Local Concentration Research Articles

Shape-Directed Dynamic Assembly of Active Colloidal Metamachines.

Modularly organizing active micromachines into high-grade metamachines makes a great leap for operating the microscopic world in a biomimetic way. However, modulating the nonreciprocal interactions among different colloidal motors through chemical reactions to achieve the controllable construction of active colloidal metamachines with specific dynamic properties remains challenging. Here, we report the phototactic active colloidal metamachines constructed by shape-directed dynamic self-assembly of chemically driven peanut-shaped TiO2 colloidal motors and Janus spherical Pt/SiO2 colloidal motors. The long-range diffusiophoretic attraction generated by the photocatalytic reaction dominates the sensing and collision of peanut TiO2 motors with Janus Pt/SiO2 motors. The coupling of local chemical concentration gradient fields between the two types of motors generates short-range site-selective interactions, promoting the shape-directed assembly toward active colloidal metamachines with well-defined spatial configurations. Metamachines, made of colloidal motors, exhibit configuration-dependent kinematics. The colloidal metamachines can be reversibly reconstructed by adjusting lighting conditions and can move phototactically along a predetermined path under the structured light field. Such chemically driven colloidal metamachines that integrate multiple active agents provide a significant avenue for fabricating active soft matter materials and intelligent robotic systems with advanced applications.

Crown ether functionalization boosts CO2 electroreduction to ethylene on copper-based MOFs.

The electroconversion of CO2 into ethylene (C2H4) offers a promising solution to environmental and energy challenges. Crown ether (CE) modification significantly enhances the C2H4 selectivity of copper-based MOFs, improving C2H4 faradaic efficiency (FE) in CuBTC, CuBDC, and CuBDC-NH2 by 3.1, 1.7, and 2.4 times, respectively. Among these, CuBTC achieves the highest FE for C2H4, reaching ca. 52% at 120 mA cm-2. Control experiments and in situ Fourier transform infrared spectroscopy (FTIR) reveal that CE stabilizes Cu+ during the catalyst's in situ reconstruction, promoting the formation of Cu2O, which is more favorable for C2H4 production. Furthermore, CE increases the local concentration of K+ at the catalyst-electrolyte interface, enhancing *CO adsorption and facilitating C-C coupling reactions. This process promotes the formation of key intermediates, such as *CO*CO, *CO*COH and *COCHO, ultimately boosting C2H4 production.

Preoperative posterior quadratus lumborum block: Determining the minimum effective ropivacaine concentration in 90% of patients (MEC90) for postoperative analgesia after laparoscopic myomectomy.

Quadratus lumborum block (QLB) has gained traction as a regional anesthesia technique to manage postoperative pain following laparoscopic surgery. However, the 90% minimum effective concentration (MEC90) of local anesthetics for posterior QLB remains undetermined. We conducted a double-blind, comparative dose-finding study involving 54 women scheduled for elective laparoscopic myomectomy under general anesthesia. Each patient received a bilateral posterior QLB with 20 mL of ropivacaine on each side. The concentration administered varied for each patient and was determined based on the response of the previous participant. The initial concentration was set at 0.20%. Upon successful block, the subsequent patient was assigned to receive either the same (probability of 0.89) or a 0.05% lower concentration (probability of 0.11). In cases of block failure, the concentration was increased by 0.05% for the next patient. The trial concluded when 45 successful blocks were achieved, with block success defined as a pain score of three or fewer 30 minutes after arrival in the post-anesthesia care unit. The 90% minimum effective concentration (MEC90) of ropivacaine was 0.340% (95% CI 0.329 to 0.344%). The optimal concentration of ropivacaine for posterior QLB to achieve satisfactory analgesia following laparoscopic myomectomy is a 20 ml volume of 0.340% ropivacaine per side. Chinese Clinical Trial Registry ChiCTR2200055743.

The Hormetic Potential of GDF15 in Skeletal Muscle Health and Regeneration: A Comprehensive Systematic Review.

