Micropolarity governs the structural organization of biomolecular condensates.

Membraneless organelles within cells have unique microenvironments that play a critical role in their functions. However, how microenvironments of biomolecular condensates affect their structure and function remains unknown. In this study, we investigated the micropolarity and microviscosity of model biomolecular condensates by fluorescence lifetime imaging coupling with environmentally sensitive fluorophores. Using both in vitro and in cellulo systems, we demonstrated that sufficient micropolarity difference is key to forming multilayered condensates, where the shells present more polar microenvironments than the cores. Furthermore, micropolarity changes were shown to be accompanied by conversions of the layered structures. Decreased micropolarities of the granular components, accompanied by the increased micropolarities of the dense fibrillar components, result in the relocation of different nucleolus subcompartments in transcription-stalled conditions. Our results demonstrate the central role of the previously overlooked micropolarity in the regulation of structures and functions of membraneless organelles.

Activity-based photoacoustic probe for biopsy-free assessment of copper in murine models of Wilson's disease and liver metastasis.

The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson's disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson's disease animals from healthy control mice in each instance.

Hypoxia-Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors.

Developing safe and precise image-guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia-responsive photosensitizer, TPA-Azo. Introducing the azo group into the photosensitizer TPA-BN with aggregation-induced emission quenches its fluorescence. When the nonfluorescent TPA-Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA-BN with an amino group that exhibits fluorescence-activatable image-guided photodynamic therapy with dual-organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence-activatable photosensitizers.

Visualizing the Multistep Process of Protein Aggregation in Live Cells.

Protein aggregation is a biological phenomenon in which aberrantly processed or mutant proteins misfold and assemble into a variety of insoluble aggregates. Decades of studies have delineated the structure, interaction, and activity of proteins in either their natively folded structures or insoluble aggregates such as amyloid fibrils. However, a variety of intermediate species exist between these two extreme states in the protein folding landscape. Herein, we collectively term these intermediate species as misfolded protein oligomers, including soluble oligomers and preamyloid oligomers that are formed by unfolded or misfolded proteins. While extensive tools have been developed to study folded proteins or amyloid fibrils, research to understand the properties and activities of misfolded protein oligomers has been limited by the lack of methods to detect and interrogate these species in live cells.In this Account, we describe our efforts in the development of chemical methods that allow for the characterization of the multistep protein aggregation process, in particular the misfolded protein oligomers, in living cells. As the start of this journey, we attempted to develop a fluorogenic method wherein the misfolded oligomers could turn on the fluorescence of chemical probes that are conjugated to the protein-of-interest (POI). To this end, we produced a series of destabilized HaloTag variants, formulating the primary component of the AgHalo sensor, which misfolds and aggregates when cells are subjected to stress. When AgHalo is covalently conjugated with a solvatochromic fluorophore, misfolding of the AgHalo conjugate would activate fluorescence, resulting in the observation of misfolded oligomers. Following this work, we extended the scope of detection from AgHalo to any protein-of-interest via the AggTag method, wherein the POIs are genetically fused to self-labeling protein tags (HaloTag or SNAP-tag). Focusing on the molecular rotor-based fluorophores, we applied the modulated fluorescent protein (FP) chromophore core as a prototype for the AggTag probes, to enable the fluorogenic detection of misfolded soluble oligomers of multiple proteins in live cells. Next, we further developed the AggTag method to distinguish insoluble aggregates from misfolded oligomers, using two classes of probes that activate different fluorescence emission toward these two conformations. To enable this goal, we applied physical organic chemistry and computational chemistry to discover a new category of triode-like fluorophores, wherein the π orbitals of either an electron density regulator or the donor-acceptor linkages are used to control the rotational barriers of fluorophores in the excited states. This mechanism allows us to rationally design molecular rotor-based fluorophores that have desired responses to viscosity, thus extending the application of the AggTag method.In summary, our work allows the direct monitoring of the misfolded protein oligomers and differentiation of insoluble aggregates from other conformations in live cells, thus enabling studies of many currently unanswered questions in protein aggregation. Future directions are to develop methods that enable quantitative analyses of the protein aggregation process. Further, new methods are needed to detect and to quantify the formation and maturation of protein or RNA condensates that form membraneless organelles.

