Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates.

V2-glycan/apex broadly neutralizing antibodies (bnAbs) recognize a closed quaternary epitope of the HIV-1 envelope glycoprotein (Env). This closed structure is necessary to elicit apex antibodies and useful to guide the maturation of other bnAb classes. To compare antigens designed to maintain this conformation, we evaluated apex-specific responses in mice engrafted with a diverse repertoire of B cells expressing the HCDR3 of the apex bnAb VRC26.25. Engineered B cells affinity matured, guiding the improvement of VRC26.25 itself. We found that soluble Env (SOSIP) variants differed significantly in their ability to raise anti-apex responses. A transmembrane SOSIP (SOSIP-TM) delivered as an mRNA-lipid nanoparticle elicited more potent neutralizing responses than multimerized SOSIP proteins. Importantly, SOSIP-TM elicited neutralizing sera from B cells engineered with the predicted VRC26.25-HCDR3 progenitor, which also affinity matured. Our data show that HCDR3-edited B cells facilitate efficient in vivo comparisons of Env antigens and highlight the potential of an HCDR3-focused vaccine approach.

Boosting Electrochemical CO2 Reduction on Copper-Based Metal-Organic Frameworks via Valence and Coordination Environment Modulation.

Cu-based metal-organic frameworks (MOFs) have attracted much attention for electrocatalytic CO2 reduction to high value-added chemicals, but they still suffer from low selectivity and instability. Here, an associative design strategy for the valence and coordination environment of the metal node in Cu-based MOFs is employed to regulate the CO2 electroreduction to ethylene. A novel "reduction-cleavage-recrystallization" method is developed to modulate the Cu(II)-Trimesic acid (BTC) framework to form a Cu(I)-BTC structure enriched with free carboxyl groups in the secondary coordination environment (SCE). In contrast to Cu(II)-BTC, the Cu(I)-BTC shows higher catalytic activity and better ethylene selectivity (≈2.2-fold) for CO2 electroreduction, which is further enhanced by increasing the content of free carboxyl groups, resulting in ethylene Faraday efficiency of up to 57% and the durability of the catalyst could last for 38 h without performance decline. It indicates that the synergistic effect between Cu(I)-O coordinated structure and free carboxyl groups considerably enhances the dimerization of *CO intermediates and hinders the hydrogenation of *CO intermediates in these competitive pathways. This work unravels the strong dependence of CO2 electroreduction on the Cu valence state and coordination environment in MOFs and provides a platform for designing highly selective electrocatalytic CO2 reduction catalysts.

The phonological congruency modulated long-term form priming of Chinese characters.

Elucidating the interaction between lexical processing and word learning is essential for a complete understanding of the underlying mechanisms of each of them. Long-term priming for words reflects an interplay between lexical processing and word learning. Although robust long-term priming effects have been found between two occurrences of the same word and between semantically similar words, it remains unclear whether long-term priming between orthographically similar words (i.e., long-term form priming) is a reliable effect. Following the theoretical analysis based on the connectionist framework, we articulated the possibility that long-term form priming might be modulated by the phonological congruency between the prime and target words, and that if this modulator was under control, reliable effects of long-term form priming would emerge. However, this hypothesis has not been adequately tested empirically. The present study tested this hypothesis by using Chinese phonograms and the phonetic radicals embedded in them as the prime and target items. In three experiments that varied in the types of stimuli and testing tasks, we consistently found that when the prime and target had the same phonology, naming the prime facilitated later processing of the target, while when they had different phonologies, the priming effect was inhibitory. These observations were consistent with the connectionist account of long-term priming for words. Our findings help confirm the reliability, generalizability, and robustness of long-term form priming and elucidate its underlying mechanisms, and suggesting promising future directions on the interactions between lexical processing and word learning.

In vitro affinity maturation of broader and more-potent variants of the HIV-1-neutralizing antibody CAP256-VRC26.25.

