In Situ Cross-Linking Strategy to Enable Highly Stable Perovskite Solar Cells.

The perovskite solar cells (PSCs) have achieved great success in power conversion efficiency due to their excellent optoelectrical properties of perovskite. However, the instability of PSCs severely impedes their commercialization. Recently, in situ cross-linking strategy has been proposed to mitigate stability issues of PSCs, enabling highly efficient and stable PSCs. Here, the critical factors that lead to the degradation of PSCs are first outlined. Then, a comprehensive review of in situ cross-linking strategy in perovskite to enhance the moisture, thermal, illumination, and bending stress resistance properties of PSCs is presented. Furthermore, the detailed mechanism underlying these advantageous effects is discussed pertaining to crystallization regulation, immobilization of ions, water resistance, and release of unfavorable stress. Finally, the current challenges and further development trends of in situ cross-linking strategy in PSCs and extension to other optoelectronic devices are prospected.

RHOA-regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia.

The Philadelphia 9;22 chromosome translocation has two common isoforms that are preferentially associated with distinct subtypes of leukemia. The p210 variant is the hallmark of chronic myeloid leukemia (CML) whereas p190 is frequently associated with B-cell acute lymphoblastic leukemia. The only sequence difference between the two isoforms is the guanidine exchange factor domain. This guanidine exchange factor is reported to activate RHO family GTPases in response to diverse extracellular stimuli. It is not clear whether and, if so, how RHOA contributes to progression of p210 CML. Here we show that knockout of RHOA in the K562 and KU812, p210-expressing cell lines leads to suppression of leukemogenesis in animal models in vivo. RNA-sequencing analysis of the mock control and null cells demonstrated a distinct change in the gene expression profile as a result of RHOA deletion, with significant downregulation of genes involved in cell activation and cell adhesion. Cellular analysis revealed that RHOA knockout leads to impaired cell adhesion and migration and, most importantly, the homing ability of leukemia cells to the bone marrow, which may be responsible for the attenuated leukemia progression. We also identified IGFBP2 as an important downstream target of RHOA. Further mechanistic investigation showed that RHOA activation leads to relocation of the serum response factor (SRF) into the nucleus, where it directly activates IGFBP2. Knockout of IGFBP2 in CML cells suppressed cell adhesion/invasion, as well as leukemogenesis in vivo. This elevated IGFBP2 expression was confirmed in primary CML samples. Thus, we demonstrate one mechanism whereby the RHOA-SRF-IGFBP2 signaling axis contributes to the development of leukemia in cells expressing the p210 BCR-ABL1 fusion kinase.

A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML.

BACKGROUND: Myeloid and lymphoid malignancies associated with chimeric FGFR1 kinases are the hallmark of stem cell leukemia and lymphoma syndrome (SCLL). In all cases, FGFR1 kinase is constitutively phosphoactivated as a result of chromosome translocations, which lead to acquisition of dimerization motifs in the chimeric proteins. Recently, we demonstrated that these chimeric kinases could be cleaved by granzyme B to generate a truncated derivative, tnFGFR1, which localized exclusively into the nucleus and was not phosphorylated. METHODS: Stem cell transduction and transplantation in syngeneic mice was used to assess the transforming ability of tnFGFR1 in bone marrow stem cells, and RPPA and RNA-Seq was used to examine the related signaling pathways and regulated target genes. RESULTS: For the first time, we show that this non-classical truncated form of FGFR1 can independently lead to oncogenic transformation of hematopoietic stem cells in an animal model in vivo. These leukemia cells show a mixed immunophenotype with a B-cell B220 + Igm- profile in the majority of cells and Kit+ in virtually all cells, suggesting a stem cell disease. tnFGFR1, however, does not activate classic FGFR1 downstream signaling pathways but induces a distinct profile of altered gene expression with significant upregulation of transmembrane signaling receptors including FLT3 and KIT. We further show that de novo human AML also express tnFGFR1 which correlates with upregulation of FLT3 and KIT as in mouse leukemia cells. ChIP analysis demonstrates tnFGFR1 occupancy at the Flt3 and Kit promoters, suggesting a direct transcriptional regulation. Cells transformed with tnFGFR1 are insensitive to FGFR1 inhibitors but treatment of these cells with the Quizartinib (AC220) FLT3 inhibitor, suppresses in vitro growth and development of leukemia in vivo. Combined treatment with FGFR1 and FLT3 inhibitors provides increased survival compared to FGFR1 inhibition alone. CONCLUSIONS: This study demonstrates a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative, which is associated with GZMB expression levels. Genes significantly upregulated by tnFGFR1 include Flt3 and Kit which promote a leukemia stem cell phenotype. In human AML, tnFGFR1 activation leads to increased FLT3 and KIT expression, and higher FLT3 and GZMB expression levels are associated with an inferior prognosis. These observations provide insights into the relative therapeutic value of targeting FGFR1 and FLT3 in treating AML with this characteristic gene expression profile.