Machine learning-aided band gap prediction of semiconductors with low concentration doping.

The important physical quantities of materials, such as band gap, have been predicted efficiently with the help of machine learning (ML), in addition to the widely used experimental or computational methods. Under this scheme, by combining density functional theory (DFT) calculations and ML predictive models, the band gaps of doped semiconductors with normal doping concentrations are predicted successfully. Our present work provides a solution to the problem of how to obtain the band gaps of semiconductors doped with extremely low concentrations, which are important cases for some device designs. The structures were constructed by configuration screening with a symmetric criterion, and three-dimensional spatial structural variation was mapped to one-dimensional features, which are the key steps for the ML predictive model. The biggest error in the predicted band gaps of dilute nitride-doped GaAs by ML models is not more than 10%, compared with values obtained from DFT. Considering the limitation of material data, a few-shot learning method was further adopted to check the performance of the predictive models. The performance of the ML models was validated using data out of training and testing datasets. Our method will efficiently accelerate the prediction of physical properties of semiconductors with extremely low-concentration doping.

Amine-functionalized cotton for the treatment of oily wastewater.

Common commercial demulsifiers are typically made from ethylene oxide and propylene oxide. The production process is dangerous and complex, with poor adaptability and high cost. In this work, cotton modified with polyethylene polyamine was utilized as a demulsifier for the treatment of oily wastewater. The chemical structure and morphology of the as-prepared sample (CPN) were characterized by IR spectrum and SEM. The effect of CPN dosage, pH value, and salinity on the demulsification performance of oily wastewater was explored through the bottle tests. The results showed that the light transmittance of separated water was 81.7% and the corresponding deoiling rate was 98.5% when a CPN dosage of 25 mg/L was used at room temperature for 30 min. The interfacial properties were also systematically investigated, and the results indicated that CPN had better interfacial activity and a stronger reduction capability of interfacial tension compared to asphaltenes. The finding initiated and accelerated the demulsification process of oily wastewater. Based on the outstanding performance of this biomass-derived demulsifier, it shows promising potential for application in the treatment of oily wastewater.

A rare case of pemphigus vulgaris disguised as a malignant gingival ulcer.

BACKGROUND: Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. CASE PRESENTATION: A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. CONCLUSIONS: In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

Reversible Handedness Inversion and Circularly Polarized Light Reflection Tuning in Self-Organized Helical Superstructures Using Visible-Light-Driven Macrocyclic Chiral Switches.

A series of macrocyclic azobenzene-based chiral photoswitches have been judiciously designed, synthesized, and characterized. In the molecular structures, binaphthyl is covalently linked to ortho-positions of azobenzene, and four different substituents are linked to 6,6'-positions of binaphthyl. The photoswitches show enhanced helical twisting power (HTP) when doping in commercially available achiral liquid crystals to form self-organized helical superstructures, i.e., cholesteric liquid crystals (CLCs). All the photoswitches exhibit reversible photoisomerization driven by visible light of different wavelengths in both organic solvent and liquid crystals. The photoswitches with shorter substituents enable handedness inversion of CLCs upon photoisomerization. These are the first examples of ortho-linked azobenzene-based photoswitches that enable handedness inversion in CLCs. The photoswitches with longer substituents display only HTP values decreasing while maintaining the same handedness.

A Photo- and Thermo-Driven Azoarene-Based Circularly Polarized Luminescence Molecular Switch in a Liquid Crystal Host.

