The electrochemical nitrogen reduction reaction (NRR) is an attractive process for next‐generation ammonia synthesis; therefore, identifying a suitable catalyst for this reaction is critical. In ...recent years, transition‐metal dichalcogenides (TMDs) and their Janus structures have gained significant attention because of their outstanding catalytic properties. However, the synthesis of Janus TMDs remains challenging, and exposing their active sites is difficult when using a low‐dimensional structure to improve the catalytic activity. To date, relatively little research has been conducted in this area. Herein, emerging Janus WSeS/WSe2 heterostructure nanowalls are systematically explored. These nanowalls are used as a nitrogen fixation catalyst in electrolytes. The nanowalls demonstrate a significant NH3 yield rate and Faradaic efficiency of 13.97 µg h‐mgcat−1 and 35.24% at −0.3 V in 0.1 m HCl, as well as 15.96 µg h‐mgcat−1 and 40.2% in 0.1 M Na2SO4. This study presents an in‐depth analysis of the properties of Janus WSeS/WSe2 heterostructure nanowalls and a conceptual framework for linking TMD‐based catalysts and the NRR.
Herein, emerging Janus WSeS/WSe2 heterostructure nanowalls are systematically explored. These nanowalls are used as a nitrogen fixation catalyst in the electrolytes. The nanowalls exhibit a high NH3 yield rate and Faradaic efficiency of 13.97 µg h‐mgcat−1 and 35.24% at −0.3 V in 0.1 HCl, as well as 15.96 μg h‐mgcat‐1and 40.2% in 0.1 m Na2SO4. This study presents an in‐depth analysis of the properties of Janus WSeS/WSe2 heterostructure nanowalls and a conceptual framework for linking TMD‐based catalysts and the NRR.
RATIONALE:Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, ...such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus–induced microvascular dysfunction is largely unknown.
OBJECTIVE:To elucidate whether lncRNA-myocardial infarction–associated transcript (MIAT) is involved in diabetes mellitus–induced microvascular dysfunction.
METHODS AND RESULTS:Using quantitative polymerase chain reaction, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes mellitus–induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a competing endogenous RNA, and formed a feedback loop with vascular endothelial growth factor and miR-150-5p to regulate endothelial cell function.
CONCLUSIONS:This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases.
Enhanced warming in the Arctic (Arctic amplification, AA) in the last decades has been linked to several factors including sea ice and the Atlantic Multidecadal Oscillation (AMO). However, how these ...factors contributed to AA variations in a long-term perspective remains unclear. By reconstructing a millennial AA index combining climate model simulations with recently available proxy data, this work determines the important influences of the AMO and anthropogenic greenhouse gas forcing on AA variations in the last millennium, leading to identification of a significant downward trend of AA on top of a sustained strong AMO modulation at the multidecadal scales. The decreased AA during the industrial era was strongly associated with the anthropogenic forcing, proving the emerging role of the forcing in reducing the AA strength.
High species diversity may result from recent rapid speciation in a 'cradle' and/or the gradual accumulation and preservation of species over time in a 'museum'. China harbours nearly 10% of ...angiosperm species worldwide and has long been considered as both a museum, owing to the presence of many species with hypothesized ancient origins, and a cradle, as many lineages have originated as recent topographic changes and climatic shifts-such as the formation of the Qinghai-Tibetan Plateau and the development of the monsoon-provided new habitats that promoted remarkable radiation. However, no detailed phylogenetic study has addressed when and how the major components of the Chinese angiosperm flora assembled to form the present-day vegetation. Here we investigate the spatio-temporal divergence patterns of the Chinese flora using a dated phylogeny of 92% of the angiosperm genera for the region, a nearly complete species-level tree comprising 26,978 species and detailed spatial distribution data. We found that 66% of the angiosperm genera in China did not originate until early in the Miocene epoch (23 million years ago (Mya)). The flora of eastern China bears a signature of older divergence (mean divergence times of 22.04-25.39 Mya), phylogenetic overdispersion (spatial co-occurrence of distant relatives) and higher phylogenetic diversity. In western China, the flora shows more recent divergence (mean divergence times of 15.29-18.86 Mya), pronounced phylogenetic clustering (co-occurrence of close relatives) and lower phylogenetic diversity. Analyses of species-level phylogenetic diversity using simulated branch lengths yielded results similar to genus-level patterns. Our analyses indicate that eastern China represents a floristic museum, and western China an evolutionary cradle, for herbaceous genera; eastern China has served as both a museum and a cradle for woody genera. These results identify areas of high species richness and phylogenetic diversity, and provide a foundation on which to build conservation efforts in China.
