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Lipid enrichment is indispensable for enhancing the coverage of targeted molecules in mass spectrometry (MS)-based lipidomics studies. In this study, we developed a simple stepwise fractionation method using a titanium- and zirconium-dioxide-coated solid-phase extraction (SPE) silica column that separates neutral lipids, phospholipids, and other lipids, including fatty acids (FAs) and glycolipids. Chloroform was used to dissolve the lipids, and neutral lipids, including steryl esters, diacylglycerols, and triacylglycerols, were collected in the loading fraction. Second, methanol with formic acid (99:1, v/v) was used to retrieve FAs, ceramides, and glycolipids, including glycosylated ceramides and glycosylated diacylglycerols, by competing for affinity with the Lewis acid sites on the metal oxide surface. Finally, phospholipids strongly retained via chemoaffinity interactions were eluted using a solution containing 5% ammonia and high water content (45:50 v/v, 2-propanol:water), which canceled the electrostatic and chelating interactions with the SPE column. High average reproducibility of <10% and coverage of ∼100% compared to those of the non-SPE samples were demonstrated by untargeted lipidomics of human plasma and mouse brain, testis, and feces. The advantage of our procedure was showcased by characterizing minor lipid subclasses, including dihexosylceramides containing very long-chain polyunsaturated FA in the testis, monogalactosyl and digalactosyl monoacylglycerols in feces, and acetylated and glycolylated derivatives of gangliosides in the brain that were not detected using conventional solvent extraction methods. Likewise, the value of our method in biology is maximized during glycolipidome profiling in the absence of neutral lipids and phospholipids that cover more than 80% of the chromatographic peaks.

Objectives: This study aimed to evaluate the effect of whitening toothpastes on the surface roughness and colour change of CAD-CAM materials., Materials and Methods: A total of 96 samples (2 × 10 × 12 mm 3 ) were prepared from Cerasmart (CS) and Celtra Duo blocks. Celtra Duo samples were divided into two groups. One group was fired with glaze paste (CDG) and the other was not treated (CD). All groups were then divided into 4 subgroups (n = 8). The groups were brushed with conventional (Colgate™ Max Fresh), silica (Opalescence™), charcoal (Curaprox™ Black in White) and blue covarine (Signal™ White Now) toothpastes for 30,000 brushing cycles. The initial and final surface roughness values were measured with contact profilometer and a dental spectrophotometer used for obtaining colour values. One sample from each brushed group was analyzed using a scanning electron microscope. Data was analyzed with Kruskal-Wallis and Mann-Whitney tests (p = 0.05)., Results: The surface roughness of CS samples brushed with Opalescence™ and Curaprox™ was significantly higher than CD and CDG. Surface roughness change values of CS samples brushed with Curaprox™ were significantly higher than the CD and CDG. Curaprox™ brushed samples showed significant difference in colour change values for all materials., Conclusions: Brushing increases the surface roughness of CAD-CAM ceramic materials. The roughness of resin-based materials is higher than zirconia-reinforced lithium silicates. Silica-contained toothpastes may cause discoloration of nanoceramic and zirconia-reinforced glass ceramic restorations., Clinical Relevance: It should be clinically considered that whitening toothpastes may cause roughness in ceramic materials and change the desired color., (© 2024. The Author(s).)

The early diagnosis of cancer in a point-of-need manner is of great significance, yet it remains challenging to achieve the necessary sensitivity and speed. Traditional lateral flow immunoassay (LFIA) methods are limited in accuracy and quantification, restricting their suitability for home-based applications. Thus, we explored a new and user-friendly electrochemical LFIA (e-LFIA) test strip to detect α-fetoprotein (AFP), a diagnostic marker for liver cancer. The specific electrochemical immunoprobe utilized in this e-LFIA test strip is characterized by significant signal boosting, resulted from the loading Ag shell into a gold nanoparticle (AuNP)-coated dendritic mesoporous silica nanoscaffold (DMSN). Leveraging the distinct electrochemical characteristics of Ag anodic stripping and the high volume-to-surface area ratio of DMSNs, the developed DMSNs/AuNPs@Ag-based e-LFIA test strip is capable of detecting AFP at a low concentration of 0.85 ng/mL within a rapid 20 min timespan, both of these values are smaller than those in current clinical testing. Furthermore, we utilized homemade screen-printed electrodes in this sensing prototype and demonstrated the high versatility and reliability of this e-LFIA device. We envision that this DMSNs/AuNPs@Ag-based e-LFIA holds substantial potential for the early diagnosis of liver cancer and household health monitoring.

In this study, we synthesized and employed an ionic gel-functionalized silica stationary phase for high-performance liquid chromatography. The successful fabrication of the stationary phase was confirmed through attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), zeta-potential measurements, and elemental analysis (EA). Comparative performance evaluation against a commercial column demonstrated the prepared column's effectiveness in the mixed mode of reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), and ion chromatography (IC). Moreover, the stationary phase exhibited exceptional retention repeatability in per aqueous liquid chromatography, showcasing its potential as an environmentally friendly analytical method. Mechanistic investigations unveiled multiple solute-stationary phase interactions, including π-π interactions, hydrogen bonding, and ion exchange. Finally, we applied the developed stationary phase for the precise detection of preservatives in carbonated beverages and jelly, achieving high levels of accuracy and recovery rates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pablo Botella Asuncion reports financial support was provided by State Agency of Research. Pablo Botella Asuncion reports financial support was provided by Government of Valencia. Pablo Botella Asuncion has patent #WO2021/099662 issued to Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Cientificas. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: The purpose of the study was to evaluate the effect of adding mesoporous silica with silver nanoparticles to conventional glass ionomer cements (GIC) on its, physical, chemical, mechanical properties and ion release analysis., Methods: Synthesized mesoporous silica with silver nanoparticles were added in 1, 3 and 5% by weight to the liquid component of GIC forming three experimental groups and compared with plain GIC as control group. Physical and chemical characterization were conducted using nano-computerized tomography (NanoCT) and Fourier transform infrared spectroscopy. Surface microhardness, water sorption and solubility were analyzed. Ion release was investigated using Inductive Coupled Plasma-Optical Emission Spectroscopy and High Performance Liquid Chromatography. Statistical analysis between different groups for the set parameters using parametric and non-parametric tests. The results were analysed using one way analysis of variance (p < 0.05)., Results: Synthesized mesoporous silica with silver nanoparticles were of 7.28 ± 5.0 nm in diameter with a spherical morphology. NanoCT revealed less porosities for 3 wt %. Microhardness showed a statistically significant difference for 5 wt% at day 1 and 21 ( p < 0.0001). Water sorption values decreased significantly on day 14 compared to day 7 for control, 1, 3 and 5 wt%. Control specimens showed highest concentration of fluoride release followed by 5, 3 and 1 wt%., Conclusion: Mesoporous silica with silver nanoparticles modified glass ionomer cements showed comparable microhardness to conventional GIC. Ion release was evident from the modified specimens. Silver remained within the GIC for atleast four weeks following incorporation., (© 2024. The Author(s).)

Electrostatic adsorption is an enzyme immobilization method that effectively maintains enzyme activity and exhibits considerable binding efficiency. However, enzymes carry different charges at their respective reaction pH levels, which prevents the use of the same carrier to immobilize enzymes with different charges. In this study, we employed a template-mediated polysaccharide-enzyme coupling self-assembly strategy to develop a charge-controllable supramolecular immobilization carrier by regulating the charge properties of carboxymethyl chitosan, enabling the universal immobilization of enzymes with different charge levels across a range of reaction pH values. By using silica nanoparticles of certain sizes as templates, the size of the carrier can be precisely controlled and the hollow network structure formed after removing the template can effectively reduce mass transfer resistance. Trypsin and papain are used as model enzymes, and the experimental results show that the supramolecular self-assembly immobilization strategy does not disrupt the secondary structure of the enzyme molecules. After 2 h of reaction, the enzyme activities of immobilized papain and immobilized trypsin are 13.2% and 7.7% higher than those of the free enzymes, respectively. After 10 consecutive reactions, the enzyme activities of immobilized papain and immobilized trypsin retained 56.3% and 64.3% of their initial values, respectively.

