Biocontrol potential of Cladosporium sphaerospermum against the wheat powdery mildew fungus Blumeria graminis f. sp. tritici.

Cladosporium spp. are known to be mycoparasites and inhibit phytopathogenic fungi. However, so far, little information is available on the impacts of Cladosporium spp. on powdery mildews. Based on the morphological characteristics and molecular analysis, C. sphaerospermum was identified as a mycoparasite on the wheat powdery mildew fungus (Blumeria graminis f. sp. tritici, Bgt, recently named as B. graminis s. str.). C. sphaerospermum was capable of preventing colony formation and conidial distribution of Bgt. The biomasses of Bgt notably decreased by 1.3, 2.2, 3.6 and 3.8 times at 2 dpi, 4 dpi, 6 dpi and 8 dpi, respectively. In addition, biomasses of C. sphaerospermum at 2 dpi, 4 dpi, 6 dpi and 8 dpi significantly increased to 5.6, 13.9, 18.2 and 67.3 times, respectively. In vitro, C. sphaerospermum exudates significantly impaired appressorial formation of Bgt. Thus, C. sphaerospermum acts as a potential biological control agent by suppressing the formation, distribution and development of Bgt conidia and is a viable alternative for managing the wheat powdery mildew. These results suggest that C. sphaerospermum is an antagonistic parasite of the wheat powdery mildew fungus, and hence, provide new knowledge about the biological control of phytopathogenic fungi.

Sea perch (Lateolabrax japonicus) UBC9 augments RGNNV infection by hindering RLRs-interferon response.

Small ubiquitin-like modifier (SUMO) is a reversible post-translational modification that regulates various biological processes in eukaryotes. Ubiquitin-conjugating enzyme 9 (UBC9) is the sole E2-conjugating enzyme responsible for SUMOylation and plays an important role in essential cellular functions. Here, we cloned the UBC9 gene from sea perch (Lateolabrax japonicus) (LjUBC9) and investigated its role in regulating the IFN response during red-spotted grouper nervous necrosis virus (RGNNV) infection. The LjUBC9 gene consisted of 477 base pairs and encoded a polypeptide of 158 amino acids with an active site cysteine residue and a UBCc domain. Phylogenetic analysis showed that LjUBC9 shared the closest evolutionary relationship with UBC9 from Paralichthys olivaceus. Tissue expression profile analysis demonstrated that LjUBC9 was significantly increased in multiple tissues of sea perch following RGNNV infection. Further experiments showed that overexpression of LjUBC9 significantly increased the mRNA and protein levels of RGNNV capsid protein in LJB cells infected with RGNNV, nevertheless knockdown of LjUBC9 had the opposite effect, suggesting that LjUBC9 exerted a pro-viral effect during RGNNV infection. More importantly, we found that the 93rd cysteine is crucial for its pro-viral effect. Additionally, dual luciferase assays revealed that LjUBC9 prominently attenuated the promoter activities of sea perch type Ⅰ interferon (IFN) in RGNNV-infected cells, and overexpression of LjUBC9 markedly suppressed the transcription of key genes associated with RLRs-IFN pathway. In summary, these findings elucidate that LjUBC9 impairs the RLRs-IFN response, resulting in enhanced RGNNV infection.

[Analysis of the Efficacy and Prognosis Factors of Acute Myeloid Leukemia with a Combination Therapy of Venetoclax].

OBJECTIVE: To explore the efficacy and prognosis factors of acute myeloid leukemia with a combination therapy of venetoclax. METHODS: A retrospective analysis was performed on the clinical data of AML patients treated with a combination therapy of venetoclax from March 2020 to April 2023 in the First Hospital of Lanzhou University. The efficacy, adverse reactions and survival were observed, and the influencing factors were analyzed. RESULTS: A total of 74 AML patients were included in this study, including 43 initially treated AML and 31 relapsed or refractory AML (R/R AML). The median age of 43 initially treated AML patients was 65 years old, the composite complete remission (cCR) rate was 67.4% (29/43), the objective response rate (ORR) was 72.1% (31/43), and the median overall survival (OS) was 17.3 months. The median age of 31 R/R AML patients was 51 years old, with a cCR rate of 38.7% (12/31), an ORR of 58.1% (18/31), and a median OS of 7.1 months. Sex, the blood cell count before VEN, gene mutation and prognosis stratification were related to whether to obtain cCR. Failure to obtain cCR was an independent risk factor for adverse outcomes. CONCLUSION: A combination therapy of venetoclax is safe and efficacious for AML. Its efficacy and survival are affected by molecular biology, cytogenetics and other factors.

