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Moon Jung Choi,1 Kang Chan Choi,1 Do Hyun Lee,1 Hwa Yeon Jeong,1 Seong Jae Kang,1 Min Woo Kim,1 In Ho Jeong,1 Young Myoung You,1 Jin Suk Lee,2 Yeon Kyung Lee,1 Chan Su Im,1 Yong Serk Park1 1Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea; 2Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaCorrespondence: Chan Su Im; Yong Serk Park, Department of Biomedical Laboratory Science, Yonsei University, Wonju, Gangwon, 220-710, Republic of Korea, Email chanzzhu@nate.com; parkys@yonsei.ac.krIntroduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.Graphical Abstract: Keywords: cell-derived nanoparticles, immune surveillance, CD47, doxorubicin, tumor targeting, cancer therapy

Molecular ferroelectrics have increasingly garnered significant attention in both fundamental scientific research and technological applications due to their ease of processing, lightweight nature, and mechanical flexibility. Among these, metal halide perovskite ferroelectrics (MHP FEs), a subset of molecule-based ferroelectrics, exhibit diverse functionalities owing to their distinctive structures, thus emerging as a focal point of molecular ferroelectrics research. However, thin films, the predominant application form for MHP FEs, primarily rely on spin-coating, which presents considerable limitations. The development of melt-processable MHP FEs has been sparse, largely due to the challenge of integrating ferroelectricity with meltability. In this context, we propose a rational strategy for the successful synthesis of a melt-processable MHP FE, (MBPA) 2 PbBr 4 (MBPA = N -methyl bromopropylammonium), featuring a notably low congruent melting temperature and excellent molten stability. The reversibility of solid and liquid states was demonstrated by X-ray diffraction and Raman and IR spectrum. Scanning electron microscopy examinations show a better quality of the melt-processed thin films compared to spin-coated ones. This study marks the successful implementation of integrating ferroelectricity and melt-processability into melt-processable MHP FEs, paving the way for a novel approach in processing MHP FEs and facilitating their future applications.

Increased levels of lactoferrin (Lf) are present in the aged brain and in the lesions of various neurodegenerative diseases, including Parkinson's disease (PD), and may contribute to the cascade of events involved in neurodevelopment and neuroprotection. However, whether Lf originates from astrocytes and functions within either the normal or pathological brain are unknown. Here, we employed mice with specific knockout of the astrocyte lactoferrin gene (named Lf-cKO) to explore its specific roles in the pathological process of PD. We observed a decrease in tyrosine hydroxylase-positive cells, mitochondrial dysfunction of residual dopaminergic neurons, and motor deficits in Lf-cKO mice, which were significantly aggravated after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. To further explore how astrocytic lactoferrin deficiency exacerbated PD-like manifestation in MPTP-treated mice, the critical molecules involved in endoplasmic reticulum (ER)-mitochondria contacts and signaling pathways were investigated. In vitro and in vivo models, we found an aberrant level of effects implicated in glutamate and calcium homeostasis, mitochondrial morphology and functions, mitochondrial dynamics, and mitochondria-associated ER membranes, accompanied by signs of oxidative stress and ER stress, which increase the fragility of dopaminergic neurons. These findings confirm the existence of astrocytic Lf and its influence on the fate of dopaminergic neurons by regulating glutamate/calcium metabolism and ER-mitochondria signaling. Our findings may be a promising target for the treatment of PD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The turnover and stabilization of soil organic carbon are tightly associated with the properties of litter input. Due to the complexity of litter decomposition and the high heterogeneity of forest soils, there are considerable uncertainties about how soil minerals, microorganisms, and environmental factors jointly regulate the transformation and stability of litter-derived soil organic carbon. Here, we present an overview of the "microbial efficiency-matrix stabilization" framework centered on microbial metabolism and organic carbon transformation, as well as the new "microbial carbon pump" and "mineral carbon pump" theories in forest soil organic carbon transformation and stabilization. We specifically highlighted a differential mechanism of "organo-organic interfaces" from the "organo-mineral interfaces" in the effects on soil organic carbon accumulation. We further expounded the transformation processes and stability of soil organic carbon based on the "carbon material cycling" and "energy fluxes", aiming to provide theoretical support for the research on carbon sequestration in forest soils.

Ferroelectrics as emerging and attractive catalysts have shown tremendous potential for applications including wastewater treatment, hydrogen production, nitrogen fixation, and organic synthesis, etc. In this study, we demonstrate that molecular ferroelectric crystal TMCM-CdCl 3 (TMCM = trimethylchloromethylammonium) with multiaxial ferroelectricity and superior piezoelectricity has an effective catalytic activity on the direct construction of the pharmacologically important substituted quinoline derivatives via one-pot [3 + 2 + 1] annulation of anilines and terminal alkynes by using N,N-dimethylformamide (DMF) as the carbon source. The recrystallized TMCM-CdCl 3 crystals from DMF remain well ferroelectricity and piezoelectricity. Upon ultrasonic condition, periodic changes in polarization contribute to the release of free charges from the surface of the ferroelectric domains in nano size, which then quickly interacts with the substrates in the solution to trigger the pivotal redox process. Our work advances the molecular ferroelectric crystal as a catalytic route to organic synthesis, not only providing valuable direction for molecular ferroelectrics but also further enriching the executable range of ferroelectric catalysis., (© 2024. The Author(s).)

Over the past years, the application potential of ferroelectric nanomaterials with unique physical properties for modern electronics is highlighted to a large extent. However, it is relatively challenging to fabricate inorganic ferroelectric nanomaterials, which is a process depending on a vacuum atmosphere at high temperatures. As significant complements to inorganic ferroelectric nanomaterials, the nanomaterials of molecular ferroelectrics are rarely reported. Here a low-cost room-temperature antisolvent method is used to synthesize free-standing 2D organic-inorganic hybrid perovskite (OIHP) ferroelectric nanosheets (NSs), that is, (CHA) 2 PbBr 4 NSs (CHA = cyclohexylammonium), with an average lateral size of 357.59 nm and a thickness ranging from 10 to 70 nm. This method shows high repeatability and produces NSs with excellent crystallinity. Moreover, ferroelectric domains in single NSs can be clearly visualized and manipulated using piezoresponse force microscopy (PFM). The domain switching and PFM-switching spectroscopy indicate the robust in-plane ferroelectricity of the NSs. This work not only introduces a feasible, low-cost, and scalable method for preparing molecular ferroelectric NSs but also promotes the research on molecular ferroelectric nanomaterials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc. , the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.

