Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Hypoxia promotes the growth and metastasis of ovarian cancer cells by suppressing ferroptosis via upregulating SLC2A12.

BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo. RESULTS: Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo. CONCLUSION: Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.

Characterization and Function Analysis of Soluble Dietary Fiber Obtained from Radish Pomace by Different Extraction Methods.

Soluble dietary fiber (SDF) benefits human health, and different extraction methods might modify the structure and functions of the SDFs. Radish is rich in dietary fiber. To assess the impact of various extraction techniques on the properties and functions of radish SDF, the SDFs were obtained from white radish pomace using alkaline, ultrasonic-assisted, and fermentation-assisted extraction methods. Analysis was conducted on the structure, physicochemical characteristics, thermal properties, and functional attributes of the SDFs. The study revealed that various extraction techniques can impact the monosaccharides composition and functionality of the SDFs. Compared with the other two extraction methods, the surface structures of SDFs obtained by fermentation-assisted extraction were looser and more porous, and the SDF had better water solubility and water/oil holding capacity. The adsorption capacities of glucose and cholesterol of the SDFs obtained from fermentation-assisted extraction were also improved. Wickerhamomyces anomalus YFJ252 seems the most appropriate strain to ferment white radish pomace to acquire SDF; the water holding, oil holding, glucose absorption capacity, and cholesterol absorption capacity at pH 2 and pH 7 have a 3.06, 1.65, 3.19, 1.27, and 1.83 fold increase than the SDF extracted through alkaline extraction method.

Unraveling Dynamic Helicity Inversion and Chirality Transfer through the Synthesis of Discrete Azobenzene Oligomers by an Iterative Exponential Growth Strategy.

Unraveling the chirality transfer mechanism of polymer assemblies and controlling their handedness is beneficial for exploring the origin of hierarchical chirality and developing smart materials with desired chiroptical activities. However, polydisperse polymers often lead to an ambiguous or statistical evaluation of the structure-property relationship, and it remains unclear how the iterative number of repeating units function in the helicity inversion of polymer assemblies. Herein, we report the macroscopic helicity and dynamic manipulation of the chiroptical activity of supramolecular assemblies from discrete azobenzene-containing oligomers (azooligomers), together with the helicity inversion and morphological transition achieved solely by changing the iterative chain lengths. The corresponding assemblies also differ from their polydisperse counterparts in terms of thermodynamic properties, chiroptical activities, and morphological control.

Precise Modulation of Circularly Polarized Luminescence via Polymer Chiral Co-assembly and Contactless Dynamic Chiral Communication.

Circularly polarized luminescence (CPL) plays a pivotal role in cutting-edge display and information technologies. Currently achieving precise color control and dynamic signal regulation in CPL still remains challenging due to the elusory relationship between fluorescence and chirality. Inspired by the natural mechanisms governing color formation and chiral interaction, we proposed an addition-subtraction principle theory to address this issue. Three fluorene-based polymers synthesized by Suzuki polycondensation with different electron-deficient monomers exhibit similar structures and UV/Vis absorption, but distinct fluorescence emissions due to intramolecular charge transfer. Based on this, precise-color CPL-active films are obtained through quantitative supramolecular co-assembly directed by addition principle. Particularly, an ideal white-emitting CPL film (CIE coordinates: (0.33, 0.33)) is facilely fabricated with a high quantum yield of 80.8 % and a dissymmetry factor (glum) of 1.4×10-2. Structural analysis reveals that the ordered stacking orientation favors higher glum. Furthermore, to address the dynamically regulated challenge, the comparable subtraction principle is proposed, involving a contactless chiral communication between excited and ground states. The representative system consisting of as-prepared fluorene-based polymers and chirality-selective absorption azobenzene (Azo)-containing polymers is constructed, achieving CPL weakening, reversal, and enhancement. Finally, a switchable quick response code is realized based on trans-cis isomerization of Azo moiety.

Switchable Phase Helicity Independent of the Absolute Configuration of the Stereocenter: Anomalous Induction between Sergeants and Soldiers in Chiral Liquid-Crystalline Polymers.

