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The pursuit of ideal short-delayed thermally activated delayed fluorescence (TADF) emitters is hampered by the mutual exclusion of a small singlet-triplet energy gap (Δ E ST ) and a large oscillator strength ( f ). Here, by attaching an multiresonance-acceptor onto a sterically-uncrowded donor, we report TADF emitters bearing hybrid electronic excitations with a main donor-to-acceptor long-range (LR) and an auxiliary bridge-phenyl short-range (SR) charge-transfer characters, balancing a small Δ E ST and a large f . Moreover, the incorporation of dual equivalent multiresonance-acceptors is found to double the f value without affecting the Δ E ST . A large radiative decay rate over an order of magnitude higher than the intersystem crossing (ISC) rate, and a decent reverse ISC rate of >10 6  s −1 are simultaneously obtained in one emitter, leading to a short delayed-lifetime of ~0.88 μs. The corresponding organic light-emitting diode exhibits a record-high maximum external quantum efficiency of 40.4% with alleviated efficiency roll-off and extended lifetime. To possess a small singlet-triplet energy gap and a large oscillator strength simultaneously is critical for efficient thermally activated delayed fluorescent emitters. Here, the authors attach an multiresonance-acceptor onto a sterically-uncrowded donor for realizing a device efficiency of 40.4%.

Background Targeting specificity has been a barrier to applying genome editing systems in functional genomics, precise medicine and plant breeding. In plants, only limited studies have used whole-genome sequencing (WGS) to test off-target effects of Cas9. The cause of numerous discovered mutations is still controversial. Furthermore, WGS-based off-target analysis of Cpf1 (Cas12a) has not been reported in any higher organism to date. Results We conduct a WGS analysis of 34 plants edited by Cas9 and 15 plants edited by Cpf1 in T0 and T1 generations along with 20 diverse control plants in rice. The sequencing depths range from 45× to 105× with read mapping rates above 96%. Our results clearly show that most mutations in edited plants are created by the tissue culture process, which causes approximately 102 to 148 single nucleotide variations (SNVs) and approximately 32 to 83 insertions/deletions (indels) per plant. Among 12 Cas9 single guide RNAs (sgRNAs) and three Cpf1 CRISPR RNAs (crRNAs) assessed by WGS, only one Cas9 sgRNA resulted in off-target mutations in T0 lines at sites predicted by computer programs. Moreover, we cannot find evidence for bona fide off-target mutations due to continued expression of Cas9 or Cpf1 with guide RNAs in T1 generation. Conclusions Our comprehensive and rigorous analysis of WGS data across multiple sample types suggests both Cas9 and Cpf1 nucleases are very specific in generating targeted DNA modifications and off-targeting can be avoided by designing guide RNAs with high specificity.

When the operating state of the power system changes, a modular multilevel converter power electronic transformer (MMC-PET) based on modular multilevel converters cannot perform efficient energy transfer and power conversion under conventional control strategies. To address the above problems, this paper proposes a passive, second-order super-helical sliding mode control strategy for MMC-PET by combining passive control and second-order super-helical sliding mode control with a stronger anti-interference capability. First, a Euler–Lagrange model based on positive and negative sequence separation is established according to the mathematical model of the MMC; second, the model of the system is passively analyzed, and a passive controller is designed according to its passivity, and the passive controller is further optimized by using the super-helical second-order sliding mode control, which improves the overall robustness and interference immunity; finally, the effectiveness and superiority of the super-twisting second-order sliding mode passive control strategy is demonstrated by verifying it through the construction of the MMC-PET simulation model and testing it under various non-ideal working conditions.