[The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis].

OBJECTIVE: To explore the correlation between gene mutations and clinical characteristics, prognosis of myelodysplastic syndromes (MDS). METHODS: Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023, which 19 of them developed into secondary acute myeloid leukemia (sAML) during follow-up time. Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes, drawn gene maps, and analyzed their correlation and prognosis based on the clinical data of patients. RESULTS: The median age of 131 MDS patients was 58(17-86) years old. The ratio of male to female was 1.3∶1. A total of 148 gene mutations and 25 types were found in the center. U2AF1 and ASXL1 were often co-mutations with other genes, which were accompanied by 20q- and normal karyotype (NK) respectively. SETBP1 and SRSF2 were more common in patients over 60 years old, while NPM1 and WT1 under 60 years. Older patients had a higher the number of genetic mutations than younger patients. The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males. The number of gene mutations in sAML was higher than MDS (1.8 vs 1.0, P =0.006). The univariate and multivariate analysis showed that IPSS-R prognostic score≥3.5, TP53 were adverse factors for poor prognosis in MDS patients. Patients with monoallelic mutation（ma-TP53）and wild-type（wt-TP53） TP53 had OS better than biallelic mutation（bi-TP53）(P =0.003). The OS of MDS patients was better than sAML(P =0.01) and transplant patients was significantly better than nontransplant patients(P =0.036). CONCLUSION: Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

Chrysanthemum (Chrysanthemum morifolium) CmHRE2-like negatively regulates the resistance of chrysanthemum to the aphid (Macrosiphoniella sanborni).

BACKGROUND: The growth and ornamental value of chrysanthemums are frequently hindered by aphid attacks. The ethylene-responsive factor (ERF) gene family is pivotal in responding to biotic stress, including insect stress. However, to date, little is known regarding the involvement of ERF transcription factors (TFs) in the response of chrysanthemum to aphids. RESULTS: In the present study, CmHRE2-like from chrysanthemum (Chrysanthemum morifolium), a transcription activator that localizes mainly to the nucleus, was cloned. Expression is induced by aphid infestation. Overexpression of CmHRE2-like in chrysanthemum mediated its susceptibility to aphids, whereas CmHRE2-like-SRDX dominant repressor transgenic plants enhanced the resistance of chrysanthemum to aphids, suggesting that CmHRE2-like contributes to the susceptibility of chrysanthemum to aphids. The flavonoids in CmHRE2-like-overexpression plants were decreased by 29% and 28% in two different lines, whereas they were increased by 42% and 29% in CmHRE2-like-SRDX dominant repressor transgenic plants. The expression of Chrysanthemum-chalcone-synthase gene(CmCHS), chalcone isomerase gene (CmCHI), and flavonoid 3'-hydroxylase gene(CmF3'H) was downregulated in CmHRE2-like overexpression plants and upregulated in CmHRE2-like-SRDX dominant repressor transgenic plants, suggesting that CmHRE2-like regulates the resistance of chrysanthemum to aphids partially through the regulation of flavonoid biosynthesis. CONCLUSION: CmHRE2-like was a key gene regulating the vulnerability of chrysanthemum to aphids. This study offers fresh perspectives on the molecular mechanisms of chrysanthemum-aphid interactions and may bear practical significance for developing new strategies to manage aphid infestation in chrysanthemums.

Feedback loop regulation between viperin and viral hemorrhagic septicemia virus through competing protein degradation pathways.

