Relationship between stress hyperglycemia ratio and prognosis in patients with aneurysmal subarachnoid hemorrhage: a two-center retrospective study.

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.

Microcephaly type 22 and autism spectrum disorder: A case report and review of literature.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular dissection as a potential underlying cause of ASD. METHODS: A 9-year-old child presented with symptoms of ASD, including social interaction difficulties, repetitive behaviors, and cognitive challenges. Despite conventional ASD treatments, significant improvement was only observed after addressing an underlying ischemic cryptogenic vascular dissection identified through DCE-CT. RESULTS: Following a reconstructive treatment approach to the vascular dissection, the patient showed marked improvement in cognitive functions, social abilities, and a reduction in ASD-related symptoms whether during the perioperative period or during approximately 5-month follow-up. CONCLUSION: This case suggests that ischemic cryptogenic vascular dissection may contribute to the symptoms of ASD. Identifying and treating underlying vascular anomalies may offer a new avenue for mitigating ASD symptoms, emphasizing the need for comprehensive diagnostic estimations in ASD management.

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants.

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, we developed Cas-SF01, a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases. Compared to natural Cas12i3, Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs. In addition, we identified an amino acid substitution, D876R, that markedly reduced the off-target effect while maintaining high on-target activity, leading to the development of Cas-SF01HiFi (high-fidelity Cas-SF01). Finally, we show that Cas-SF01 has high gene editing activities in mice and plants. Our results suggest that Cas-SF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

Caveolin-1 promotes glioma progression and maintains its mitochondrial inhibition resistance.

BACKGROUND: Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy. METHODS: From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival. RESULTS: Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells' resistant to oxidative phosphorylation inhibitors. CONCLUSION: Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas.

PWL1, a G-type lectin receptor-like kinase, positively regulates leaf senescence and heat tolerance but negatively regulates resistance to Xanthomonas oryzae in rice.

Plant leaf senescence, caused by multiple internal and environmental factors, has an important impact on agricultural production. The lectin receptor-like kinase (LecRLK) family members participate in plant development and responses to biotic and abiotic stresses, but their roles in regulating leaf senescence remain elusive. Here, we identify and characterize a rice premature withered leaf 1 (pwl1) mutant, which exhibits premature leaf senescence throughout the plant life cycle. The pwl1 mutant displayed withered and whitish leaf tips, decreased chlorophyll content, and accelerated chloroplast degradation. Map-based cloning revealed an amino acid substitution (Gly412Arg) in LOC_Os03g62180 (PWL1) was responsible for the phenotypes of pwl1. The expression of PWL1 was detected in all tissues, but predominantly in tillering and mature leaves. PWL1 encodes a G-type LecRLK with active kinase and autophosphorylation activities. PWL1 is localized to the plasma membrane and can self-associate, mainly mediated by the plasminogen-apple-nematode (PAN) domain. Substitution of the PAN domain significantly diminished the self-interaction of PWL1. Moreover, the pwl1 mutant showed enhanced reactive oxygen species (ROS) accumulation, cell death, and severe DNA fragmentation. RNA sequencing analysis revealed that PWL1 was involved in the regulation of multiple biological processes, like carbon metabolism, ribosome, and peroxisome pathways. Meanwhile, interfering of biological processes induced by the PWL1 mutation also enhanced heat sensitivity and resistance to bacterial blight and bacterial leaf streak with excessive accumulation of ROS and impaired chloroplast development in rice. Natural variation analysis indicated more variations in indica varieties, and the vast majority of japonica varieties harbour the PWL1Hap1 allele. Together, our results suggest that PWL1, a member of LecRLKs, exerts multiple roles in regulating plant growth and development, heat-tolerance, and resistance to bacterial pathogens.

Vimentin promotes glioma progression and maintains glioma cell resistance to oxidative phosphorylation inhibition.

