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To investigate the role of iodine-125 (Both in vivo and in vitro experiments were conducted. CCK-8 assay was performed to determine the cells viability after EPI treatment. HepG2 and SMMC7721 cells were treated with EPI orEPI promotedEPI combined with

Subarachnoid haemorrhage (SAH) has a high rate of disability and mortality. Extremely damaging molecules, including adenosine triphosphate (ATP), are released from extravasated red blood cells and nerve cells, which activate microglia and induce sterile tissue injury and organ dysfunction. P2X purinoceptor 7 (P2X7) is one of the most important purine receptors on the microglial surface and is involved in the proinflammatory activation of microglia. While P2X7 can also affect microglial phagocytosis, the mechanism is not clear. Here, we demonstrated that microglial phagocytosis is progressively impaired under continued BzATP exposure and P2X7 activation. Furthermore, we found that P2X7 activation leads to increased intracellular Ca

Haematopoietic cell transplantation (HCT) is the only curative treatment for haematological complications in patients with Fanconi anaemia (FA). Haploidentical (haplo-) HCT is a promising alternative for FA. We aimed to analyse the outcomes of unmanipulated haplo-HCT in patients with FA with radiation-free conditioning. A total of 56 patients from 11 centres between 2013 and 2021 in China were retrospectively analysed. The mean (SD) cumulative incidence was 96.4% (0.08%) for 30-day neutrophil engraftment and 85.5% (0.24%) for 100-day platelet engraftment. With a median (range) follow-up of 2.4 (0.2-5.8) years, favourable mean (SD) overall survival of 80.9% (5.5%) and event-free survival of 79.3% (5.6%) were achieved. The mean (SD) incidences of acute graft-versus-host disease (aGvHD) Grade II-IV and Grade III-IV were 55.4% (0.45%) and 42.9 (0.45%) respectively. The mean (SD) cumulative incidence of 3-year chronic graft-versus-host disease (cGvHD) was 34.7% (0.86%) and that of moderate-to-severe cGvHD was 9.0% (0.19%). Our data demonstrate that in unmanipulated haplo-HCT for patients with FA, radiation-free regimens based on fludarabine and low-dose cyclophosphamide ± busulfan achieved favourable engraftment and survival with relatively high incidences of aGvHD and cGvHD. These results prompt the use of low-intensity conditioning without radiation and intensive GvHD prophylaxis when considering unmanipulated haplo-HCT in patients with FA.

DNA can act as a scaffold for the cooperative binding of protein oligomers. For example, the phage 186 CI repressor forms a wheel of seven dimers wrapped in DNA with specific binding sites, while phage λ CI repressor dimers bind to two well-separated sets of operators, forming a DNA loop. Atomic force microscopy was used to measure transcription elongation by Escherichia coli RNA polymerase (RNAP) through these protein complexes. 186 CI, or λ CI, bound along unlooped DNA negligibly interfered with transcription by RNAP. Wrapped and looped topologies induced by these scaffolded, cooperatively bound repressor oligomers did not form significantly better roadblocks to transcription. Thus, despite binding with high affinity, these repressors are not effective roadblocks to transcription.

This paper examines the role of the Belt and Road Initiative (BRI) in enhancing political relations between China and its partner countries. We postulate that an international economic cooperation scheme such as the BRI may facilitate commercial exchanges and increase the participating countries’ economic gains. This should generate incentives for these countries to avoid political tensions that may jeopardize mutually beneficial economic exchanges, and to expand the constellation of domestic coalitions in support of cordial diplomatic and political relations. We test the effect of the BRI on bilateral political relations using data on political relations between China and 91 countries along the BRI route between 2006 and 2018. Treating the promulgation of the BRI in 2013 as a policy shock, our difference‐in‐difference analysis lends substantial support to our hypotheses. Further analyses of the underlying causal mechanisms suggest that the BRI bolsters political relations by strengthening economic ties with partner countries through trade and investment related to economic cooperation.

Background In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non‐small cell lung cancer (NSCLC) and its related mechanism is still unclear. Methods In this study, we explored the anticancer effect induced by iodine‐125 (125I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl‐2/Bax expression level, cell cycle, CCK‐8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125I and SCU. Results SCU at a sensitizing concentration promoted the 125I‐induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125I and SCU. Conclusions The results of our study suggested that SCU promotes the anticancer effects induced by 125I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment., Scutellarin (SCU) enhanced inhibition of 125I‐induced proliferation, promoted 125I‐induced apoptosis, and boosted 125I‐induced tumor inhibition in vivo in non‐small cell lung cancer (NSCLC) cells, as well as enhanced downregulation of the 125I‐induced AKT/mTOR pathway.