Improving the availability of soil phosphorus (P) and promoting tree growth through tree species selection and assembly are the critical issue. We conducted an afforestation experiment following randomized block experimental design with 1, 2, 4, and 6 tree species richness in south subtropics, including Pinus massoniana , Mytilaria laosensis , Erythrophleum fordii , Castanopsis hystrix , Michelia macclurei , Manglietia glauca , Aquilaria sinensis , and Dalbergia odorifera . We measured the bioavailable P components (CaCl 2 -P, citrate-P, enzyme-P and HCl-P) and examined the effects of different tree species assembly on bioavailable P components and tree growth. The results showed that, compared with non-nitrogen-fixing tree species, the mixing of nitrogen-fixing tree species ( E. fordii and D. odorifera ) effectively increased the contents of soil water, total nitrogen, total phosphorus, and microbial biomass P (MBP). The assembly of specific tree species improved the accumulation of bioavailable P. Mixing of nitrogen-fixing tree species significantly increased CaCl 2 -P content by 46.2% to 160.3%, the enzyme-P content produced by microbial mineralization by 69.3% to 688.2%, and HCl-P by 31.5% to 81.3%, increased MBP by 81.8% to 149.4%, and microbial biomass N (MBN) by 88.1% to 160.6%, respectively. Redundancy and correlation analysis results showed that MBP, available P, total phosphorus, L-leucine aminopeptidase, cellobiose, acid phosphatase, MBN and soil organic carbon were key factors driving the variation of rhizosphere soil bioavailable P. Mixing of nitrogen-fixing tree species increased enzyme-P and citrate-P, and the availability of which were positively correlated to tree basal area. In this study, mixing of nitrogen-fixing tree species increased the rhizosphere soil bioavailable P content, which facilitates tree growth.

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)BF 4 ] 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)BF 4 . 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., (© 2024. The Author(s).)

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature ( T m ) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N -methylation and I-substitution. Structural-property analysis reveals that the N -methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low T m and wide melt-processable windows, e.g., (DMIPA) 2 PbI 4 showcasing a low T m of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the T m and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

On the path of persisting Moore's Law, one of the biggest obstacles is the "Boltzmann tyranny," which defines the lower limit of power consumption of individual transistors. Negative capacitance (NC) in ferroelectrics could provide a solution and has garnered significant attention in the fields of nanoelectronics, materials science, and solid-state physics. Molecular ferroelectrics, as an integral part of ferroelectrics, have developed rapidly in terms of both performance and functionality, with their inherent advantages such as easy fabrication, mechanical flexibility, low processing temperature, and structural tunability. However, studies on the NC in molecular ferroelectrics are limited. In this study, the focus is centered on the fabricated high-quality thin films of trimethylchloromethyl ammonium trichlorocadmium(II), and a pioneering investigation on their NC responses is conducted. The findings demonstrate that the NC exhibited by molecular ferroelectrics is comparable to that of conventional HfO 2 -based ferroelectrics. This underscores the potential of molecular material systems for next-generation electronic devices., (© 2023 Wiley-VCH GmbH.)

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., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Implantable neural stimulation devices are becoming prevalent in bioelectronic medicine for the precise treatment of various clinical diseases. Nevertheless, the limited lifespan and buckling size of the implanted devices remain significant obstacles for chronic clinical application. In this study, we developed an ultrasound-driven battery-free neurostimulator based on a high-performance mini-sized nanogenerator and demonstrated its successful application for the deep-brain-stimulation (DBS) therapy of Parkinson's disease in a rat model. This soft piezoelectric-triboelectric hybrid nanogenerators (PTNG) are made of porous thin-films of molecular piezoelectric materials, which have great advantages of facile, scalable, low-temperature, and flexible processing. Without any bucky accessory control circuits, the subcutaneously implanted soft PTNG can function as a wirelessly powered neurostimulator, allowing for the adjustment of stimulation parameters through external programmable ultrasound pulses. This DBS electroceutical application of energy-harvesting thin-film devices based on molecular piezoelectric materials provides valuable insight into the development of a soft high-performance bioelectronic device.

The spiders Psechrus triangulus and Hippasa lycosina are widely distributed in Yunnan Province, China, and are important natural enemies of agricultural pests, yet studies regarding the composition of their venom are lacking. In this study, cDNA libraries were constructed from venom gland tissue of P. triangulus and H. lycosina and used for transcriptomic analysis. From the analysis, 39 and 31 toxin-like sequences were predicted for P. triangulus and H. lycosina, respectively. The predicted neurotoxin sequences were categorized according to cysteine sequence motifs, and the predicted neurotoxin sequences of P. triangulus and H. lycosina could be classified into 9 and 6 toxin families, respectively. In addition, potential acetylcholinesterase, hyaluronidase, and astaxanthin-like metalloproteinases were identified through annotation. In summary, transcriptomic techniques were invaluable in mining the gene expression information from these two spider species to explore the toxin composition of their venom and determine how they differ. Studies of this type provide essential baseline data for studying the evolution and physiological activities of spider toxins and for the potential development of medicinal compounds., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2023. Published by Elsevier Inc.)

Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl 3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.

Abundant chemical diversity and structural tunability make organic-inorganic hybrid perovskites (OIHPs) a rich ore for ferroelectrics. However, compared with their inorganic counterparts such as BaTiO 3 , their ferroelectric key properties, including large spontaneous polarization (P s ), low coercive field (E c ), and strong second harmonic generation (SHG) response, have long been great challenges, which hinder their commercial applications. Here, a quasi-one-dimensional OIHP DMAGeI 3 (DMA = Dimethylamine) is reported, with notable ferroelectric attributes at room temperature: a large P s of 24.14 μC/cm 2 (on a par with BaTiO 3 ), a low E c below 2.2 kV/cm, and the strongest SHG intensity in OIHP family (about 12 times of KH 2 PO 4 (KDP)). Revealed by the first-principles calculations, its large P s originates from the synergistic effects of the stereochemically active 4s 2 lone pair of Ge 2+ and the ordering of organic cations, and its low kinetic energy barrier of small DMA cations results in a low E c . Our work brings the comprehensive ferroelectric performances of OIHPs to a comparable level with commercial inorganic ferroelectric perovskites., (© 2023. The Author(s).)