PURPOSE: Glioma has been demonstrated as one of the most malignant intracranial tumors and currently there is no effective treatment. Based on our previous RNA-sequencing data for oxidative phosphorylation (OXPHOS)-inhibition resistant and OXPHOS-inhibition sensitive cancer cells, we found that vimentin (VIM) is highly expressed in the OXPHOS-inhibition resistant cancer cells, especially in glioma cancer cells. Further study of VIM in the literature indicates that it plays important roles in cancer progression, immunotherapy suppression, cancer stemness and drug resistance. However, its role in glioma remains elusive. This study aims to decipher the role of VIM in glioma, especially its role in OXPHOS-inhibition sensitivity, which may provide a promising therapeutic target for glioma treatment. METHODS: The expression of VIM in glioma and the normal tissue has been obtained from The Cancer Genome Atlas (TCGA) database, and further validated in Human Protein Atlas (HPA) and Chinese Glioma Genome Atlas (CGGA). And the single-cell sequencing data was obtained from TISCH2. The immune infiltration was calculated via Tumor Immune Estimation Resource (TIMER), Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data (ESTIMATE) and ssGSEA, and the Immunophenoscore (IPS) was calculated via R package. The differentiated expressed genes were analyzed including GO/KEGG and Gene Set Enrichment Analysis (GSEA) between the VIM-high and -low groups. The methylation of VIM was checked at the EWAS and Methsurv. The correlation between VIM expression and cancer stemness was obtained from SangerBox. We also employed DepMap data and verified the role of VIM by knocking down it in VIM-high glioma cell and over-expressing it in VIM-low glioma cells to check the cell viability. RESULTS: Vim is highly expressed in the glioma patients compared to normal samples and its high expression negatively correlates with patients' survival. The DNA methylation in VIM promoters in glioma patients is lower than that in the normal samples. High VIM expression positively correlates with the immune infiltration and tumor progression. Furthermore, Vim is expressed high in the OXPHOS-inhibition glioma cancer cells and low in the OXPHOS-inhibition sensitive ones and its expression maintains the OXPHOS-inhibition resistance. CONCLUSIONS: In conclusion, we comprehensively deciphered the role of VIM in the progression of glioma and its clinical outcomes. Thus provide new insights into targeting VIM in glioma cancer immunotherapy in combination with the current treatment.

Deciphering the role of QPCTL in glioma progression and cancer immunotherapy.

Background: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy. Methods: QPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors. Results: In contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p < 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p < 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness. Conclusion: High QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.

Predictors of recurrence and complications for the endovascular treatment of unruptured middle cerebral artery aneurysm: A high-volume center experience over 12 years.

OBJECT: To assess the safety and efficacy of endovascular treatment (EVT) of unruptured middle cerebral artery (MCA) aneurysms in a retrospective cohort in a high-volume center. Predictors of complications and recurrence were determined. METHODS: Retrospectively reviewed our database of prospectively collected information for all patients with unruptured MCA aneurysms that were treated by endovascular approach from March 2008 to December 2020. A multivariate analysis was conducted to identify predictors of complications and recurrence. RESULTS: Three hundred and fifty-one patients with 370 unruptured MCA aneurysms underwent EVT were included in this study. Seventy-three aneurysms (19.7%) were treated by coiling without stent, 297 (80.3%) with stent-assisted coiling. The procedures were performed with a technical success rate of 100%. Procedure-related neurological complications occurred in 15 patients (4.1%), including 1 patient died from post-procedural stent thrombosis. Age ≥ 65 years (P = 0.039; OR = 3.400; 95% CI, 1.065-10.860) and aneurysm size ≥ 5 mm (P = 0.009; OR = 15.524; 95% CI, 1.988-121.228) were significantly associated with ischemic complications of EVT. Three hundred and six aneurysms were (87.2%) completed image follow-up (235 DSA and 71 CE-MRA). The median angiographic follow-up time were 7.0 ± 4.3 months (range from 1 to 88 months). Follow-up angiograms showed that 249 aneurysms (81.4%) were completed occluded, 29 aneurysms (9.5%) were improved, 17 aneurysms (5.6%) were stable, and 11 aneurysms (3.6%) were recanalized and 10 of them accepted retreatments. Aneurysm size ≥ 10 mm was a predictor of recanalization (P = 0.004; OR = 11.213; 95% CI, 2.127-59.098) and stent-assisted coiling can significantly reduce recanalization (P = 0.004; OR = 0.105; 95% CI, 0.023-0.479). CONCLUSIONS: EVT is a safe and effective therapeutics for unruptured MCA aneurysms management, and provides durable aneurysm occlusion rate during follow-up. Large MCA aneurysms have higher recurrence and ischemic complications risk after EVT. Stent-assisted coiling can significantly reduce the recurrence rate without increasing the risk of complications.

