Phospholipid-Anchored Ligand Conjugation on Extracellular Vesicles for Enhanced Cancer Targeting.

Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.

Transcription factor ZmNAC19 promotes embryo development in Arabidopsis thaliana.

KEY MESSAGE: Overexpression of ZmNAC19, a NAC transcription factor gene from maize, improves embryo development in transgenic Arabidopsis. NAC proteins are plant-specific transcription factors that are involved in multiple aspects of plant growth, development and stress response. Although functions of many NAC transcription factors have been elucidated, little is known about their roles in seed development. In this study, we report the function of a maize NAC transcription factor ZmNAC19 in seed development. ZmNAC19 is highly expressed in embryos of developing maize seeds. ZmNAC19 localizes to nucleus and exhibits transactivation activity in yeast cells. Overexpression of ZmNAC19 in Arabidopsis significantly increases seed size and seed yield. During 3 to 7 days after flowering, embryos of ZmNAC19-overexpression Arabidopsis lines developed faster compared to Col-0, while no visible differences were detected for their endosperms. Furthermore, overexpression of ZmNAC19 in Arabidopsis leads to increased transcription levels of two embryo development-related genes YUC1 and RGE1, and several elements proven to be binding sites of NAC transcription factors were observed in promoters of these two genes. Taken together, these results suggest that ZmNAC19 acts as a positive regulator in plant embryo development.

Multi-stimuli-responsive actuator based on bilayered thermoplastic film.

Recently, soft actuators have attracted considerable interest owing to their biomimetic performance. Unfortunately, it remains a great challenge to fabricate multi-stimuli-responsive soft actuators by a facile but low-cost method. Herein, a thermoplastic film with bilayered architecture was designed and fabricated by a one-step method. This bilayered thermoplastic film can act as a soft actuator, demonstrating versatile shape-programmable performance in response to acetone vapor exposure and temperature change. Interestingly, diverse biomimetic devices including a worm-like self-walker, crawler-type robot and soft gripper can be realized, which highlights its promising applications in biomimetic robots, artificial muscles and automatic devices. Considering the one-step preparation process and the low-cost raw materials, this approach can be cost-effectively scaled up for practical production.

Light trapping transparent electrodes with a wide-angle response.

The angle dependent transmission of light trapping transparent electrodes is investigated. The electrodes consist of triangular metallic wire arrays embedded in a dielectric cover layer. Normal incidence illumination of the structure produces light trapping via total internal reflection, virtually eliminating all shadowing losses. It is found that varying the external angle of incidence can affect the light trapping efficiency ηLT due to partial loss of internal reflection and increased interaction with neighboring wires. Despite these effects, a judicious selection of geometry and materials can reduce shadowing losses by more than 85% over a surprisingly large angular range of 120°. It is demonstrated that the angle-averaged shadowing losses in an encapsulated silicon solar cell under illumination with unpolarized light can be reduced by more than a factor of two for incident angles between -60° and +60° off-normal across the entire AM1.5 solar spectrum.

Functions of PPR Proteins in Plant Growth and Development.

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.

Scale dependent performance of metallic light-trapping transparent electrodes.

The optical and electrical performance of light trapping metallic electrodes is investigated. Reflection losses from metallic contacts are shown to be dramatically reduced compared to standard metallic contacts by leveraging total internal reflection at the surface of an added dielectric cover layer. Triangular wire arrays are shown to exhibit increased performance with increasing size, whereas cylindrical wires continue to exhibit diffractive losses as their size is increased. These trends are successfully correlated with radiation patterns from individual metallic wires. Triangular metallic electrodes with a metal areal coverage of 25% are shown to enable a polarization-averaged transmittance of >90% across the wavelength range 0.46-1.1 µm for an electrode width of 2 µm, with a peak transmission of 97%, a degree of polarization of <0.2%, and a sheet resistance of 0.35 Ω/sq. A new figure of merit is introduced to evaluate the light trapping potential of surface-shaped electrodes.

Analysis of factors influencing the trajectory of fatigue in maintenance haemodialysis patients: a longitudinal study.