Achieving a periodic domain structure in ferroelectric materials to tailor the macroscopic properties or realize new functions has always been a hot topic. However, methods to construct periodic domain structures, such as epitaxial growth, direct writing by scanning tips, and the patterned electrode method, are difficult or inefficient to implement in emerging molecular ferroelectrics, which have the advantages of lightweight, flexibility, biocompatibility, etc. An efficient method for constructing and controlling periodic domain structures is urgently needed to facilitate the development of molecular ferroelectrics in nanoelectronic devices. In this work, it is demonstrated that large-area, periodic and controllable needle-like domain structures can be achieved in thin films of the molecular ferroelectric trimethylchloromethyl ammonium trichlorocadmium (TMCM-CdCl 3 ) upon the application of tensile strain. The domain evolution under various tensile strains can be clearly observed, and such processes are accordingly identified. Furthermore, the domain wall exhibits a superior piezoelectric response, with up to fivefold enhancement compared to that of the pristine samples. Such large-area tunable periodic domain structure and abnormally strong piezoresponse are not only of great interests in fundamental studies, but also highly important in the future applications in functional molecular materials., (© 2023 Wiley-VCH GmbH.)

The electrocaloric effect (ECE) is an efficient and environmentally friendly method for solid-state refrigeration driven by an electric field. However, disregarding the ECE performance, the mass of materials also limits the amount of energy transferred in the cooling process. While molecular ECE materials have been attracting intensive attention with their excellent ECE properties, most reported molecular compounds can only be utilized in the form of thin films or single crystals. Unlike inorganic ceramics, molecular thin films and single crystals are very difficult to prepare in a large amount, which greatly restrains the future application of those materials. In this work, we report an excellent molecular ECE material in the form of polycrystalline molecular ceramics. Such molecular ceramics are composed of plastic molecular ferroelectrics, and can fulfil the requirement of large mass, easy processing, excellent performance and low energy consumption. Our molecular ceramic of HQReO 4 (HQ: protonated quinuclidine) demonstrates an isothermal entropy change of 5.8 J K -1 kg -1 and an adiabatic temperature change of 3.1 K. Notably, by a simple low-temperature pressing process without added adhesives (about 373 K), an HQReO 4 molecular ceramic block can be obtained, and its ECE performance is observed to be comparable to that of single crystals, for the first time. This work proposes a new application form for molecular electrocaloric materials, which opens up new ideas for solid-state refrigeration.

Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric ( d 33 ) and piezoelectric voltage ( g 33 ) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d 33 and g 33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me 3 NCH 2 Cl]CdBrCl 2 (You et al. d 33 (∼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me 3 NCH 2 Cl]CdCl 3 (You et al. Science 2017 , 357 , 306-309). More strikingly, [Me 3 NCH 2 Cl]CdBrCl 2 simultaneously shows a giant g 33 of 6215 × 10 -3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me 3 NCH 2 Cl]CdBrCl 2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.

Molecular ferroelectrics with large piezoelectric responses have long been sought for their advantages of light weight, mechanical flexibility, and easy preparation, in contrast to the widely used inorganic counterparts. Representatively, a molecular ferroelectric crystal [Me 3 NCH 2 Cl]CdCl 3 (TMCM-CdCl 3 ) has been found to show a large piezoelectric coefficient d 33 (You 3 (You et al. Science 2017 , 357 , 306-309). However, although the d 33 of molecular ferroelectrics has achieved great progress, their electromechanical coupling factor k 33 , which is essential for various piezoelectric applications, including ultrasonic transducers and actuators, was rarely explored and is far below the level of inorganic ferroelectrics. The major reason for this situation is the great challenge of growing large-size crystals which is a key limiting factor for measuring k 33 . Here, we grew inch-size crystals of organic-inorganic perovskite ferroelectric TMCM-CdCl 3 with a high d 33 (383 pC/N) for investigating its piezoelectric responses including the k 33 (0.483) by the resonance method. Such high k 33 (0.483) is much larger than those of other molecular ferroelectrics and competitive with that of BaTiO 3 (0.5). In addition, TMCM-CdCl 3 has a low elastic modulus of 13.03 GPa, an order of magnitude lower than that of BaTiO 3 . This finding sheds light on the exploration of large electromechanical coupling factors in molecular ferroelectrics for potential applications in flexible and portable piezoelectric devices.

Chirality exists everywhere from natural amino acids to particle physics. The introduction of point chirality has recently been shown to be an efficient strategy for the construction of molecular ferroelectrics. In contrast to point chirality, however, axial chirality is rarely used to design ferroelectrics so far. Here, based on optically active 1,1'-bi-2-naphthol (BINOL), which has been applied extensively as a versatile chiral reagent in asymmetric catalysis, chiral recognition, and optics, we successfully design a pair of axial-chiral BINOL multiferroics, ( R )-BINOL-DIPASi and ( S )-BINOL-DIPASi. They experience a 2F1-type full ferroelectric/ferroelastic phase transition at a high temperature of 362 and 363 K, respectively. Piezoelectric force microscopy and polarization-voltage hysteresis loops demonstrate their ferroelectric domains and domain switching, and polarized light microscopy visualizes the evolution of stripe-shaped ferroelastic domains. The axial-chiral BINOL building block promotes the generation of the polar structure and ferroelectricity, and the organosilicon component increases the rotational energy barrier and thus the phase transition temperature. This work presents the first axial-chiral high-temperature multiferroic crystals, offering an efficient path for designing molecular multiferroics through the introduction of axial chirality.

