Human iPSC-based breast cancer model identifies S100P-dependent cancer stemness induced by mutation.

Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs).

Breaking a chromatin domain boundary by deleting a single CTCF motif impacts development.

Chromatin domain boundaries are crucial for development by spatially constraining enhancer activity to ensure precise spatiotemporal gene regulation. In this issue of Developmental Cell, Chakraborty et al. demonstrate that the loss of a chromatin domain boundary caused by deletion of a single CTCF motif can lead to severe developmental defects.

Revisiting the classical biodiversity-ecosystem functioning and stability relationships in microbial microcosms.

The question of how biodiversity influences ecosystem functioning and stability has been a central focus in ecological research. Yet, this question remains unresolved, primarily because of the widely divergent definitions of functioning, stability, and diversity. Consequently, forecasts of ecosystem services will remain speculative until we can establish more precise and comprehensive definitions for these concepts than previously.

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.

RAF protein kinases are major RAS effectors that function by phosphorylating MEK. Although all three RAF isoforms share a conserved RAS binding domain and bind to GTP-loaded RAS, only ARAF uniquely enhances RAS activity. Here we uncovered the molecular basis of ARAF in regulating RAS activation.

Research on wear and grinding models of high-speed turnouts based on semi-Hertz contact.

In order to reduce turnout rail wear, the paper establishes a coupled dynamics model and a turnout rail wear model that consider the true profile of the turnout rail, the vehicle's continuous traction force while passing, and the operational resistance. Comparative analysis of various models for predicting turnout rail wear indicates that the wear energy model is better suited for this purpose. The ideal profile update step for the turnout rail is 0.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Nuclear remodeling during cell fate transitions.

Totipotent stem cells, the earliest cells in embryonic development, can differentiate into complete embryos and extra-embryonic tissues, making them essential for understanding both development and regenerative medicine. This review examines recent advances in the dynamic remodeling of nuclear structures during the transition between totipotency and pluripotency, as well as other cell fate transition processes. Additionally, we highlight innovative experimental and computational methods that elucidate the relationship between nuclear architecture and cell fate decisions.

Disorganized chromatin hierarchy and stem cell aging in a male patient of atypical laminopathy-based progeria mandibuloacral dysplasia type A.

Studies of laminopathy-based progeria offer insights into aging-associated diseases and highlight the role of LMNA in chromatin organization. Mandibuloacral dysplasia type A (MAD) is a largely unexplored form of atypical progeria that lacks lamin A post-translational processing defects. Using iPSCs derived from a male MAD patient carrying homozygous LMNA p.

Multiscale 3D genome rewiring during PTF1A-mediated somatic cell reprogramming into neural stem cells.

The genome is intricately folded into chromatin compartments, topologically associating domains (TADs) and loops unique to each cell type. How this higher-order genome organization regulates cell fate transition remains elusive. Here we show how a single non-neural progenitor transcription factor, PTF1A, reorchestrates the 3D genome during fibroblast transdifferentiation into neural stem cells (NSCs).

High Areal Capacitance and Rate Capability of 3D-Printed Thick Electrodes with Optimized Conductive Networks from the Core-Sheath Structure.

Material extrusion 3D printing has received enormous attention to potentially overcome its limits by tailoring and designing thick electrodes. In this work, we prepared a thick reduced graphene oxide/carbon nanotube-reduced graphene oxide/carbon nanotubes/manganese oxide@carbon nanotubes (rGC-rGCMC) electrode with controlled lattice architectures, core-sheath structure, and hierarchical porosity by material coaxial extrusion 3D printing, freeze-drying, and thermal treatment. The volume ratios of core to sheath, including 100%-0%, 0%-100%, 20%-80%, 30%-70%, 40%-60%, and 50%-50%, were designed to investigate the influences of the core-sheath structure on thick electrodes.

Xiaoyao Pills, a Chinese patent medicine, treats mild and moderate depression: A randomized clinical trial combined with DNA methylation analysis.

Background: Xiaoyao pills (XYP) is a commercial Chinese patent medicine used in the treatment of depression. However, the mechanisms underlying its therapeutic effects, as well as the patients who can benefit from XYP, have not been evaluated so far.