Growth Differentiation Factor 15 (GDF15) has been described as influencing skeletal physiology. Nevertheless, no systematic appraisal of the effect of GDF15 on skeletal muscle tissues has been developed to the present day. The aim of the present work was to review the evidence on the topic. In this preregistered systematic review (https://osf.io/wa8xr), articles were retrieved from MEDLINE/PubMed, EMBASE, and WebOfScience. Inclusion criteria comprised studies on humans or animal models, assessment of peripheral or local tissue GDF15 concentrations, as well as the direct expression of GDF15 in skeletal muscle, and direct or indirect correlates of GDF15 with physical activity/ sarcopenia/trophism/ function. A total of 646 studies were retrieved, and 144 finally included. Molecular inducers or inhibitors of GDF15 in skeletal muscle tissues were described. GDF15 was reported to promote skeletal muscle health, metabolic homeostasis, and overall physical conditioning. In pathology, GDF15 seems to be correlated to the degree of muscle impairment and mitochondrial stress. GDF15 has also been described as having the potential to stratify patients based on clinical prognosis and functional outcome. A hormetic hypothesis for GDF15 on skeletal muscle was proposed. In fact, GDF15 exhibited beneficial effects when expressed at high levels facing acute stressors (i.e., "myoprotection"). Conversely, GDF15 exhibited maladaptive effects, such as chronic low-grade inflammation, when chronically expressed in pathological processes (e.g., obesity, aging). GDF15 may be a potential molecular target for disease-modifying interventions. The current review underscores the need for further research on GDF15 to elucidate its therapeutic potential across different pathological states. The study protocol, registered before data collection and analysis, can be retrieved at https://osf.io/wa8xr. It should be noted that the study deviated from the protocol after peer review, including other electronic databases beyond MEDLINE/PubMed alone.

Selective aggregation of natural ligands into efficient AIEgens on a human telomeric duplex-G-quadruplex junction.

DNA structures with the potential to concurrently recruit multiple ligands are promising in pharmaceutical and sensing applications when concentrated in a local environment. Herein, we found that human telomeric G-quadruplex (htG4) structures with a junction can selectively aggregate a natural ligand of tetrahydropalmatine (THP) into AIEgens. The htG4 monomer favors formation of a THP dimer emitting at ∼525 nm. In addition, only a hybrid htG4 folding supports formation of the emissive THP dimer. However, overhanging a duplex beyond the 5' end of the hybrid htG4 structure preferentially forms THP J-aggregates with member molecularity being more than two. It is demonstrated that the junction between the duplex and the hybrid htG4 structure is responsible for formation of the THP J-aggregates, as confirmed by the fact that the pairing state of the junction affects the molecularity of the J-aggregates. Nevertheless, such J-aggregates cannot be grown at the junction of two tandem htG4s. Therefore, G4-initiated ligand aggregation (GILA) for natural compounds provides a new way to design pharmaceuticals and sensors with a high local concentration at the site of interest.

Tannic acid-modified FK506-loaded nanoparticles targeting lymph nodes for acute heart transplant rejection treatment.

Significant efforts have been made to deliver immunosuppressants-loaded nanoparticles (NPs) to lymph nodes (LNs) to mitigate transplant rejection. However, conventional administration techniques encounter challenges in enhancing the retention of NPs in the LNs. Attributing the strong affinity of tannic acid (TA) molecules to the elastin of LN conduits, we developed a novel formulation of NPs encapsulating Tacrolimus (FK506), and subsequently modified with TA to produce TA-FNP with a final diameter of approximately 86.07 ± 2.78 nm. These particles could traverse the the intercellular gaps in the lymphatic endothelial cells layers, enter the paracortex through LN capsule-associated conduits, and releases FK506 to inhibit the activation and proliferation of allogeneic T cells. Our finding demonstrated that TA-FNP could accumulate in LNs, significantly increasing the local concentration of FK506 from 69.06 ± 21.96 ng/g to 1041.28 ± 343.59 ng/g compared to the free FK506 treatment group. Subsequently, the therapeutic efficacy of TA-FNP was assessed in heart transplantation model, where treatment with TA-FNP resulted in decreased T cells infiltration within the grafts, reduced rejection grades, and a significant extension of graft survival time. In contrast, FNP without TA showed relatively poor therapeutic outcomes. Consequently, this study reveals a promising strategy utilizing TA to enhance the prolonged retention of FK506 within LNs, underscoring its potential therapeutic application in preventing heart transplant rejection.

