Resting-State fMRI Study of Vigilance Under Circadian and Homeostatic Modulation Based on Fractional Amplitude of Low-Frequency Fluctuation and Regional Homogeneity in Humans Under Normal Entrained Conditions.

BACKGROUND: How brain neural activity changes at multiple time points throughout the day and the neural mechanisms underlying time-dependent modulation of vigilance are less clear. PURPOSE: To explore the effect of circadian rhythms and homeostasis on brain neural activity and the potential neural basis of time-dependent modulation of vigilance. STUDY TYPE: Prospective. SUBJECTS: A total of 30 healthy participants (22-27 years old). FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted imaging, echo-planar functional MRI (fMRI). ASSESSMENT: Six resting-state fMRI (rs-fMRI) scanning sessions were performed at fixed times (9:00 h, 13:00 h, 17:00 h, 21:00 h, 1:00 h, and 5:00 h) to investigate fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) diurnal variation. The fALFF/ReHo and the result of the psychomotor vigilance task were used to assess local neural activity and vigilance. STATISTICAL TESTS: One-way repeated measures analysis of variance (ANOVA) was used to assess changes in vigilance (P < 0.05) and neural activity in the whole brain (P < 0.001 at the voxel level and P < 0.01 at the cluster level, Gaussian random field [GRF] corrected). Correlation analysis was used to examine the relationship between neural activity and vigilance at all-time points of the day. RESULTS: The fALFF/ReHo in the thalamus and some perceptual cortices tended to increase from 9:00 h to 13:00 h and from 21:00 h to 5:00 h, whereas the key nodes of the default mode network (DMN) tended to decrease from 21:00 h to 5:00 h. The vigilance tended to decrease from 21:00 h to 5:00 h. The fALFF/ReHo in the thalamus and some perceptual cortices was negatively correlated with vigilance at all-time points of the day, whereas the fALFF/ReHo in the key nodes of the DMN was positively correlated with vigilance. DATA CONCLUSION: Neural activities in the thalamus and some perceptual cortices show similar trends throughout the day, whereas the key nodes of the DMN show roughly opposite trends. Notably, diurnal variation of the neural activity in these brain regions may be an adaptive or compensatory response to changes in vigilance. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 1.

The transcription factor BnaWRKY10 regulates cytokinin dehydrogenase BnaCKX2 to control cytokinin distribution and seed size in Brassica napus.

Cytokinins (CKs) are phytohormones that promote cell division and differentiation. However, the regulation of CK distribution and homeostasis in Brassica napus is poorly understood. Here, the endogenous CKs were first quantified by LC-ESI-MS/MS in rapeseed tissues and visualized by TCSn::GUS reporter lines. Interestingly, the cytokinin oxidase/dehydrogenase BnaCKX2 homologs were mainly expressed in reproductive organs. Subsequently, the quadruple mutants of the four BnaCKX2 homologs were generated. Endogenous CKs were increased in the seeds of the BnaCKX2 quadruple mutants, resulting in a significantly reduced seed size. In contrast, overexpression of BnaA9.CKX2 resulted in larger seeds, probably by delaying endosperm cellularization. Furthermore, the transcription factor BnaC6.WRKY10b, but not BnaC6.WRKY10a, positively regulated BnaA9.CKX2 expression by binding directly to its promoter region. Overexpression of BnaC6.WRKY10b rather than BnaC6.WRKY10a resulted in lower concentration of CKs and larger seeds by activating BnaA9.CKX2 expression, indicating that the functional differentiation of BnaWRKY10 homologs might have occurred during B. napus evolution or domestication. Notably, the haploid types of BnaA9.CKX2 were associated with 1000-seed weight in the natural B. napus population. Overall, the study reveals the distribution of CKs in B. napus tissues, and shows that BnaWRKY10-mediated BnaCKX2 expression is essential for seed size regulation, providing promising targets for oil crop improvement.

Altered static and dynamic indices of intrinsic brain activity in patients with subcortical ischemic vascular disease: a resting-state functional magnetic resonance imaging analysis.