Developing efficient piezocatalytic systems for two-electron water splitting (TEWS) with producing H

BACKGROUND AND PURPOSE Dioscin has multiple biological activities and is beneficial for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of dioscin against subarachnoid haemorrhage and the molecular mechanisms involved. EXPERIMENTAL APPROACH Dioscin was administered after subarachnoid haemorrhage induced in rats. MCC950, a potent selective nod-like receptor pyrin domain-containing 3 (NLRP3) inhibitor, was used to suppress NLRP3 and EX527 (selisistat) was used to inhibit sirtuin 1 (SIRT1). KEY RESULTS In vivo, dioscin inhibited acute inflammatory response, oxidative damage, neurological impairment and neural cell degeneration after subarachnoid haemorrhage along with dramatically suppressing NLRP3 inflammasome activation. While pretreatment with MCC950 reduced the inflammatory response and improved neurological outcomes it did not lessen ROS production. However, giving dioscin after MCC950 reduced acute brain damage and ROS production. Dioscin increased SIRT1 expression after subarachnoid haemorrhage, whereas EX527 abolished the up-regulation of SIRT1 induced by dioscin and offset the inhibitory effects of dioscin on NLRP3 inflammasome activation. EX527 pretreatment also reversed the neuroprotective effects of dioscin against subarachnoid haemorrhage. Similarly, in vitro, dioscin dose-dependently suppressed inflammatory response, oxidative damage and neuronal degeneration and improved cell viability in neurons and microglia co-culture system. These effects were associated with inhibition of the NLRP3 inflammasome and stimulation of SIRT1 signalling, which could be inhibited by EX527 pretreatment. CONCLUSION AND IMPLICATIONS Dioscin provides protection against subarachnoid haemorrhage via the suppression of NLRP3 inflammasome activation through SIRT1-dependent pathway. Dioscin may be a new candidate to ameliorate early brain injury after subarachnoid haemorrhage.

Background and purpose Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action. Experimental approach A weight-drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed. Key results Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor-erythroid 2-related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down-regulated the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro. Conclusion and implications Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.

Theoretical studies have shown that surface terminations, such as MAI or PbI layers, greatly affect the environmental stability of organic-inorganic perovskite. However, until now, there has been little effort to experimentally detect the existence of MAI or PbI terminations on MAPbI3 grains, let alone disclose their effects on the humidity degradation pathway of perovskite solar cell. Here, we successfully modified and detected the surface terminations of MAI and PbI species on polycrystalline MAPbI3 films. MAI-terminated perovskite film followed the moisture degradation process from MAPbI3 to hydrate MAPbI3 ⋅H2 O and then into PbI2 , with penetration of water molecules being the main driving force leading to the degradation of MAPbI3 layer by layer. In contrast, for the PbI-terminated perovskite film in a humid atmosphere, a deprotonation degradation pathway was confirmed, in which the film preferentially degraded directly from MAPbI3 into PbI2 , here the iodine defects played a key role in promoting the dissociation of water molecules into OH- and further catalyzing the decomposition of perovskite.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β1 (TGF‐β1) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

We examine the relation between social trust and the speed of leverage adjustment (SOA) around the world. Using a large international sample (65 countries, 1996–2016), we find that social trust has a positive effect on SOA. In the cross section, we find that the positive effect of social trust on the SOA is more pronounced for: (i) over-levered firms; (ii) firms with higher information asymmetry; (iii) firms with lower ease of financing; and (iv) firms located in countries with weaker governance quality. Overall, we highlight the role of social trust in shaping corporate capital structure.

Previously, it was found that the hepatitis C virus NS5A interacted with ACBD3 in a genotype-dependent manner. However, the region in NS5A responsible for association with ACBD3 is not clear. Domain I of NS5A was identified as critical for ACBD3 binding. By comparing the differences of amino acids in domain I from different genotypes of NS5A, it was found that key amino acids potentially corresponded to the affinity of the NS5A-ACBD3 interaction. The findings not only revealed that domain I of NS5A associates with ACBD3 but they also shed mechanistic light on how NS5A is associated with ACBD3 in a genotype-dependent manner.