A subtle connection between crossed cerebellar diaschisis and supratentorial collateral circulation in subacute and chronic ischemic stroke.

OBJECTIVES: It has not been reported whether collateral circulation, a factor closely related to the prognosis of patients with cerebral infarction, is related to the occurrence of crossed cerebellar diaschisis(CCD) or not. Our research attempts to verify the relationship between the collateral circulation grade and the occurrence of CCD, mainly by means of CTA and CTP. MATERIALS AND METHODS: A total of 47 patients were divided into a CCD-positive (Kim et al., 2019) or a CCD-negative group Furlanis et al. (2018) by calculating the asymmetry index (AI) value (<10%) of bilateral cerebellar cerebral blood flow (CBF). A 4-scale grading method was used to evaluate collateral circulation in the supratentorial infarct area, and the four perfusion parameters of the supratentorial and subtentorial brain regions were analyzed and compared between the two groups. The extent of vascular lesions was evaluated by MR sequences including DWI and MRA. RESULTS: Among the four perfusion parameters, except for CBV, were significantly different between the bilateral cerebellum in the CCD-positive group, but only TTP in the supratentorial cerebral infarction area was statistically different in the two groups. Moreover, the collateral circulation sore in the CCD-positive group was significantly lower than that in the CCD-negative group. But no statistical difference was found in the comparison of DWI positive rates between the two groups. CONCLUSION: The collateral score in the supratentorial infarct area is correlated with the occurrence of CCD,which may be used to explain the effect of CCD on the prognosis of patients.

IRAK1-regulated IFN-γ signaling induces MDSC to facilitate immune evasion in FGFR1-driven hematological malignancies.