OBJECTIVE: To explore the potential categories and influencing factors of fatigue trajectory in maintenance haemodialysis patients. METHODS: Between June 2023 and December 2023, a convenience sample of 306 maintenance haemodialysis patients in a tertiary hospital haemodialysis centre in Zhenjiang City was selected as the study population, and patient information was collected monthly after the baseline survey using the General Information Questionnaire, Pittsburgh Sleep Quality Scale, Piper Fatigue Revision Scale, Collaborative Social Support Scale, Patient Health Questionnaire Depression Scale, Comprehensive Economic Toxicity Rating Scale, and Fear of Disease Progression Simplified Scale, for a total of six follow-up visits. In addition, the potential category growth model was used to identify the developmental trajectory of fatigue, and univariate analysis and binary logistic regression were used to analyse its determinants. RESULTS: The 6 month fatigue trajectory of maintenance haemodialysis patients could be divided into two categories: persistent low-fatigue group (59.8%) and fluctuating high-fatigue group (40.2%). Age, surgical history, level of social support, sleep, economic toxicity, and changes in ultrafiltration volume during dialysis were the influencing factors for repeated fatigue in maintenance haemodialysis patients (p < 0.05). CONCLUSION: The fatigue trajectory of maintenance haemodialysis patients is heterogeneous, suggesting that clinical workers should focus on the haemodialysis patients with repeated fatigue and make targeted interventions to improve their fatigue status and reduce the occurrence of adverse events in patients.

Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.

Liquid crystal-mediated self-assembly of copper nanoclusters with induced circular dichroism and amplified circularly polarized luminescence.

Elucidating the mechanism of chiral transfer is key to regulating chiral expression and generalizing the structure-property relationship of chiral functional systems. However, it is still an important challenge to select novel building blocks to achieve chiral induction, chiral transfer and chiral modulation. Liquid crystals (LCs) can be considered as promising smart soft materials due to their responsiveness and adaptability. Confining chiral metal nanoclusters (NCs) in an achiral LC phase to construct chiral LCs provides an expanded strategy for the self-assembly of chiral metal NCs in different matrices. Herein, chiral glutathione-stabilized copper NCs (G-SH-Cu NCs)/polyoxyethylene tert-octylphenyl ether (TX-100) LCs were constructed and systematically investigated. The results showed that the introduction of G-SH-Cu NCs into TX-100 LCs induced the generation of supramolecular chirality. More interestingly, the circular dichroism (CD) handedness can be controlled by changing the amount of TX-100 or G-SH-Cu NCs; when the ratio of G-SH-Cu NCs and TX-100 was proportionally matched, the strength of the noncovalent interactions was sufficient to induce chiral inversion. Meanwhile, TX-100 LCs provide effective confinement of G-SH-Cu NCs, which improves the expression of asymmetry at the aggregation level and induces a 2-fold enhancement of the circularly polarized luminescence (CPL) signal. This work realizes the spatial amplification of chirality through dopants in LCs, which provides an effective method for accurately regulating the supramolecular chirality of metal NCs in the LC phase.

Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol's mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1ß, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1ß, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

In Vitro Antibacterial and Anti-Inflammatory Properties of Imidazolium Poly(ionic liquids) Microspheres Loaded in GelMA-PEG Hydrogels.

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

Supporting Expressive and Faithful Pictorial Visualization Design with Visual Style Transfer.

Pictorial visualizations portray data with figurative messages and approximate the audience to the visualization. Previous research on pictorial visualizations has developed authoring tools or generation systems, but their methods are restricted to specific visualization types and templates. Instead, we propose to augment pictorial visualization authoring with visual style transfer, enabling a more extensible approach to visualization design. To explore this, our work presents Vistylist, a design support tool that disentangles the visual style of a source pictorial visualization from its content and transfers the visual style to one or more intended pictorial visualizations. We evaluated Vistylist through a survey of example pictorial visualizations, a controlled user study, and a series of expert interviews. The results of our evaluation indicated that Vistylist is useful for creating expressive and faithful pictorial visualizations.

Erato: Cooperative Data Story Editing via Fact Interpolation.

As an effective form of narrative visualization, visual data stories are widely used in data-driven storytelling to communicate complex insights and support data understanding. Although important, they are difficult to create, as a variety of interdisciplinary skills, such as data analysis and design, are required. In this work, we introduce Erato, a human-machine cooperative data story editing system, which allows users to generate insightful and fluent data stories together with the computer. Specifically, Erato only requires a number of keyframes provided by the user to briefly describe the topic and structure of a data story. Meanwhile, our system leverages a novel interpolation algorithm to help users insert intermediate frames between the keyframes to smooth the transition. We evaluated the effectiveness and usefulness of the Erato system via a series of evaluations including a Turing test, a controlled user study, a performance validation, and interviews with three expert users. The evaluation results showed that the proposed interpolation technique was able to generate coherent story content and help users create data stories more efficiently.

Slippery lubricant-infused silica nanoparticulate film processing for anti-biofouling applications.

