BET inhibition decreases HMGCS2 and sensitizes resistant pancreatic tumors to gemcitabine.

Efforts to develop targetable molecular bases for drug resistance for pancreatic ductal adenocarcinoma (PDAC) have been equivocally successful. Using RNA-seq and ingenuity pathway analysis we identified that the superpathway of cholesterol biosynthesis is upregulated in gemcitabine resistant (gemR) tumors using a unique PDAC PDX model with resistance to gemcitabine acquired in vivo. Analysis of additional in vitro and in vivo gemR PDAC models showed that HMG-CoA synthase 2 (HMGCS2), an enzyme involved in cholesterol biosynthesis and rate limiting in ketogenesis, is overexpressed in these models. Mechanistic data demonstrate the novel findings that HMGCS2 contributes to gemR and confers metastatic properties in PDAC models, and that HMGCS2 is BRD4 dependent. Further, BET inhibitor JQ1 decreases levels of HMGCS2, sensitizes PDAC cells to gemcitabine, and a combination of gemcitabine and JQ1 induced regressions of gemR tumors in vivo. Our data suggest that decreasing HMGCS2 may reverse gemR, and that HMGCS2 represents a useful therapeutic target for treating gemcitabine resistant PDAC.

Antibacterial Ingredients and Modes of the Methanol-Phase Extract from the Fruit of Amomum villosum Lour.

Epidemics of infectious diseases threaten human health and society stability. Pharmacophagous plants are rich in bioactive compounds that constitute a safe drug library for antimicrobial agents. In this study, we have deciphered for the first time antibacterial ingredients and modes of the methanol-phase extract (MPE) from the fruit of Amomum villosum Lour. The results have revealed that the antibacterial rate of the MPE was 63.64%, targeting 22 species of common pathogenic bacteria. The MPE was further purified by high performance liquid chromatography (Prep-HPLC), and three different constituents (Fractions 1-3) were obtained. Of these, the Fraction 2 treatment significantly increased the cell membrane fluidity and permeability, reduced the cell surface hydrophobicity, and damaged the integrity of the cell structure, leading to the leakage of cellular macromolecules of Gram-positive and Gram-negative pathogens (p < 0.05). Eighty-nine compounds in Fraction 2 were identified by ultra HPLC-mass spectrometry (UHPLC-MS) analysis, among which 4-hydroxyphenylacetylglutamic acid accounted for the highest 30.89%, followed by lubiprostone (11.86%), miltirone (10.68%), and oleic acid (10.58%). Comparative transcriptomics analysis revealed significantly altered metabolic pathways in the representative pathogens treated by Fraction 2 (p < 0.05), indicating multiple antibacterial modes. Overall, this study first demonstrates the antibacterial activity of the MPE from the fruit of A. villosum Lour., and should be useful for its application in the medicinal and food preservative industries against common pathogens.

O-GlcNAcylation stimulates the deubiquitination activity of USP16 and regulates cell cycle progression.

Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase for uH2A, ubiquitin-specific peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein interaction, alters enzyme activity or protein folding, and changes protein subcellular localization. In our study, we first confirmed that USP16 is glycosylated on Thr203 and Ser214, as reported in a previous chemoenzymatic screen. We then discovered that mutation of the O-GlcNAcylation site Thr203, which is adjacent to deubiquitination-required Cys204, reduces the deubiquitination activity toward H2AK119ub in vitro and in cells, while mutation on Ser214 had the opposite effects. Using USP16 Ser552 phosphorylation-specific antibodies, we demonstrated that O-GlcNAcylation antagonizes cyclin-dependent kinase 1-mediated phosphorylation and promotes USP16 nuclear export. O-GlcNAcylation of USP16 is also required for deubiquitination of Polo-like kinase 1, a mitotic master kinase, and the subsequent chromosome segregation and cytokinesis. In summary, our study revealed that O-GlcNAcylation of USP16 at Thr203 and Ser214 coordinates deubiquitination of uH2A and Polo-like kinase 1, thus ensuring proper cell cycle progression.

Role of histone variants H2BC1 and H2AZ.2 in H2AK119ub nucleosome organization and Polycomb gene silencing.