The hybrid rare-earth double perovskite (HREDP) system provides great convenience for the construction of multifunctional materials. However, suffering from the high symmetry of their intrinsic structure, HREDPs face the challenges in the realization and optimization of ferroelectric and piezoelectric properties. For the first time, after a systematic investigation of the chirality transformation principle, it is found that the introduction of chirality is an efficient strategy for the targeted construction of multifunctionality, which simultaneously increases the possibility of obtaining multiaxial ferroelectricity and ferroelasticity, and effectively realizes a large piezoelectric response. Moreover, chirality induced ferroelasticity will also achieve excellent magnetic or optical response driven by pressure-sensitive. To verify the feasibility of the above ideas, by using rare-earth ions (Ce 3+ ) and suitable chiral organic cations, a new HREDP, (R-N-methyl-3-hydroxylquinuclidinium) 2 RbCe(NO 3 ) 6 (R1) is successfully designed, in which ferroelasticity, multiaxial ferroelectricity, satisfactory piezoelectric response, and the pressure-driven single-ion magnetics switch are simultaneously achieved for the first time. This work shows that the induction of chirality and the HREDP system provide an effective strategy and ideal platform for the expansion and optimization of the functions in perovskite ferroelectrics., (© 2022 Wiley-VCH GmbH.)

Ferroelectric domains and domain walls are unique characteristics of ferroelectric materials. Among them, charged domain walls (CDWs) are a special kind of peculiar microstructure that highly improve conductivity, piezoelectricity, and photovoltaic efficiency. Thus, CDWs are believed to be the key to ferroelectrics' future application in fields of energy, sensing, information storage, and so forth. Studies on CDWs are one of the most attractive directions in conventional inorganic ferroelectric ceramics. However, in newly emerged molecular ferroelectrics, which have advantages such as lightweight, easy preparation, simple film fabrication, mechanical flexibility, and biocompatibility, CDWs are rarely observed due to the lack of free charges. In inorganic ferroelectrics, doping is a traditional method to induce free charges, but for molecular ferroelectrics fabricated by solution processes, doping usually causes phase separation or phase transition, which destabilizes or removes ferroelectricity. To realize stable CDWs in molecular systems, we designed and synthesized an n-type molecular ferroelectric, 1-adamantanammonium hydroiodate. In this compound, negative charges are induced by defects in the I - vacancy, and CDWs can be achieved. Nanometer-scale CDWs that are stable at temperatures as high as 373 K can be "written" precisely by an electrically biased metal tip. More importantly, this is the first time that the charge diffusion of CDWs at variable temperatures has been investigated in molecular ferroelectrics. This work provides a new design strategy for n-type molecular ferroelectrics and may shed light on their future applications in flexible electronics, microsensors, and so forth.

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival. Additionally, LPIN1 increased the production of lipid droplets, which play an important role in TKI drug resistance. All results were recapitulated in a patient-derived EGFR-mutant NSCLC cell line. In in vivo tumorigenesis assay, we identified that both shRNA-mediated depletion and pharmaceutical inhibition of LPIN1 clearly reduced tumor growth and confirmed that gefitinib treatment induced LPIN1 expression and LPIN1-dependent NF-κB activation (an increase in p-IκBα level) in tumor tissues. These results suggest an effective strategy of co-treating TKIs and LPIN1 inhibitors to prevent TKI resistance in NSCLC patients.

Objective: To investigate the value of CD44 + mononuclear cells (MNC) and spleen stiffness measurement (SSM) in minimal residual disease (MRD) in acute myeloid leukemia (AML) and its prognosis., Methods: Flow cytometry was used to detected the proportion of CD44 + and CD24 + MNC in 44 AML patients after induction chemotherapy. The SSM was tested by FS. The value of MNC and SSM in MRD and its prognosis was explored., Results: The percentage of CD44 + MNC and SSM in MRD positive group were significantly higher than those in MRD negative group (P<0.05). In MRD positive group, there were positive correlation between CD44 + MNC, SSM and MRD level (r=0.998, r=0.939, P<0.05). The median EFS and OS in HCD44 + MNC and HSSM groups were significantly shorter than those in LCD44 + MNC and LSSM (P<0.05). CD24 + MNC showed no association with MRD and its prognosis., Conclusion: HCD44 + MNC and HSSM may be used to predict high level MRD and poor prognosis.

Objective: To detect the relationship between leukocytes derived microparticle (CD45 + MP) and minimal residual disease (MRD) and prognosis of acute myeloid leukemia (AML)., Methods: The expression of CD45 + MP, CD44 + MP and CD24 + MP in peripheral blood of 47 AML patients at the time after induction chemotherapy were detected by using flow cytometry, and the relationship between MP, MRD and prognosis were analyzed., Results: The percentages of CD45 + MP, CD44 + MP and CD24 + MP in MRD positive group were significantly higher than those in MRD negative group. In MRD positive group, there were positive correlation between CD45 + MP, CD44 + MP, CD24 + MP and MRD level. The AUC of CD45 + MP, CD44 + MP, CD24 + MP in predicting positive MRD was 0.949, 0.782, and 0.817, respectively. The EFS and OS in HCD45 + MP, HCD44 + MP and HCD24 + MP groups were significantly shorter than low level group., Conclusion: High level of CD45 + MP, CD44 + MP, CD24 + MP can be used to predict high level MRD and poor prognosis.

