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Background: Aptasensors have been extensively utilized in target detection due to their advantages of high sensitivity and fast response. However, the reliability of the detection results of the single-mode aptasensor cannot be verified in time. Developing efficient detection methods with cross-validation capability is beneficial to achieving highly reliable detection. This study aims to design a colorimetric and fluorescent dual-mode aptasensor by skillfully engineering G-quadruplex assembly and rolling circle amplification for highly reliable IFN-γ detection., Results: The complexes of anti-IFN-γ aptamers and complement sequences (cDNA) were modified on the magnetic beads. In the presence of IFN-γ, the preferential combination of aptamers with IFN-γ resulted in the release of cDNAs. The cDNAs were collected by magnetic separation and then used as primers to trigger rolling circle amplification reaction to generate enriched G-quadruplexes. The G-quadruplex could be utilized to combine with hemin to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine for colormetric mode or to couple with the fluorogenic dye Thioflavin T for fluorescent mode. The developed dual-mode aptasensor displayed a linear range of 1-10000 pM with a detection limit of 0.406 pM for the colormetric mode and a range of 0.1-10000 pM with a detection limit of 0.037 pM for the fluorescent mode. Further, the designed aptasensor was applied to IFN-γ detection in serum samples and achieved satisfactory recoveries., Significance: This innovative dual-mode detection strategy skillfully leverages the effective target-binding ability of aptamer, dual-function of the G-quadruplex and the signal amplifying ability of rolling circle amplification. This approach not only provides a reliable testing tool for the detection of IFN-γ, but also promotes the development of multimode sensing platforms., 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 B.V. All rights reserved.)

Bipolar nanopores, with asymmetric charge distributions, can induce significant ionic current rectification (ICR) at ultrashort lengths, finding potential applications in nanofluidic devices, energy conversion, and other related fields. Here, with simulations, we investigated the characteristics of ion transport and modulation of the ICR inside bipolar nanopores. With bipolar nanopores of half-positive and half-negative surfaces, the most significant ICR phenomenon appears at various concentrations. In these cases, the ICR ratios are independent of electrolyte types. In other cases where nanopores have oppositely charged surfaces of different lengths, ICR ratios are related to the mobility of anions and cations. The pore length and surface charge density can enhance ICR. As the pore length increases, ICR ratios first increase and then approach their saturation, which is determined by the surface charge density. External surface charges of nanopores can promote the ICR phenomenon mainly due to the enhancement of ion enrichment inside the nanopores by external surface conductance. The effective width of exterior charged surfaces under various conditions is also explored, which is inversely proportional to the pore length and salt concentration and linearly related to the pore diameter, surface charge density, and applied voltage. Our results may provide guidance for the design of bipolar porous membranes.

Food allergens elicit abnormal immune system responses among allergic individuals and sensitive detection for allergenic ingredient is greatly significant. To address this need, a novel fluorescent aptasensor, assisted by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), have been developed for food allergens. In this study, aptamer offers distinctive recognition capabilities in binding specific targets, while CRISPR-associated-12a protein (Cas12a) holds precise cis-cleavage for cutting fluorescent signal probes. Notably, the utilization of Cas12a cis-cleavage activity, rather than trans-cleavage, eliminates the necessity for additional fluorescent probes, thus reducing interference between substances and enhancing sensitivity. Throughout the process, complementary DNA (cDNA) plays a crucial dual role in target recognition conversion and signal presentation, representing a key challenge and innovative aspect of this study. To evaluate the performance of the aptasensor, lysozyme (LYS) is employed as a representative model target of food allergens. Under optimal conditions, the developed aptasensor could achieve an exceptional low limit of detection (LOD) of 6.10 pM with a dynamic detection range of 10 pM-320 pM. The aptasensor demonstrates high selectivity and great recovery rates. This strategy yields promising outcomes, holding the potential to serve as a valuable reference for various food allergens detection., 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.)

Ionic current rectification (ICR) of charged conical nanopores has various applications in fields including nanofluidics, biosensing, and energy conversion, whose function is closely related to the dynamic response of nanopores. The occurrence of ICR originates from the ion enrichment and depletion in conical pores, whose formation is found to be affected by the scanning rate of voltages. Here, through time-dependent simulations, we investigate the variation of ion current under electric fields and the dynamic formation of ion enrichment and depletion, which can reflect the response time of conical nanopores. The response time of nanopores when ion enrichment forms, i.e., at the "on" state is significantly longer than that with the formation of ion depletion, i.e., at the "off" state. Our simulation results reveal the regulation of response time by different nanopore parameters including the surface charge density, pore length, tip, and base radius, as well as the applied conditions such as the voltage and bulk concentration. The response time of nanopores is closely related to the surface charge density, pore length, voltage, and bulk concentration. Our uncovered dynamic response mechanism of the ionic current can guide the design of nanofluidic devices with conical nanopores, including memristors, ionic switches, and rectifiers.

Excessive exudation from the wound site and the difficulty of determining the state of wound healing can make medical management more difficult and, in extreme cases, lead to wound deterioration. In this study, we fabricated a pH-sensitive colorimetric chronic wound dressing with self-pumping function using electrostatic spinning technology. It consisted of three layers: a polylactic acid-curcumin (PCPLLA) hydrophobic layer, a hydrolyzed polyacrylonitrile (HPAN) transfer layer, and a polyacrylonitrile-purple kale anthocyanin (PAN-PCA) hydrophilic layer. The results showed that the preparation of porous PLLA fiber membrane loaded with 0.2 % Cur was achieved by adjusting the spinning-related parameters, which could ensure that the composite dressing had sufficient anti-inflammatory, antibacterial and antioxidant properties. The HPAN membrane treated with alkali for 30 min had significantly enhanced liquid wetting ability, and the unidirectional transport of liquid could be achieved by simple combination with the 20 um PCPLLA fiber membrane. In addition, the 4 % loaded PCA showed more obvious color difference than the colorimetric membrane. In vivo and ex vivo experiments have demonstrated the potential of multifunctional dressings for the treatment of chronic wounds., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.

