Litoamentenes A-K, eleven undescribed cembranoids with cytotoxicity from the South China Sea soft coral Litophyton amentaceum.

Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.

Boosting Enzyme Activity in Enzyme Metal-Organic Framework Composites.

Enzymes, as highly efficient biocatalysts, excel in catalyzing diverse reactions with exceptional activity and selective properties under mild conditions. Nonetheless, their broad applications are hindered by their inherent fragility, including low thermal stability, limited pH tolerance, and sensitivity to organic solvents and denaturants. Encapsulating enzymes within metal-organic frameworks (MOFs) can protect them from denaturation in these harsh environments. However, this often leads to a compromised enzyme activity. In recent years, extensive research efforts have been dedicated to enhancing enzymatic activity within MOFs, leading to the development of new enzyme-MOF composites that not only preserve their catalytic potential but also outperform their free counterparts. This Review provides a comprehensive review on recent developments in enzyme-MOF composites with a specific emphasis on their enhanced enzymatic activity compared to free enzymes.

Psychological interventions for depression in children and adolescents: A bibliometric analysis.

BACKGROUND: Depression has gradually become a common psychological disorder among children and adolescents. Depression in children and adolescents affects their physical and mental development. Psychotherapy is considered to be one of the main treatment options for depressed children and adolescents. However, our understanding of the global performance and progress of psychological interventions for depression in children and adolescents (PIDCA) research is limited. AIM: To identify collaborative research networks in this field and explore the current research status and hotspots through bibliometrics. METHODS: Articles and reviews related to PIDCA from January 2010 to April 2023 were identified from the Web of Science Core Collection database. The Charticulator website, CiteSpace and VOSviewer software were used to visualize the trends in publications and citations, the collaborative research networks (countries, institutions, and authors), and the current research status and hotspots. RESULTS: Until April 16, 2023, 1482 publications were identified. The number of documents published each year and citations had increased rapidly in this field. The United States had the highest productivity in this field. The most prolific institution was the University of London. Pim Cuijpers was the most prolific author. In the context of research related to PIDCA, both reference co-citation analysis and keywords co-occurrence analysis identified 10 research hotspots, including third-wave cognitive behavior therapy, short-term psychoanalytic psychotherapy, cognitive behavioral analysis system of psychotherapy, family element in psychotherapy, modular treatment, mobile-health, emotion-regulation-based transdiagnostic intervention program, dementia risk in later life, predictors of the efficacy of psychological intervention, and risks of psychological intervention. CONCLUSION: This bibliometric study provides a comprehensive overview of PIDCA from 2010 to present. Psychological intervention characterized as psychological-process-focused, short, family-involved, modular, internet-based, emotion-regulation-based, and personalized may benefit more young people.

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy.

T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro. Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions. Due to their vast clinical utility, aAPCs have been employed as an off-the-shelf technology for T cell activation in FDA-approved ACTs, and the development of aAPCs is constantly advancing with the emergence of aAPCs with more sophisticated designs and additional functionalities. Here, we review the recent advancements in particle-based aAPCs for T cell activation in ACTs. Following a brief introduction, we first describe the manufacturing processes of ACT products. Next, the design and synthetic strategies for micro- and nanoparticle-based aAPCs are discussed separately to emphasize their features, advantages, and limitations. Then, the impact of design parameters of aAPCs, such as size, shape, ligand density/mobility, and stiffness, on their functionality and biomedical performance is explored to provide deeper insights into the design concepts and principles for more efficient and safer aAPCs. The review concludes by discussing current challenges and proposing future perspectives for the development of more advanced aAPCs.

Identification of Treg-related prognostic molecular subtypes and individualized characteristics in clear cell renal cell carcinoma through single-cell transcriptomes and bulk RNA sequencing.

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored. METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies. RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy. CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.

Ligand Phase Separation-Promoted, "Squeezing-Out" Mode Explaining the Mechanism and Implications of Neutral Nanoparticles That Escaped from Lysosomes.

Neutral nanomaterials functionalized with PEG or similar molecules have been popularly employed as nanomedicines. Compared to positive counterparts that are capable of harnessing the well-known proton sponge effect to facilitate their escape from lysosomes, it is yet unclear how neutral substances got their entry into the cytosol. In this study, by taking PEGylated, neutral Au nanospheres as an example, we systematically investigated their time-dependent translocation postuptake. Specifically, we harnessed dissipative particle dynamics simulations to uncover how nanospheres bypass lysosomal entrapment, wherein a mechanism termed as "squeezing-out" mode was discovered. We next conducted a comprehensive investigation on how nanomaterials implicate lysosomes in terms of integrity and functionality. By using single-molecule imaging, specific preservation of PEG-terminated with targeting moieties in lysosomes supports the "squeezing-out" mode as the mechanism underlying the lysosomal escape of nanomaterials. All evidence points out that such a process is benign to lysosomes, wherein the escape of nanomaterials proceeds at the expense of targeting moieties loss. Furthermore, we proved that by fine-tuning of the efficacy of nanomaterials escaping from lysosomes, modulation of distinct pathways and metabolic machinery can be achieved readily, thereby offering us a simple and robust tool to implicate cells.