Phytophthora infestans -induced potato late blight is considered the "cancer of the potato crop." In this work, mesoporous silica nanoparticles (MSNs) with ultrahigh specific surface area (786.28 m 2 /g) were synthesized, which significantly inhibited P. infestans compared with some commercial fungicides. Moreover, MSNs inhibited the growth and reproductive of P. infestans processes, including germination, sporangia infection, and zoospore release. MSNs targeted key biological pathways and induced a stress response in the P. infestans , leading to reactive oxygen species (•O 2- , •OH, and 1 O 2 ) production and structural damage of sporangia. Pot experiments showed that MSNs are translocated from leaves to roots of potato plants, enhancing physiological and biochemical processes, alleviating drought stress, improving resistance to pathogens, and exhibiting soil microbe-friendly. This study systematically reveals the mechanism of MSNs to weaken the reproduction process of P. infestans and confirm the safety and feasibility of MSNs as a green and sustainable fungicide.

In biological systems, nanoparticles interact with biomolecules, which may undergo protein corona formation that can result in noncontrolled aggregation. Therefore, comprehending the behavior and evolution of nanoparticles in the presence of biological fluids is paramount in nanomedicine. However, traditional lab-based colloid methods characterize diluted suspensions in low-complexity media, which hinders in-depth studies in complex biological environments. Here, we apply X-ray photon correlation spectroscopy (XPCS) to investigate silica nanoparticles (SiO 2 ) in various environments, ranging from low to high complex biological media. Interestingly, SiO 2 revealed Brownian motion behavior, irrespective of the complexity of the chosen media. Moreover, the SiO 2 surface and media composition were tailored to underline the differences between a corona-free system from protein corona and aggregates formation. Our results highlighted XPCS potential for real-time nanoparticle analysis in biological media, surpassing the limitations of conventional techniques and offering deeper insights into colloidal behavior in complex environments.

Dentine hypersensitivity (DH) is often related to the exposure of dentin tubules. Mineral particles, such as hydroxyapatite and bioactive glass, can provide calcium and phosphate ions to temporarily block dentin tubules via the biomineralization process, serving as feasible alternatives for DH treatment. However, due to the acidic microenvironment caused by dietary acids, these particles are easily eroded and dissolved, making it difficult to achieve efficient dentin tubule occlusion. Given the significant stability of silica in dietary acids and its excellent ability to bond with calcium and phosphate ions to form mineralized hydroxyapatite, we proposed to develop a micron-sized monetite/amorphous silica complex (MMSi) hydrosol to effectively seal the exposed dentin tubules. In this study, we hypothesized that the MMSi hydrosol could tolerate acid erosion and concurrently provide active sites for the calcium and phosphate ions to promote biomineralization in comparison to a micron-sized monetite (MM) hydrosol. Hence, the composition and microstructure including the surface morphology, silica content and phase composition of MMSi were investigated to verify the presence of silica. The results of the ion release and in vitro biomineralization process indicated that silica did not hinder the calcium and phosphate ion release and the formation of hydroxyapatite via the biomineralization process. The acid-resistant test suggested that the MMSi hydrosol exhibited a significantly slower corrosion rate than the MM hydrosol when treated with citric acid. Notably, the silica in the MMSi hydrosol retained the ability to induce the nucleation and crystallization of hydroxyapatite during de/remineralization processes. Finally, the MMSi hydrosol was mixed with commercialized toothpaste to explore its efficacy in dentin tubule occlusion via cycling de/remineralization processes. As a result, compared to the MM hydrosol, the toothpaste containing the MMSi hydrosol presented excellent acid-resistant ability and dentin tubule occlusion outcomes, which indicated that the MMSi hydrosol could be a potential promise in the long-term treatment of DH.

Potassium cations play many important roles in living organisms, especially in electro-physiology, since they are involved in neurotransmission and muscle contractions. We report the synthesis of a ratiometric fluorescent microsensor for potassium (K + ) detection, based on the fluorescent probe ION potassium green 4. Potassium-sensitive fluorescent microparticles were obtained by using silica as the core material. We obtained silica-based microsensors with sizes in the micrometer range, spherical shapes, good monodispersity, optimal selectivity and a sensitivity range of 0 to 40 mM. The microsensors also proved to be non-toxic in cell cultures and suitable for fluorescence imaging, offering new possibilities for non-invasive optical detection, quantification and in situ monitoring of K + variations in cell culture systems.

Over the last 20 years, mesoporous silica nanoparticles (MSNs) have drawn considerable attention in the biomedical field due to their large surface area, porous network, biocompatibility, and abundant modification possibilities. In situ MSN modification refers to the incorporation of materials such as alkoxysilanes, ions and nanoparticles (NPs) in the silica matrix during synthesis. Matrix modification is a popular approach for endowing MSNs with additional functionalities such as imaging properties, bioactivity, and degradability, while leaving the mesopores free for drug loading. As such, in situ modified MSNs are considered promising theranostic agents. This review provides an extensive overview of different materials and modification strategies that have been used and their effect on MSN properties. We also highlight how in situ modified MSNs have been applied in theranostic applications, oncology and regenerative medicine. We conclude with perspectives on the future outlooks and current challenges for the widespread clinical use of in situ modified MSNs.

We introduce a swift, label-free electrochemical biosensor designed for the precise on-site detection of Gram-positive bacteria via electrochemical impedance spectroscopy. The biosensor was prepared by electroplating the electrode surface with gold nanoclusters (AuNCs) on the gold-interdigitated wave-shaped electrode with a printed circuit board (Au-PCB) electrode, which plays a role in cost-effective and promising lab-on-a-chip microsystems and integrated biosensing systems. This was followed by the application of silica nanoparticle-modified vancomycin (SiNPs-VAN) that binds to Gram-positive bacteria and facilitates their detection on the AuNC-coated surface. The biosensor demonstrated remarkable sensitivity and specificity. It could detect as few as 10 2 colony-forming units (CFU)/mL of Staphylococcus aureus , 10 1 CFU/mL of Bacillus cereus , and 10 2 CFU/mL of Micrococcus luteus within 20 min. Additionally, SiNPs-VAN is also known for its high stability, low cost, and ease of preparation. It is effective in identifying Gram-positive bacteria in water samples across a concentration range of 10 2 -10 5 CFU/mL and shows selective identification of Gram-positive bacteria with minimal interference from Gram-negative bacteria like Escherichia coli . The ability of the biosensor to quantify Gram-positive bacteria aligns well with the results obtained from the quantitative real-time polymerase chain reaction (qRT-PCR). These findings highlight the potential of electrochemical biosensors for the detection of pathogens and other biological entities, marking a significant advancement in this field.