High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (μ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (μ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Solid-state micro/nanopores play an important role in the sensing field because of their high stability and controllable size. Aiming at problems of complex processes and high costs in pore manufacturing, we propose a convenient and low-cost micro/nanopore fabrication technique based on the needle punching method. The thin film is pierced by controlling the feed of a microscale tungsten needle, and the size variations of the micropore are monitored by the current feedback system. Based on the positive correlation between the micropore size and the current threshold, the size-controllable preparation of micropores is achieved. The preparation of nanopores is realized by the combination of needle punching and chemical etching. First, a conical defect is prepared on the film with the tungsten needle. Then, nanopores are obtained by unilateral chemical etching of the film. Using the prepared conical micropores, resistive-pulse detection of nanoparticles is performed. Significant ionic current rectification is also obtained with our conical nanopores. It is proved that the properties of micro/nanopores prepared by our method are comparable to those prepared by the track-etching method. The simple and controllable fabrication process proposed here will advance the development of low-cost micro/nanopore sensors., Competing Interests: The authors have no conflict of interest., (© 2024 Author(s).)

The vulnerability of mixed halide perovskite nanocrystals (NCs) remains challenging because of the weak interaction between commonly employed ligands, oleic acid/oleylamine (OAm/OA) and halide anions, coupled with substantial surface phonon energy. Here, we introduce 3-aminopropyltriethoxysilane (APTES) as a capping ligand to modify CsPbBrI 2 NCs to enhance the interactions between them. The optical properties have been significantly enhanced, and halide segregation has been suppressed, both of which can be attributed to the reduced phonon energy and exciton-phonon coupling strength. Moreover, these APTES-CsPbBrI 2 NCs exhibit a broad color gamut and sustained color stability during long-term operation, indicating their promising potential in display technologies. This work may offer insights into surface engineering to enhance the properties and band stability of mixed halide perovskite NCs.

Short nanopores find extensive applications, capitalizing on their high throughput and detection resolution. Ionic behaviors through long nanopores are mainly determined by charged inner-pore walls. When pore lengths decrease to sub-200 nm, charged exterior surfaces provide considerable modulation to ion current. We find that the charge status of inner-pore walls affects the modulation of ion current from charged exterior surfaces. For 50-nm-long nanopores with neutral inner-pore walls, the charged exterior surfaces on the voltage (surfaceV) and ground (surfaceG) sides enhance and inhibit the ion transport by forming ion enrichment and depletion zones inside nanopores, respectively. For nanopores with both charged inner-pore and exterior surfaces, continuous electric double layers enhance the ion transport through nanopores significantly. The charged surfaceV results in higher ion current by simultaneously weakening the ion depletion at pore entrances and enhancing the intra-pore ion enrichment. The charged surfaceG expedites the exit of ions from nanopores, resulting in a decrease in ion enrichment at pore exits. Through adjustment in the width of charged-ring regions near pore boundaries, the effective charged width of the charged exterior is explored at ∼20 nm. Our results may provide a theoretical guide for further optimizing the performance of nanopore-based applications, such as seawater desalination, biosensing, and osmotic energy conversion., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The lubrication modification of biomedical devices significantly enhances the functionality of implanted interventional medical devices, thereby providing additional benefits for patients. Polymer brush coating provides a convenient and efficient method for surface modification while ensuring the preservation of the substrate's original properties. The current research has focused on a "trial and error" method to finding polymer brushes with superior lubricity qualities, which is time-consuming and expensive, as obtaining effective and long-lasting lubricity properties for polymer brushes is difficult. This review summarizes recent research advances in the biomedical field in the design, material selection, preparation, and characterization of lubricating and antifouling polymer brushes, which follow the polymer brush development process. This review begins by examining various approaches to polymer brush design, including molecular dynamics simulation and machine learning, from the fundamentals of polymer brush lubrication. Recent advancements in polymer brush design are then synthesized and potential avenues for future research are explored. Emphasis is placed on the burgeoning field of zwitterionic polymer brushes, and highlighting the broad prospects of supramolecular polymer brushes based on host-guest interactions in the field of self-repairing polymer brush applications. The review culminates by providing a summary of methodologies for characterizing the structural and functional attributes of polymer brushes. It is believed that a development approach for polymer brushes based on "design-material selection-preparation-characterization" can be created, easing the challenge of creating polymer brushes with high-performance lubricating qualities and enabling the on-demand creation of coatings. STATEMENT OF SIGNIFICANCE: Biomedical devices have severe lubrication modification needs, and surface lubrication modification by polymer brush coating is currently the most promising means. However, the design and preparation of polymer brushes often involves "iterative testing" to find polymer brushes with excellent lubrication properties, which is both time-consuming and expensive. This review proposes a polymer brush development process based on the "design-material selection-preparation-characterization" strategy and summarizes recent research advances and trends in the design, material selection, preparation, and characterization of polymer brushes. This review will help polymer brush researchers by alleviating the challenges of creating polymer brushes with high-performance lubricity and promises to enable the on-demand construction of polymer brush lubrication coatings., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Additive engineering has emerged as one of the most promising strategies to improve the performance of perovskite solar cells (PSCs). Among additives, perovskite nanocrystals (NCs) have a similar chemical composition and matched lattice structure with the perovskite matrix, which can effectively enhance the efficiency and stability of PSCs. However, relevant studies remain limited, and most of them focus on bromide-involved perovskite NCs, which may undergo dissolution and ion exchange within the FAPbI 3 host, potentially resulting in an enlarged band gap. In this work, we employ butylamine-capped CsPbI 3 NCs (BPNCs) as additives in PSCs, which can be well maintained and serve as seeds for regulating the crystallization and growth of perovskite films. The resultant perovskite film exhibits larger domain sizes and fewer grain boundaries without compromising the band gap. Moreover, BPNCs can alleviate lattice strain and reduce defect densities within the active layer. The PSCs incorporating BPNCs show a champion power conversion efficiency (PCE) of up to 25.41 %, well over both Control of 22.09 % and oleic acid/oleylamine capped CsPbI 3 NC (PNC)-based devices of 23.11 %. This work illustrates the key role of nanosized seed surfaces in achieving high-performance photovoltaic devices., (© 2023 Wiley-VCH GmbH.)

