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Optical metasurfaces have revolutionized analog computing and image processing at subwavelength scales with faster speed and lower power consumption. They typically involve spatial differentiation with an engineered angular dispersion. Quasi-bound states in the continuum (quasi-BICs) have emerged as powerful tools for customizing optical resonances. While quasi-BICs have been widely used with high Q -factors and enhanced field confinement, their potential in image processing remains unexplored. Here, we demonstrate edge detection imaging by leveraging quasi-BIC in an all-dielectric metasurface. This metasurface, composed of four nanodisks per unit cell, supports a polarization-independent quasi-BIC through structural perturbations, allowing simultaneously engineering Q -factor and angular dispersion. It can perform isotropic two-dimensional spatial differentiation, which is crucial for edge detection. We fabricate the metasurfaces and validate their efficient, high-quality edge detection under different polarizations. Our findings illuminate the mechanisms of edge detection with quasi-BIC metasurfaces, opening new avenues for ultracompact, low-power optical computing devices.

Wearable strain sensors play a pivotal role in real-time human motion detection and health monitoring. Traditional fabric-based strain sensors, typically with a positive Poisson's ratio, face challenges in maintaining sensitivity and comfort during human motion due to conflicting resistance changes in different strain directions. In this work, high-performance stretchable strain sensors are developed based on graphene-modified auxetic fabrics (GMAF) for human motion detection in smart wearable devices. The proposed GMAF sensors, with a negative Poisson's ratio achieved through commercially available warp-knitting technology, exhibit an 8-fold improvement in sensitivity compared to conventional plain fabric sensors. The unique auxetic fabric structure enhances sensitivity by synchronizing resistance changes in both wale and course directions. The GMAF sensors demonstrate excellent washability, showing only slight degradation in auxeticity and an acceptable increase in resistance after 10 standard wash cycles. The GMAF sensors maintain stability under different strain levels and various motion frequencies, emphasizing their dynamic performance. The sensors exhibit superior conformability to joint movements, which effectively monitor a full range of motions, including joint bending, sports activities, and subtle actions like coughing and swallowing. The research underscores a promising approach to achieve industrial-scale production of wearable sensors with improved performance and comfort through fabric structure design.

We show empirically that a phase-space non-Born-Oppenheimer electronic Hamiltonian approach to quantum chemistry (where the electronic Hamiltonian is parametrized by both nuclear position and momentum, Ĥ PS ( R , P )) is both a practical and accurate means to recover vibrational circular dichroism spectra. We further hypothesize that such a phase-space approach may lead to very new dynamical physics beyond spectroscopic circular dichroism, with potential implications for understanding chiral induced spin selectivity (CISS), noting that classical phase-space approaches conserve the total nuclear plus electronic momentum, whereas classical Born-Oppenheimer approaches do not (they conserve only the nuclear momentum).

Phage display panning is a powerful tool to select strong peptide binders to a given target, and when applied to inorganic materials (e.g., silica) as a target, it provides information on binding events and molecular recognition at the peptide-mineral interface. The panning process has limitations with the phage chemical elution being affected by bias toward positively charged binders, resulting in the potential loss of information on binder diversity; the presence of fast growing phages with an intrinsic growth advantage; and the presence of false positives from target unrelated peptides. To overcome some of these limitations, we developed a panning approach based on the sequential use of different eluents (Gly-HCl, pH-2.2; MgCl 2 , pH-6.1; and TEA, pH-11.0), or pH conditions (Gly-HCl 2.2 < pH < 11.0) that allows the identification of a diverse and comprehensive pool of strong binders. We have assessed and tested the authenticity of the identified silica binders via a complementary experimental (in vivo phage recovery rates and TEM imaging) and bioinformatics approach. We provide experimental evidence of the nonspecificity of the Gly-HCl eluent as typically used. Using a fluorimetric assay, we investigate in vitro binding of two peptides that differ by pI-S4 (HYIDFRW, pI 7.80) and S5 (YSLKQYQ, pI 9.44)─modified at the C terminal with an amide group to simulate net charges in the phage display system, confirming the vital role of electrostatic interactions as driving binding forces in the phage panning process. The presented optimized phage panning approach provides an opportunity to match known surface interactions at play with suitable elution conditions; to select only sequences relevant to a particular interfacial system. The approach has the potential to open up avenues to design interfacial systems to advance our understanding of peptide-assisted mineral growth, among other possibilities.

Ferritin, a spherical protein shell assembled from 24 subunits, functions as an efficient iron storage and release system through its channels. Understanding how various chemicals affect the structural behavior of ferritin is crucial for unravelling the origins of iron-related diseases in living organisms including humans. In particular, the influence of chemicals on ferritin's dynamics and iron release is barely explored at the single-protein level. Here, by employing optical nanotweezers using double-nanohole (DNH) structures, we examined the effect of ascorbic acid (reducing reagent) and pH on individual ferritin's conformational dynamics. The dynamics of ferritin increased as the concentration of ascorbic acid approached saturation. At pH 2.0, ferritin exhibited significant structural fluctuations and eventually underwent a stepwise disassembly into fragments. This work demonstrated the disassembly pathway and kinetics of a single ferritin molecule in solution. We identified four critical fragments during its disassembly pathway, which are 22-mer, 12-mer, tetramer, and dimer subunits. Moreover, we present single-molecule evidence of the cooperative disassembly of ferritin. Interrogating ferritin's structural change in response to different chemicals holds importance for understanding their roles in iron metabolism, hence facilitating further development of medical treatments for its associated diseases.

Reactions of singlet oxygen are numerous, some of which are desired but many are unwanted. Therefore, the ability to correctly predict and interpret this reactivity for complex molecular systems is essential to our understanding of singlet oxygen reactions. DFT is widely used for predicting many reactions but is not suited to degenerate electronic structures; application to isolated singlet oxygen often uses the spin-unrestricted formalism, which results in severe spin contamination. In this work, we demonstrate that spin-restricted DFT can correctly describe the reaction pathway for four prototypical singlet oxygen reactions. By careful benchmarking with XMS-CASPT2, we show that, from the first transition state onward, the degeneracy of the 1 Δ g state is broken due to differing interactions of the (degenerate) π* orbitals with the organic substrate; this result is well replicated with DFT. These findings demonstrate the utility of using spin-restricted DFT to explore reactions, opening the way to confidently use this computationally efficient method for molecular systems of medium to large organic molecules.

Confining DNA in nanochannels is an important approach to studying its structure and transportation dynamics. Graphene nanochannels are particularly attractive for studying DNA confinement due to their atomic flatness, precise height control, and excellent mechanical strength. Here, using femtosecond laser etching and wetting transfer, we fabricate graphene nanochannels down to less than 4.3 nm in height, with the length-to-height ratios up to 10 3 . These channels exhibit high stability, low noise, and self-cleaning ability during the long-term ionic current recording. We report a clear linear relationship between DNA length and the residence time in the channel and further utilize this relationship to differentiate DNA fragments based on their lengths, ranging widely from 200 bps to 48.5 kbps. The graphene nanochannel presented here provides a potential platform for label-free analyses and reveals fundamental insights into the conformational dynamics of DNA and proteins in confined space.