Retreatment with a flow diverter for recurrent blood blister-like aneurysms after embolization: A single-center case series.

Background and purpose: Treatment of blood blister-like aneurysms (BBAs) has been a significant challenge mainly due to their high recurrence rate even after stent-assisted coiling (SAC) embolization. This study aims to evaluate the safety and efficacy of treating recurrent BBAs after SAC with a flow diverter (FD). Methods: A retrospective series of patients with recurrent BBAs who underwent the retreatment with the FD from June 2018 to December 2021 was included to analyze perioperative safety and immediate postoperative and follow-up outcomes. Results: The study enrolled 13 patients with recurrent BBAs previously treated with SAC. Within previous stents, an FD was deployed for retreatment, including eight Tubridge FDs and five PEDs. The time interval between initial treatment and FD implantation was 14-90 days. A total of 11 cases were treated with a single FD alone; two cases were treated with further endovascular coiling embolization, followed by FD implantation. The angiographic follow-up (6-12 months) was available in 12 patients, and all 12 recurrent BBAs were completely occluded. No perioperative complication was detected, and no rebleeding was found during the clinical follow-up (6-36 months). Conclusion: The use of the FD to manage recurrent BBAs after SAC is technically feasible, safe, and effective. The key to the success of the procedure is to ensure that the FD stent is fully open and has good apposition with the previously implanted stent.

Development of Designer Transcription Activator-Like Effector-Based Plant Growth Regulator for Higher Yield in Rice.

Recent studies have shown that reprogramming of gene expression in a genome can induce the production of proteins enabling yield increase. The transcription activator-like effectors (TALEs) from several species of bacterial Xanthomonas have been extensively studied, and a series of research tools, such as genome editing tool TALENs and gene expression activators, have been developed based on the specific protein-nucleic acid recognition and binding mechanisms of TALEs. In this proof-of-principle study, we designed and constructed a designer TALE (dTALE), designated as dTALE-NOG1, to specifically target the promoter of OsNOG1 gene in rice, and demonstrated that this dTALE can be used as a new type of plant growth regulator for better crop growth and harvest. In doing so, the dTALE-NOG1 was transferred into the non-pathogenic Xanthomonas oryzae pv. oryzae (Xoo) strain PH to generate a genetically engineered bacteria (GEB) strain called PH-dtNOG1. Functional verification showed that dTALE-NOG1 could significantly induce the expression of OsNOG1. By spraying cell suspension of PH-dtNOG1 on the rice plants during the tillering stage, the transcription level of OsNOG1 was highly enhanced, the grain number of rice plants was increased by more than 11.40%, and the grain yield per plant increased by more than 11.08%, demonstrating that the dTALE-NOG1 was highly effective in enhancing rice yield. This work provided a new strategy for manipulating agronomical traits by reprogramming gene expression in a crop genome.

DNA Damage Response Evaluation Provides Novel Insights for Personalized Immunotherapy in Glioma.

Background: DNA damage response (DDR) proficiency is the principal mechanism of temozolomide (TMZ) resistance in glioma. Accumulating evidence has also suggested the determining role of DDR in anticancer immunity. We propose that a comprehensive investigation of the DDR landscape can optimize glioma treatment. Methods: We identified the pronounced enrichment of DDR in TMZ-resistant glioma cells by RNA sequencing. Nine differentially expressed genes between TMZ-sensitive/resistant glioma cells were selected to construct the DDR score through lasso regression analysis. Two glioma cohorts from TCGA and CGGA were interrogated to evaluate the predictive ability of DDR score. Multiple algorithms were applied to estimate the immunotherapeutic responses of two DDR phenotypes. Immunohistochemistry was used to determine the protein levels of PD-L1 and TGFß in glioma specimens. The oncoPredict package was employed to predict the candidate chemotherapy agents. Results: DDR score exhibited a robust prognostic capability in TCGA and CGGA cohorts and served as an independent predictive biomarker in glioma patients. Functional enrichment analyses revealed that high and low DDR score groups were characterized by distinct immune activity and metabolic processes. Elevated levels of infiltrating immune cells (including CD8+ T cells, CD4+ T cells, and dendritic cells) were observed in the high DDR score glioma. Further, high DDR scores correlated with increased mutation burden, up-regulated immune checkpoints, and tumor immunity activation, indicating a profound interplay between DDR score and glioma immunogenicity. In addition, PD-L1 and TGFß were overexpressed in recurrent glioma specimens compared with primary ones. Finally, we estimated that PI3K inhibitors may serve as latent regimens for high DDR score patients. Conclusion: Our study highlighted the promising prognostic role of DDR score in glioma. Individual assessment of DDR status for patients with glioma may provide new clues for developing immunotherapeutic strategies.