Three variable 2 (V2) loops of HIV-1 envelope glycoprotein (Env) trimer converge at the Env apex to form the epitope of an important classes of HIV-1 broadly neutralizing antibodies (bNAbs). These V2-glycan/apex antibodies are exceptionally potent but less broad (∼60 to 75%) than many other bNAbs. Their CDRH3 regions are typically long, acidic, and tyrosine sulfated. Tyrosine sulfation complicates efforts to improve these antibodies through techniques such as phage or yeast display. To improve the breadth of CAP256-VRC26.25 (VRC26.25), a very potent apex antibody, we adapted and extended a B cell display approach. Specifically, we used CRISPR/Cas12a to introduce VRC26.25 heavy- and light-chain genes into their respective loci in a B cell line, ensuring that each cell expresses a single VRC26.25 variant. We then diversified these loci through activation-induced cytidine deaminase-mediated hypermutation and homology-directed repair using randomized CDRH3 sequences as templates. Iterative sorting with soluble Env trimers and further randomization selected VRC26.25 variants with successively improving affinities. Three mutations in the CDRH3 region largely accounted for this improved affinity, and VRC26.25 modified with these mutations exhibited greater breadth and potency than the original antibody. Our data describe a broader and more-potent form of VRC26.25 as well as an approach useful for improving the breadth and potency of antibodies with functionally important posttranslational modifications.

Unveiling the Dual Role of Oxophilic Cr4+ in Cr-Cu2O Nanosheet Arrays for Enhanced Nitrate Electroreduction to Ammonia.

Cuprous oxide (Cu2O)-based catalysts present a promising activity for the electrochemical nitrate (NO3-) reduction to ammonia (eNO3RA), but the electrochemical instability of Cu+ species may lead to an unsatisfactory durability, hindering the exploration of the structure-performance relationship. Herein, we propose an efficient strategy to stabilize Cu+ through the incorporation of Cr4+ into the Cu2O matrix to construct a Cr4+-O-Cu+ network structure. In situ and quasi-in situ characterizations reveal that the Cu+ species are well maintained via the strong Cr4+-O-Cu+ interaction that inhibits the leaching of lattice oxygen. Importantly, in situ generated Cr3+-O-Cu+ from Cr4+-O-Cu+ is identified as a dual-active site for eNO3RA, wherein the Cu+ sites are responsible for the activation of N-containing intermediates, while the assisting Cr3+ centers serve as the electron-proton mediators for rapid water dissociation. Theoretical investigations further demonstrated that the metastable state Cr3+-O-Cu+ favors the conversion from the endoergic hydrogenation of the key *ON intermediate to an exoergic reaction in an ONH pathway, and facilitates the subsequent NH3 desorption with a low energy barrier. The superior eNO3RA with a maximum 91.6% Faradaic efficiency could also be coupled with anodic sulfion oxidation to achieve concurrent NH3 production and sulfur recovery with reduced energy input.

p-d Orbital Hybridization in Ag-based Electrocatalysts for Enhanced Nitrate-to-Ammonia Conversion.

Considering the substantial role of ammonia, developing highly efficient electrocatalysts for nitrate-to-ammonia conversion has attracted increasing interest. Herein, we proposed a feasible strategy of p-d orbital hybridization via doping p-block metals in an Ag host, which drastically promotes the performance of nitrate adsorption and disassociation. Typically, a Sn-doped Ag catalyst (SnAg) delivers a maximum Faradaic efficiency (FE) of 95.5±1.85 % for NH3 at -0.4 V vs. RHE and reaches the highest NH3 yield rate to 482.3±14.1 mg h-1 mgcat. -1. In a flow cell, the SnAg catalyst achieves a FE of 90.2 % at an ampere-level current density of 1.1 A cm-2 with an NH3 yield of 78.6 mg h-1 cm-2, during which NH3 can be further extracted to prepare struvite as high-quality fertilizer. A mechanistic study reveals that a strong p-d orbital hybridization effect in SnAg is beneficial for nitrite deoxygenation, a rate-determining step for NH3 synthesis, which as a general principle, can be further extended to Bi- and In-doped Ag catalysts. Moreover, when integrated into a Zn-nitrate battery, such a SnAg cathode contributes to a superior energy density of 639 Wh L-1, high power density of 18.1 mW cm-2, and continuous NH3 production.

