Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

BACKGROUND: Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. METHODS: A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. RESULTS: Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.534-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. No associations were observed for the other medications. CONCLUSIONS: Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

Giant piezoresponse in nanoporous (Ba,Ca)(Ti,Zr)O3 thin film.

Lattice strain effects on the piezoelectric properties of crystalline ferroelectrics have been extensively studied for decades; however, the strain dependence of the piezoelectric properties at nano-level has yet to be investigated. Herein, a new overview of the super-strain of nanoporous polycrystalline ferroelectrics is reported for the first time using a nanoengineered barium calcium zirconium titanate composition (Ba0.85Ca0.15)(Ti0.9Zr0.1)O3 (BCZT). Atomic-level investigations show that the controlled pore wall thickness contributes to highly strained lattice structures that also retain the crystal size at the optimal value (<30 nm), which is the primary contributor to high piezoelectricity. The strain field derived from geometric phase analysis at the atomic level and aberration-corrected high-resolution scanning transmission electron microscopy (STEM) yields of over 30% clearly show theoretical agreement with high piezoelectric properties. The uniqueness of this work is the simplicity of the synthesis; moreover the piezoresponse d 33 becomes giant, at around 7500 pm V-1. This response is an order of magnitude greater than that of lead zirconate titanate (PZT), which is known to be the most successful ferroelectric over the past 50 years. This concept utilizing nanoporous BCZT will be highly useful for a promising high-density electrolyte-free dielectric capacitor and generator for energy harvesting in the future.

A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test (n = 20) (Pearson's r = 0.99) and validation (n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to therapy.

Disentangling oncogenic amplicons in esophageal adenocarcinoma.

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons' origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.

Mesoporous Gold: Substrate-Dependent Growth Dynamics, Strain Accumulation, and Electrocatalytic Activity for Biosensing.

Understanding the growth of mesoporous crystalline materials, such as mesoporous metals, on different substrates can provide valuable insights into the crystal growth dynamics and the redox reactions that influence their electrochemical sensing performance. Herein, it is demonstrated how the amorphous nature of the glass substrate can suppress the typical <111> oriented growth in mesoporous Au (mAu) films. The suppressed <111> growth is manifested as an accumulation of strain, leading to the generation of abundant surface defects, which are beneficial for enhancing the electrochemical activity. The fine structuring attained enables dramatically accelerated diffusion and enhances the electrochemical sensing performance for disease-specific biomolecules. As a proof-of-concept, the as-fabricated glass-grown mAu film demonstrates high sensitivity in electrochemical detection of SARS-CoV-2-specific RNA with a limit of detection (LoD) as low as 1 attomolar (aM).

A mesoporous gold biosensor to investigate immune checkpoint protein heterogeneity in single lung cancer cells.

Immune checkpoint proteins (ICPs) play a major role in a patient's immune response against cancer. Tumour cells usually express those proteins to communicate with immune cells as a process of escaping the anti-cancer immune response. Detecting the major functional immune checkpoint proteins present on cancer cells (such as circulating tumor cells or CTCs) and examining the heterogeneity in their expression at the single-cell level could play a crucial role in both cancer diagnosis and the monitoring of therapy. In this study, we develop a mesoporous gold biosensor to precisely assess ICP heterogeneity in individual cancer cells within a lung cancer model. The platform utilizes a nanostructured mesoporous gold surface to capture CTCs and a Surface Enhanced Raman Scattering (SERS) readout to identify and monitor the expression of key ICP proteins (PD-L1, B7H4, CD276, CD80) in lung cancer cells. The homogeneous and abundant pores in mesoporous 3D gold nanostructures enable increased antibody loading on-chip and an enhanced SERS signal, which are key to our single cell capture, and accurate analysis of ICPs in cancer cells with high sensitivity. Our lung cancer cell line model data showed that our method can detect single cells and analyse the expression of four lung cancer associated ICPs on individual cell surfaces during treatment. To show the potential of our mesoporous gold biosensor in analysing clinical samples, we tested 9 longitudinal Peripheral Blood Mononuclear Cells (PBMC) samples from lung cancer patient before and after therapy. Our mesoporous biosensor successfully captured single CTCs and found that the expression of ICPs in CTCs is highly heterogeneous in both pre-treatment and treated PBMC samples isolated from lung cancer patient blood. We suggest that our findings will help clinicians in selecting the most appropriate therapy for patients.

Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma.

A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.

Au-Loaded Superparamagnetic Mesoporous Bimetallic CoFeB Nanovehicles for Sensitive Autoantibody Detection.

Construction of a well-defined mesoporous nanostructure is crucial for applying nonnoble metals in catalysis and biomedicine owing to their highly exposed active sites and accessible surfaces. However, it remains a great challenge to controllably synthesize superparamagnetic CoFe-based mesoporous nanospheres with tunable compositions and exposed large pores, which are sought for immobilization or adsorption of guest molecules for magnetic capture, isolation, preconcentration, and purification. Herein, a facile assembly strategy of a block copolymer was developed to fabricate a mesoporous CoFeB amorphous alloy with abundant metallic Co/Fe atoms, which served as an ideal scaffold for well-dispersed loading of Au nanoparticles (∼3.1 nm) via the galvanic replacement reaction. The prepared Au-CoFeB possessed high saturation magnetization as well as uniform and large open mesopores (∼12.5 nm), which provided ample accessibility to biomolecules, such as nucleic acids, enzymes, proteins, and antibodies. Through this distinctive combination of superparamagnetism (CoFeB) and biofavorability (Au), the resulting Au-CoFeB was employed as a dispersible nanovehicle for the direct capture and isolation of p53 autoantibody from serum samples. Highly sensitive detection of the autoantibody was achieved with a limit of detection of 0.006 U/mL, which was 50 times lower than that of the conventional p53-ELISA kit-based detection system. Our assay is capable of quantifying differential expression patterns for detecting p53 autoantibodies in ovarian cancer patients. This assay provides a rapid, inexpensive, and portable platform with the potential to detect a wide range of clinically relevant protein biomarkers.

Magnetic Hydrogel Composite for Wastewater Treatment.

Nanocomposite hydrogels are highly porous colloidal structures with a high adsorption capacity, making them promising materials for wastewater treatment. In particular, magnetic nanoparticle (MNP) incorporated hydrogels are an excellent adsorbent for aquatic pollutants. An added advantage is that, with the application of an external magnetic field, magnetic hydrogels can be collected back from the wastewater system. However, magnetic hydrogels are quite brittle and structurally unstable under compact conditions such as in fixed-bed adsorption columns. To address this issue, this study demonstrates a unique hydrogel composite bead structure, providing a good adsorption capacity and superior compressive stress tolerance due to the presence of hollow cores within the beads. The gel beads contain alginate polymer as the matrix and MNP-decorated cellulose nanofibres (CNF) as the reinforcing agent. The MNPs within the gel provide active adsorption functionality, while CNF provide a good stress transfer phenomenon when the beads are under compressive stress. Their adsorption performance is evaluated in a red mud solution for pollutant adsorption. Composite gel beads have shown high performance in adsorbing metal (aluminium, potassium, selenium, sodium, and vanadium) and non-metal (sulphur) contaminations. This novel hybrid hydrogel could be a promising alternative to the conventionally used toxic adsorbent, providing environmentally friendly operational benefits.

Hydrogel Nanoarchitectonics: An Evolving Paradigm for Ultrasensitive Biosensing.

The integration of nanoarchitectonics and hydrogel into conventional biosensing platforms offers the opportunities to design physically and chemically controlled and optimized soft structures with superior biocompatibility, better immobilization of biomolecules, and specific and sensitive biosensor design. The physical and chemical properties of 3D hydrogel structures can be modified by integrating with nanostructures. Such modifications can enhance their responsiveness to mechanical, optical, thermal, magnetic, and electric stimuli, which in turn can enhance the practicality of biosensors in clinical settings. This review describes the synthesis and kinetics of gel networks and exploitation of nanostructure-integrated hydrogels in biosensing. With an emphasis on different integration strategies of hydrogel with nanostructures, this review highlights the importance of hydrogel nanostructures as one of the most favorable candidates for developing ultrasensitive biosensors. Moreover, hydrogel nanoarchitectonics are also portrayed as a promising candidate for fabricating next-generation robust biosensors.

Cu-based MOF-derived architecture with Cu/Cu2O nanospheres anchored on porous carbon nanosheets for efficient capacitive deionization.