Controlling the secondary phase in chiral liquid-crystalline (LC) polymers is of great importance since it transfers and amplifies molecular information to the macroscopic properties. However, the chiral superstructures of the LC phase are determined exclusively by the inherent configuration of the parent chiral source. Here, we report the switchable supramolecular chirality of heteronuclear structures by the untraditional command between common chiral "sergeant" units and various achiral "soldier" units. Different chiral induction pathways between sergeants and soldiers were observed for copolymer assemblies with mesogenic and non-mesogenic soldier units, demonstrating the formation of a helical phase independent of the absolute configuration of the stereocenter. In the presence of non-mesogenic soldier units, the classical SaS (Sergeants and Soldiers) effect in the amorphous phase was observed; whereas in a full LC system, bidirectional command of sergeants was activated in response to the phase transition. Meanwhile, a full spectrum of morphological phase diagrams including spherical micelles, worms, nanowires, spindles, tadpoles, anisotropic ellipsoidal vesicles, and isotropic spherical vesicles were successfully achieved. Such spindles, tadpoles, and anisotropic ellipsoidal vesicles have rarely been obtained previously from chiral polymer systems.

Physically interacting humans regulate muscle coactivation to improve visuo-haptic perception.

When moving a piano or dancing tango with a partner, how should I control my arm muscles to sense their movements and follow or guide them smoothly? Here we observe how physically connected pairs tracking a moving target with the arm modify muscle coactivation with their visual acuity and the partner's performance. They coactivate muscles to stiffen the arm when the partner's performance is worse and relax with blurry visual feedback. Computational modeling shows that this adaptive sensing property cannot be explained by the minimization of movement error hypothesis that has previously explained adaptation in dynamic environments. Instead, individuals skillfully control the stiffness to guide the arm toward the planned motion while minimizing effort and extracting useful information from the partner's movement. The central nervous system regulates muscle activation to guide motion with accurate task information from vision and haptics while minimizing the metabolic cost. As a consequence, the partner with the most accurate target information leads the movement.NEW & NOTEWORTHY Our results reveal that interacting humans inconspicuously modulate muscle activation to extract accurate information about the common target while considering their own and the partner's sensorimotor noise. A novel computational model was developed to decipher the underlying mechanism: muscle coactivation is adapted to combine haptic information from the interaction with the partner and own visual information in a stochastically optimal manner. This improves the prediction of the target position with minimal metabolic cost in each partner, resulting in the lead of the partner with the most accurate visual information.

Simultaneous Chiral Fixation and Chiral Regulation Endowed by Dynamic Covalent Bonds.

The construction of chiral superstructures through the self-assembly of non-chiral polymers usually relies on the interplay of multiple non-covalent bonds, which is significantly limited by the memory ability of induced chirality. Although the introduction of covalent crosslinking can undoubtedly enhance the stability of chiral superstructures, the concurrent strong constraining effect hinders the application of chirality-smart materials. To address this issue, we have made a first attempt at the reversible fixation of supramolecular chirality by introducing dynamic covalent crosslinking into the chiral self-assembly of side-chain polymers. After chiral induction, the reversible [2+2] cycloaddition reaction of the cinnamate group in the polymer chains can be further controlled by light to manipulate inter-chain crosslinking and decrosslinking. Based on this photo-programmable and dynamic chiral fixation strategy, a novel pattern-embedded storage mechanism of chiral polymeric materials was established for the first time.

A Subtle Change in the Flexible Achiral Spacer Does Matter in Supramolecular Chirality: Two-Fold Odd-Even Effect in Polymer Assemblies.

Precise control over the chirality and morphologies of polymer assemblies, a remaining challenge for both chemists and materials scientists, is receiving ever-increasing attention in the recent years. Herein, we report the subtle manipulation of the achiral spacers from the chiral stereocenter to the azobenzene (Azo) unit, of which the chiroptical consistency or chiroptical inversion of self-assemblies could be successfully controlled and present "two-fold" odd-even effect. Furthermore, morphological transitions from 0D spherical micelles, 1D worms, and nanowires to 3D vesicles, spindle- and dumbbell-shaped vesicles were also unexpectedly found to exhibit odd-even correlations. These observations were collectively elucidated by mesomorphic properties, stacking modes, chiroptical dynamics, and stimuli-responsive behaviors. Negligible modifications to the spacer structures can enable remarkable modulation of supramolecular chirality and anisotropic topologies in polymer assemblies, which is of great significance for the design of complex chiral functional polymers.

NeRD: a multichannel neural network to predict cellular response of drugs by integrating multidimensional data.

