Understanding the site interaction nature of single‐atom catalysts (SACs), especially densely populated SACs, is vital for their application to various catalytic reactions. Herein, we report a site ...distance effect, which emphasizes how well the distance of the adjacent copper atoms (denoted as dCu1−Cu1) matches with the reactant peroxydisulfate (PDS) molecular size to determine the Fenton‐like reaction reactivity on the carbon‐supported SACs. The optimized dCu1−Cu1 in the range of 5–6 Å, which matches the molecular size of PDS, endows the catalyst with a nearly two times higher turnover frequency than that of dCu1−Cu1 beyond this range, accordingly achieving record‐breaking kinetics for the oxidation of emerging organic contaminants. Further studies suggest that this site distance effect originates from the alteration of PDS adsorption to a dual‐site structure on Cu1−Cu1 sites when dCu1−Cu1 falls within 5–6 Å, significantly enhancing the interfacial charge transfer and consequently resulting in the most efficient catalyst for PDS activation so far.
Site distance effects are important in a Cu1/N‐doped graphene (Cu1/GN) single‐atom catalyst with record‐breaking kinetics in the oxidation of emerging organic pollutants. A strategy is reported to achieve the desired catalyst behavior by matching the active site with the properties of the reaction molecule peroxydisulfate (PDS).
In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial ...chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population.
In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m
, leucovorin 400 mg/m
, fluorouracil bolus 400 mg/m
on day 1, and fluorouracil infusion 2,400 mg/m
for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment.
Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75;
< .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 46%
28 18%;
< .001) and a longer median progression-free survival (9.6 95% CI, 7.4 to 11.9
5.4 months 95% CI, 3.8 to 7.0,
< .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30%
19%,
= .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related.
FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.
Ligands are the most commonly used means to control the regioselectivity of organic reactions. It is very important to develop new regioselective control methods for organic synthesis. In this study, ...we designed and synthesized a single-atomic-site catalyst (SAC), namely, Cu1-TiC, with strong electronic metal–support interaction (EMSI) effects by studying various reaction mechanisms. π cloud back-donation to the alkyne on the metal catalytic intermediate was enhanced during the reaction by using transient electron-rich characteristics. In this way, the reaction achieved highly linear-E-type regioselective conversion of electronically unbiased alkynes and completely avoided the formation of branched isomers (ln:br >100:1, TON up to 612, 3 times higher than previously recorded). The structural elements of the SACs were designed following the requirements of the synthesis mechanism. Every element in the catalyst played an important role in the synthesis mechanism. This demonstrated that the EMSI, which is normally thought to be responsible for the improvement in catalytic efficiency and durability in heterogeneous catalysis, now first shows exciting potential for regulating the regioselectivity in homogeneous catalysis.
Cancer stem cells (CSCs) play a critical role in invasive growth and metastasis of human head and neck squamous cell carcinoma (HNSCC). Although significant progress has been made in understanding ...the self-renewal and pro-tumorigenic potentials of CSCs, a key challenge remains on how to eliminate CSCs and halt metastasis effectively. Here we show that super-enhancers (SEs) play a critical role in the transcription of cancer stemness genes as well as pro-metastatic genes, thereby controlling their tumorigenic potential and metastasis. Mechanistically, we find that bromodomain-containing protein 4 (BRD4) recruits Mediators and NF-κB p65 to form SEs at cancer stemness genes such as TP63, MET and FOSL1, in addition to oncogenic transcripts. In vivo lineage tracing reveals that disrupting SEs by BET inhibitors potently inhibited CSC self-renewal and eliminated CSCs in addition to elimination of proliferating non-stem tumor cells in a mouse model of HNSCC. Moreover, disrupting SEs also inhibits the invasive growth and lymph node metastasis of human CSCs isolated from human HNSCC. Taken together, our results suggest that targeting SEs may serve as an effective therapy for HNSCC by eliminating CSCs.
Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical appli- cations. The mechanism underlying their toxicity, such as the induction of inflammatory ...response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na^＋ overload was found to accompany the cell death. Depletion of Na^＋ in culture medium or pretreatment of cells with the Na^＋/K^＋- ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na^＋/K^＋-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na^＋/K^＋-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na^＋/K^＋-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery.
Abstract
As the most well-known electrocatalyst for cathodic hydrogen evolution in water splitting electrolyzers, platinum is unfortunately inefficient for anodic oxygen evolution due to its ...over-binding with oxygen species and excessive dissolution in oxidative environment. Herein we show that single Pt atoms dispersed in cobalt hydrogen phosphate with an unique Pt(OH)(O
3
)/Co(P) coordination can achieve remarkable catalytic activity and stability for oxygen evolution. The catalyst yields a high turnover frequency (35.1 ± 5.2 s
−1
) and mass activity (69.5 ± 10.3 A mg
−1
) at an overpotential of 300 mV and excellent stability. Mechanistic studies elucidate that the superior catalytic performance of isolated Pt atoms herein stems from optimal binding energies of oxygen intermediate and also their strong electronic coupling with neighboring Co atoms that suppresses the formation of soluble Pt
x
>4
species. Alkaline water electrolyzers assembled with an ultralow Pt loading realizes an industrial-level current density of 1 A cm
−2
at 1.8 volts with a high durability.
