The heteroporous MoS2/Ni3S2 catalyst exhibits excellent electrocatalytic activity for the overall urea splitting with only a cell voltage of 1.45 V at 20 mA cm−2 in 1 M KOH with 0.33 M urea. This ...value is the best of all the bifunctional urea splitting electrocatalysts, including Pt, reported to date.
Hydrogen and other renewable resources derived by sunlight have attracted great attention to sustainable development. But the photochemical performance of diverse systems is restricted because of the ...poor efficiency of photon absorption, easy recombination of photogenerated electron–hole pairs, and slow transfer of charge carriers. Single-atom catalysts (SACs), in which isolated atoms are supported on the supports without forming nanoparticles, have received increasing interests in photocatalysis due to the high catalytic activity, selectivity, stability, and 100% atom utilization. In this review, we highlight and introduce recent advances in the preparation method of SACs and concrete examples of single-atom photocatalysts used for the hydrogen evolution from water, overall water splitting, CO2 and N2 reduction reaction. At last, we discuss the underlying mechanisms for photocatalytic performance of single-atom catalysts and the prospects for the development of SACs.
The jet breaks in the afterglow light curves of short gamma-ray bursts (SGRBs), rarely detected so far, are crucial for estimating the half-opening angles of the ejecta (θj) and hence the neutron ...star merger rate. In this work, we report the detection of jet decline behaviors in GRB 150424A and GRB 160821B, and find θj ∼ 0.1 rad. Together with five events reported before 2015 and three others "identified" recently (GRB 050709, GRB 060614, and GRB 140903A), we have a sample consisting of nine SGRBs and one long-short GRB with reasonably estimated θj. In particular, three Swift bursts in the sample have redshifts z ≤ 0.2, with which we estimate the local neutron star merger rate density to be or if the narrowly beamed GRB 061201 is excluded. Inspired by the typical θj ∼ 0.1 rad found currently, we further investigate whether the off-beam GRBs (in the uniform jet model) or the off-axis events (in the structured jet model) can significantly enhance the GRB/GW association. For the former, the enhancement is at most moderate, while for the latter the enhancement can be much greater and a high GRB/GW association probability of ∼10% is possible. We also show that the data of GRB 160821B may contain a macronova/kilonova emission component with a temperature of ∼3100 K at ∼3.6 days after the burst and more data are needed to ultimately clarify.
Factors shaping the interspecific variations in herbivory have puzzled ecologists for decades and several hypotheses have been proposed to explain interspecific variation in leaf herbivory. In a ...tropical rainforest in Yunnan Province, China, we collected 6732 leaves from 129 species with canopy heights ranging from 1.6 to 65.0 m above the ground. We tested the role of canopy height, the diversity, composition and structural heterogeneity of neighbors and leaf traits in shaping the interspecific variations in herbivory. Results show that leaf herbivory decreased with canopy height and specific leaf area (SLA) and increased with leaf size. However, neighboring species' diversity, composition, and structural heterogeneity showed no association with herbivory. Therefore, neither the visual apparency effect nor the associational resistance effect was detected in this hyperdiverse tropical rainforest. These findings highlight the importance of vertical structure in shaping herbivory patterns in natural communities.
Abstract
Investigations of CRISPR gene knockout editing profiles have contributed to enhanced precision of editing outcomes. However, for homology-directed repair (HDR) in particular, the editing ...dynamics and patterns in clinically relevant cells, such as human iPSCs and primary T cells, are poorly understood. Here, we explore the editing dynamics and DNA repair profiles after the delivery of Cas9-guide RNA ribonucleoprotein (RNP) with or without the adeno-associated virus serotype 6 (AAV6) as HDR donors in four cell types. We show that editing profiles have distinct differences among cell lines. We also reveal the kinetics of HDR mediated by the AAV6 donor template. Quantification of T50 (time to reach half of the maximum editing frequency) indicates that short indels (especially +A/T) occur faster than longer (>2 bp) deletions, while the kinetics of HDR falls between NHEJ (non-homologous end-joining) and MMEJ (microhomology-mediated end-joining). As such, AAV6-mediated HDR effectively outcompetes the longer MMEJ-mediated deletions but not NHEJ-mediated indels. Notably, a combination of small molecular compounds M3814 and Trichostatin A (TSA), which potently inhibits predominant NHEJ repairs, leads to a 3-fold increase in HDR efficiency.
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%).
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.
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.
Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for ...systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.
Precise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR ...efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs).
Here, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs. We find that a 600 bp homology in both arms leads to high-level genome knockin, with 97-100% of the donor insertion events being mediated by HDR. The combined use of CCND1, a cyclin that functions in G1/S transition, and nocodazole, a G2/M phase synchronizer, doubles HDR efficiency to up to 30% in iPSCs.
Taken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.
In our previous work (Zhang and Shu in Eur Phys J. C 84(3):256, 2024), we have explored quantum gravity induced entanglement of masses (QGEM) in curved spacetime, observing entanglement formation ...between particles moving along geodesics in a Schwarzschild spacetime background. We find that long interaction time induces entanglement, even for particles with microscopic mass, addressing decoherence concerns. In this work, we build upon our previous work (Zhang and Shu 2024) by extending our investigation to a time-dependent spacetime. Specifically, we explore the entanglement induced by the mutual gravitation of massive particles in the Friedmann–Lemaître–Robertson–Walker (FLRW) universe. With the help of the phase shift and the QGEM spectrum, our proposed scheme offers a potential method for observing the formation of entanglement caused by the quantum gravity of massive particles as they propagate in the FLRW universe. Consequently, it provides insights into the field of entanglement in cosmology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences.
We show that large deletions are ubiquitous but ...are dependent on editing sites and cell types. Human primary T cells display more significant deletions than hematopoietic stem and progenitor cells (HSPCs), whereas we observe low levels in induced pluripotent stem cells (iPSCs). We find that the homology-directed repair (HDR) with single-stranded oligodeoxynucleotides (ssODNs) carrying short homology reduces the deletion damage by almost half, while adeno-associated virus (AAV) donors with long homology reduce large deletions by approximately 80%. In the absence of HDR, the insertion of a short double-stranded ODN by NHEJ reduces deletion indexes by about 60%.
Timely bridging of broken ends by HDR and NHEJ vastly decreases the unintended consequences of dsDNA cleavage. These strategies can be harnessed in gene editing applications to attenuate unintended outcomes.
PDF