Mesoporous silica offers an easy way to transform liquids into solids, due to their high loading capacity for liquid or dissolved active ingredients and the resulting enhanced dissolution properties. However, the compression of both unloaded and loaded mesoporous silica bulk material into tablets is challenging, due to poor/non-existing binding capacity. This becomes critical when high drug loads are to be achieved and the fraction of additional excipients in the final tablet formulation needs to be kept at a minimum. Our study aimed to investigate the mechanism of compression and tabletability dependent on the Liquid Load Level of the silica and type of filler/binder in binary tabletting mixtures. To this end, Vivapur® 101, FlowLac® 90, Pearlitol® 200 SD and tricalcium citrate tetrahydrate were selected and mixed with Syloid® XDP 3050 at various Liquid Load Levels. Compaction characteristics were analysed using the StylOne® Classic 105 ML compaction simulator. Additionally, the Overall Liquid Load (OLL) was defined as a new critical quality attribute for liquisolid tablets. The Overall Liquid Load allows straightforward, formulation-relevant comparisons between various fillers/binders, liquid components, and silica types. Results indicate strong binding capacity and high plasticity of the fillers/binders as key components for successful high liquid load silica tablet formulation. A volumetric combination of 30% Vivapur® 101 and 70% 0.75 mL/g loaded Syloid® XDP 3050 proved to be the most effective mixture, achieving an Overall Liquid Load of 36-41% [v/v] and maintaining a tensile strength of 1.5 N/mm 2 with various liquid vehicles., (© 2024. The Author(s).)

Blood clotting is vital for preventing bleeding after an injury. Hemostasis is a complex cascade involving numerous plasma proteins. Uncontrolled bleeding leads to mortality. The presence of Ca (calcium) activates and promotes the different phases in the coagulation cascade. Even nonbiological surfaces such as silicates may activate coagulation factor XII (FXII). This causes the clotting of the blood. The exceptional hemostatic ability of the mesoporous calcium-decorated silica nanoparticles (MCSNs) is achieved by stimulating the factors needed to form fibrin mesh, a durable clot, thereby establishing hemostasis. This may be used as a hemostatic agent during an accident surgical procedure and other bleeding-related trauma conditions. This study investigates the mechanistic activation of the coagulation cascade by MCSN through blood coagulation index, clotting time, and coagulation activation studies like PT and aPTT. Our finding demonstrates that MCSN induces platelet adhesion and RBC aggregation and activates thrombin generation through distinct pathways.

Cellular forces play a crucial role in numerous biological processes, including tissue development, morphogenesis, and disease progression. However, existing methods for detecting cellular forces, such as traction force microscopy and atomic force microscopy, often face limitations in terms of high throughput, real-time monitoring, and applicability to complex biological systems. In this study, we utilized a novel Photonic Crystal Cellular Force Microscopy (PCCFM) system to visualize and quantify dynamic cellular forces. This system consists of a conventional optical microscope and a photonic crystal substrate formed by the periodic arrangement of silica nanoparticles within polyacrylamide hydrogels. Taking MDCK cells and BMSCs as examples, we found that PCCFM can capture dynamic cellular forces with high spatial and temporal resolution during the cell adhesion, spread, proliferation, and osteogenic differentiation. The application of this technique revealed distinct force patterns in different cellular stages, offering insights into the interplay between cellular forces and morphological changes. By investigating the migration of cells from MDCK cyst fragments, we could gain significant insights into tumour cell migration behaviours. The real-time, high-throughput analysis of cellular biomechanics from the PCCFM system offers valuable information on the mechanisms of tumour metastasis, potentially guiding therapeutic development and improving disease treatment strategies.

Bimetallic nanomaterial-based systems have been widely utilized across various fields due to their remarkable expandability and flexibility, including nanomedicine, diagnostics, and molecular information technology. Here, we constructed an electrochemical immunosensor using bimetallic gold/silver functionalized carbon spheres (AuAg@CSs) and mesoporous silica nanoparticles (MSNs) for the sensitive determination of cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) and ensuring information protection for textual data. The AuAg@CSs demonstrated exceptional catalytic activity towards hydrogen peroxide, generating a significant current signal. The introduction of CYFRA 21-1 facilitated the binding of MSNs, thereby forming a sandwich-type electrochemical immunosensor that resulted in a notable decrease in current. Notably, the detection limit for CYFRA 21-1 was determined to be 31 fg mL -1 , accompanied by high selectivity. Furthermore, extensive textual information can be encrypted and concealed within the current responses of the electrochemical nanosensing system. By establishing a threshold, these current signals can be represented as a series of binary strings, which can subsequently be segmented into shorter strings. Through information coding methods, these shorter binary strings can be assembled and decrypted, ultimately merging into meaningful textual content. This study promotes the synthesis and multifunctional application of bimetallic nanomaterials, providing innovative solutions to enhance the sensing sensitivity of electrochemical immunosensors and paving the way for advancements in molecular digitization.

Frustules, or the silica based cell walls of diatomaceous algae Aulacoseira granulata , provide large numbers of reliably cylindrical microstructures with an inner cavity and surface chemistry suitable for constructing bubble-based, acoustically-powered micro-swimmers. In this way, microswimmers can be made in a scalable, accessible and low-cost manner, enabling studies of their individual and collective behavior as active colloids.

Biocatalytic processes using microorganisms are considered efficient and economically and environmentally friendly reactions. However, the viability and function of these microorganisms are prone to being hindered by various practical environments. Here, we reported a bacteria-induced nanochannel structure that endowed the microorganism with biocatalytic ability in harsh conditions. We revealed that the bacteria could trigger the fusion of silica nanoparticles on their surface by the secreted alkaline metabolite, resulting in silica shells with nanochannels on bacteria (bacteria@nSiO 2 ). The nanochannel structure in silica shells endowed bacteria with biocatalytic ability in multiple harsh conditions. We revealed that these nanochannels could influence the mass transfer from the extracellular to the intracellular environment, which protected the bacteria from excessive toxic substance while preserving the mass exchange during biocatalysis. This feature ensured bacteria@nSiO 2 with efficient bioactivity under harsh conditions for industrial catalysis and degradation of pollution, which cannot be achieved by corresponding native bacteria. Using the crude oil spill as a practical example, we presented that bacteria@nSiO 2 could degrade highly concentrated crude oil, which any reported bacteria cannot achieve. This work emphasized the role of nanochannels in the regulation of cellular functions for enhanced biocatalysis. It also demonstrated a bacteria-triggered nanostructure formation, which is a promising methodology for nanotechnology and provides a strategy for more advanced organism-material hybrids.

The concurrent preservation of morphological, structural, and genomic attributes within biological samples is paramount for comprehensive insights into biological phenomena and disease mechanisms. However, current preservation methodologies (e.g., cryopreservation, chemical reagent fixation, and bioplasticization) exhibit limitations in simultaneously achieving these critical combined goals. To address this gap, inspired by natural fossilization, here we propose "deep silicification," a room temperature technology that eliminates fixation requirements and overcomes the cold chain problem. By harnessing the synergy between ethanol and dimethyl sulfoxide, deep silicification significantly enhances silica penetration and accumulation within bioorganisms, thereby reinforcing structural integrity. This versatile and cost-effective approach demonstrates remarkable efficacy in preserving organismal morphology across various scales. Accelerated aging experiments underscore a 4,723-fold enhancement in genomic information storage over millennia, with whole-genome sequencing confirming nearly 100% fidelity. With its simplicity and reliability, "deep silicification" represents a paradigm shift in biological sample storage., Competing Interests: Competing interests statement:The authors declare no competing interest.