Anthracene- and pyrene-based twisted porous graphene ( AN-Pyre-PG ) with an ordered pore structure has been synthesized through bottom-up solution phase synthesis from a conjugated microporous polymer ( AN-Pyre-CMP ) via a heterogeneous Scholl cyclization reaction. The regular-ordered pores embedded within the graphene structures were analyzed through a Raman spectrum, different morphological analyses, and theoretical studies. A significant change in surface area from AN-Pyre-CMP to AN-Pyre-PG was observed, from 143 to 640 m 2 /g, respectively. Surface area-driven capacitive properties were also observed. Twisted-structure and ordered porous graphene shows better specific capacitance compared to CMP. AN-Pyre-PG shows a specific capacitance of 629 F g -1 at 1 A g -1 , with 91% retention of capacitance after 3000 charge-discharge cycles, whereas AN-Pyre-CMP shows a maximum specific capacitance of 200 F g -1 was observed at 2 A g -1 .

The need for anticancer therapies that overcome metallodrug resistance while minimizing adverse toxicities is targeted, herein, using titanium coordination complexes. Octahedral titanium(IV) trans , mer -[Ti{R 1 N(CH 2 -2-MeO-4-R 1 -C 6 H 2 ) 2 } 2 ] [R 1 = Et, allyl, n -Pr, CHO, F, CH 2 (morpholino), the latter from the formyl derivative; R 2 = Me, Et; not all combinations] are attained from Mannich reactions of commercial 2-methoxyphenols (27-74% overall yield, 2 steps). These crystalline (four X-ray structures) Ti(IV)-complexes are active against MCF-7, HCT-116, HT-29, PANC-1, and MDA-MB-468 cancer cell lines (GI 50 = 0.5-38 μM). Their activity and cancer selectivity (vs nontumor MRC-5 cells) typically exceeds that of cisplatin (up to 16-fold). Proteomic analysis (in MCF-7) supported by other studies (G2/M cell cycle arrest, ROS generation, γH2AX production, caspase activation, annexin positivity, western blot, and kinase screens in MCF-7 and HCT-116) suggest apoptosis elicited by more than one mechanism of action. Comparison of these data to the modes of action proposed for salan Ti(IV) complexes is made.

The coupling between sub-bandgap defect states and surface plasmon resonances in Au nanoparticles and its effects on the photoconductivity performance of TiO 2 are investigated in both the ultraviolet (UV) and visible spectrum. Incorporating a 2 nm gold nanoparticle layer in the photodetector device architecture creates additional trapping pathways, resulting in a faster current decay under UV illumination and a significant enhancement in the visible photocurrent of TiO 2 , with an 8-fold enhancement of the defects-related photocurrent. We show that hot electron injection (HEI) and plasmonic resonance energy transfer (PRET) jointly contribute to the observed photoconductivity enhancement. In addition to shedding light on the below-band-edge photoconductivity of TiO 2 , our work provides insight into new methods to probe and examine the surface defects of metal oxide semiconductors using plasmonic resonances., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Energy harvesting textiles have emerged as a promising solution to sustainably power wearable electronics. Textile-based solar cells (SCs) interconnected with on-body electronics have emerged to meet such needs. These technologies are lightweight, flexible, and easy to transport while leveraging the abundant natural sunlight in an eco-friendly way. In this Review, we comprehensively explore the working mechanisms, diverse types, and advanced fabrication strategies of photovoltaic textiles. Furthermore, we provide a detailed analysis of the recent progress made in various types of photovoltaic textiles, emphasizing their electrochemical performance. The focal point of this review centers on smart photovoltaic textiles for wearable electronic applications. Finally, we offer insights and perspectives on potential solutions to overcome the existing limitations of textile-based photovoltaics to promote their industrial commercialization.

Ab initio calculations were performed to determine the sensing behavior of g-C 3 N 4 and Li metal-doped g-C 3 N 4 (Li/g-C 3 N 4 ) quantum dots toward toxic compounds acetamide (AA), benzamide (BA), and their thio-analogues, namely, thioacetamide (TAA) and thiobenzamide (TAA). For optimization and interaction energies, the ωB97XD/6-31G(d,p) level of theory was used. Interaction energies ( E int ) illustrate the high thermodynamic stabilities of the designed complexes due to the presence of the noncovalent interactions. The presence of electrostatic forces in some complexes is also observed. The observed trend of E int in g-C 3 N 4 complexes was BA > TAA > AA > TBA, while in Li/g-C 3 N 4 , the trend was BA > AA > TBA > TAA. The electronic properties were studied by frontier molecular orbital (FMO) and natural bond orbital analyses. According to FMO, lithium metal doping greatly enhanced the conductivity of the complexes by generating new HOMOs near the Fermi level. A significant amount of charge transfer was also observed in complexes, reflecting the increase in charge conductivity. NCI and QTAIM analyses evidenced the presence of significant noncovalent dispersion and electrostatic forces in Li/g-C 3 N 4 and respective complexes. Charge decomposition analysis gave an idea of the transfer of charge density between quantum dots and analytes. Finally, TD-DFT explained the optical behavior of the reported complexes. The findings of this study suggested that both bare g-C 3 N 4 and Li/g-C 3 N 4 can effectively be used as atmospheric sensors having excellent adsorbing properties toward toxic analytes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Single unmodified biomolecules in solution can be observed and characterized by interferometric imaging approaches; however, Rayleigh scattering limits this to larger proteins (typically >30 kDa). We observe real-time image tracking of unmodified proteins down to 14 kDa using interference imaging enhanced by surface plasmons launched at an aperture in a metal film. The larger proteins show slower diffusion, quantified by tracking. When the diffusing protein is finally trapped by the nanoaperture, we perform complementary power spectral density and noise amplitude analysis, which gives information about the protein. This approach allows for rapid protein characterization with minimal sample preparation and opens the door to characterizing protein interactions in real time., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Cerium dioxide (CeO 2 ; ceria) nanoparticles (CeNPs) are promising nanozymes that show a variety of biological activity. Effective nanozymes need to retain their activity in the face of surface speciation in biological environments, and characterizing surface speciation is therefore critical to understanding and controlling the therapeutic capabilities of CeNPs. In particular, adsorbed phosphates can impact the enzymatic activity exploited to convert phosphate prodrugs into therapeutics in vivo and also define the early stages of the phosphate-scavenging processes that lead to the transformation of active CeO 2 into inactive CePO 4 . In this work, we utilize ab initio lattice-dynamics calculations to study the interaction of phosphates with the three major surfaces of ceria and to predict the infrared (IR) and Raman spectral signatures of adsorbed phosphate species. We find that phosphates adsorb strongly to CeO 2 surfaces in a range of stable binding configurations, of which 5-fold coordinated P species in a trigonal bipyramidal coordination may represent a stable intermediate in the early stages of phosphate scavenging. We find that the phosphate species show characteristic spectral fingerprints between 500 and 1500 cm -1 , whereas the bare CeO 2 surfaces show no active modes above 600 cm -1 , and the 5-fold coordinated P species in particular show potential diagnostic P-O stretching modes between 650 and 700 cm -1 in both IR and Raman spectra. This comprehensive exploration of different binding modes for phosphates on CeO 2 and the set of reference spectra provides an important step toward the experimental characterization of phosphate speciation and, ultimately, control of its impact on the performance of ceria nanozymes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Wearable electronic textiles (e-textiles) have emerged as a promising platform for seamless integration of electronic devices into everyday life, enabling nonintrusive monitoring of human health. However, the development of efficient, flexible, and scalable energy storage solutions remains a significant challenge for powering such devices. Here, we address this challenge by leveraging the distinct properties of two-dimensional (2D) material based heterostructures to enhance the performance of wearable textile supercapacitors. We report a highly scalable and controllable synthesis method for graphene and molybdenum disulfide (MoS 2 ) through a microfluidization technique. Subsequently, we employ an ultrafast and industry-scale hierarchical deposition approach using a pad-dry method to fabricate 2D heterostructure based textiles with various configurations suitable for wearable e-textiles applications. Comparative analyses reveal the superior performance of wearable textile supercapacitors based on 2D material heterostructures, demonstrating excellent areal capacitance (∼105.08 mF cm -2 ), high power density (∼1604.274 μW cm -2 ) and energy density (∼58.377 μWh cm -2 ), and outstanding capacitive retention (∼100% after 1000 cycles). Our findings highlight the pivotal role of 2D material based heterostructures in addressing the challenges of performance and scalability in wearable energy storage devices, facilitating large-scale production of high-performance wearable supercapacitors.