Viperin is an antiviral protein that exhibits a remarkably broad spectrum of antiviral activity. Viperin-like proteins are found all kingdoms of life, suggesting it is an ancient component of the innate immune system. However, viruses have developed strategies to counteract viperin's effects. Here, we describe a feedback loop between viperin and viral hemorrhagic septicemia virus (VHSV), a common fish pathogen. We show that Lateolabrax japonicus viperin (Ljviperin) is induced by both IFN-independent and IFN-dependent pathways, with the C-terminal domain of Ljviperin being important for its anti-VHSV activity. Ljviperin exerts an antiviral effect by binding both the nucleoprotein (N) and phosphoprotein (P) of VHSV and induces their degradation through the autophagy pathway, which is an evolutionarily conserved antiviral mechanism. However, counteracting viperin's activity, N protein targets and degrades transcription factors that up-regulate Ljviperin expression, interferon regulatory factor (IRF) 1 and IRF9, through ubiquitin-proteasome pathway. Together, our results reveal a previously unknown feedback loop between viperin and virus, providing potential therapeutic targets for VHSV prevention. Importance: Viral hemorrhagic septicaemia (VHS) is a contagious disease caused by the viral hemorrhagic septicaemia virus (VHSV), which poses a threat to over 80 species of marine and freshwater fish. Currently, there are no effective treatments available for this disease. Understanding the mechanisms of VHSV-host interaction is crucial for preventing viral infections. Here, we found that, as an ancient antiviral protein, viperin degrades the N and P proteins of VHSV through the autophagy pathway. Additionally, the N protein also impacts the biological functions of IRF1 and IRF9 through the ubiquitin-proteasome pathway, leading to the suppression of viperin expression. Therefore, the N protein may serve as a potential virulence factor for the development of VHSV vaccines and screening of antiviral drugs. Our research will serve as a valuable reference for the development of strategies to prevent VHSV infections.

Mitochondrial-regulated Tregs: potential therapeutic targets for autoimmune diseases of the central nervous system.

Regulatory T cells (Tregs) can eliminate autoreactive lymphocytes, induce self-tolerance, and suppress the inflammatory response. Mitochondria, as the energy factories of cells, are essential for regulating the survival, differentiation, and function of Tregs. Studies have shown that patients with autoimmune diseases of the central nervous system, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and autoimmune encephalitis, have aberrant Tregs and mitochondrial damage. However, the role of mitochondrial-regulated Tregs in autoimmune diseases of the central nervous system remains inconclusive. Therefore, this study reviews the mitochondrial regulation of Tregs in autoimmune diseases of the central nervous system and investigates the possible mitochondrial therapeutic targets.

Integrated physio-biochemical and RNA sequencing analysis revealed mechanisms of long non-coding RNA-mediated response to cadmium toxicity in wheat.

The yield and quality of wheat (Triticum aestivum L.) is seriously affected by soil cadmium (Cd), a hazardous material to plant and human health. Long non-coding RNAs (lncRNAs) of plants are shown actively involved in response to various biotic and abiotic stresses by mediating the gene regulatory networks. However, the functions of lncRNAs in wheat against Cd stress are still obscure. Using deep strand-specific RNA sequencing, 10,044 confident novel lncRNAs in wheat roots response to Cd stress were identified. It was found that 69 lncRNA-target pairs referred to cis-acting regulation and impacted the expressions of their neighboring genes involving in Cd transport and detoxification, photosynthesis, and antioxidant defense. These findings were positively corelated with the physio-biochemical results, i.e. Cd stress affected Cd accumulation, photosynthesis system and ROS in wheat. Overexpression of lncRNA37228 (targeted to a photosystem II protein D1 coding gene), resulted in enhancing Arabidopsis thaliana resistance against Cd stress. By genome-wide identification and characterization, the possible functions of photosystem II protein gene family in wheat under Cd condition were illustrated. Our findings provide novel knowledge into the molecular mechanisms of lncRNAs-regulated wheat tolerance to Cd toxicity and lay foundations for the further studies concerning lncRNAs in food safety production.

Methyltransferase-like 3 suppresses red spotted grouper nervous necrosis virus and viral hemorrhagic septicemia virus infection by enhancing type I interferon responses in sea perch.

Methylation at the N6 position of adenosine (m6A) is the most abundant internal mRNA modification in eukaryotes, tightly associating with regulation of viral life circles and immune responses. Here, a methyltransferase-like 3 homolog gene from sea perch (Lateolabrax japonicus), designated LjMETTL3, was cloned and characterized, and its negative role in fish virus pathogenesis was uncovered. The cDNA of LjMETTL3 encoded a 601-amino acid protein with a MT-A70 domain, which shared the closest genetic relationship with Echeneis naucrates METTL3. Spatial expression analysis revealed that LjMETTL3 was more abundant in the immune tissues of sea perch post red spotted grouper nervous necrosis virus (RGNNV) or viral hemorrhagic septicemia virus (VHSV) infection. LjMETTL3 expression was significantly upregulated at 12 and 24 h post RGNNV and VHSV infection in vitro. In addition, ectopic expression of LjMETTL3 inhibited RGNNV and VHSV infection in LJB cells at 12 and 24 h post infection, whereas knockdown of LjMETTL3 led to opposite effects. Furthermore, we found that LjMETTL3 may participate in boosting the type I interferon responses by interacting with TANK-binding kinase. Taken together, these results disclosed the antiviral role of fish METTL3 against RGNNV and VHSV and provided evidence for understanding the potential mechanisms of fish METTL3 in antiviral innate immunity.