The design of high-performance electrode materials with excellent desalination ability has always been a research goal for efficient capacitive deionization (CDI). Herein, a hybrid architecture with Cu/Cu2O nanospheres anchored on porous carbon nanosheets (Cu/Cu2O/C) was first synthesized by pyrolyzing a two-dimensional (2D) Cu-based metal-organic framework and then evaluated as a cathode for hybrid CDI. The as-prepared Cu/Cu2O/C exhibits a hierarchically porous structure with a high specific surface area of 305 m2 g-1 and large pore volume of 0.55 cm3 g-1, which is favorable to accelerating ion migration and diffusion. The porous carbon nanosheet matrix with enhanced conductivity will facilitate the Faradaic reactions of Cu/Cu2O nanospheres during the desalination process. The Cu/Cu2O/C hybrid architecture displays a high specific capacitance of 142.5 F g-1 at a scan rate of 2 mV s-1 in 1 M NaCl solution. The hybrid CDI constructed using the Cu/Cu2O/C cathode and a commercial activated carbon anode exhibits a high desalination capacity of 16.4 mg g-1 at an operation voltage of 1.2 V in 500 mg L-1 NaCl solution. Additionally, the hybrid CDI exhibits a good cycling stability with 18.3% decay in the desalination capacity after 20 electrosorption-desorption cycles. Thus, the Cu/Cu2O/C composite is expected to be a promising cathode material for hybrid CDI.

Recent progress of functional metal-organic framework materials for water treatment using sulfate radicals.

Human health is being threatened by the ever-increasing water pollution. Sulfate radical (SO4•-)-based advanced oxidation processes (SR-AOPs) are rapidly being developed and gaining considerable attention due to their high oxidation potential and selectivity as a way to purify water by degrading organic contaminants in it. Among the catalytic materials that can activate the precursor to generate SO4•-, metal-organic frameworks (MOFs) are the most promising heterogeneous catalytic material in SR-AOPs because of their various structure possibilities, large surface area, ordered porous structure, and regular activation sites. Herein, an in-depth overview of MOFs and their derivatives for water purification with SR-AOPs is provided. The latest studies on pristine MOFs, MOF composites, and MOF derivatives (metal oxides, metal-carbon hybrids, and carbon materials) are summarized. The mechanisms of decomposition of pollutants in water via radical and non-radical pathways are also discussed. This review suggests future research directions for water purification through MOF-based SR-AOP.

MgB2 Superconducting Joint Architecture with the Functionality to Screen External Magnetic Fields for MRI Magnet Applications.

A superconducting joint architecture to join unreacted carbon-doped multifilament magnesium diboride (MgB2) wires with the functionality to screen external magnetic fields for magnetic resonance imaging (MRI) magnet applications is proposed. The intrinsic diamagnetic property of a superconducting MgB2 bulk was exploited to produce a magnetic field screening effect around the current transfer path within the joint. Unprecedentedly, the joint fabricated using this novel architecture was able to screen magnetic fields up to 1.5 T at 20 K and up to 2 T at 15 K and thereby almost nullified the effect of the applied magnetic field by maintaining a constant critical current (Ic). The joint showed an Ic of 30.8 A in 1.5 T at 20 K and an ultralow resistance of about 3.32 × 10-14 Ω at 20 K in a self-field. The magnetic field screening effect shown by the MgB2 joint is expected to be extremely valuable for MRI magnet applications, where the Ic of the joints is lower than the Ic of the connected MgB2 wires in a given magnetic field and temperature.

Efficient lithium-ion storage using a heterostructured porous carbon framework and its in situ transmission electron microscopy study.

A heterostructured porous carbon framework (PCF) composed of reduced graphene oxide (rGO) nanosheets and metal organic framework (MOF)-derived microporous carbon is prepared to investigate its potential use in a lithium-ion battery. As an anode material, the PCF exhibits efficient lithium-ion storage performance with a high reversible specific capacity (771 mA h g-1 at 50 mA g-1), an excellent rate capability (448 mA h g-1 at 1000 mA g-1), and a long lifespan (75% retention after 400 cycles). The in situ transmission electron microscopy (TEM) study demonstrates that its unique three-dimensional (3D) heterostructure can largely tolerate the volume expansion. We envisage that this work may offer a deeper understanding of the importance of tailored design of anode materials for future lithium-ion batteries.

Macroscopic MOF Architectures: Effective Strategies for Practical Application in Water Treatment.