Two-dimensional material nanochannels with molecular-scale confinement can be constructed by Van der Waals assembly and show unexpected fluid transport phenomena. The crystal structure of the channel surface plays a key role in controlling fluid transportation, and many strange properties are explored in these confined channels. Here, we use black phosphorus as the channel surface to enable ion transport along a specific crystal orientation. We observed a significant nonlinear and anisotropic ion transport phenomenon in the black phosphorus nanochannels. Theoretical results revealed an anisotropy of ion transport energy barrier on the black phosphorus surface, with the minimum energy barrier along the armchair direction approximately ten times larger than that along the zigzag direction. This difference in energy barrier affects the electrophoretic and electroosmotic transport of ions in the channel. This anisotropic transport, which depends on the orientation of the crystal, may provide new approaches to controlling the transport of fluids.

The development of highly luminescent two-dimensional covalent organic frameworks (COFs) for sensing applications remains challenging. To suppress commonly observed photoluminescence quenching of COFs, we propose a strategy involving interrupting the intralayer conjugation and interlayer interactions using cyclohexane as the linker unit. By variation of the building block structures, imine-bonded COFs with various topologies and porosities are obtained. Experimental and theoretical analyses of these COFs disclose high crystallinity and large interlayer distances, demonstrating enhanced emission with record-high photoluminescence quantum yields of up to 57% in the solid state. The resulting cyclohexane-linked COF also exhibits excellent sensing performance for the trace recognition of Fe 3+ ions, explosive and toxic picric acid, and phenyl glyoxylic acid as metabolites. These findings inspire a facile and general strategy to develop highly emissive imine-bonded COFs for detecting various molecules.

The specificity of ions in inducing conformational changes in macromolecules is introduced as the Hofmeister series; however, the detailed underlying mechanism is not comprehensible yet. We utilized surface-specific sum frequency generation (SFG) vibrational spectroscopy to explore the Hofmeister effect at the air/polyvinylpyrrolidone (PVP)/water interface. The spectral signature observed from the ssp polarization scheme reveals ion-specific ordering of water molecules following the Hofmeister series attributed to the ion-macromolecule interactions. Along with this, the presence of ions does not reflect any significant influence on the structure of the PVP macromolecule. However, the ppp-SFG spectra in the CH-stretch region reveal the impact of ions on the orientation angle of vinyl chain CH 2 -groups, which follows the Hofmeister series: SO 4 2- > Cl - > NO 3 - > Br - > ClO 4 - > SCN - . The minimal orientation angle of CH 2 -groups indicates significant reordering in PVP vinyl chains in the presence of chaotropic anions ClO 4 - , and SCN - . The observation is attributed to the ion-specific water-macromolecule interactions at the air/aqueous interface. It is compelling to observe the signature of spectral blue shifts in the OH-stretch region in the ppp configuration in the presence of chaotropic anions. The origin of spectral blue shifts has been ascribed to the existence of weaker interactions between the interfacial water molecules and the backbone CH- and CH 2 -moieties of the PVP macromolecules. The ion-specific modulation in water-macromolecule interactions is endorsed by the relative propensity of anion's adsorption toward the air/aqueous interface. The experimental findings highlight the existence and cooperative participation of ion-specific water-macromolecule interactions in the mechanism of the Hofmeister effect, along with the illustrious ion-water and ion-macromolecule interactions.

Ferritin is a protein that stores and releases iron to prevent diseases associated with iron dysregulation in plants, animals, and bacteria. The conversion between iron-loaded holo-ferritin and empty apo-ferritin is an important process for iron regulation. To date, studies of ferritin have used either ensemble measurements to quantify the characteristics of a large number of proteins or single-molecule approaches to interrogate labeled or modified proteins. Here we demonstrate the first real-time study of the dynamics of iron ion loading and biomineralization within a single, unlabeled ferritin protein. Using optical nanotweezers, we trapped single apo- and holo-ferritins indefinitely, distinguished one from the other, and monitored their structural dynamics in real time. The study presented here deepens the understanding of the iron uptake mechanism of ferritin proteins, which may lead to new therapeutics for iron-related diseases.

Exploring a covalent organic framework (COF) material as an efficient metal-free photocatalyst and as an adsorbent for the removal of pollutants from contaminated water is very challenging in the context of sustainable chemistry. Herein, we report a new porous crystalline COF, C 6 -TRZ-TPA COF, via segregation of donor-acceptor moieties through the extended Schiff base condensation between tris(4-formylphenyl)amine and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)trianiline. This COF displayed a Brunauer-Emmett-Teller (BET) surface area of 1058 m 2 g -1 with a pore volume of 0.73 cc g -1 . Again, extended π-conjugation, the presence of heteroatoms throughout the framework, and a narrow band gap of 2.2 eV, all these features collectively work for the environmental remediation in two different perspectives: it could harness solar energy for environmental clean-up, where the COF has been explored as a robust metal-free photocatalyst for wastewater treatment and as an adsorbent for iodine capture. In our endeavor of wastewater treatment, we have conducted the photodegradation of rose bengal (RB) and methylene blue (MB) as model pollutants since these are extremely toxic, are health hazard, and bioaccumulative in nature. The catalyst C 6 -TRZ-TPA COF showed a very high catalytic efficiency of 99% towards the degradation of 250 parts per million (ppm) of RB solution in 80 min under visible light irradiation with the rate constant of 0.05 min -1 . Further, C 6 -TRZ-TPA COF is found to be an excellent adsorbent as it efficiently adsorbed radioactive iodine from its solution as well as from the vapor phase. The material exhibits a very rapid iodine capturing tendency with an outstanding iodine vapor uptake capacity of 4832 mg g -1 .