Oral administration of Synechococcus sp. PCC7942 trans-vp19 and trans-vp (19+28) genes improve the immune and antioxidant capacity in Procambarus clarkii under white spot syndrome virus stress.

This study aimed to evaluate antioxidant capacity and protection from white spot syndrome virus (WSSV) challenge of Procambarus clarkii fed trans-vp19 and trans-vp (19 + 28) genes of Synechococcus sp. PCC7942 (Syn7942). P. clarkii were fed transgenic cyanobacteria continuously for 7 days, and then infected with WSSV after 12 h starvation. The daily mortality in each group was measured for 10 days and hepatopancreas and muscle of P. clarkii were examined for enzymes phenoloxidase (PO) activity, catalase (CAT) activity, glutathione peroxidase (GSH-px) activity, and malondialdehyde (MDA) concentration after immunization and viral challenge at different times. Compared with the WSSV-infected crayfish in positive control group (challenge and no vaccination) and wild type group (challenge, feeding wild-type Syn7942), vp19 group (challenge, feeding Syn7942 trans-vp19 gene) and vp (19 + 28) group [challenge, feeding Syn7942 trans-vp (19 + 28) genes] significantly improved the survival rate from 0% to 60% and 56.7%, respectively. Consistently, significantly greater PO, CAT, and GSH-px activity and significantly lower MDA concentration in the vp19 and vp (19 + 28) groups compared to the control group. These results demonstrate that the trans-vp19 and trans-vp (19 + 28) gene of Syn7942 significantly facilitated the immune and antioxidant capacity of crayfish. Therefore, the trans-vp19 and trans-vp (19 + 28) genes of Syn7942 could provide protection for crayfish as an anti-WSSV oral medication.

Reprogramming of the heavy-chain CDR3 regions of a human antibody repertoire.

B cells have been engineered ex vivo to express an HIV-1 broadly neutralizing antibody (bNAb). B cell reprograming may be scientifically and therapeutically useful, but current approaches limit B cell repertoire diversity and disrupt the organization of the heavy-chain locus. A more diverse and physiologic B cell repertoire targeting a key HIV-1 epitope could facilitate evaluation of vaccines designed to elicit bNAbs, help identify more potent and bioavailable bNAb variants, or directly enhance viral control in vivo. Here we address the challenges of generating such a repertoire by replacing the heavy-chain CDR3 (HCDR3) regions of primary human B cells. To do so, we identified and utilized an uncharacterized Cas12a ortholog that recognizes PAM motifs present in human JH genes. We also optimized the design of 200 nucleotide homology-directed repair templates (HDRT) by minimizing the required 3'-5' deletion of the HDRT-complementary strand. Using these techniques, we edited primary human B cells to express a hemagglutinin epitope tag and the HCDR3 regions of the bNAbs PG9 and PG16. Those edited with bNAb HCDR3 efficiently bound trimeric HIV-1 antigens, implying they could affinity mature in vivo in response to the same antigens. This approach generates diverse B cell repertoires recognizing a key HIV-1 neutralizing epitope.

Unlabelled LRET biosensor based on double-stranded DNA for the detection of anthraquinone anticancer drugs.

Based on upconversion nanoparticles (UCNPs) as energy donor and herring sperm DNA (hsDNA) as molecular recognition element, an unlabelled upconversion luminescence (UCL) affinity biosensor was constructed for the detection of anthraquinone (AQ) anticancer drugs in biological fluids. AQ anticancer drugs can insert into the double helix structure of hsDNA on the surface of UCNPs, thereby shortening the distance from UCNPs. Therefore, the luminescence resonance energy transfer (LRET) phenomenon is effectively triggered between UCNPs and AQ anticancer drugs. Hence, AQ anticancer drugs can be quantitatively detected according to the UCL quenching rate. The biosensor showed good sensitivity and stability for the detection of daunorubicin (DNR) and doxorubicin (ADM). For the detection of DNR, the linear range is 1-100 µg·mL-1 with a limit of detection (LOD) of 0.60 µg·mL-1, and for ADM, the linear range is 0.5-100 µg·mL-1 with a LOD of 0.38 µg·mL-1. The proposed biosensor provides a convenient method for monitoring AQ anticancer drugs in clinical biological fluids in the future.