Thrombosis of extracorporeal circuits causes significant morbidity and mortality worldwide. In this study, plasma treatment technology and chemical grafting method were used to construct heparinized surfaces on the PVC substrate, which could not only reduce thrombosis but also decrease the side effects of the direct injection of anticoagulants. The PVC substrate was modified by plasma treatment technology firstly to obtain the active surface with the hydroxyl groups used for grafting. Then, heparin was grafted onto the modified PVC surface using different grafting strategies to prepare different heparinized surfaces. The experimental results indicated that the sodium alginate (SA) and carboxymethyl chitosan (CCS) used as interlayers could significantly increase the graft density of heparin to improve the anticoagulant effects and hemocompatibility of heparinized surfaces. In addition, the modification of heparin can further improve the anticoagulant effects. The CCS/low-molecular-weight heparin (LWMH) surface has the best anticoagulant properties, which can prolong the activated partial thromboplastin time (APTT) values of human plasma for about 35 s, reduce the hemolysis rates to <0.3 %, and perform well in the in-vitro blood circulation test. The heparinized surfaces prepared in this work have great application potential in anticoagulant treatment for medical devices., 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 Elsevier B.V. All rights reserved.)

Short nanopores have various applications in biosensing, desalination, and energy conversion. Here, the modulation of ionic transport by charged exterior surfaces is investigated through simulations with sub-200 nm long nanopores under applied voltages. Detailed analysis of the ionic current, electric field strength, and fluid flow inside and outside nanopores reveals that charged exterior surfaces can increase ionic conductance by increasing both the concentration and migration speed of charge carriers. The electric double layers near charged exterior surfaces provide an ion pool and an additional passageway for counterions, which lead to enhanced exterior surface conductance and ionic concentrations at pore entrances and inside the nanopores. We also report that charges on the membrane surfaces increase the electric field strength inside nanopores. The effective width of a ring with surface charges placed at pore entrances ( L cs ) is considered as well by studying the dependence of the current on L cs . We find a linear relationship between the effective L cs and the surface charge density and voltage, and an inverse relationship between the geometrical pore length and salt concentration. Our results elucidate the modulation mechanism of ionic transport through short nanopores by charged exterior surfaces, which is important for the design and fabrication of porous membranes.

Microfluidic chips have been widely applied in biology and medical research for stably generating uniform droplets that can be solidified into hydrogel microspheres. However, issues such as low microsphere yield, lengthy experimental processes, and susceptibility to environmental interference need to be addressed. In this work, a simple and effective method was developed to modify microfluidic chips at room temperature to improve the production performance of hydrogel microspheres. Numerical simulation-assisted experiments were conducted to comprehensively understand the effect of solution viscosity, hydrophilicity, and flow rate ratio on droplet formation during microsphere production. Chitosan was selected as the main component and combined with poly(ethylene glycol) diacrylate to prepare photocurable hydrogel microspheres as a demonstration. As a result, grafting fluoro-silane (FOTS) increased the contact angle of the channel from 90 to approximately 110°, which led to a 12.2% increase in droplet yield. Additionally, FOTS-modification attenuated the impact of the flow rate ratio on droplet yield by 19.1%. Alternatively, depositing dopamine decreased the channel's contact angle from 90 to 60°, resulting in a 21.4% increase in particle size and enabling the chip to adjust droplet size over a wider range. Further study demonstrates that the obtained hydrogel microspheres can be modified with layers of aldehyde, which can potentially be used for controlled drug release. Overall, this study proposed a facile method for adjusting the yield and droplet size through surface treatment of microfluidic chips while also enhancing the understanding of the synergistic effects of multiple factors in microfluidics-based microsphere production.

Antibacterial hemostatic medical dressings have become feasible solutions in response to the challenging wound-healing process. In this study, a novel fiber-type medical dressing with excellent breathable, antibacterial, and hemostatic qualities was created using sodium alginate (SA), microcrystalline cellulose (MCC), polyvinyl alcohol (PVA), and Euphorbia humifusa Willd (EHW) based on microfluidic spinning technology, and the properties of the dressing were characterized. The orthogonal test demonstrates that PVA and MCC can enhance the mechanical properties of the fiber, which is a crucial requirement for fiber assembly to form the dressing. Moreover, the presence of EHW enhances the dressing's antibacterial and hemostatic qualities. The dressings have been proven to have potent antibacterial and hemostatic properties as well as the ability to considerably speed up wound healing and skin tissue regeneration in the in-vitro and in-vivo tests. In conclusion, this innovative fiber-type medical dressing containing SA, MCC, PVA, and EHW has enormous potential for managing wounds caused by bacteria., 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 Elsevier B.V. All rights reserved.)

As an important property of porous membranes, the surface charge property determines many ionic behaviors of nanopores, such as ionic conductance and selectivity. Based on the dependence of electric double layers on bulk concentrations, ionic conductance through nanopores at high and low concentrations is governed by the bulk conductance and surface charge density, respectively. Here, through the investigation of ionic conductance inside track-etched single polyethylene terephthalate (PET) nanopores under various concentrations, the surface charge density of PET membranes is extracted as ∼-0.021 C/m 2 at pH 10 over measurements with 40 PET nanopores. Simulations show that surface roughness can cause underestimation in surface charge density due to the inhibited electroosmotic flow. Then, the averaged pore size and porosity of track-etched multipore PET membranes are characterized by the developed ionic conductance method. Through coupled theoretical predictions in ionic conductance under high and low concentrations, the averaged pore size and porosity of porous membranes can be obtained simultaneously. Our method provides a simple and precise way to characterize the pore size and porosity of multipore membranes, especially for those with sub-100 nm pores and low porosities., (© 2022 Wiley-VCH GmbH.)

