Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of Aspergillus fumigatus.

The hydrophobic layer of Aspergillus conidia, composed of RodA, plays a crucial role in conidia transfer and immune evasion. It self-assembles into hydrophobic rodlets through intramolecular disulfide bonds. However, the secretory process of RodA and its regulatory elements remain unknown. Since protein disulfide isomerase (PDI) is essential for the secretion of many disulfide-bonded proteins, we investigated whether PDI is also involved in RodA secretion and assembly. By gene knockout and phenotypic analysis, we found that Pdi1, one of the four PDI-related proteins of Aspergillus fumigatus, determines the hydrophobicity and integrity of the rodlet layer of the conidia. Preservation of the thioredoxin-active domain of Pdi1 was sufficient to maintain conidial hydrophobicity, suggesting that Pdi1 mediates RodA assembly through its disulfide isomerase activity. In the absence of Pdi1, the disulfide mismatch of RodA in conidia may prevent its delivery from the inner to the outer layer of the cell wall for rodlet assembly. This was demonstrated using a strain expressing a key cysteine-mutated RodA. The dormant conidia of the Pdi1-deficient strain (Δpdi) elicited an immune response, suggesting that the defective conidia surface in the absence of Pdi1 exposes internal immunogenic sources. In conclusion, Pdi1 ensures the correct folding of RodA in the inner layer of conidia, facilitating its secretion into the outer layer of the cell wall and allowing self-assembly of the hydrophobic layer. This study has identified a regulatory element for conidia rodlet assembly.IMPORTANCEAspergillus fumigatus is the major cause of invasive aspergillosis, which is mainly transmitted by the inhalation of conidia. The spread of conidia is largely dependent on their hydrophobicity, which is primarily attributed to the self-assembly of the hydrophobic protein RodA on the cell wall. However, the mechanisms underlying RodA secretion and transport to the outermost layer of the cell wall are still unclear. Our study identified a critical role for Pdi1, a fungal protein disulfide isomerase found in regulating RodA secretion and assembly. Inhibition of Pdi1 prevents the formation of correct S-S bonds in the inner RodA, creating a barrier to RodA delivery and resulting in a defective hydrophobic layer. Our findings provided insight into the formation of the conidial hydrophobic layer and suggested potential drug targets to inhibit A. fumigatus infections by limiting conidial dispersal and altering their immune inertia.

Robust and Durable Superhydrophobic Coatings with Antipollution Flashover Performance via Silane-Modified Polyurea.

The inadequate hydrophobicity and the degradation in usage seriously hampered the applications of the existing antipollution flashover coatings. In this paper, a superhydrophobic polyurea coating with antipollution flashover ability was fabricated through chemically grafting the silica onto the chains of polyurea by utilizing silane coupling agent and hydrophobic modification. It is demonstrated that the coating exhibits outstanding antipollution flashover performances. Noteworthy, the surface pollution flashover voltage has been increased by 33.8% compared with the room temperature vulcanizing silicone rubber (RTV silicone rubber). In addition, the volume resistivity is above 1.0 × 1012 Ω·m, and the dielectric strength achieves to 28.85 kV/mm, which represents excellent insulating property. Furthermore, the superhydrophobic polyurea coating exhibits outstanding abrasion resistance, adhesion, acid-base resistance, and durability. As a result, it holds great promise for use in preventing pollution flashover in electrical insulators.

Substrate-Independent Superhydrophobic Coating Capable of Photothermal-Induced Repairability for Multiple Damages Fabricated via Simple Blade Coating.

Repairable superhydrophobic surfaces have promising application potential in many fields. However, so far, it is still a challenge to develop a superhydrophobic surface with repairability for multiple types of damage through a simple method. In this paper, a repairable superhydrophobic coating was obtained on various substrates by blade-coating mixtures of polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), and multiwalled carbon nanotubes (MWCNTs) modified with dopamine (PDA) and octadecylamine (ODA). The obtained coating has a good liquid-repellent property with a water contact angle above 150° and a water sliding angle of ∼6° and possesses an excellent absorbance (∼97%) in the wavelength range of 250-2500 nm. Due to its high absorbance, the coating displays an outstanding photothermal effect with a temperature rise of ∼65 °C under irradiation by 1.0 kW/m2 of simulated sunlight. Furthermore, after being degraded by multiple stimuli, including plasma treatment, acid/alkali/oil immersion, sand impact, and the icing-thawing cycle, the coating can recover superhydrophobicity via sunlight irradiation, demonstrating the good photothermal-induced repairability of the coating. It can be expected that the good water-repellent property, photothermal effect, and repairability give this coating a promising prospect in practical applications.

