Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, ...microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti‑inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.
Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene‐containing Ir(III) photosensitizer (IrFc1) that can ...bind with transferrin and be transported into triple‐negative breast cancer (TNBC) cells via a transferrin receptor‐mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self‐amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T‐cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule‐based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self‐amplifying process.
A Ir(III)‐based photosensitizer with self‐amplifying properties is reported in this work. IrFc1 can cause lipid oxidation leading to ferroptosis in transferrin receptor overexpressing cancer cells, which envokes intense anticaner immnuoenhancement both in vitro and in vivo.
Abstract
The absence of two-dimensional (2D) van der Waals (vdW) ferromagnetic crystals with both above-room-temperature strong intrinsic ferromagnetism and large perpendicular magnetic anisotropy ...(PMA) severely hinders practical applications of 2D vdW crystals in next-generation low-power magnetoelectronic and spintronic devices. Here, we report a vdW intrinsic ferromagnetic crystal Fe
3
GaTe
2
that exhibits record-high above-room-temperature Curie temperature (
Tc
, ~350-380 K) for known 2D vdW intrinsic ferromagnets, high saturation magnetic moment (40.11 emu/g), large PMA energy density (~4.79 × 10
5
J/m
3
), and large anomalous Hall angle (3%) at room temperature. Such large room-temperature PMA is better than conventional widely-used ferromagnetic films like CoFeB, and one order of magnitude larger than known 2D vdW intrinsic ferromagnets. Room-temperature thickness and angle-dependent anomalous Hall devices and direct magnetic domains imaging based on Fe
3
GaTe
2
nanosheet have been realized. This work provides an avenue for room-temperature 2D ferromagnetism, electrical control of 2D ferromagnetism and promote the practical applications of 2D-vdW-integrated spintronic devices.
Both high-fidelity and mismatch-tolerant recombination, catalyzed by RAD51 and DMC1 recombinases, respectively, are indispensable for genomic integrity. Here, we use cryo-EM, MD simulation and ...functional analysis to elucidate the structural basis for the mismatch tolerance of DMC1. Structural analysis of DMC1 presynaptic and postsynaptic complexes suggested that the lineage-specific Loop 1 Gln244 (Met243 in RAD51) may help stabilize DNA backbone, whereas Loop 2 Pro274 and Gly275 (Val273/Asp274 in RAD51) may provide an open "triplet gate" for mismatch tolerance. In support, DMC1-Q244M displayed marked increase in DNA dynamics, leading to unobservable DNA map. MD simulation showed highly dispersive mismatched DNA ensemble in RAD51 but well-converged DNA in DMC1 and RAD51-V273P/D274G. Replacing Loop 1 or Loop 2 residues in DMC1 with RAD51 counterparts enhanced DMC1 fidelity, while reciprocal mutations in RAD51 attenuated its fidelity. Our results show that three Loop 1/Loop 2 residues jointly enact contrasting fidelities of DNA recombinases.
The spin-valve effect has been the focus of spintronics over the last decades due to its potential for application in many spintronic devices. Two-dimensional (2D) van der Waals (vdW) materials are ...highly efficient to build spin-valve heterojunctions. However, the Curie temperatures (TC) of the vdW ferromagnetic (FM) 2D crystals are mostly below room temperature (∼30–220 K). It is very challenging to develop room-temperature, FM 2D crystal-based spin-valve devices. Here, we report room-temperature, FM 2D-crystal-based all-2D vdW Fe3GaTe2/MoS2/Fe3GaTe2 spin-valve devices. The magnetoresistance (MR) of the device was up to 15.89% at 2.3 K and 11.97% at 10 K, which are 4–30 times the MR of the spin valves of Fe3GeTe2/MoS2/Fe3GeTe2 and conventional NiFe/MoS2/NiFe. The typical spin valve effect showed strong dependence on the MoS2 spacer thickness in the vdW heterojunction. Importantly, the spin valve effect (0.31%) robustly existed even at 300 K with low working currents down to 10 nA (0.13 A cm−2). This work provides a general vdW platform to develop room-temperature, 2D FM-crystal-based 2D spin-valve devices.
•HBO-PC reduced infarct volume ratio and neurobehavioral deficit in MCAO rats.•It also increased the expression of Sirt1 and Nrf2/antioxidant defense pathway.•The neuroprotective effects of HBO-PC ...were inhibited by Sirt1 or Nrf2 siRNA.•Sirt1 siRNA inhibited Nrf2 expression, but Nrf2 siRNA had no effect on Sirt1 expression.•The findings suggest possible therapeutic avenues in cases of cerebral ischemia.