Besides the dominant NaCl, natural seawater/river water contains trace multivalent ions, which can provide effective screening of surface charges. Here, in both negatively and positively charged nanopores, influences from divalent ions as counterions and co-ions have been investigated with respect to the performance of osmotic energy conversion (OEC) under natural salt gradients. As counterions, trace Ca 2+ ions can suppress the electric power and conversion efficiency significantly. The reduced OEC performance is due to the bivalence and low diffusion coefficient of Ca 2+ ions instead of the uphill transport of divalent ions discovered in the previous work. Effectively screened charged surfaces by Ca 2+ ions induce an enhanced diffusion of Cl - ions which simultaneously decreases the net ion penetration and ionic selectivity of the nanopore. As co-ions, Ca 2+ ions have weak effects on the OEC performance. The promotion from charged exterior surfaces in OEC processes for ultrashort nanopores is also studied, with an effective region of ∼200 nm in width beyond pore boundaries independent of the presence of Ca 2+ ions. Our results shed light on the physical details of the nanofluidic OEC process under natural seawater/river water conditions, which can provide a useful guide for high-performance osmotic energy harvesting.

High-performance osmotic energy conversion requires both large ionic throughput and high ionic selectivity, which can be significantly promoted by exterior surface charges simultaneously, especially for short nanopores. Here, we investigate the enhancement of ionic diffusion by charged exterior surfaces under various conditions and explore corresponding effective charged areas. From simulations, ionic diffusion is promoted more significantly by exterior surface charges through nanopores with a shorter length, wider diameter, and larger surface charge density or under higher salt gradients. Effective widths of the charged ring regions near nanopores are reversely proportional to the pore length and linearly dependent on the pore diameter, salt gradient, and surface charge density. Due to the important role of effective charged areas in the propagation of ionic diffusion through single nanopores to cases with porous membranes, our results may provide useful guidance to the design and fabrication of porous membranes for practical high-performance osmotic energy harvesting.

All-inorganic lead halide perovskite (CsPbX 3 , X = Cl, Br, I, or their mixture) nanocrystals (NCs) have achieved inspiring advancements in optoelectronic fields but still suffer from poor durability when exposed to environmental stimuli such as water, irradiation and heat. Herein, a strategy of employing pyrophosphate as the inert shell for CsPbX 3 NCs is reported. The strong binding between pyrophosphate and CsPbBr 3 surface can stabilize the perovskite structure well. The as-obtained core@shell CsPbBr 3 @NH 4 AlP 2 O 7 NCs exhibit impressive stability against water and maintain the initial optical properties with negligible change in 400 days. Furthermore, significant improvement of irradiation/thermal resistance is realized due to the protecting role of pyrophosphate. The NCs can retain 100% and ≈90% of the original PL after hundreds of heating/cooling cycles and several hundred hours of UV light irradiation, respectively. As a result, the core@shell products can be directly used for high-resolution inkjet printing, enabling the printed fluorescent information to be resistant under harsh environmental conditions. This work provides a promising way for the synthesis of highly stable encapsulated perovskite NCs and demonstrates a great potential in practical applications., (© 2022 Wiley-VCH GmbH.)

Solar-driven interfacial steam generation (SISG) has attracted much attention in recent years as a solution to freshwater scarcity and the energy crisis. Currently, research interests are mainly focused on standard conditions under "1-sun" illumination, which we believe are insufficient on their own. Gaining insight and understanding about SISG under both weak and strong irradiation have important implications for real-world use that are rarely presented in relevant discussions. In this review, we aim to discuss SISG under weak (<1 sun) and strong solar irradiation (>1 sun), both of which are often undervalued but necessary for real application. By analyzing state-of-the-art techniques and recent research progress, we provide some possible strategies, in terms of both energy and water management, for improving the performance of SISG under different irradiation powers. Finally, we also give a summary and our perspectives on the directions that the future development of this exciting field might take.

Nanopores that exhibit ionic current rectification (ICR) behave like diodes such that they transport ions more efficiently in one direction than in the other. Conical nanopores have been shown to rectify ionic current, but only those with at least 500 nm in length exhibit significant ICR. Here, through the finite element method, we show how ICR of conical nanopores with lengths below 200 nm can be tuned by controlling individual charged surfaces, that is, the inner pore surface (surface inner ) and exterior pore surfaces on the tip and base side (surface tip and surface base ). The charged surface inner and surface tip can induce obvious ICR individually, while the effects of the charged surface base on ICR can be ignored. The fully charged surface inner alone could render the nanopore counterion-selective and induces significant ion concentration polarization in the tip region, which causes reverse ICR compared to nanopores with all surfaces charged. In addition, the direction and degree of rectification can be further tuned by the depth of the charged surface inner . When considering the exterior membrane surface only, the charged surface tip causes intrapore ionic enrichment and depletion under opposite biases, which results in significant ICR. Its effective region is within ∼40 nm beyond the tip orifice. We also found that individual charged parts of the pore system contributed to ICR in an additive way because of the additive effect on the ion concentration regulation along the pore axis. With various combinations of fully/partially charged surface inner and surface tip , diverse ICR ratios from ∼2 to ∼170 can be achieved. Our findings shed light on the mechanism of ICR in ultrashort conical nanopores and provide a useful guide to the design and modification of ultrashort conical nanopores in ionic circuits and nanofluidic sensors.

The removal of oil from the water surface is vital to protect the environment and living organisms against the threats posed by industrial oily wastewater and offshore oil spills. High cost, low efficiency, and environmental pollution limit the widespread use of the commercial methods of oil-water separation. In this study, the prewetting polypropylene-wood pulp fiber composite nonwoven fabric (PWNF) has been used in the gravity-driven separation of the oil-water mixture. The prewetting PWNF displayed superior underwater oleophobic properties, and the underwater kerosene contact angle was 137.65° ± 4.27°. The oil-water interfacial tension in the microchannels among the PWNF fibers prevented the oil from passing through the microchannels; however, it allowed the passage of water. The PWNF membrane maintained an excellent oil-water separation performance after repeated separation and long-term soaking cycles. The separation membrane maintained 75% and 50% of the initial separation performance after 40 repeat cycles and water immersion for more than 20 days, respectively. The separation rate of the PWNF membrane was also investigated as a function of salt solution concentration, temperature, and pH. Meanwhile, the influences of prewetting time, prewetting temperature, and different dyeing condition of the mixture on the separation rate were clarified. The destruction of the oil-water contact interface was suggested as the main failure mode of the developed PWNF separation membrane. The maximum kerosene height that the PWNF separation membrane could sustain was 800 mm. The obtained results confirmed that the PWNF separation membrane exhibited the high potential of widespread use in various environments for achieving efficient and stable separations, especially for the oily wastewater treatment.