The development of chiral optical active materials with switchable circularly polarized luminescence (CPL) signals remains a challenge. Here an azoarene-based circularly polarized luminescence molecular switch, (S, R, S)-switch 1 and (R, R, R)-switch 2, are designed and prepared with an (R)-binaphthyl azo group as a chiral photosensitive moiety and two (S)- or (R)-binaphthyl fluorescent molecules with opposite or the same handedness as chiral fluorescent moieties. Both switches exhibit reversible trans/cis isomerization when irradiated by 365 nm UV light and 520 nm green light in solvent and liquid crystal (LC) media. In contrast with the control (R, R, R)-switch 2, when switch 1 is doped into nematic LCs, polarization inversion and switching-off of the CPL signals are achieved in the resultant helical superstructure upon irradiation with 365 nm UV and 520 nm green light, respectively. Meanwhile, the fluorescence intensity of the system is basically unchanged during this switching process. In particular, these variations of the CPL signals could be recovered after heating, realizing the true sense of CPL reversible switching. Taking advantage of the unique CPL switching, the proof-of-concept for "a dual-optical information encryption system" based on the above CPL active material is demonstrated.

A Dual-Responsive Liquid Crystal Elastomer for Multi-Level Encryption and Transient Information Display.

Information security has gained increasing attention in the past decade, leading to the development of advanced materials for anti-counterfeiting, encryption and instantaneous information display. However, it remains challenging to achieve high information security with simple encryption procedures and low-energy stimuli. Herein, a series of strain/temperature-responsive liquid crystal elastomers (LCEs) are developed to achieve dual-modal, multi-level information encryption and real-time, rewritable transient information display. The as-prepared polydomain LCEs can change from an opaque state to a transparent state under strain or temperature stimuli, with the transition strains or temperatures highly dependent on the concentration of long-chain flexible spacers. Information encrypted by different LCE inks can be decrypted under specific strains or temperatures, leading to multi-level protection of information security. Furthermore, with the combination of the phase transition of polydomain LCEs and the photothermal effect of multi-walled carbon nanotubes (MWCNTs), we achieved a repeatable transient information display by using near-infrared (NIR) light as a pen for writing. This study provides new insight into the development of advanced encryption materials with versatility and high security for broad applications.

Comprehensive Genomic Analysis of Marine Strain Streptomyces sp. 891, an Excellent Producer of Chrysomycin A with Therapeutic Potential.

Chrysomycin A is one of the most promising therapeutic candidates for treating infections caused by multidrug-resistant Gram-positive bacteria. By hybridizing next-step generation (Illumina) and third-generation (PacBio) sequencing technologies, a high-quality chromosome-level genome together with a plasmid was firstly assembled for chrysomycin A-producing marine strain 891. Phylogenetic analysis of the 16S rRNA gene and genome sequences revealed that this strain unambiguously belonged to the genus Streptomyces, and its genomic features and functional genes were comprehensively analyzed and annotated. AntiSMASH analysis of this strain unveiled one key biosynthetic gene cluster, T2PKS, responsible for the biosynthesis of chrysomycin, the biosynthesis pathway of which was putatively proposed. These findings definitely shed light on further investigation for construction of a robust industrial strain with high-yield chrysomycin A production using genetic engineering techniques and combinatorial biology approaches.

Rational Design of Crystallization-Induced-Emission Probes To Detect Amorphous Protein Aggregation in Live Cells.

Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation-induced-emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to a nonpolar and viscous environment mimicking the interior of amorphous aggregated proteins. We identified a generally applicable moiety (dimethylaminophenylene) for selective binding and fluorescence enhancement. Regulation of the electron-withdrawing groups tuned the emission wavelength while retaining selective detection. Finally, we utilized the optimized probe to systematically image aggregated proteome upon proteostasis network regulation. Overall, we present a rational approach to develop amorphous protein aggregation sensors from AIEgens with controllable sensitivity, spectral coverage, and cellular performance.

Covalent Probes for Aggregated Protein Imaging via Michael Addition.

Covalent chemical reactions to modify aggregated proteins are rare. Here, we reported covalent Michael addition can generally occur upon protein aggregation. Such reactivity was initially discovered by a bioinspired fluorescent color-switch probe mimicking the photo-conversion mechanism of Kaede fluorescent protein. This probe was dark with folded proteins but turned on red fluorescence (620 nm) when it non-covalently bound to misfolded proteins. Supported by the biochemical and mass spectrometry results, the probe chemoselectively reacted with the reactive cysteines of aggregated proteins via covalent Michael addition and gradually switched to green fluorescence (515 nm) upon protein aggregation. Exploiting this Michael addition chemistry in the malachite green dye derivatives demonstrated its general applicability and chemical tunability, resulting in different fluorescence color-switch responses. Our work may offer a new avenue to explore other chemical reactions upon protein aggregation and design covalent probes for imaging, chemical proteomics, and therapeutic purposes.