Microbial biofilm build-up in water distribution systems can pose a risk to human health and pipe material integrity. The impact is more devastating in space stations and to astronauts due to the isolation from necessary replacement parts and medical resources. As a result, there is a need for coatings to be implemented onto the inner region of the pipe to minimize the adherence and growth of biofilms. Lubricant-infused surfaces has been one such interesting material for anti-biofouling applications in which their slippery property promotes repellence to many liquids and thus prevents bacterial adherence. Textured and porous films are suitable substrate candidates to infuse and contain the lubricant. However, there is little investigation in utilizing a nanoparticulate thin film as the substrate material for lubricant infusion. A nanoparticulate film has high porosity within the structure which can promote greater lubricant infusion and retention. The implementation as a thin film structure aids to reduce material consumption and cost. In our study, we utilized a well-studied nanoporous thin film fabricated via layer-by-layer assembly of polycations and colloid silica and then calcination for greater stability. The film was further functionalized to promote fluorinated groups and improve affinity with a fluorinated lubricant. The pristine nanoporous film was characterized to determine its morphology, thickness, wettability, and porosity. The lubricant-infused film was then tested for its lubricant layer stability upon various washing conditions and its performance against bacterial biofilm adherence as a result of its slippery property. Overall, the modified silica nanoparticulate thin film demonstrated potential as a base substrate for lubricant-infused surface fabrication that repelled against ambient aqueous solvents and as an anti-biofouling coating that demonstrated low biofilm coverage and colony forming unit values. Further optimization to improve lubricant retention or incorporation of a secondary function can aid in developing better coatings for biofilm mitigation.

Sample Size Effects on Petrophysical Characterization and Fluid-to-Pore Accessibility of Natural Rocks.

Laboratory-scale analysis of natural rocks provides petrophysical properties such as density, porosity, pore diameter/pore-throat diameter distribution, and fluid accessibility, in addition to the size and shape of framework grains and their contact relationship with the rock matrix. Different types of laboratory approaches for petrophysical characterization involve the use of a range of sample sizes. While the sample sizes selected should aim to be representative of the rock body, there are inherent limitations imposed by the analytical principles and holding capacities of the different experimental apparatuses, with many instruments only able to accept samples at the µm-mm scale. Therefore, a total of nine (three limestones, three shales, two sandstones, and one dolomite) samples were collected from Texas to fill the knowledge gap of the sample size effect on the resultant petrophysical characteristics. The sample sizes ranged from 3 cm cubes to <75 µm particles. Using a combination of petrographic microscopy, helium expansion pycnometry, water immersion porosimetry, mercury intrusion porosimetry, and (ultra-) small-angle X-ray scattering, the impact of sample size on the petrophysical properties of these samples was systematically investigated here. The results suggest that the sample size effect is influenced by both pore structure changes during crushing and sample size-dependent fluid-to-pore connectivity.

Environmental factors influencing potential distribution of Schisandra sphenanthera and its accumulation of medicinal components.

Schisandrae Sphenantherae Fructus (SSF), the dry ripe fruit of Schisandra sphenanthera Rehd. et Wils., is a traditional Chinese medicine with wide application potential. The quality of SSF indicated by the composition and contents of secondary metabolites is closely related to environmental factors, such as regional climate and soil conditions. The aims of this study were to predict the distribution patterns of potentially suitable areas for S. sphenanthera in China and pinpoint the major environmental factors influencing its accumulation of medicinal components. An optimized maximum entropy model was developed and applied under current and future climate scenarios (SSP1-RCP2.6, SSP3-RCP7, and SSP5-RCP8.5). Results show that the total suitable areas for S. sphenanthera (179.58×104 km2) cover 18.71% of China's territory under the current climatic conditions (1981-2010). Poorly, moderately, and highly suitable areas are 119.00×104 km2, 49.61×104 km2, and 10.98×104 km2, respectively. The potentially suitable areas for S. sphenanthera are predicted to shrink and shift westward under the future climatic conditions (2041-2070 and 2071-2100). The areas of low climate impact are located in southern Shaanxi, northwestern Guizhou, southeastern Chongqing, and western Hubei Provinces (or Municipality), which exhibit stable and high suitability under different climate scenarios. The contents of volatile oils, lignans, and polysaccharides in SSF are correlated with various environmental factors. The accumulation of major secondary metabolites is primarily influenced by temperature variation, seasonal precipitation, and annual precipitation. This study depicts the potential distribution of S. sphenanthera in China and its spatial change in the future. Our findings decipher the influence of habitat environment on the geographical distribution and medicinal quality of S. sphenanthera, which could have great implications for natural resource conservation and artificial cultivation.

Influence of different factors on registration error in a 1.5 T MR-guided linac.