The electrochemical reduction of deuterons (2D + + 2e - → D 2 ) at Pt nanodisk electrodes (radius = 15-100 nm) in D 2 O solutions containing deuterium chloride (DCl) results in the formation of a single gas nanobubble at the electrode surface. Analogous to that previously observed for the electrochemical generation of H 2 nanobubbles, the nucleation and growth of a stable D 2 nanobubble is characterized in voltammetric experiments by a highly reproducible and well-resolved sudden drop in the faradaic current, a consequence of restricted mass transport of D + to the electrode surface following the liquid-to-gas phase transition. D 2 nanobubbles are stable under potential control due to a dynamic equilibrium existing between D 2 gas dissolution and electrochemical generation of D 2 at the circumference of the Pt nanodisk electrode. Remarkably, within the error of the experimental measurement (<6%), the electrochemical current required to nucleate a D 2 gas phase in a D 2 O solution is identical to that for the H 2 gas phase in a H 2 O solutions, indicating that the concentration required for nucleating a D 2 nanobubble in D 2 O (0.29 M) is ∼1.25 times larger than that for a H 2 nanobubble (0.23 M), while the supersaturation is ∼300 in each case. We further demonstrate that individual nanobubbles can be electrogenerated in mixed D 2 O/H 2 O solutions containing both D + and H + at respective individual concentrations well below those required to nucleate a gas phase containing either pure D 2 or H 2 . This latter finding indicates that the resulting nanobubbles comprise a mixture of D 2 , H 2 , and HD molecules with the chemical composition of a nanobubble determined by the concentrations and diffusivities of D + and H + in the mixed D 2 O/H 2 O solutions.

Electrochemical processes occurring at solid/solid and solid/membrane interfaces govern the behavior of a variety of energy storage devices, including electrocatalytic reactions at electrode/membrane interfaces in fuel cells and ion insertion at electrode/electrolyte interfaces in solid-state batteries. Due to the heterogeneity of these systems, interrogation of interfacial activity at nanometer length scales is desired to understand system performance, yet the buried nature of the interfaces makes localized activity inaccessible to conventional electrochemical techniques. Herein, we demonstrate nanoscale electrochemical imaging of hydrogen evolution at individual Pt nanoparticles (PtNPs) positioned at a buried interface using scanning electrochemical cell microscopy (SECCM). Specifically, we image the hydrogen evolution reaction (HER) at individual carbon-supported PtNP electrocatalysts covered by a 100 to 800 nm thick layer of the proton exchange membrane Nafion. The rate of hydrogen evolution at PtNP at this buried interface is shown to be a function of Nafion thickness, with the highest activity observed for ∼200 nm thick films.

Post-transcriptional regulation by miRNAs plays an important role in the pathogenesis of rheumatoid arthritis (RA), however, the roles of specific miRNAs in RA pathogenesis remain largely unclear. This study performed dual-omics (miRNA and mRNA) integration analysis and in-depth cellular and molecular functional exploration to identify novel RA-associated miRNAs and to understand their underlying pathogenic mechanism. Based on the miRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from a discovery sample set (25 RA cases and 18 healthy controls), 18 differentially expressed miRNAs (DEMIRs) (|Fold-change|>2 and P < 0.05) were identified and corresponding interaction networks of DEMIRs and mRNA were constructed. After the expression validation of the DEMIRs in a validation sample set (35 RA cases and 35 healthy controls), miR-99b-5p was highlighted. The over-expression of newly discovered miR-99b-5p is able to suppress T cell apoptosis, promote cell proliferation and activation, increase expression of proinflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ), and inhibit expression of its target genes mTOR and RASSF4. This study comprehensively identified PBMC-expressed miRNAs along with corresponding regulatory networks significant for RA and discovered miR-99b-5p as a novel post-transcriptional mediator involved in RA pathogenesis. The findings improved our understanding of RA pathogenesis and provided novel insights into the molecular mechanisms underlying RA pathogenesis.

Ion transport through nanopores is a process of fundamental significance in nature and in engineering practice. Over the past decade, it has been found that the ion conductivity in nanopores could be drastically enhanced, and different mechanisms have been proposed to explain this observation. To date, most reported studies have been carried out with relatively dilute electrolytes, while ion transport in nanopores under high electrolyte concentrations (>1 M) has been rarely explored. Through systematic experimental and atomistic simulation studies with NaCl solutions, here we show that at high electrolyte concentrations, ion mobility in small nanopores could be significantly reduced from the corresponding bulk value. Subsequent molecular dynamics studies indicate that in addition to the low mobility of surface-bound ions in the Stern layer, enhanced pairing and collisions between partially dehydrated ions of opposite charges also make important contributions to the reduced ion mobility. Furthermore, we show that the extent of mobility reduction depends on the association constant between cations and anions in different electrolytes with a more drastic reduction for a larger association constant.

Single nanopores have attracted much scientific interest because of their versatile applications. The majority of experiments have been performed with nanopores being in contact with the same electrolyte on both sides of the membrane, although solution gradients across semipermeable membranes are omnipresent in natural systems. In this manuscript, we studied ionic and fluidic movement through thin nanopores under viscosity gradients both experimentally and using simulations. Ionic-current rectification was observed under these conditions because solutions with different conductivities filled across the pore under different biases caused by electroosmotic flow. We found that a pore filled with high-viscosity solutions exhibited a current increase with applied voltage in a steeper slope beyond a threshold voltage, which abnormally reduced the current-rectification ratio. Through simulations, we found that reversed electroosmotic flow, which filled the pore with aqueous solutions of lower viscosities, was responsible for this behavior. The reversed electroosmotic flow could be explained by slower depletion of co-ions than of counterions along the pore. By increasing the surface charge density of pore surfaces, current-rectification ratio could reach the value of the viscosity gradient across thin nanopores. Our findings shed light on fundamental aspects to be considered when performing experiments with viscosity gradients across nanopores and nanofluidic channels.