Adjusting the chromatographic properties of poly(ionic liquid)-modified stationary phases by substitution on the imidazolium cation.

Poly(ionic liquid)-modified stationary phases can have multiple interactions with solutes. However, in most stationary phases, separation selectivity is adjusted by changing the poly(ionic liquid) anions. In this work, two poly(ionic liquid)-modified silica stationary phases were prepared by introducing the cyano or tetrazolyl group on the pendant imidazolium cation on the polymer chains. Various analytes were selected to investigate their mechanism of retention in the stationary phases using different mobile phases. Two poly(ionic liquid)-modified stationary phases can provide various interactions toward solutes. Compared to the cyano-functionalized poly(ionic liquid) stationary phase, the tetrazolyl-functionalized poly(ionic liquid) stationary phase provides additional cation-exchange and π-π interactions, resulting in different separation selectivity toward analytes. Finally, applicability of the developed stationary phases was demonstrated by the efficient separation of nonsteroidal anti-inflammatory drugs.

Simultaneous photoacoustic imaging of intravascular and tissue oxygenation.

Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.

Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy.

Reconstituted high density lipoprotein (rHDL) is a biomimetic nanoparticle with plaque targeting and anti-atherosclerotic efficacy. In this work, we report on a strategy to rational design of lovastatin (LOV)-loaded spherical rHDL (LOV-s-rHDL) for efficient and safe anti-atherosclerotic therapy. Briefly, three LOV-s-rHDLs were formulated with LOV/s-rHDL at ratios of 8:1, 10:1, and 15:1 upon their respective median-effect values ( Dm). The combined inhibitory effect between LOV and s-rHDL of different LOV-s-rHDL formulations on DiI-labeled oxLDL internalization was systemically investigated in RAW 264.7 cells based on the median-effect principle. Median-effect analysis demonstrated that the optimized LOV-s-rHDL was formulated with a ratio of 10:1 ( Dm LOV: Dm s-rHDL), in which LOV and s-rHDL carrier showed the best synergistic effect, presumably ascribed to their inhibitory effect on CD36 and SR-A expression according to the Western blot analysis. In vivo pharmacodynamics studies showed that the optimized LOV-s-rHDL displayed the most pronounced anti-atherosclerotic effect on decreasing plaque area and reducing the MMP level following an 8-week dosing regimen. In vivo atherosclerotic plaque targeting analysis revealed that s-rHDL had potent plaque targeting efficacy, probably owing to the interaction between apoA-I and scavenger receptor B-I. Furthermore, we observed that the optimized LOV-s-rHDL exhibited a favorable safety profile as evidenced by the results of a hemolysis assay, cell cytotoxicity study, and in vivo safety test. Collectively, the rational design of the biomimetic LOV-s-rHDL based on the median-effect analysis provides an efficient strategy to achieve a synergistic and safe anti-atherosclerotic therapy.

Coastline Detection with Gaofen-3 SAR Images Using an Improved FCM Method.

The coastline detection is one of the main applications of the Gaofen-3 satellite in the ocean field. However, the capability of Gaofen-3 SAR image in coastline detection has not yet been validated. In this paper, two Gaofen-3 SAR images, acquired in 2016, were used to extract the coastlines of the regions of Bohai and Taihu in China, respectively. The classical Fuzzy C-means (FCM) method was used in the coastline detection, but had been improved by combining the Wavelet decomposition algorithm to better suppress the inherent speckle noises of SAR image. Coastline detection results obtained from two Sentinel-1 SAR images acquired on the same regions were compared with those of the Gaofen-3 images. By using the manually delineated coastlines as the standards in the qualitative evaluations, improvements of about 12.0%, 8.3%, 23.8%, and 9.4% can be achieved by the improved FCM method with respect to the indicators of mean, RMSE, PGSD, and P90%, respectively; demonstrating that the Gaofen-3 data is superior to the Sentinel-1 data in the detection of coastline.