BACKGROUND: Stem Cell leukemia/lymphoma syndrome (SCLL) presents as a myeloproliferative disease which can progress to acute myeloid leukemia and is associated with the coincident development of B-cell and T-cell lymphomas. SCLL is driven by the constitutive activation of fibroblast growth factor receptor-1 (FGFR1) as a result of chromosome translocations with poor outcome. Mouse models have been developed which faithfully recapitulate the human disease and have been used to characterize the molecular genetic events that are associated with development and progression of the disease. METHODS: CRISPR/Cas9 approaches were used to generate SCLL cells null for Interleukin receptor associated kinase 1 (IRAK1) and interferon gamma (IFNG) which were introduced into syngeneic hosts through tail vein injection. Development of the disease and changes in immune cell composition and activity were monitored using flow cytometry. Bead-based immunoassays were used to compare the cytokine and chemokine profiles of control and knock out (KO) cells. Antibody mediated, targeted depletion of T cell and MDSCs were performed to evaluate their role in antitumor immune responses. RESULTS: In SCLL, FGFR1 activation silences miR-146b-5p through DNMT1-mediated promoter methylation, which derepresses the downstream target IRAK1. IRAK1 KO SCLL cells were xenografted into immunocompetent syngeneic mice where the typical rapid progression of disease was lost and the mice remained disease free. IRAK1 in this system has no effect on cell cycle progression or apoptosis and robust growth of the KO cells in immunodeficient mice suggested an effect on immune surveillance. Depletion of T-cells in immunocompetent mice restored leukemogenesis of the KO cells, and tumor killing assays confirmed the role of T cells in tumor clearance. Analysis of the immune cell profile in mice transplanted with the IRAK1 expressing mock control (MC) cells shows that there is an increase in levels of myeloid-derived suppressor cells (MDSCs) with a concomitant decrease in CD4+/CD8+ T-cell levels. MDSC suppression assays and depletion experiments showed that these MDSCs were responsible for suppression of the T cell mediated leukemia cell elimination. Immuno-profiling of a panel of secreted cytokines and chemokines showed that activation of IFN-γ is specifically impaired in the KO cells. In vitro and in vivo expression assays and engraftment with interferon gamma receptor-1 (IFNGR1) null mice and IFNG KO SCLL cells, showed the leukemia cells produced IFN-γ directly participating in the induction of MDSCs to establish immune evasion. Inhibition of IRAK1 using pacritinib suppresses leukemogenesis with impaired induction of MDSCs and attenuated suppression of CD4+/CD8+ T-cells. CONCLUSIONS: IRAK1 orchestrates a previously unknown FGFR1-directed immune escape mechanism in SCLL, through induction of MDSCs via regulation of IFN-γ signaling from leukemia cells, and targeting IRAK1 may provide a means of suppressing tumor growth in this syndrome by restoring immune surveillance.

DNA methyltransferase 1-mediated CpG methylation of the miR-150-5p promoter contributes to fibroblast growth factor receptor 1-driven leukemogenesis.

MicroRNA-150-5p (miR-150-5p) plays a complex role in normal early hematopoietic development and is also implicated in the development of various different leukemias. We have reported previously that, in myeloid and lymphoid malignancies associated with dysregulated fibroblast growth factor receptor 1 (FGFR1) activities, miR-150-5p is down-regulated compared with healthy cells. Here, using murine cells, we found that this down-regulation is accompanied by CpG methylation of the miR-150-5p promoter region. Of note, analysis of human acute lymphoblastic leukemia (ALL) cohorts also revealed an inverse relationship between miR-150-5p expression and disease progression. We also found that the DNA methyltransferase 1 (DNMT1) enzyme is highly up-regulated in FGFR1-driven leukemias and lymphomas and that FGFR1 inhibition reduces DNMT1 expression. DNMT1 knockdown in stem cell leukemia/lymphoma (SCLL) cells increased miR-150-5p levels and reduced levels of the MYB proto-oncogene transcription factor, a key regulator of leukemogenesis. FGFR1 directly activates the MYC proto-oncogene basic helix-loop-helix transcription factor, which, as we show here, binds and activates the DNMT1 promoter. MYC knockdown decreased DNMT1 expression, which, in turn, increased miR-150-5p expression. One of the known targets of miR-150-5p is MYB, and treatment of leukemic cells with the MYB inhibitor mebendazole dose-dependently increased apoptosis and reduced cell viability. Moreover, mebendazole treatment of murine xenografts models of FGFR1-driven leukemias enhanced survival. These findings provide evidence that MYC activates MYB by up-regulating DNMT1, which silences miR-150-5p and promotes SCLL progression. We propose that inclusion of mebendazole in a combination therapy with FGFR1 inhibitors may be a valuable option to manage SCLL.

Critical individual roles of the BCR and FGFR1 kinase domains in BCR-FGFR1-driven stem cell leukemia/lymphoma syndrome.