Antibacterial PVDF Coral-Like Hierarchical Structure Composite Film Fabrication for Self-Cleaning and Radiative Cooling Effect.

Passive radiative cooling (PRC) is a zero-energy-consumption technology that reflects sunlight and radiates heat to cold outer space. In this work, a porous poly(vinylidene fluoride)-poly(methyl methacrylate) (PVDF-PMMA) composite film is fabricated by decorating zinc-imidazolate metal-organic framework (MOF) (ZIF-8) particles obtained by phase inversion. Due to the competent scattering via the coral-like hierarchical structures and the vibration excitations of specific functional groups, the prepared film exhibits good solar reflectance (92.6%) and intermediate infrared emittance (99.1%), with an average sub-ambient cooling of 10.4 °C under a solar radiation intensity of 0.6 AM1.5. Additionally, poly(vinylidene fluoride) has a low surface energy, while the ZIF-8 particles and coral-like hierarchical structures enhance the surface roughness, endowing the surface with significant superhydrophobicity characterized by a water contact angle (WCA) of 157.5° and a sliding angle (SA) of 2°. These films exhibit excellent antibacterial properties. When the content of ZIF-8 particles in the film is 300 mg·L-1, the antibacterial rate reaches 100% after 1 h of treatment. Thus, the ZIF-8 porous poly(vinylidene fluoride)-poly(methyl methacrylate) composite (ZPPP) film has potential application prospects in areas with high health and environmental requirements, such as cold chain transportation and public spaces.

An injectable bone paste of poly (lactic acid)/zinc-doped nano hydroxyapatite composite microspheres for skull repair.

In this study, poly (lactic acid)/zinc-doped nano hydroxyapatite (PLA/nano-ZnHA) composite microspheres were prepared and formed into injectable bone paste with sodium alginate (SA) and polyvinyl alcohol (PVA) for bone defect repair. The effect of component of bone paste on injectability and zinc doping content related biological properties were mainly discussed. An injectable bone paste of PLA/nano-ZnHA composite microspheres (CM) was formed in mass ratio of (2.5-25):(0.25-4): (0-2.5):(20-65) of CM, SA, PVA and water with the favorable injectability (average force:4.46±1.72 N). In vitro 5%-10% zinc doping content displayed significantly higher promotion on cell proliferation and osteogenic differentiation than 15%-20% zinc doping content. Furthermore, in vivo the significant promoting effect of 0-5% zinc doping in ZnHA on bone repair was observed. Although 5% zinc doping content did not show a significant enhancement in bone volume/tissue volume (BV/TV), it has the ability to improve the bone mineral density (BMD) in early stage of bone repair compared with the 0% zinc doping content. The PLA/nano-ZnHA composite microsphere injectable paste with convenient surgical operation and well filling ability has the potential to become a competitive tissue repair material.

Regioselective Syntheses of 1,4- and 1,6-Dicarbonyl Compounds via Photoredox-Based Oxidative Heterocoupling of Enolsilanes with Oxygen as an Oxidant.

A photoredox-based oxidative heterocoupling of enolsilanes to the corresponding 1,4- and 1,6-dicarbonyl compounds was developed by using Mes-Acr+BF4- as the photocatalyst, and oxygen was used as the oxidant. This newly developed chemistry adheres to the principles of atom economy, step economy, and redox economy, making it a concise and efficient method.

Experimental Study on Energy-Free Superhydrophobic Radiative Cooling Versatile Film with Enhanced Environmental Tolerance.