Adenosine triphosphate (ATP), ubiquitous in all living organisms, is conventionally recognized as a fundamental energy currency essential for a myriad of cellular processes. While its traditional role in energy metabolism requires only micromolar concentrations, the cellular content of ATP has been found to be significantly higher at the millimolar level. Recent studies have attempted to correlate this higher concentration of ATP with its nonenergetic role in maintaining protein homeostasis, leaving the investigation of ATP's nontrivial activities in biology an open question. Here, by coupling computer simulations and experiments, we uncover new insights into ATP's role as a cryoprotectant against cold-salt stress, highlighting the necessity for higher cellular ATP concentrations. We present direct evidence at charged silica interfaces, demonstrating ATP's ability to restore native intersurface interactions disrupted by combined cold-salt stress, thereby inhibiting cold-responsive aggregation in high-salt conditions. ATP desorbs salt cations from negatively charged surfaces through predominant interactions between ATP and the salt cations. Although the mode of ATP's action remains unchanged with temperature, the extent of interaction scales with temperature, requiring less ATP activity at lower temperatures, justifying the reason for reduction in cellular ATP content due to the cold effect, reported in previous experimental studies. The trend observed in inorganic nanostructures is recurrent and robustly transferable to charged protein interfaces. A thorough comparison of ATP's cryoprotective activity with traditionally known biological cryoprotectants (glycine and betaine) reveals ATP's greater efficiency. In retrospect, our findings highlight ATP's additional biological role in cryopreservation, expanding its potential biomedical applications by offering effective protection of cells from cryoinjuries and avoiding the significant challenges associated with the toxicity of organic cryoprotectants.

We report on a surface-enhanced Raman scattering (SERS) platform for the detection of five beta-blockers (β-blockers): atenolol, esmolol, labetalol, sotalol, and propranolol. Key to this platform was a two-dimensional substrate formed by self-assembling large Ag@SiO 2 nanoparticles (Ag@SiO 2 NPs) on a silicon wafer. The close arrangement of these large nanoparticles on the surface generated a strong and uniform electromagnetic field, which enhanced SERS signal intensity for the detection of small amounts of the target molecules. The intensities of characteristic peaks of the five β-blocker drugs increased linearly with the increase of their concentrations in the range of 10 -5 to 10 -8 mol/L. The detection limits were 10 -10 mol/L for propranolol, 10 -9 mol/L for atenolol, labetalol, and sotalol, and 10 -8 mol/L for esmolol. Determination of these five β-blocker drugs added to human urine samples, using a portable Raman spectroscopy instrument, showed quantitative recovery (93-101%). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of SERS spectral data improved the differentiation among these five β-blockers. This study highlights the potential of the developed SERS platform for rapid, on-site detection of illicit drugs and for antidoping screening.

In situ visualization of microRNA (miRNA) in cancer cells and diseased tissues is essential for advancing our comprehension of the onset and progression of associated diseases. Two-photon (TP) imaging, as an imaging technology with high spatiotemporal resolution, deep tissue penetration, and accurate target quantification, has distinctive advantages over single-photon imaging and has attracted increasing attention. Extensive research has been conducted on two-photon dye-doped silica nanoparticles, which exhibit a large two-photon absorption (TPA) cross-section, high fluorescence quantum yield, and excellent biocompatibility. However, the low abundance of RNA in tumor cells leads to insufficient signal output. Based on functional nucleic acid, a catalyzed hairpin self-assembly (CHA) signal amplification strategy, which has simplicity, robustness, and nonenzymatic characteristics, can achieve the amplification of DNA or RNA signals. Here, a two-photon silica nanoamplifier (TP-SNA) utilizing TP dye-doped silica nanoparticles (SiNPs) and functional nucleic acid was constructed, employing triggering catalyzed hairpin self-assembly and fluorescence resonance energy transfer (FRET) for highly sensitive detection and precise TP imaging of endogenous miRNAs in tumor cells and tissues at varying depths. The TP-SNA demonstrated the capability to detect miR-203 with a detection limit of 33 pM. The maximum two-photon tissue penetration depth of the two-photon nanoamplifier was 210 μm. The two-photon nanoamplifier developed in this study makes full use of the advantages of accurate TP ratiometric bioimaging and the CHA signal amplification strategy, which shows good application value for future transformation into clinical diagnosis.

Antiviral drugs have garnered considerable attention, particularly in the global battle against the COVID-19 pandemic, amid heightened concerns regarding environmentally acquired antiviral resistance. A comprehensive understanding of their transport in subsurface environments is imperative for accurately predicting their environmental fate and risks. This study investigated the mobility and retention characteristics of six COVID-19 antiviral drugs in saturated quartz sand columns. Results showed that the mobility of the drugs was primarily contingent on their hydrophobicity, with ribavirin and favipiravir exhibiting the highest transportability, while arbidol displaying the greatest retention. The transport characteristics of ribavirin and favipiravir remained largely unaffected by pH, whereas the retention of the other four antivirals remained consistently minimal under alkaline conditions. Elevating ionic strength marginally facilitated the transport of these antivirals, while the presence of Ca 2+ notably enhanced their retention in quartz sand compared to Na + . Ribavirin and remdesivir warrant particular attention due to their relatively high transportability and propensity for environmentally acquired antiviral resistance. These findings contribute to an enhanced understanding of the leachate potential and transport of COVID-19-related antivirals in sandy porous media, furnishing fundamental data for predicting their environmental fate and associated risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, a sensitive dual-signal electrochemiluminescence (ECL) immunosensor was developed for okadaic acid (OA) detection utilizing copper nanoclusters (CuNCs) and Ru(bpy) 3 2+ -doped silica nanoparticles (RuSiNPs). Interestingly, the CuNCs could simultaneously enhance both cathodic (-0.95 V) and anodic (+1.15 V) ECL signals of RuSiNPs, forming a dual-signal ECL sensing platform. Further, RuSiNPs@CuNCs were used as immunomarkers by covalently conjugating them with an anti-OA monoclonal antibody (mAb) to form probes. Finally, dual ECL signals of the immunosensor were fabricated and showed good linear relationships with OA concentrations in the range of 0.05-70 ng mL -1 , having a median inhibitory concentration (IC 50 ) of 1.972 ng mL -1 and a limit of detection of 0.039 ng mL -1 . Moreover, the constant ratio of the cathodic and anodic ECL peaks achieved self-calibration of the detection signal and improved the reliability of the results. Finally, we successfully applied the ECL sensor to detect OA in spiked oyster samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