The resistive-pulse technique provides a fast and label-free method for nanoparticle detection. To achieve higher sensitivity, thin nanopores such as silicon nitride nanopores are usually considered. In this study, nanoparticle detection has been mimicked with simulations. We found that the surface charges of particles can significantly affect current blockade in short pores, particularly under high electric fields. For particles with surface charge densities higher than -0.02 C m -2 , current blockade ratios depend closely on the applied voltage. From our simulation results, an optimal voltage can be found for particle detection, at which the current blockade ratio does not depend on the surface charge density of the particle. This optimal voltage was obtained from the balance of current increase and decrease caused by cations and anions, respectively, due to negative surface charges of the particles. From this systematic study, the optimal voltage was found to represent a property of the system that only depends on the electrolyte type. We think our findings can provide some help for accurate particle detection in experiments.

The poor stability of CsPbX 3 (X = Cl, Br, I) nanocrystals (NCs) has severely impeded their practical applications. Although there are some successful examples on encapsulating multiple CsPbX 3 NCs into an oxide or polymer matrix, it has remained a serious challenge for the surface modification/encapsulation using oxides or polymers at a single particle level. In this work, monodisperse CsPbX 3 /SiO 2 and CsPbBr 3 /Ta 2 O 5 Janus nanoparticles were successfully prepared by combining a water-triggered transformation process and a sol-gel method. The CsPbBr 3 /SiO 2 NCs exhibited a photoluminescence quantum yield of 80% and a lifetime of 19.8 ns. The product showed dramatically improved stability against destruction by air, water, and light irradiation. Upon continuous irradiation by intense UV light for 10 h, a film of the CsPbBr 3 /SiO 2 Janus NCs showed only a slight drop (2%) in the PL intensity, while a control sample of unmodified CsPbBr 3 NCs displayed a 35% drop. We further highlighted the advantageous features of the CsPbBr 3 /SiO 2 NCs in practical applications by using them as the green light source for the fabrication of a prototype white light emitting diode, and demonstrated a wide color gamut covering up to 138% of the National Television System Committee standard. This work not only provides a novel approach for the surface modification of individual CsPbX 3 NCs but also helps to address the challenging stability issue; therefore, it has an important implication toward their practical applications.

Extensive molecular dynamics simulations are employed to optimize nanopore size and surface charge density in order to obtain high ionic selectivity and high water throughput for seawater desalination systems. It is demonstrated that with the help of surface charge exclusion, nanopores with diameter as large as 3.5 nm still have high ionic selectivity. The mechanism of the salt rejection in a surface-charged nanopore is mainly attributed to the ion concentration difference between the cations and anions induced by the surface charges. Increasing surface charge density is beneficial to enhance ionic selectivity. However, there exists a critical value for the surface charge density. Once the surface charge density exceeds the critical value, charge inversion occurs inside a nanopore. Further increasing the surface charge density will deteriorate the ionic selectivity because the highly charged nanopore surface will allow more coions to enter the nanopore in order to keep the whole system in charge neutrality. Besides the surface charge density, the nanopore length also affects the ionic selectivity. Based on our systematic simulations, nanopores with surface charge density between -0.09 C/m 2 and -0.12 C/m 2 , diameters smaller than 3.5 nm, and membrane thickness ranging between 8 and 10 graphene layers show an excellent performance for the ionic selectivity.

Our manuscript addresses the issue of probing an effective surface charge that any surface can acquire at the solid/liquid interface. Even if a particle is predicted to be neutral based on its chemical structure, the particle can carry finite surface charges when placed in a solution. We present tools to probe the presence of surface charge densities of meso-particles, characterized with zeta potentials below 10 mV. The tools are based on the resistive-pulse technique, which uses single pores to probe properties of individual objects including molecules, particles, and cells. The presented experiments were performed with particles 280 and 400 nm in diameter and single pores with opening diameter tuned between ∼ 200 nm and one micron. Surface charge properties were probed in two modes: (i) the passage of the particles through pores of diameters larger than the particles, as well as (ii) an approach curve of a particle to a pore that is smaller than the particle diameter. The curve in the latter mode has a biphasic character starting with a low-amplitude current decrease, followed by a current enhancement reaching an amplitude of ∼10% of the baseline current. The current increase was long-lasting and stable, and shown to strongly depend on the particle surface charge density. The results are explained via voltage-modulation of ionic concentrations in the pore.

Resistive-pulse sensing is a label-free method for characterizing individual particles as they pass through ion-conducting channels or pores. During a resistive pulse experiment, the ionic current through a conducting channel is monitored as particles suspended in the solution translocate through the channel. The amplitude of the current decrease during a translocation, or 'pulse', depends not only on the ratio of the particle and channel sizes, but also on the particle position, which is difficult to resolve with the resistive pulse signal alone. We present experiments of simultaneous electrical and optical detection of particles passing through microfluidic channels to resolve the positional dependencies of the resistive pulses. Particles were tracked simultaneously in the two signals to create a mapping of the particle position to resistive pulse amplitude at the same instant in time. The hybrid approach will improve the accuracy of object characterization and will pave the way for observing dynamic changes of the objects such as deformation or change in orientation. This combined approach of optical detection and resistive pulse sensing will join with other attempts at hybridizing high-throughput detection techniques such as imaging flow cytometry.

Rectifying pores, which transport ions mainly in one direction blocking the ionic flow in the other, were shown to be important in the preparation of chemical sensors, components of ionic circuits, and mimics of biological channels. Ionic rectification has been shown with various engineered systems, but pores with similar opening diameters often rectify to a various uncontrolled extent. In this Letter we present a system of single meso-pores, whose current-voltage curves and rectification can be tuned with great precision via viscosity and conductivity gradients of solutions placed on both sides of the membrane. The mechanism of rectification is based on electroosmotically induced flow, which fills the entire volume of the pore with a single solution from either side of the membrane. The highly predictable rectifying system can find various applications, including measuring viscosity of unknown media and tuning electrokinetic passage of particles.