Background Sulfonylureas are potentially toxic broad-spectrum herbicides. They pose a persistent threat to food safety and the environment. It is therefore important to develop a rapid and efficient pretreatment and detection method to prevent their harmful effects on human health. Results In the present work, a novel and highly selective absorbent for chlorosulfuron (CS) detection was prepared by the simple self-polymerization of dopamine on the surface of magnetic graphene oxide using a CS template. The resultant imprinted nanoparticles (MGO@PDA-MIPs) were characterized by transmission electron microscopy, X-ray diffraction, vibrating-sample magnetometry, thermogravimetric analysis, and nitrogen adsorption-desorption. The adsorption experiments demonstrated that the MGO@PDA-MIPs have excellent selectivity with regard to CS, with a high imprinting factor of 3.41 compared with a non-imprinted polymer. The nanoparticles rapidly achieve adsorption equilibrium and efficient desorption because there are numerous binding sites on the thin polydopamine imprinting layer. Under optimized conditions, the MGO@PDA-MIPs can be used to detect sulfonylurea residues in cereal samples by magnetic solid phase extraction coupled with high performance liquid chromatography (HPLC). The nanoparticles have a satisfactory recovery rate (80.65-101.01%) with a relative standard deviation (RSD) of less than 7.15%, and a limit of detection with regard to CS of 1.61 μg kg-1 (S/N = 3). They can also be re-used at least seven times. Conclusion The MGO@PDA-MIPs have outstanding recognition performance, and can be prepared by a facile, single-step, and environmentally friendly process. They therefore have excellent potential for the recognition and separation of trace sulfonylurea herbicides in complex matrices. © 2020 Society of Chemical Industry.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes the recent COVID‐19 public health crisis. Bat is the widely believed original host of SARS‐CoV‐2. However, its intermediate host before transmitting to humans is not clear. Some studies proposed pangolin, snake, or turtle as the intermediate hosts. Angiotensin‐converting enzyme 2 (ACE2) is the receptor for SARS‐CoV‐2, which determines the potential host range for SARS‐CoV‐2. On the basis of structural information of the complex of human ACE2 and SARS‐CoV‐2 receptor‐binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS‐CoV‐2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS‐CoV‐2 RBD. We found that nearly half of the key residues in turtle, snake, and bird were changed. The simulated structures showed several key contacts with SARS‐CoV‐2 RBD in turtle and snake ACE2 were abolished. This study demonstrated that neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. This study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS‐CoV‐2., Research Highlights Affinities to SARS‐CoV‐2 S protein of the 20 key residues in ACE2 from mammal, bird, turtle and snake were analyzed.ACE2 proteins from Primates, Bovidae, Cricetidae and Cetacea were predicted to associate with SARS‐CoV‐2 RBD.Neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2

The present work reported a novel hydrophilic and selective solid-phase microextraction fiber by improved multiple co-polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high-performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid-phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross-linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid-phase microextraction conditions, satisfactory linearity (5-1000 µg/L) and detection limits (0.38-0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3-104.4%.

The synthesis of NH-sulfoximines from sulfides has been first developed under mild conditions in an aqueous solution with surfactant TPGS-750-M as the catalyst at room temperature. In this newly developed process, a simple and convenient recycling strategy to regenerate the indispensable hypervalent iodine(III) is used. The resulting 1,2,3-trifluoro-5-iodobezene can be recovered almost quantitively from the mixture by liquid-liquid extraction and then oxidized to give the corresponding iodine(III) species. This optimized procedure is compatible with a broad range of functional groups and can be easily performed on a gram scale, providing a green protocol for the synthesis of sulfoximines.

More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement. However, most patients inevitably develop crizotinib resistance due to acquired secondary mutations in the ALK kinase domain, such as the gatekeeper mutation L1196M and the most refractory mutation, G1202R. Here, we develop XMU‐MP‐5 as a new‐generation ALK inhibitor to overcome crizotinib resistance mutations, including L1196M and G1202R. XMU‐MP‐5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild‐type or mutant EML4‐ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo. Structural analysis provides insights into the mode of action of XMU‐MP‐5. In addition, XMU‐MP‐5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models, further demonstrating its pharmacological efficacy and potential for clinical application. These preclinical data support XMU‐MP‐5 as a novel selective ALK inhibitor with high potency and selectivity. XMU‐MP‐5 holds great promise as a new therapeutic against clinically relevant secondary ALK mutations., Despite the clinical success of ALK inhibitors in NSCLC, multiple drug‐resistant mutations in ALK are inevitably reported. XMU‐MP‐5 overcomes resistance to first and second generation ALK inhibitors in vitro and in vivo, thus holds great promise for the therapeutic use against ALK‐positive NSCLC.

As low-dimensional lead-free hybrids with higher stability and lower toxicity than those of three-dimensional lead perovskites, organic antimony(III) halides show great application potential in opt-electronic field owing to diverse topologies along with exceptional optical properties. We report herein an antimony(III) hybrid (MePPh3 )2 SbCl5 with a zero-dimensional (0D) structure, which exhibits brilliant orange emission peaked at 593 nm with near-unity photoluminescent quantum yield (99.4 %). The characterization of photophysical properties demonstrates that the broadband emission with a microsecond lifetime (3.24 μs) arises from self-trapped emission (STE). Electrically driven organic light-emitting diodes (OLEDs) based on neat and doped films of (MePPh3 )2 SbCl5 were fabricated. The doped devices show significant improvement in comparison to non-doped OLEDs. Owing to the much improved surface morphology and balanced carrier transport in light-emitting layers of doped devices, the peak luminance, current efficiency (CE) and external quantum efficiency (EQE) are boosted from 82 cd m-2 to 3500 cd m-2 , 1.1 cd A-1 to 6.8 cd A-1 , and 0.7 % to 3.1 % relative to non-doped devices, respectively.