The intense research activities on the hybrid organic-inorganic perovskites (HOIPs) have led to the greatly improved light absorbers for solar cells with high power conversion efficiency (PCE). However, it is still challenging to find an alternative lead-free perovskite to replace the organohalide lead perovskites to achieve high PCE. This is because both previous experimental and theoretical investigations have shown that the Pb 2+ cations play a dominating role in contributing the desirable frontier electronic bands of the HOIPs for light absorbing. Recent advances in the chemical synthesis of three-dimensional (3D) metal-free perovskites, by replacing Pb 2+ with NH 4 + , have markedly enriched the family of multifunctionalized perovskites (Ye et al., Science2018, 361, 151-155). These metal-free perovskites possess the chemical formula of A(NH 4 )X 3 , where A is divalent organic cations and X denotes halogen atoms. Without involving transition-metal cations, the metal-free A(NH 4 )X 3 perovskites can entail notably different frontier electronic band features from those of the organohalide lead perovskites. Indeed, the valence and conduction bands of A(NH 4 )X 3 perovskites are mainly attributed by the halogen atoms and the divalent A 2+ organic cations, respectively. Importantly, a linear relationship between the bandgaps of A(NH 4 )X 3 perovskites and the lowest unoccupied molecular orbital energies of the A 2+ cations is identified, suggesting that bandgaps can be tailored via molecular design, especially through a chemical modification of the A 2+ cations. Our comprehensive computational study and molecular design predict a metal-free perovskite, namely, 6-ammonio-1-methyl-5-nitropyrimidin-1-ium-(NH 4 )I 3 , with a desirable bandgap of ∼1.74 eV and good optical absorption property, both being important requirements for photovoltaic applications. Moreover, the application of strain can further fine-tune the bandgap of this metal-free perovskite. Our proposed design principle not only offers chemical insights into the structure-property relationship of the multifunctional metal-free perovskites but also can facilitate the discovery of highly efficient alternative, lead-free perovskites for potential photovoltaic or optoelectronic applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

This research aimed at exploring the effect of Zanthoxylum alkylamides on lipid metabolism and its potential mechanisms using high-fat diet rat model. Treatment with Zanthoxylum alkylamides for 6 weeks, food efficiency and atherogenic index of the low, medium, and high doses of Zanthoxylum alkylamides-treated groups were significantly reduced. Meanwhile, the histopathological structure of the livers showed that hepatic steatosis in the groups treated with Zanthoxylum alkylamides was reduced, particularly the HD group. Moreover, the related genes were studied, such as, liver X receptor (LXR), cholesterol 7 alpha-hydroxylase (CYP7A1), hepatic 3-hydroxyl-2-methylglutaryl CoA (HMG-CoA) reductase, sterol regulatory element-binding protein 2 (SREBP-2), ileal bile acid-binding protein (IBABP), sodium-dependent bile acid transporter (ASBT), and transient receptor potential vanilloid subtype1 (TRPV1). These results demonstrated that Zanthoxylum alkylamides could ameliorate abnormal lipid metabolism in rats fed with a high-fat diet. The underlying mechanism may be the downregulation of the expression levels of cholesterol synthesis and bile acid reabsorption-related genes, reduction of endogenous cholesterol synthesis, and increase in bile acid and neutral sterol excretion. PRACTICAL APPLICATIONS: High-energy diet is a potential risk of lipid metabolic disorder. Many studies have shown that hyperlipidemia can lead to atherosclerosis and even hemangioma, cerebral thrombosis, coronary heart disease, and other diseases, which seriously threaten human health. Therefore, seeking an effective and safe way to prevent the obesity-related disease is necessary. This research found that Zanthoxylum alkylamide could ameliorate abnormal lipid metabolism in rats fed with a high-fat diet. The underlying mechanism may be the downregulation of the expression levels of cholesterol synthesis and ileal absorption of bile acid genes, reduction of endogenous cholesterol synthesis, and increase in bile acid and neutral sterol excretion. Therefore, Zanthoxylum alkylamide has the potential for preventing or alleviating high-energy intake-related obesity., (© 2020 Wiley Periodicals LLC.)

Hepatocellular carcinoma (HCC) is reported to associate with abnormal expression of SCF E3 ubiquitin ligases. FBXW10, an F-box protein of the E3 ubiquitin ligases, was abnormally regulated in HCC patients. However, whether FBXW10 is associated with HCC has not yet been evaluated. Here, we analyzed the associations between overall survival and various risk factors in 191 HCC tissues. Univariate and multivariate analyses demonstrated that FBXW10 was an independent risk factor related to HCC prognosis. The results showed that FBXW10, gender and tumor state were strongly associated with overall survival in HCC patients. Furthermore, high expression of FBXW10 was associated with poor survival among male HCC patients but not female HCC patients. FBXW10 was more highly expressed in male HCC tissues and more strongly related to vascular invasion in male HCC patients. Consistent with these findings, the male FBXW10-Tg(+) mice were more susceptible to tumorigenesis, changes in regenerative capacity, and liver injury and inflammation but not changes in liver function than FBXW10-Tg(-) mice. FBXW10 promoted cell proliferation and migration in HCC cell lines. Our findings reveal that FBXW10, an independent risk factor for HCC, promotes hepatocarcinogenesis in male patients, and is also a potential prognostic marker in male patients with HCC., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Organic-inorganic hybrid perovskites (OIHPs) hold a great potential for scientific and technological endeavors in the field of ferroelectrics, solar cells, and electroluminescent devices, because of their structural diversity, low cost of manufacture, and ease of fabrication. However, lead iodide perovskite ferroelectrics with narrow band gap have rarely been reported. Here, we present a new two-dimensional (2D) layered lead iodide perovskite ferroelectric, (4,4-DFHHA) 2 PbI 4 (4,4-DFHHA = 4,4-difluorohexahydroazepine), with a spontaneous polarization ( P s ) of 1.1 μC/cm 2 at room temperature, a direct bandgap of 2.32 eV, and a high Curie temperature T c of 454 K (beyond that of BaTiO 3 , 393 K). On the basis of the nonferroelectrics (HHA)I, (4-FHHA)I, and (4,4-DFHHA)I (HHA = hexahydroazepine, 4-FHHA = 4-fluorohexahydroazepine), we assembled them with PbI 2 to form lead iodide perovskites. Because the space between adjacent one-dimensional (1D) chains is relatively large and the confinement effect is not obvious, the cations are still in a disordered state, and 1D OIHPs (HHA)PbI 3 and (4-FHHA)PbI 3 are also nonferroelectrics at room temperature. In the confined environment of the 2D PbI 4 2- framework for (4,4-DFHHA) 2 PbI 4 , the 4,4-DFHHA cations become ordered, and their asymmetric distribution leads to the spontaneous polarization. This work offers an efficient strategy for enriching the family of lead iodide perovskite ferroelectrics through the confinement effect and should inspire further exploration of the interplay between ferroelectricity and photovoltaics.