A Crop Classification Method Integrating GF-3 PolSAR and Sentinel-2A Optical Data in the Dongting Lake Basin.

With the increasing of satellite sensors, more available multi-source data can be used for large-scale high-precision crop classification. Both polarimetric synthetic aperture radar (PolSAR) and multi-spectral optical data have been widely used for classification. However, it is difficult to combine the covariance matrix of PolSAR data with the spectral bands of optical data. Using Hoekman's method, this study solves the above problems by transforming the covariance matrix to an intensity vector that includes multiple intensity values on different polarization basis. In order to reduce the features redundancy, the principal component analysis (PCA) algorithm is adopted to select some useful polarimetric and optical features. In this study, the PolSAR data acquired by satellite Gaofen-3 (GF-3) on 19 July 2017 and the optical data acquired by Sentinel-2A on 17 July 2017 over the Dongting lake basin are selected for the validation experiment. The results show that the full feature integration method proposed in this study achieves an overall classification accuracy of 85.27%, higher than that of the single dataset method or some other feature integration modes.

Spatiotemporal analysis of national carbon emission and regional carbon simulation in China.

Land use and land cover (LULC) will cause large flows of carbon sources and sinks. As the world's largest carbon emitter with a complicated LULC, China's carbon emissions have profound implications for its ecological environment and future development. In this paper, we account for the land-use changes and carbon emissions of 30 Chinese provinces and cities in China from 2000 to 2020. Furthermore, the spatial correlation of carbon emissions among the study areas is explored. Four typical regions with spatial association (Beijing, Hebei, Sichuan, and Anhui) are selected, and their land-use change trends in 2025 and 2030 are simulated to predict the total carbon emissions in the future. The results show that the distribution of land-use in China is mainly cultivated and woodland, but the growth of urban built-up (UBL) land area indirectly leads to the continuous increase of carbon emissions. Total carbon emissions have increased over the past two decades, albeit at a slower growth rate, with some provinces experiencing no further growth. In the typical regional carbon emission simulation, it is found that the carbon emissions of the four provinces would show a downward trend in the future. The main reason is the reduction in indirect carbon emissions from fossil energy in UBL, while the other part is the influx of carbon sinks due to grassland, woodland, etc. We recommended that future carbon reduction measures should focus and prioritize controlling fossil energy and mitigating carbon emissions from UBL. Simultaneously, the significant contribution of forests and other land types as carbon sinks should be acknowledged to better implement China's carbon neutral commitment.

Photochromic Carbon Nanomaterials: An Emerging Class of Light-Driven Hybrid Functional Materials.

Photochromic molecules have remarkable potential in memory and optical devices, as well as in driving and manipulating molecular motors or actuators and many other systems using light. When photochromic molecules are introduced into carbon nanomaterials (CNMs), the resulting hybrids provide unique advantages and create new functions that can be employed in specific applications and devices. This review highlights the recent developments in diverse photochromic CNMs. Photochromic molecules and CNMs are also introduced. The fundamentals of different photochromic CNMs are discussed, including design principles and the types of interactions between CNMs and photochromic molecules via covalent interactions and non-covalent bonding such as π-π stacking, amphiphilic, electrostatic, and hydrogen bonding. Then the properties of photochromic CNMs, e.g., in photopatterning, fluorescence modulation, actuation, and photoinduced surface-relief gratings, and their applications in energy storage (solar thermal fuels, photothermal batteries, and supercapacitors), nanoelectronics (transistors, molecular junctions, photo-switchable conductance, and photoinduced electron transfer), sensors, and bioimaging are highlighted. Finally, an outlook on the challenges and opportunities in the future of photochromic CNMs is presented. This review discusses a vibrant interdisciplinary research field and is expected to stimulate further developments in nanoscience, advanced nanotechnology, intelligently responsive materials, and devices.