Prognostic significance of white blood cell to platelet ratio in delayed cerebral ischemia and long-term clinical outcome after aneurysmal subarachnoid hemorrhage.

Objectives: The ratio of white blood cell to platelet count (WPR) is considered a promising biomarker in some diseases. However, its prediction of delayed cerebral ischemia (DCI) and prognosis after aneurysmal subarachnoid hemorrhage (aSAH) has not been studied. The primary objective of this study was to investigate the predictive value of WPR in DCI after aSAH and its impact on 90-day functional outcome. Materials and methods: This study retrospectively analyzed the data of blood biochemical parameters in 447 patients with aSAH at early admission. Univariate and multivariate analyses were used to determine the risk factors for DCI. According to multivariate analysis results, a nomogram for predicting DCI is developed and verified by R software. The influence of WPR on 90-day modified Rankin score (mRS) was also analyzed. Results: Among 447 patients with aSAH, 117 (26.17%) developed DCI during hospitalization. Multivariate logistic regression analysis showed that WPR [OR = 1.236; 95%CI: 1.058-1.444; p = 0.007] was an independent risk factor for DCI. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of WPR for DCI, and the cut-off value of 5.26 (AUC 0.804, 95% CI: 0.757-0.851, p < 0.001). The ROC curve (AUC 0.875, 95% CI: 0.836-0.913, p < 0.001) and calibration curve (mean absolute error = 0.017) showed that the nomogram had a good predictive ability for the occurrence of DCI. Finally, we also found that high WPR levels at admission were closely associated with poor prognosis. Conclusion: WPR level at admission is a novel serum marker for DCI and the poor prognosis after aSAH. A nomogram model containing early WPR will be of great value in predicting DCI after aSAH.

Clinical characteristics and prognostic factors for short-term outcomes of autoimmune glial fibrillary acidic protein astrocytopathy: a retrospective analysis of 33 patients.

Background: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered inflammatory central nervous system (CNS) disease, whose clinical characteristics and prognostic factors for short-term outcomes have not been defined yet. We aimed to assess the symptoms, laboratory tests, imaging findings, treatment, and short-term prognosis of GFAP-A. Methods: A double-center retrospective cohort study was performed between May 2018 and July 2022. The clinical characteristics and prognostic factors for short-term outcomes were determined. Results: We enrolled 33 patients with a median age of 28 years (range: 2-68 years), 15 of whom were children (<18 years). The clinical spectrum is dominated by meningoencephalomyelitis. Besides, we also found nausea, vomiting, poor appetite, and neuropathic pain in some GFAP-A patients, which were not mentioned in previous reports. And adults were more prone to limb numbness than children. Magnetic resonance imaging revealed lesions involving the brain parenchyma, meninges, and spinal cord, exhibiting patchy, linear, punctate, and strip T2 hyperintensities. First-line immunotherapy, including corticosteroid and gamma globulin, was effective in most patients in the acute phase (P = 0.02). However, patients with overlapping AQP4 antibodies did not respond well to first-line immunotherapy and coexisting neural autoantibodies were more common in women. Additionally, the short-term prognosis was significantly better in children than in adults (P = 0.04). Positive non-neural autoantibodies and proven viral infection were independent factors associated with poor outcomes (P = 0.03, 0.02, respectively). Conclusion: We expanded the spectrum of clinical symptoms of autoimmune GFAP-A. The clinical symptoms and short-term prognosis differed between children and adults. Positive non-neural autoantibodies and proven viral infection at admission suggest a poor short-term prognosis.

First Report of Powdery Mildew Caused by Golovinomyces bolayi on Veronica persica in Central China.

