Abstract only
e21669
Background: In the new era of immunotherapy, the regimen based on bevacizumab is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) ...patients without driver mutations. However, the prognostic factors for bevacizumab are still missing. We aimed to determine the integrative value of computed tomography (CT), epigenetic modifications, clinicopathological and systemic inflammatory factors for predicting the survival of advanced NSCLC patients with bevacizumab. Methods: Clinicopathological parameters, dynamic systemic inflammatory factors, radiomics features, and DNA methylation profiling in advanced non-squamous NSCLC patients receiving first- or second- line bevacizumab plus chemotherapy were included in this study. The prognostic radiomics signature were constructed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A multi-omics prediction nomogram for progression-free survival (PFS) based on radiomics, clinicopathological and systemic inflammatory features was established and independently validated. Furthermore, radiomics signature-related DNA methylation were submitted to functional enrichment analysis. Results: Total of 272 patients were included in analysis, 224 in training cohort and 48 in validation cohort. Five radiomics features, including Information Measure Corr1, Inverse Variance, Local Std Max, Gauss Area, Spherical Disproportion, were finally selected to construct radiomics signature with the AUC of 0.71. Smoking history, anatomical feature, liver metastasis, LDH4, NLR2 and radiomics signature were found to be independent prognostic factors for PFS. A multi-omics nomogram was developed based on these features in training cohort with the C-index of 0.76, and external validated with the C-index of 0.75. The tissue slices of 20 patients receiving bevacizumab were used for DNA methylation profiling. Functional enrichment analysis indicated widespread and statistically significant associations between radiomics features and DNA methylation changes which involved in several pathways related to angiogenesis and immune system, such as Notch signaling pathway, small GTPase Rho signal transduction, TGFβ signal transduction. Conclusions: This multi-omics nomogram integrating radiomics, clinicopathological, systemics inflammatory features improved the prediction of PFS in advanced NSCLC patients receiving bevacizumab. And the radiomics signature were found to be related to angiogenesis and immune status.
Mechanoluminescence (ML) materials exhibit great potential in the fields of light sources, displays, and stress sensors because they can convert mechanical stimuli into luminescence. Most ML ...materials exhibit weak brightness and limited colors; therefore, tunable colors are highly desired. Herein, a facile strategy for tuning the ML of a flexible composite of zinc sulfide (ZnS) phosphor and all-inorganic CsPbX3 (X = Cl, Br, and I) perovskite quantum dots (PeQDs) is demonstrated. A broad color expression with a narrow emission band was achieved under low stretching–releasing stress by changing the halide component of CsPbX3. The color conversion between ZnS and PeQDs is a radiative combination and reabsorption process, and full color tuning from 510 to 710 nm occurred because of the bandgap tailoring of PeQDs. Furthermore, some proof-of concept devices, including multicolor displays and white light sources, were demonstrated by changing the composition of PeQDs. This work provides a versatile approach to fine–tune the ML spectrum, thereby paving the way for applications such as piezophotonic displays and white light sources.
Display omitted
•Tunable ML spectrum in a broad range of 510—710 nm is achieved from the ZnS/PeQDs composite.•The composite emits intense ML light due to the large absorption coefficients and high PLQY of PeQDs.•The composite exhibits a low threshold of 10 N because of the high sensitivity of ZnS and energy conversion of PeQDs.•Multicolor displays and bright white color emission under small mechanical stress has been demonstrated.
Purpose
Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation ...between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics.
Methods
Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters.
Results
Compared to HCs, the performance of alertness in the patient group was typically worse (
p
< 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (
p
< 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs.
Conclusion
Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs.
To investigate the longitudinal alterations of cortical structural-functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2-year follow-up, thereby exploring the ...neuropathophysiological mechanisms of TLE.
Twenty-eight TLE patients and 42 age- and gender-matched healthy controls (HCs) were recruited. We used resting-state functional MRI and diffusion-weighted imaging to estimate and compare SF coupling at the multiscale network level (whole-brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow-up to the expression of regional TLE-specific genes.