Ubiquitination of histone H2A at lysine 119 residue (H2AK119ub) plays critical roles in a wide range of physiological processes, including Polycomb gene silencing 1,2 , replication 3-5 , DNA damage repair 6-10 , X inactivation 11,12 , and heterochromatin organization 13,14 . However, the underlying mechanism and structural basis of H2AK119ub remains largely elusive. In this study, we report that H2AK119ub nucleosomes have a unique composition, containing histone variants H2BC1 and H2AZ.2, and importantly, this composition is required for H2AK119ub and Polycomb gene silencing. Using the UAB domain of RSF1, we purified H2AK119ub nucleosomes to a sufficient amount and purity. Mass spectrometry analyses revealed that H2AK119ub nucleosomes contain the histone variants H2BC1 and H2AZ.2. A cryo-EM study resolved the structure of native H2AK119ub nucleosomes to a 2.6A resolution, confirming H2BC1 in one subgroup of H2AK119ub nucleosomes. Tandem GST-UAB pulldown, Flag-H2AZ.2, and HA-H2BC1 immunoprecipitation revealed that H2AK119ub nucleosomes could be separated into distinct subgroups, suggesting their composition heterogeneity and potential dynamic organization. Knockout or knockdown of H2BC1 or H2AZ.2 reduced cellular H2AK119ub levels, establishing H2BC1 and H2AZ.2 as critical determinants of H2AK119ub. Furthermore, genomic binding profiles of H2BC1 and H2AZ.2 overlapped significantly with H2AK119ub binding, with the most significant overlapping in the gene body and intergenic regions. Finally, assays in developing embryos reveal an interaction of H2AZ.2, H2BC1, and RING1A in vivo . Thus, this study revealed, for the first time, that the H2AK119ub nucleosome has a unique composition, and this composition is required for H2AK119ub and Polycomb gene silencing.

The male pachynema-specific protein MAPS drives phase separation in vitro and regulates sex body formation and chromatin behaviors in vivo.

Dynamic chromosome remodeling and nuclear compartmentalization take place during mammalian meiotic prophase I. We report here that the crucial roles of male pachynema-specific protein (MAPS) in pachynema progression might be mediated by its liquid-liquid phase separation in vitro and in cellulo. MAPS forms distinguishable liquid phases, and deletion or mutations of its N-terminal amino acids (aa) 2-9 disrupt its secondary structure and charge properties, impeding phase separation. Maps-/- pachytene spermatocytes exhibit defects in nucleus compartmentalization, including defects in forming sex bodies, altered nucleosome composition, and disordered chromatin accessibility. MapsΔ2-9/Δ2-9 male mice expressing MAPS protein lacking aa 2-9 phenocopy Maps-/- mice. Moreover, a frameshift mutation in C3orf62, the human counterpart of Maps, is correlated with nonobstructive azoospermia in a patient exhibiting pachynema arrest in spermatocyte development. Hence, the phase separation property of MAPS seems essential for pachynema progression in mouse and human spermatocytes.