Veronica persica, Persian speedwell, is a flowering plant belonging to the family Plantaginaceae. Due to its showy flowers, this plant is widely planted in many home gardens, city parks and universities in China. From April to June 2021, signs and symptoms of powdery mildew were found on leaves of V. persica growing on the campus of Henan Normal University, Henan Province, China. Signs initially appeared as thin white colonies and subsequently white powdery masses were abundant on the adaxial and abaxial surfaces of leaves and covered up to 99 % of the leaf area. The infected leaves showed chlorotic, deformed or senescence features. About 150 V. persica plants were monitored and more than 90 % of the plants showed these signs and symptoms. Conidiophores (n = 20) were 108 to 220 × 10 to 13 µm and composed of foot cells, followed by short cells and conidia. Conidia were hyaline, doliiform-subcylindrical shaped, 21 to 37 × 15 to 22 µm, and showed distinct fibrosin bodies. Conidial germ tubes were produced at the perihilar position. No chasmothecia were observed. The observed morphological characteristics were consistent with those of previously documented Golovinomyces bolayi (Braun and Cook 2012). To further confirm the powdery mildew fungus, structures of the pathogen were harvested and total genomic DNA was isolated using the method previously described by Zhu et al. (2019, 2021). Using the primers ITS1/ITS4, the internal transcribed spacer (ITS) region of rDNA was amplified (White et al. 1990) and the amplicon was sequenced. The resulting sequence was deposited into GenBank under Accession No. MZ343575 and was 100 % identical (592/592 bp) to G. bolayi on Kalanchoe blossfeldiana (LC417096) (Braun et al. 2019). The additional phylogenetic analysis clearly illustrated that the identified fungus and G. bolayi were clustered in the same branch (Zhu et al. 2022a; Zhu et al. 2022b). To test pathogenicity, healthy V. persica plants were collected from the campus of Henan Normal University and leaf surfaces of three plants were inoculated by dusting fungal conidia from mildew-infested leaves using pressurized air. Three plants without inoculation served as a control. The spore-treated and non-treated plants were separately placed in two growth chambers (temperature, 18℃; humidity, 60%; light/dark, 16h/8h). Seven- to eight-days post-inoculation, pathogen signs were noticeable on inoculated plants, whereas control plants remained healthy. Similar results were obtained by conducting the pathogenicity assays twice. Therefore, based on the analysis, G. bolayi was identified and confirmed as the causal agent of the powdery mildew. This pathogen has been reported on V. persica in Iran (Golmohammadi et al. 2019). However, to our best knowledge, there is no report concerning the powdery mildew caused by G. bolayi on V. persica in China. Recently, G. bolayi was segregated from species clades of G. orontii complex (Braun et al. 2019). Our record of the molecular characterization of G. bolayi will support the further phylogeny and taxonomy analysis of the G. orontii complex. The sudden outbreak of powdery mildew caused by G. bolayi on V. persica may detract from plant health and ornamental value. The identification and confirmation of this disease expands the understanding of this causal agent and will offer support for future powdery mildew control.

Ring Finger Protein 34 Facilitates Nervous Necrosis Virus Evasion of Antiviral Innate Immunity by Targeting TBK1 and IRF3 for Ubiquitination and Degradation in Teleost Fish.

Ubiquitination, as one of the most prevalent posttranslational modifications of proteins, enables a tight control of host immune responses. Many viruses hijack the host ubiquitin system to regulate host antiviral responses for their survival. Here, we found that the fish pathogen nervous necrosis virus (NNV) recruited Lateolabrax japonicus E3 ubiquitin ligase ring finger protein 34 (LjRNF34) to inhibit the RIG-I-like receptor (RLR)-mediated interferon (IFN) response via ubiquitinating Lateolabrax japonicus TANK-binding kinase 1 (LjTBK1) and interferon regulatory factor 3 (LjIRF3). Ectopic expression of LjRNF34 greatly enhanced NNV replication and prevented IFN production, while deficiency of LjRNF34 led to the opposite effect. Furthermore, LjRNF34 targeted LjTBK1 and LjIRF3 via its RING domain. Of note, the interactions between LjRNF34 and LjTBK1 or LjIRF3 were conserved in different cellular models derived from fish. Mechanically, LjRNF34 promoted K27- and K48-linked ubiquitination and degradation of LjTBK1 and LjIRF3, which in turn diminished LjTBK1-induced translocation of LjIRF3 from the cytoplasm to the nucleus. Ultimately, NNV capsid protein (CP) was found to bind with LjRNF34, CP induced LjTBK1 and LjIRF3 degradation, and IFN suppression depended on LjRNF34. Our finding demonstrates a novel mechanism by which NNV CP evaded host innate immunity via LjRNF34 and provides a potential drug target for the control of NNV infection. IMPORTANCE Ubiquitination plays an essential role in the regulation of innate immune responses to pathogens. NNV, a type of RNA virus, is the causal agent of a highly destructive disease in a variety of marine and freshwater fish. A previous study reported NNV could hijack the ubiquitin system to manipulate the host's immune responses; however, how NNV utilizes ubiquitination to facilitate its own replication is not well understood. Here, we identified a novel distinct role of E3 ubiquitin ligase LjRNF34 as an IFN antagonist to promote NNV infection. NNV capsid protein utilized LjRNF34 to target LjTBK1 and LjIRF3 for K27- and K48-linked ubiquitination and degradation. Importantly, the interactions between LjRNF34 and CP, LjTBK1, or LjIRF3 are conserved in different cellular models derived from fish, suggesting it is a general immune evasion strategy exploited by NNV to target the IFN response via RNF34.