A Generalized Polymer Precursor Ink Design for 3D Printing of Functional Metal Oxides.

Three-dimensional-structured metal oxides have myriad applications for optoelectronic devices. Comparing to conventional lithography-based manufacturing methods which face significant challenges for 3D device architectures, additive manufacturing approaches such as direct ink writing offer convenient, on-demand manufacturing of 3D oxides with high resolutions down to sub-micrometer scales. However, the lack of a universal ink design strategy greatly limits the choices of printable oxides. Here, a universal, facile synthetic strategy is developed for direct ink writable polymer precursor inks based on metal-polymer coordination effect. Specifically, polyethyleneimine functionalized by ethylenediaminetetraacetic acid is employed as the polymer matrix for adsorbing targeted metal ions. Next, glucose is introduced as a crosslinker for endowing the polymer precursor inks with a thermosetting property required for 3D printing via the Maillard reaction. For demonstrations, binary (i.e., ZnO, CuO, In2O3, Ga2O3, TiO2, and Y2O3) and ternary metal oxides (i.e., BaTiO3 and SrTiO3) are printed into 3D architectures with sub-micrometer resolution by extruding the inks through ultrafine nozzles. Upon thermal crosslinking and pyrolysis, the 3D microarchitectures with woodpile geometries exhibit strong light-matter coupling in the mid-infrared region. The design strategy for printable inks opens a new pathway toward 3D-printed optoelectronic devices based on functional oxides.

Granular Ionogel Particle Inks for 3D Printed Tough and Stretchable Ionotronics.

Ionogels have garnered great attention as promising soft conducting materials for the fabrication of flexible energy storage devices, soft actuators, and ionotronics. However, the leakage of the ionic liquids, weak mechanical strength, and poor manufacturability have greatly limited their reliability and applications. Here, we propose a new ionogel synthesis strategy by utilizing granular zwitterionic microparticles to stabilize ionic liquids. The ionic liquids swell the microparticles and physically crosslink microparticles via either electronic interaction or hydrogen bonding. Further introducing a photocurable acrylic monomer enables the fabrication of double-network (DN) ionogels with high stretchability (>600%) and ultrahigh toughness (fracture energy > 10 kJ/m2). The synthesized ionogels exhibit a wide working temperature of -60 to 90 °C. By tuning the crosslinking density of microparticles and physical crosslinking strength of ionogels, we synthesize DN ionogel inks and print them into three-dimensional (3D) motifs. Several ionogel-based ionotronics are 3D printed as demonstrations, including strain gauges, humidity sensors, and ionic skins made of capacitive touch sensor arrays. Via covalently linking ionogels with silicone elastomers, we integrate the ionogel sensors onto pneumatic soft actuators and demonstrate their capacities in sensing large deformation. As our last demonstration, multimaterial direct ink writing is harnessed to fabricate highly stretchable and durable alternating-current electroluminescent devices with arbitrary structures. Our printable granular ionogel ink represents a versatile platform for the future manufacturing of ionotronics.

Nanoparticle elasticity regulates the formation of cell membrane-coated nanoparticles and their nano-bio interactions.

Cell membrane-coated nanoparticles are emerging as a new type of promising nanomaterials for immune evasion and targeted delivery. An underlying premise is that the unique biological functions of natural cell membranes can be conferred on the inherent physiochemical properties of nanoparticles by coating them with a cell membrane. However, the extent to which the membrane protein properties are preserved on these nanoparticles and the consequent bio-nano interactions are largely unexplored. Here, we synthesized two mesenchymal stem cell (MSC) membrane-coated silica nanoparticles (MCSNs), which have similar sizes but distinctly different stiffness values (MPa and GPa). Unexpectedly, a much lower macrophage uptake, but much higher cancer cell uptake, was found with the soft MCSNs compared with the stiff MCSNs. Intriguingly, we discovered that the soft MCSNs enabled the forming of a more protein-rich membrane coating and that coating had a high content of the MSC chemokine CXCR4 and MSC surface marker CD90. This led to the soft MCSNs enhancing cancer cell uptake mediated by the CD90/integrin receptor-mediated pathway and CXCR4/SDF-1 pathways. These findings provide a major step forward in our fundamental understanding of how the combination of nanoparticle elasticity and membrane coating may be used to facilitate bio-nano interactions and pave the way forward in the development of more effective cancer nanomedicines.

