A membrane associated tandem kinase from wild emmer wheat confers broad-spectrum resistance to powdery mildew.

Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.

Harnessing Synchronous Photothermal and Photocatalytic Effects of Substoichiometric MoO3-x Nanoparticle-Decorated Membranes for Clean Water Generation.

Solar-driven interfacial evaporation provides a promising pathway for sustainable freshwater and energy generation. However, developing highly efficient photothermal and photocatalytic nanomaterials is challenging. Herein, substoichiometric molybdenum oxide (MoO3-x) nanoparticles are synthesized via step-by-step reduction treatment of l-cysteine under mild conditions for simultaneous photothermal conversion and photocatalytic reactions. The MoO3-x nanoparticles of low reduction degree are decorated on hydrophilic cotton cloth to prepare a MCML evaporator toward rapid water production, pollutant degradation, as well as electricity generation. The obtained MCML evaporator has a strong local light-to-heat effect, which can be attributed to excellent photothermal conversion via the local surface plasmon resonance effect in MoO3-x nanoparticles and the low heat loss of the evaporator. Meanwhile, the rich surface area of MoO3-x nanoparticles and the localized photothermal effect together effectively accelerate the photocatalytic degradation reaction of the antibiotic tetracycline. With the benefit of these advantages, the MCML evaporator attains a superior evaporation rate of 4.14 kg m-2 h-1, admirable conversion efficiency of 90.7%, and adequate degradation efficiency of 96.2% under 1 sun irradiation. Furthermore, after being rationally assembled with a thermoelectric module, the hybrid device can be employed to generate 1.0 W m-2 of electric power density. This work presents an effective complementary strategy for freshwater production and sewage treatment as well as electricity generation in remote and off-grid regions.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

Oral-gut microbial transmission promotes diabetic coronary heart disease.

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

UV absorption enhanced polydopamine coating.

Mussel-inspired polydopamine (PDA) coatings have gained significant attention in various fields, including biomedicine, energy, detection, and UV protection, owing to their versatile and promising properties. Among these properties, UV shielding stands out as a key feature of PDA coatings. Nevertheless, the current methods for tuning the UV-shielding properties of PDA coatings are quite limited, and only rely on thickness adjustment, which might involve additional issues like color and visible light transmittance to the coating layer. In this study, we propose a facile and modular approach to enhance the UV absorption of PDA coatings by incorporating thiol-heterocycle (TH) derivatives. Both pre- and post-modification strategies can effectively impede the formation of conjugated structures within PDA, leading to enhanced UV absorption within the PDA layers. More importantly, these strategies can improve the UV absorption of PDA coatings while reducing the visible light absorption. Furthermore, this method enabled efficient regulation of the UV absorption of PDA coatings by altering the ring type (benzene ring or pyridine ring) and substituent on the ring (methoxyl group or hydrogen atom). These PDA coatings with enhanced UV absorption demonstrate great promise for applications in UV protection, antibacterial activity, wound healing and dye degradation.

Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Eumelanin-like Poly(levodopa) Nanoscavengers for Inflammation Disease Therapy.

In the current years, polydopamine nanoparticles (PDA NPs) have been extensively investigated as an eumelanin mimic. However, unlike natural eumelanin, PDA NPs contain no 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-derived units and may be limited in certain intrinsic properties; superior eumelanin-like nanomaterials are still actively being sought. Levodopa (l-DOPA) is a natural eumelanin precursor and expected to convert into DHICA and further remain within the final product through covalent or physical interactions. Herein, poly(levodopa) nanoparticles [P(l-DOPA) NPs] were synthesized with the assistance of zinc oxide as a supplement to synthetic eumelanin. This study found that P(l-DOPA) NPs had ∼90% DHICA-derived subunits on their surface and exhibited superior antioxidant activity compared to PDA NPs due to their looser polymeric microstructure. Benefitting from a stronger ROS scavenging ability, P(l-DOPA) NPs outperformed PDA NPs in treating cellular oxidative stress and acute inflammation. This research opens up new possibilities for the development and application of novel melanin-like materials.