With the development of proteomics and epigenetics, a large number of RNA‐binding proteins (RBPs) have been discovered in recent years, and the interaction between long non‐coding RNAs (lncRNAs) and ...RBPs has also received increasing attention. It is extremely important to conduct in‐depth research on the lncRNA‐RBP interaction network, especially in the context of its role in the occurrence and development of cancer. Increasing evidence has demonstrated that lncRNA‐RBP interactions play a vital role in cancer progression; therefore, targeting these interactions could provide new insights for cancer drug discovery. In this review, we discussed how lncRNAs can interact with RBPs to regulate their localization, modification, stability, and activity and discussed the effects of RBPs on the stability, transport, transcription, and localization of lncRNAs. Moreover, we explored the regulation and influence of these interactions on lncRNAs, RBPs, and downstream pathways that are related to cancer development, such as N6‐methyladenosine (m6A) modification of lncRNAs. In addition, we discussed how the lncRNA‐RBP interaction network regulates cancer cell phenotypes, such as proliferation, apoptosis, metastasis, drug resistance, immunity, tumor environment, and metabolism. Furthermore, we summarized the therapeutic strategies that target the lncRNA‐RBP interaction network. Although these treatments are still in the experimental stage and various theories and processes are still being studied, we believe that these strategies may provide new ideas for cancer treatment.
The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in ...radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.
Targeted oral delivery of a drug via the intestinal lymphatic system (ILS) has the advantages of protecting against hepatic first‐pass metabolism of the drug and improving its pharmacokinetic ...performance. It is also a promising route for the oral delivery of vaccines and therapeutic agents to induce mucosal immune responses and treat lymphatic diseases, respectively. This article describes the anatomical structures and physiological characteristics of the ILS, with an emphasis on enterocytes and microfold (M) cells, which are the main gateways for the transport of particulate delivery vehicles across the intestinal epithelium into the lymphatics. A comprehensive overview of recent advances in the rational engineering of particulate vehicles, along with the challenges and opportunities that they present for improving ILS drug delivery, is provided, and the mechanisms by which such vehicles target and transport through enterocytes or M cells are discussed. The use of naturally sourced materials, such as yeast microcapsules and their derived polymeric β‐glucans, as novel ILS‐targeting delivery vehicles is also reviewed. Such use is the focus of an emerging field of research. Their potential use in the oral delivery of nucleic acids, such as mRNA vaccines, is proposed.
The rational engineering of effective vehicles for lymphatic delivery of drugs, through targeting enterocytes or M cells, prevents their first‐pass metabolism by the liver, markedly increasing the bioavailability of oral drugs. By achieving increased bioavailability, high drug concentrations are attainable at the lesions of interest with beneficial therapeutic effects, making intestinal lymphatic transport a unique modality of drug delivery.
As a type of elementary organic compounds containing N−N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2‐retention and N2‐removal ...modes. We report herein an unprecedented protocol for the realization of division utilization of the N2‐moiety of hydrazone by a radical facilitated N−N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann‐Löffler‐Freytag reaction by the reaction of N‐homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino‐N migration and H‐atom transfer. Consequently, a series of structurally significant ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters are efficiently produced via continuous C−C bond and dual C−N bonds forging.
A novel conversion mode for hydrazone by the division use of N2‐moiety is developed by the photocatalytic redox neutral reaction of N‐homoallyl‐N‐mesitylenesulfonyl (Mts)‐hydrazones with ICF2CO2Et. The reaction merges olefin carboamination and Hofmann‐Löffler‐Freytag (HLF) reaction by radical addition/crucial distal N and H transfer sequences to yield ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters under tandem C−C and dual C−N bonds forging.
Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8+ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant ...remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma‐released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector‐like tumor‐specific CD8+ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD‐L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD‐L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.
We demonstrate a crucial role for tumor‐released exosomes in promoting metastatic progression. We provide extensive evidence that exosomes from tumor cells act alone as contributors to driving tumor‐specific CD8+ T cell exhaustion in vivo. We also find that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis.
Abstract
We report the properties of more than 800 bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio Telescope during ...an extremely active episode on UTC 2021 September 25th-28th in a series of four papers. In this fourth paper of the series, we present a systematic search of the spin period and linear acceleration of the source object from both 996 individual pulse peaks and the dedispersed time series. No credible spin period was found from this data set. We rule out the presence of significant periodicity in the range between 1 ms and 100 s with a pulse duty cycle <0.49 ± 0.08 (when the profile is defined by a von-Mises function, not a boxcar function) and linear acceleration up to 300 m s
−2
in each of the four one-hour observing sessions, and up to 0.6 m s
−2
in all 4 days. These searches contest theoretical scenarios involving a 1 ms–100 s isolated magnetar/pulsar with surface magnetic field <10
15
G and a small duty cycle (such as in a polar-cap emission mode) or a pulsar with a companion star or black hole up to 100
M
⊙
and
P
b
> 10 hr. We also perform a periodicity search of the fine structures and identify 53 unrelated millisecond-timescale “periods” in multi-components with the highest significance of 3.9
σ
. The “periods” recovered from the fine structures are neither consistent nor harmonically related. Thus they are not likely to come from a spin period. We caution against claiming spin periodicity with significance below ∼4
σ
with multi-components from one-off FRBs. We discuss the implications of our results and the possible connections between FRB multi-components and pulsar microstructures.
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