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Abstract Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (T c) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a T c value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high T c and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-T c ferroelectrics with various physical properties.

Abstract With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next‐generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high‐quality thin films of molecular ferroelectrics. To address the above issue, a volume‐confined method is utilized to achieve ultrasmooth single‐crystal molecular ferroelectric thin films at the sub‐centimeter scale, with the thickness controlled in the range of 100–1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two‐dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high‐performance devices based on molecular ferroelectric thin films.

Ferroelectrics are attractive due to their great application potential in information storage, optoelectronics, spintronics and sensing. As an important characteristic affecting semiconducting applications, the energy band structure is important for the development of light-emitting devices. Although it is a tremendous challenge to tune the bandgap in inorganic ferroelectric materials due to the strict requirement of structural symmetry for the fragile ferroelectricity, hybrid organic–inorganic perovskite (HOIP) ferroelectrics, which have a flexible structure, provide a new method to optimize the ferroelectric performance and bandgap. Based on the overview of methods for designing ferroelectrics, this Perspective systematically provides in-depth insight into the relationships between the structure–property and bandgap of HOIP ferroelectrics. In addition, we discussed the challenges and directions of HOIP ferroelectrics in semiconducting applications for the future.

Space-based Earth observation is now developing rapidly because of the advantages in coverage, convenience, and flexibility. However, it is difficult for one single satellite to realize the quick observation of wide areas. In order to catch all the significant information of a wide area in a short time, multi-satellite observation mission would be proposed. In this article, a mission planning method for online multi-satellite wide area observation is established to serve future multi-satellite observation missions. Firstly, a method for area division is proposed, and the whole area is divided into subareas. Then the multi-satellite observation path planning is realized by a strategy of path deduction. After that, a remaining time allocation method to maximize the observation gazing time of each subarea is proposed. Finally, the algorithms for the whole mission planning process are provided. Numerical simulations show that the mission planning method is able to ensure the complete coverage of different wide target areas, with high reliability and low computational complexity.

Abstract Background and purpose Magnetic resonance imaging is indispensable for the preoperative diagnosis of glioma. This study aimed to investigate the role of the apparent diffusion coefficient values as predictors of survival in patients with gliomas. Methods and materials A retrospective analysis was conducted on 101 patients with gliomas who underwent surgery between 2015 and 2020. Diffusion-weighted MRI was performed before the surgery. The regions of interest were categorized into parenchymal area, non-enhancing peritumoral area, and necrotic or cystic area. All the patients were divided into three subgroups: the parenchyma group, the non-enhancing peritumoral signal abnormality group, and the necrosis or cyst group. Univariate and multivariate analyses were performed using COX regression. Results In the parenchymal group, Ki67, P53, IDH, and the high or low ADC values were identified as independent prognosticators for disease-free survival, while Ki67, IDH, and the high or low ADC values for overall survival. In the non-enhancing peritumoral signal abnormality group, Ki67, P53, IDH, and the ADC parenchymal area/ADC non−enhancing peritumoral area ratio were identified as independent prognostic factors for disease-free survival, while Ki67, IDH, and the ADC parenchymal area/ADC non−enhancing peritumoral area ratio for overall survival. In the necrosis or cyst group, Ki67 was significantly associated with disease-free survival, while Ki67 and the ADC value of the necrotic or cystic area for overall survival. Conclusions The ADC values, including the ADC value in the parenchymal area, the ADC parenchymal area/ADC non−enhancing peritumoral area ratio, and the ADC value in the necrotic or cystic area, can serve as an efficient and potential index for predicting the survival of patients with glioma.

Abstract Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody‐based lysosome‐targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer‐based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin‐streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono‐targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono‐/dual‐targets degradation, expanding the possibilities of targeted protein degradation.

Abstract Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.