A New Regional Background Atmospheric Station in the Yangtze River Delta Region for Carbon Monoxide: Assessment of Spatiotemporal Characteristics and Regional Significance

A new meteorological station (DMS) was established at the Morning Glory summit in Zhejiang Province to provide regional background information on atmospheric composition in the Yangtze River Delta (YRD) region, China. This study investigated the first carbon monoxide (CO) records at DMS from September 2020 to January 2022. The annual average concentration of CO was 233.4 ± 3.8 ppb, which exceeded the measurements recorded at the other Asian background sites. The winter CO concentration remained elevated but peaked in March in the early spring due to the combined effect of regional emissions within the YRD and transportation impacts of North China and Southeast Asia sources. The diurnal cycle had a nocturnal peak and a morning valley but with a distinct afternoon climb, as the metropolis in the YRD contributed to a local concentration enhancement. The back trajectory analysis and the Weighted Potential Sources Contribution Function (WPSCF) maps highlighted emissions from Anhui, Jiangxi, Zhejiang, and Jiangsu provinces as significant sources. Due to well-mixed air conditions and fewer anthropogenic influences, DMS records closely aligned with the CO averages derived from the Copernicus Atmospheric Monitoring Service (CAMS) covering the YRD, confirming its representativeness for regional CO levels. This study underscored DMS as a valuable station for monitoring and understanding CO spatiotemporal characteristics in the YRD region.

Temperature Sensing in Agarose/Silk Fibroin Translucent Hydrogels: Preparation of an Environment for Long-Term Observation.

Environmental changes, such as applied medication, nutrient depletion, and accumulation of metabolic residues, affect cell culture activity. The combination of these factors reflects on the local temperature distribution and local oxygen concentration towards the cell culture scaffold. However, determining the temporal variation of local temperature, independent of local oxygen concentration changes in biological specimens, remains a significant technological challenge. The process of triplet-triplet annihilation upconversion (TTA-UC), performed in a nanoconfined environment with a continuous aqueous phase, appears to be a possible solution to these severe sensing problems. This process generates two optical signals (delayed emitter fluorescence (dF) and residual sensitizer phosphorescence (rPh)) in response to a single external stimulus (local temperature), allowing the application of the ratiometric-type sensing procedure. The ability to incorporate large amounts of sacrificial singlet oxygen scavenging materials, without altering the temperature sensitivity, allows long-term protection against photo-oxidative damage to the sensing moieties. Translucent agarose/silk fibroin hydrogels embedding non-ionic micellar systems containing energetically optimized annihilation couples simultaneously fulfill two critical functions: first, to serve as mechanical support (for further application as a cell culture scaffold); second, to allow tuning of the material response window to achieve a maximum temperature sensitivity better than 0.5 K for the physiologically important region around 36 °C.

Mechanism of solid electrolyte interphase film formation using ethylene carbonate-based local high concentration electrolyte in sodium-ion batteries.