Molecular ferroelectrics are attracting tremendous interest because of their easy and environmental-friendly processing, low acoustic impedance, and mechanical flexibility. Their ferroelectric mechanism is mainly ascribed to the order-disorder transition of molecules such as spherical 1,4-diazabicyclo[2.2.2] octane (DABCO) and quinuclidine. Here, we present two molecular ferroelectrics, [HDABCO][TFSA] and its deuterated one [DDABCO][TFSA] (TFSA = bis(trifluoromethylsulfonyl)ammonium), whose ferroelectricity is triggered by the proton ordering. This is the first time that the protons show a thermally fluctuated bistability with a double-well potential in DABCO-based ferroelectrics. A large deuterium isotope effect (Δ T = ∼53 K) not only proves that they are hydrogen-bonded ferroelectrics but also extends the ferroelectric working temperature range to room temperature. The superfast polarization switching of 100 kHz and ultralow coercive voltage of 1 V (far less than 5 V required for commercially available ferroelectric devices), benefiting from the low energy for proton transfer, allow [DDABCO][TFSA] a great potential for memory devices with low-voltage, high-speed operation. This work should inspire further exploration of hydrogen-bonded molecular ferroelectrics for flexible and wearable devices with the low-power information storage.

Using the paired correlation equation g(r) in the spatial point patterns, we investigated the regeneration characteristics and spatial patterns of Castanopsis hystrix seedlings and the spatial correlation with the seed trees in the plantation by large diameter wood cultivation in south subtropical China. The results showed that natural seedling regeneration in C. hystrix plantation was good, which were widely distributed in the whole plantation. The seedling regeneration were mainly contributed by root sprouts, accounting for 73.6% of the total. The number distribution of C. hystrix seedlings in different age classes showed a pyramidal shape, with the contribution of diameter class1, 2 and 3 being 64.3%, 29.3% and 6.4% of the total, respectively. The C. hystrix seedlings mainly presented aggregated distribution in small scale (<15 m). With the increases of size classes and spatial scales, the aggregation strength gradually weakened and finally presented random distribution. The spatial correlation between seedlings and seed trees was not significant with the increases of size classes or spatial scale.

Topological defects, such as vortices and skyrmions, provide a wealth of splendid possibilities for new nanoscale devices because of their marvelous electronic, magnetic, and mechanical behaviors. Recently, great advances have been made in the study of the ferroelectric vortex in conventional perovskite oxides, such as BaTiO 3 and BiFeO 3 . Despite extensive interest, however, no intriguing ferroelectric vortex structures have yet been found in organic-inorganic hybrid perovskites (OIHPs), which are desirable for their mechanical flexibility, ease of fabrication, and low acoustical impedance. We observed the robust vortex-antivortex topological configurations in a two-dimensional (2D) layered OIHP ferroelectric (4,4-DFPD) 2 PbI 4 (4,4-DFPD is 4,4-difluoropiperidinium). This provides future directions for the study of perovskites and makes it a promising alternative for nanoscale ferroelectric devices in medical, micromechanical, and biomechanical applications.

Molecular ferroelectrics have attracted considerable interests because of their easy and environmentally friendly processing, low acoustical impedance and mechanical flexibility. Herein, a molecular thermochromic ferroelectric, N,N'-dimethyl-1,4-diazoniabicyclo[2.2.2]octonium tetrachlorocuprate(II) ([DMe-DABCO]CuCl 4 ) is reported, which shows both excellent ferroelectricity and intriguing thermochromism. [DMe-DABCO]CuCl 4 undergoes a ferroelectric phase transition from Pca2 1 to Pbcm at a significantly high Curie temperature of 413 K, accompanied by a color change from yellow to red that is due to the remarkable deformation of [CuCl 4 ] 2- tetrahedron, where the ferroelectric and paraelectric phases correspond to yellow and red, respectively. Combined with multiple bistable physical properties, [DMe-DABCO]CuCl 4 would be a promising candidate for next-generation smart devices, and should inspire further exploration of multifunctional molecular ferroelectrics., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Piezoelectric sensors that can work under various conditions with superior performance are highly desirable with the arrival of the Internet of Things. For practical applications, a large piezoelectric voltage coefficient g and a high Curie temperature T c are critical to the performance of piezoelectric sensors. Here, we report a two-dimensional perovskite ferroelectric (4-aminotetrahydropyran) 2 PbBr 4 [(ATHP) 2 PbBr 4 ] with a saturated polarization of 5.6 μC cm -2 , high T c of 503 K [above that of BaTiO 3 (BTO, 393 K)], and extremely large g 33 of 660.3 × 10 -3 V m N -1 [much beyond that of Pb(Zr,Ti)O 3 (PZT) ceramics (20 to 40 × 10 -3 V m N -1 ), more than 2 times higher than that of poly(vinylidene fluoride) (PVDF, about 286.7 × 10 -3 V m N -1 )]. Combined with the advantages of molecular ferroelectrics, such as light weight, easy and environmentally friendly processing, and mechanical flexibility, (ATHP) 2 PbBr 4 would be a competitive candidate for next-generation smart piezoelectric sensors in flexible devices, soft robotics, and biomedical devices.