PURPOSE: To explore the static and dynamic characteristics of intrinsic brain activity (IBA) in subcortical ischemic vascular disease (SIVD) patients with or without cognitive impairment. METHODS: In total, 90 participants were recruited, including 32 SIVD patients with cognitive impairment (SIVD-CI, N = 32), 26 SIVD patients with no cognitive impairment (SIVD-NCI, N = 26), and 32 healthy controls (HC, N = 32) matched for age, gender, and education. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and neuropsychological tests. Amplitude of low-frequency fluctuation (ALFF) was calculated to reflect static alterations of regional IBA. Sliding window analysis was conducted in order to explore the dynamic characteristics. RESULTS: Both SIVD-CI and SIVD-NCI group showed significantly decreased ALFF in left angular gyrus (ANG), whereas SIVD-CI group showed increased ALFF in right superior frontal gyrus (SFG), compared with HCs. Furthermore, SIVD-CI group showed significantly decreased ALFF dynamics (dALFF) in right precuneus (PreCu) and left dorsal anterior cingulate cortex (dACC), compared with HC and SIVD-NCI groups (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). No dynamic changes were detected between SIVD-NCI group and HC group. The mean ALFF value in left ANG of SIVD-CI group was correlated with the score of delayed memory scale. CONCLUSION: ANG may be a vulnerable brain region in SIVD patients. Temporal dynamic analysis could serve as a sensitive and promising method to investigate IBA alterations in SIVD patients.

Enhancing the antitumor immunosurveillance of PD-L1-targeted gene therapy for metastatic melanoma using cationized Panax Notoginseng polysaccharide.

Improved curative effects with reduced toxicity has always been the ultimate goal of gene delivery vectors for tumor immunotherapy. Panax notoginseng polysaccharide (PNP), a natural plant-derived macromolecule, not only has antitumor immune activity but also has the typical structural characteristics useful for gene delivery. In this work, positively charged polyethyleneimine (PEI) was directly grafted to the backbone of PNP to induced its charge reversal and generate a functional gene vector (PNP-PEI). Moreover, a short hairpin RNA targeting the programmed death-ligand 1 (PD-L1) was loaded into PNP-PEI to generate a potentially therapeutic nanoparticle (PNP-PEI/shPD-L1). In vitro and in vivo experiments demonstrated that PNP-PEI could efficiently carry the therapeutic shPD-L1 into tumor cells and that PNP-PEI/shPD-L1 could significantly inhibit the expression of PD-L1 and growth of B16-F10 cells. Noteworthily, treatment with PNP-PEI reversed the phenotype of macrophages from M2 to M1 subtype and promoted dendritic cell maturation, which encouraged the host immunity and enhanced the therapeutic antitumor effects. In summary, this study describes a PNP-based gene delivery vector and highlights the beneficial immunopotentiating therapeutic outcomes of PNP-PEI for tumor immunotherapy.

PICALM rs3851179 Variants Modulate Left Postcentral Cortex Thickness, CSF Amyloid ß42, and Phosphorylated Tau in the Elderly.

PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer's disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid ß (Aß) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF Aß, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher Aß42 levels and Aß42/40 ratios, and lower P/T-tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, Aß42 level, and P/T-tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.

Occurrence Characteristics of Fine-Grained Pyrite in Coal and Its Scaling Effect on Flotation Desulfurization.

To explore the occurrence and distribution characteristics of fine-grained pyrites in coal and the effect of pyrite particle size on flotation efficiency, coal samples from Guizhou province and Shanxi province, China, were selected for pyrite morphology observation and sulfur content test before and after flotation desulfurization experiments with different coal particle sizes. Experimental results showed that the fine-grained fine pyrites in coal have various occurrence forms and complex connections with the coal matrix. The fragmentation process can change the distribution of pyrite content in coal. Flotation desulfurization experiments showed that the sum of pyrite content in the cleaned coal and middlings gradually became significantly higher in coal particles with size 15-37 µm compared with particle sizes 37-44 and 44-75 µm. The complex occurrence morphology and crystal structure of fine-grained pyrite make it difficult to be removed from the coal matrix by ore grinding during flotation. Fine-grained pyrite mainly occurs in the form of framboïdal pyrite, disseminated pyrite, and monomer pyrite with a size of 0.69-33.94 µm in the middlings and cleaned coal. Therefore, 37 µm is considered as the critical dimension for ore grinding to improve the effective flotation desulphurization efficiency in this study, and some more effective methods should be used to increase the desulfurization efficiency of fine-grained pyrite.

