Carbonyl-amine condensation coupled ozonolysis of dipropylamine and styrene: Decay kinetics, reaction mechanism, secondary organic aerosol formation and cytotoxicity.

Oxidation of organic amines (OAs) or aromatic hydrocarbons (AHs) produces carbonyls, which further react with OAs to form carbonyl-amine condensation products, threatening environmental quality and human health. However, there is still a lack of systematic understanding of the carbonyl-amine condensation reaction processes of OAs or between OAs and AHs, and subsequent environmental health impact. This work systematically investigated the carbonyl-amine condensation coupled ozonolysis kinetics, reaction mechanism, secondary organic aerosol (SOA) formation and cytotoxicity from the mixture of dipropylamine (DPA) and styrene (STY) by a combined method of product mass spectrometry identification, particle property analysis and cell exposure evaluation. The results from ozonolysis of DPA and STY mixture revealed that STY inhibited the ozonolysis of DPA to different degrees to accelerate its own decay rate. The barycenter of carbonyl-amine condensation reactions was shifted from inside of DPA to between DPA and STY, which accelerated STY ozonolysis, but slowed down DPA ozonolysis. For the first time, ozonolysis of DPA and STY mixture to complex carbonyl-amine condensation products through the reactions of DPA with its carbonyl products, DPA with STY's carbonyl products and DPA's bond breakage product with STY's carbonyl products was confirmed. These condensation products significantly contributed to the formation and growth of SOA. The SOA containing particulate carbonyl-amine condensation products showed definite cytotoxicity. These findings are helpful to deeply and comprehensively understand the transformation, fate and environmental health effects of mixed organics in atmospheric environment.

Visualizing, Quantifying and Mapping Chromatin Remodelers at Work with Single-Molecule and Single-Cell Imaging.

Chromatin remodeling, carried out by four major subfamilies of ATP-dependent remodeler complexes across eukaryotes, alleviates the topological challenge posed by nucleosomes to regulate genome access. Recently, single-molecule and single-cell imaging techniques have been widely employed to probe this crucial process, both in vitro and in cellulo. Herein, we provide an integrated account of key recent efforts that leverage these approaches to visualize, quantify and map chromatin remodelers at work, elucidating diverse aspects of the remodeling process in both space and time, including molecular mechanisms of DNA wrapping/unwrapping, nucleosome translocation and histone exchange, dynamics of chromatin binding/target search and their intranuclear organization into hotspots or phase condensates, as well as functional coupling with transcription. The mechanistic insights and quantitative parameters revealed shed light on a multi-modal yet shared landscape for regulating remodeling across molecular and cellular scales, and pave the way for further interrogating the implications of its misregulation in disease contexts.

A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis.

Transcriptional factors (TFs) act as key determinants of cell death and survival by differentially modulating gene expression. Here, we identified many TFs, including TEAD4, that form condensates in stressed cells. In contrast to YAP-induced transcription-activating condensates of TEAD4, we found that co-factors such as VGLL4 and RFXANK alternatively induced repressive TEAD4 condensates to trigger cell death upon glucose starvation. Focusing on VGLL4, we demonstrated that heterotypic interactions between TEAD4 and VGLL4 favor the oligomerization and assembly of large TEAD4 condensates with a nonclassical inhibitory function, i.e., causing DNA/chromatin to be aggregated and entangled, which eventually impede gene expression. Based on these findings, we engineered a peptide derived from the TEAD4-binding motif of VGLL4 to selectively induce TEAD4 repressive condensation. This "glue" peptide displayed a strong antitumor effect in genetic and xenograft mouse models of gastric cancer via inhibition of TEAD4-related gene transcription. This new type of repressive TF phase separation exemplifies how cofactors can orchestrate opposite functions of a given TF, and offers potential new antitumor strategies via artificial induction of repressive condensation.

[Synthesis of Coumarin-oligonucleiotide Conjugates for Application in DNA-encoded Libraries].