Integrated serum metabolomics and network pharmacology analysis on the bioactive metabolites and mechanism exploration of Bufei huoxue capsule on chronic obstructive pulmonary disease rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufei Huoxue capsule (BHC) as a classic Chinese patent medicine formula, has the efficacy of tonifying the lungs and activating the blood. It has been extensively used in China for the treatment of chronic obstructive pulmonary disease (COPD) clinically. However, its mechanism is still unclear, which hampers the applications of BHC in treating COPD. AIM OF THE STUDY: The purpose of the present study was to demonstrate the protective efficacy and mechanism of BHC on COPD model rats by integrating serum metabolomics analysis and network pharmacology study. MATERIALS AND METHODS: A COPD rat model was established by cigarette fumigation combined with lipopolysaccharide (LPS) airway drip for 90 consecutive days. After oral administration for 30 days, the rats were placed in the body tracing box of the EMKA Small Animal Noninvasive Lung Function Test System to determine lung function related indexes. Histopathological alteration was observed by H&E staining and Masson staining. The serum levels of inflammatory cytokine, matrix metalloprotein 9, and laminin were determined by ELISA kits. Oxidative stress levels were tested by biochemical methods. UHPLC-Q-TOF/MS analysis of serum metabolomics and network pharmacology were performed to reveal the bioactive metabolites, key components and pathways for BHC treating COPD. WB and ELISA kits were used to verify the effects of BHC on key pathway. RESULTS: BHC could improve lung function, immunity, lung histopathological changes and collagen deposition in COPD model rats. It also could significantly reduce inflammatory response in vivo, regulate oxidative stress level, reduce laminin content, and regulate protease-antiprotease balance. Metabolomics analysis found 46 biomarkers of COPD, of which BHC significantly improved the levels of 23 differential metabolites including arachidonic acid, leukotriene B4 and prostaglandin E2. Combined with the results of network pharmacology, the components of BHC, such as calycosin, oxypaeoniflora, (S)-bavachin and neobavaisoflavone could play therapeutic roles through the arachidonic acid pathway. In addition, the results of WB and ELISA indicated that BHC could suppress the expressions of COX2 and 5-LOX in lung tissues and inhibit the generation of AA and its metabolites in serum samples. Regulation of arachidonic acid metabolic pathway may be the crucial mechanism for BHC treating COPD. CONCLUSIONS: In summary, the studies indicated that BHC exhibited the protective effect on COPD model rats by anti-inflammatory and anti-oxidative properties through arachidonic acid metabolism pathway. This study provided beneficial support for the applications of BHC in treating COPD.

A method for estimating yield of maize inbred lines by assimilating WOFOST model with Sentinel-2 satellite data.

Maize is the most widely planted food crop in China, and maize inbred lines, as the basis of maize genetic breeding and seed breeding, have a significant impact on China's seed security and food safety. Satellite remote sensing technology has been widely used for growth monitoring and yield estimation of various crops, but it is still doubtful whether the existing remote sensing monitoring means can distinguish the growth difference between maize inbred lines and hybrids and accurately estimate the yield of maize inbred lines. This paper explores a method for estimating the yield of maize inbred lines based on the assimilation of crop models and remote sensing data, initially solves the problem. At first, this paper analyzed the WOFOST(World Food Studies)model parameter sensitivity and used the MCMC(Markov Chain Monte Carlo) method to calibrate the sensitive parameters to obtain the parameter set of maize inbred lines differing from common hybrid maize; then the vegetation indices were selected to establish an empirical model with the measured LAI(Leaf Area Index) at three key development stages to obtain the remotely sensed estimated LAI; finally, the yield of maize inbred lines in the study area was estimated and mapped pixel by pixel using the EnKF(Ensemble Kalman Filter) data assimilation algorithm. Also, this paper compares a method of assimilation by setting a single parameter. Instead of the WOFOST parameter optimization process, a parameter representing the growth weakness of the inbred lines was set in WOFOST to distinguish the inbred lines from the hybrids. The results showed that the yield estimated by the two methods compared with the field measured yield data had R2: 0.56 and 0.18, and RMSE: 684.90 Kg/Ha and 949.95 Kg/Ha, respectively, which proved that the crop growth model of maize inbred lines established in this study combined with the data assimilation method could initially achieve the growth monitoring and yield estimation of maize inbred lines.

Recognition of H2AK119ub plays an important role in RSF1-regulated early Xenopus development.

Polycomb group (PcG) proteins are key regulators of gene expression and developmental programs via covalent modification of histones, but the factors that interpret histone modification marks to regulate embryogenesis are less studied. We previously identified Remodeling and Spacing Factor 1 (RSF1) as a reader of histone H2A lysine 119 ubiquitination (H2AK119ub), the histone mark deposited by Polycomb Repressive Complex 1 (PRC1). In the current study, we used Xenopus laevis as a model to investigate how RSF1 affects early embryonic development and whether recognition of H2AK119ub is important for the function of RSF1. We showed that knockdown of Xenopus RSF1, rsf1, not only induced gastrulation defects as reported previously, but specific targeted knockdown in prospective neural precursors induced neural and neural crest defects, with reductions of marker genes. In addition, similar to knockdown of PRC1 components in Xenopus, the anterior-posterior neural patterning was affected in rsf1 knockdown embryos. Binding of H2AK119ub appeared to be crucial for rsf1 function, as a construct with deletion of the UAB domain, which is required for RSF1 to recognize the H2AK119ub nucleosomes, failed to rescue rsf1 morphant embryos and was less effective in interfering with early Xenopus development when ectopically expressed. Furthermore, ectopic deposition of H2AK119ub on the Smad2 target gene gsc using a ring1a-smad2 fusion protein led to ectopic recruitment of RSF1. The fusion protein was inefficient in inducing mesodermal markers in the animal region or a secondary axis when expressed in the ventral tissues. Taken together, our results reveal that rsf1 modulates similar developmental processes in early Xenopus embryos as components of PRC1 do, and that RSF1 acts at least partially through binding to the H2AK119ub mark via the UAB domain during development.