A correlation and prediction study of the poor prognosis of high-grade aneurysmal subarachnoid hemorrhage from the neutrophil percentage to albumin ratio.

OBJECTIVE: Inflammatory response and nutritional status play crucial roles in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study mainly investigated the correlation between neutrophil percentage to albumin ratio (NPAR) and clinical prognosis in aSAH patients with high-grade Hunt-Hess and its predictive model. METHODS: A retrospective analysis was conducted based on 806 patients with aneurysmal subarachnoid hemorrhage who were admitted to the studied hospital from January 2017 to December 2021. Modified Fisher grade and Hunt-Hess grade were obtained according to their status at admission and hematological parameters within 48 h after hemorrhage. Univariate and multivariate logistic regression analysis were conducted to evaluate the relationship between NPAR and the clinical prognosis of patients with aSAH. And propensity matching analysis of patients with aSAH in the severe group. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value of NPAR at admission to predict prognosis and its sensitivity and specificity. The nomogram diagram and Calibration curve were further used to examine the prediction model. RESULTS: According to the mRS score at discharge, 184 (22.83 %) cases were classified as having poor outcomes (mRS > 2). Through multivariate logistic regression analysis, it was found that the Modified Fisher grade at admission, Hunt-Hess grade, eosinophils, neutrophil to lymphocyte ratio (NLR), and NPAR were independent risk factors for poor outcome in patients with aSAH (p < 0.05). The NPAR of aSAH patients with poor outcomes in the high-grade group was significantly higher than that in the low-grade group. The optimal cut-off value for NPAR was 21.90, the area under the ROC curve was 0.780 (95 % CI 0.700 - 0.861, p < 0.001). The Calibration curves show that the predicted probability of the drawn nomogram is overall consistent with the actual probability. (Mean absolute error = 0.031) CONCLUSION: The NPAR value of patients with aSAH at admission is significantly correlated with Hunt-Hess grade in a positive manner, namely, the higher the Hunt-Hess grade, the higher the NPAR value, and the worse the prognosis. Findings indicate that early NPAR value can be used as a feasible biomarker to predict the clinical prognosis of patients with aSAH.

EDTA plasma in glass and polyethylene terephthalate tubes is suitable for measurement of B-type natriuretic peptide on the Mindray CL-6000i.

AIMS: To explore differences in B-type natriuretic peptide (BNP) concentration and stability and evaluate BNP accuracy in different collection tubes. METHODS: BNP concentrations in heparin/glass, EDTA/glass, and EDTA/polyethylene terephthalate (PET) tubes were measured on the Mindray CL-6000i at 0.5, 1, 2, and 4 h after collection. Differences were evaluated using Wilcoxon's paired tests and Bland-Altman plots. BNP stability and measurement accuracies were estimated using Kruskal-Wallis H tests and recovery tests. RESULTS: BNP concentrations in EDTA/glass tubes were 31.4% higher than those in heparin/glass tubes and 3.04% lower than those in EDTA/PET tubes. BNP stability significantly decreased in the heparin/glass tube. BNP remained stable in EDTA/glass and EDTA/PET tubes at room temperature for 4 h. BNP recovery rates in heparin/glass, EDTA/glass, and EDTA/PET tubes were 77.46, 86.04, and 88.23%, respectively. CONCLUSIONS: Plasma in EDTA/glass and EDTA/PET tubes is suitable for BNP measurement on the Mindray CL-6000i.

Single internal carotid cavernous sinus aneurysm presented as bilateral painful ophthalmoplegia: a case report.