Designing N-coordinated porous single-atom catalysts (SACs) for the oxygen reduction reaction (ORR) is a promising approach to achieve enhanced energy conversion due to maximized atom utilization and higher activity. Here, we report two Co(II)-porphyrin/ [2,1,3]-benzothiadiazole (BTD)-based covalent organic frameworks (COFs; Co@ rhm -PorBTD and Co@ sql -PorBTD), which are efficient SAC systems for O 2 electrocatalysis (ORR). Experimental results demonstrate that these two COFs outperform the mass activity (at 0.85 V) of commercial Pt/C (20%) by 5.8 times (Co@ rhm -PorBTD) and 1.3 times (Co@ sql -PorBTD), respectively. The specific activities of Co@ rhm -PorBTD and Co@ sql -PorBTD were found to be 10 times and 2.5 times larger than that of Pt/C, respectively. These COFs also exhibit larger power density and recycling stability in Zn-air batteries compared with a Pt/C-based air cathode. A theoretical analysis demonstrates that the combination of Co-porphyrin with two different BTD ligands affords two crystalline porous electrocatalysts having different d-band center positions, which leads to reactivity differences toward alkaline ORR. The strategy, design, and electrochemical performance of these two COFs offer a pyrolysis-free bottom-up approach that avoids the creation of random atomic sites, significant metal aggregation, or unpredictable structural features.

Organofunctionalization of polyoxometalates (POMs) allows the preparation of hybrid molecular systems with tunable electronic properties. Currently, there are only a handful of approaches that allow for the fine-tuning of POM frontier molecular orbitals in a predictable manner. Herein, we demonstrate a new functionalization method for the Wells-Dawson polyoxotungstate [P 2 W 18 O 62 ] 6- using arylarsonic acids which enables modulation of the redox and photochemical properties. Arylarsonic groups facilitate orbital mixing between the organic and inorganic moieties, and the nature of the organic substituents significantly impacts the redox potentials of the POM core. The photochemical response of the hybrid POMs correlates with their computed and experimentally estimated lowest unoccupied molecular orbital energies, and the arylarsonic hybrids are found to exhibit increased visible light photosensitivity comparable with that of arylphosphonic analogues. Arylarsonic hybridization offers a route to stable and tunable organic-inorganic hybrid systems for a range of redox and photochemical applications.

Organopnictogen cations show promise as powerful, tunable main-group Lewis acid catalysts. The synthesis, solid-state structures, and reactivity of a series of weakly coordinated triarylchlorostibonium salts [Ar 3 SbCl][B(C 6 F 5 ) 4 ] (Ar = Ph, 3-FC 6 H 4 , 4-FC 6 H 4 , 3,5-F 2 C 6 H 3 , 2,4,6-F 3 C 6 H 2 ) are reported. The cation in each adopts a tetrahedral coordination environment of antimony, with near complete separation from the anion. Structural, computational, and reactivity studies reveal that the Lewis acidity of [Ar 3 SbCl] + generally increases with increased fluorination of the Ar substituents, with a secondary quenching effect from para fluorination. [Ar 3 SbCl] + is reduced to Ar 3 Sb in the presence of Et 3 SiH, and the mechanism of this reaction has been modeled computationally. Preliminary studies demonstrate that they are useful catalysts for the dimerization of 1,1-diphenylethylene and the Friedel-Crafts alkylation of benzene., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The crystal packing of organic chromophores has a profound impact on their photophysical properties. Molecular crystal engineering is generally incapable of producing precisely spaced arrays of molecules for use in photovoltaics, light-emitting diodes, and sensors. A promising alternative strategy is the incorporation of chromophores into crystalline metal-organic frameworks (MOFs), leading to matrix coordination-induced emission (MCIE) upon confinement. However, it remains unclear how the precise arrangement of chromophores and defects dictates photophysical properties in these systems, limiting the rational design of well-defined photoluminescent materials. Herein, we report new, robust Zr-based MOFs constructed from the linker tetrakis(4-carboxyphenyl)ethylene (TCPE 4- ) that exhibit an unexpected structural transition in combination with a prominent shift from green to blue photoluminescence (PL) as a function of the amount of acid modulator (benzoic, formic, or acetic acid) used during synthesis. Time-resolved PL (TRPL) measurements provide full spectral information and reveal that the observed hypsochromic shift arises due to a higher concentration of linker substitution defects at higher modulator concentrations, leading to broader excitation transfer-induced spectral diffusion. Spectral diffusion of this type has not been reported in a MOF to date, and its observation provides structural information that is otherwise unobtainable using traditional crystallographic techniques. Our findings suggest that defects have a profound impact on the photophysical properties of MOFs and that their presence can be readily tuned to modify energy transfer processes within these materials.

Identification and analysis of small molecule bioactivity in target-agnostic cellular assays and monitoring changes in phenotype followed by identification of the biological target are a powerful approach for the identification of novel bioactive chemical matter in particular when the monitored phenotype is disease-related and physiologically relevant. Profiling methods that enable the unbiased analysis of compound-perturbed states can suggest mechanisms of action or even targets for bioactive small molecules and may yield novel insights into biology. Here we report the enantioselective synthesis of natural-product-inspired 8-oxotetrahydroprotoberberines and the identification of Picoberin, a low picomolar inhibitor of Hedgehog (Hh)-induced osteoblast differentiation. Global transcriptome and proteome profiling revealed the aryl hydrocarbon receptor (AhR) as the molecular target of this compound and identified a cross talk between Hh and AhR signaling during osteoblast differentiation.

Evaporation is an interfacial phenomenon in which a water molecule breaks the intermolecular hydrogen (H-) bonds and enters the vapor phase. However, a detailed demonstration of the role of interfacial water structure in the evaporation process is still lacking. Here, we purposefully perturb the H-bonding environment at the air/water interface by introducing kosmotropic (HPO 4 -2 , SO 4 -2 , and CO 3 -2 ) and chaotropic ions (NO 3 - and I - ) to determine their influence on the evaporation process. Using time-resolved interferometry on aqueous salt droplets, we found that kosmotropes reduce evaporation, whereas chaotropes accelerate the evaporation process, following the Hofmeister series: HPO 4 -2 < SO 4 -2 < CO 3 -2 < Cl - < NO 3 - < I - . To extract deeper molecular-level insights into the observed Hofmeister trend in the evaporation rates, we investigated the air/water interface in the presence of ions using surface-specific sum frequency generation (SFG) vibrational spectroscopy. The SFG vibrational spectra reveal the significant impact of ions on the strength of the H-bonding environment and the orientation of free OH oscillators from ∼36.2 to 48.4° at the air/water interface, where both the effects follow the Hofmeister series. It is established that the slow evaporating water molecules experience a strong H-bonding environment with free OH oscillators tilted away from the surface normal in the presence of kosmotropes. In contrast, the fast evaporating water molecules experience a weak H-bonding environment with free OH oscillators tilted toward the surface normal in the presence of chaotropes at the air/water interface. Our experimental outcomes showcase the complex bonding environment of interfacial water molecules and their decisive role in the evaporation process.

