservation, and resuscitation, and provided detailed precautions in this paper. These organoids exhibit genetic similarity to the original HCC tissues and can be utilized for diverse applications, including the identification of potential therapeutic targets for tumors and subsequent drug development.