An organic-inorganic hybrid nanoprobe, namely LML-D-SBA@Eu 3+ -Gd 3+ , was constructed, with SBA-15 acting as the carrier material, and luminol and Eu 3+ acting as fluorescence channels to achieve ratiometric signals that eliminate external interference (accurate detection). Gd 3+ was used as a sensitizer to amplify the red emission of Eu 3+ (ultrasensitive detection). In TCs detection, the luminol emission at 428 nm was quenched due to the photoinduced electron transfer mechanism, and the Eu 3+ emission at 617 nm was sensitized due to the synergistic energy transfer from TCs and Gd 3+ to Eu 3+ . The fluorescence intensity at 617 and 428 nm showed ratiometric changes as indicated by notable color changes from blue to red. The detection limits for TC and OTC were 0.21 and 0.08 ng/mL, respectively. To realize a facile, rapid, and cost-effective detection, we constructed a portable intelligent sensing platform based on smartphones, and it demonstrated great potential for on-site detection of TCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Intelligent shape memory polymer can be potentially used in manufacturing implantable devices that enables a benign variation of implant dimensions with the external stimuli, thus effectively lowering insertion forces and evading associated risks. However, in surgical implantation, biomaterials-associated infection has imposed a huge burden to healthcare system that urgently requires an efficacious replacement of antibiotic usages. Preventing the initial attachment and harvesting a biocidal function upon native surfaces may be deemed as a preferable strategy to tackle the issues of bacterial infection. Herein, a functionalized polylactic acid (PLA) composite membrane assembled with graphene (GE, a widely used photothermal agent) was fabricated through a blending process and then polydimethylsiloxane utilized as binders to pack hydrophobic SiO 2 tightly onto polymer surface (denoted as PLA-GE/SiO 2 ). Such an active platform exhibited a moderate shape-memory performance upon near-infrared (NIR) light stimulation, which was feasible for programmed deformation and shape recovery. Particularly stirring was that PLA-GE/SiO 2 exerted a pronounced bacteria-killing effect under NIR illumination, 99.9 % of E. coli and 99.8 % of S. aureus were effectively eradicated in a lean period of 5 min. Furthermore, the obtained composite membrane manifested excellent antiadhesive properties, resulting in a bacteria-repelling efficacy of up to 99 % for both E. coli and S. aureus species. These findings demonstrated the potential value of PLA-GE/SiO 2 as a shape-restorable platform in "kill&repel" integration strategy, further expanding its applications for clinical anti-infective treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sorafenib-resistant (SR) hepatocellular carcinoma (HCC) is a current serious problem in liver cancer treatment. Numerous phytochemicals derived from plants exhibit anticancer activity but have never been tested against drug-resistant cells., Methods: Avocado seed extract (APE) isolated by maceration was analysed for its phytochemical composition and anticancer activity. Novel design charge-switchable pH-responsive nanocarriers of aminated mesoporous silica nanoparticles with conjugated galactose (GMSN) were synthesised for delivering APE and their physicochemical properties were characterized. The drug loading efficiency (%LE) and entrapment efficiency (%EE) were evaluated. Anticancer activity of APE loaded GMSN was measured against HCC (HepG2, Huh-7) and SR-HCC (SR-HepG2)., Results: Anticancer activity of APE against non-resistant HepG2 (IC 50 50.9 ± 0.83 μg mL -1 ), Huh-7 (IC 50 42.41 ± 1.88 μg mL -1 ), and SR-HepG2 (IC 50 62.58 ± 2.29 μg mL -1 ) cells was confirmed. The APE loaded GMSN had a diameter of 131.41 ± 14.41 nm with 41.08 ± 2.09%LE and 44.96 ± 2.26%EE. Galactose functionalization (55%) did not perturb the original mesoporous structure. The GMSN imparted positive surface charges, 10.3 ± 0.61mV at acidic medium pH 5.5 along with rapid release of APE 45% in 2 h. The GMSN boosted cellular uptake by HepG2 and SR-HepG2 cells, whereas the amine functionalized facilitated their endosomal escape. Their anticancer activity was demonstrated in non-resistant HCC and SR-HCC cells with IC 50 values at 30.73 ± 3.14 (HepG2), 21.86 ± 0.83 (Huh-7), 35.64 ± 1.34 (SR-HepG2) μg mL -1 , respectively, in comparison to the control and non-encapsulated APE., Conclusion: APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further in vivo investigation., Competing Interests: The authors declare no competing interests over the publication of this manuscript., (© 2024 Basu et al.)

The clinical need for bone adhesives as an alternative to osteosynthesis is evident. However, this is a challenging problem due to the moist environment in surgical sites with bone surfaces covered with blood and biomolecules like lipids or proteins. A nanoparticle-loaded hydrogel that is based on a freeze-dried powder of silica-coated calcium phosphate/carboxymethyl cellulose nanoparticles (CaP/CMC/SiO 2 ) and an aqueous solution of sodium alginate (2 wt%) was developed and optimized with respect to the gluing ability in air and in water. The final paste was crosslinked within about one minute by calcium ions released from the calcium phosphate nanoparticles and contained about 20 wt% nanoparticles and 80 wt% water. The mechanical properties of the hydrogel were determined by extensive rheological tests. The thixotropic pasty hydrogel can be applied with a syringe. The adhesion strength was about 84 kPa between moist bone fragments in air. The hydrogel kept fragments of cortical bone well connected for >3 months during complete submersion in water. Besides water, the material consists only of biocompatible and biodegradable components (calcium phosphate, CMC, alginate). It carries only a very low dose of these materials into the bone site (mainly calcium phosphate nanoparticles). In-vitro cell culture with hMSCs that differentiated to osteoblasts confirmed a good biocompatibility of the bone adhesive formulation., (© 2024. The Author(s).)

Silica encapsulation under ambient conditions is commonly used to shield protein-based nanosystems from chemical stress. However, encapsulation-induced photo- and structural instabilities at elevated temperatures have been overlooked. Using bovine serum albumin-capped fluorescent gold nanoclusters (BSA-AuNCs) as a model, we demonstrated that chaperone/polymer layer-by-layer complexation can stabilize the template to resist encapsulation-induced fragmentation/reorganization and emission increases at 37 °C or higher temperatures. We first wrapped BSA-AuNCs with α-crystallin chaperones (α-Crys) to gain the highest thermal stability at a 1:50 molar ratio and then enfolded BSA-AuNC/α-Crys with thermoresponsive poly- N -isopropylacrylamide (PNIPAM) at 60 °C to shield silica interaction and increase the chaperone-client protein accessibility. The resulting BSA-AuNC/α-Crys/PNIPAM (BαP) was encapsulated by a sol-gel process to yield BαP-Si (∼80 ± 4.5 nm), which exhibited excellent structural integrity and photostability against chemical and thermal stresses. Moreover, targeted BαP-Si demonstrated prolonged fluorescence stability for cancer cell imaging. This template stabilization strategy for silica encapsulation is biocompatible and applicable to other protein-based nanosystems.

Multi drug resistance (MDR) in breast carcinoma still poses a significant impairment to successful chemotherapy. As the arsenal of anticancer agents increases with improved preclinical methods, the growth of therapeutic drug combinations is now unprecedented. The malignancies addressed by mono drugs often fail to limit cancer progression, resulting in resistant cancer, thereby offering combinatorial therapies a terrific edge over monodrug regimes. However, the selection of drug combinations required enough preliminary evidence for their synergistic effect. The fundamental mechanisms of MDR to chemotherapeutics are associated with the overexpression of membrane efflux pumps, alternations in drug targets, and increased drug metabolism. Unfortunately, it is very difficult for drugs to overcome resistance produced on their own or by another different drug action. In this context, herein, we report a simple delivery system for coencapsulation and intracellular codelivery of dual-drug thymoquinone (TQ) and doxorubicin (DOX) to resensitize DOX-resistant MDA MB231 cell line (231 R). The 231 R cell line developed in our lab showed an enhanced expression of the ATP-binding cassette (ABC) transporters P-gp1/MDR-1 and a declined miR-298 expression. The present delivery system is based on amine-functionalized mesoporous silica nanoparticles (MSNs), in which the side chain amine functional group was used to react with the carbonyl group of TQ, which acts as a pro-drug system (TQ-MSN) to release TQ and DOX simultaneously. DOX was encapsulated later into the above TQ-MSN by a simple diffusion method. The drugs containing MSNs were further coated with a hyaluronic acid-conjugated PEG-PLGA polymer (HA@TQ-DOX-MSN). This simple nanostrategy interferes with the MDR-1/miR-298 cross-talk, thereby allowing a significant reduction in drug efflux from the cell and highlighting a promising nanotechnology-based combinatorial delivery approach in managing breast cancer chemoresistance.

Embedded 3D printing (EMB3D) is an additive manufacturing technique that enables complex fabrication of soft materials including tissues and silicones. In EMB3D, a nozzle writes continuous filaments into a support bath consisting of a yield stress fluid. Lack of fusion defects between filaments can occur because the nozzle pushes support fluid into existing filaments, preventing coalescence. Interfacial tension was previously proposed as a tool to drive interfilament fusion. However, interfacial tension can also drive rupture and shrinkage of printed filaments. Here, we evaluate the efficacy of interfacial tension as a tool to control defects in EMB3D. Using polydimethylsiloxane (PDMS)-based inks with varying amounts of fumed silica and surfactant, printed into Laponite in water supports, we evaluate the effect of rheology, interfacial tension, print speeds, and interfilament spacings on defects. We print pairs of parallel filaments at varying orientations in the bath and use digital image analysis to quantify shrinkage, rupture, fusion, and positioning defects. By comparing disturbed filaments to printed pairs of filaments, we disentangle the effects of nozzle movement and filament extrusion. Critically, we find that capillary instabilities and interfilament fusion scale with the balance between support rheology and interfacial tension. Less viscous supports and higher interfacial tensions lead to more shrinkage and rupture at all points in the printing process, from relaxation after writing, to disturbance of the line, to writing of a second line. It is necessary to overextrude material to achieve interfilament fusion, particularly at high support viscosities and low interfacial tensions. Finally, fusion quality varies with printing orientation, and writing neighboring filaments causes displacement of existing structures. As such, specialized slicers are needed for EMB3D that consider the tighter spacings and orientation-dependent spacings necessary to achieve precise control over printed shapes.