Sodium-ion batteries (SIBs) have the advantages of abundant resources and low cost, making them potential candidates for the next-generation large-scale energy storage technology. However, the capacity fade during cycling used in sodium-ion batteries is a major challenge. The rational design of the electrolyte is one of the ways to solve these problems. In this work, 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (HFE) is introduced into a sodium hexafluorophosphate (NaPF6)/ethylene carbonate (EC) electrolyte to design a locally high concentration electrolyte (LHCE), which helps stabilize the solid electrolyte interphase (SEI) in sodium-ion batteries (SIBs). By modulating the solvation structure of the electrolyte, a NaF-rich SEI is formed on the surfaces of electrodes. With sodium iron phosphate (NFPO) as the cathode, the cell maintained a capacity retention rate of 91.5 % after 300 cycles at 0.5C. In addition, a sodium nickel iron manganese oxide (NFMO)||Hard carbon (HC) pouch cell achieves a capacity retention of 84.2 % after 500 cycles at 1C. This study provides a new perspective for the understanding and design of locally high concentration electrolytes for sodium-ion batteries.

Photospheric Swirls in a Quiet-Sun Region

Abstract Swirl-shaped flow structures have been observed throughout the solar atmosphere, in both emission and absorption, at different altitudes and locations, and are believed to be associated with magnetic structures. However, the distribution patterns of such swirls, especially their spatial positions, remain unclear. Using the Automated Swirl Detection Algorithm, we identified swirls from the high-resolution photospheric observations, centered on Fe i 630.25 nm, of a quiet region near the Sun's central meridian by the Swedish 1-m Solar Telescope. Via a detailed study of the locations of the detected small-scale swirls with an average radius of ~300 km, we found that most of them are located in lanes between mesogranules (which have an average diameter of ~5.4 Mm) instead of the commonly believed intergranular lanes. The squared rotation, expansion/contraction and vector speeds, and proxy kinetic energy are all found to follow Gaussian distributions. Their rotation speed, expansion/contraction speed, and circulation are positively correlated with their radius. All these results suggest that photospheric swirls at different scales and locations across the observational 56 . ″ 5 × 57 . ″ 5 field of view could share the same triggering mechanism at preferred spatial and energy scales. A comparison with our previous work suggests that the number of photospheric swirls is positively correlated with the number of local magnetic concentrations, stressing again the close relation between swirls and local magnetic concentrations: the number of swirls should positively correlate with the number and strength of local magnetic concentrations.

Targeted Enrichment of Nucleic Acid Bionic Arms Enhances the Hydrolysis Activity of Nanozymes for Degradation and Real-Time Monitoring of Organophosphorus Pesticides in Water.

Organophosphorus pesticides (OPs) pose significant environmental and health risks, and their detoxification through catalytic hydrolysis using zirconium-based metal-organic frameworks (Zr-MOFs) has attracted considerable interest due to the strong Lewis acid metal ions. Albeit important, the defects of the materials for OP hydrolysis (e.g., poor degradation efficiency, rate, and selectivity) limit their further application. Herein, a nucleic acid bionic arm-modified biomimetic nanozyme (MOF-808-Apt) was designed through a Zr-MOF and a specific aptamer against OPs, which was employed for the efficient and selective degradation of OPs. At the system, the functionalized biomimetic nanozyme can continuously capture trace OPs onto its catalytic sites for degradation with the fabricated nucleic acid bionic arms, significantly improving their catalytic activities compared to bare MOF-808 using paraoxon as a model of OPs, providing better performances including (i) an excellent degradation efficiency, boosting from 4 to over 60% within 6 min; (ii) a satisfactory catalytic rate (the pseudo-first-order rate constants of paraoxon hydrolysis improved from 0.09 to 0.14 min-1); and (iii) good selective degradation because of aptamers used. Besides, this dynamic degradation process could be visually recorded in real time with high sensitivity (limit of detection, 0.18 μM) because of the obvious color change of the reaction solution and signal amplification ascribed to increasing local concentrations of targets by the nucleic acid bionic arms. Summarily, this work provides a new strategy for the effective and selective degradation of typical OPs and concurrent monitoring of their dynamic degradation process.

Quantitative Measurement of Molecular Permeability to a Synthetic Bacterial Microcompartment Shell System.

