Clostridioides difficile ferrosome organelles combat nutritional immunity.

Iron is indispensable for almost all forms of life but toxic at elevated levels1-4. To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis1,5,6. Recent studies showed that three Gram-negative environmental anaerobes produce iron-containing ferrosome granules7,8. However, it remains unclear whether ferrosomes are generated exclusively by Gram-negative bacteria. The Gram-positive bacterium Clostridioides difficile is the leading cause of nosocomial and antibiotic-associated infections in the USA9. Here we report that C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. We found that a membrane protein (FezA) and a P1B6-ATPase transporter (FezB), repressed by both iron and the ferric uptake regulator Fur, are required for ferrosome formation and play an important role in iron homeostasis during transition from iron deficiency to excess. Additionally, ferrosomes are often localized adjacent to cellular membranes as shown by cryo-electron tomography. Furthermore, using two mouse models of C. difficile infection, we demonstrated that the ferrosome system is activated in the inflamed gut to combat calprotectin-mediated iron sequestration and is important for bacterial colonization and survival during C. difficile infection.

Design of Soft/Hard Interface with High Adhesion Energy and Low Interfacial Thermal Resistance via Regulation of Interfacial Hydrogen Bonding Interaction.

Adhesion ability and interfacial thermal transfer capacity at soft/hard interfaces are of critical importance to a wide variety of applications, ranging from electronic packaging and soft electronics to batteries. However, these two properties are difficult to obtain simultaneously due to their conflicting nature at soft/hard interfaces. Herein, we report a polyurethane/silicon interface with both high adhesion energy (13535 J m-2) and low thermal interfacial resistance (0.89 × 10-6 m2 K W-1) by regulating hydrogen interactions at the interface. This is achieved by introducing a soybean-oil-based epoxy cross-linker, which can destroy the hydrogen bonds in polyurethane networks and meanwhile can promote the formation of hydrogen bonds at the polyurethane/silicon interface. This study provides a comprehensive understanding of enhancing adhesion energy and reducing interfacial thermal resistance at soft/hard interfaces, which offers a promising perspective to tailor interfacial properties in various material systems.

Comprehensive Characterization of HATs and HDACs in Human Cancers Reveals Their Role in Immune Checkpoint Blockade.

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

Grafted Alkene Chains: Triggers for Defeating Contact Thermal Resistance in Composite Elastomers.

The pursuit of enhancing the heat transfer performance of composite elastomers as the thermal interface materials (TIMs) is a compelling and timely endeavor, given the formidable challenges posed by interfacial thermal transport in the domains of energy science, electronic technology, etc. Despite the efficacy of phase change materials (PCMs) in enhancing composite elastomers' interfacial compatibility, thereby reducing contact thermal resistance for heat transfer improvement, their leakage post-transition has impeded the widespread adoption of this approach. Herein, a strategy is proposed for developing a solid-solid phase change composite elastomer by grafting alkene chains onto the crosslink network to eliminate the possibility of leakage. A series characterization suggest that the resulting material possesses a self-adjusting interfacial compatibility feature to help reduce contact thermal resistance for heat transfer facilitating. The investigations on adhesion strength and surface energy reveal that the presence of amorphous grafted alkane chains at the interface facilitates easier absorption onto the contacting solid surface, enhancing intermolecular interactions at the interface to promote across-boundary heat transfer. By integrating these findings with the thermal performance evaluation of composite elastomers using a real test vehicle, valuable insights are gained for the design of composite elastomers, establishing their suitability as TIMs in relevant fields.

Elastomer Composites with High Damping and Low Thermal Resistance via Hierarchical Interactions and Regulating Filler.