Abstract The tumour‐targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an “all‐in‐one” red blood cell (RBC)‐derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are “immolated” under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Abstract Background To establish a novel model using radiomics analysis of pre-treatment and post-treatment magnetic resonance (MR) images for prediction of progression-free survival in the patients with stage II–IVA nasopharyngeal carcinoma (NPC) in South China. Methods One hundred and twenty NPC patients who underwent chemoradiotherapy were enrolled (80 in the training cohort and 40 in the validation cohort). Acquiring data and screening features were performed successively. Totally 1133 radiomics features were extracted from the T2-weight images before and after treatment. Least absolute shrinkage and selection operator regression, recursive feature elimination algorithm, random forest, and minimum-redundancy maximum-relevancy (mRMR) method were used for feature selection. Nomogram discrimination and calibration were evaluated. Harrell’s concordance index (C-index) and receiver operating characteristic (ROC) analyses were applied to appraise the prognostic performance of nomograms. Survival curves were plotted using Kaplan–Meier method. Results Integrating independent clinical predictors with pre-treatment and post-treatment radiomics signatures which were calculated in conformity with radiomics features, we established a clinical-and-radiomics nomogram by multivariable Cox regression. Nomogram consisting of 14 pre-treatment and 7 post-treatment selected features has been proved to yield a reliable predictive performance in both training and validation groups. The C-index of clinical-and-radiomics nomogram was 0.953 (all P

Autologous tumor cell vaccines can elicit anti-tumor immune responses. Here, the authors report the design of dendritic polymer-based nanoparticles loaded with doxorubicin and the tyrosine kinase inhibitor apatinib that can induce immunogenic cell death and the in situ production of immuno-stimulatory micrometer-sized vesicles, promoting anti-tumor immune responses in preclinical models.

As a canonical non-climacteric fruit, strawberry (Fragaria spp.) ripening is mainly mediated by abscisic acid (ABA), which involves multiple other phytohormone signalings. Many details of these complex associations are not well understood. We present an coexpression network, involving ABA and other phytohormone signalings, based on weighted gene coexpression network analysis of spatiotemporally resolved transcriptome data and phenotypic changes of strawberry receptacles during development and following various treatments. This coexpression network consists of 18,998 transcripts and includes transcripts related to phytohormone signaling pathways, MADS and NAC family transcription factors and biosynthetic pathways associated with fruit quality. Members of eight phytohormone signaling pathways are predicted to participate in ripening and fruit quality attributes mediated by ABA, of which 43 transcripts were screened to consist of the hub phytohormone signalings. In addition to using several genes reported from previous studies to verify the reliability and accuracy of this network, we explored the role of two hub signalings, small auxin up-regulated RNA 1 and 2 in receptacle ripening mediated by ABA, which are also predicted to contribute to fruit quality. These results and publicly accessible datasets provide a valuable resource to elucidate ripening and quality formation mediated by ABA and involves multiple other phytohormone signalings in strawberry receptacle and serve as a model for other non-climacteric fruits.

Abstract Chemically manipulating bacterial surface structures, a cutting‐edge research direction in the biomedical field, predominantly relies on metabolic labeling by now. However, this method may involve daunting precursor synthesis and only labels nascent surface structures. Here, we report a facile and rapid modification strategy based on a tyrosinase‐catalyzed oxidative coupling reaction (TyOCR) for bacterial surface engineering. This strategy employs phenol‐tagged small molecules and tyrosinase to initiate direct chemical modification of Gram‐positive bacterial cell walls with high labeling efficiency, while Gram‐negative bacteria are inert to this modification due to the hindrance of an outer membrane. By using the biotin‒avidin system, we further present the selective deposition of various materials, including photosensitizer, magnetic nanoparticle, and horseradish peroxidase, on Gram‐positive bacterial surfaces, and realize the purification/isolation/enrichment and naked‐eye detection of bacterial strains. This work demonstrates that TyOCR is a promising strategy for engineering live bacterial cells.

In drug development research, the specific affinity of drug delivery systems for particular pathological sites, cells, and even subcellular structures can largely reduce the side effects, systemic toxicity, and minimally required drug dose. Since endoplasmic reticulum (ER) plays an essential role in many important cellular activities and functions, including the synthesis and intracellular transport of secretory and membrane-associated proteins, the synthesis and transport of steroids and lipids, Ca2+ signaling, and stress response, the ER dysfunction is associated with many diseases. Developing delivery systems that can effectively enter the cell and target ER is highly important for achieving satisfactory therapeutic performance in certain diseases, such as cancer. This review summarizes the currently available ER-targeting nanoparticle systems for cancer therapy. We first discuss the background knowledge involved in the ER-targeted nanotherapies for cancer. Then, we describe the examples about ER-targetable nanoparticles from several aspects, such as the components, the construction, and the therapeutic effect and mechanisms of these nanoparticles. Finally, we summarize the ER-targeted nanotherapeutic strategies for cancer and point out the current challenges and future research directions in this field. We hope that this review will promote the further development of ER-targeting nanotheranostics and inspire future research on ER-targeted cancer treatments.