Functional Polyphenol-Based Nanoparticles Boosted the Neuroprotective Effect of Riluzole for Acute Spinal Cord Injury.

Riluzole is commonly used as a neuroprotective agent for treating traumatic spinal cord injury (SCI), which works by blocking the influx of sodium and calcium ions and reducing glutamate activity. However, its clinical application is limited because of its poor solubility, short half-life, potential organ toxicity, and insufficient bioabilities toward upregulated inflammation and oxidative stress levels. To address this issue, epigallocatechin gallate (EGCG), a natural polyphenol, was employed to fabricate nanoparticles (NPs) with riluzole to enhance the neuroprotective effects. The resulting NPs demonstrated good biocompatibility, excellent antioxidative properties, and promising regulation effects from the M1 to M2 macrophages. Furthermore, an in vivo SCI model was successfully established, and NPs could be obviously aggregated at the SCI site. More interestingly, excellent neuroprotective properties of NPs through regulating the levels of oxidative stress, inflammation, and ion channels could be fully demonstrated in vivo by RNA sequencing and sophisticated biochemistry evaluations. Together, the work provided new opportunities toward the design and fabrication of robust and multifunctional NPs for oxidative stress and inflammation-related diseases via biological integration of natural polyphenols and small-molecule drugs.

Predictions of Aeroengines' Infrared Radiation Characteristics Based on HKELM Optimized by the Improved Dung Beetle Optimizer.

To solve the problems of high computational cost and the long time required by the simulation and calculation of aeroengines' exhaust systems, a method of predicting the characteristics of infrared radiation based on the hybrid kernel extreme learning machine (HKELM) optimized by the improved dung beetle optimizer (IDBO) was proposed. Firstly, the Levy flight strategy and variable spiral strategy were introduced to improve the optimization performance of the dung beetle optimizer (DBO) algorithm. Secondly, the superiority of IDBO algorithm was verified by using 23 benchmark functions. In addition, the Wilcoxon signed-rank test was applied to evaluate the experimental results, which proved the superiority of the IDBO algorithm over other current prominent metaheuristic algorithms. Finally, the hyperparameters of HKELM were optimized by the IDBO algorithm, and the IDBO-HKELM model was applied to the prediction of characteristics of infrared radiation of a typical axisymmetric nozzle. The results showed that the RMSE and MAE of the IDBO-HKELM model were 20.64 and 8.83, respectively, which verified the high accuracy and feasibility of the proposed method for predictions of aeroengines' infrared radiation characteristics.

Spatial representation of multidimensional information in emotional faces revealed by fMRI.

Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces.

Mechanically Controlled Enzymatic Polymerization and Remodeling.

In nature, proteins possess the remarkable ability to sense and respond to mechanical forces, thereby triggering various biological events, such as bone remodeling and muscle regeneration. However, in synthetic systems, harnessing the mechanical force to induce material growth still remains a challenge. In this study, we aimed to utilize low-frequency ultrasound (US) to activate horseradish peroxidase (HRP) and catalyze free radical polymerization. Our findings demonstrate the efficacy of this mechano-enzymatic chemistry in rapidly remodeling the properties of materials through cross-linking polymerization and surface coating. The resulting samples exhibited a significant enhancement in tensile strength, elongation, and Young's modulus. Moreover, the hydrophobicity of the surface could be completely switched within just 30 min of US treatment. This work presents a novel approach for incorporating mechanical sensing and rapid remodeling capabilities into materials.

Clinical effect of roxadustat vs. erythropoietin in non-dialysis CKD with diabetes: a single center propensity score matching analysis.

PURPOSE: Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. METHODS: Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4 weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). RESULTS: After 4, 12, and 24 weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5 g/L, 104 g/L, and 106.5 g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91 g/L, 94.5 g/L, and 94.5 g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. CONCLUSION: In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels.

Analysis of resistance risk and mechanism of the 14α-demethylation inhibitor ipconazole in Fusarium pseudograminearum.