Single pores in the resistive-pulse technique are used as an analytics tool to detect, size, and characterize physical as well as chemical properties of individual objects such as molecules and particles. Each object passing through a pore causes a transient change of the transmembrane current called a resistive pulse. In high salt concentrations when the pore diameter is significantly larger than the screening Debye length, it is assumed that the particle size and surface charge can be determined independently from the same experiment. In this article we challenge this assumption and show that highly charged hard spheres can cause a significant increase of the resistive-pulse amplitude compared to neutral particles of a similar diameter. As a result, resistive pulses overestimate the size of charged particles by even 20%. The observation is explained by the effect of concentration polarization created across particles in a pore, revealed by numerical modeling of ionic concentrations, ion current, and local electric fields. It is notable that in resistive-pulse experiments with cylindrical pores, concentration polarization was previously shown to influence ionic concentrations only at pore entrances; consequently, additional and transient modulation of resistive pulses was observed when a particle entered or left the pore. Here we postulate that concentration polarization can occur across transported particles at any particle position along the pore axis and affect the magnitude of the entire resistive pulse. Consequently, the recorded resistive pulses of highly charged particles reflect not only the particles' volume but also the size of the depletion zone created in front of the moving particle. Moreover, the modeling identified that the effective surface charge density of particles depended not only on the density of functional groups on the particle but also on the capacitance of the Stern layer. The findings are of crucial importance for sizing particles and characterizing their surface charge properties.

Through molecular dynamics simulations considering thermal vibration of surface atoms, ionic behaviors in concentrated NaCl solutions confined between discretely charged silicon surfaces have been investigated. The electric double layer structure was found to be sensitive to the density and distribution of surface charges. Due to the discreteness of the surface charge, a slight charge inversion appeared which depended on the surface charge density, bulk concentration, and confinement. In the nanoconfined NaCl solutions concentrated from 0.2 to 4.0 M, the locations of accumulation layers for Na(+) and Cl(-) ions remained stable, but their peak values increased. The higher the concentration was, the more obvious the charge inversion appeared. In 4.0 M NaCl solution, Na(+) and Cl(-) ions show obvious alternating layered distributions which may correspond to the solidification found in experiments. By changing surface separation, the confinement had a large effect on the ionic distribution. As both surfaces approached each other, many ions and water molecules were squeezed out of the confined space. Two adjacent layers in ion or water distribution profiles can be forced closer to each other and merge together. From ionic hydration analysis, the coordination number of Na(+) ions in highly confined space was much lower than that in the bulk.

Conically shaped pores such as glass pipets as well as asymmetric pores in polymers became an important analytics tool used for the detection of molecules, viruses, and particles. Electrokinetic or pressure driven passage of single particles through a single pore causes a transient change of the transmembrane current, called a resistive-pulse, whose amplitude is the measure of the particle volume. The shape of the pulse reflects the pore topography, and in a conical pore, resistive pulses have a shape of a tick point. Passage of particles in both directions was reported to produce pulses of the same amplitude and shapes that are mirror images of each other. In this manuscript we identify conditions at which the amplitude of resistive-pulses in a conical mesopore is direction dependent. Neutral particles entering the pore from the larger entrance of a conical pore, called the base, block the current to a larger extent than the particles traveling in the opposite direction. Negatively charged particles on the other hand size larger when being transported in the direction from tip to base. The findings are explained via voltage-regulated ionic concentrations in the pore such that for one voltage polarity a weak depletion zone is formed, which increases the current blockage caused by a particle. For the opposite polarity, an enhancement of ionic concentrations was predicted. The findings reported here are of crucial importance for the resistive-pulse technique, which relates the current blockage with the size of the passing object.

Passage time through single micropores is an important parameter used to quantify the surface charge and zeta potential of particles. In the resistive-pulse technique, the measured time of pressure- or electric-field-induced translocation is assumed to be direction independent. This assumption is supported by the low velocities of the particles and the supporting fluid such that the transport reversibility known for Stokes flow is expected to apply. In this article, we present examples of micropores in which passage time of ∼400 nm diameter particles becomes direction-dependent; that is, the particles' translocation times from left to right and right to left are different. These pores are characterized by an undulating inner diameter such that at least one wider zone called a cavity separates two narrower regions of different lengths. We propose that the observed direction-dependence of the translocation velocity is caused by an asymmetric efficiency of particle focusing toward the pore axis, which leads to a direction-dependent set of particle trajectories. The reported pores present the simplest system in which time-broken symmetry has been observed. The results are of importance for sensing of particles and molecules by the resistive-pulse technique since pores used for detection are often characterized by finite roughness or noncylindrical shape. This article also points to the role of particle focusing in the magnitude and distribution of the translocation times.

Anaplastic lymphoma kinase (ALK) gene fusion is a driving mutation underlying the development of non-small cell lung cancer (NSCLC). Accurate detection of ALK fusion is critical for the use of ALK inhibitors in the treatment of NSCLC. Commonly utilized methods for ALK detection include fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). However, these methods are time-consuming and costly. In the present study, a method for assessing ALK gene fusion based on the differential expression levels of the ALK kinase and non-kinase domains was developed and evaluated, with the aim of providing a convenient and reliable method for the detection of ALK fusion. In addition, another method was established to determine the integrity of exons 19-20 and 20-21 of ALK, two genomic loci that are typically broken in ALK fusions. These novel methods were applied to detect ALK fusion in 100 NSCLC patients, and were compared with IHC and FISH methods. The novel methods developed in the present study successfully detected ALK fusions in 10 samples. The concordances between the novel methods and IHC and FISH were 100%. Furthermore, the differential expression method was able to detect ALK fusions in cell-free urine samples, which was advantageous over FISH and IHC. The novel methods developed in the present study are cost-effective and easy to perform, and may provide simple and convenient techniques for the clinical assessment of ALK fusions, facilitating the use of targeted therapy for NSCLC.

Single micropores in resistive-pulse technique were used to understand a complex dependence of particle mobility on its surface charge density. We show that the mobility of highly charged carboxylated particles decreases with the increase of the solution pH due to an interplay of three effects: (i) ion condensation, (ii) formation of an asymmetric electrical double layer around the particle, and (iii) electroosmotic flow induced by the charges on the pore walls and the particle surfaces. The results are important for applying resistive-pulse technique to determine surface charge density and zeta potential of the particles. The experiments also indicate the presence of condensed ions, which contribute to the measured current if a sufficiently high electric field is applied across the pore.