Modern microelectronics and emerging technologies such as wearable electronics and soft robotics require elastomers to integrate high damping with low thermal resistance to avoid damage caused by vibrations and heat accumulation. However, the strong coupling between storage modulus and loss factor makes it generally challenging to simultaneously increase both thermal conductance and damping. Here, a strategy of introducing hierarchical interaction and regulating fillers in polybutadiene/spherical aluminum elastomer composites is reported to simultaneously achieve extraordinary damping ability of tan δ > 1.0 and low thermal resistance of 0.15 cm2 K W-1, which surpasses state-of-the-art elastomers and their composites. The enhanced damping is attributed to increased energy dissipation via introducing the hierarchical hydrogen bond interactions in polybutadiene networks and the addition of spherical aluminum, which also functions as a thermally conductive filler to achieve low thermal resistance. As a proof of concept, the polybutadiene/spherical aluminum elastomer composites are used as thermal interface materials, showing effective heat dissipation for electronic devices in vibration scenarios. The combination of outstanding damping performance and extraordinary heat dissipation ability of the elastomer composites may create new opportunities for their applications in electronics.

2D Tantalum Disulfide Reduction Strategy Customized Ta2O5/rGO Heterointerface Aerogel Toward Boosting Electromagnetic Wave Absorption and Flame Retardancy.

The exceptional and substantial electron affinity, as well as the excellent chemical and thermal stability of transition metal oxides (TMOs), infuse infinite vitality into multifunctional applications, especially in the field of electromagnetic wave (EMW) absorption. Nonetheless, the suboptimal structural mechanical properties and absence of structural regulation continue to hinder the advancement of TMOs-based aerogels. Herein, a novel 2D tantalum disulfide (2H-TaS2) reduction strategy is demonstrated to synthesize Ta2O5/reduced graphene oxide (rGO) heterointerface aerogels with unique characters. As the prerequisite, the defects, interfaces, and configurations of aerogels are regulated by varying the concentration of 2H-TaS2 to ensure the Ta2O5/rGO heterointerface aerogels with appealing EMW absorption properties such as a minimum reflection loss (RLmin) of -61.93 dB and an effective absorption bandwidth (EAB) of 8.54 GHz (7.80-16.34 GHz). This strategy provides valuable insights for designing advanced EMW absorbers. Meanwhile, the aerogel exhibits favorable thermal insulation performance with a value of 36 mW m-1 K-1, outstanding fire resistance capability, and exceptional mechanical energy dissipation performance, making it promising for applications in the aerospace industry and consumer electronics devices.

Thermally Conductive Elastomer Composites with High Toughness, Softness, and Resilience Enabled by Regulating Interfacial Structure and Dynamics.

The emerging applications of thermally conductive elastomer composites in modern electronic devices for heat dissipation require them to maintain both high toughness and resilience under thermomechanical stresses. However, such a combination of thermal conductivity and desired mechanical characteristics is extremely challenging to achieve in elastomer composites. Here this long-standing mismatch is resolved via regulating interfacial structure and dynamics response. This regulation is realized both by tuning the molecular weight of the dangling chains in the polymer networks and by silane grafting of the fillers, thereby creating a broad dynamic-gradient interfacial region comprising of entanglements. These entanglements can provide the slipping topological constraint that allows for tension equalization between and along the chains, while also tightening into rigid knots to prevent chain disentanglement upon stretching. Combined with ultrahigh loading of aluminum-fillers (90 wt%), this design provides a low Young's modulus (350.0 kPa), high fracture toughness (831.5 J m-2), excellent resilience (79%) and enhanced thermal conductivity (3.20 W m-1 k-1). This work presents a generalizable preparation strategy toward engineering soft, tough, and resilient high-filled elastomer composites, suitable for complex environments, such as automotive electronics, and wearable devices.

Correlating Young's Modulus with High Thermal Conductivity in Organic Conjugated Small Molecules.

Attaining elevated thermal conductivity in organic materials stands as a coveted objective, particularly within electronic packaging, thermal interface materials, and organic matrix heat exchangers. These applications have reignited interest in researching thermally conductive organic materials. The understanding of thermal transport mechanisms in these organic materials is currently constrained. This study concentrates on N, N'-dioctyl-3,4,9,10-perylenedicarboximide (PTCDI-C8), an organic conjugated crystal. A correlation between elevated thermal conductivity and augmented Young's modulus is substantiated through meticulous experimentation. Achievement via employing the physical vapor transport method, capitalizing on the robust C═C covalent linkages running through the organic matrix chain, bolstered by π-π stacking and noncovalent affiliations that intertwine the chains. The coexistence of these dynamic interactions, alongside the perpendicular alignment of PTCDI-C8 molecules, is confirmed through structural analysis. PTCDI-C8 thin film exhibits an out-of-plane thermal conductivity of 3.1 ± 0.1 W m-1 K-1, as determined by time-domain thermoreflectance. This outpaces conventional organic materials by an order of magnitude. Nanoindentation tests and molecular dynamics simulations elucidate how molecular orientation and intermolecular forces within PTCDI-C8 molecules drive the film's high Young's modulus, contributing to its elevated thermal conductivity. This study's progress offers theoretical guidance for designing high thermal conductivity organic materials, expanding their applications and performance potential.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