Purpose. Accurate image registration is an important step in online image-guided adaptive radiotherapy. The aim of this study was to investigate the effects of different factors on registration accuracy in a magnetic resonance (MR)-guided adaptive radiotherapy workflow.Materials and Methods. A thorax motion phantom was used to obtain computed tomography (CT) simulations in 8 different motion modes and to generate 8 reference plans. Daily pretreatment online MR images were obtained at 5 different positions in each reference plan. Online MR and CT simulations were separately registered using bone structures and the gross tumor volume (GTV) as ROIs, and the image shift distance was recorded by the online treatment planning system. The difference between the shift distance and the real isocentric distance was the registration error. The registration error was analyzed, and the effects of the setup position, motion mode and ROI selection on the registration error were investigated by multivariate analysis of variance.Result. The minimum values of registration error (ΔX, ΔY, ΔZ) were -1.90 mm, -2.70 mm and -2.40 mm, respectively, and the maximum values were 1.70 mm, 4.30 mm and -0.90 mm. ΔY showed the maximum mean standard deviation of 1.25 mm, and ΔZshowed the minimum mean standard deviation of 0.27 mm. The standard deviation of the registration error is largest in the inferior/superior direction. The motion mode of the phantom and ROI selection were significantly correlated with ΔX, ΔY, and ΔZ(p< 0.05).Conclusion. The registration result with the spine as the selected ROI was better than that with the GTV as the ROI. In 1.5 T MR-linac clinical treatment, more attention should be given to patient movement repeatability and to controlling the intrafractional motion as much as possible. It is not recommended to make the GTV-PTV margin expansion less than 2 mm for MR-linac.

BiFeO3 photocathodes for efficient H2O2 production via charge carrier dynamics engineering.

Metal oxide semiconductors are promising candidate photoelectrodes for photoelectrochemical H2O2 production if the issues of poor efficiency and selectivity can be resolved. An unfavorable charge transport barrier causes poor carrier collection and kinetics, limiting their efficiency and selectivity. Herein, BiFeO3 was used as the model photocathode, and its interfacial charge transport barrier between fluorine-doped tin oxide substrates was modulated by introducing a LaNiO3 layer as the charge collection layer. Our findings show the significantly enhanced photoelectrochemical activity of the composite photocathode with an improved photocurrent by three times (-0.9 mA cm-2 at 0.6 V vs. RHE) and the H2O2 formation up to 278 µmol L-1 with doubled faradaic efficiency. It is shown that these enhancements are due to the promoted charge carrier collection and kinetics. This work demonstrates the significant role of the charge collection layer in improving the collection and usage of photocarriers to accelerate the application of solar-to-fuel conversion.

Tuning the Ferroelectric Phase Transition of P(VDF-TrFE) through a Simple Approach of Modification by Introducing Double Bonds.

Electroactive polymer (EAP) is a kind of intelligent material that, driven by external electric field, could produce changes in shape or volume. As an important class of EAP materials, poly(vinylidene fluoride) (PVDF) based relaxor ferroelectric polymers show remarkable potential for applications in sensors, actuator, and artificial muscles because of their excellent electrostrictive properties. However, the strain of PVDF-based relaxor ferroelectrics relies strongly on a high electric field, which seriously damages their reliability and limits their practical applications as wearable devices. To explore more suitable materials for actuator applications, in this present work, we report the influences of a double bond (DB) on the electroactive properties of P(VDF-TrFE) (TrFE: trifluoroethylene). The crystalline phase of P(VDF-TrFE) is partially destroyed after the DB is introduced, and the molecular chain flexibility of the product P(VDF-TrFE-DB) can be greatly improved. Therefore, P(VDF-TrFE-DB) has a larger electric displacement while having a lower dipole orientation electric field compared with that of P(VDF-TrFE). The result confirms that the DB could tune the ferroelectric properties and effectively reduce the driving electric field of the PVDF-based relaxor ferroelectric polymers. This work offers a strategy for the preparation of novel EAPs with low driving electric fields.

Dhh signaling pathway regulates reconstruction of seminiferous tubule-like structure.

The reconstruction of a tubule-like structure in vitro has provided a promising system to analyze factors that drive morphogenesis and the underlying mechanisms. In this study, we took advantage of the inhibitor cyclopamine and a smoothened agonist to detect the role of the Dhh signaling pathway in the reconstructed tubule-like structure. Sertoli cells did not show polarity, rounded peritubular myoid cells and scattered Leydig cells were observed, combined with less laminin and lower proliferation of Leydig, peritubular myoid, germ, and Sertoli cells. However, in the presence of SAG, elongated peritubular myoid cells gathered at the bottom of polarized Sertoli cells, and most of the Leydig cells gathered at the outer part of the elongated peritubular myoid cells. Moreover, SAG promoted the secretion of laminin, assisting in the formation of the basal membrane and promoting the proliferation of Leydig, peritubular myoid, and germ cells. The level of Gli1 was significantly downregulated when treated with cyclopamine, whereas it was significantly upregulated when treated with SAG. These results indicate that the Dhh signaling pathway regulates the reconstruction of tubule-like structures by regulating the expression of Gli1.