Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates.

Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

High-gain ultra-wideband bismuth-doped fiber amplifier operating in the O + E + S band.

We present a double-pass bismuth (Bi)-doped fiber amplifier (BDFA) providing high-gain wideband amplification from 1330 to 1480 nm. A peak gain of 38 dB with 4.7 dB noise figure (NF) was obtained at 1420 nm for a -23 dBm input signal, with >20 dB gain from 1335 to 1475 nm. We achieved 30  and 21.5 dB peak gains with 122 nm (1341-1463 nm) and 140 nm (1333-1473 nm) 6 dB-gain bandwidth for -10 and 0 dBm input signal, respectively. For a 0 dBm signal, the power conversion efficiency (PCE) reached 23.7%, and the in-band optical-signal-to-noise ratio (OSNR) across the wideband BDFA was >44 dB. Also, the absorption and luminescence characteristics have been studied for different Bi-doped phosphosilicate fibers (BPSFs) fabricated in-house.

Fine-tuned local coordination environment of Pt-N in nanocarbons for efficient propane dehydrogenation.

Based on the disturbance of electronic density, nitrogen-doped nanocarbons show promising properties to anchor metal clusters. However, precisely regulating the coordination mode between N species and the active site remains challenging. Herein, we rationally designed three N types (graphitic N, pyridinic N and pyrrolic N) in nanocarbons to anchor Pt clusters for the benchmark propane dehydrogenation. The specific activity of the pyridinic-N-doped catalyst was 147.54 molC3H6 molPt-1 h-1 at 550 °C, which was 1.3 times higher than those of graphitic- and pyrrolic-N-doped catalysts. Unlike the regular tetrahedron Pt cluster in the graphitic-N catalyst or the distorted three-layered Pt cluster in the pyrrolic-N catalyst, the Pt cluster in the pyridinic-N catalyst was an inverted tetrahedron, which increased the contact degree without geometric repulsion towards C-H bond scission. The geometric parameters of detached H and C atoms in the methylene group for the pyridinic N catalyst was decreased to strengthen the C-H bond scission. After CH3CHCH3* adsorption, the Bader charge of the Pt active site also became highly positive, which tailored the d-band center closer to the Fermi level and provided more vacant orbitals for C-H bond breakage. Therefore, pyridinic N in nanocarbons is promising to anchor small-sized Pt for alkane dehydrogenation in terms of geometric and electronic effects.

Radiation-resistant cerium co-doped erbium-doped fibers for C- and L-band amplifiers in a high-dose gamma-radiation environment.

We experimentally demonstrate a comparative study on the radiation-resistant cerium (Ce) co-doped erbium-doped fiber amplifiers (EDFAs) exposed to a high-dose gamma-radiation environment of 1.8 kGy/h dose rate in the C and L bands. Our results show that Ce is an effective co-dopant in the aluminosilicate EDFs for suppressing radiation-induced attenuation (RIA) of more than an order of magnitude lower than the Ce-free EDF. After exposure to a high-dose gamma-radiation of up to 10 kGy, the Ce co-doped EDF still exhibits good radiation tolerance, providing 41.6 ± 2.9 dB gain and 5 ± 0.8 dB NF from 1535-1560 nm for a -25 dBm input signal. In the L-band, we report, for the first time, the radiation-resistant EDFA with the radiation-induced gain degradation (RIGD) of 3.7 dB under 2.5 kGy irradiation and 4.4 dB under 10 kGy irradiation at 1600 nm. Also, the radiation-dependent gain coefficient and gain saturation were studied in the C and L bands. A comparison of different Ce co-doped EDFs exposed to different total gamma doses reveals the radiation impact on the amplifier performance, indicating the feasibility of using Ce co-doped EDFs for space-based optical communications, requiring robust radiation stability.

Flat-gain L-band amplifier containing AlPO4 units in aluminophosphosilicate erbium-doped fibers.

We present a flat-gain single-stage L-band erbium-doped fiber amplifier (EDFA) with a gain ripple of ±0.7 dB from 1580 to 1615 nm, by using aluminophosphosilicate erbium-doped fiber (APS-EDF) with an estimated AlPO4 composition of 13.3 mol%. A series of APS-EDFs were fabricated with increasing AlPO4 and Er concentrations, while maintaining a low background loss of 0.031 ± 0.005 dB/m and preventing Er ion clustering. The spectroscopic study shows a slightly narrowing Er cross section and flattened emission cross-section spectrum in the L-band with more AlPO4, thus favoring the L-band amplification with an improved gain flatness. Also, the gain coefficient, gain saturation, and temperature-dependent gain characteristics were reported. A better temperature tolerance was observed with increasing AlPO4.