Background: Tomato (Solanum lycopersicum L.) production is severely threatened by bacterial wilt, caused by the phytopathogenic bacterium Ralstonia solanacearum. Recently, nano-enabled strategies have shown tremendous potential in crop disease management., Objectives: This study investigates the efficacy of biogenic nanoformulations (BNFs), comprising biogenic silica nanoparticles (SiNPs) and melatonin (MT), in controlling bacterial wilt in tomato., Methods: SiNPs were synthesized using Zizania latifolia leaves extract. Further, MT containing BNFs were synthesized through the one-pot approach. Nanomaterials were characterized using standard characterization techniques. Greenhouse disease assays were conducted to assess the impact of SiNPs and BNFs on tomato plant immunity and resistance to bacterial wilt., Results: The SiNPs and BNFs exhibited a spherical morphology, with particle sizes ranging from 13.02 nm to 22.33 nm for the SiNPs and 17.63 nm to 21.79 nm for the BNFs, indicating a relatively uniform size distribution and consistent shape across both materials. Greenhouse experiments revealed that soil application of BNFs outperformed SiNPs, significantly enhancing plant immunity and reducing bacterial wilt incidence by 78.29% in tomato plants by maintaining oxidative stress homeostasis via increasing the activities of antioxidant enzymes such as superoxide dismutase (31.81%), peroxidase (32.9%), catalase (32.65%), and ascorbate peroxidase (47.37%) compared to untreated infected plants. Additionally, BNFs induced disease resistance by enhancing the production of salicylic acid and activating defense-related genes (e.g., SlPAL1, SlICS1, SlNPR1, SlEDS, SlPD4, and SlSARD1) involved in phytohormones signaling in infected tomato plants. High-throughput 16 S rRNA sequencing revealed that BNFs promoted growth of beneficial rhizosphere bacteria (Gemmatimonadaceae, Ramlibacter, Microscillaceae, Anaerolineaceae, Chloroplast and Phormidium) in both healthy and diseased plants, while suppressing R. solanacearum abundance in infected plants., Conclusion: Overall, these findings suggest that BNFs offer a more promising and sustainable approach for managing bacterial wilt disease in tomato plants., (© 2024. The Author(s).)

The exploitation of drought is a critical worldwide challenge that influences wheat growth and productivity. This study aimed to investigate a synergistic amendment strategy for drought using the single and combined application of plant growth-promoting microorganisms (PGPM) ( Trichoderma harzianum ) and biogenic silica nanoparticles (SiO 2 NPs) from rice husk ash (RHA) on Saudi Arabia's Spring wheat Summit cultivar ( Triticum aestivum L.) for 102 DAS (days after sowing). The significant improvement was due to the application of 600 ppm SiO 2 NPs and T. harzianum + 600 ppm SiO 2 NPs, which enhanced the physiological properties of chlorophyll a, carotenoids, total pigments, osmolytes, and antioxidant contents of drought-stressed wheat plants as adaptive strategies. The results suggest that the expression of the studied genes ( TaP5CS1 , TaZFP34 , TaWRKY1 , TaMPK3 , TaLEA , and the wheat housekeeping gene TaActin ) in wheat remarkably enhanced wheat tolerance to drought stress. We discovered that the genes and metabolites involved significantly contributed to defense responses, making them potential targets for assessing drought tolerance levels. The drought tolerance indices of wheat were revealed by the mean productivity (MP), stress sensitivity index (SSI), yield stability index (YSI), and stress tolerance index (STI). We employed four databases, such as BAR, InterPro, phytozome, and the KEGG pathway, to predict and decipher the putative domains in prior gene sequencing. As a result, we discovered that these genes may be involved in a range of important biological functions in specific tissues at different developmental stages, including response to drought stress, proline accumulation, plant growth and development, and defense response. In conclusion, the sole and/or dual T. harzianum application to the wheat cultivar improved drought tolerance strength. These findings could be insightful data for wheat production in Saudi Arabia under various water regimes.

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO 2 ), zinc oxide (ZnO), silica (SiO 2 ), cerium oxide (CeO 2 ), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO 2 and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO 2 . This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks.

Oral administration of protein-based therapeutics is highly desirable due to lower cost, enhanced patient compliance, and convenience. However, the harsh pH environment of the gastrointestinal tract poses significant challenges. Silica-based carriers have emerged as potential candidates for the delivery of protein molecules, owing to their tuneable surface area and pore volume. We explored the use of a commercial mesoporous silica carrier, SYLOID, for the delivery of octreotide and bovine serum albumin (BSA) using a solvent evaporation method in three different solvents. The loading of proteins into SYLOID was driven by diffusion, as described by the Stokes-Einstein equation. Various parameters were investigated, such as protein size, diffusion, and solubility. Additionally, 3D fluorescence confocal imaging was employed to identify fluorescence intensity and protein diffusion within the carrier. Our results indicated that the loading process was influenced by the molecular size of the protein as octreotide exhibited a higher recovery rate (71%) compared to BSA (32%). The methanol-based loading of octreotide showed uniform diffusion into the silica carrier, whereas water and ethanol loading resulted in the drug being concentrated on the surface, as shown by confocal imaging, and further confirmed by scanning electron microscopy (SEM). Pore volume assessment supported these findings, showing that octreotide loaded with methanol had a low pore volume (1.2 cc/g). On the other hand, BSA loading was affected by its solubility in the three solvents, its tendency to aggregate, and its low solubility in ethanol and methanol, which resulted in dispersed particle sizes of 223 and 231 μm, respectively. This reduced diffusion into the carrier, as confirmed by fluorescence intensity and diffusivity values. This study underscores the importance of protein size, solvent properties, and diffusion characteristics when using porous carriers for protein delivery. Understanding these factors allows for the development of more effective oral protein-based therapeutics by enhancing loading efficiency. This, in turn, will lead to advances in targeted drug delivery and improved patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al Tahan, Michaelides, Somasekharan Nair, AlShatti, Russell and Al-Khattawi.)

Dendritic cells (DCs) within the tumor microenvironment (TME) have an insufficient capacity to activate T cells through antigen presentation. Furthermore, the programmed cell-death ligand 1 (PD-L1), abundantly expressed on tumor-associated DCs, binds the programmed cell-death 1 (PD-1)-positive T cells and suppresses their immune function. The binding of PD-L1 to CD80 (B7.1) on the same DC via cis -interactions further prevents T cell costimulation through CD28. Here, we present a strategy to simultaneously promote antigen cross-presentation and block the inhibitory interactions of PD-L1 on DCs to amplify T cell-mediated antitumor responses within the TME. Mesoporous silica nanoparticles (MSNPs) were loaded with clotrimazole (CLT) to boost MHC II-mediated antigen presentation by DCs, surface-modified with mannose to target CD206 on DCs, and then decorated with PD-L1 binding peptide (PDL1bp) to block PD-L1-mediated interactions. PDL1bp was cleaved from the mannosylated and CLT-loaded MSNPs (MSNP-MaN/CLT) under conditions simulating the TME and tethered to PD-L1 to reverse CD80 sequestration on DC2.4 cells. The blocking of PD-L1 by PDL1bp-decorated NPs (MSNP-MaN-PDL1bp) increased the cellular interactions between DC2.4 and EL4 T cells and the amount of IL-2 secretion. The MSNP-MaN/CLT were taken up rapidly by DC2.4 cells, promoted MHC II presentation of hen egg lysozyme (HEL), and increased IL-2 production from HEL antigen-primed 3A9 T cells, which was further enhanced by PDL1bp. In vivo investigation revealed that administration of the CLT-loaded and PDL1bp-functionalized MSNPs remarkably inhibited subcutaneous B16-F10 melanoma tumor growth when compared with anti-PD-L1 therapy. MSNP-MaN-PDL1bp/CLT treatment upregulated the levels of effector molecules such as granzyme B and proinflammatory cytokines (IFNγ and INFα) in the tumor tissue, indicating antitumoral T cell responses. This strategy of utilizing nanoparticles to trigger DC activation while promoting T cell stimulation can be used to amplify the antitumor T cell responses and represents a promising alternative to anti-PD-L1 immunotherapy.