A Self-Attention Integrated Learning Model for Landing Gear Performance Prediction.

The landing gear structure suffers from large loads during aircraft takeoff and landing, and an accurate prediction of landing gear performance is beneficial to ensure flight safety. Nevertheless, the landing gear performance prediction method based on machine learning has a strong reliance on the dataset, in which the feature dimension and data distribution will have a great impact on the prediction accuracy. To address these issues, a novel MCA-MLPSA is developed. First, an MCA (multiple correlation analysis) method is proposed to select key features. Second, a heterogeneous multilearner integration framework is proposed, which makes use of different base learners. Third, an MLPSA (multilayer perceptron with self-attention) model is proposed to adaptively capture the data distribution and adjust the weights of each base learner. Finally, the excellent prediction performance of the proposed MCA-MLPSA is validated by a series of experiments on the landing gear data.

Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection.

Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD. Accordingly, this review focuses on the independent and interactive roles of immunity and metabolism in AD to provide further insights into the pathogenesis, novel ideas for diagnosis and new strategies for treatment or early prevention of AD.

Single-entity Electrochemistry Unveils Dynamic Transformation during Tandem Catalysis of Cu2 O and Co3 O4 for Converting NO3 - to NH3.

Electrochemically converting nitrate to ammonia is an essential and sustainable approach to restoring the globally perturbed nitrogen cycle. The rational design of catalysts for the nitrate reduction reaction (NO3 RR) based on a detailed understanding of the reaction mechanism is of high significance. We report a Cu2 O+Co3 O4 tandem catalyst which enhances the NH3 production rate by ≈2.7-fold compared to Co3 O4 and ≈7.5-fold compared with Cu2 O, respectively, however, most importantly, we precisely place single Cu2 O and Co3 O4 cube-shaped nanoparticles individually and together on carbon nanoelectrodes provide insight into the mechanism of the tandem catalysis. The structural and phase evolution of the individual Cu2 O+Co3 O4 nanocubes during NO3 RR is unveiled using identical location transmission electron microscopy. Combining single-entity electrochemistry with precise nano-placement sheds light on the dynamic transformation of single catalyst particles during tandem catalysis in a direct way.

Glutamate blunts cell-killing effects of neutrophils in tumor microenvironment.

Neutrophils are the first defenders of the innate system for injury and infection. They have gradually been recognized as important participants in tumor initiation and development due to their heterogeneity and plasticity. In the tumor microenvironment (TME), neutrophils can exert antitumor and protumor functions, depending on the surroundings. Tumor cells systemically alter intracellular amino acid (AA) metabolism and extracellular AA distribution to meet their proliferation need, leading to metabolic reprogramming and TME reshaping. However, the underlying mechanisms that determine how altered AAs affect neutrophils in TME are less-explored. Here, we identified that abundant glutamate releasing from tumor cells blunted neutrophils' cell-killing effects toward tumor cells in vitro and in vivo. Mass spectrometric detection, flow cytometry, and western blot experiments proved that increased levels of pSTAT3/RAB10/ARF4, mediated by glutamate, were accompanied with immunosuppressive phenotypes of neutrophils in TME. We also discovered that riluzole, an FDA-approved glutamate release inhibitor, significantly inhibited tumor growth by restoring neutrophils' cell-killing effects and decreasing glutamate secretion from tumor cells. These findings highlight the importance of tumor-released glutamate on neutrophil transformation in TME, providing new possible cancer treatments targeting altered glutamate metabolism.

Development of SSR markers and genetic diversity analysis based on RAD-seq technology among Chinese populations of Daphnia magna.