Constitutive activation of FGFR1, as a result of diverse chromosome translocations, is the hallmark of stem cell leukemia/lymphoma syndrome. The BCR-FGFR1 variant is unique in that the BCR component contributes a serine-threonine kinase (STK) to the N-terminal end of the chimeric FGFR1 kinase. We have deleted the STK domain and mutated the critical Y177 residue and demonstrate that the transforming activity of these mutated genes is reduced compared to the BCR-FGFR1 parental kinase. In addition, we demonstrate that deletion of the FGFR1 tyrosine kinase domain abrogates transforming ability, which is not compensated for by BCR STK activity. Unbiased screening for proteins that are inactivated as a result of loss of the BCR STK identified activated S6 kinase and SHP2 kinase. Genetic and pharmacological inhibition of SHP2 function in SCLL cells expressing BCR-FGFR1 in vitro leads to reduced viability and increased apoptosis. In vivo treatment of SCLL in mice with SHP099 leads to suppression of leukemogenesis, supporting an important role for SHP2 in FGFR1-driven leukemogenesis. In combination with the BGJ398 FGFR1 inhibitor, cell viability in vitro is further suppressed and acts synergistically with SHP099 in vivo suggesting a potential combined targeted therapy option in this subtype of SCLL disease.

High-Resolution Vessel Wall Magnetic Resonance Imaging of the Middle Cerebral Artery: Comparison of 3D CUBE T1-Weighted Sequence with and without Fat Suppression.

BACKGROUND Fat suppression is an important technique in magnetic resonance imaging (MRI). Comprehensive and quantitative assessment of the influence of fat suppression (FS) on T1-weighted imaging of intracranial vessel wall imaging is needed. In this study, we compared the three-dimensional (3D) variable-flip-angle turbo-spin-echo (CUBE) T1-weighted sequence with and without FS to investigate the differences between the 2 sequences in imaging of the middle cerebral artery (MCA) vessel walls. MATERIAL AND METHODS A 3D CUBE T1-weighted sequence with and without FS by 3.0T MRI was used to obtain intracranial vessel wall images of 105 MCA stenosis patients. The image signal intensity, signal-to-noise ratio, and contrast-to-noise ratio were calculated and compared. Two observers evaluated the image quality of the 2 sequences twice, and interobserver and intraobserver consistency were determined. Differences between the 2 sequences in the area of lumen and plaque were compared. RESULTS The signal intensity, signal-to-noise ratio, and contrast-to-noise ratio of the 3D CUBE T1-weighted sequence without FS were higher, whereas the noise level was lower. In terms of subjective scores, the 3D CUBE T1-weighted sequence without FS performed better. No significant difference was observed in the measurement of the vascular lumen area between the 2 sequences, although there were statistically significant differences in the measurement of plaque area (i.e., the measurement obtained with 3D CUBE T1-weighted sequence without FS was larger). CONCLUSIONS 3D CUBE T1-weighted sequence without FS performed better for MCA vessel walls imaging than 3D CUBE T1-weighted sequence with FS.

Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome.

Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.

Salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promotes erythropoiesis at early stage targeted by ufmylation pathway.

Ufmylation was proved to play a crucial role in hematopoietic stem cell (HSC) survival and erythroid differentiation, ufmylation deficiency induces acute anemia and lethality of embryos and adults in mouse models. To screen some compounds to rescue phenotypes induced by gene deletion, in this study, we used DDRGK1F/F ; CreERT2 conditional knockout mice, DDRGK1F/F ; CreERT2 bone marrow (BM) and fetal liver cells (FL), Uba5, and DDRGK1 knockdown human CD34 cell in vivo and in vitro, we found salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promoted erythropoiesis at early stage, and partly rescued the acute anemia induce by DDRGK1 deficiency through upregulation of ufmylation and erythroid transcription factors. In phenylhydrazine (PHZ)-induced hemolytic anemia mice, interestingly, salubrinal could significantly improve hemocrit and red blood cell (RBC) indices of the mice treated with PHZ via upregulation of ufmylation. Its novel function was verified to attenuate unfolded protein response (UPR) and cell death programs, and to keep endoplasmic reticulum (ER) homeostasis in HSCs. Taken together results, it suggested that salubrinal may be a promising antianemic agent targeted by ufmylation.

Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function.

LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. However, LTR sequences are disproportionately present in human long, non-coding RNAs (lncRNAs). Whether and how the LTR lncRNAs serve biological functions are largely unknown. Here we show that in primary human erythroblasts, lncRNAs transcribed from the LTR retrotransposons of ERV-9 human endogenous retrovirus activated transcription of key erythroid genes and modulated ex vivo erythropoiesis. To dissect the functional mechanism of ERV-9 lncRNAs, we performed genome-wide RNA and ChIRP analyses before and after global knockdown or locus-specific deletion of ERV-9 lncRNAs in human erythroblasts carrying ∼4000 copies of the ERV-9 LTRs and in transgenic mouse erythroblasts carrying a single copy of the primate-specific ERV-9 LTR in the 100 kb human ß-globin gene locus. We found that ERV-9 lncRNAs acted in cis to stabilize assembly of the ERV-9 LTR enhancer complex and facilitate long-range LTR enhancer function in activating transcription of downstream, cis-linked globin genes. Our findings suggested that LTR lncRNAs transcribed from many of the 4000 copies of ERV-9 LTR retrotransposons acted by a similar cis mechanism to modulate LTR enhancer function in activating transcription of downstream genes critical to cellular processes including erythropoiesis.

Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas.

Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810. Two mutually exclusive mechanisms for resistance were demonstrated; an activating V561M mutation in the FGFR1 kinase domain and mutational inactivation of PTEN resulting in increased PI3K/AKT activity. Ectopic expression of PTEN in the PTEN-mutant cells resensitizes them to FGFR inhibitors. Treatment of resistant cells with BGJ398, in combination with the BEZ235 PI3K inhibitor, shows an additive effect on growth in vitro and prolongs survival in xenograft models in vivo. These studies provide the first direct evidence for both the involvement of the FGFR1 V561M mutation and PTEN inactivation in the development of resistance in leukemias overexpressing chimeric FGFR1. These studies also provide a potential strategy to treat leukemias and lymphomas driven by FGFR1 activation that become resistant to FGFR1 inhibitors.

Hydroxyurea differentially modulates activator and repressors of γ-globin gene in erythroblasts of responsive and non-responsive patients with sickle cell disease in correlation with Index of Hydroxyurea Responsiveness.

Hydroxyurea (HU), the first of two drugs approved by the US Food and Drug Administration for treating patients with sickle cell disease (SCD), produces anti-sickling effect by re-activating fetal γ-globin gene to enhance production of fetal hemoglobin. However, approximately 30% of the patients do not respond to HU therapy. The molecular basis of non-responsiveness to HU is not clearly understood. To address this question, we examined HU-induced changes in the RNA and protein levels of transcription factors NF-Y, GATA-1, -2, BCL11A, TR4, MYB and NF-E4 that assemble the γ-globin promoter complex and regulate transcription of γ-globin gene. In erythroblasts cultured from peripheral blood CD34+ cells of patients with SCD, we found that HU-induced changes in the protein but not the RNA levels of activator GATA-2 and repressors GATA-1, BCL11A and TR4 correlated with HU-induced changes in fetal hemoglobin (HbF) levels in the peripheral blood of HU high and low responders. However, HU did not significantly induce changes in the protein or RNA levels of activators NF-Y and NF-E4. Based on HU-induced changes in the protein levels of GATA-2, -1 and BCL11A, we calculated an Index of Hydroxyurea Responsiveness (IndexHU-3). Compared to the HU-induced fold changes in the individual transcription factor protein levels, the numerical values of IndexHU-3 statistically correlated best with the HU-induced peripheral blood HbF levels of the patients. Thus, IndexHU-3 can serve as an appropriate indicator for inherent HU responsiveness of patients with SCD.

Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis.

BACKGROUND: Leukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression. METHODS: Single cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression. RESULTS: scRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis. CONCLUSION: We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

Spike-based dynamic computing with asynchronous sensing-computing neuromorphic chip.

By mimicking the neurons and synapses of the human brain and employing spiking neural networks on neuromorphic chips, neuromorphic computing offers a promising energy-efficient machine intelligence. How to borrow high-level brain dynamic mechanisms to help neuromorphic computing achieve energy advantages is a fundamental issue. This work presents an application-oriented algorithm-software-hardware co-designed neuromorphic system for this issue. First, we design and fabricate an asynchronous chip called "Speck", a sensing-computing neuromorphic system on chip. With the low processor resting power of 0.42mW, Speck can satisfy the hardware requirements of dynamic computing: no-input consumes no energy. Second, we uncover the "dynamic imbalance" in spiking neural networks and develop an attention-based framework for achieving the algorithmic requirements of dynamic computing: varied inputs consume energy with large variance. Together, we demonstrate a neuromorphic system with real-time power as low as 0.70mW. This work exhibits the promising potentials of neuromorphic computing with its asynchronous event-driven, sparse, and dynamic nature.

Correlation of the middle cerebral artery atherosclerotic plaque characteristics with ischemic stroke recurrence: a vessel wall magnetic resonance imaging study.

This study aims to analyze the imaging features of atherosclerotic plaques in the middle cerebral artery (MCA) of patients with recurrent ischemic stroke using vessel wall magnetic resonance imaging (VWMRI) and investigate the correlation between these imaging features and the recurrence of ischemic stroke. Consecutive patients with ischemic stroke caused by atherosclerotic stenosis of the MCA were collected. The patients were divided into recurrent and non-recurrent ischemic stroke groups. We obtained VWMRI images of MCA plaques using 3.0T MRI by black-blood sequences, and the differences in VWMRI characteristics and clinical information between the two groups were compared. A binary Logistic regression model was used to analyze the VWMRI characteristics and clinical information related to ischemic stroke recurrence. 179 patients were collected from August 2018 to May 2020, and 81 patients were included in the study. The recurrent ischemic stroke group patients had a higher stenosis rate (0.69 vs 0.64). Meanwhile, the rate of centripetal wall thickening was significantly higher in patients with recurrent ischemic stroke (33.3% vs 11.7%). Binary Logistic regression analysis showed that sex (P=0.036, OR:2.983, CI:1.075-8.279), stenosis rate (P=0.038, OR:148.565, CI:1.331-16583.631), and vessel wall thickening pattern (P=0.012, OR:0.171, CI:0.043-0.678) were related to ischemic stroke recurrence. The patients with ischemic stroke caused by atherosclerotic stenosis of MCA, female patients, and those with concentric wall thickening and a high degree of stenosis have a higher risk of recurrence. Our results suggest that VWMRI is a valuable tool for predicting the risk of ischemic stroke recurrence in patients with MCA plaques.

Green Solvent Polishing Enables Highly Efficient Quasi-2D Perovskite Solar Cells.

Preferred crystalline orientation at the surface of quasi-2D organic-inorganic halide perovskites is crucial to promote vertical carrier transport and interface carrier extraction, which further contribute to device efficiency and stability in photovoltaic applications. However, loose unoriented and defective surfaces are inevitably formed in the crystallization process, especially with the introduction of bulky organic cations into the quasi-2D perovskites. Here, a facile and effective surface polishing method using a natural-friendly green solvent, 2,2,2-trifluoroethanol, is proposed to reconstruct the surface. After solvent polishing, the randomly oriented phases containing trap sites on the surface are successfully removed, and the compact vertical-oriented phases underneath are revealed with less defectiveness and better smoothness, which greatly facilitates carrier transport and interfacial charge extraction. Consequently, the green solvent polished devices show a boosting efficiency of 18.38% with a high open-circuit voltage of 1.21 V. The devices also show improved storage and operational stability.