Nanomaterials with bone-mimicking characteristics and easily internalized by the cell could create suitable microenvironments in which to regulate the therapeutic effects of bone regeneration. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone injury repair. First, an overview of the hierarchical architecture from the macroscale to the nanoscale of natural bone is presented, as these bone tissue microstructures and compositions are the basis for constructing bone substitutes. Next, urgent clinical issues associated with bone injury that require resolution and the potential of nanomaterials to overcome them are discussed. Finally, nanomaterials are classified as inorganic or organic based on their chemical properties. Their basic characteristics and the results of related bone engineering studies are described. This review describes theoretical and technical bases for the development of innovative methods for repairing damaged bone and should inspire therapeutic strategies with potential for clinical applications.

Additive manufacturing of Zr-based bulk metallic glasses (BMGs) is subject to growing scientific and industrial attention. Laser-based powder bed fusion of metals (PBF-LB/M) becomes a key technology to overcome current restrictions of size and geometry in the manufacturing of BMGs. For industrial application, further knowledge about defect formation, such as porosity and crystallization, is mandatory to develop processing strategies and suitable quality assurance. In this context, the influence of the particle size distribution, oxygen contamination, and applied process parameters during the PBF-LB/M of the glass-forming alloy AMZ4 (in at.% Zr59.3Cu28.8Al10.4Nb1.5) on the structural and mechanical properties were evaluated. It was found that the addition of SiO2 flow aid to the feedstock is suitable to increase flowability without impeding fabrication of the amorphous material. Furthermore, the processing of partially crystalline powder particles into amorphous samples is demonstrated. It indicates that today’s high effort producing amorphous powders and thus the production costs can be reduced. Flexural bending tests and high-energy synchrotron X-ray diffraction reveal that the powder feedstock’s oxygen content is crucial for the amorphization, embrittlement, and flexural strength of PBF-LB/M processed Zr-based BMGs.

BackgroundHigh mobility group box 1 (HMGB1) causes microvascular endothelial cell barrier dysfunction during acute lung injury (ALI) in sepsis, but the mechanisms have not been well understood. We studied the roles of RAGE and Rho kinase 1 (ROCK1) in HMGB1-induced human pulmonary endothelial barrier disruption.MethodsIn the present study, the recombinant human high mobility group box 1 (rhHMGB1) was used to stimulate human pulmonary microvascular endothelial cells (HPMECs). The endothelial cell (EC) barrier permeability was examined by detecting FITC-dextran flux. CCK-8 assay was used to detect cell viability under rhHMGB1 treatments. The expression of related molecules involved in RhoA/ROCK1 pathway, phosphorylation of myosin light chain (MLC), F-actin, VE-cadherin and ZO-1 of different treated groups were measured by pull-down assay, western blot and immunofluorescence. Furthermore, we studied the effects of Rho kinase inhibitor (Y-27632), ROCK1/2 siRNA, RAGE-specific blocker (FPS-ZM1) and RAGE siRNA on endothelial barrier properties to elucidate the related mechanisms.ResultsIn the present study, we demonstrated that rhHMGB1 induced EC barrier hyperpermeability in a dose-dependent and time-dependent manner by measuring FITC-dextran flux, a reflection of the loss of EC barrier integrity. Moreover, rhHMGB1 induced a dose-dependent and time-dependent increases in paracellular gap formation accompanied by the development of stress fiber rearrangement and disruption of VE-cadherin and ZO-1, a phenotypic change related to increased endothelial contractility and endothelial barrier permeability. Using inhibitors and siRNAs directed against RAGE and ROCK1/2, we systematically determined that RAGE mediated the rhHMGB1-induced stress fiber reorganization via RhoA/ROCK1 signaling activation and the subsequent MLC phosphorylation in ECs.ConclusionHMGB1 is capable of disrupting the endothelial barrier integrity. This study demonstrates that HMGB1 activates RhoA/ROCK1 pathway via RAGE, which phosphorylates MLC inducing stress fiber formation at short time, and HMGB1/RAGE reduces AJ/TJ expression at long term independently of RhoA/ROCK1 signaling pathway.