Visible-Light-Promoted Cascade Coupling of 2-Isocyanonaphthalenes with Elemental Sulfur and Amines to Construct Naphtho[2,1-d]thiazol-2-Amines.

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation.

Epoxy Resins With Controllable "Thermally Conductive-Self-Healing" Synergies: a New Material to Meet the Needs of Flexible Electronic Devices.

With the popularization of 5G technology and artificial intelligence, thermally conductive epoxies with self-healing ability will be widely used in flexible electronic materials. Although many compounds containing both performances have been synthesized, there is little systematic theory to explain the coordination mechanism. In this paper, alkyl chains of different lengths were introduced to epoxies to discuss the thermally conductive, the self-healing performance, and the synergistic effect. A series of electronic-grade biphenyl epoxies (4,4'-bis(oxiran-2-ylmethoxy)-1,1'-biphenyl (1), 4,4'-bis(2-(oxiran-2-yl)ethoxy)-1,1'-biphenyl (2), 4,4'-bis(3-(oxiran-2-yl)propoxy)-1,1'-biphenyl (3), and 4,4'-bis(4-(oxiran-2-yl)butoxy)-1,1'-biphenyl (4) were synthesized and characterized. Furthermore, they were cured with decanedioic acid to produce polymers. Results showed that alkyl chains can both affect the two properties, and the epoxies suitable for specific application scenarios can be prepared by adjusting the length of alkyl chains. In terms of thermal conductivity, compound 1 was a most promising material. However, compound 4 was expected to be utilized in flexible electronic devices because of its acceptable thermal conductivity, self-healing ability, transparency, and flexibility.

Carbon Nanotube Loading Strategies for Peptide Drugs: Insights from Molecular Dynamics Simulations.

Carbon nanotubes (CNTs) can be regarded as a potential platform for transmembrane drug delivery as many experimental works have demonstrated their capability to effectively transport bioactive molecules into living cells. Within this framework, the loading of a peptide drug onto either the interior or exterior of CNTs has gained considerable interest. This study aims to conduct a comprehensive comparison of these two loading methods. To this end, we performed molecular dynamics simulations and the umbrella sampling technique to investigate the interaction energy, conformational changes, and free energy changes of a model peptide drug containing α-helical structure interacting with the inner or outer walls of a 14.7-nm-long (20,20) CNT. Our finding reveals that, for a tube of such dimensions, it is thermodynamically more favorable for the peptide to be loaded onto the inner tube wall than the outer tube wall, primarily due to a larger free energy change for the former strategy. Conversely, unloading the drug from the tube interior poses greater challenges. Moreover, the tube's curvature plays an essential role in influencing the conformation of the adsorbed peptide. Despite the relatively weaker van der Waals interaction between the CNT exterior and the peptide, loading the peptide onto the exterior may induce significant conformational changes, particularly affecting the peptide's α-helix structure. In contrast, loading of the peptide on the CNT interior could maintain most of the α-helical content. CNTs do not typically attract specific peptide residues, with adsorbed groups primarily determined by the peptide's configurations and orientations. Finally, we offer a guideline for selecting an optimal loading strategy for CNT-based drug delivery.

Adhesion Energy-Assisted Low Contact Thermal Resistance Epoxy Resin-Based Composite.