Favorable growth of asymmetric hetero‐nanostructures consisting of plasmonic metals and semiconductors or topological nanomaterials is highly desired because the performance of nonlinear optical ...antennas is closely related to their composition and morphology symmetry. In this work, two methods are proposed to overgrow PtSe2, a semiconductor or topological semimetal material, onto Au nanorods (AuNRs) to form Au/AuPt/PtSe2 and Au/AgPtSe2 heterorods via wet chemical technique. Both Au/AuPt/PtSe2 and Au/AgPtSe2 heterorods show asymmetric morphologies: the Au/AuPt/PtSe2 heterorods show a partially hollow morphology with an etched AuNR coated by AuPt and PtSe2 shells; the Au/AgPtSe2 heterorods prepared by Ag‐mediated overgrowth method have a toothbrush shape with AgPtSe2 attached on the side surface near one end of AuNRs. The two asymmetric heterorods show significantly enhanced nonlinear radiations of second harmonic generation with the excitation laser wavelength tuning from 1220 to 1315 nm, and a maximal nonlinear enhancement factor of 16 is achieved, which is attributed to the interaction of gold core with platinum selenide shell and the broken symmetry of heterostructures. The findings provide a strategy to prepare metal‐topological heterostructures as optical antennas with optimized performance in the application of nonlinear photonic nanodevices.
Wet‐chemical method is applied to synthesize asymmetric heterorods through growing platinum selenide onto 1D Au nanorods. The asymmetric Au/AuPt/PtSe2 and Au/AgPtSe2 heterorods exhibit largely enhanced nonlinear emission of second harmonic generation, which is attributed to plasmonic interaction of gold core with platinum selenide shell and symmetry breaking of heterostructures.
Rechargeable aqueous zinc ion batteries (AZIBs) are attracting extensive attention owing to environmental friendliness and high safety. However, its practical applications are limited to the poor ...Coulombic efficiency and stability of a Zn anode. Herein, we demonstrate a periodically stacked CuS-CTAB superlattice, as a competitive conversion-type anode for AZIBs with greatly improved specific capacity, rate performance, and stability. The CuS layers react with Zn2+ to endow high capacity, while CTAB layers serve to stabilize the structure and facilitate Zn2+ diffusion kinetics. Accordingly, CuS-CTAB shows superior rate performance (225.3 mA h g–1 at 0.1 A g–1 with 144.4 mA h g–1 at 10 A g–1) and a respectable cyclability of 87.6% capacity retention over 3400 cycles at 10 A g–1. In view of the outstanding electrochemical properties, full batteries constructed with a CuS-CTAB anode and cathode (Zn x FeCo(CN)6 and Zn x MnO2) are evaluated in coin cells, which demonstrate impressive full-battery performance.
Completing a genome is an important goal of genome assembly. However, many assemblies, including reference assemblies, are unfinished and have a number of gaps. Long reads obtained from ...third-generation sequencing (TGS) platforms can help close these gaps and improve assembly contiguity. However, current gap-closure approaches using long reads require extensive runtime and high memory usage. Thus, a fast and memory-efficient approach using long reads is needed to obtain complete genomes.
We developed LR_Gapcloser to rapidly and efficiently close the gaps in genome assembly. This tool utilizes long reads generated from TGS sequencing platforms. Tested on de novo assembled gaps, repeat-derived gaps, and real gaps, LR_Gapcloser closed a higher number of gaps faster and with a lower error rate and a much lower memory usage than two existing, state-of-the art tools. This tool utilized raw reads to fill more gaps than when using error-corrected reads. It is applicable to gaps in the assemblies by different approaches and from large and complex genomes. After performing gap-closure using this tool, the contig N50 size of the human CHM1 genome was improved from 143 kb to 19 Mb, a 132-fold increase. We also closed the gaps in the Triticum urartu genome, a large genome rich in repeats; the contig N50 size was increased by 40%. Further, we evaluated the contiguity and correctness of six hybrid assembly strategies by combining the optimal TGS-based and next-generation sequencing-based assemblers with LR_Gapcloser. A proposed and optimal hybrid strategy generated a new human CHM1 genome assembly with marked contiguity. The contig N50 value was greater than 28 Mb, which is larger than previous non-reference assemblies of the diploid human genome.
LR_Gapcloser is a fast and efficient tool that can be used to close gaps and improve the contiguity of genome assemblies. A proposed hybrid assembly including this tool promises reference-grade assemblies. The software is available at http://www.fishbrowser.org/software/LR_Gapcloser/.
PDF