Ipconazole is a broad-spectrum triazole fungicide that is highly effective against Fusarium pseudograminearum. However, its risk of developing resistance and mechanism are not well understood in F. pseudograminearum. Here, the sensitivities of 101 F. pseudograminearum isolates to ipconazole were investigated, and the average EC50 value was 0.1072 µg/mL. Seven mutants resistant to ipconazole were obtained by fungicide adaption, with all but one showing reduced fitness relative to the parental isolates. Cross-resistance was found between ipconazole and mefentrifluconazole and tebuconazole, but none between ipconazole and pydiflumetofen, carbendazim, fludioxonil, or phenamacril. In summary, these findings suggest that there is a low risk of F. pseudograminearum developing resistance to ipconazole. Additionally, a point mutation, G464S, was seen in FpCYP51B and overexpression of FpCYP51A, FpCYP51B and FpCYP51C was observed in ipconazole-resistant mutants. Assays, including transformation and molecular docking, indicated that G464S conferred ipconazole resistance in F. pseudograminearum.

Resistance risk, resistance mechanism and the effect on DON production of a new SDHI fungicide cyclobutrifluram in Fusarium graminearum.

Fusarium head blight in wheat is caused by Fusarium graminearum, resulting in significant yield losses and grain contamination with deoxynivalenol (DON), which poses a potential threat to animal health. Cyclobutrifluram, a newly developed succinate dehydrogenase inhibitor, has shown excellent inhibition of Fusarium spp. However, the resistance risk of F. graminearum to cyclobutrifluram and the molecular mechanism of resistance have not been determined. In this study, we established the average EC50 of a range of F. graminearum isolates to cyclobutrifluram to be 0.0110 µg/mL. Six cyclobutrifluram-resistant mutants were obtained using fungicide adaptation. All mutants exhibited impaired fitness relative to their parental isolates. This was evident from measurements of mycelial growth, conidiation, conidial germination, virulence, and DON production. Interestingly, cyclobutrifluram did not seem to affect the DON production of either the sensitive isolates or the resistant mutants. Furthermore, a positive cross-resistance was observed between cyclobutrifluram and pydiflumetofen. These findings suggest that F. graminearum carries a moderate to high risk of developing resistance to cyclobutrifluram. Additionally, point mutations H248Y in FgSdhB and A73V in FgSdhC1 of F. graminearum were observed in the cyclobutrifluram-resistant mutants. Finally, an overexpression transformation assay and molecular docking indicated that FgSdhBH248Y or FgSdhC1A73V could confer resistance of F. graminearum to cyclobutrifluram.

Polyphenolic Platform Ameliorated Sanshool for Skin Photoprotection.

Natural evolution has nurtured a series of active molecules that play vital roles in physiological systems, but their further applications have been severely limited by rapid deactivation, short cycle time, and potential toxicity after isolation. For instance, the instability of structures and properties has greatly descended when sanshool is derived from Zanthoxylum xanthoxylum. Herein, natural polyphenols are employed to boost the key properties of sanshool by fabricating a series of nanoparticles (NPs). The intracellular evaluation and in vivo animal model are conducted to demonstrate the decreased photodamage score and skin-fold thickness of prepared NPs, which can be attributed to the better biocompatibility, improved free radical scavenging, down-regulated apoptosis ratios, and reduced DNA double-strand breaks compared to naked sanshool. This work proposes a novel strategy to boost the key properties of naturally occurring active molecules with the assistance of natural polyphenol-based platforms.

Extraction of cellulose nanofibrils from pine sawdust by integrated chemical pretreatment.

Reducing energy consumption is major challenge in the industrialization of chemical pretreatments for the extraction of cellulose nanofibrils (CNF). In this study, an integrated chemical pretreatment with alkaline/acid-chlorite/TEMPO-oxidant was used for the nano-fibrillation of CNF from pine sawdust (WS). The alkaline and acid-chlorite pretreatments effectively eliminated the non-cellulosic components present in WS, resulting in the delamination of individual cell layers and swelling of the internal structures within the cellulose fiber bundles and cellulose microfibrils that form these layers. The spacing between CNF within the cellulose microfibrils increased from 3.7 nm to 5.5 nm. These loosely packed hierarchical structures facilitated the penetration of the reagent, which led to an increase in the specific surface area during the TEMPO-oxidant reaction and consequently accelerated the reaction rate. The WS was pretreated in a very dilute solution (1 % NaOH and 0.5 % NaClO2) under mild conditions (70 °C for 1 h), which resulted in a significant reduction of the TEMPO reaction time (from 3 h to 30 min) and a lower consumption of the reaction reagent (one fourth of the amount consumed compared to the direct oxidation of WS to achieve the same degree of cellulose nano-fibrillation).