The future of water-derived hydrogen as the "sustainable energy source" straightaway bets on the success of the sluggish oxygen-generating half-reaction. The endeavor to emulate the natural photosystem II for efficient water oxidation has been extended across the spectrum of organic and inorganic combinations. However, the achievement has so far been restricted to homogeneous catalysts rather than their pristine heterogeneous forms. The poor structural understanding and control over the mechanistic pathway often impede the overall development. Herein, we have synthesized a highly crystalline covalent organic framework (COF) for chemical and photochemical water oxidation. The interpenetrated structure assures the catalyst stability, as the catalyst's performance remains unaltered after several cycles. This COF exhibits the highest ever accomplished catalytic activity for such an organometallic crystalline solid-state material where the rate of oxygen evolution is as high as ∼26,000 μmol L -1 s -1 (second-order rate constant k ≈ 1650 μmol L s -1 g -2 ). The catalyst also proves its exceptional activity ( k ≈ 1600 μmol L s -1 g -2 ) during light-driven water oxidation under very dilute conditions. The cooperative interaction between metal centers in the crystalline network offers 20-30-fold superior activity during chemical as well as photocatalytic water oxidation as compared to its amorphous polymeric counterpart.

Low-cost large-area chirality meta-devices (CMDs) with adjustable optical chirality are of great interest for polarization-sensitive imaging, stereoscopic display, enantioselectivity analysis, and catalysis. Currently, CMDs with adjusted chiroptical responses in the mid-infrared to terahertz band have been demonstrated by exploiting photocarriers of silicon, pressure, and phase-change of GSTs but are still absent in the visible band, which in turn limits the development of chiral nanophotonic devices. Herein, by employing a phase-change material (Sb 2 S 3 ), we present a protocol for the fabrication of wafer-scale visible-band enantiomeric CMDs with handedness, spectral, and polarization adjustability. As measured by circular dichroism, the chirality signs of CMDs enantiomers can be adjusted with Sb 2 S 3 from amorphous to crystalline, and the chirality resonance wavelength can also be adjusted. Our results suggest a new type of meta-devices with adjustable chiroptical responses that may potentially enable a wide range of chirality nanophotonic applications including highly sensitive sensing and surface-enhanced nanospectroscopy.

In recent decades, food-packaging markets have attracted researchers' interest in many ways because such industries can directly affect human health. In this framework, the present study emphasizes the interesting and smart properties provided by new nanocomposites based on conducting polymers (CPs), silver nanoparticles (AgNPs), and cellulose fibers (CFs) and their possible applications as active food packaging. Polyaniline and poly(3,4-ethylenedioxythiophene) containing AgNPs were elaborated on via a simple one-step in situ chemical oxidative polymerization on CFs. Spectroscopic and microscopic characterization allowed a full discussion of the morphology and chemical structure of the nanocomposites and confirmed the successful polymerization of the monomer as well as the incorporation of AgNPs into the CP-based formulation. This study aims to demonstrate that it is possible to produce a highly efficient package with enhanced protective properties. Thus, the synthesized nanocomposites were tested as volatile organic compounds, sensors, and antibacterial and antioxidant agents. It is shown that the elaborated materials can, on the one hand, inhibit the development of biofilms and decrease the oxidation reaction rate of foodstuffs and, on the other hand, detect toxic gases generated by spoiled food. The presented method has unlocked massive opportunities for using such formulations as an interesting alternative for classical food containers. The smart and novel properties offered by the synthesized composites can be operated for future industrial applications to prevent any degradation of the packaged products by offering optimum protection and creating an atmosphere that can extend the shelf life of foodstuffs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Resonant metasurfaces provide a unique platform for enhancing multiwave nonlinear interactions. However, the difficulties over mode matching and material transparency place significant challenges in the enhancement of these multiwave processes. Here we demonstrate efficient nonlinear sum-frequency generation (SFG) in multiresonant GaP metasurfaces based on guided-wave bound-state in the continuum resonances. The excitation of the metasurface by two near-infrared input beams generates strong SFG in the visible spectrum with a conversion efficiency of 2.5 × 10 -4 W -1 , 2 orders of magnitude higher than the one reported in Mie-type resonant metasurfaces. In addition, we demonstrate the nontrivial polarization dependence on the SFG process. In contrast to harmonic generation, the SFG process is enhanced when using nonparallel polarized input-beams. Importantly, by varying the input pump beam polarization it is possible to direct the SFG emission to different diffraction orders, thereby opening up new opportunities for nonlinear light sources and infrared to visible light conversion.

Covalent organic frameworks (COFs) are promising hosts in heterogeneous catalysis. Herein, we report a dual metalation strategy in a single two-dimensional-COF TpBpy for performing a variety of C-N cross-coupling reactions. [Ir(ppy) 2 (CH 3 CN) 2 ]PF 6 [ppy = 2-phenylpyridine], containing two labile CH 3 CN groups, and NiCl 2 are used as iridium and nickel-metal precursors, respectively, for postsynthetic decoration of the TpBpy COF. Moving from the traditional approach, we focus on the COF-backbone host for visible-light-mediated nickel-catalyzed C-N coupling reactions. The controlled metalation and recyclability without deactivation of both catalytic centers are unique with respect to previously reported coupling strategies. We performed various photoluminescence, electrochemical, kinetic, and Hammett correlation studies to understand the salient features of the catalyst and reaction mechanism. Furthermore, theoretical calculations delineated the feasibility of electron transfer from the Ir center to the Ni center inside the confined pore of the TpBpy COF. The dual metal anchoring within the COF backbone prevented nickel-black formation. The developed protocol enables selective and reproducible coupling of a diverse range of amines (aryl, heteroaryl, and alkyl), carbamides, and sulfonamides with electron-rich, neutral, and poor (hetero) aryl iodides up to 94% isolated yield. The reaction can also be performed on a gram scale. Furthermore, to establish the practical implementation of this approach, we have applied the synthetic strategy for the late-stage diversification of the derivatives of ibuprofen, naproxen, gemfibrozil, helional, and amino acids. The methodology could also be applied to synthesize pharmacophore N,5-diphenyloxazol-2-amine and Food and Drug Administration-approved drugs, including flufenamic acid, flibanserin, and tripelennamine.

Two-dimensional covalent organic frameworks (2D COFs) represent a family of crystalline porous polymers with a long-range order and well-defined open nanochannels that hold great promise for electronics, catalysis, sensing, and energy storage. To date, the development of highly conductive 2D COFs has remained challenging due to the finite π-conjugation along the 2D lattice and charge localization at grain boundaries. Furthermore, the charge transport mechanism within the crystalline framework remains elusive. Here, time- and frequency-resolved terahertz spectroscopy reveals intrinsically Drude-type band transport of charge carriers in semiconducting 2D COF thin films condensed by 1,3,5-tris(4-aminophenyl)benzene (TPB) and 1,3,5-triformylbenzene (TFB). The TPB-TFB COF thin films demonstrate high photoconductivity with a long charge scattering time exceeding 70 fs at room temperature which resembles crystalline inorganic materials. This corresponds to a record charge carrier mobility of 165 ± 10 cm 2 V -1 s -1 , vastly outperforming that of the state-of-the-art conductive COFs. These results reveal TPB-TFB COF thin films as promising candidates for organic electronics and catalysis and provide insights into the rational design of highly crystalline porous materials for efficient and long-range charge transport.

