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Rose black spot disease caused by Marssonina rosae is among the most destructive diseases that affects the outdoor cultivation and production of roses; however, the molecular mechanisms underlying the defensive response of roses to M. rosae have not been clarified. To investigate the diversity of response to M. rosae in resistant and susceptible rose varieties, we performed transcriptome and metabolome analyses of resistant (KT) and susceptible (FG) rose varieties and identified differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in response to M. rosae at different time points. In response to M. rosae, DEGs and DAMs were mainly upregulated compared to the control and transcription factors were concentrated in the WRKY and AP2/ERF families. Gene Ontology analysis showed that the DEGs of FG were mainly enriched in biological processes, such as the abscisic acid-activated signaling pathway, cell wall, and defense response, whereas the DEGs of KT were mainly enriched in Golgi-mediated vesicle transport processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs of both varieties were concentrated in plant–pathogen interactions, plant hormone signal transduction, and mitogen-activated protein kinase signaling pathways, with the greatest number of DEGs associated with brassinosteroid (BR) in the plant hormone signal transduction pathway. The reliability of the transcriptome results was verified by qRT-PCR. DAMs of KT were significantly enriched in the butanoate metabolism pathway, whereas DAMs of FG were significantly enriched in BR biosynthesis, glucosinolate biosynthesis, and tryptophan metabolism. Moreover, the DAMs in these pathways were significantly positively correlated with the DEGs. Disease symptoms were aggravated when FG leaves were inoculated with M. rosae after 24-epibrassinolide treatment, indicating that the response of FG to M. rosae involves the BR signaling pathway. Our results provide new insights into the molecular mechanisms underlying rose response to M. rosae and lay a theoretical foundation for formulating rose black spot prevention and control strategies and cultivating resistant varieties.

This paper addresses the innovation management problem of financial trading strategies for power system planning through the utilization of the BO-BERT-GRNN model. The BO-BERT-GRNN model, which combines Bayesian optimization, BERT model, and gated recurrent neural network, is divided into three parts to optimize hyperparameters, extract features from historical data, and model and predict power system planning. The objective is to achieve electricity asset allocation, market risk management, and revenue maximization. Experimental analysis demonstrates that the BO-BERT-GRNN model outperforms in power system planning price prediction, energy transaction risk management, and energy asset allocation, showcasing its potential for practical application. This paper addresses the innovation management problem of financial trading strategies for power system planning through the utilization of the BO-BERT-GRNN model. The BO-BERT-GRNN model, which combines Bayesian optimization, BERT model, and gated recurrent neural network, is divided into three parts to optimize hyperparameters, extract features from historical data, and model and predict power system planning. The objective is to achieve electricity asset allocation, market risk management, and revenue maximization. Experimental analysis demonstrates that the BO-BERT-GRNN model outperforms in power system planning price prediction, energy transaction risk management, and energy asset allocation, showcasing its potential for practical application.

Neurodegenerative diseases (NDs) have become a serious global health problem as the population ages. Traditionally, treatment strategies for NDs have included oral and intravenous administration; however, the blood–brain barrier (BBB) can prevent drugs from reaching the brain, rendering the treatment incomplete and the effect unsatisfactory. Additionally, the prolonged or excessive use of drugs that can cross the BBB can damage liver and kidney function. Recent studies have shown that nose-to-brain drug delivery can noninvasively bypass the BBB, allowing drugs to enter the brain through the olfactory or trigeminal nerve pathways; additionally, nanoparticle carriers can enhance drug delivery. This review introduces drug carrier nanoparticles for nose-to-brain delivery systems, compares the advantages and disadvantages of different nanoparticles, and discusses the factors influencing nose-to-brain nanomedicine delivery and enhancement strategies. We also summarize nose-to-brain delivery and nanomedicines for treating NDs, the current challenges of this approach, and the future promise of nanomedicine-based ND treatment.

IntroductionNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune central nervous system diseases characterized by the immune system's abnormal attack on glial cells and neurons. Optic neuritis (ON) is one of the indicators of NMOSD, often starting unilaterally and potentially affecting both eyes later in the disease progression, leading to visual impairment. Optical coherence tomography angiography (OCTA) has the potential to aid in the early diagnosis of NMOSD by examining ophthalmic imaging and may offer a window for disease prevention.MethodsIn this study, we collected OCTA images from 22 NMOSD patients (44 images) and 25 healthy individuals (50 images) to investigate retinal microvascular changes in NMOSD. We employed effective retinal microvascular segmentation and foveal avascular zone (FAZ) segmentation techniques to extract key OCTA structures for biomarker analysis. A total of 12 microvascular features were extracted using specifically designed methods based on the segmentation results. The OCTA images of NMOSD patients were classified into two groups: optic neuritis (ON) and non-optic neuritis (non-ON). Each group was compared separately with a healthy control (HC) group.ResultsStatistical analysis revealed that the non-ON group displayed shape changes in the deep layer of the retina, specifically in the FAZ. However, there were no significant microvascular differences between the non-ON group and the HC group. In contrast, the ON group exhibited microvascular degeneration in both superficial and deep retinal layers. Sub-regional analysis revealed that pathological variations predominantly occurred on the side affected by ON, particularly within the internal ring near the FAZ.DiscussionThe findings of this study highlight the potential of OCTA in evaluating retinal microvascular changes associated with NMOSD. The shape alterations observed in the FAZ of the non-ON group suggest localized vascular abnormalities. In the ON group, microvascular degeneration in both superficial and deep retinal layers indicates more extensive vascular damage. Sub-regional analysis further emphasizes the impact of optic neuritis on pathological variations, particularly near the FAZ's internal ring.ConclusionThis study provides insights into the retinal microvascular changes associated with NMOSD using OCTA imaging. The identified biomarkers and observed alterations may contribute to the early diagnosis and monitoring of NMOSD, potentially offering a time window for intervention and prevention of disease progression.

Hibiscus manihot L. seed oil is an emerging high-value edible vegetable oil that also has a variety of important health functions, and concerns about its pressing method have great significance for commercial and consumer health. This study compared triacylglycerols (TAGs), diacylglycerol (DAG), free fatty acids (FFAs), and volatile flavor compounds for discriminating cold-pressed oil from hot-pressed oil. The profiles of TAGs, DAGs, FFAs, and flavor compounds were established by a lipidomic approach and electronic-nose (E-nose). Our results demonstrated that a slight decrease in TAG content and a significant increase in FFA and DAG contents were observed after roasting. The E-nose results showed that sulfides, terpenes, methane, compounds containing oxygen and nitrogen, alcohol and aromatic compounds greatly influenced the oil flavor. The PCA result of the E-nose data indicated that flavor compounds showed great promise for distinguishing the two samples. The quality indices and the oxidative stability of oil samples were detected to identify their nutritional value and edible quality. This study revealed that roasting greatly influenced the lipid and flavor substances of the Hibiscus manihot L. seed oil. Our findings could provide useful information on the impact of the pressing method for Hibiscus manihot L. seed oil.

BackgroundThe causality between plasma branched-chain amino acids (BCAAs) levels and stroke remains uncertain and the stratified research on the association between BCAAs levels and subtypes of stroke is not well studied. Therefore, the association of genetically proxied circulating BCAA levels with the risks of stroke and its subtypes was explored by Mendelian randomization (MR) in this study.MethodsSummary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Data for plasma BCAA levels (n = 16,596) were obtained from a meta-analysis of GWAS. The MEGASTROKE consortium provided data for ischemic stroke (n = 440,328) and its subtypes and data for hemorrhagic stroke were available from 2 meta-analyses of GWAS of European-ancestry groups (intracerebral hemorrhage, n = 3,026; subarachnoid hemorrhage, n = 77,074). The inverse variance weighted (IVW) method was selected as the primary MR analysis. Supplementary analysis used included the weighted median, MR-Egger regression, Cochran’s Q statistic, MR Pleiotropy Residual Sum and Outlier global test, and leave-one-out analysis method.ResultsAccording to IVW analysis, 1-SD increment in genetically determined circulating isoleucine was associated with increased risks of cardioembolic stroke (CES) (OR: 1.56, 95% CI: 1.21–2.20, P = 0.0007), but not with risks of other stroke subtypes. We could not discover any proof that leucine and valine levels could increase risk of any stroke subtype. All heterogeneity tests produced stable findings, and there was no concrete evidence to indicate the perturbation of horizontal multiplicity.ConclusionIncreasing plasma isoleucine level had a causal effect on the risk of CES but not on the risk of other stroke subtypes. Further research is needed to identify the mechanisms of the causal associations between BCAAs and stroke subtypes.