Our previous study showed that Calreticulin (CRT) promoted the development of pancreatic cancer (PC) through ERK/MAPK pathway. We next investigate whether CRT promotes EGF-induced epithelial–mesenchymal transition (EMT) in PC via Integrin/EGFR-ERK/MAPK signaling, which has not been reported yet to our knowledge. EGF simultaneously induced EMT and activated Integrin/EGFR–ERK/MAPK signaling pathway in 3 PC cells. However, CRT silencing significantly inhibited EGF function, including inhibiting EGF-induced EMT-like cell morphology, EGF-enhanced cell invasion and migration, and EGF induced the decrease of E-cadherin, ZO-1, and β -catenin and the increase of the key proteins in Integrin/EGFR-ERK/MAPK signaling (pEGFR-tyr1173, Fibronectin, Integrin β 1, c-Myc and pERK). Conversely, CRT overexpression rescued the change of EMT-related proteins induced by EGF in CRT silencing PC cells. Additionally, CRT was co-stained with pEGFR1173 (with EGF), Fibronectin and Integrin β 1 by IF under confocal microscopy and was co-immunoprecipitated with Fibronectin, Integrin β 1 and c-Myc in both PC cells, all of which indicating a close interaction of CRT with Integrin/EGFR–ERK/MAPK signaling pathway in PC. In vivo , CRT silencing inhibited subcutaneous tumor growth and liver metastasis of pancreatic tumor. A positive relationship of CRT with Fibronectin, Integrin β 1, c-Myc and pERK and a negative association of CRT with E-cad was also observed in vivo and clinical samples. Meanwhile, overexpression of the above proteins was closely associated with multiple aggressive clinicopathological characteristics and the poor prognosis of PC patients. CRT promotes EGF-induced EMT in PC cells via Integrin/EGFR-ERK/MAPK signaling pathway, which would be a promising therapy target for PC.

Coupled magmatic and tectonic activity plays an important role in high-temperature hydrothermal circulation at mid-ocean ridges. The circulation patterns for such systems have been elucidated by microearthquakes and geochemical data over a broad spectrum of spreading rates, but such data have not been generally available for ultra-slow spreading ridges. Here we report new geophysical and fluid geochemical data for high-temperature active hydrothermal venting at Dragon Horn area (49.7°E) on the Southwest Indian Ridge. Twin detachment faults penetrating to the depth of 13 ± 2 km below the seafloor were identified based on the microearthquakes. The geochemical composition of the hydrothermal fluids suggests a long reaction path involving both mafic and ultramafic lithologies. Combined with numerical simulations, our results demonstrate that these hydrothermal fluids could circulate ~ 6 km deeper than the Moho boundary and to much greater depths than those at Trans-Atlantic Geotraverse and Logachev-1 hydrothermal fields on the Mid-Atlantic Ridge. Magmatic and tectonic activity at mid-oceanic ridges can give detailed insights into high-temperature hydrothermal circulation of fluids. The authors here present geochemical and geophysical datasets that suggest a hydrothermal system penetrating the upper lithospheric mantle at an ultra-slow spreading mid-oceanic ridge.

Mesenchymal stem cell (MSC) therapy holds promise in biomedical applications but faces challenges in efficient transfection without compromising cell viability. Here, we show a serum-tolerant MSC transfection nanotool, APOs@BP, composed of an apolipoprotein (APO) corona and a boronated polyethyleneimine (BP) core. The APOs corona’s serum-protein resistance and cytomembrane affinity enable APOs@BP to achieve 10.4-fold higher transfection efficiency and improved cytocompatibility in serum-containing medium compared to high-molecular-weight polycationic transfectants. For MSC neural differentiation, miRNA-124 and all-trans retinoic acid derivative (atRAN) are further loaded into APOs@BP, forming a polymeric complex for sequential drug release triggered by lysosomal acid and cytosolic reactive oxygen species post-transplantation. Transcriptomic analysis confirms that this system enhances MSC neural differentiation through sequential activation of atRAN-induced differentiation potential and miRNA-124-directed neurogenesis via cGMP-PKG, MAPK, and PI3K-Akt pathways. Transplantation of engineered MSCs reconstructs neural circuits and alleviates cognitive impairment in Alzheimer’s disease model mice. Collectively, this system provides a robust and convenient method for MSC-based regenerative medicine. Stem cell therapies have huge potential but face challenges. Here, the authors report on a serum-tolerant boronated polyethyleneimine assembly with apolipoprotein corona, to carry miRNA-124 and all-trans retinoic acid derivative to achieve efficient stem-cell transfection and neural differentiation.