BACKGROUND: Considering the heterogeneity of tumors, it is a key issue in precision medicine to predict the drug response of each individual. The accumulation of various types of drug informatics and multi-omics data facilitates the development of efficient models for drug response prediction. However, the selection of high-quality data sources and the design of suitable methods remain a challenge. METHODS: In this paper, we design NeRD, a multidimensional data integration model based on the PRISM drug response database, to predict the cellular response of drugs. Four feature extractors, including drug structure extractor (DSE), molecular fingerprint extractor (MFE), miRNA expression extractor (mEE), and copy number extractor (CNE), are designed for different types and dimensions of data. A fully connected network is used to fuse all features and make predictions. RESULTS: Experimental results demonstrate the effective integration of the global and local structural features of drugs, as well as the features of cell lines from different omics data. For all metrics tested on the PRISM database, NeRD surpassed previous approaches. We also verified that NeRD has strong reliability in the prediction results of new samples. Moreover, unlike other algorithms, when the amount of training data was reduced, NeRD maintained stable performance. CONCLUSIONS: NeRD's feature fusion provides a new idea for drug response prediction, which is of great significance for precise cancer treatment.

Activation of cGAS-STING pathway - A possible cause of myofiber atrophy/necrosis in dermatomyositis and immune-mediated necrotizing myopathy.

OBJECTIVE: The objective was to investigate the expression of the cGAS-STING pathway-associated protein in idiopathic inflammatory myopathy (IIM) and to investigate whether it is related to myofiber atrophy/necrosis in patients with dermatomyositis and immune-mediated necrotizing myopathy. MATERIAL AND METHODS: Muscle specimens obtained by open biopsy from 26 IIM patients (14 with dermatomyositis (DM), 8 with immune-mediated necrotizing myopathy (IMNM), and 4 with other types of IIM), 4 dystrophinopathy, and 9 control patients were assessed for expression of cGAS-STING pathway members via Western blot, quantitative real-time PCR analysis (qRT-PCR), and immunochemistry. Meanwhile, analysis its location distribution througn immunochemistry. RESULTS: Compared to the control group, the expression of cGAS, STING, and related molecules was obviously increased in muscle samples of IIM patients. Upregulated cGAS and STING were mainly located in the vascular structure, inflammatory infiltrates, and atrophic and necrotic fibers. While comparing to the Dys patients, the mRNA level of cGAS, STING, and TNF-a was upregulated, meanwhile, the protein of the TBK1, P-TBK1, and P-IRF3 associated with interferon upregulation was overexpressed through Western blot in IMNM and DM. Considering that cGAS and STING are located in necrotic and Mx1-positive atrophic fibers, it is really possible that the cGAS-STING pathway may lead to fibers atrophy/necrosis by producing IFNs. CONCLUSION: The cGAS-STING pathway was activated in the muscle samples of IIM patients and its activation may be the reason of myofiber atrophy and necrosis in DM and IMNM patients.

Polymerization-Induced Helicity Inversion Driven by Stacking Modes and Self-Assembly Pathway Differentiation.

Regulating the mutual stacking arrangements is of great interest for understanding the origin of chirality at different hierarchical levels in nature. Different from molecular level chirality, the control and manipulation of hierarchical chirality in polymer systems is limited to the use of external factors as the energetically demanding switching stimulus. Herein, the first self-assembly strategy of polymerization-induced helicity inversion (PIHI), in which the controlled packing and dynamic stereomutation of azobenzene (Azo) building blocks are realized by in situ polymerization without any external stimulus, is reported. A multiple helicity inversion and intriguing helix-helix transition of polymeric supramolecular nanofibers occurs during polymerization, which is collectively confirmed to be mediated by the transition between functionality-oriented π-π stacking, H-, and J-aggregation. The studies further reveal that helicity inversion proceeds through a delicate interplay of the thermodynamically and kinetically controlled, pathway-dependent interconversion process, which should provide new insight into the origin and handedness control of helical nanostructures with desired chirality.

Engineering Achiral Liquid Crystalline Polymers for Chiral Self-Recovery.