Compared with HCs, TLE patients showed higher baseline SF couplings within the whole-brain, limbic, and default-mode modules. SF couplings within visual and dorsal attention modules were increased at follow-up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene.
Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE-specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE.
BackgroundOsteoprotegerin (OPG) is supposed to participate in the development of atherosclerosis and cardio-cerebrovascular disease. However, the results of research on relationship between OPG and ...ischemic stroke (IS) are controversial. Therefore, we carried out the first systematic review and meta-analysis to evaluate prognostic effect of osteoprotegerin in patients with IS.MethodsWe comprehensively searched databases of PubMed, Embase, and the Cochrane Library through 21 August 2023 to identify observational studies that evaluated effect of OPG on poor functional outcome (modified Rankin Scale mRS Score of 3-6) and mortality in patients with IS. Adjusted odds ratios (aOR) with a 95% confidence interval (CI) of each included study were used as much as possible to assess the pooled effect.ResultsFive studies that enrolled 4,506 patients in total fulfilled our inclusion criteria. Three studies were included in the pooled analysis for each endpoint since one of the included studies had provided data on poor functional outcome as well as mortality. OPG was neither associated with poor functional outcome (aOR 1.29, 95% CI 0.90-1.85) nor with mortality (aOR 1.57, 95% CI 0.90-2.74) in patients with IS.ConclusionsThere is insufficient evidence to demonstrate the correlation between OPG and mortality or poor functional outcome in IS patients. OPG cannot be applied to predict worse neurological function in IS patients based on the current evidence.
4-Formylaminooxyvinylglycine (FVG) is an oxyvinylglycine-type nonproteinogenic amino acid that inhibits seed germination and the fire blight pathogen Erwinia amylovora. Despite the simple chemical ...structure of FVG, its biosynthesis has remained obscure for nearly a decade. Herein, we characterize the amidinotransferase GvgD and pyridoxal 5′-phosphate (PLP) dependent enzyme GvgH in vitro. GvgD catalyzes a reversible amidinotransfer reaction between l-canaline and l-canavanine. GvgH is supposed to install the aminooxy group in FVG via an elimination–addition reaction. The γ-elimination of O-succinylhomoserine and O-acetylhomoserine is validated to yield 2-aminobut-3-enoic acid. Besides, 2-mercaptoethanol acts as a non-specific substrate of GvgH for the subsequent addition, although the true substrate remains elusive. This work provides important insights into the biosynthesis of FVG.
Triboelectric nanogenerators (TENGs) that convert mechanical energy into electricity have attracted tremendous attention and kinds of strategies are proposed to optimize the electrical performance of ...TENG. In this work, we fabricated a TENG based on a sandwich-structured polyimide (PI)/boron nitride nanosheet (BNNS)/PI nanocomposite film (named PBP). The PBP-TENG exhibits an optimized open-circuit voltage of 65.9 V and a short-circuit current of 4.5 μA. When the load resistance was 10 MΩ, the introduction of a BNNS interlayer raised the power density of the TENG up to 21.4 μW/cm2, which is 15 times higher than that of TENG without a BNNS interlayer (PP-TENG). It is found that the relatively high dielectric constant of BNNS leads to enhancing the output performance of the TENG. More importantly, PBP-TENG also maintains excellent output even in a high-humidity environment.
Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that is the most significant etiological agent of childhood viral neurological infections. However, no specific antiviral drug is currently ...available to treat JEV infections. The JEV envelope (E) protein is a class II viral fusion protein that mediates host cell entry, making interference with the interaction between the E protein of JEV and its cognate receptors an attractive strategy for anti-JEV drug development. In this study, we identified a peptide derived from a phage display peptide library against the E protein of JEV, designated P1, that potentially inhibits in vitro and in vivo JEV infections. P1 inhibits JEV infection in BHK-21 cells with 50% inhibitory capacity at a concentration of 35.9 μM. The time-of-addition assay indicates that JEV replication is significantly inhibited during pre-infection and co-infection of P1 with JEV while post-infection treatments with P1 have very little impact on JEV proliferation, showing that P1 inhibits JEV infection at early stages and indicating the potential prophylactic effect of P1. We adapted an in vitro BiFC assay system and demonstrated that P1 interacts with JEV E proteins and blocks their entry into cells. We also evaluated the therapeutic efficacy of P1 in a lethal JEV mouse model exhibiting systemic and brain infections. Interestingly, P1 treatment protected C57BL/6 mice against mortality, markedly reduced the viral loads in blood and brain, and diminished the histopathological lesions in the brain cells. In addition to controlling systemic infection, P1 has a very low level of cytotoxicity and acts in a sequence-specific manner, as scrambled peptide sP1 does not show any antiviral activity. In conclusion, our in vitro and in vivo experimental findings show that P1 possesses antiviral activity against JEV infections, is safe to use, and has potential for further development as an antiviral treatment against JEV infections.
•Peptide P1 target to E protein by phage display screening inhibits JEV infection by blocking JEV attachment to host cells.•P1 decreases histopathological damages and viral load in mouse brain.•P1 increases survival rate of mice in lethal JEV challenge after preincubation with JEV.
•Some JEV strains caused notable mortality in newly hatched domestic ducklings.•JEV infection resulted in stunted growth in newly hatched domestic ducklings.•Response and susceptibility of ducklings ...to JEV infection differed among JEV strains.
Japanese encephalitis virus (JEV) is a zoonotic flavivirus that is transmitted by mosquitoes and vertebrate-amplifying hosts, including birds. Domestic ducks are susceptible to JEV infection and develop various levels of viremia. We tested the pathogenicities of seven JEV strains in newly hatched domestic ducklings. All inoculated ducklings showed stunted growth. Two JEV strains caused notable mortalities of 12.7% and 31.7%, respectively, highlighting that some emerged JEV strains may thus be pathogenic in newly hatched domestic ducklings.
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis results in severe neuropsychiatric symptoms and persistent cognitive impairment; however, the underlying mechanism is still not fully ...understood. The present study utilized the degree centrality (DC), functional connectivity (FC) and multivariate pattern analysis (MVPA) to further explore neurofunctional symptoms in patients with anti-NMDAR encephalitis. A total of 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs) were enrolled for neuropsychological assessment and resting-state functional MRI (rs-fMRI) scans. DC, FC and MVPA were examined to investigate cerebral functional activity and distinguish neuroimaging characteristics between the patient and HC groups based on the rs-fMRI data. Compared with the HCs, the patients exhibited cognitive deficits, anxiety and depression. In the DC analysis, the patients exhibited significantly decreased DC strength in the left rectus gyrus, left caudate nucleus (LCN) and bilateral superior medial frontal gyrus, as well as increased DC strength in the cerebellar anterior lobe, compared with the HCs. In the subsequent FC analysis, the LCN showed decreased FC strength in the bilateral middle frontal gyrus and right precuneus. Furthermore, correlation analysis indicated that disrupted cerebral functional activity was significantly correlated with the alerting effect and Hamilton Depression Scale score. Using DC maps and receiver operating characteristic curve analysis, the MVPA classifier exhibited an area under curve of 0.79, and the accuracy classification rate was 76.36%, with a sensitivity of 79.31% and a specificity of 78.18%. The present study revealed that the disrupted functional activity of hub and related networks in the cerebellum, including the default mode network and executive control network, contributed to deficits in cognition and emotion in patients with anti-NMDAR encephalitis. In conclusion, the present study provided imaging evidence and primary diagnostic markers for pathological and compensatory mechanisms of anti-NMDAR encephalitis, with the aim of improving the understanding of this disease.