Inorganic perovskite materials are possible candidates for conversion of solar energy to electrical energy due to their high absorption coefficient. Perovskite solar cells (PSCs) introduced a new type of device structure that has attention due to better efficiencies and interest in PSCs that has been increasing in recent years. Halide perovskite materials such as CsPbIBr 2 show remarkable optical and structural performance with their better physical properties. Perovskite solar cells are a possible candidate to replace conventional silicon solar panels. In the present study, CsPbIBr 2 perovskite materials' thin films were prepared for light-absorbing application. Five thin films were deposited on the glass substrates by subsequent spin-coating of CsI and PbBr 2 solutions, subsequently annealed at different temperature values (as-deposited, 100, 150, 200 and 250 °C) to get CsPbIBr 2 thin films with a better crystal structure. Structural characterizations were made by using X-ray diffraction. CsPbIBr 2 thin films were found to be polycrystalline in nature. With increasing annealing temperature, the crystallinity was improved, and the crystalline size was increased. Optical properties were studied by using transmission data, and by increasing annealing temperature, a small variation in optical band gap energy was observed in the range of 1.70-1.83 eV. The conductivity of CsPbIBr 2 thin films was determined by a hot probe technique and was found to have little fluctuating response toward p-type conductivity, which may be due to intrinsic defects or presence of CsI phase, but a stable intrinsic nature was observed. The obtained physical properties of CsPbIBr 2 thin films suggest them as a suitable candidate as a light-harvesting layer. These thin films could be an especially good partner with Si or other lower band gap energy materials in tandem solar cells (TSC). CsPbIBr 2 material will harvest light having energy of ∼1.7 eV or higher, while a lower energy part of the solar spectrum will be absorbed in the partner part of the TSC., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

We report on the feasibility to harness embryonic development in vitro for the identification of small-molecule cytokine mimetics and signaling activators. Here, a phenotypic, target-agnostic, high-throughput assay is presented that probes bone morphogenetic protein (BMP) signaling during mesodermal patterning of embryonic stem cells. The temporal discrimination of BMP- and transforming growth factor-β (TGFβ)-driven stages of cardiomyogenesis underpins a selective, authentic orchestration of BMP cues that can be recapitulated for the discovery of BMP activator chemotypes. Proof of concept is shown from a chemical screen of 7000 compounds, provides a robust hit validation workflow, and afforded 2,3-disubstituted 4 H -chromen-4-ones as potent BMP potentiators with osteogenic efficacy. Mechanistic studies suggest that Chromenone 1 enhances canonical BMP outputs at the expense of TGFβ-Smads in an unprecedented manner. Pharmacophoric features were defined, providing a set of novel chemical probes for various applications in (stem) cell biology, regenerative medicine, and basic research on the BMP pathway.

Relative to two-dimensional (2D) culture, three-dimensional (3D) culture of primary neurons has yielded increasingly physiological responses from cells. Electrospun nanofiber scaffolds are frequently used as a 3D biomaterial support for primary neurons in neural tissue engineering, while hydrophobic surfaces typically induce aggregation of cells. Poly-l-lactic acid (PLLA) was electrospun as aligned PLLA nanofiber scaffolds to generate a structure with both qualities. Primary cortical neurons from E18 Sprague-Dawley rats cultured on aligned PLLA nanofibers generated 3D clusters of cells that extended highly aligned, fasciculated neurite bundles within 10 days. These clusters were viable for 28 days and responsive to AMPA and GABA. Relative to the 2D culture, the 3D cultures exhibited a more developed profile; mass spectrometry demonstrated an upregulation of proteins involved in cortical lamination, polarization, and axon fasciculation and a downregulation of immature neuronal markers. The use of artificial neural network inference suggests that the increased formation of synapses may drive the increase in development that is observed for the 3D cell clusters. This research suggests that aligned PLLA nanofibers may be highly useful for generating advanced 3D cell cultures for high-throughput systems.

This study, which performs an extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres, presents the first draft of the human brain interhemispheric proteome. This high-resolution proteomics data provides comprehensive coverage of 3300 experimentally measured (nonhypothetical) proteins across multiple regions, allowing the characterization of protein-centric interhemispheric differences and synapse biology, and portrays the regional mapping of specific regions for brain disorder biomarkers. In the context of the Human Proteome Project (HPP), the interhemispheric proteome data reveal specific markers like chimerin 2 (CHN2) in the cerebellar vermis, olfactory marker protein (OMP) in the olfactory bulb, and ankyrin repeat domain 63 (ANKRD63) in basal ganglia, in line with regional brain transcriptomes mapped in the Human Protein Atlas (HPA). In addition, an in silico analysis pipeline was used to predict the structure and function of the uncharacterized uPE1 protein ANKRD63, and parallel reaction monitoring (PRM) was applied to validate its region-specific expression. Finally, we have built the Interhemispheric Brain Proteome Map (IBPM) Portal (www.brainprot.org) to stimulate the scientific community's interest in the brain molecular landscape and accelerate and support research in neuroproteomics. Data are available via ProteomeXchange with identifier PXD019936.

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported.

A metal-free protocol for the synthesis of substituted 1,6-dihydropyridines with quaternary stereogenic centers via a cascade aza-Wittig/6π-electrocyclization process has been developed. The high functional group compatibility and broad scope of this method were demonstrated by using a wide range of easily available vinyliminophosphoranes and ketones, with yields up to 97%. A modification of the obtained products allowed for an increase in complexity and chemical diversity. Finally, attempts for asymmetric synthesis of 1,6-dihydropyridines are demonstrated.

An increase in temperature of up to 2 °C occurs when the amount of CO 2 reaches a range of 450 ppm. The permanent use of mineral oil is closely related to CO 2 emissions. Maintaining the sustainability of fossil fuels and eliminating and reducing CO 2 emissions is possible through carbon capture and storage (CCS) processes. One of the best ways to maintain CCS is hydrate-based gas separation. Selected type T1-5 (0.01 mol % sodium dodecyl sulphate (SDS) + 5.60 mol % tetrahydrofuran (THF), with the help of this silica gel promotion was strongly stimulated. A pressure of 36.5 bar of CO 2 is needed in H 2 O to investigate the CO 2 hydrate formation. Therefore, ethylene glycol monoethyl ether (EGME at 0.10 mol %) along with SDS (0.01 mol %) labeled as T1A-2 was used as an alternative to THF at the comparable working parameters in which CO 2 uptake of 5.45 mmol of CO 2 /g of H 2 O was obtained. Additionally, it was found that with an increase in tetra- n -butyl ammonium bromide (TBAB) supplementation of CO 2 , the hydrate and operating capacity of the process increased. When the bed height was reduced from 3 cm to 2 cm with 0.1 mol % TBAB and 0.01% SDS (labelled as T3-2) in fixed bed reactor (FBR), the outcomes demonstrated a slight expansion in gas supply to 1.54 mmol of CO 2 /g of H 2 O at working states of 283 K and 70 bar. The gas selectivity experiment by using the high-pressure volume analysis through hydrate formation was performed in which the highest CO 2 uptake for the employment of silica contacts with water in fuel gas mixture was observed in the non-IGCC conditions. Thus, two types of reactor configurations are being proposed for changing the process from batch to continuous with the employment of macroporous silica contacts with new consolidated promoters to improve the formation of CO 2 hydrate in the IGCC conditions. Later, much work should be possible on this with an assortment of promoters and specific performance parameters. It was reported in previous work that the repeatability of equilibrium moisture content and gas uptake attained for the sample prepared by the highest rates of stirring was the greatest with the CIs of ±0.34 wt % and ±0.19 mmol of CO 2 /g of H 2 O respectively. This was due to the amount of water occluded inside silica gel pores was not an issue or in other words, vigorous stirring increased the spreadability. The variation of pore size to improve the process can be considered for future work., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