Naturally evolved and synthetically designed forms of compartmentalization benefit encapsulated function by increasing local concentrations of substrates and protecting cargo from destabilizing environments and inhibitors. Crucial to understanding the fundamental principles of compartmentalization are experimental systems enabling the measurement of the permeability rates of small molecules. Here, we report the experimental measurement of the small-molecule permeability of a 40 nm icosahedral bacterial microcompartment shell. This was accomplished by heterologous loading of light-producing luciferase enzymes and kinetic measurement of luminescence using stopped-flow spectrophotometry. Compared to free enzyme, the luminescence signal kinetics was slower when the luciferase was encapsulated in bacterial microcompartment shells. The results indicate that substrates and products can still exchange across the shell, and modeling of the experimental data suggest that a 50× permeability rate increase occurs when shell vertices were vacant. Overall, our results suggest design considerations for the construction of heterologous bacterial microcompartment shell systems and compartmentalized function at the nanoscale.

Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates.

Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization. We observed that the psi (Ψ) packaging signal and the dimerization initiation sequence (DIS) had stabilizing effects on RSV Gag condensates, while RNAs lacking these features promoted or antagonized condensation, depending on local protein concentration and condensate architecture. An RNA containing Ψ, DIS, and the dimerization linkage structure (DLS) that is capable of stable dimer formation was observed to act as a bridge between RSV Gag condensates. These observations suggest additional, condensate-related roles for Gag-Ψ binding, gRNA dimerization, and Gag dimerization/multimerization in gRNA selection and packaging, representing a significant step forward in our understanding of how these interactions collectively facilitate efficient genome packaging.

Using the appropriate modulus of elasticity of periodontal ligament matters in stress analysis of human first premolar tooth and periodontium structures

Although the modulus of elasticity of the human periodontal ligament (EPDL) values used in dentistry widely ranged from 0.01 to 175 MPa, the exact EPDL value has not been determined. This study aimed to verify whether and how EPDL values affect the stress distribution over the tooth and periodontium structures, and to determine the appropriate EPDL range. A 3D multi-component human first premolar model was created based on a cone-beam computed tomography dataset. Finite element analysis was performed to analyze stress distribution and deformation of the structures under an average Asian occlusal force with different EPDL values (0.0689–68.9 MPa). The low EPDL caused excessive PDL deformation, contributing to a non-uniform stress distribution and localized stress concentration, especially in the cementum, enamel, and dentin. With the low EPDL value, the stress magnitude was overestimated by 1,195%, potentially leading to erroneous conclusions regarding material failure and tooth movement. The EPDL value significantly affects the stress magnitude and distribution over the tooth and periodontium. The appropriate EPDL range of 0.964 ± 0.276 MPa is suggested for human first premolars to ensure accurate and reliable FEA simulations and help avoid misinterpretation of the stress results, which could compromise orthodontic planning and restoration design.

Probing Macromolecular Conformation in Restricted Geometry by PEF: Application to Hydrophobically Modified PAMAM Dendrimers Isolated Inside Surfactant Micelles.

The conformation of a series of zero-generation polyamidoamine dendrimers end-labeled with four 1-pyrene-butyroyl, -hexanoyl, -octanoyl, -decanoyl, and -dodecanoyl derivatives, referred to as the PyCX-PAMAM-G0 samples with X = 4, 6, 8, 10, and 12, respectively, was characterized in N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and aqueous solutions of 50 mM sodium dodecyl sulfate (SDS) or 50 mM dodecyltrimethylammonium bromide (DTAB). The conformation of the PyCX-PAMAM-G0 samples was determined from the global model-free analysis (MFA) of the fluorescence decays, which yielded the average rate constant (⟨k⟩) for pyrene excimer formation (PEF) between an excited and a ground-state pyrenyl labels, with ⟨k⟩ being proportional to the local concentration ([Py]loc) of the pyrenyl labels within the macromolecular volume; ⟨k⟩-vs-[Py]loc plots yielded straight lines passing through the origin in DMF and DMSO, demonstrating that the internal segments of the dendrimers obeyed Gaussian statistics in these two solvents. In aqueous surfactant solutions, the hydrophobic pyrenyl labels induced the interactions of the PyCX-PAMAM-G0 dendrimers with the SDS and DTAB micelles. Plots of ⟨k⟩ as a function of [Py]loc yielded straight lines passing through the origin for the PyCX-PAMAM-G0 samples with X equal to 4, 6, and 8, indicating that the internal segments of these three dendrimers obeyed Gaussian statistics within the surfactant micelles. However, ⟨k⟩ departed from the straight lines for the PyCX-PAMAM-G0 samples with X = 10 and 12 associated with the SDS and DTAB micelles. This behavior indicated that [Py]loc was much larger than expected for the dendrimers prepared with longer alkanoyl linkers. This behavior was attributed to strong hydrophobic interactions between the longer linkers and the dodecyl tails of the surfactants in the hydrophobic core of the micelles, which induced a conformational change for the dendrimers inside the micelles, that could be probed at the molecular level by PEF.