Flexible construction of permanently stored supramolecular chirality with stimulus-responsiveness remains a big challenge. Herein, we describe an efficient method to realize the transfer and storage of chirality in intrinsically achiral films of a side-chain polymeric liquid crystal system by combining chiral doping and cross-linking strategy. Even the helical structure was destroyed by UV light irradiation, the memorized chiral information in the covalent network enabled complete self-recovery of the original chiral superstructure. These results allowed the building of a novel chiroptical switch without any additional chiral source in multiple types of liquid crystal polymers, which may be one of the competitive candidates for use in stimulus-responsive chiro-optical devices.

Metagenomic profiling of antibiotic resistance and virulence removal: Activated sludge vs. algal wastewater treatment system.

Conventional activated sludge-based (CAS) wastewater treatment plants are known to be a source of antibiotic resistance genes (ARGs) and virulence genes (VGs). As an alternative, a single-step mixotrophic algal wastewater treatment (A-WWT) system is proposed here to effectively reduce ARGs and VGs in the final effluent while meeting all the discharge standards. In this study, we applied the metagenomic profiling approach to compare the A-WWT system against the CAS system in terms of removal efficacy of ARG and VGs. A total of 111 ARG and 93 VG subtypes belonging to 10 antibiotic resistant classes and 19 virulence classes were detected in this study. Although the CAS system reduced the relative abundance of most classes of ARGs (7 of 10) and VGs (11 of 19), 3 ARG classes and 7 VG classes had increased abundances. On the other hand, the A-WWT system reduced the relative abundance of all classes of ARGs and VGs, and effectively eliminated most subtypes of ARGs and VGs. In the CAS system, the bacterial genera carrying ARGs and VGs was expanded, and the diversity index was increased greatly, suggesting the occurrence of horizontal gene transfer (HGT). In contrast, the A-WWT system narrowed down the potential host range and decreased their diversity substantially. Results of this study highlight the potential risk of ARGs and VGs in CAS system and demonstrate the feasibility of the algal-based system in removing ARGs and VGs.

Controlling the Multiple Chiroptical Inversion in Biphasic Liquid-Crystalline Polymers.

While controlling the chirality and modulating the helicity is a challenging task, it attracts great research interest for gaining a better understanding of the origin of chirality in nature. Herein, structurally similar azobenzene (Azo) vinyl monomers were designed in which the alkyl chains comprised the chiral stereocenter with different achiral tail lengths. Combining the synchronous polymerization, supramolecular stacking and self-assembly, the multiple chiroptical inversion of the Azo-polymer supramolecular assemblies can be modulated by the tail length and DP of Azo blocks during in situ polymerization. The DP-, UV light-, temperature-, aging time-dependent chiroptical properties and liquid-crystalline (LC) characterization indicated that the amorphous-to-LC phase transition and biphasic LC interconversion allow the transcription of intra-chain π-π stacking, inter-chain H- and J-aggregation, thereby controlling the dynamic multiple reversal of supramolecular chirality.

Transfer, Amplification, Storage, and Complete Self-Recovery of Supramolecular Chirality in an Achiral Polymer System.

Supramolecular chirality and its complete self-recovery ability are highly mystical in nature and biological systems, which remains a major challenge today. Herein, we demonstrate that partially cross-linked azobenzene (Azo) units can be employed as the potential chiral trigger to fully heal the destroyed helical superstructure in achiral nematic polymer system. Combining the self-assembly of Azo units and terminal hydroxyl groups in polymer side chains allows the vapor-induced chiral nematic phase and covalent fixation of the superstructure via acetal reaction. The induced helical structure of Azo units can be stored by inter-chain cross-linking, even after removal of the chiral source. Most interestingly, the stored chiral information can trigger perfect chiral self-recovery (CSR) behavior after being destroyed by UV light, heat, and solvents. The results pave a new way for producing novel chiroptical materials with reversible chirality from achiral sources.

Supramolecular Chirality in Azobenzene-Containing Polymer System: Traditional Postpolymerization Self-Assembly Versus In Situ Supramolecular Self-Assembly Strategy.