We undertake steps to overcome four challenges that have hindered the understanding of ZnO/biomolecule interfaces at the atomic scale: parametrization of a classical force field, ZnO surface termination and amino acid protonation state in methanol, and convergence of enhanced sampling molecular dynamics simulations. We predict adsorption free energies for histidine, serine, cysteine, and tryptophan in remarkable agreement with experimental measurements obtained via a novel indicator-displacement assay. Adsorption is driven by direct surface/amino-acid interactions mediated by terminal hydroxyl groups and stabilized by strongly structured methanol solvation shells.

The dynamic effect of an electric field on dielectric liquids is called liquid dielectrophoresis. It is widely used in several industrial and scientific applications, including inkjet printing, microfabrication, and optical devices. Numerical simulations of liquid-dielectrophoresis are necessary to understand the fundamental physics of the phenomenon, but also to explore situations that might be difficult or expensive to implement experimentally. However, such modeling is challenging, as one needs to solve the electrostatic and fluid dynamics equations simultaneously. Here, we formulate a new lattice-Boltzmann method capable of modeling the dynamics of immiscible dielectric fluids coupled with electric fields within a single framework, thus eliminating the need of using separate algorithms to solve the electrostatic and fluid dynamics equations. We validate the numerical method by comparing it with analytical solutions and previously reported experimental results. Beyond the benchmarking of the method, we study the spreading of a droplet using a dielectrowetting setup and quantify the mechanism driving the variation of the apparent contact angle of the droplet with the applied voltage. Our method provides a useful tool to study liquid-dielectrophoresis and can be used to model dielectric fluids in general, such as liquid-liquid and liquid-gas systems.

For benzene, toluene, aniline, fluorobenzene, and phenol, even sophisticated treatments of electron correlation, such as MRCI and XMS-CASPT2 calculations, show oscillator strengths typically lower than experiment. Inclusion of a simple pseudo-diabatization approach to perturb the S 1 state with approximate vibronic coupling to the S 2 state for each molecule results in more accurate oscillator strengths. Their absolute values agree better with experiment for all molecules except aniline. When the coupling between the S 1 and S 2 states is strong at the S 0 geometry, the simple diabatization scheme performs less well with respect to the oscillator strengths relative to the adiabatic values. However, we expect the scheme to be useful in many cases where the coupling is weak to moderate (where the maximum component of the coupling has a magnitude less than 1.5 au). Such calculations give an insight into the effects of vibronic coupling of excited states on UV/vis spectra.

Bottom-up mass spectrometry-based protein analysis methods employing protease digestion are routinely used to identify and characterize proteins with high specificity and sensitivity. Method performance is generally measured by sequence coverage capability and the total number of characteristic peptides identified, when compared to predicted databases. Limitations to commonly used solvent-based digestion methods currently employed include long digestion times (18-24 h or more), leading to protease autolysis, which also precludes automation, decreases sensitivity, and increases both intra- and inter-day performance variability. This report describes the development and validation of a simple, 5 min tryptic denaturing organic digestion (DOD) method for use with tandem mass spectrometry in bottom-up protein identification and characterization. It has been evaluated across select protein toxins and diagnostic clinical protein targets, substantially improving digestion performance when compared to other solution-based and enzyme-immobilized methods. The method was compared to two currently used bottom-up methods, the 24 h filter-aided sample prep (FASP) and Flash Digest (1 and 4 h) methods. Single proteins used to compare the methods included the ricin light chain, ricin heavy chain, ricin holotoxin, serotype A Clostridium botulinum toxin, Staphylococcus enterotoxin B, ribonuclease A, and thyroglobulin. In tests, across the proteins investigated, the 5 min DOD digestion method resulted in sequence coverages ranging from 55 to 100%, with relatively high reproducibility and precision; results were better than or equal to FASP method results and were greatly enhanced when compared to Flash method results. Importantly, DOD method intra- and inter-day precision was much improved as compared to results for both FASP and Flash digestions. These data indicated that the DOD method, when compared to the FASP and Flash Digest methods, dramatically reduced digestion time, while maintaining or improving the ability to detect and characterize targeted proteins, and reduced analytical variability for tryptic digestion, resulting in markedly faster and more precise analyses.

The polymer layer-by-layer assembly is accounted among the most attractive approaches for the design of advanced drug delivery platforms and biomimetic materials in 2D and 3D. The multilayer capsules can be made of synthetic or biologically relevant ( e.g. , natural) polymers. The biopolymers are advantageous for bioapplications; however, the design of such "biocapsules" is more challengeable due to intrinsic complexity and lability of biopolymers. Until now, there are no systematic studies that report the formation mechanism for multilayer biocapsules templated upon CaCO 3 crystals. This work evaluates the structure-property relationship for 16 types of capsules made of different biopolymers and proposes the capsule formation mechanism. The capsules have been fabricated upon mesoporous cores of vaterite CaCO 3 , which served as a sacrificial template. Stable capsules of polycations poly-l-lysine or protamine and four different polyanions were successfully formed. However, capsules made using the polycation collagen and dextran amine underwent dissolution. Formation of the capsules has been correlated with the stability of the respective polyelectrolyte complexes at increased ionic strength. All formed capsules shrink upon core dissolution and the degree of shrinkage increased in the series of polyanions: heparin sulfate < dextran sulfate < chondroitin sulfate < hyaluronic acid. The same trend is observed for capsule adhesiveness to the glass surface, which correlates with the decrease in polymer charge density. The biopolymer length and charge density govern the capsule stability and internal structure; all formed biocapsules are of a matrix-type, other words are microgels. These findings can be translated to other biopolymers to predict biocapsule properties.

Poly( N -isopropylacrylamide) (pNIPAM) hydrogels have broad potential applications as drug delivery vehicles because of their thermoresponsive behavior. pNIPAM loading/release performances are directly affected by the gel network structure. Therefore, there is a need with the approaches for accurate design of 3D pNIPAM assemblies with the structure ordered at the nanoscale. This study demonstrates size-selective spontaneous loading of macromolecules (dextrans 10-500 kDa) into pNIPAM microgels by microgel heating from 22 to 35 °C (microgels collapse and trap dextrans) followed by the dextran release upon further cooling down to 22 °C (microgels swell back) . This temperature-mediated behavior is fully reversible. The structure of pNIPAM microgels was tailored via hard templating and cross-linking of the hydrogel using sacrificial mesoporous cores of vaterite CaCO 3 microcrystals. In addition, the fabrication of hollow thermoresponsive pNIPAM microshells has been demonstrated, utilizing vaterite microcrystals that had narrower pores. The proposed approach for heating-triggered encapsulation and cooling-triggered release into/from pNIPAM microgels may pave the ways for applications of pNIPAM hydrogels for skin and transdermal cooling-responsive drug delivery in the future.