Proton Accumulation Modulated Surface Potential in Proton Conducting Ceramics Revealed by Near-Ambient Pressure X-ray Photoelectron Spectroscopy.

Proton conducting electrochemical cells (PCECs) are efficient and clean intermediate-temperature energy conversion devices. The proton concentration across the PCECs is often nonuniform, and characterizing the distribution of proton concentration can help to locate the position of rate-limiting reactions. However, the determination of the local proton concentration under operating conditions remains challenging. Here, we employed in situ near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) to investigate an Au/BaZr0.9Y0.1O3-δ/Au symmetric cell with DC bias of 1 V applied between the working and counter electrodes (CE). The relative intensity of hydroxyl groups, deconvoluted from the O 1s XPS spectra, reveals the distribution of proton concentration across the electrolyte. The applied electric field induces proton accumulation at the counter electrode, imposing binding energy shifts of the surface components for metal elements relative to their lattice components. Combined XPS and impedance analysis suggests that the accumulation layer of protons is much thicker at 500 K compared to that at 670 K, as a result of a larger amount of hydroxyl groups at the lower temperature. This nonuniform distribution of proton concentration affects the chemical environment of metal elements, and the local electrical potential, as revealed by the in situ XPS. This work demonstrates in situ NAP-XPS as a tool to probe the distribution of proton concentration and its impact on the defect chemistry and local electrical potential of PCECs, thereby advancing the understanding of the impact of proton defect chemistry and the performance improvement of PCECs.

Study on the Stress Accumulation Characteristics of a Rotating Metal Hydride Reactor

The reactor is the core device used in guaranteeing the alloy's stable high-level reversible hydrogen storage. This work investigates a rotating reactor as new structure to alleviate stress accumulation using inertial force and counterforce, compared to typical statics reactors. The rotating reactor’s strain and response exhibited notable differences in the whole five stages at the 8th absorption/desorption cycle. In the cycle of vertical reactor, plastic deformation began by the 4th cycle, followed by a rapid linear increase in strain values leading swiftly to failure in the 19th cycle. When inverted, plastic deformation began by the 17th cycle and fracture occurred after 29th cycles, and for rotating reactor at 1.39 rpm, the curve of stress accumulation changed gently, sudden fracture occurred after 36th cycles. Particle size distribution of rotating reactor was skewed toward the large size as a herald of more strong anti-pulverization. Meanwhile, the expansion area was located in lower part, and the bulging notably shifted upwards compared to vertical reactor. This was attributed to the fact that the dynamic inertial force and counterforce effect improved the uniformity of alloy filling and prevented the formation of high-density areas at the representative bottom obviously alleviating local stress concentration phenomena.