BACKGROUND: Daphnia magna belongs to the Cladocera order and plays an important role in the aquatic ecosystem. With the intensification of water pollution, the wild population of D. magna has declined rapidly in recent years, and insufficient molecular markers have limited effective research and conservation of this species. METHODS AND RESULTS: 26 novel microsatellite (SSR) markers were developed in an artificially domesticated D. magna and 12 wild D. magna populations using restriction site-associated DNA sequencing (RAD-seq). The results showed that the observed heterozygosity (Ho) and expected heterozygosity (He) ranged from 0.083 to 0.999 and 0.085 to 0.862, respectively. The PIC ranged from 0.368 to 0.805. These results indicate that the developed SSR marker is highly polymorphic. Nei's genetic identity (H) ranged from 0.0926 to 0.3462. Shannon's Information index (I) ranged from 0.1333 to 0.4799. Genetic distance and Nei's genetic identity analysis, NJ tree diagram analysis, and PCoA analysis were conducted on populations of D. magna from different regions. The results show that the D. magna genetic relationship between Liaoning and Shanxi, Hunan and Anhui, and Beijing and Hainan are relatively close, while the genetic structure of D. magna in Guangdong, Jiangsu, and Sichuan is quite different from other sampling sites. An analysis of population genetic structure divided the D. magna samples into two major groups. CONCLUSIONS: These results indicate that the genetic structure of D. magna differs considerably in different regions. Our research results and the newly developed polymorphic SSR markers for D. magna are of great significance in terms of the genetic breeding of D. magna, identification of wild and artificially domesticated populations and conservation genetics research.

Comparison of planktonic bacterial communities indoor and outdoor of aquaculture greenhouses.

AIMS: Greenhouses are widely used in agriculture systems to shield crops from unfavourable weather to achieve a year-round food supply. In recent years, aquaculture ponds have been placed in greenhouses in many regions. The impacts of the greenhouses on planktonic bacterial communities should be uncovered. METHODS AND RESULTS: In this study, two polyolefin film greenhouses accommodating aquaculture ponds were established and planktonic bacterial communities were compared from samples taken in aquaculture ponds inside and outside the greenhouses, using Illumina 16S rRNA sequencing. CONCLUSIONS: The results showed there were significant variations in bacterial community structure between indoor and outdoor samples. Obvious differences were also found between two greenhouses, whereas the differences in indoor samples were weaker than outdoor samples. Significantly higher temperature (in summer), pH and permanganate index were found in the outdoor pond samples. Results of redundancy analysis showed that Proteobacteria and Bacteroidota were positively related to the dissolved oxygen, total nitrogen and total phosphorus, and Actinobacteriota were positively related to pH, temperature and permanganate index, whereas Cyanobacteria were positively related to the salinity, conductivity, total dissolved solids and ammonia nitrogen. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study revealed that greenhouses significantly influenced planktonic bacterial communities in aquaculture ponds. This study is expected to provide a scientific basis for aquaculture in greenhouses.

Rapid and Large-Scale Quality Assessment of Two-Dimensional MoS2 Using Sulfur Particles with Optical Visualization.

The efficient nondestructive assessment of quality and homogeneity for two-dimensional (2D) MoS2 is critically important to advance their practical applications. Here, we presented a rapid and large-area assessment method for visually evaluating the quality and uniformity of chemical vapor deposition (CVD)-grown MoS2 monolayers simply with conventional optical microscopes. This was achieved through one-pot adsorbing abundant sulfur particles selectively onto as-grown poorer-quality MoS2 monolayers in a CVD system without any additional treatment. We further revealed that this favorable adsorption of sulfur particles on MoS2 originated from their intrinsic higher-density sulfur vacancies. Based on unadsorbed MoS2 monolayers, superior performance field effect transistors with a mobility of ∼49 cm2 V-1 s-1 were constructed. Importantly, the assessment approach was noninvasive due to the all-vapor-phase and moderate adsorption-desorption process. Our work offers a new route for the performance and yield optimization of devices by quality assessment of 2D semiconductors prior to device fabrication.

Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency.

Sodium taurocholate cotransporting polypeptide (NTCP, encoded by Slc10a1/SLC10A1) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in Slc10a1-/- mice, and we also assessed changes of TBA levels in 33 young individuals with SLC10A1 loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both Slc10a1-/- mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic Slc10a1-/- mice, including inhibition of bile acid (BA) synthesis, enhancement of BA detoxification, and altered BA transport. Members of the sulfotransferase (SULT) family showed the most dramatic increases in livers of hypercholanemic Slc10a1-/- mice, and one of their BA sulfates, taurolithocholic acid 3-sulfate, significantly increased. Importantly, consistent with the mouse studies, comprehensive profiling of 58 BA species in sera of p.Ser267Phe individuals revealed a markedly increased level of BA sulfates. Together, our findings indicate that the enhanced BA sulfation is a major mechanism for BA detoxification and elimination in both mice and humans with Slc10a1/SLC10A1 deficiency.