Increasing concern over rising levels of antibiotic resistance among pathogenic bacteria has prompted significant research into developing efficacious alternatives to antibiotic treatment. Previously, we have reported on the therapeutic activity of a dinuclear ruthenium(II) complex against pathogenic, multi-drug-resistant bacterial pathogens. Herein, we report that the solubility properties of this lead are comparable to those exhibited by orally available therapeutics that in comparison to clinically relevant antibiotics it induces very slow evolution of resistance in the uropathogenic, therapeutically resistant, E. coli strain EC958, and this resistance was lost when exposure to the compound was temporarily removed. With the aim of further investigating the mechanism of action of this compound, the regulation of nine target genes relating to the membrane, DNA damage, and other stress responses provoked by exposure to the compound was also studied. This analysis confirmed that the compound causes a significant transcriptional downregulation of genes involved in membrane transport and the tricarboxylic acid cycle. By contrast, expression of the chaperone protein-coding gene, spy , was significantly increased suggesting a requirement for repair of damaged proteins in the region of the outer membrane. The complex was also found to display activity comparable to that in E. coli in a range of other therapeutically relevant Gram-negative pathogens., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

We have previously shown that phenyl saligenin phosphate (PSP), an organophosphorus compound which is classed as a weak inhibitor of acetylcholinesterase, triggered cytotoxicity in mitotic and differentiated H9c2 cardiomyoblasts. The aim of this study was to assess whether sublethal concentrations of PSP could disrupt the morphology of differentiating rat H9c2 cardiomyoblasts and human-induced pluripotent stem-cell-derived cardiomyocyte progenitor cells (hiPSC-CMs) and to assess the underlying cytoskeletal changes. PSP-induced changes in protein expression were monitored via Western blotting, immunocytochemistry, and proteomic analysis. PSP-mediated cytotoxicity was determined by measuring MTT reduction, LDH release, and caspase-3 activity. Sublethal exposure to PSP (3 μM) induced morphological changes in differentiating H9c2 cells (7, 9, and 13 days), reflected by reduced numbers of spindle-shaped cells. Moreover, this treatment (7 days) attenuated the expression of the cytoskeletal proteins cardiac troponin I, tropomyosin-1, and α-actin. Further proteomic analysis identified nine proteins (e.g., heat shock protein 90-β and calumenin) which were down-regulated by PSP exposure in H9c2 cells. To assess the cytotoxic effects of organophosphorus compounds in a human cell model, we determined their effects on human-induced pluripotent stem-cell-derived cardiomyocyte progenitor cells. Chlorpyrifos and diazinon-induced cytotoxicity (48 h) was evident only at concentrations >100 μM. By contrast, PSP exhibited cytotoxicity in hiPSC-CMs at a concentration of 25 μM following 48 h exposure. Finally, sublethal exposure to PSP (3 μM; 7 days) induced morphological changes and decreased the expression of cardiac troponin I, tropomyosin-1, and α-actin in hiPSC-CMs. In summary, our data suggest cardiomyocyte morphology is disrupted in both cell models by sublethal concentrations of PSP via modulation of cytoskeletal protein expression.

The development of various ionization and fragmentation techniques has been of key importance for establishing mass spectrometry (MS) as a powerful tool for protein characterization. One example of this is matrix-assisted laser desorption/ionization (MALDI) combined with in-source decay (ISD) fragmentation that allows mapping of N- and C-terminal regions of large proteins without the need for proteolysis. Positive ion mode ISD fragments are commonly assigned in the mass region above m / z 1000, while MALDI matrix ions generally hamper the detection of smaller singly charged fragments. The ultrahigh resolving power provided by Fourier transform ion cyclotron resonance (FT-ICR) MS partially overcomes this limitation, but to further increase the detection of smaller fragments we have revisited the application of negative ion mode MALDI-ISD and found good coverage of the peptide chain termini starting from c'2 and z'2 fragment ions. For the first time, we demonstrate that the combination of negative and positive ion MALDI FT-ICR MS is a useful tool to improve the characterization of mAbs. The different specificities of the two ion modes allowed us to selectively cover the sequence of the light and heavy chains of mAbs at increased sensitivity. A comprehensive evaluation of positive and negative ion mode MALDI-ISD FT-ICR MS in the m / z range 46-13 500 showed an increased sequence coverage for three standard proteins, namely, myoglobin, SiLuLite mAb, and NIST mAb. The data obtained in the two ion modes were, in part, complementary.

Methotrexate (MTX) is a chemotherapeutic agent that can cause a range of toxic side effects including gastrointestinal damage, hepatotoxicity, myelosuppression, and nephrotoxicity and has potentially complex interactions with the gut microbiome. Following untargeted UPLC-qtof-MS analysis of urine and fecal samples from male Sprague-Dawley rats administered at either 0, 10, 40, or 100 mg/kg of MTX, dose-dependent changes in the endogenous metabolite profiles were detected. Semiquantitative targeted UPLC-MS detected MTX excreted in urine as well as MTX and two metabolites, 2,4-diamino- N -10-methylpteroic acid (DAMPA) and 7-hydroxy-MTX, in the feces. DAMPA is produced by the bacterial enzyme carboxypeptidase glutamate 2 (CPDG2) in the gut. Microbiota profiling (16S rRNA gene amplicon sequencing) of fecal samples showed an increase in the relative abundance of Firmicutes over the Bacteroidetes at low doses of MTX but the reverse at high doses. Firmicutes relative abundance was positively correlated with DAMPA excretion in feces at 48 h, which were both lower at 100 mg/kg compared to that seen at 40 mg/kg. Overall, chronic exposure to MTX appears to induce community and functionality changes in the intestinal microbiota, inducing downstream perturbations in CPDG2 activity, and thus may delay MTX detoxication to DAMPA. This reduction in metabolic clearance might be associated with increased gastrointestinal toxicity.

Determining conical intersection geometries is of key importance to understanding the photochemical reactivity of molecules. While many small- to medium-sized molecules can be treated accurately using multireference approaches, larger molecules require a less computationally demanding approach. In this work, minimum energy crossing point conical intersection geometries for a series of molecules have been studied using spin-flip TDDFT (SF-TDDFT), within the Tamm-Dancoff Approximation, both with and without explicit calculation of nonadiabatic coupling terms, and compared with both XMS-CASPT2 and CASSCF calculated geometries. The less computationally demanding algorithms, which do not require explicit calculation of the nonadiabatic coupling terms, generally fare well with the XMS-CASPT2 reference structures, while the relative energetics are only reasonably replicated with the MECP structure as calculated with the BHHLYP functional and full nonadiabatic coupling terms. We also demonstrate that, occasionally, CASSCF structures deviate quantitatively from the XMS-CASPT2 structures, showing the importance of including dynamical correlation.