Active fluorobenzene diluent regulated tetraglyme electrolyte enabling high-performance Li metal batteries

Electrolytes with superior compatibility with Li metal anodes and high-voltage cathodes are crucial for high-voltage Li metal batteries. Herein, tetraglyme (G4) with both high oxidation stability and reduction stability is employed to design localized high concentration electrolyte (G4-FB) regulated by active diluent fluorobenzene (FB) via active diluent-anion synergy strategy. FB possesses high activity for generating LiF and cooperates with anions to construct robust LiF-rich solid electrolyte interphases (SEIs) and cathode-electrolyte interphases (CEIs), effectively enhancing the interfacial stability of Li metal anodes and LiNi0.8Mn0.1Co0.1O2 (NCM811) cathodes. G4-FB enables high-efficiency (99.7%), long-term (1439 h) and dendrite-free cycle of Li||Li cells and Li||Cu cells. Parasitic interface reactions and structural damages of NCM811 are significantly suppressed by the robust LiF-rich CEIs. G4-FB markedly boosts the performance of NCM811||Li cells even under harsh conditions, including high voltage (4.5 V), high temperature (60°C), high cathode loading (3.6 mAh cm−2) and thin Li metal anode (50 μm), which display a high capacity retention of 86.3% after 300 cycles. The powerful diluent effect of FB remarkably decreases viscosity, increases ionic conductivity and enhances wettability of G4-FB. This work presents a promising design strategy of highly efficient electrolytes for Li metal batteries.

Ion concentration polarization causes a nearly pore-length-independent conductance of nanopores.

There has been a great amount of interest in nanopores as the basis for sensors and templates for preparation of biomimetic channels as well as model systems to understand transport properties at the nanoscale. The presence of surface charges on the pore walls has been shown to induce ion selectivity as well as enhance ionic conductance compared to uncharged pores. Here, using three-dimensional continuum modeling, we examine the role of the length of charged nanopores as well as applied voltage for controlling ion selectivity and ionic conductance of single nanopores and small nanopore arrays. First, we present conditions where the ion current and ion selectivity of nanopores with homogeneous surface charges remain unchanged, even if the pore length decreases by a factor of 6. This length-independent conductance is explained through the effect of ion concentration polarization (ICP), which modifies local ionic concentrations, not only at the pore entrances but also in the pore in a voltage-dependent manner. We describe how voltage controls the ion selectivity of nanopores with different lengths and present the conditions when charged nanopores conduct less current than uncharged pores of the same geometrical characteristics. The manuscript provides different measures of the extent of the depletion zone induced by ICP in single pores and nanopore arrays, including systems with ionic diodes. The modeling shown here will help design selective nanopores for a variety of applications where single nanopores and nanopore arrays are used.

Protein abundance of drug transporters and drug-metabolizing enzymes in paired healthy and tumor tissue from colorectal cancer patients.

The widespread prevalence of colorectal cancer and its high mortality rate emphasize the urgent need for more effective therapies. When developing new drug products, a key aspect is ensuring that sufficiently high concentrations of the active drug are reached at the site of action. Drug transporters and drug-metabolizing enzymes can significantly influence the absorption and local accumulation of drugs in intestinal tissue. To understand how their presence may affect local drug disposition, the protein abundance of multiple drug transporters and drug-metabolizing enzymes was quantified in paired healthy colonic mucosa and colorectal adenocarcinoma tissue from colorectal cancer patients, utilizing mass spectrometry-based targeted proteomics. Statistically significant changes in protein expression were observed for two transporters (MRP1 and BCRP) and three of the studied enzymes (CES1, CES2 and UGT2B17). MRP1 displayed higher levels in cancerous tissue compared to healthy mucosa samples, while BCRP, CES1, CES2 and UGT2B17 showed the opposite. Other proteins of interest which could be quantified in colonic samples were the drug transporters P-gp, MRP3, MRP4, OATP2B1, MCT1 and enzymes CYP4F2, CYP2J2 and UGT1A1. The insights from this study enhance our understanding of the extent to which drug disposition in tumor tissue of colorectal cancer patients could be impacted by drug transporters and drug-metabolizing enzymes and may facilitate a more accurate prediction of local drug concentrations.