Genomics-Assisted Improvement of Super High-Yield Hybrid Rice Variety "Super 1000" for Resistance to Bacterial Blight and Blast Diseases.

The two-line rice hybrid "Super 1000" (GX24S × R900) represents a major landmark achievement of breeding for super-hybrid rice in China. However, both male parent R900 and hybrid "Super 1000" have an obvious defect of high susceptibility to rice bacterial blight (BB) and blast. Thus, improving disease resistance and maintaining the original high-yield capacity are essential for the sustainable application of "Super 1000." In this study, the application of closely linked single-nucleotide polymorphism (SNP) markers for foreground selection of dominant resistance gene loci together with genome-wide SNP markers for the background selection rapidly improved the disease resistance of R900 without disturbing its high-yield capacity. A series of improved R900 lines (iR900, in BC2Fn and BC3Fn generations) were developed to stack resistance genes (Xa23+Pi9, Xa23+Pi1+Pi2/9) by marker-assisted backcrossing and field selection for phenotypes, and further crossed with the female line GX24S to obtain improved hybrid variety Super 1000 (iS1000). The genetic backgrounds of iS1000 and "Super 1000" were profiled by using a 56 K SNP-Chip, and results showed that they shared 98.76% of similarity. Meanwhile, evaluation of the field disease resistance showed that the iR900 lines and iS1000 hybrids possess significantly enhanced resistance to both BB and rice blast. Resistance spectrum assays revealed that the iR900 lines and their derived hybrids exhibited high-level resistance to 28 Xoo strains tested, and enhanced resistance to leaf blast at the seedling stage when infected with 38 Magnaporthe oryzae isolates. Between 2019 and 2020, the multi-location field trials across the middle and lower reaches of the Yangtze River were launched and showed that the iS1000 slightly out-yielded than the original variety. In a large-scale demonstration site (6.73 ha, Yunnan, China), the iS1000 achieved 17.06 t/hm2 of yield in 2019. Moreover, the high similarity was observed in main agronomic traits and grain quality when comparing the improved lines/hybrids to original ones (iR900 vs. R900, iS1000 vs. S1000). This work presented a typical genomics-assisted breeding strategy and practice, which involves in directional introgression and rapid stack of multiple disease resistance genes, endowing the super-high-yield hybrid rice variety with holistic disease resistance but without yield penalty.

WATER-SOAKED SPOT1 Controls Chloroplast Development and Leaf Senescence via Regulating Reactive Oxygen Species Homeostasis in Rice.

Transmembrane kinases (TMKs) play important roles in plant growth and signaling cascades of phytohormones. However, its function in the regulation of early leaf senescence (ELS) of plants remains unknown. Here, we report the molecular cloning and functional characterization of the WATER-SOAKED SPOT1 gene which encodes a protein belongs to the TMK family and controls chloroplast development and leaf senescence in rice (Oryza sativa L.). The water-soaked spot1 (oswss1) mutant displays water-soaked spots which subsequently developed into necrotic symptoms at the tillering stage. Moreover, oswss1 exhibits slightly rolled leaves with irregular epidermal cells, decreased chlorophyll contents, and defective stomata and chloroplasts as compared with the wild type. Map-based cloning revealed that OsWSS1 encodes transmembrane kinase TMK1. Genetic complementary experiments verified that a Leu396Pro amino acid substitution, residing in the highly conserved region of leucine-rich repeat (LRR) domain, was responsible for the phenotypes of oswss1. OsWSS1 was constitutively expressed in all tissues and its encoded protein is localized to the plasma membrane. Mutation of OsWSS1 led to hyper-accumulation of reactive oxygen species (ROS), more severe DNA fragmentation, and cell death than that of the wild-type control. In addition, we found that the expression of senescence-associated genes (SAGs) was significantly higher, while the expression of genes associated with chloroplast development and photosynthesis was significantly downregulated in oswss1 as compared with the wild type. Taken together, our results demonstrated that OsWSS1, a member of TMKs, plays a vital role in the regulation of ROS homeostasis, chloroplast development, and leaf senescence in rice.