Six-Fold Vertices in a Single-Component Organic Ferroelectric with Most Equivalent Polarization Directions.

Topological defects such as vortices in ferroelectric materials are attracting tremendous interest because of their splendid possibilities for unique physical phenomena and potential applications in nanoelectronic devices. However, reports of the vortex structure have been scarce in organic ferroelectrics, which are highly desirable for their mechanical flexibility, easy and environment-friendly processing, and low acoustical impedance. Here, we successfully observed the robust triangular domains in a single-component organic ferroelectric, 2-(hydroxymethyl)-2-nitro-1,3-propanediol (1), six of which can form a 6-fold vertex domain structure. To our knowledge, it is the first time that such an intriguing topological vortex gets experimentally confirmed in ferroelectrics. Moreover, the symmetry change of 1 with an Aizu notation of m3mF1 leads to the most 48 crystallographically equivalent polarization directions among all ferroelectrics. With those benefits and excellent piezoelectric properties, compound 1 shows great potential as a reconfigurable electronic element or a mechanical sensor for soft robotics, flexible and wearable devices, and biomachines.

Superior Transverse Piezoelectricity in a Halide Perovskite Molecular Ferroelectric Thin Film.

Piezoelectric materials with inherent mechanical-electric coupling effect are a crucial family of functional materials in high-end information technology. For practical applications, the transverse piezoelectric performance (d31 or d32) is mainly considered, because this parameter is a vitally important index to characterize the performance of piezoelectric thin films. However, the transverse piezoelectricity of the thin films as a key figure of merit is seldom mentioned in molecular ferroelectrics. Herein, we report that a new 1D halide perovskite ferroelectric N,N-dimethylallylammoniumCdCl3 (DMAACdCl3) exhibits an above room-temperature ferroelectric phase transition with a saturated polarization of 1.9 µC cm-2 and a coercive field of 5.0 kV cm-1. The thin film of DMAACdCl3 is successfully fabricated using an easy processing spinning method and maintains well ferroelectric properties verified by piezoresponse force microscopy (PFM). More significantly, the ferroelectric thin film offers superior transverse piezoelectricity with an in-plane piezoelectric response of about 41 pC N-1, which is about twice that of well-known piezoelectric polymer PVDF (21 pC N-1). Transverse piezoelectricity has been scarcely studied in molecular ferroelectrics, and its exploitation would play an important role in the design of next-generation smart piezoelectric devices.

The Soft Molecular Polycrystalline Ferroelectric Realized by the Fluorination Effect.

For a century ferroelectricity has attracted widespread interest from science and industry. Inorganic ferroelectric ceramics have dominated multibillion dollar industries of electronic ceramics, ranging from nonvolatile memories to piezoelectric sonar or ultrasonic transducers, whose polarization can be reoriented in multiple directions so that they can be used in the ceramic and thin-film forms. However, the realization of macroscopic ferroelectricity in the polycrystalline form is challenging for molecular ferroelectrics. In pursuit of low-cost, biocompatible, and mechanically flexible alternatives, the development of multiaxial molecular ferroelectrics is imminent. Here, from quinuclidinium perrhenate, we applied fluorine substitution to successfully design a multiaxial molecular ferroelectric, 3-fluoroquinuclidinium perrhenate ([3-F-Q]ReO4), whose macroscopic ferroelectricity can be realized in both powder compaction and thin-film forms. The fluorination effect not only increases the intrinsic polarization but also reduces the coercive field strength. More importantly, it is also, as far as we know, the softest of all known molecular ferroelectrics, whose low Vickers hardness of 10.5 HV is comparable with that in poly(vinylidene difluoride) (PVDF) but almost 2 orders of magnitude lower than that in BaTiO3. These attributes make it an ideal candidate for flexible and wearable devices and biomechanical applications.