Hybrid perovskite materials are famous for their great application potential in photovoltaics and optoelectronics. Among them, lead-iodide-based perovskites receive great attention because of their good optical absorption ability and excellent electrical transport properties. Although many believe the ferroelectric photovoltaic effect (FEPV) plays a crucial role for the high conversion efficiency, the ferroelectricity in CH 3 NH 3 PbI 3 is still under debate, and obtaining ferroelectric lead iodide perovskites is still challenging. In order to avoid the randomness and blindness in the conventional method of searching for perovskite ferroelectrics, a design strategy of fluorine modification is developed. As a demonstration, a nonpolar lead iodide perovskite is modified and a new 2D fluorinated layered hybrid perovskite material of (4,4-difluorocyclohexylammonium) 2 PbI 4 , 1, is obtained, which possesses clear ferroelectricity with controllable spontaneous polarization. The direct bandgap of 2.38 eV with strong photoluminescence also guarantees the direct observation of polarization-induced FEPV. More importantly, the 2D structure and fluorination are also expected to achieve both good stability and charge transport properties. 1 is not only a 2D fluorinated lead iodide perovskite with confirmed ferroelectricity, but also a great platform for studying the effect of ferroelectricity and FEPV in the context of lead halide perovskite solar cells and other optoelectronic applications., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The X-site ion in organic-inorganic hybrid ABX 3 perovskites (OHPs) varies from halide ion to bridging linkers like HCOO - , N 3 - , NO 2 - , and CN - . However, no nitrite-based OHP ferroelectrics have been reported so far. Now, based on non-ferroelectric [(CH 3 ) 4 N][Ni(NO 2 ) 3 ], through the combined methodologies of quasi-spherical shape, hydrogen bonding functionality, and H/F substitution, we have successfully synthesized an OHP ferroelectric, [FMeTP][Ni(NO 2 ) 3 ] (FMeTP=N-fluoromethyl tropine). As an unprecedented nitrite-based OHP ferroelectric, the well-designed [FMeTP][Ni(NO 2 ) 3 ] undergoes the ferroelectric phase transition at 400 K with an Aizu notation of 6/mmmFm, showing multiaxial ferroelectric characteristics. This work is a great step towards not only enriching the molecular ferroelectric families but also accelerating the potential practical applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Piezoelectric materials produce electricity when strained, making them ideal for different types of sensing applications. The most effective piezoelectric materials are ceramic solid solutions in which the piezoelectric effect is optimized at what are termed morphotropic phase boundaries (MPBs). Ceramics are not ideal for a variety of applications owing to some of their mechanical properties. We synthesized piezoelectric materials from a molecular perovskite (TMFM) x (TMCM) 1- x CdCl 3 solid solution (TMFM, trimethylfluoromethyl ammonium; TMCM, trimethylchloromethyl ammonium, 0 ≤ x ≤ 1), in which the MPB exists between monoclinic and hexagonal phases. We found a composition for which the piezoelectric coefficient d 33 is ~1540 picocoulombs per newton, comparable to high-performance piezoelectric ceramics. The material has potential applications for wearable piezoelectric devices., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC). Methods: Hydrophobic QDs were effectively incorporated into lipid bilayers, and then therapeutic siRNAs were complexed with QD-lipid nanocarriers (QLs). Finally, anti-EGFR aptamer-lipid conjugates were inserted into the QLs for TNBC targeting (aptamo-QLs). TNBC-targeting aptamo-QLs were directly compared to anti-EGFR antibody-coupled immuno-QLs. The in vitro delivery of therapeutic siRNAs and QDs to target cells was assessed by flow cytometry and confocal microscopy. The in vivo targeting of siRNAs to tumors and their therapeutic efficacy were evaluated in mice carrying MDA-MB-231 tumors. Results: Both types of EGFR-targeting QLs showed enhanced delivery to target cancer cells, resulting in more effective gene silencing and enhanced tumor imaging compared to non-targeting control QLs. Moreover, combinatorial therapy with Bcl-2 and PKC-ι siRNAs loaded into the anti-EGFR QLs was remarkably effective in inhibiting tumor growth and metastasis. Conclusion: In general, the aptamo-QLs showed competitive in vivo delivery and therapeutic efficacy compared to immuno-QLs under the same experimental conditions. Our results show that the anti-EGFR aptamer-guided lipid carriers may be a potential theranostic delivery vehicle for RNA interference and fluorescence imaging of TNBCs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Ferroelectric thin films are extensively attractive as next-generation nonvolatile memories. Recently, molecular ferroelectrics (MFe), as an emerging new class, have been a new research focus because of their desirable characteristics such as good solution processability, tunable chemical properties, and bio-friendly compositions. However, traditional uniaxial MFe only possess one polar axis which greatly limits their application, as it requires restricted orientational control in single crystal. To achieve macroscopic ferroelectricity and thus fully realize technological advantages of MFe, development of multiaxes is imperative to maximize effective polarization in specific crystallographic orientations. Herein, we present an early exploration on polycrystalline multiaxial MFe thin films of [Hdabco][ReO 4 ] with a two-dimensional graphene hybrid nonvolatile memory device. The polarization switching of MFe is experimentally realized by the nonvolatile modulation of two current states in graphene. Such a hybrid device can exhibit large memory window ∼35 V implying its great potential in memory applications. Hence, by taking the advantages of multiple polarization axes of MFe, the low cost and large area MFe/graphene hybrid memory manifests new possibilities for the integration of these materials as flexible next generation memory devices.

Cancer theranosis is an emerging field of personalized medicine which enables individual anti-cancer treatment by monitoring the therapeutic responses of cancer patients. Based on a consideration of the nano-bio interactions related to the blood circulation of systemically administered nanoparticles in humans, as well as extravasation and active targeting, lipid micellar nanoparticles were co-loaded with paclitaxel (PTX) and quantum dots (QDs) to generate a theranostic delivery vehicle. To provide with a tumor-targeting capability, either an antibody or an aptamer against the epidermal growth factor receptor (EGFR) was conjugated to the micelle surface. The QD-containing micelles (QDMs), antibody-coupled QDMs (immuno-QDMs), and aptamer-coupled QDMs (aptamo-QDMs) were able to effectively circulate in blood for at least 8 h when administered intravenously into mice bearing EGFR-positive LS174T tumor xenografts. In vivo fluorescence imaging and a bio-distribution study showed that both the immuno-QDMs and aptamo-QDMs were largely localized in the tumor tissue. The tumor targeting capability enhanced the therapeutic efficacy of PTX for the target cancer cells. Both the immuno-PTX-QDMs and the aptamo-PTX-QDMs caused a stronger inhibition of LS174T tumor growth in mice, compared to the non-targeted PTX-QDMs. These results suggest that the anti-EGFR immuno-PTX-QDMs and anti-EGFR aptamo-PTX-QDMs could be utilized as a tumor-targeted theranostic delivery system for cancer treatment in the clinic.