In order to study the effect of loading rate on rockburst, an indoor test of single-face fast unloading-three directions and five-face stress-vertical continuous loading is conducted under different loading rates using a new true-triaxial rockburst test system. The entire process of rockburst inoculation-occurrence-development is completely and accurately reproduced. The fragmentation degree, fractal dimension, and Weibull distribution characteristics of rockburst fragments under different loading rates are compared and analyzed. The results indicate that the rockburst ejection failure process can be summarized as four stages: grain ejection, rock spalling into plates, rock shearing into fragments, and rock fragment ejection. Rockburst fragments are mostly coarse-grained, medium-grained, and fine-grained. The macroscopic block characteristics of rockburst fragments reflect the fragmentation degree of rock, and the fragmentation degree of rockburst fragments increases with the loading rate. The fractal dimension shows the same trend with different loading rates, that is, the fractal dimension grows as the loading rate increases. As the loading rate increases, the crack expansion rate accelerates, which aggravates the damage to the rock specimen by decreasing its compressive strength and causing greater fragmentation when the specimen is failed. The loading rate has a significant effect on the energy consumption of rockburst fragments.

Fetal head circumference (HC) is an important biological parameter to monitor the healthy development of the fetus. Since there are some HC measurement errors that affected by the skill and experience of the sonographers, a rapid, accurate and automatic measurement for fetal HC in prenatal ultrasound is of great significance. We proposed a new one-stage network for rotating elliptic object detection based on anchor-free method, which is also an end-to-end network for fetal HC auto-measurement that no need for any post-processing. The network structure used simple transformer structure combined with convolutional neural network (CNN) for a lightweight design, meanwhile, made full use of powerful global feature extraction ability of transformer and local feature extraction ability of CNN to extract continuous and complete skull edge information. The two complement each other for promoting detection precision of fetal HC without significantly increasing the amount of computation. In order to reduce the large variation of intersection over union (IOU) in rotating elliptic object detection caused by slight angle deviation, we used soft stage-wise regression (SSR) strategy for angle regression and added KLD that is approximate to IOU loss into total loss function. The proposed method achieved good results on the HC18 dataset to prove its effectiveness. This study is expected to help less experienced sonographers, provide help for precision medicine, and relieve the shortage of sonographers for prenatal ultrasound in worldwide.

Hepatocellular carcinoma (HCC) is a common cancer in the world, and its incidence is increasing yearly. Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are important causes of HCC. Liver cirrhosis, age, sex, smoking and drinking, and metabolic risk factors will increase the risk of cancer in HBV/HCV patients. And viral load, APRI, FIB-4, and liver stiffness can all predict the risk of HCC in patients with viral infection. In addition, effective prevention strategies are essential in reducing the risk of HCC. The prevention of HCC involves mainly tertiary prevention strategies, while the primary prevention is based on standardized vaccine injections to prevent the occurrence of HBV/HCV. Eliminating the route of transmission and vaccination will lead to a decrease in the incidence of HCC. Secondary prevention involves effective antiviral treatment of HBV/HCV to prevent the disease from progressing to HCC, and tertiary prevention is actively treating HCC to prevent its recurrence.

Purpose: To investigate the thickness changes of outer retinal layers in subjects with white matter hyperintensities (WMH) and Parkinson's Disease (PD).Methods: 56 eyes from 31 patients with WMH, 11 eyes from 6 PD patients, and 58 eyes from 32 healthy controls (HC) were enrolled in this study. A macular-centered scan was conducted on each participant using a spectral-domain optical coherence tomography (SD-OCT) device. After speckle noise reduction, a state-of-the-art deep learning method (i.e., a context encoder network) was employed to segment the outer retinal layers from OCT B-scans. Thickness quantification of the outer retinal layers was conducted on the basis of the segmentation results.Results: WMH patients had significantly thinner Henle fiber layers, outer nuclear layers (HFL+ONL) and photoreceptor outer segments (OS) than HC (p = 0.031, and p = 0.005), while PD patients showed a significant increase of mean thickness in the interdigitation zone and the retinal pigment epithelium/Bruch complex (IZ+RPE) (19.619 ± 4.626) compared to HC (17.434 ± 1.664). There were no significant differences in the thickness of the outer plexiform layer (OPL), the myoid and ellipsoid zone (MEZ), and the IZ+RPE layer between WMH and HC subjects. Similarly, there were also no obvious differences in the thickness of the OPL, HFL+ONL, MEZ and the OS layer between PD and HC subjects.Conclusion: Thickness changes in HFL+ONL, OS, and IZ+RPE layers may correlate with brain-related diseases such as WMH and PD. Further longitudinal study is needed to confirm HFL+ONL/OS/IZ+RPE layer thickness as potential biomarkers for detecting certain brain-related diseases.