Classification and localization of maize leaf spot disease based on weakly supervised learning.

Precisely discerning disease types and vulnerable areas is crucial in implementing effective monitoring of crop production. This forms the basis for generating targeted plant protection recommendations and automatic, precise applications. In this study, we constructed a dataset comprising six types of field maize leaf images and developed a framework for classifying and localizing maize leaf diseases. Our approach involved integrating lightweight convolutional neural networks with interpretable AI algorithms, which resulted in high classification accuracy and fast detection speeds. To evaluate the performance of our framework, we tested the mean Intersection over Union (mIoU) of localized disease spot coverage and actual disease spot coverage when relying solely on image-level annotations. The results showed that our framework achieved a mIoU of up to 55.302%, indicating the feasibility of using weakly supervised semantic segmentation based on class activation mapping techniques for identifying disease spots in crop disease detection. This approach, which combines deep learning models with visualization techniques, improves the interpretability of the deep learning models and achieves successful localization of infected areas of maize leaves through weakly supervised learning. The framework allows for smart monitoring of crop diseases and plant protection operations using mobile phones, smart farm machines, and other devices. Furthermore, it offers a reference for deep learning research on crop diseases.

Maize-YOLO: A New High-Precision and Real-Time Method for Maize Pest Detection.

The frequent occurrence of crop pests and diseases is one of the important factors leading to the reduction of crop quality and yield. Since pests are characterized by high similarity and fast movement, this poses a challenge for artificial intelligence techniques to identify pests in a timely and accurate manner. Therefore, we propose a new high-precision and real-time method for maize pest detection, Maize-YOLO. The network is based on YOLOv7 with the insertion of the CSPResNeXt-50 module and VoVGSCSP module. It can improve network detection accuracy and detection speed while reducing the computational effort of the model. We evaluated the performance of Maize-YOLO in a typical large-scale pest dataset IP102. We trained and tested against those pest species that are more damaging to maize, including 4533 images and 13 classes. The experimental results show that our method outperforms the current state-of-the-art YOLO family of object detection algorithms and achieves suitable performance at 76.3% mAP and 77.3% recall. The method can provide accurate and real-time pest detection and identification for maize crops, enabling highly accurate end-to-end pest detection.

Cropformer: A new generalized deep learning classification approach for multi-scenario crop classification.

Accurate and efficient crop classification using remotely sensed data can provide fundamental and important information for crop yield estimation. Existing crop classification approaches are usually designed to be strong in some specific scenarios but not for multi-scenario crop classification. In this study, we proposed a new deep learning approach for multi-scenario crop classification, named Cropformer. Cropformer can extract global features and local features, to solve the problem that current crop classification methods extract a single feature. Specifically, Cropformer is a two-step classification approach, where the first step is self-supervised pre-training to accumulate knowledge of crop growth, and the second step is a fine-tuned supervised classification based on the weights from the first step. The unlabeled time series and the labeled time series are used as input for the first and second steps respectively. Multi-scenario crop classification experiments including full-season crop classification, in-season crop classification, few-sample crop classification, and transfer of classification models were conducted in five study areas with complex crop types and compared with several existing competitive approaches. Experimental results showed that Cropformer can not only obtain a very significant accuracy advantage in crop classification, but also can obtain higher accuracy with fewer samples. Compared to other approaches, the classification performance of Cropformer during model transfer and the efficiency of the classification were outstanding. The results showed that Cropformer could build up a priori knowledge using unlabeled data and learn generalized features using labeled data, making it applicable to crop classification in multiple scenarios.