Bi-doped fiber amplifiers in the E + S band with a high gain per unit length.

We present a bismuth (Bi)-doped fiber amplifier (BDFA) operating in the 1400-1480 nm range using 35 m of Bi-doped germanosilicate fiber. A maximum gain of 23 dB for an input signal of -23dBm at 1440 nm has been achieved, which, to the best of our knowledge, is the highest gain per unit length of 0.66 dB/m reported for a BDFA. The 3 dB bandwidth is measured to be 40 nm (1415-1455 nm), and the gain coefficient is 0.2 dB/mW. A further temperature dependence study of BDFA across the temperature range of -60°C to 80°C also showed a negligible effect of temperature on the E + S band BDFA gain.

Revealing the promotion of carbonyl groups on vacancy stabilized Pt4/nanocarbons for propane dehydrogenation.

Nanocarbons are promising supports for Pt clusters applied in propane dehydrogenation (PDH), owing to their large surface areas and tunable chemical properties. The vacancies and oxygen-containing groups (OCGs) in nanocarbons can enhance catalytic performance by tailoring the coordination environment of Pt clusters. Herein, 46 nanocarbons with coexisting vacancies and OCGs were designed to support Pt clusters, of which the influences on PDH were revealed by density functional theory calculations. Nanocarbons with divacancies (V2) and CO edge groups were screened out as the most appropriate support for Pt clusters in PDH. Due to the V2, tetrahedral Pt clusters were distorted into three-layered configurations, contributing to enhanced binding strength and a favorable reactive pathway starting from the methylene group in propane. This changed the rate-determining step to the first C-H bond scission with a low energy barrier. The introduction of CO edge groups coexisting with V2 further improved the stabilization of Pt clusters, resulting from the increased electron transfer from Pt atoms to C atoms. The abilities to break C-H bonds and inhibit C-C bond cracking were also enhanced as compared to the nanocarbons with only V2. Therefore, this work provides references on the regulation of vacancies and OCGs in carbon-based catalysts.

Tailoring the catalytic performance of single platinum anchored on graphene by vacancy engineering for propane dehydrogenation: a theoretical study.

Propane dehydrogenation (PDH) is an effective approach to produce propylene. Downsizing the Pt species to single atom catalysts (SACs) has become a hotspot, owing to the maximum utilization and excellent catalytic behavior. However, the agglomeration of SACs is the decisive limitation for high temperature PDH. Herein, single Pt atoms were anchored on graphene with different types of vacancies, and their catalytic performances on PDH were explored based on density functional theory (DFT). As the vacancy size increased, the catalytic activity decreased. It was because the combined site of the detached H atom in propane would transfer from the Pt atom to the C atom around vacancies, thus increasing the migration distance and lowering the activity. However, with the increase of vacancy size, the selectivity to propylene was improved, owing to the enhanced repulsion between C atoms in graphene and propylene. Therefore, instead of stabilizing the single atom, vacancies in carbon materials can also tailor the catalytic performance by geometric disturbance. This fundamental work opens up the possibility for purposeful SAC design in PDH.

Exploring the reaction mechanism of ethanol synthesis from acetic acid over a Ni2In(100) surface.

A low-cost and high-efficiency nickel-indium bimetallic catalyst is designed to improve the activity of acetic acid hydrogenation to ethanol, which can make full use of the overproduced acetic acid. In this work, density functional theory (DFT) calculations are carried out to explore the mechanism of ethanol synthesis from acetic acid on the Ni2In(100) surface and tailor the catalyst to acquire enhanced properties. The results show that the most feasible pathway is CH3COOH → CH3CO → CH3CHO → CH3CHOH → CH3CH2OH, and the rate-determining step is the hydrogenation of CH3CHOH* to CH3CH2OH, with an activation barrier of 1.20 eV and an endothermic energy of 0.15 eV. Compared with the Cu2In(100) surface, the Ni2In(100) surface converts the reaction pathway to the acetyl species direction, which shows great advantages for the following CH3CHO* formation. Furthermore, the effects of indium doping in the nickel catalyst on the side reaction is also discussed by comparing with the monometallic Ni(111) surface. The addition of indium turns out to cause a significant inhibition on the C-C bond breaking and is beneficial for promoting the acetic acid hydrogenation to ethanol. Electronic analysis proves that the role of In is to donate electrons, which can increase the electron density of Ni and enhance the catalytic activity.

The synergistic effects of Cu clusters and In2O3 on ethanol synthesis from acetic acid hydrogenation.