Metal-organic frameworks (MOFs) have potential applications in removing pollutants such as heavy metals, oils, and toxins from water. However, due to the intrinsic fragility of MOFs and their fine powder form, there are still technical barriers to their practical application such as blockage of pipes, difficulty in recovery, and potential environmental toxicity. Therefore, attention has focused on approaches to convert nanocrystalline MOFs into macroscopic materials to overcome these limitations. Recently, strategies for shaping MOFs into beads (0D), nanofibers (1D), membranes (2D), and gels/sponges (3D) with macrostructures are developed including direct mixing, in situ growth, or deposition of MOFs with polymers, cotton, foams or other porous substrates. In this review, successful strategies for the fabrication of macroscopic materials from MOFs and their applications in removing pollutants from water including adsorption, separation, and advanced oxidation processes, are discussed. The relationship between the macroscopic performance and the microstructure of materials, and how the range of 0D to 3D macroscopic materials can be used for water treatment are also outlined.

Recent Advances and Perspectives of Battery-Type Anode Materials for Potassium Ion Storage.

Potassium ion energy storage devices are competitive candidates for grid-scale energy storage applications owing to the abundancy and cost-effectiveness of potassium (K) resources, the low standard redox potential of K/K+, and the high ionic conductivity in K-salt-containing electrolytes. However, the sluggish reaction dynamics and poor structural instability of battery-type anodes caused by the insertion/extraction of large K+ ions inhibit the full potential of K ion energy storage systems. Extensive efforts have been devoted to the exploration of promising anode materials. This Review begins with a brief introduction of the operation principles and performance indicators of typical K ion energy storage systems and significant advances in different types of battery-type anode materials, including intercalation-, mixed surface-capacitive-/intercalation-, conversion-, alloy-, mixed conversion-/alloy-, and organic-type materials. Subsequently, host-guest relationships are discussed in correlation with the electrochemical properties, underlying mechanisms, and critical issues faced by each type of anode material concerning their implementation in K ion energy storage systems. Several promising optimization strategies to improve the K+ storage performance are highlighted. Finally, perspectives on future trends are provided, which are aimed at accelerating the development of K ion energy storage systems.

Effect of Heat Treatments under High Isostatic Pressure on the Transport Critical Current Density at 4.2 K and 20 K in Doped and Undoped MgB2 Wires.

Annealing undoped MgB2 wires under high isostatic pressure (HIP) increases transport critical current density (Jtc) by 10% at 4.2 K in range magnetic fields from 4 T to 12 T and significantly increases Jtc by 25% in range magnetic fields from 2 T to 4 T and does not increase Jtc above 4 T at 20 K. Further research shows that a large amount of 10% SiC admixture and thermal treatment under a high isostatic pressure of 1 GPa significantly increases the Jtc by 40% at 4.2 K in magnetic fields above 6 T and reduces Jtc by one order at 20 K in MgB2 wires. Additionally, our research showed that heat treatment under high isostatic pressure is more evident in wires with smaller diameters, as it greatly increases the density of MgB2 material and the number of connections between grains compared to MgB2 wires with larger diameters, but only during the Mg solid-state reaction. In addition, our study indicates that smaller wire diameters and high isostatic pressure do not lead to a higher density of MgB2 material and more connections between grains during the liquid-state Mg reaction.

Extracellular Vesicle Nanoarchitectonics for Novel Drug Delivery Applications.

Extracellular vesicles (EVs) can transfer intercellular messages in various (patho)physiological processes and transport biomolecules to recipient cells. EVs possess the capacity to evade the immune system and remain stable over long periods, identifying them as natural carriers for drugs and biologics. However, the challenges associated with EVs isolation, heterogeneity, coexistence with homologous biomolecules, and lack of site-specific delivery, have impeded their potential. In recent years, the amalgamation of EVs with rationally engineered nanostructures has been proposed for achieving effective drug loading and site-specific delivery. With the advancement of nanotechnology and nanoarchitectonics, different nanostructures with tunable size, shapes, and surface properties can be integrated with EVs for drug loading, target binding, efficient delivery, and therapeutics. Such integration may enable improved cellular targeting and the protection of encapsulated drugs for enhanced and specific delivery to target cells. This review summarizes the recent development of nanostructure amalgamated EVs for drug delivery, therapeutics, and real-time monitoring of disease progression. With a specific focus on the exosomal cargo, diverse drug delivery system, and biomimetic nanostructures based on EVs for selective drug delivery, this review also chronicles the needs and challenges of EV-based biomimetic nanostructures and provides a future outlook on the strategies posed.