Oligonucleotides, including DNA and RNA, can be functionalized by chemical modification based on synthetic organic chemistry. For example, ligand-oligonucleotide conjugates have a wide variety of applications. Conjugates of functional ligands and oligonucleotides have attracted attention in recent years as a drug delivery system (DDS) for improving the efficacy of oligonucleotide therapeutics. In addition, oligonucleotide conjugates with drug candidate compounds as ligands have been applied to drug screening using DNA-encoded libraries (DELs). Against this background, we have focused on the development of practical synthetic methods for ligand-oligonucleotide conjugates. Recently, we have developed a new synthetic method to construct oligonucleotides conjugated with coumarins and dipeptides, which are expected to have bioactivity, for application to DDS research of oligonucleotide therapeutics and drug discovery research using DEL. In this review, we will discuss the details, including how to construct a coumarin scaffold on oligonucleotides based on Knoevenagel condensation.

Nanomolar Hg2+ detection via phenothiazine fluorogenic chemosensor: Applications in water analysis and intracellular imaging.

A Knoevenagel condensation reaction paved the way for the development of the PTZ-BCN probe namely (z)-2-(1H-benzo[d]imidazole-2-yl)-3-(10-ethyl-10H-phenothiazin-3-yl) acrylonitrile. PTZ-BCN's spectral characteristics were verified through the application of IR, 1H NMR, 13C NMR, and HRMS techniques. The PTZ-BCN probe showed a high selectivity and sensitivity toward Hg2+ ions over other interfering competing metal ions in CH3CN: HEPES buffer (9:1, v/v) system. The addition of Hg2+ results in a notable redshift and fluorescence quenching of the PTZ-BCN probe. An examination of the interaction between the PTZ-BCN probe and Hg2+ involved recoding 1H NMR titration spectra, HRMS, DFT analysis, and Job's plot respectively. Quantification of the lowest detectable Hg2+ concentration at 2.3 nM, exhibiting a correlation coefficient of R2 = 0.9985. PTZ-BCN probe has proven effective in quantitatively determining the existence of Hg2+ in real-time water samples, test strips, solid state, and Hela living cells.

π-π interactions drive the homotypic phase separation of the prion-like diatom pyrenoid scaffold PYCO1.

CO2 fixation in most unicellular algae relies on the pyrenoid, a biomolecular condensate, which sequesters the cell's carboxylase Rubisco. In the marine diatom Phaeodactylum tricornutum, the pyrenoid tandem repeat protein Pyrenoid Component 1 (PYCO1) multivalently binds Rubisco to form a heterotypic Rubisco condensate. PYCO1 contains prion-like domains and can phase-separate homotypically in a salt-dependent manner. Here we dissect PYCO1 homotypic liquid-liquid phase separation (LLPS) by evaluating protein fragments and the effect of site-directed mutagenesis. Two of PYCO1's six repeats are required for homotypic LLPS. Mutagenesis of a minimal phase-separating fragment reveals tremendous sensitivity to the substitution of aromatic residues. Removing positively charged lysines and arginines instead enhances the propensity of the fragment to condense. We conclude that PYCO1 homotypic LLPS is mostly driven by π-π interactions mediated by tyrosine and tryptophan stickers. In contrast π-cation interactions involving arginine or lysine are not significant drivers of LLPS in this system.

TDP-43 nuclear condensation and neurodegenerative proteinopathies.

RNA-binding proteins (RBPs) can undergo phase separation and form condensates, processes that, in turn, can be critical for their functionality. In a recent study, Huang, Ellis, and colleagues show that cellular stress can trigger transient alterations in nuclear TAR DNA-binding protein 43 (TDP-43), leading to changes crucial for proper neuronal function. These findings have implications for understanding neurological TDP-43 proteinopathies.

High-Efficiency Condensation Heat Transfer Interfaces Based on Superwetting Copper Microgroove/Nanocone Structure.

Utilizing superhydrophobic micro/nanostructures to enhance condensation heat transfer (CHT) of copper surfaces has attracted intensive interest in recent years due to its significance in multiple industrial fields including nuclear power generation, thermal management, water harvesting, and desalination. However, superhydrophobic surfaces have instability risk caused by microcavity defect-induced vapor penetration and/or hydrophobic chemistry destruction. Here, we report a superwetting copper hierarchical microgroove/nanocone (MGNC) structure strategy that can realize high-efficiency CHT over a whole range of surface subcooling. By regulating groove width, fin width, groove depth, and nanostructure growth time, we obtain the optimal MGNC structure, where the CHT coefficient is 121% and 107% higher than that of hydrophilic flat surfaces at surface subcooling of 2 and 15 K, respectively. Such remarkable enhancement can be ascribed to the synergy of three interface effects: more nucleation sites for phase-change energy exchanging, thinner condensate films for reducing thermal resistance, and parallel microchannels for timely drainage. Compared with superhydrophobic strategies, our strategy not only can be mass-producible but also has other inherent advantages: no microcavity-induced performance failure risk as well as being free of chemistry modification, which makes the fabrication process simpler and more economic. Hierarchical micropillar/nanocone structure is also fabricated as the contrast sample for highlighting the superiority of the superwetting MGNC structure in enhancing CHT. This work not only enriches research systems of superwettability surfaces but also helps develop high-performance chips' cooling devices and explore more potential applications.