The Pleiotropic Ubiquitin-Specific Peptidase 16 and Its Many Substrates.

Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase that plays a role in the regulation of gene expression, cell cycle progression, and various other functions. It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. The strong connection to immune response and the fact that multiple oncogene products are substrates of USP16 suggests that USP16 may be a potential therapeutic target for the treatment of certain human diseases.

Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16's recruitment to chromatin, thereby blocking USP16-mediated H2A deubiquitination and repressing target gene expression, including CDKN1A and CLUSTERIN. Depletion of lncEPAT promoted USP16-induced cell cycle arrest and cellular senescence, and then repressed GBM cell tumorigenesis. Thus, the EGFR-lncEPAT-ubH2A coupling represents a previously unidentified mechanism for epigenetic gene regulation and senescence resistance during GBM tumorigenesis.

PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression.

Polycomb group (PcG) proteins are known to repress developmental genes during embryonic development and tissue homeostasis. Here, we report that PCGF6 controls neuroectoderm specification of human pluripotent stem cells (PSCs) by activating SOX2 gene. Human PSCs with PCGF6 depletion display impaired neuroectoderm differentiation coupled with increased mesendoderm outcomes. Transcriptome analysis reveals that de-repression of the WNT/ß-catenin signaling pathway is responsible for the differentiation of PSC toward the mesendodermal lineage. Interestingly, PCGF6 and MYC directly interact and co-occupy a distal regulatory element of SOX2 to activate SOX2 expression, which likely accounts for the regulation in neuroectoderm differentiation. Supporting this notion, genomic deletion of the SOX2-regulatory element phenocopies the impaired neuroectoderm differentiation, while overexpressing SOX2 rescues the neuroectoderm phenotype caused by PCGF6-depletion. Together, our study reveals that PCGF6 can function as lineage switcher between mesendoderm and neuroectoderm in human PSCs by both suppression and activation mechanisms.

[Determination of eight active components of Bufei Huoxue Capsules in rat plasma and their pharmacokinetics by UHPLC-MS/MS].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) µg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.

The male germline-specific protein MAPS is indispensable for pachynema progression and fertility.

Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail 1700102P08Rik, one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking Maps (Maps-/- ) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps-/- spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult Maps-/- spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult Maps-/- pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in Maps-/- pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.

Glass Transition Temperature and Ion Binding Determine Conductivity and Lithium-Ion Transport in Polymer Electrolytes.

Polymer electrolytes with high Li+-ion conductivity provide a route toward improved safety and performance of Li+-ion batteries. However, most polymer electrolytes suffer from low ionic conduction and an even lower Li+-ion contribution to the conductivity (the transport number, t+), with the anion typically transporting over 80% of the charge. Here, we show that subtle and potentially undetected associations within a polymer electrolyte can entrain both the anion and the cation. When removed, the conductivity performance of the electrolyte can be improved by almost 2 orders of magnitude. Importantly, while some of this improvement can be attributed to a decreased glass transition temperature, Tg, the removal of the amide functional group reduces interactions between the polymer and the Li+ cations, doubling the Li+ t+ to 0.43, as measured using pulsed-field-gradient NMR. This work highlights the importance of strategic synthetic design and emphasizes the dual role of Tg and ion binding for the development of polymer electrolytes with increased total ionic conductivity and the Li+ ion contribution to it.

Room temperature 3D printing of super-soft and solvent-free elastomers.

Super-soft elastomers derived from bottlebrush polymers show promise as advanced materials for biomimetic tissue and device applications, but current processing strategies are restricted to simple molding. Here, we introduce a design concept that enables the three-dimensional (3D) printing of super-soft and solvent-free bottlebrush elastomers at room temperature. The key advance is a class of inks comprising statistical bottlebrush polymers that self-assemble into well-ordered body-centered cubic sphere phases. These soft solids undergo sharp and reversible yielding at 20°C in response to shear with a yield stress that can be tuned by manipulating the length scale of microphase separation. The addition of a soluble photocrosslinker allows complete ultraviolet curing after extrusion to form super-soft elastomers with near-perfect recoverable elasticity well beyond the yield strain. These structure-property design rules create exciting opportunities to tailor the performance of 3D-printed elastomers in ways that are not possible with current materials and processes.