[A child suffering from severe acute respiratory distress syndrome due to multiple trauma was treated with veno-veous extracorporeal membrane oxygenation with the dual lumen cannula: a case report].

Veno-veous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in the treatment for severe acute respiratory distress syndrome (ARDS). Up to now, the routine access to establish VV-ECMO involves two-sites single lumen cannula via femoral vein and internal jugular venous in adult and children, while few studies about the dual lumen cannula (DLC) in VV-ECMO implemented in adult and children have been reported. On December 16, 2021, an unconscious child with severe ARDS due to multiple trauma caused by fatal falling from a height was admitted to Taihe Hospital. The initial diagnosis was hemorrhagic shock, bilateral hemopneumothorax, sternal fracture, cavity organ perforation, splenic rupture, and pelvic fracture and severe ARDS. Despite mechanical ventilation, he progressed to refractory hypoxemia and was treated with VV-ECMO after successful DLC placement in the right internal jugular vein by the mobile ECMO team of intensive care unit of the Union Hospital eventually. In addition, he received endoscopic sputum aspiration, prone position ventilation, anti-infection and nutritional treatment. His oxygenation gradually improved and he was successfully weaned from ECMO after 11 days. In this case, DLC simplified the process without any related complications, suggesting that it can be safely and effectively used in the treatment of Child's severe ARDS.

3D-Printable Cellular Composites for the Production of Recombinant Proteins.

The incorporation of living cells into materials promises both significant challenges and new possibilities. Although recent years have seen important advances in this field, there is still much to be learned about engineering interfaces between cells and materials. Here, we present a new class of 3D-printable materials, based on poly(N-hydroxymethylacrylamide) (PNHMAA), in which the spore-forming bacterium Bacillus subtilis is effectively cross-linked into the surrounding polymeric scaffold. After dehydration and subsequent re-swelling in nutrient-rich media, embedded cells and spores become metabolically active and are capable of heterologous protein production and secretion. Strikingly, the leak-free scaffold allows protein production while preventing escape of embedded cells. The successful construction of complex three-dimensional structures by stereolithographic printing of living PNHMAA composite materials suggests utility in a broad range of applications.

Stress-Tolerant, Recyclable, and Renewable Biocatalyst Platform Enabled by Engineered Bacterial Spores.

Here, we describe a stress-tolerant, recyclable, and renewable biocatalyst platform based on T7 RNA polymerase-enabled high-density protein display on bacterial spores (TIED). TIED uses high-level T7 RNA polymerase-driven expression of recombinant proteins specifically in sporulating cells to allow spontaneous assembly of recombinant fusion proteins on the Bacillus subtilis spore surface. TIED enables high loading density in the range of 106 to 107 recombinant enzymes per spore, robust catalytic activity of displayed enzymes comparable to the respective free enzymes, and enhanced kinetic stability of displayed enzymes in methanol and elevated temperatures. Furthermore, we demonstrate TIED enzymes to be not only recyclable but also fully renewable after the loss of activity through induction of germination and sporulation, enabling perpetual regeneration of these immobilized biocatalysts.

Microfluidic Nanoparticles for Drug Delivery.

Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial-scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented.

Influence of nanoparticle mechanical property on protein corona formation.

A protein corona forms around nanoparticles when they are intravenously injected into the bloodstream. The composition of the protein corona dictates the interactions between nanoparticles and the biological systems thus their immune evasion, blood circulation, and biodistribution. Here, we report for the first time the impact of nanoparticle stiffness on protein corona formation using a unique emulsion core silica shell nanocapsules library with a wide range of mechanical properties over four magnitudes (700 kPa to 10 GPa). The nanocapsules with different stiffness showed distinct proteomic fingerprints. The protein corona of the stiffest nanocapsules contained the highest amount of complement protein (Complement C3) and immunoglobulin proteins, which contributed to their high macrophage uptake, confirming the important role of nanocapsules stiffness in controlling the protein corona formation thus their in vitro and in vivo behaviors.

Colloidal oxide nanoparticle inks for micrometer-resolution additive manufacturing of three-dimensional gas sensors.