The development of high efficiency catalysts for acetic acid hydrogenation to ethanol could ameliorate the petroleum crisis and acetic acid overproduction. Cu and In2O3 catalysts both show catalytic activity for acetic acid hydrogenation. However, monometallic Cu catalysts are less active in the dissociative adsorption of acetic acid through C-O bond breaking, while the H2 adsorption and dissociation ability of In2O3 is weak. In this work, Cu4/In2O3 is designed to enhance the dissociation of both acetic acid and H2. The detailed mechanism of acetic acid hydrogenation to ethanol on Cu4/In2O3 is explored using periodic density functional theory (DFT). The results show that the H2 adsorption and dissociation are enhanced by the Cu cluster, while the H atom spillover from Cu to In2O3 is favorable on the Cu4/In2O3(110) surface. Additionally, a synergistic effect exists between the Cu cluster and In2O3 surface: H2 adsorbs on the Cu cluster and the dissociated H atoms react with acetic acid activated by the In2O3 oxygen vacancy. Finally, compared with a Cu2In(100) surface, the Cu4/In2O3(110) surface possesses higher catalytic activity owing to the reduced energy barriers of acetic acid dissociation and hydrogenation of the intermediates (CH3COO*, CH3CHO*, and CH3CH2O*). The Cu4/In2O3 catalyst proposed in this work can provide promising guidance for related catalyst design.

Liquid-liquid phase separation (LLPS) in DNA and chromatin systems from the perspective of colloid physical chemistry.

DNA is a highly charged polyelectrolyte and is prone to associative phase separation driven by the presence of multivalent cations, charged surfactants, proteins, polymers and colloids. The process of DNA phase separation induced by positively charged species is often called DNA condensation. Generally, it refers to either intramolecular DNA compaction (coil-globule transition) or intermolecular DNA aggregation with macroscopic phase separation, but the formation of a DNA liquid crystalline system is also displayed. This has traditionally been described by polyelectrolyte theory and qualitative (Flory-Huggins-based) polymer theory approaches. DNA in the cell nucleus is packed into chromatin wound around the histone octamer (a protein complex comprising two copies each of the four histone proteins H2A, H2B, H3 and H4) to form nucleosomes separated by linker DNA. During the last decade, the phenomenon of the formation of biomolecular condensates (dynamic droplets) by liquid-liquid phase separation (LLPS) has emerged as a generally important mechanism for the formation of membraneless organelles from proteins, nucleic acids and their complexes. DNA and chromatin droplet formation through LLPS has recently received much attention by in vitro as well as in vivo studies that established the importance of this for compartmentalisation in the cell nucleus. Here, we review DNA and chromatin LLPS from a general colloid physical chemistry perspective. We start with a general discussion of colloidal phase separation in aqueous solutions and review the original (pre-LLPS era) work on DNA (macroscopic) phase separation for simpler systems with DNA in the presence of multivalent cations and well-defined surfactants and colloids. Following that, we discuss and illustrate the similarities of such macroscopic phase separation with the general behaviour of LLPS droplet formation by associative phase separation for DNA-protein systems, including chromatin; we also note cases of segregative association. The review ends with a discussion of chromatin LLPS in vivo and its physiological significance.

Recent Advances in Investigating Functional Dynamics of Chromatin.

Dynamics spanning the picosecond-minute time domain and the atomic-subcellular spatial window have been observed for chromatin in vitro and in vivo. The condensed organization of chromatin in eukaryotic cells prevents regulatory factors from accessing genomic DNA, which requires dynamic stabilization and destabilization of structure to initiate downstream DNA activities. Those processes are achieved through altering conformational and dynamic properties of nucleosomes and nucleosome-protein complexes, of which delineating the atomistic pictures is essential to understand the mechanisms of chromatin regulation. In this review, we summarize recent progress in determining chromatin dynamics and their modulations by a number of factors including post-translational modifications (PTMs), incorporation of histone variants, and binding of effector proteins. We focus on experimental observations obtained using high-resolution techniques, primarily including nuclear magnetic resonance (NMR) spectroscopy, Förster (or fluorescence) resonance energy transfer (FRET) microscopy, and molecular dynamics (MD) simulations, and discuss the elucidated dynamics in the context of functional response and relevance.

H3K27ac mediated SS18/BAFs relocation regulates JUN induced pluripotent-somatic transition.