Although intense efforts have been devoted to the development of thermally conductive epoxy resin composites, most previous works ignore the importance of the contact thermal resistance between epoxy resin composites and mating surfaces. Here, we report on epoxy resin/hexagonal boron nitride (h-BN) composites, which show low contact thermal resistance with the contacting surface by tuning adhesion energy. We found that adhesion energy increases with increasing the ratio of soybean-based epoxy resin/amino silicone oil and h-BN contents. The adhesion energy has a negative correlation with the contact thermal resistance; that is, enhancing the adhesion energy will lead to reduced contact thermal resistance. The contact thermal conductance increases with the h-BN contents and is low to 0.025 mm2·K/W for the epoxy resin/60 wt % h-BN composites, which is consistent with the theoretically calculated value. By investigating the wettability and chain dynamics of the epoxy resin/h-BN composites, we confirm that the low contact thermal resistance stems from the increased intermolecular interaction between the epoxy resin chains. The present study provides a practical approach for the development of epoxy resin composites with enhanced thermal conductivity and reduced contact thermal resistance, aiming for effective thermal management of electronics.

Insight into the fracture energy dissipation mechanism in elastomer composites via sacrificial bonds and fillers.

Most tough elastomer composites are reinforced by introducing sacrificial structures and fillers. Understanding the contribution of fillers and sacrificial bonds in elastomer composites to the energy dissipation is critical for the design of high-toughness materials. However, the energy dissipation mechanism in elastomer composites remains elusive. In this study, using a tearing test and time-temperature superposition, we investigate the effect of fillers and sacrificial bonds on the energy dissipation of elastomer composites consisting of poly(lipoic acid)/silver-coated Al fillers. We found that the fillers and sacrificial bonds mutually enhance both the intrinsic fracture energy and the bulk energy dissipation, and moreover the sacrificial bonds play a more important role in enhancing fracture toughness than the fillers. It is unreasonable to rely solely on the loss factor for bulk energy dissipation. The addition of sacrificial bonds results in a chain segment experiencing greater binding force compared to the addition of fillers. This suggests that the chain segment consumes more energy during its movement. By calculating the length of the Kuhn chain segment and the Kuhn number, it is evident that the addition of sacrificial bonds results in a greater binding force for the chain segment than the addition of fillers, and this enhanced binding force increases the energy consumption during the motion of the chain segment.

The dynamic changes in phytoplankton and environmental factors within Dongping Lake (China) before and after the South-to-North Water Diversion Project.

Dongping Lake is one of the most important regulation and storage lakes along the eastern route of the South-to-North Water Diversion Project in China, the water quality condition of which directly influences the safety of water diverting, because it serves as a Yangtze River water redistribution control point. However, the changes in algae, and in environmental factors affecting their community structures, before and after the water diversion project are rarely reported. In this study, the temporal variations of phytoplankton abundance were examined based on monthly samples collected at three stations from May 2010 to April 2022. The total abundance of algae greatly decreased after the water diversion project was implemented, with a relatively stable biodiversity and evenness before and after the water translocation. Multiple statistical methods were used together with the water quality indices (WQIs) and the nutrient status index (TSIM) to evaluate overall water condition and analyse relationships among environmental factors. The WQIs demonstrated a general "Good" water quality with a seasonal differentiation, and that water conditions during water transfer periods were better than during non-water transfer periods, which may be ascribed to the improved hydraulic conditions and purified water environment during water transfer periods. Redundancy analysis showed that water temperature, ammonia nitrogen, water transparency, and total phosphorus were the most important environmental factors, with relatively decreased contribution rates towards phytoplankton communities after the water translocation. Importantly, some dominant phytoplankton genera of Chlorophyta, Bacillariophyceae, and Cyanophyceae were similarly affected by water transparency, and nitrogen and phosphorus nutrients in summer after the water translocation. These research findings helped us gain a comprehensive understanding of the changing patterns of water quality and microalgae and their relationships before and after the water diversion project, providing a guidance for future lake management in regulating hydraulic conditions and improving water quality of Dongping Lake.

Can Adhesion Energy Optimize Interface Thermal Resistance at a Soft/Hard Material Interface?