The application of patch methods for repairing abdominal wall wounds presents a variety of challenges, such as adhesion and limited mobility due to inadequate mechanical strength and nonabsorbable materials. Among these complications, postoperative visceral adhesion and wound infection are particularly serious. In this study, a bilayered composite patch with a gelatin methacryloyl (GelMA)/sodium alginate (SA)-vancomycin (Van)@polycaprolactone (PCL) (GelMA/SA-Van@PCL) antibacterial layer was prepared via coaxial 3D printing and a polycaprolactone (PCL)-silicon dioxide (SiO 2 ) antiadhesive layer (PCL-SiO 2 ) was prepared via electrospinning and electrostatic spray for hernia repair. The evaluation of the physicochemical properties revealed that the composite patch had outstanding tensile properties (16 N cm -1 ), excellent swelling (swelling rate of 243.81 ± 12.52%) and degradation (degradation rate of 53.14 ± 3.02%) properties. Furthermore, the composite patch containing the antibiotic Van exhibited good antibacterial and long-term drug release properties. Both in vivo and in vitro experiments indicated that the composite patch displayed outstanding biocompatibility and antiadhesive properties and could prevent postoperative infections. In summary, the bilayered composite patch can effectively prevent postoperative complications while promoting tissue growth and repair and holds significant application potential in hernia repair.

Macrophages are usually present in solid tumors where they participate in tumor progression, angiogenesis, immunosuppression and metastasis. The design of nanocarriers capable of delivering therapeutic agents to specific cell populations has received considerable attention in the last decades. However, the capacity of many of these nanosystems to deliver multiple therapeutic agents with very different chemical properties is more limited. Herein, a novel multitasking nanoplatform capable of delivering large macromolecules and cytotoxic drugs to macrophages is presented. This novel nanosystem has exhibited excellent skills in performing simultaneous tasks, macrophage depletion and glucose starvation, maintaining the oxygen levels in the tissue. This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. The external surface of the silica core was coated with a lipid bilayer to avoid the premature release of the housed drugs. Finally, polymeric nanocapsules loaded with catalase were covalently anchored on the outer lipid bilayer, and carboxy-mannose was attached to the exposed side of the nanocapsules to provide selectivity to the macrophages. These nanoassemblies were able to transport enzymes (Gox and CAT), maintaining their catalytic activity. Therefore, they could induce glucose starvation, keeping the oxygen levels in the tissue, owing to the tandem enzymatic reaction. The capacity of these nanoassemblies to deliver therapeutic agents to macrophages was evaluated both in static and under flow conditions, showing a rapid capture of the nanoparticles by the macrophages. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.

Accurate tumor detection is crucial for the early discovery and subsequent treatment of small neoplastic foci. Molecular imaging, which combines non-invasiveness, high specificity, and strong sensitivity, excels in diagnosing early tumors and stands out among tumor diagnosis methods. Here, we introduced a dual-modal imaging probe capable of actively targeting tumor cells, suitable for both near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). Dendritic mesoporous silica was used as a carrier for the probe, encapsulating Ag 2 S quantum dots (QDs) for NIR fluorescence imaging. Additionally, the probe conjugated the MRI contrast agent Gd-DOTA and cetuximab, which targeted EGFR on the tumor cell membrane surface, to achieve dual-modal imaging in the tumor area. This strategy provided a methodology for the accurate diagnosis of early-stage tumor lesions and guides precise lesion resection during surgery, offering significant potential for clinical application.

Here, we describe the preparation of bridged ethylene polyethylene oxide (BE-PEO) surface-modified silica packing materials for size exclusion chromatography. BE-PEO surface-modified silica was hydrolyzed and subsequent 1 H nuclear magnetic resonance analysis of hydrolysis products confirmed the successful formation of BE-PEO bonded surface. Silica particles exhibiting 3 µm diameters and 1000 Å nominal pore diameters were selected as a base material for this work out of the critical need to improve analytical capabilities for the testing of cell and gene therapy drug products. Accelerated high pH aging study revealed significant enhancement in column stability. Multi-angle light scattering noise measurements showed inordinately lower baseline noise. Moreover, we evaluated the chromatographic performance of BE-PEO silica-packed columns through separations of a protein test mixture, DNA ladder, monoclonal antibody-based therapeutics, and adeno-associated viruses. BE-PEO silica columns demonstrated high resolution, high recovery separations that were confirmed to be reproducible and capable of extended column lifetimes and exhibited low ionic and hydrophobic secondary interactions. In summary, BE-PEO silica particles have yielded a new level of performance, improved base stability, and inherently lower baseline noise. These novel widepore particles will facilitate more sensitive size-based detection and characterization of large biologics in the form of advanced gene therapy products., (© 2024 Waters Corporation. Journal of Separation Science published by Wiley‐VCH GmbH.)

Immunofluorescence analysis of individual extracellular vesicles (EVs) in common fluorescence microscopes is gaining popularity due to its accessibility and high fluorescence sensitivity; however, EV number and size are only measurable using fluorescent stains requiring extensive sample manipulations. Here we introduce highly sensitive label-free EV size photometry (SP) based on interferometric scattering (iSCAT) imaging of immersed EVs immobilized on a glass coverslip. We implement SP on a common inverted epifluorescence microscope with LED illumination and a simple 50:50 beamsplitter, permitting seamless integration of SP with fluorescence imaging (SPFI). We present a high-throughput SPFI workflow recording >10,000 EVs in 7 min over ten 88 × 88 µm 2 fields of view, pre- and post-incubation imaging to suppress background, along with automated image alignment, aberration correction, spot detection and EV sizing. We achieve an EV sizing range from 37 to ∼220 nm in diameter with a dual 440 and 740 nm SP illumination scheme, and suggest that this range can be extended by more advanced image analysis or additional hardware customization. We benchmark SP to flow cytometry using calibrated silica nanoparticles and demonstrate superior, label-free sensitivity. We showcase SPFI's potential for EV analysis by experimentally distinguishing surface and volumetric EV dyes, observing the deformation of EVs adsorbed to a surface, and by uncovering distinct subpopulations in <100 nm-in-diameter EVs with fluorescently tagged membrane proteins., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies., Results: Herein, we have developed a nanoplatforms Cy-NMNO@SiO 2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1 O 2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO 2 realized efficient drug loading and drug delivery., Conclusions: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules., (© 2024. The Author(s).)