Sirtuin 1 (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress. HBO-PC increased the expression of Sirt1 and reduced infarct volume ratio and neurobehavioral deficit in MCAO rats. Meanwhile, HBO-PC also increased expression of Nrf2, HO-1, and SOD1 and decreased MDA content. Furthermore, either Sirt1 or Nrf2 knockdown by short interfering RNA (siRNA) inhibited the expression of Nrf2, HO-1, and SOD1 and eliminated the neuroprotective effects of HBO-PC. Taken together, the results suggest that the Nrf2/antioxidant defense pathway is involved in the long lasting neuroprotective effects of Sirt1 induced by HBO-PC against transient focal cerebral ischemia.
Background LLNM can occur in mid-low rectal cancer, but LLND in patients with rectal cancer presents certain challenges. Recent years have seen the progressive application of ICG fluorescence imaging ...technology in colorectal surgery. This study aimed to explore the effectiveness of ICG-guided laparoscopic LLND for rectal cancer. Methods We applied ICG-guided laparoscopic lateral lymph node dissection in 11 patients diagnosed as rectal cancer with lateral lymph node metastasis. Results All 11 patients in this group successfully completed ICG-guided laparoscopic LLND for rectal cancer with good lateral lymph node imaging. Conclusions ICG-guided laparoscopic LLND for rectal cancer is safe and represents a feasible solution, thereby providing valuable guidance for intraoperative lymph node dissection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recognition of handwritten mathematical expressions (MEs) is an important problem that has wide applications in practice. Handwritten ME recognition is challenging due to the variety of writing ...styles and ME formats. As a result, recognizers trained by optimizing the traditional supervision loss do not perform satisfactorily. To improve the robustness of the recognizer with respect to writing styles, in this work, we propose a novel paired adversarial learning method to learn semantic-invariant features. Specifically, our proposed model, named PAL-v2, consists of an attention-based recognizer and a discriminator. During training, handwritten MEs and their printed templates are fed into PAL-v2 simultaneously. The attention-based recognizer is trained to learn semantic-invariant features with the guide of the discriminator. Moreover, we adopt a convolutional decoder to alleviate the vanishing and exploding gradient problems of RNN-based decoder, and further, improve the coverage of decoding with a novel attention method. We conducted extensive experiments on the CROHME dataset to demonstrate the effectiveness of each part of the method and achieved state-of-the-art performance.
The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, ...five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1–regulated stresses.
This study attempted to clarify the carrying-over effect of different nitrogen treatments applied to the main crop on the crop population growth and yield formation of ratoon rice under mechanized ...cultivation in Southeast China. Based on the constant total nitrogen application amounts (225.00 kg ha−1) in the main crop, an experiment with different ratios of basal and topdressing nitrogen fertilizer (the ratio of basal fertilizer:primary tillering fertilizer:secondary tillering fertilizer:booting fertilizer at 3:1:2:4 (N1), 3:2:1:4 (N2), 3:3:0:4 (N3), and 4:3:0:3 (N4), respectively, and a control without nitrogen treatment (N0)) was set up across two consecutive years in field using hybrid rice variety Yongyou 1540 as the test materials. The results showed that the total tiller number and effective tillering percentage increased in the main crop under the N1 treatment, more nitrogen fertilizer applied in late growth stage of the main crop, and its effective tillering percentage of the main crop was the highest at up to 70.18%, which was 9.15% higher than that of conventional fertilization treatment (N4), more nitrogen fertilizer applied in early growth stage of the main crop. The same tendency was observed in leaf area index (LAI) value of the main crop and its subsequent ratoon rice, which were 16.52 and 29.87% higher, respectively, in the N1 treatment than that in the N4 treatment at the full heading stage. The same was true in the case of the transport rates of stem and sheath dry mater and the canopy light interception rates in both the main and its ratoon crops. The transport rate of stem and sheath in main crop rice under N1 treatment increased by 50.57% compared with N4 treatment. The canopy light interception rate of N1 treatment increased by 5.07% compared with N4 treatment at the full heading stage of the ratoon crop. Therefore, the total actual yield was the highest in the main and its ratoon crops under N1 treatment, averaging 17 351.23 kg ha−1 in two-year trials, which was 23.00% higher than that in the conventional fertilization treatment (N4). The results showed that appropriate nitrogen treatment was able to produce a good crop stand in the main crop, which was essential for producing a good ratoon crop population and high yield especially under mechanized cultivation with low stubble height of the main crop. The study suggested that shifting the proper nitrogen application amounts to the late growth stage of the main crop, such as N1 treatment, not only had a higher productive effect on ensuring the yield of the main crop, but also had a positive effect on the axillary bud sprouts from the stubbles for ratoon rice, resulting in an increased percentage of productive panicles and achieving the goal of one planting with two good harvests under the conditions of our study.
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