Objective: To explore the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the short-term prognosis of NSTEMI and STEMI.Methods: This study was a single-center, retrospective and observational study. 2618 patients including 1289 NSTMI and 1329 STEMI patients were enrolled from June 2013 to February 2018 in Zhongda Hospital, Southeast University. The demographic information, clinical characteristics, medical history, laboratory examination, treatment, and outcome of individuals at admission and during hospitalization were extracted from the electronic medical record system. Outcome was defined as the all-cause death during hospitalization.Results: (1) In the NSTEMI group, the ability of NLR in predicting in-hospital death (AUC = 0.746) was higher than the neutrophil-monocyte ratio (NMR) (AUC = 0.654), the platelet-lymphocyte ratio (PLR) (AUC = 0.603) and the lymphocyte-monocyte ratio (LMR) (AUC = 0.685), and also higher than AST (AUC = 0.621), CK (AUC = 0.595), LDH (AUC = 0.653) and TnI (AUC = 0.594). The AUC of NLR in the STEMI group was only 0.621. (2) The optimal cut-off value of NLR in NSTEMI group was 5.509 (Youden index = 0.447, sensitivity = 77.01%, specificity = 67.72%). After adjusting variables including age, sex, diabetes history, smoking history, LDL-C and Cr, the logistic regression showed that the patients with NLR>5.509 had higher hazard risk of death (HR4.356; 95%CI 2.552–7.435; P < 0.001) than the patients with NLR ≤ 5.509. (3) Stratification analysis showed that the in-hospital mortality of patients with NLR > 5.509 was 14.611-fold higher than those with NLR ≤ 5.509 in patients aged 71. The HR in patients with or without diabetes were 6.586 and 3.375, respectively. The HR in smoking or no smoking patients were 6.646 and 4.145, respectively. The HR in patients with LDL-C ≥ 2.06 or

Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were still produced, although α4-α4’ is supposedly vital for CP dimerization and nucleocapsid formation. We further analyzed two mutants (ΔC20-43 and ΔC64-96 viruses) with relatively large deletions that still replicated well in BHK-21 cells. Our data indicate that internal deletions within CP impaired viral replication or assembly, resulting in attenuated virus proliferation in cells and attenuated virulence in duck embryos, and these deletion mutations are quite stable in cell culture. An in vivo assay indicated that both ΔC20-43 virus and ΔC64-96 virus were highly attenuated in ducklings but still immunogenic. Single-dose immunization with ΔC20-43 virus or ΔC64-96 virus could protect ducklings from a lethal challenge with good antigen clearance. Together, our data shed light on replication/assembly defective TMUV with internal deletions in CP and provide an effective approach to attenuate viral virulence in live vaccines without changing the antigen composition.

Our previous studies reported that duck Tembusu virus nonstructural protein 2A (NS2A) is a major inhibitor of the IFNβ signaling pathway through competitively binding to STING with TBK1, leading to a reduction in TBK1 phosphorylation. Duck TMUV NS2B3 could cleave and bind STING to subvert the IFNβ signaling pathway. Here, we found that overexpression of duck TMUV NS4B could compete with TBK1 in binding to STING, reducing TBK1 phosphorylation and inhibiting the IFNβ signaling pathway by using the Dual-Glo® Luciferase Assay System and the NanoBiT protein-protein interaction (PPI) assay. We further identified the E2, M3, G4, W5, K10 and D34 residues in NS4B that were important for its interaction with STING and its inhibition of IFNβ induction, which were subsequently introduced into a duck TMUV replicon and an infectious cDNA clone. We found that the NS4B M3A mutant enhanced RNA replication and exhibited significantly higher titer levels than WT at 48-72 hpi but significantly decreased mortality (80%) in duck embryos compared to WT (100%); the NS4B G4A and R36A mutants slightly reduced RNA replication but exhibited the same titer levels as WT. However, the NS4B R36A mutant did not attenuate the virulence in duck embryos, whereas the G4A mutant significantly decreased the mortality (70%) of duck embryos. In addition, the NS4B W5A mutant did not affect viral replication, whereas the D34A mutant slightly reduced RNA replication, and both mutants exhibited significantly lower titer levels than the WT and significantly decreased mortality (90% and 70%, respectively) in duck embryos. Hence, our findings provide new insight into the development of attenuated flaviviruses by targeting the disabling viral strategies used to evade the innate defense mechanisms.