Ectopic Expression of Executor Gene Xa23 Enhances Resistance to Both Bacterial and Fungal Diseases in Rice.

Bacterial blight (BB) and bacterial leaf streak (BLS), caused by phytopathogenic bacteria Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, are the most serious bacterial diseases of rice, while blast, caused by Magnaporthe oryzae (M. oryzae), is the most devastating fungal disease in rice. Generating broad-spectrum resistance to these diseases is one of the key approaches for the sustainable production of rice. Executor (E) genes are a unique type of plant resistance (R) genes, which can specifically trap transcription activator-like effectors (TALEs) of pathogens and trigger an intense defense reaction characterized by a hypersensitive response in the host. This strong resistance is a result of programed cell death induced by the E gene expression that is only activated upon the binding of a TALE to the effector-binding element (EBE) located in the E gene promoter during the pathogen infection. Our previous studies revealed that the E gene Xa23 has the broadest and highest resistance to BB. To investigate whether the Xa23-mediated resistance is efficient against Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of BLS, we generated a new version of Xa23, designated as Xa23p1.0, to specifically trap the conserved TALEs from multiple Xoc strains. The results showed that the Xa23p1.0 confers broad resistance against both BB and BLS in rice. Moreover, our further experiment on the Xa23p1.0 transgenic plants firstly demonstrated that the E-gene-mediated defensive reaction is also effective against M. oryzae, the causal agent of the most devastating fungal disease in rice. Our current work provides a new strategy to exploit the full potential of the E-gene-mediated disease resistance in rice.

Low profile visualized intraluminal support stent-assisted Hydrocoil embolization for acutely ruptured wide-necked intracranial aneurysms: A propensity score-matched cohort study.

PURPOSE: To compare the safety and efficacy of low profile visualized intraluminal support (LVIS) stent-assisted hydrogel coil embolization and LVIS stent-assisted bare platinum coil embolization for acutely ruptured wide-necked intracranial. METHODS: 89 patients who underwent LVIS stent-assisted hydrogel coil embolization (hydrogel coil group) and 145 patients who underwent LVIS stent-assisted bare platinum coil embolization (platinum coil group) were retrospectively reviewed after 1:2 propensity score matching (PSM). Procedure-related complications, clinical and angiographic follow-up outcomes were compared between the two groups. RESULTS: All baseline characteristics were equivalent between hydrogel coil group and platinum coil group after PSM. There were no statistical differences in immediate postoperative embolization results, clinical and angiographic follow-up outcomes between the two groups (P = 0.514, P = 0.323 and P = 0.949, respectively). Intraprocedural aneurysm rupture, intraprocedural thrombosis and postprocedural thrombosis occurred in 2 patients (2.2%, 2/89), 1 patient (1.1%, 1/89) and 1 patient (1.1%, 1/89) of the hydrogel coil group compared with 1 patient (0.7%, 1/145), 1 patient (0.7%, 1/145) and 2 patients (1.4%, 2/145) of the platinum coil group, respectively (P = 0.559, P = 1.000 and P = 1.000). Nevertheless, the rate of postprocedural aneurysm early rebleeding in the hydrogel coil group was significantly lower than that in the platinum coil group (0.0% vs 4.8%, P = 0.046). CONCLUSION: LVIS stent-assisted hydrogel coil embolization may reduce the risk of aneurysm early rebleeding compared with LVIS stent-assisted bare platinum coil embolization for the treatment of acutely ruptured wide-necked intracranial aneurysms, which implies that hydrogel coil may improve the safety of stent placement for ruptured intracranial aneurysms.

Plant Executor Genes.