Additive manufacturing of bulk metallic glasses (BMGs) through laser powder bed fusion (LPBF) has drawn growing interest in the last years, especially concerning industry-relevant alloys based on iron or zirconium. The process-inherent high cooling rates and localized melting pools allow to overcome geometrical restrictions given for the production of BMGs by classical casting routes. Yet, the achievable surface qualities are still limited, making an adequate post-processing necessary. In this work, we report on applying thermoplastic forming on LPBF-formed parts for the first time to decrease surface roughness and imprint finely structured surface patterns without the need for complex abrasive machining. This BMG-specific post-processing approach allows to functionalize surface areas on highly complex LPBF-formed specimens, which could be of interest especially for medical or jewelry applications.

Three polyhydroxyl-bridged tetranuclear MnIII complexes [Mn4(L1a)2(μ3-OMe)2(μ2-OMe)2(MeOH)2] (1), [Mn4(L2a)2(μ3-OMe)2(μ2-OMe)2(H2O)2] (2), and [Mn4(L3a)2(μ3-OMe)2(μ2-OMe)2(H2O)2] (3) derived from Mnn+-promoted reactivity of Schiff base ligands (HL1 = 1-(4-{[(E)-3,5-dichlorine-2-hydroxybenzylidene]amino}phenyl)ethanone O-benzyloxime, HL2 = 1-(4-{[(E)-3-bromine-5-chloro-2-hydroxybenzylidene]amino}phenyl) ethanone O-benzyloxime, and HL3 = 1-(4-{[(E)-3,5-dibromine-2-hydroxybenzylidene]amino}phenyl)ethanone O-benzyloxime) have been synthesized and characterized. In the MnIII complexes 1, 2, and 3, the newly formed ligands (L1a)4−, (L2a)4−, and (L3a)4− are derived from the chemoselective cleavage of the C=N bond in the original Schiff base ligands HL1, HL2, and HL3 to form corresponding halogenated salicylaldehyde, 3,5-dichlorosalicylaldehyde, 3-bromine-5-chlorosalicylaldehyde, and 3,5-dibrominesalicylaldehyde, respectively. Then, the further addition of acetone to two halogenated salicylaldehyde molecules in situ α,α double aldol reaction promoted by Mnn+ ions in the presence of base to give the new ligands ((Lna)4−. X-ray crystallographic analyses of the MnIII complexes 1, 2, and 3 show that the three complexes are all tetranuclear structure and crystallizes in the triclinic system, space group P-1. The four MnIII ions and bridging alkoxido groups are arranged in a face-shared dicubane-like core with two missing vertices. In the three MnIII complexes, the asymmetric unit contains two kinds of different MnIII ions (Mn1 and Mn2), where the MnIII ions are all hexacoordinated with slightly distorted octahedral geometries. Simultaneously in the synthesis of multinuclear Mnn+ complexes above, we explored the crystal structure, spatial configuration, and spectroscopic properties of the multinuclear MnIII complexes with different halogen substituents.

Two new Co(II) complexes, [{Co(L)}2{Co(Pic)2(CH3OH)2}] (1) and [{CoL(μ-OAc)}2Co] (2), where H2L = 2,2′-[Ethylenedioxybis(nitrilomethylidyne)]dinaphthol, were designed, synthesized and characterized by elemental analysis, FT-IR spectra, UV-Vis spectra, and X-ray crystallography. Complex 1 consists of two [CoL] and one [Co(Pic)2(CH3OH)2] (Pic = picrate) units and in the [CoL] unit, the Co(II) atom is tetra-coordinated with a slightly distorted square-planar geometry. In the [Co(Pic)2(CH3OH)2] unit, the Co(II) atom is hexa-coordinated with a slightly distorted octahedral geometry. Meanwhile in complex 2, two acetate ions coordinate to three Co(II) atoms through Co-O-C-O-Co bridges and four μ-naphthoxo oxygen atoms from two [CoL] units also coordinated to the central Co(II) atom. Thus, complex 2 has two distorted square pyramidal coordination geometries around the terminal Co(II) atom and an octahedral geometry around the central Co(II) atom. The supramolecular structures of complex 1 is a 3D-network supramolecular structure linked by C-H···O hydrogen bonds and π···π stacking interaction, but complex 2 possesses a self-assembled 2D-layer supramolecular structure linked by C-H···π and π···π stacking interactions. The structure determinations show that the coordination anions are important factors influencing the crystalline array.