Solvent-Exchange Triggered Solidification of Peptide/POM Coacervates for Enhancing the On-Site Underwater Adhesion.

Peptide-based biomimetic underwater adhesives are emerging candidates for understanding the adhesion mechanism of natural proteins secreted by sessile organisms. However, there is a grand challenge in the functional recapitulation of the on-site interfacial spreading, adhesion and spontaneous solidification of native proteins in water using peptide adhesives without applied compressing pressure. Here, a solvent-exchange strategy was utilized to exert the underwater injection, on-site spreading, adhesion and sequential solidification of a series of peptide/polyoxometalate coacervates. The coacervates were first prepared in a mixed solution of water and organic solvents by rationally suppressing the non-covalent interactions. After switching to a water environment, the solvent exchange between bulk water and the organic solvent embedded in the matrix of the peptide/polyoxometalate coacervates recovered the hydrophobic effect by increasing the dielectric constant, resulting in a phase transition from soft coacervates to hard solid with enhanced bulk cohesion and thus compelling underwater adhesive performance. The key to this approach is the introduction of suitable organic solvents, which facilitate the control of the intermolecular interactions and the cross-linking density of the peptide/polyoxometalate adhesives in the course of solidification under the water line. The solvent-exchange method displays fascinating universality and compatibility with different peptide segments.

Natural polyphenolic antibacterial bio-adhesives for infected wound healing.

Bio-adhesives used clinically, commonly have the ability to fill surgical voids and support wound healing, but which are devoid of antibacterial activity, and thus, could not meet the particular needs of the infected wound site. Herein, a series of natural polyphenolic antibacterial bio-adhesives were prepared via simple mixing and heating of polyphenols and acid anhydrides without any solvent or catalyst. Upon the acid anhydride ring opening and acylation reactions, various natural polyphenolic bio-adhesives could adhere to various substrates (i.e., tissue, wood, glass, rubber, paper, plastic, and metal) based on multi-interactions. Moreover, these bio-adhesives showed excellent antibacterial and anti-infection activity, rapid hemostatic performance and appropriate biodegradability, which could be widely used in promoting bacterial infection wound healing and hot burn infection wound repair. This work could provide a new strategy for strong adhesives using naturally occurring molecules, and provide a method for the preparation of novel multifunctional wound dressings for infected wound healing.

Waste Tea-Derived Theabrownins for Solar-Driven Steam Generation.

Solar-driven seawater desalination has been considered an effective and sustainable solution to mitigate the global freshwater crisis. However, the substantial cost associated with photothermal materials for evaporator fabrication still hinders large-scale manufacturing for practical applications. Herein, we successfully obtained high yields of theabrownins (TB), which were oxidation polymerization products of polyphenols from waste and inferior tea leaves using a liquid-state fermentation strategy. Subsequently, a series of photothermal complexes were prepared based on the metal-phenolic networks assembled from TB and metal ions (Fe(III), Cu(II), Ni(II), and Zn(II)). Also, the screened TB@Fe(III) complexes were directly coated on a hydrophilic poly(vinylidene fluoride) (PVDF) membrane to construct the solar evaporation device (TB@Fe(III)@PVDF), which not only demonstrated superior light absorption property and notable hydrophilicity but also achieved a high water evaporation rate of 1.59 kg m-2 h-1 and a steam generation efficiency of 90% under 1 sun irradiation. More importantly, its long-term stability and exceptionally low production cost enabled an important step toward the possibility of large-scale practical applications. We believe that this study holds the potential to pave the way for the development of sustainable and cost-effective photothermal materials, offering new avenues for utilization of agriculture resource waste and solar-driven water remediation.