Inorganic perovskite ferroelectrics are widely used in nonvolatile memory elements, capacitors, and sensors because of their excellent ferroelectric and other properties. Organic ferroelectrics are desirable for their mechanical flexibility, low weight, environmentally friendly processing, and low processing temperatures. Although almost a century has passed since the first ferroelectric, Rochelle salt, was discovered, examples of highly desirable organic perovskite ferroelectrics are lacking. We found a family of metal-free organic perovskite ferroelectrics with the characteristic three-dimensional structure, among which MDABCO ( N -methyl- N' -diazabicyclo[2.2.2]octonium)-ammonium triiodide has a spontaneous polarization of 22 microcoulombs per square centimeter [close to that of barium titanate (BTO)], a high phase transition temperature of 448 kelvins (above that of BTO), and eight possible polarization directions. These attributes make it attractive for use in flexible devices, soft robotics, biomedical devices, and other applications., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Though dominating most of the practical applications, inorganic ferroelectric thin films usually suffer from the high processing temperatures, the substrate limitation, and the complicated fabrication techniques that are high-cost, energy-intensive, and time-consuming. By contrast, molecular ferroelectrics offer more opportunities for the next-generation flexible and wearable devices due to their inherent flexibility, tunability, environmental-friendliness, and easy processability. However, most of the discovered molecular ferroelectrics are uniaxial, one major obstacle for improving the thin-film performance and expanding the application potential. In this Perspective, we overview the recent advances on multiaxial molecular ferroelectric thin films, which is a solution to this issue. We describe the strategies for screening multiaxial molecular ferroelectrics and characterizations of the thin films, and highlight their advantages and future applications. Upon rational and precise design as well as optimizing ferroelectric performance, the family of multiaxial molecular ferroelectric thin films surely will get booming in the near future and inject vigor into the century-old ferroelectric field.

Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance. Depletion of RNF25 expression substantially sensitized NSCLC cells to gefitinib treatment, while forced expression of RNF25 augmented gefitinib resistance in sensitive cells. We demonstrated that RNF25 mediates NF-κB activation in gefitinib-treated cells, which, in turn, induces reactivation of ERK signal to cause the drug resistance. We identified that the ERK reactivation occurs via the function of cytokines, such as IL-6, whose expression is transcriptionally induced in a gefitinib-dependent manner by RNF25-mediated NF-κB signals. These results suggest that RNF25 plays an essential role in gefitinib resistance of NSCLC by mediating cross-talk between NF-κB and ERK pathways, and provide a novel target for the combination therapy to overcome TKI resistance of NSCLC.

Molecular piezoelectrics are attracting tremendous interest because of their easy processing, light weight, low acoustical impedance, and mechanical flexibility. However, reports of molecular piezoelectrics with a piezoelectric coefficient d 33 comparable to piezoceramics such as barium titanate (BTO, 90-190 pC/N) have been scarce. Here, we present a uniaxial molecular ferroelectric, trimethylchloromethylammonium tribromocadmium(II) (TMCM-CdBr 3 ), in which the halogen bonding might be a possible critical point for the stabilization of one-dimensional (1D) {CdBr 3 } - chain and further reservation of its ferroelectricity in such organic-inorganic hybrid crystalline systems. It has a large d 33 of 139 pC/N, 1 order of magnitude higher than those of most classically uniaxial ferroelectrics such as LiNbO 3 (6-16 pC/N) and Rochelle salt (∼7 pC/N), and comparable with those of multiaxial ferroelectrics such as BTO and trimethylbromomethylammonium tribromomanganese(II) (112 pC/N). Moreover, the simple single-crystal growth and easy-to-find polar axis enable it to hold a great potential for applying in the single-crystal form. In light of the strong, specific, and directional halogen-bonding interactions, this work provides possibilities to explore new classes of molecular piezoelectrics and contribute to further developments.

Piezoelectric materials have been widely used in various applications, such as high-voltage sources, actuators, sensors, motors, frequency standard, vibration reducer, and so on. In the past decades, lead zirconate titanate (PZT) binary ferroelectric ceramics have dominated the commercial piezoelectric market due to their excellent properties near the morphotropic phase boundary (MPB), although they contain more than 60% toxic lead element. Here, we report a lead-free and one-composition molecular ferroelectric trimethylbromomethylammonium tribromomanganese(II) (TMBM-MnBr 3 ) with a large piezoelectric coefficient d 33 of 112 pC/N along polar axis, comparable with those of typically one-composition piezoceramics such as BaTiO 3 along polar axis [001] (∼90 pC/N) and much greater than those of most known molecular ferroelectrics (almost below 40 pC/N). More significantly, the effective local piezoelectric coefficient of TMBM-MnBr 3 films is comparable to that of its bulk crystals. In terms of ferroelectric performance, it is the low coercive voltages, combined with the multiaxial characteristic, that ensure the feasibility of piezo film applications. Based on these, along with the common superiorities of molecular ferroelectrics like light weight, flexibility, low acoustical impedance, easy and environmentally friendly processing, it will open a new avenue for the exploration of next-generation piezoelectric devices in industrial and medical applications.

Recently, a plastic crystal of quinuclidinium perrhenate (HQReO&#95;{4}) was reported to have the feasibility of controlling the crystallographic orientation in the grown crystal, but the corresponding temperature window is only about 22 K (345-367 K). Such a narrow window and uncertain ferroelectricity at room temperature would extremely limit its application potential. In this report, we prepared a large area high-quality polycrystalline thin film of HQReO&#95;{4} and for the first time observed ferroelectricity in the temperature range from 298 to 367 K. Density functional theory calculations revealed the origin of room-temperature ferroelectricity is ascribed to the collaborative flipping of HQ (protonated quinuclidine) and ReO&#95;{4}^{-}, which is dynamically preferred in the presence of a N─H⋯O hydrogen bond. A local piezoresponse force microscopy measurement was also employed to study the mechanisms of multiaxial polarization rotation and domain dynamics. By extending the ferroelectric temperature window to room temperature and the extraordinary thin-film processability, HQReO&#95;{4} would certainly become a suitable candidate for next generation ferroelectric materials.

Competing Interests: The authors declare no conflict of interest.