CRISPR-Cas12a is a promising genome editing system for targeting AT-rich genomic regions. Comprehensive genome engineering requires simultaneous targeting of multiple genes at defined locations. Here, to expand the targeting scope of Cas12a, we screen nine Cas12a orthologs that have not been demonstrated in plants, and identify six, ErCas12a, Lb5Cas12a, BsCas12a, Mb2Cas12a, TsCas12a and MbCas12a, that possess high editing activity in rice. Among them, Mb2Cas12a stands out with high editing efficiency and tolerance to low temperature. An engineered Mb2Cas12a-RVRR variant enables editing with more relaxed PAM requirements in rice, yielding two times higher genome coverage than the wild type SpCas9. To enable large-scale genome engineering, we compare 12 multiplexed Cas12a systems and identify a potent system that exhibits nearly 100% biallelic editing efficiency with the ability to target as many as 16 sites in rice. This is the highest level of multiplex edits in plants to date using Cas12a. Two compact single transcript unit CRISPR-Cas12a interference systems are also developed for multi-gene repression in rice and Arabidopsis . This study greatly expands the targeting scope of Cas12a for crop genome engineering. CRISPR-Cas12a is a promising system for targeting AT-rich regions of the genome. Here the authors identify Cas12a orthologs with expanded targeting scope and develop a highly multiplexable editing system in rice.

The internal quality detection is extremely important. To solve the challenges of walnut quality detection, we presented the first comprehensive investigation of walnut quality detection method using X-ray imaging and deep learning model. An X-ray machine vision system was designed, and a walnut kernel detection (called WKD) dataset was constructed. Then, an effective walnut kernel detection network (called WKNet) was developed by employing Transformer, GhostNet, and criss-cross attention (called CCA) module to the YOLO v5s model, aiming to solve the time consuming and parameter redundancy issues. The WKNet achieved an mAP_0.5 of 0.9869, precision of 0.9779, and recall of 0.9875 for walnut kernel detection. The inference time per image is only 11.9 ms. Extensive comparison experiments with the state-of-the-art (SOTA) deep learning models demonstrated the advanced nature of WKNet. The online test of walnut internal quality detection also shows satisfactory performance. The innovative combination of X-ray imaging and WKNet provide significant implications for walnut quality control.

Objective To evaluate the prognostic impact and describe suturing tools of mesenteric closure after laparoscopic right hemicolectomy (LRH). Methods PubMed, Embase, Cochrane library, Web of Science, and Scopus databases, were searched and publications relating to mesenteric closure data and tools were extracted. Search terms: “Mesenteric Defects” and “Mesenteric Closure” were used, and manual searches of eligible articles from literature reference lists performed. Result A total of 7 publications were identified. 5 focused on prognostic impact and 4 referred to tools for mesenteric closure, two of which concerned both prognostic data and tools. All studies related to prognostic impact were single center with “low” modified GRADE quality. A high degree of heterogeneous was found. Conclusion The evidence from current research does not support routine closure of mesenteric defects. Use of a polymer ligation clip has produced favorable results in a small sample size trial and further investigation is merited. A large randomized controlled trial is still warranted.

A suitable host material is pivotal for efficient and stable deep-blue phosphorescent organic light-emitting diodes (PhOLEDs). Here, we construct a deuterated exciplex-forming host with improved molecular stability and charge transport and firstly unveil an “external deuteration effect” on dopant, which reduces the shoulder emissions for slightly blue-shifted colours and also accelerates the radiative decay rates for improved photoluminescence efficiency. The corresponding deep-blue PhOLEDs based on two platinum complexes, PtON-TBBI and PtON-tb-DTB, achieve lower operational voltages and higher maximum external quantum efficiencies of 27.4/19.9% and power efficiency of 41.2/33.6 lm/W, respectively, compared to the hydrogen-based counterparts. Moreover, lifetimes of 370 and 557 h to reach 90% of the initial luminance of 1000 cd/m 2 with Commission Internationale de l’Eclairage coordinates of (0.148, 0.165) and (0.153, 0.213) are achieved, 1.6 and 1.4 times longer than the ones based on the non-deuterated hosts with even blue-shifted colours. The stability of deep-blue phosphorescent organic light-emitting diodes is critical for commercialization. Here, the authors employ a deuterated exciplex-forming host, achieving largely improved lifetime of 370 and 557 h with blue-shifted colours.