Clean, energy-free methods of cooling are an effective way to respond to the global energy crisis. To date, cooling materials using passive daytime radiative cooling (RC) technology have been applied in the fields of energy-efficient buildings, solar photovoltaic cooling, and insulating textiles. However, RC materials frequently suffer from comprehensive damage to their microstructure, resulting in the loss of their initial cooling effect in complex outdoor environments. Here, a superhydrophobic daytime passive RC porous film with environmental tolerance (SRCP film) was fabricated, which integrated strong solar reflectivity (approximately 90%), mid-infrared emissivity (approximately 0.97), and superhydrophobicity (water contact angle (WCA) of 160° and sliding angle of 3°). This study revealed that SRCP film had an average reflectivity of 14.3% higher than SiO2 particles in the 0.3-2.5 µm wavelength region, achieving a cooling effect of 13.2 °C in ambient conditions with a solar irradiance of 946 W·m-2 and a relative humidity of 74% due to the synergistic effect of effective solar reflection and thermal infrared emission. In addition, empirical results showed that the attained films possessed outstanding environmental tolerance, maintaining high WCA (156°), stable cooling effect (8.3 °C), and low SiO2 loss (less than 5.1%) after 30 consecutive days of UV irradiation and 14 days of corrosion with acidic and alkaline solutions. More importantly, this work could be flexibly prepared by various methods without the use of any fluorine-containing reagents, which greatly widens the practical application scope.

Smart diabetic foot ulcer scoring system.

Current assessment methods for diabetic foot ulcers (DFUs) lack objectivity and consistency, posing a significant risk to diabetes patients, including the potential for amputations, highlighting the urgent need for improved diagnostic tools and care standards in the field. To address this issue, the objective of this study was to develop and evaluate the Smart Diabetic Foot Ulcer Scoring System, ScoreDFUNet, which incorporates artificial intelligence (AI) and image analysis techniques, aiming to enhance the precision and consistency of diabetic foot ulcer assessment. ScoreDFUNet demonstrates precise categorization of DFU images into "ulcer," "infection," "normal," and "gangrene" areas, achieving a noteworthy accuracy rate of 95.34% on the test set, with elevated levels of precision, recall, and F1 scores. Comparative evaluations with dermatologists affirm that our algorithm consistently surpasses the performance of junior and mid-level dermatologists, closely matching the assessments of senior dermatologists, and rigorous analyses including Bland-Altman plots and significance testing validate the robustness and reliability of our algorithm. This innovative AI system presents a valuable tool for healthcare professionals and can significantly improve the care standards in the field of diabetic foot ulcer assessment.

Global Marine Cold Seep Metagenomes Reveal Diversity of Taxonomy, Metabolic Function, and Natural Products.

Cold seeps in the deep sea are closely linked to energy exploration as well as global climate change. The alkane-dominated chemical energy-driven model makes cold seeps an oasis of deep-sea life, showcasing an unparalleled reservoir of microbial genetic diversity. Here, by analyzing 113 metagenomes collected from 14 global sites across 5 cold seep types, we present a comprehensive Cold Seep Microbiomic Database (CSMD) to archive the genomic and functional diversity of cold seep microbiomes. The CSMD includes over 49 million non-redundant genes and 3175 metagenome-assembled genomes, which represent 1895 species spanning 105 phyla. In addition, beta diversity analysis indicates that both the sampling site and cold seep type have a substantial impact on the prokaryotic microbiome community composition. Heterotrophic and anaerobic metabolisms are prevalent in microbial communities, accompanied by considerable mixotrophs and facultative anaerobes, highlighting the versatile metabolic potential in cold seeps. Furthermore, secondary metabolic gene cluster analysis indicates that at least 98.81% of the sequences potentially encode novel natural products, with ribosomally synthesized and post-translationally modified peptides being the predominant type widely distributed in archaea and bacteria. Overall, the CSMD represents a valuable resource that would enhance the understanding and utilization of global cold seep microbiomes.

Bimetal doped Cu-Fe-ZIF-8/g-C3N4 nanocomposites for the adsorption of tetracycline hydrochloride from water.