What can we learn from the experiment of electrostatic conveyor beltfor excitons?

Motivated by the experiment of electrostatic conveyor belt for indirect excitons [A. G. Winbow, \textit{et al.}, Phys. Rev. Lett. \textbf{106}, 196806 (2011)], we study the exciton patterns for understanding the exciton dynamics. By analyzing the exciton diffusion, we find that the patterns mainly come from the photoluminescence of two kinds of excitons. The patterns near the laser spot come from the hot excitons which can be regarded as the classical particles. However, the patterns far from the laser spot come from the cooled excitons or coherent excitons. Taking into account of the finite lifetime of Bosonic excitons and of the interactions between them, we build a time-dependent nonlinear Schr"{o}dinger equation including the non-Hermitian dissipation to describe the coherent exciton dynamics. The real-time and imaginary-time evolutions are used alternately to solve the Schr"{o}dinger equation in order to simulate the exciton diffusion accompanied with the exciton cooling in the moving lattices. By calculating the escape probability, we obtain the transport distances of the coherent excitons in the conveyor which are consistent with the experimental data. The cooling speed of excitons is found to be important in the coherent exciton transport. Moreover, the plateau in the average transport distance cannot be explained by the dynamical localization-delocalization transition induced by the disorders.

Ultrahigh Subcooling Dropwise Condensation Heat Transfer on Slippery Liquid-like Monolayer Grafted Surfaces.

Rapid and continuous droplet shedding is crucial for many applications, including thermal management, water harvesting, and microfluidics, among others. Superhydrophobic surfaces, though effective, suffer from droplet pinning at high subcooling temperature (Tsub). Conversely, slippery liquid-like surfaces covalently bonded with flexible hydrophobic molecules show high stability and low droplet adhesion attributed to their dense and ultrasmooth water repellent polymer chains, enhancing dropwise condensation and rapid shedding. In this work, linear poly(dimethylsiloxane) chains of various viscosities are covalently bonded onto silicon substrates to form thin and smooth monolayer coated surfaces. The formation of the monolayer is characterized by cryogenic transmission electron microscopy. On these surfaces a very low contact angle hysteresis is reported within wide surface temperature ranges as well as continuous dropwise condensation at ultrahigh Tsub of 60 K. In particular, one of the highest condensation heat fluxes of 1392.60 kW·m-2 and a heat transfer coefficient of 23.21 kW·m-2·K-1 at ultrahigh Tsub of 60 K is reported. The experimental heat transfer performance is further compared to the theoretical heat transfer via the individual droplets with the droplet distribution elucidated via both macroscopic observations as well as environmental scanning electron microscopy. Finally, only a mild decrease in the heat transfer coefficient of 20.3% after 100 h of condensation test at Tsub of 60 K is reported. Slippery liquid-like surfaces promote droplet shedding and sustain dropwise condensation at high Tsub without flooding empowered by the lower frictional forces, addressing challenges in heat transfer performance and durability.

Promoter DNA methylation and transcription factor condensation are linked to transcriptional memory in mammalian cells.

The regulation of genes can be mathematically described by input-output functions that are typically assumed to be time invariant. This fundamental assumption underpins the design of synthetic gene circuits and the quantitative understanding of natural gene regulatory networks. Here, we found that this assumption is challenged in mammalian cells. We observed that a synthetic reporter gene can exhibit unexpected transcriptional memory, leading to a shift in the dose-response curve upon a second induction. Mechanistically, we investigated the cis-dependency of transcriptional memory, revealing the necessity of promoter DNA methylation in establishing memory. Furthermore, we showed that the synthetic transcription factor's effective DNA binding affinity underlies trans-dependency, which is associated with its capacity to undergo biomolecular condensation. These principles enabled modulating memory by perturbing either cis- or trans-regulation of genes. Together, our findings suggest the potential pervasiveness of transcriptional memory and implicate the need to model mammalian gene regulation with time-varying input-output functions. A record of this paper's transparent peer review process is included in the supplemental information.

VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation.

The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance.Genomic expression intricately hinges on localized interactions among its products. Conventional variant prioritization, biased towards known disease genes and the structure-function paradigm, overlooks the potential impact of variants shaping the composition, location, size, and properties of biomolecular condensates, genuine membraneless organelles swiftly sensing and responding to environmental changes, and modulating expressivity.To address this complexity, we propose to focus on the nexus of genetic variants within biomolecular condensates determinants. Scrutinizing variant effects in these membraneless organelles could refine prioritization, enhance diagnostics, and unveil the molecular underpinnings of rare diseases. Integrating comprehensive genome sequencing, transcriptomics, and computational models can unravel variant pathogenicity and disease mechanisms, enabling precision medicine. This paper presents the rationale driving our proposal and describes a protocol to implement this approach. By fusing state-of-the-art knowledge and methodologies into the clinical practice, we aim to redefine rare diseases diagnosis, leveraging the power of scientific advancement for more informed medical decisions.

Molecular Dynamics Simulations of the miR-155 Duplex: Impact of Ionic Strength on Structure and Na+ and Cl- Ion Distribution.

MiR-155 is a multifunctional microRNA involved in many biological processes. Since miR-155 is overexpressed in several pathologies, its detection deserves high interest in clinical diagnostics. Biosensing approaches often exploit the hybridization of miR-155 with its complementary strand. Molecular Dynamics (MD) simulations were applied to investigate the complex formed by miR-155 and its complementary strand in aqueous solution with Na+ and Cl- ions at ionic strengths in the 100-400 mM range, conditions commonly used in biosensing experiments. We found that the main structural properties of the duplex are preserved at all the investigated ionic strengths. The radial distribution functions of both Na+ and Cl- ions around the duplex show deviation from those of bulk with peaks whose relative intensity depends on the ionic strength. The number of ions monitored as a function of the distance from the duplex reveals a behavior reminiscent of the counterion condensation near the duplex surface. The occurrence of such a phenomenon could affect the Debye length with possible effects on the sensitivity in biosensing experiments.

Reconstruction and Solidification of Dion-Jacobson Perovskite Top and Buried Interfaces for Efficient and Stable Solar Cells.

Quasi-two-dimensional (Q-2D) perovskites show great potential in the field of photonic and optoelectronic device applications. However, defects and local lattice dislocation still limit performance and stability improvement by nonradiative recombination, unpreferred phase distribution, and unbonded amines. Here, a low-temperature synergistic strategy for both reconstructing and solidifying the perovskite top and buried interface is developed. By post-treating the 1,4-phenylenedimethanammonium (PDMA) based (PDMA)MA4Pb5I16 films with cesium acetate (CsAc) before thermal annealing, a condensation reaction between R-COO- and -NH2 and ion exchange between Cs+ and MA+ occur. It converts the unbonded amines to amides and passivates uncoordinated Pb2+. Meanwhile, it adjusts film composition and improves the phase distribution without changing the out-of-plane grain orientation. Consequently, performance of 18.1% and much-enhanced stability (e.g., stability for photo-oxygen increased over 10 times, light-thermal for T90 over 4 times, and reverse bias over 3 times) of (PDMA)MA4Pb5I16 perovskite solar cells are demonstrated.

A Stereoselective Synthesis of a Novel α,ß-Unsaturated Imine-Benzodiazepine through Condensation Reaction, Crystal Structure, and DFT Calculations.

The stereoisomers (E)-2,2-dimethyl-4-(4-subsitutedstyryl)-2,3-dihydro-1H-[1,5]-benzodiazepine 3(a-d) were synthesized via the condensation reaction of 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine (BZD) 1 with the benzaldehyde derivatives 2(a-d) in ethanol. The chemical structure of the prepared products was confirmed by NMR (1H and 13C), HRMS, and X-ray analysis of the crystal structure 3d. The condensation reaction was examined using DFT calculations at the theoretical level of B3LYP/6-31G(d) to elucidate the chemo-, regio-, and stereoselectivity and the reaction mechanism of the produced isomer. Furthermore, we identified each reagent's reactive sites by the measurement of the reactivity indices. We also looked at how the electron-withdrawing groups (EWGs) of various aldehydes affected the reaction's mechanism and the stability of products 3(a-d).

Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation.

FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.

Step-by-step synthetic route to access eugenol-1,2,3-triazole-chalcone hybrid.

Molecular hybridization represents a strategic approach in drug design, where two or more pharmacophoric elements from distinct bioactive molecules are integrated into a single hybrid compound. In this study, we synthesized hybrid compounds of chalcone, triazole, and eugenol through straightforward reactions using 4-hydroxyacetophenone as the starting material. Initially, 4-hydroxyacetophenone (1) underwent alkylation with 1,4-dibromobutane to produce compound 2 with an 84 % yield. Compound 2 was then subjected to azidation, resulting in azidobutoxyacetophenone 3 with a 71 % yield. Subsequently, compound 3 was reacted with either benzaldehyde or 4-methoxybenzaldehyde via base-catalyzed aldol condensation, yielding azidobutoxychalcones 4a (69 %) and 4b (84 %). Finally, azide-alkyne [3+2] cycloaddition between 4a/4b and propargylated eugenol afforded chalcone derivatives bearing eugenol-1,2,3-triazole hybrids 5a and 5b, each with a 90 % yield.•Synthesized chalcones featuring an eugenol-1,2,3-triazole scaffold using 4-hydroxyacetophenone as the starting material.•Synthesis was accomplished through a four-step reaction sequence.•Products were obtained in good yield.

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation.

A one-pot three-component synthesis of substituted meta-hetarylanilines from heterocycle-substituted 1,3-diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21-85% isolated yield) demonstrates the synthetic utility of the developed method.

Investigation and thermodynamic analysis of hydrogen liquefaction cycles: Energy and exergy study.

The use of hydrogen as a clean fuel has drawn the attention of many scientists due to the problem of energy and environmental pollution caused by fossil fuels. One of the important requirements for expanding the use of hydrogen is the investigation and thermodynamic analysis of liquefaction cycle; this includes the thermodynamic investigation of different cycles of hydrogen liquefaction in pre-cooling and cryogenic cooling. Thermodynamic analysis comprises an examination of the cycle's energy and exergy, as well as the equipment employed. In this research, three liquefaction cycles with different pre-cooling cycle and cryo-cooling cycle have been evaluated. The use of organic Rankine cycle ( O R C ) and liquefied natural gas ( L N G ) has also been applied in the cycles and the arrangement of the equipment. Simulations and analyzes have been done in Aspen HYSYS V12. The results show that in the pre-cooling process of cycles 1, 2, and 3, the amount of useful exergy is 49.87 %, 58.87 %, and 61.21 %, respectively, which means that the third cycle uses the input exergy better. Also, in the pre-cooling process of cycles 1, 2, and 3, the amount of exergy loss is 33.86 %, 26.77 %, and 19.73 %, respectively, which means that the third cycle has less exergy loss in the pre-cooling process. The findings indicate that in each of the three cycles, over 50 % of the input exergy is wasted in the cryo-cooling process. Value of specific energy consumption ( SEC ) for cycle 1,2, and 3 is equal to 6.605 k W h / k g L H 2 , 6.601 k W h / k g L H 2 and 6.618 k W h / k g L H 2 , respectively. The three cycles under examination had COP values of 0.19945, 0.19936, and 0.19884, in that order. Also, the values for EXE cycles 1, 2, and 3 are 45.816 %, 45.883 %, and 45.797 %, respectively. Analyzing the energy and exergy of liquefaction cycles is a good step toward increasing cycle efficiency, identifying weak places, and altering cycles to improve efficiency.

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties.

For the first time, herein, we report the synthetic part of the truxene-centred mono-, di- and tri-substituted dipyromethanes (DPMs) in good yields (60-80%) along with their preliminary photophysical (absorption, emission and time resolved fluorescence lifetime) properties. The condensation reaction for assembling the required DPMs were catalyzed with trifluoroacetic acid (TFA) at 0 °C to room temperature (rt), and the stable dipyrromethanes were purified through silica-gel column chromatography. After successfully synthesizing these easy-to-make yet interesting molecules, they were fully characterized by means of the standard spectroscopic techniques (1H NMR, 13C NMR and HRMS). We are of the opinion that these truxene-based systems will be useful for diverse applications in future studies.