Intermediate Phase Free α-FAPbI3 Perovskite via Green Solvent Assisted Perovskite Single Crystal Redissolution Strategy.

Perovskite single-crystal redissolution (PSCR) strategy is highly desired for efficient formamidinium lead triiodide (FAPbI3 ) perovskite photovoltaics with enhanced phase purity, improved film quality, low trap-state density, and good stability. However, the phase transition and crystallization dynamics of FAPbI3 remain unclear in the PSCR process compared to the conventional fabrication from the mixing of precursor materials. In this work, a green-solvent-assisted (GSA) method is employed to synthesize centimeter-sized α-FAPbI3 single crystals, which serve as the high-purity precursor to fabricate perovskite films. The α-FAPbI3 PSCR strategy facilitates direct α-phase formation and inhibits the complex intermediate phases monitored by in situ grazing-incidence wide-angle X-ray scattering. Moreover, the α-phase stability is prolonged due to the relaxation of the residual lattice strain through the isotropic orientation phase growth. Consequently, the GSA-assisted PSCR strategy effectively promotes crystallization and suppresses non-radiative recombination in perovskite solar cells, which boosts the device efficiency from 22.08% to 23.92% with significantly enhanced open circuit voltage. These findings provide deeper insight into the PSCR process in terms of its efficacy in phase formation and lattice strain release. The green low-cost solvent may also offer a new and ideal solvent candidate for large-scale production of perovskite photovoltaics.

Application and interpretation of vessel wall magnetic resonance imaging for intracranial atherosclerosis: a narrative review.

Background and Objective: Atherosclerosis is a systemic disease that occurs in the arteries, and it is the most important causative factor of ischemic stroke. Vessel wall magnetic resonance imaging (VWMRI) is one of the best non-invasive methods for displaying the vascular features of intracranial atherosclerosis. The main clinical applications of this technique include the exploration of the pathogenesis of intracranial atherosclerotic lesions, follow-up monitoring, and treatment prognosis judgment. As the demand for intracranial VWMRI increases in clinical practice, radiologists should be aware of the selection of imaging parameters and how they affect image quality, clinical indications, evaluation methods, and limitations in interpreting these images. Therefore, this review focused on describing how to perform and interpret VWMRI of intracranial atherosclerotic lesions. Methods: We searched the studies on the application of VWMRI in the PubMed database from January 1, 2000 to March 31, 2022, and focused on the analysis of related studies on VWMRI in atherosclerotic lesions, including technical application, expert consensus, imaging characteristics, and the clinical significance of intracranial atherosclerotic lesions. Key Content and Findings: We reviewed and summarized recent advances in the clinical application of VWMRI in atherosclerotic diseases. Currently accepted principles and expert consensus recommendations for intracranial VWMRI include high spatial resolution, multiplanar two and three-dimensional imaging, multiple tissue-weighted sequences, and blood and cerebrospinal fluid suppression. Understanding the characteristics of VWMRI of normal intracranial arteries is the basis for interpreting VWMRI of atherosclerotic lesions. Evaluating VWMRI imaging features of intracranial atherosclerotic lesions includes plaque morphological and enhancement characteristics. The evaluation of atherosclerotic plaque stability is the highlight of VWMRI. Conclusions: VWMRI has a wide range of clinical applications and can address important clinical questions and provide critical information for treatment decisions. VWMRI plays a key role in the comprehensive evaluation and prevention of intracranial atherosclerosis. However, intracranial VWMRI is still unable to obtain in vivo plaque pathological specimens for imaging-pathological comparison is the most significant limitation of this technique. Further technical improvements are expected to reduce acquisition time and may ultimately contribute to a better understanding of the underlying pathology of lesions on VWMRI.