Objectives: To this end, we conducted a double-blinded, random, and placebo-controlled clinical trial of orally administered XYP in patients with depression.

The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation.

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood.

Precise prediction of phase-separation key residues by machine learning.

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme.

[Role of Liquid-Liquid Phase Separation in Cell Fate Transition and Diseases].

Liquid-liquid phase separation (LLPS), a novel mechanism of the organization and formation of cellular structures, plays a vital role in regulating cell fate transitions and disease pathogenesis and is gaining widespread attention. LLPS may lead to the assemblage of cellular structures with liquid-like fluidity, such as germ granules, stress granules, and nucleoli, which are classic membraneless organelles. These structures are typically formed through the high-concentration liquid aggregation of biomacromolecules driven by weak multivalent interactions.

Photo-Induced, Phenylhydrazine-Promoted Transition-Metal-Free Dehalogenation of Aryl Fluorides, Chlorides, Bromides, and Iodides.

In this study, we present a straightforward and highly effective photo-triggered hydrogenation method for aryl halides, devoid of transition-metal catalysts. Through the synergistic utilization of light, PhNHNH, and a base, we have successfully initiated the desired radical-mediated hydrogenation process. Remarkably, utilizing mild reaction conditions, a wide range of aryl halides, including fluorides, chlorides, bromides, and iodides, can be selectively transformed into their corresponding (hetero)arene counterparts, with exceptional yields.

Simultaneous profiling of chromatin architecture and transcription in single cells.

The three-dimensional structure of chromatin plays a crucial role in development and disease, both of which are associated with transcriptional changes. However, given the heterogeneity in single-cell chromatin architecture and transcription, the regulatory relationship between the three-dimensional chromatin structure and gene expression is difficult to explain based on bulk cell populations. Here we develop a single-cell, multimodal, omics method allowing the simultaneous detection of chromatin architecture and messenger RNA expression by sequencing (single-cell transcriptome sequencing (scCARE-seq)).

Electronic Beam Steering Metamaterial Antenna with Dual-Tuned Mode of Liquid Crystal Material.

In this study, a dual-tuned mode of liquid crystal (LC) material was proposed and adopted on reconfigurable metamaterial antennas to expand the fixed-frequency beam-steering range. The novel dual-tuned mode of the LC is composed of double LC layers combined with composite right/left-handed (CRLH) transmission line theory. Through a multi-separated metal layer, the double LC layers can be loaded with controllable bias voltage independently.

A decade of liver organoids: Advances in disease modeling.

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches.

The dynamics of three-dimensional chromatin organization and phase separation in cell fate transitions and diseases.

Cell fate transition is a fascinating process involving complex dynamics of three-dimensional (3D) chromatin organization and phase separation, which play an essential role in cell fate decision by regulating gene expression. Phase separation is increasingly being considered a driving force of chromatin folding. In this review, we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure.

Apoptotic vesicles inherit SOX2 from pluripotent stem cells to accelerate wound healing by energizing mesenchymal stem cells.

Billions of cells undergo apoptosis every day in the human body, resulting in the generation of a large number of apoptotic vesicles (apoVs) to maintain organ and tissue homeostasis. However, the characteristics and function of pluripotent stem cell (PSC)-derived apoVs (PSC-apoVs) are largely unknown. In this study, we showed that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) produced larger numbers of apoVs than human umbilical cord mesenchymal stem cells (UMSCs) do when induced by staurosporine.

CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation.

Chromatin is spatially organized into three-dimensional structures at different levels including A/B compartments, topologically associating domains and loops. The canonical CTCF-mediated loop extrusion model can explain the formation of loops. However, the organization mechanisms underlying long-range chromatin interactions such as interactions between A-A compartments are still poorly understood.

Estrogen and BRCA1 deficiency synergistically induce breast cancer mutation-related DNA damage.

Estrogen (E2) is crucial for the development of breast cancer caused by BRCA1 mutation, and can increase the DNA damage in BRCA1-deficient cells. However, the mechanisms through which BRCA1 deficiency and E2 synergistically induce DNA damage remains unclear. In this study, we analyzed the distribution of DNA damage in E2-treated BRCA1-deficient cells.