Micrometer-resolution 3D printing of functional oxides is of growing importance for the fabrication of micro-electromechanical systems (MEMSs) with customized 3D geometries. Compared to conventional microfabrication methods, additive manufacturing presents new opportunities for the low-cost, energy-saving, high-precision, and rapid manufacturing of electronics with complex 3D architectures. Despite these promises, methods for printable oxide inks are often hampered by challenges in achieving the printing resolution required by today's MEMS electronics and integration capabilities with various other electronic components. Here, a novel, facile ink design strategy is presented to overcome these challenges. Specifically, we first prepare a high-solid loading (∼78 wt%) colloidal suspension that contains polyethyleneimine (PEI)-coated stannic dioxide (SnO2) nanoparticles, followed by PEI desorption that is induced by nitric acid (HNO3) titration to optimize the rheological properties of the printable inks. Our achieved ∼3-5 µm printing resolution is at least an order of magnitude higher than those of other printed oxide studies employing nanoparticle ink-based printing methods demonstrated previously. Finally, various SnO2 structures were directly printed on a MEMS-based microelectrode for acetylene detection application. The gas sensitivity measurements reveal that the device performance is strongly dependent on the printed SnO2 structures. Specifically, the 3D structured SnO2 gas sensor exhibits the highest response of ∼ 29.9 to 100 ppm acetylene with the fastest total response time of ∼ 65.8 s. This work presents a general ink formulation and printing strategy for functional oxides, which further provides a pathway for the additive manufacturing of oxide-based MEMSs.

Mdm-MIR393b-mediated adventitious root formation by targeted regulation of MdTIR1A expression and weakened sensitivity to auxin in apple rootstock.

Adventitious root (AR) formation is of great significance for apple rootstock breeding. It is widely accepted that miR393 influences AR formation in many plant species; however, the molecular mechanism by which factors regulate AR formation remains insufficient. In this study, the evolutionary relationship of mdm-miR393 and candidate target genes MdTIR1/AFB was systematically identified, and the expression patterns were analysed. Multisequence alignment analysis of miR393 family members suggests that miR393 conservatively evolved between different species. The evolutionary relationship of the TIR1/AFBs can be divided into G1, G2 and G3 subgroups. During AR formation, the expression level of mdm-miR393a/b/c was significantly upregulated at 1 d and 7 d by exogenous auxin treatment. Furthermore, the expression levels of MdTIR1A, MdTIR1D, MdAFB1, MdAFB2, MdAFB3, MdAFB4 and MdAFB8 also appeared to be significantly changed by exogenous auxin induction. Subsequently, tissue-specific expression analysis showed that the expression levels of mdm-miR393 and MdTIR1/AFBs in different tissues exhibited significant differences. The promoter of mdm-miR393 contains multiple elements that respond to ABA, adversity and light signals; auxin treatment can activate the mdm-MIR393b promoter but is obviously inhibited by NPA treatment. The targeting relationship between mdm-MIR393b and MdTIR1A was verified by expression patterns, degradation group data, transient tobacco conversion results, and genes functions experiments. Heterologous overexpression of mdm-MIR393b (35S::mdm-MIR393b) decreased the number of ARs in the phenotype and reduced the expression level of the target gene NtTIR1 in tobacco. Compared to the wild type, the 35S::mdm-MIR393b transgenic plants demonstrated insensitivity to auxin. Furthermore, tir1 mutant exhibited reduced root system structure relative to the control. The above results illustrated that mdm-MIR393b is involved in mediating AR formation by targeted regulation of MdTIR1A expression in apple rootstock.

Facile bioinspired synthesis of iron oxide encapsulating silica nanocapsules.

Iron oxide nanoparticles have been extensively studied for a wide variety of applications. However, there remains a challenge in developing hierarchical magnetic iron oxide nanoparticles as existing synthetic techniques require harsh, toxic chemical conditions and high temperatures or give poorly defined product with weak magnetic properties. In addition, drug loading is limited to post-loading methods such as chemical conjugation or surface adsorption that have poor loading efficiency and are prone to premature drug release. We report a facile biomimetic method for making iron oxide nanoparticle-loaded silica nanocapsules based on a bimodal catalytic peptide surfactant stabilized nanoemulsion template. Iron oxide nanoparticles can be preloaded into the oil phase of the nanoemulsion at tunable concentrations, and the excellent surface activity of the designed bimodal peptide in combination with sufficient electrostatic repulsion promotes the stability of the nanoemulsions. Biosilicification induced by the catalytic peptide module leads to the formation of silica shell nanocapsules containing a magnetic oil core. The bioinspired silica nanocapsules encapsulating iron oxide nanoparticles demonstrate the next-generation of magnetic nanostructures for drug delivery applications.

Biomimetic core-shell silica nanoparticles using a dual-functional peptide.

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces.

Nanoparticle elasticity regulates phagocytosis and cancer cell uptake.

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

A general approach for biomimetic mineralization of MOF particles using biomolecules.

Biomineralization of metal organic frameworks (MOFs) using biomolecules has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule encapsulation, protection and controlled release. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process. A library of biomolecules (peptides and proteins) with different charges were systematically studied to fundamentally understand the role of biomolecules and their proprieties in biomolecule-mediated MOF biomineralization. Biomolecule charge, amino acid sequence and stirring speed have been demonstrated to play important roles in controlling biomineralization reaction rate, particle shape and morphology.