BACKGROUND: Intracranial aneurysms are the most common vascular cause of painful ophthalmoplegia. Symptoms include retro-orbital pain, diplopia, ophthalmoplegia, trigeminal neuropathy, or a combination of these. Most single aneurysms cause ipsilateral, painful ophthalmoplegia. Here, we report the first, to our knowledge, case of bilateral painful ophthalmoplegia possibly caused by an aneurysm of the cavernous segment of the left internal carotid artery. CASE PRESENTATION: A 62-year-old male patient presented with headache and bilateral ptosis. Laboratory tests revealed hypopituitary function. Computerized tomography angiography showed a large aneurysm in the cavernous sinus segment of the left internal carotid artery. Aneurysm embolization was performed in the Nerve Interventional Department. Four months after surgery, the patient's symptoms returned to normal. CONCLUSIONS: This case suggests that patients with bilateral painful ophthalmoplegia should be screened for aneurysms using computed tomography angiography or magnetic resonance angiography immediately.

Corrigendum: Clinical value and prognosis of C reactive protein to lymphocyte ratio in severe aneurysmal subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2022.868764.].

Risk factors and predictive models of poor prognosis and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage complicated with hydrocephalus.

Objective: To evaluate the correlation of serum biological markers and related scales to the occurrence of delayed cerebral ischemia and clinical prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) complicated with acute hydrocephalus before admission. Methods: The clinical data of 227 patients with pre-admission aSAH complicated with acute hydrocephalus admitted to Henan Provincial People's Hospital from April 2017 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of delayed cerebral ischemia (DCI) after surgery and the prognosis at 6 months after discharge. Univariate and multivariable logistic regression analysis were performed to analyze the relationship between serum biological indicators combined with aneurysm related clinical score scale and the occurrence and prognosis of delayed cerebral ischemia. ROC curves and nomogram were drawn. Results: Multivariable Logistic regression analysis showed that high Hunt-Hess grade and surgical clipping were independent risk factors for postoperative DCI (P < 0.05). Older age, higher Hunt-Hess grade, higher CRP and neutrophil levels were independent risk factors for poor prognosis at 6 months after surgery (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of Hunt-Hess grade and surgical method for predicting DCI in patients with aSAH combined with hydrocephalus after surgery were 0.665 and 0.593. The combined AUC of Hunt-Hess grade and surgical method was 0.685, the sensitivity was 64.9%, and the specificity was 64.7%. The AUC of CRP, neutrophil, age and Hunt-Hess grade for predicting poor prognosis in patients with aSAH combined with hydrocephalus at 6 months after surgery were 0.804, 0.735, 0.596, 0.757, respectively. The combined AUC of CRP, neutrophil, age, Hunt-Hess grade was 0.879, the sensitivity was 79%, and the specificity was 84.5%. According to the correction curve, the predicted probability of the nomogram is basically consistent with the actual probability. Conclusion: Hunt-Hess grade and surgical method are independent predictors of postoperative DCI in patients with aSAH complicated with hydrocephalus. "CRP," "neutrophil," "age" and "Hunt-Hess grade" at admission are independent predictors of clinical prognosis in patients with aSAH complicated with hydrocephalus. The combination of the above indicators has high predictive value.

Design, synthesis and biological evaluation of novel 4-aminopiperidine derivatives as SMO/ERK dual inhibitors.

The hedgehog (Hh) pathway is tightly related with the formation, metastasis and recurrence of various cancers, which makes it a perfect anticancer target. Smoothened (SMO) is one of its key members. Three drugs targeting the Hh pathway have been successfully used in clinic, and they are all known as SMO inhibitors. However, serious drug resistant problem has limited their clinical application. The interaction of oncogenic ERK pathway with the Hh pathway in multiple ways has been proved as one of the main factors that result in drug resistance. Dual inhibition of the Hh and ERK pathways has displayed synergistic suppression to cancer cells overexpressing both pathways. Herein, we designed and synthesized a series of novel 4-aminopiperidine derivatives as SMO/ERK dual inhibitors, and evaluated their biological activities. The results showed that compounds I-13 displayed strong inhibitory activities towards both SMO and ERK, and it also exhibited significant cytotoxicity against human cholangiocarcinoma RBE cells which overexpress both the Hh and ERK pathways. All the results indicate that compound I-13 is a promising anticancer candidate as a SMO/ERK dual inhibitor.