Bimetal doped Cu-Fe-zeolitic imidazole framework-8 (ZIF-8)/graphitic carbon nitride (GCN) (Cu-Fe-ZIF-8/GCN) nanocomposites were prepared via one-pot and ion-exchange methods. The main influencing factors, such as adsorbent concentration, TC concentration, initial pH, and coexisting ions, were evaluated in detail. Due to the suitable pore structures and the presence of multiple interactions on the surface, the nanocomposite showed a high adsorption capacity up to 932 mg g-1 for tetracycline hydrochloride (TC), outperforming ZIF-8 by 4.8 times. The adsorption kinetics and adsorption isotherm were depicted in good detail using pseudo-second-order kinetic and Langmuir models, respectively. Thermodynamic calculation revealed that the adsorption of the nanocomposite under experimental conditions was a spontaneous heat absorption process, and was primarily driven by chemisorption. After four cycles of use, the nanocomposite retained 87.2% of its initial adsorption capacity, confirming its high reusability and broad application prospects in removing tetracycline-type pollutants from wastewater.

Exploring genetic codon expansion for unnatural amino acid incorporation in filamentous fungus Aspergillus nidulans.

Genetic code expansion technology allows the incorporation of unnatural amino acids (UAAs) into proteins, which is useful in protein engineering, synthetic biology, and gene therapy. Despite its potential applications in various species, filamentous fungi remain unexplored. This study aims to address this gap by developing these techniques in Aspergillus nidulans. We introduced an amber stop codon into a specific sequence within the reporter gene expressed in A. nidulans and replaced the anticodon of the fungal tRNATyr with CUA. This resulted in the synthesis of the target protein, confirming the occurrence of amber suppression in the fungus. When exogenous E. coli tRNATyrCUA (Ec. tRNATyrCUA) and E. coli tyrosyl-tRNA (Ec.TyrRS) were introduced into A. nidulans, they successfully synthesized the target protein via amber suppression and were shown to be orthogonal to the fungal translation system. By replacing the wild-type Ec.TyrRS with a mutant with a higher affinity for the UAA O-methyl-L-tyrosine, the fungal system was able to initiate the synthesis of the UAA-labeled protein (UAA-protein). We further increased the expression level of the UAA-protein through several rational modifications. The successful development of a genetic code expansion technique for A. nidulans has introduced a potentially valuable approach to the study of fungal protein structure and function.

The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.

Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets.

Transcriptional super-enhancers and the BET bromodomain protein BRD4 are emerging as critical drivers of tumorigenesis and therapeutic targets. Characterized by substantial accumulation of histone H3 lysine 27 acetylation (H3K27ac) signals at the loci of cell identity genes and critical oncogenes, super-enhancers are recognized, bound and activated by BRD4, resulting in considerable oncogene over-expression, malignant transformation, cancer cell proliferation, survival, tumor initiation and progression. Small molecule compound BRD4 BD1 and BD2 bromodomain inhibitors block BRD4 binding to super-enhancers, suppress oncogene transcription and expression, reduce cancer cell proliferation and survival, and repress tumor progression in a variety of cancer types. Like other targeted therapy agents, BRD4 inhibitors show moderate anticancer effects on their own, and exert synergistic anticancer effects in vitro and in preclinical models, when combined with other anticancer agents including CDK7 inhibitors, CBP/p300 inhibitors and histone deacetylase inhibitors. More recently, BRD4 BD2 bromodomain selective inhibitors, proteolysis-targeting chimera (PROTAC) BRD4 protein degraders, and dual BRD4 and CBP/p300 bromodomain co-inhibitors have been developed and shown better anticancer efficacy and/or safety profile. Importantly, more than a dozen BRD4 inhibitors have entered clinical trials in patients with cancer of various organ origins. In summary, super-enhancers and their reader BRD4 are critical tumorigenic drivers, and BRD4 BD1 and BD2 bromodomain inhibitors, BRD4 BD2 bromodomain selective inhibitors, PROTAC BRD4 protein degraders, and dual BRD4 and CBP/p300 bromodomain co-inhibitors are promising novel anticancer agents for clinical translation.