Recently, the design of novel supramolecular chiral materials has received a great deal of attention due to rapid developments in the fields of supramolecular chemistry and molecular self-assembly. Supramolecular chirality has been widely introduced to polymers containing photoresponsive azobenzene groups. On the one hand, supramolecular chiral structures of azobenzene-containing polymers (Azo-polymers) can be produced by nonsymmetric arrangement of Azo units through noncovalent interactions. On the other hand, the reversibility of the photoisomerization also allows for the control of the supramolecular organization of the Azo moieties within polymer structures. The construction of supramolecular chirality in Azo-polymeric self-assembled system is highly important for further developments in this field from both academic and practical points of view. The postpolymerization self-assembly strategy is one of the traditional strategies for mainly constructing supramolecular chirality in Azo-polymers. The in situ supramolecular self-assembly mediated by polymerization-induced self-assembly (PISA) is a facile one-pot approach for the construction of well-defined supramolecular chirality during polymerization process. In this review, we focus on a discussion of supramolecular chirality of Azo-polymer systems constructed by traditional postpolymerization self-assembly and PISA-mediated in situ supramolecular self-assembly. Furthermore, we will also summarize the basic concepts, seminal studies, recent trends, and perspectives in the constructions and applications of supramolecular chirality based on Azo-polymers with the hope to advance the development of supramolecular chirality in chemistry.

In Situ Controlled Construction of a Hierarchical Supramolecular Chiral Liquid-Crystalline Polymer Assembly.

Hierarchical supramolecular chiral liquid-crystalline (LC) polymer assemblies are challenging to construct in situ in a controlled manner. Now, polymerization-induced chiral self-assembly (PICSA) is reported. Hierarchical supramolecular chiral azobenzene-containing block copolymer (Azo-BCP) assemblies were constructed with π-π stacking interactions occurring in the layered structure of Azo smectic phases. The evolution of chirality from terminal alkyl chain to Azo mesogen building blocks and further induction of supramolecular chirality in LC BCP assemblies during PICSA is achieved. Morphologies such as spheres, worms, helical fibers, lamellae, and vesicles were observed. The morphological transition had a crucial effect on the chiral expression of Azo-BCP assemblies. The supramolecular chirality of Azo-BCP assemblies destroyed by 365 nm UV irradiation can be recovered by heating-cooling treatment; this dynamic reversible achiral-chiral switching can be repeated at least five times.

Topological Glycopolymers as Agglutinator and Inhibitor: Cyclic versus Linear.

Carbohydrates play an important role in biological processes for their specific interactions with proteins. Cyclic glycopolymers are promising to mimic the topology of natural macrocycle-biomacromolecules due to their unique architecture of lacking chain ends. To systematically study the effect of glycopolymer architecture on the interactions with protein, the cyclic glycopolymers bearing galactose side-chain (cyclic PMAGn ) with three degrees of polymerization (n = 14, 24, 47) are prepared for the first time. The cyclic PMAGn exhibits unique properties in agglutinating and inhibiting proteins in subsequent studies by comparison with the linear precursor with the same molecular weights. More impressively, the cyclic PMAGn highlight the improved performance of cyclic architecture. For example, the cyclic PMAGn shows superior inhibition abilities to suppress amyloid formation from amyloid ß protein fragment 1-42 aggregation and block the specific interaction between bacteria and galactose-modified surface compared to that of respective linear counterpart. This interesting finding suggests that the architecture of cyclic glycopolymers may be capable of optimizing the ability to bind or inhibit proteins in biological processes.

Analysis and Adjustment of Positioning Error of PSD System for Mobile SOF-FTIR.

A PSD-based solar spot position detection system is developed for solar tracking closed-loop control of mobile SOF-FTIR (Solar Occultation Flux method based on Fourier Transform Infrared spectrometer). The positioning error factors of PSD (position sensitive detector) are analyzed in detail. A voltage model for PSD signal conditioning circuit has been established to investigate the noise factors. The model shows that the positioning error is mainly related to PSD dark current and circuit gain. A static voltage deduction calibration method based on genetic algorithm is proposed to eliminate the effect of dark current. The gain ratio between channels is calculated based on the fitting curve slope of discrete position data of PSD center point with different light intensity for circuit gain calibration. The positioning accuracy and precision are greatly enhanced, especially when the light intensity is weak, compared with uncalibrated results. The positioning accuracy of center, middle and edge areas of PSD can reach 0.14%, 0.49%, and 1.09%, respectively, after correction in the range of light intensity voltage from 40 mV to 20 V. The corresponding standard deviations of each region are 0.005, 0.009, and 0.014, respectively. The adjustment methods proposed in this paper improve both measurement accuracy and detection limit. The results demonstrate that the calibrated PSD positioning accuracy can meet the requirements of SOF-FTIR for solar tracking.