Executor (E) genes comprise a new type of plant resistance (R) genes, identified from host-Xanthomonas interactions. The Xanthomonas-secreted transcription activation-like effectors (TALEs) usually function as major virulence factors, which activate the expression of the so-called "susceptibility" (S) genes for disease development. This activation is achieved via the binding of the TALEs to the effector-binding element (EBE) in the S gene promoter. However, host plants have evolved EBEs in the promoters of some otherwise silent R genes, whose expression directly causes a host cell death that is characterized by a hypersensitive response (HR). Such R genes are called E genes because they trap the pathogen TALEs in order to activate expression, and the resulting HR prevents pathogen growth and disease development. Currently, deploying E gene resistance is becoming a major component in disease resistance breeding, especially for rice bacterial blight resistance. Currently, the biochemical mechanisms, or the working pathways of the E proteins, are still fuzzy. There is no significant nucleotide sequence homology among E genes, although E proteins share some structural motifs that are probably associated with the signal transduction in the effector-triggered immunity. Here, we summarize the current knowledge regarding TALE-type avirulence proteins, E gene activation, the E protein structural traits, and the classification of E genes, in order to sharpen our understanding of the plant E genes.

Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT.

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.

Endovascular Aneurysm Treatment with the Numen Coil Embolization System: A Prospective Randomized Controlled Open-Label Multicenter Noninferiority Trial in China.

OBJECTIVE: We investigated the safety and efficacy of the Numen coil compared with the Axium coil in the treatment of intracranial aneurysms. METHODS: Because CATCH (Coil Application Trial in China) is a prospective randomized controlled open-label noninferiority trial conducted in 10 centers across China, patients who fulfilled the inclusion and exclusion criteria were randomized 1:1 to either a test group (Numen) or a control group (Axium). The primary outcome was based on successful aneurysm occlusion at 6 months follow-up, whereas secondary outcomes included technical success, the recanalization and retreatment rates, and the rate of serious adverse events (SAEs) at 6 months and 12 months follow-up. RESULTS: Between August 2017 and December 2019, 350 patients presenting with 350 aneurysms were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 91.18% for the test group compared with 91.85% in the control group, with a difference of -0.68% (P = 0.8419), and the overall mortality during the 30-day follow-up period was 1.19% and 1.81% in the test and control group, respectively, showing no significant difference between the 2 groups (P = 0.6837), whereas the SAE incidence during the 12-month follow-up period was 12.50% and 17.47% in the test and control groups, respectively, which was not statistically significant (P = 0.2222). CONCLUSIONS: This trial showed that the Numen coil was noninferior to the Axium coil in terms of intracranial aneurysm embolization and can be considered as a safe and effective coil for treating patients with intracranial aneurysm in clinical practice.

Predictors of unfavorable outcome in stent-assisted coiling for symptomatic unruptured intracranial spontaneous vertebral artery dissecting aneurysms (uis-VADAs): results from a multicenter study.

OBJECTIVE: To evaluate predictors of unfavorable outcome in stent-assisted coiling for symptomatic unruptured intracranial spontaneous vertebral artery dissecting aneurysms (uis-VADAs) based on 608 reconstructed lesions in 30 medical centres. METHODS: A total of 608 patients (male:female=479:129; mean age, 53.26±10.26 years) with 608 symptomatic uis-VADAs underwent reconstructive treatments using stent(s) with coils between January 2009 and December 2015. Treatments and predictors of unfavorable outcomes were retrospectively analyzed. RESULTS: Mainly, three methods were used to treat patients with uis-VADAs, including routine single-stent in 208 patients (such as Enterprise and others), new low-profile LVIS single stent in 107 patients, and multiple stents in 293 patients. During the median 66 months of clinical follow-up, 14 patients died, and 16 of the remaining 594 survivors had unfavorable outcomes (modified Rankin Scale score 3-5). The overall mortality rate was 2.3% (14/608), and the unfavorable outcome (mRS score 3-6) rate was 4.9% (30/608). Multivariate logistic regression analysis indicated that preprocedural ischemic infarctions (OR=3.78; 95% CI 1.52 to 9.40; p<0.01), diabetes mellitus (OR=3.74; 95% CI 1.31 to 10.68; p=0.01), and procedural complications (OR=14.18; 95% CI 5.47 to 36.80; p<0.01) were predictors of unfavorable outcome in the reconstructed VADAs. CONCLUSIONS: This multicenter study indicated that preprocedural ischemic infarctions, diabetes mellitus, and procedural complications were related to unfavorable clinical outcomes in the reconstructed uis-VADAs.