In contemporary floriculture, particularly within the cut flower industry, there is a burgeoning interest in innovative methodologies aimed at enhancing the aesthetic appeal and prolonging the postharvest longevity of floral specimens. Within this context, the application of nanotechnology, specifically the utilization of silicon and selenium nanoparticles, has emerged as a promising approach for augmenting the qualitative attributes and extending the vase life of cut roses. This study evaluated the impact of silicon dioxide (SiO 2 -NPs) and selenium nanoparticles (Se-NPs) in preservative solutions on the physio-chemical properties of 'Black Magic' roses. Preservative solutions were formulated with varying concentrations of SiO 2 -NPs (25 and 50 mg L -1 ) and Se-NPs (10 and 20 mg L -1 ), supplemented with a continuous treatment of 3% sucrose. Roses treated with 20 mg L -1 Se-NPs exhibited the lowest relative water loss, highest solution uptake, maximum photochemical performance of PSII (Fv/Fm), and elevated antioxidative enzyme activities. The upward trajectory of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) levels in petals was mitigated by different levels of SiO 2 and Se-NPs, with the lowest H 2 O 2 and MDA observed in preservatives containing 50 mg L -1 SiO 2 - and 20 mg L -1 Se-NPs at the 15th day, surpassing controls and other treatments. Extended vase life and a substantial enhancement in antioxidative capacity were noted under Se and Si nanoparticles in preservatives. The levels of total phenols, flavonoids, and anthocyanin increased during the vase period, particularly in the 50 and 20 mg L -1 Se-NPs and SiO 2 -NPs. Petal carbohydrate exhibited a declining trend throughout the longevity, with reductions of 8% and 66% observed in 20 mg L -1 Se-NPs and controls, respectively. The longest vase life was achieved with Se-NPs (20 mg L -1 ), followed by SiO 2 -NPs (50 mg L -1 ) up to 16.6 and 15th days, respectively. These findings highlight the significant potential of SiO 2 - and Se-NPs in enhancing the vase life and physiological qualities of 'Black Magic' roses, with SiO 2 -NPs showing broad-spectrum efficacy., (© 2024. The Author(s).)

Drawing inspiration from the unique properties of cactus spines and desert beetle shells, we have designed a biomimetic stainless steel mesh specifically for efficient water-in-oil emulsion separation. The tapered arrays of cactus spines are prepared by a light-curing-templating method, and the hydrophobic regions are constructed by adhering hydrophobic silica nanoparticles to the surface of the mesh. This innovative design takes full advantage of the unique properties of these two natural plants, which can agglomerate tiny emulsified water to achieve an emulsion-breaking effect only under static conditions. At the same time, the stainless steel mesh with the conical arrays has a high water-in-oil emulsion separation efficiency (up to 99.6%), high permeance (2400 L·m -2 ·h -1 ·bar -1 ), and good cycling performance. The concept of dual biomimetic explored in this work may extend beyond oil-water separation to encompass various applications, such as fog collection, droplet manipulation, and more.

This study investigates the adsorption of pollutants with different chemical structures; organic Naphtol Green B (NGB) dye and copper on a nanocomposite material with a hexagonal structure of the SBA-15 type. This research is divided into two main parts: the first carries out the synthesis of SBA-15 (Santa Barbra Amourphous) and its derivatives phases functionalized by 3-aminopropyl-triethoxylane (APTES) and calcined at 823 K. The second part presents the influence of the adsorption conditions on the adsorption efficiency of NGB dye and copper. High-resolution X-ray diffractogram (XRD) showed three distinct peaks characteristic of highly ordered mesoporous material. Nitrogen adsorption-desorption isotherm of SBA-15 at 77 K° is type IV typical of mesoporous materials. In addition, Fourier transform infrared spectroscopy (FT-IR) was also used in the characterization before and after the adsorption of the selected pollutants. At optimal conditions of pH 5.2, initial concentration of 50 mg/L, adsorbent dosage of 20 mg, and at adsorption time of 90 min the maximum removal of pollutants reached 76% and the adsorption capacity was 227.25 mg/g for NGB dye and 221.006 mg/g for copper. Furthermore, the adsorption kinetics followed the pseudo-second-order model, indicating that chemisorption was the dominant mechanism and the Sips isotherm model best described the adsorption data. Our research demonstrates that the SBA-15 material after modification is an effective adsorbent for removing effluents regardless of their different chemical structure (organic and inorganic)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Supported lipid bilayers (SLBs) are useful structures for mimicking cellular membranes, and they can be integrated with a variety of sensors. Although there are a variety of methods for forming SLBs, many of these methods come with limitations in terms of the lipid compositions that can be employed and the substrates upon which the SLBs can be deposited. Here we demonstrate the use of an all-aqueous chaotropic agent exchange process that can be used to form SLBs on two different substrate materials: SiO 2 , which is compatible with traditional SLB formation by vesicle fusion, and Al 2 O 3 , which is not compatible with vesicle fusion. When examined with a quartz crystal microbalance with dissipation monitoring, the SLBs generated by chaotropic agent exchange (CASLBs) have similar frequency and dissipation shifts to SLBs formed by the vesicle fusion technique. The CASLBs block nonspecific protein adsorption on the substrate and can be used to sense protein-lipid interactions. Fluorescence microscopy was used to examine the CASLBs, and we observed long-range lateral diffusion of fluorescent probes, which confirmed that the CASLBs were composed of a continuous, planar lipid bilayer. Our CASLB method provides another option for forming planar lipid bilayers on a variety of surfaces, including those that are not amenable to the widely used vesicle fusion method.

This study aimed to recover high-purity silica from hematite tailings (HTs) using superconducting high-gradient magnetic separation (S-HGMS) technology. This process involved converting silica into a silicone-rich concentrate and subsequently employing a fluorine-free mixed acid to leach the silicon-rich concentrate to remove impurities and achieve refinement and purification. The optimization of the S-HGMS process was conducted using the "Box-Behnken Design" method, resulting in the following optimal conditions: a pulp concentration of 50 g/L, a magnetic velocity ratio of 0.076 T s/m, and a pulp velocity of 500 mL/min. These conditions yielded a silica grade range of 61.905% in the HTs to 91.818% in the silicon-rich concentrate, with corresponding recovery rates of 53.031%. Under the optimized leaching process, this resulted in an increase in the silica content from 91.818% in the silicon-rich concentrate to 99.938% in high-purity silica. Additionally, by analyzing the production process of 1 kg of high-purity silica from HTs using the process LCA method, environmental hotspots were identified, and corresponding solutions were proposed. This approach is vital for efficient utilization of HTs as a resource. This process has low energy consumption and is environmentally friendly, enabling the reduction of hematite tailings. It has a wide range of applications and offers substantial economic benefits, rendering it a promising candidate for industrial applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Current research on tumor fibrosis has focused on cancer-associated fibroblasts, which may exert dual functions of tumor promotion and inhibition. Little attention has been paid to whether tumor cells themselves can undergo fibrotic transformation and whether they can inhibit parenchymal cells similar to pulmonary fibrosis, thus achieving the goal of inhibiting the malignant progression of tumors. To explore the significance of inducing tumor fibrosis for cancer treatment. This study utilizes mesoporous silica nanoparticles (MSN) loaded with Trehalose dimycolate (TDM) to induce tumor cell fibrosis through the dual effects of TDM-induced inflammatory granuloma and MSN-induced foreign body granuloma. The results show that TDM/MSN (TM) can effectively induce tumor fibrosis, manifested specifically by collagen internalization, and suppression of proliferation and invasion capabilities, suggesting the potential role of tumor fibrosis therapy. However, further investigation reveals that extrachromosomal DNA (ecDNA) mediates resistance to fibrosis induction. To comprehensively enhance the efficacy, WRN exonuclease is conjugated to TM to form new nanoparticles (TMW) capable of effectively eliminating ecDNA, globally promoting tumor cell fibroblast-like transformation, and validated in a PDX model to inhibit cancer progression. Therefore, TMW, through inducing tumor cell fibrosis to inhibit its malignant progression, holds great potential as a clinical treatment strategy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)