A series of nanopores with diameters ranging from 2.5 to 63 nm are fabricated on a reduced Si3N4 membrane by focused ion beam and high energy electron beam. Through measuring the blocked ionic currents for DNA strands threading linearly through those solid-state nanopores, it is found that the blockade ionic current is proportional to the square of the hydrodynamic diameter of the DNA strand. With the nanopore diameter reduced to be comparable with that of DNA strands, the hydrodynamic diameter of the DNA becomes smaller, which is attributed to the size confinement effects. The duration time for the linear DNA translocation events increases monotonically with the nanopore length. By comparing the spatial configurations of DNA strands through nanopores with different diameters, it is found that the nanopore with large diameter has enough space to allow the DNA strand to translocate through with complex conformation. With the decrease of the nanopore diameter, the folded part of the DNA is prone to be straightened by the nanopore, which leads to the increase in the occurrence frequency of the linear DNA translocation events. Reducing the diameter of the nanopore to 2.5 nm allows the detection and discrimination of three nucleotide "G" and three nucleotide "T" homopolymer DNA strands based on differences in their physical dimensions.

The resistive-pulse technique has been used to detect and size objects which pass through a single pore. The amplitude of the ion current change observed when a particle is in the pore is correlated with the particle volume. Up to date, however, the resistive-pulse approach has not been able to distinguish between objects of similar volume but different shapes. In this manuscript, we propose using pores with longitudinal irregularities as a sensitive tool capable of distinguishing spherical and rod-shaped particles with different lengths. The ion current modulations within resulting resistive pulses carry information on the length of passing objects. The performed experiments also indicate the rods rotate while translocating, and displace an effective volume that is larger than their geometrical volume, and which also depends on the pore diameter.

Direct force measurements between two mica surfaces in aqueous electrolyte solutions over broad ranges of LaCl3 concentrations and pH values were carried out with a surface forces apparatus. Charge inversion on mica surfaces is detected once the LaCl3 concentration reaches a critical value. With the continual increase of LaCl3 concentrations, the mica surface will be overscreened by the counterions. It is demonstrated that the two mica surfaces may experience the jump-in contact even at high LaCl3 concentrations, which is seldom seen in monovalent salt solutions. The strong adhesion cannot be attributed to the van der Waals force alone, but should include the ion-ion correlation forces. Through adjusting the pH values in LaCl3 solutions, the ion-ion correlation force can be evaluated quantitatively. These results provide important insight into the fundamental understanding in the role of ion-ion correlations in ion screening mechanism and interactions between charged objects.

Disease-related changes in serum proteins are reasonable targets for early detection particularly due to the noninvasive approach in obtaining samples. Glycoproteins specifically have been implicated in a variety of disease types ranging from immune diseases to cancers. High-throughput screening methods that can assess glycosylation states of all serum proteins in normal and diseased sample groups can facilitate early detection as well as shed light on disease progression mechanisms. Outlined here is a combination of liquid separation, protein microarray, and mass spectrometry approach to highlight candidate proteins involved in diseases through glycosylation mechanisms.

Colorectal cancer (CRC) remains a major worldwide cause of cancer-related morbidity and mortality largely due to the insidious onset of the disease. The current clinical procedures utilized for disease diagnosis are invasive, unpleasant, and inconvenient; hence, the need for simple blood tests that could be used for the early detection of CRC. In this work, we have developed methods for glycoproteomics analysis to identify plasma markers with utility to assist in the detection of colorectal cancer (CRC). Following immunodepletion of the most abundant plasma proteins, the plasma N -linked glycoproteins were enriched using lectin affinity chromatography and subsequently further separated by nonporous silica reversed-phase (NPS-RP)-HPLC. Individual RP-HPLC fractions were printed on nitrocellulose coated slides which were then probed with lectins to determine glycan patterns in plasma samples from 9 normal, 5 adenoma, and 6 colorectal cancer patients. Statistical tools, including principal component analysis, hierarchical clustering, and Z-statistics analysis, were employed to identify distinctive glycosylation patterns. Patients diagnosed with colorectal cancer or adenomas were shown to have dramatically higher levels of sialylation and fucosylation as compared to normal controls. Plasma glycoproteins with aberrant glycosylation were identified by nano-LC-MS/MS, while a lectin blotting methodology was used to validate proteins with significantly altered glycosylation as a function of cancer progression. The potential markers identified in this study for diagnosis to distinguish colorectal cancer from adenoma and normal include elevated sialylation and fucosylation in complement C3, histidine-rich glycoprotein, and kininogen-1. These potential markers of colorectal cancer were subsequently validated by lectin blotting in an independent set of plasma samples obtained from 10 CRC patients, 10 patients with adenomas, and 10 normal subjects. These results demonstrate the utility of this strategy for the identification of N -linked glycan patterns as potential markers of CRC in human plasma, and may have the utility to distinguish different disease states.

Bacterial cold adaptation in Exiguobacterium sibiricum 255-15 was studied on a proteomic scale using a 2-D liquid phase separation coupled with MS technology. Whole-cell lysates of E. sibiricum 255-15 grown at 4 degrees C and 25 degrees C were first fractionated according to pI by chromatofocusing (CF), and further separated based on hydrophobicity by nonporous silica RP HPLC (NPS-RP-HPLC) which was on-line coupled with an ESI-TOF MS for intact protein M(r) measurement and quantitative interlysate comparison. Mass maps were created to visualize the differences in protein expression between different growth temperatures. The differentially expressed proteins were then identified by PMF using a MALDI-TOF MS and peptide sequencing by MS/MS with a MALDI quadrupole IT TOF mass spectrometer (MALDI-QIT-TOF MS). A total of over 500 proteins were detected in this study, of which 256 were identified. Among these proteins 39 were cold acclimation proteins (Caps) that were preferentially or uniquely expressed at 4 degrees C and three were homologous cold shock proteins (Csps). The homologous Csps were found to be similarly expressed at 4 degrees C and 25 degrees C, where these three homologous Csps represent about 10% of the total soluble proteins at both 4 degrees C and 25 degrees C.