Adaptive Hierarchical Origami Metastructures

Shape-morphing capabilities are crucial for enabling multifunctionality in both biological and artificial systems. Various strategies for shape morphing have been proposed for applications in metamaterials and robotics. However, few of these approaches have achieved the ability to seamlessly transform into a multitude of volumetric shapes post-fabrication using a relatively simple actuation and control mechanism. Taking inspiration from thick origami and hierarchies in nature, we present a new hierarchical construction method based on polyhedrons to create an extensive library of compact origami metastructures. We show that a single hierarchical origami structure can autonomously adapt to over 103 versatile architectural configurations, achieved with the utilization of fewer than 3 actuation degrees of freedom and employing simple transition kinematics. We uncover the fundamental principles governing theses shape transformation through theoretical models. Furthermore, we also demonstrate the wide-ranging potential applications of these transformable hierarchical structures. These include their uses as untethered and autonomous robotic transformers capable of various gait-shifting and multidirectional locomotion, as well as rapidly self-deployable and self-reconfigurable architecture, exemplifying its scalability up to the meter scale. Lastly, we introduce the concept of multitask reconfigurable and deployable space robots and habitats, showcasing the adaptability and versatility of these metastructures

Discovery of New Eunicellins from an Indonesian Octocoral Cladiella sp.

Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (–)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study

Excavatoids O and P, New 12-Hydroxybriaranes from the Octocoral Briareum excavatum

Two new 12-hydroxybriarane diterpenoids, designated as excavatoids O (1) and P (2), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1 and 2 were established on the basis of extensive spectral data analysis. Excavatoid P (2) is the first metabolite which possesses a 6β -chlorine atom in briarane analogues

Solution processed graphene structures for perovskite solar cells

Organometallic trihalide perovskite light absorber based solar cells have drawn increasing attention because of their recent rapid increase in power conversion efficiency (PCE). These photovoltaic cells have relied significantly on transparent conducting oxide (TCO) electrodes which are costly and brittle. Herein, solution processed transparent conductive graphene films (TCGFs) are utilized, for the first time, as an alternative to traditional TCO electrodes at the electron collecting layer in perovskite solar cells (PSCs). By investigating and optimizing the trade-off between transparency and sheet resistance (Rs) of the graphene films, a PCE of 0.62% is achieved. This PCE is further improved to 0.81% by incorporating graphene structures into both compact and mesoporous TiO2 layers of the solar cell. We anticipate that the present study will lead to further work to develop graphene-based transparent conductive electrodes for future solar cell devices

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse

BACKGROUND: Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%). RESULTS: We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects. CONCLUSIONS: These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components

Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast cancer and their prognostic value has not been well documented in Asians.</p> <p>Methods</p> <p>A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by centralized pathology review. The average follow-up of the patients was 53.4 months. Overall and disease-free survival by molecular subtypes of breast cancer were evaluated.</p> <p>Results</p> <p>The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative subtypes were 48.6%, 16.7%, 13.7%, and 12.9%, respectively. The luminal A subtype was more likely to be diagnosed in older women (P = 0.03) and had a stronger correlation with favorable clinicopathological factors (smaller tumor size, lower histologic grade, and earlier TNM stage) than the triple-negative or HER2 subtypes. Women with triple-negative breast cancer had a higher frequency of family history of breast cancer than women with other subtypes (P = 0.048). The 5-year overall/disease-free survival percentages for the luminal A, luminal B, HER2, and triple-negative subtypes were 92.9%/88.6%, 88.6%/85.1%, 83.2%/79.1%, and 80.7%/76.0%, respectively. A similar pattern was observed in multivariate analyses. Immunotherapy was associated with improved overall and disease-free survival for luminal A breast cancer, but reduced disease-free survival (HR = 2.21, 95% CI, 1.09-4.48) for the HER2 subtype of breast cancer.</p> <p>Conclusions</p> <p>The triple-negative and HER2 subtypes were associated with poorer outcomes compared with the luminal A subtype among these Chinese women. The HER2 subtype was more prevalent in this Chinese population compared with Western populations, suggesting the importance of standardized HER2 detection and anti-HER2 therapy to potentially benefit a high proportion of breast cancer patients in China.</p

Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Model-independent evidence for J/ψpJ/\psi p contributions to Λb0→J/ψpK−\Lambda_b^0\to J/\psi p K^- decays

The data sample of $\Lambda_b^0\to J/\psi p K^-$ decays acquired with the LHCb detector from 7 and 8~TeV $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$, is inspected for the presence of $J/\psi p$ or $J/\psi K^-$ contributions with minimal assumptions about $K^- p$ contributions. It is demonstrated at more than 9 standard deviations that $\Lambda_b^0\to J/\psi p K^-$ decays cannot be described with $K^- p$ contributions alone, and that $J/\psi p$ contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for $P_c^+\to J/\psi p$ charmonium-pentaquark states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the end