Thermal resistance at a soft/hard material interface plays an undisputed role in the development of electronic packaging, sensors, and medicine. Adhesion energy and phonon spectra match are two crucial parameters in determining the interfacial thermal resistance (ITR), but it is difficult to simultaneously achieve these two parameters in one system to reduce the ITR at the soft/hard material interface. Here, we report a design of an elastomer composite consisting of a polyurethane-thioctic acid copolymer and microscale spherical aluminum, which exhibits both high phonon spectra match and high adhesion energy (>1000 J/m2) with hard materials, thus leading to a low ITR of 0.03 mm2·K/W. We further develop a quantitative physically based model connecting the adhesion energy and ITR, revealing the key role the adhesion energy plays. This work serves to engineer the ITR at the soft/hard material interface from the aspect of adhesion energy, which will prompt a paradigm shift in the development of interface science.

Drug-Loaded Mesoporous Silica Nanoparticles Enhance Antitumor Immunotherapy by Regulating MDSCs.

Myeloid-derived suppressor cells (MDSCs) are recognized as major immune suppressor cells in the tumor microenvironment that may inhibit immune checkpoint blockade (ICB) therapy. Here, we developed a Stattic-loaded mesoporous silica nanoparticle (PEG-MSN-Stattic) delivery system to tumor sites to reduce the number of MDSCs in tumors. This approach is able to significantly deplete intratumoral MSDCs and thereby increase the infiltration of T lymphocytes in tumors to enhance ICB therapy. Our approach may provide a drug delivery strategy for regulating the tumor microenvironment and enhancing cancer immunotherapy efficacy.

Polysaccharides from Dendrobium officinale improve obesity-induced insulin resistance through the gut microbiota and the SOCS3-mediated insulin receptor substrate-1 signaling pathway.

BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation. RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors. CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.

Transcriptome data-based screening of potential host of genetic transformation for a blue-hued Bougainvillea transgene.

Bougainvillea is a popular ornamental plant. Although Bougainvillea is abundant in germplasm resources, cultivars and flower colors, there is no rare blue colour varieties, due to the absence of delphinidin-based anthocyanins. This study analyzed the Bougainvillea leaf and bract transcriptome to select hosts of genetic transformation that would be suitable for the accumulation of delphinidin. A total of 36 gigabyte (GB) of raw data was obtained by transcriptome sequencing, with 4,058 significantly differentially expressed genes, including 1,854 upregulated and 2,204 downregulated genes. Annotation of these genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Through annotation, two CHS genes, one F3H gene, one DFR gene, and one F3'H gene involved in the delphinidin biosynthesis pathway were identified. The expression levels of these genes and total flavonoid content in the bracts of six Bougainvillea varieties were examined through quantitative real-time PCR and spectrophotometry, respectively. Through the comprehensive evaluation based on membership function method, the suitable host order for a blue-hued Bougainvillea transgene is Singapore White>Elizabeth Angus>Ratana Yellow>China Beauty>Orange King>Brilliant Variegata. Thus, Singapore White variety was the most appropriate transgene host for blue-hued Bougainvillea. The results of this study provide a reference for the directed breeding of blue-hued Bougainvillea.

Two-Electron Oxidations at a Single Cerium Center.

Two-electron oxidations are ubiquitous and play a key role in the synthesis and catalysis. For transition metals and actinides, two-electron oxidation often takes place at a single-metal site. However, redox reactions at rare-earth metals have been limited to one-electron processes due to the lack of accessible oxidation states. Despite recent advancements in nontraditional oxidation state chemistry, the low stability of low-valent compounds and large disparity among different oxidation states prevented the implementation of two-electron processes at a single rare-earth metal center. Here we report two-electron oxidations at a cerium(II) center to yield cerium(IV) terminal oxo and imido complexes. A series of cerium(II-IV) complexes supported by a tripodal tris(amido)arene ligand were synthesized and characterized. Experimental and theoretical studies revealed that the cerium(II) complex is best described as a 4f2 ion stabilized by δ-backdonation to the anchoring arene, while the cerium(IV) oxo and imido complexes exhibit multiple bonding characters. The accomplishment of two-electron oxidations at a single cerium center brings a new facet to molecular rare-earth metal chemistry.