BACKGROUND: The exit from pluripotency or pluripotent-somatic transition (PST) landmarks an event of early mammalian embryonic development, representing a model for cell fate transition. RESULTS: In this study, using a robust JUN-induced PST within 8 h as a model, we investigate the chromatin accessibility dynamics (CAD) as well as the behaviors of corresponding chromatin remodeling complex SS18/BAFs, to probe the key events at the early stage of PST. Here, we report that, JUN triggers the open of 34661 chromatin sites within 4 h, accomplished with the activation of somatic genes, such as Anxa1, Fosl1. ChIP-seq data reveal a rapid relocation of SS18/BAFs from pluripotent loci to AP-1 associated ones. Consistently, the knockdown of Brg1, core component of BAF complexes, leads to failure in chromatin opening but not closing, resulting in delay for JUN induced PST. Notably, the direct interaction between SS18/BAFs and JUN-centric protein complexes is undetectable by IP-MS. Instead, we show that H3K27ac deposited by cJUN dependent process regulates SS18/BAFs complex to AP1-containing loci and facilitate chromatin opening and gene activation. CONCLUSIONS: These results reveal a rapid transfer of chromatin remodeling complexes BAF from pluripotent to somatic loci during PST, revealing a simple mechanistic aspect of cell fate control.

Subsurface-Regulated PtGa Nanoparticles Confined in Silicalite-1 for Propane Dehydrogenation.

Propane dehydrogenation (PDH) is one of the most promising techniques to produce propylene. Industrial Pt-based catalysts often suffer from short-time stability under high temperature due to serious sintering and coke deposition via undesired side reactions. Detailed reaction mechanism on the surface of Pt-based nanoparticle has been well studied, while the subsurface effect remains mostly unstudied. Herein, supported PtGa nanoparticles with different surface and subsurface composition was evidenced by extended X-ray absorption fine structure (EAXFS) spectra and energy dispersive X-ray spectroscopy (EDS). Theoretical simulation demonstrated subsurface regulation would increase the electron density of surface Pt and thus weaken propylene adsorption. Propylene selectivity on the PtGa-subsurface nanoparticles was up to 98% at 600 °C while that on the Pt-subsurface nanoparticles was only 95%. Furthermore, rational designed PtGa alloy nanoparticles were encapsulated in MFI zeolite to inhibit sintering and coke deposition for enhanced catalytic stability.

SS18 regulates pluripotent-somatic transition through phase separation.

The transition from pluripotent to somatic states marks a critical event in mammalian development, but remains largely unresolved. Here we report the identification of SS18 as a regulator for pluripotent to somatic transition or PST by CRISPR-based whole genome screens. Mechanistically, SS18 forms microscopic condensates in nuclei through a C-terminal intrinsically disordered region (IDR) rich in tyrosine, which, once mutated, no longer form condensates nor rescue SS18-/- defect in PST. Yet, the IDR alone is not sufficient to rescue the defect even though it can form condensates indistinguishable from the wild type protein. We further show that its N-terminal 70aa is required for PST by interacting with the Brg/Brahma-associated factor (BAF) complex, and remains functional even swapped onto unrelated IDRs or even an artificial 24 tyrosine polypeptide. Finally, we show that SS18 mediates BAF assembly through phase separation to regulate PST. These studies suggest that SS18 plays a role in the pluripotent to somatic interface and undergoes liquid-liquid phase separation through a unique tyrosine-based mechanism.

Screening Genes Promoting Exit from Naive Pluripotency Based on Genome-Scale CRISPR-Cas9 Knockout.

Two of the main problems of stem cell and regenerative medicine are the exit of pluripotency and differentiation to functional cells or tissues. The answer to these two problems holds great value in the clinical translation of stem cell as well as regenerative medicine research. Although piling researches have revealed the truth about pluripotency maintenance, the mechanisms underlying pluripotent cell self-renewal, proliferation, and differentiation into specific cell lineages or tissues are yet to be defined. To this end, we took full advantage of a novel technology, namely, the genome-scale CRISPR-Cas9 knockout (GeCKO). As an effective way of introducing targeted loss-of-function mutations at specific sites in the genome, GeCKO is able to screen in an unbiased manner for key genes that promote exit from pluripotency in mouse embryonic stem cells (mESCs) for the first time. In this study, we successfully established a model based on GeCKO to screen the key genes in pluripotency withdrawal. Our strategies included lentiviral package and infection technology, lenti-Cas9 gene knockout technology, shRNA gene knockdown technology, next-generation sequencing, model-based analysis of genome-scale CRISPR-Cas9 knockout (MAGeCK analysis), GO analysis, and other methods. Our findings provide a novel approach for large-scale screening of genes involved in pluripotency exit and offer an entry point for cell fate regulation research.