Permeability Response Characteristics of Primary Undeformed Coal and Tectonically Deformed Coal under Loading-Unloading Conditions in Huainan Coalfield, China.

Reservoir pressure relief is a practical method to enhance permeability for coalbed methane (CBM) extraction in tectonically deformed coal (TDC) reservoirs. To explore the coal permeability response to stress changes, the primary undeformed coal (PUC) and TDC from the same coal seam were sampled for the pore-fissure structure analysis, mechanical property test, and permeability experiments under different stress loading-unloading methods in this study. The experimental results demonstrated that the coal permeability is more sensitive to the changes in confining pressure (perpendicular to airflow) than axial stress (parallel to airflow). Coal permeability decreases negatively exponentially as the confining pressure increases, and its change process with increased axial pressure can be divided into five stages in this study. The pore structures and mechanical properties of coal samples affected their permeability response to stress changes. Under the stress loading condition, the coal matrix and fractures of PUC samples were compressed simultaneously, and the permeability was regulated by the pore-fissure structures in the coal matrix. Due to the deformation and displacement of coal particles, the permeability of the TDC sample is predominantly dependent on changes in intergranular pores. At the initial stress unloading stage, the fissure recovery and expansion lead to a rapid increase in permeability, but the permeability cannot rereach the original value when the stress is fully released. Furthermore, the influencing factors of coal permeability in response to stress loading-unloading also include confining pressure conditions and coal matrix adsorption swelling. Research on the permeability response characteristics of the stress loading-unloading process can provide some clarifications for the reservoir depressurization and permeability enhancement of CBM extraction in the TDC reservoir.

Improvement of Resistance to Clubroot Disease in the Ogura CMS Restorer Line R2163 of Brassica napus.

Oilseed rape (Brassica napus) has significant heterosis and Ogura CMS is a major way to use it. Ogura CMS has the advantages of complete and stable male sterility and easy-to-breed maintainers. Therefore, to breed better restorers has become an important goal for this system. Incidentally, clubroot is a soil-borne disease that is difficult to control by fungicidal chemicals, and it has been the main disease of oilseed rape in recent years in China, severely restricting the development of the oilseed rape industry. At present, the most effective method for controlling clubroot disease is to cultivate resistant varieties. One Ogura CMS restorer line (R2163) has shown much better combining ability, but lacks the clubroot disease resistance. This study was carried out to improve R2163 through marker-assisted backcross breeding (MABB). The resistant locus PbBa8.1 was introduced into the restorer R2163, and we then selected R2163R with clubroot disease resistance. Using the new restorer R2163R as the male parent and the sterile lines 116A and Z11A as the female parent, the improved, new resistant hybrids Kenyouza 741R and Huayouza 706R performed well, providing strong resistance and good agronomic traits. This work advances the utilization of heterosis and breeding for clubroot disease resistance in B. napus.

Clinical features and high-resolution chest computerized tomography findings of children infected by the B.1.617.2 variant of coronavirus disease 2019.

PURPOSE: To analyse the clinical symptoms, laboratory examinations and chest CT findings of children infected by the B.1.617.2 variant of COVID-19 and to compare the differences between clinical subtypes. METHODS: Fifty-three children (28 males, 25 females; age ranging from 4 months to 17 years) were included with B.1.617.2 variant infection in Nanjing, China, from July 21 to August 12 2021. Clinical data from patients were collected and analysed in groups of mild and common types. Imaging data were divided into three stages for evaluation: early, intermediate and late stages. RESULTS: In our study, fever (53%), cough (34%) and pharyngeal discomfort (28%) were the main symptoms. There were no differences in clinical symptoms between the mild and common type. The most common laboratory test items outside the normal range were decreased mean corpuscular volume (68%), lymphocyte percentage (64% elevated and 2% decreased) and decreased serum alkaline phosphatase concentration (66%). The differences in haemoglobin and monocyte percentages between the mild and common types were statistically significant (p = .037 and .033, respectively). No influencing factor was statistically significant in the regression analysis of both symptoms and clinical subtypes. The main CT findings were ground-glass opacity and consolidation located in the periphery and bilateral multilobed involvement. The mean CT score was 1.6. CT score correlated with packet cell volume, haemoglobin, mean erythrocyte volume, mean platelet volume and platelet distribution width. CONCLUSION: The pathogenetic condition of children with B.1.617.2 variant infection is mild. Although there were intergroup differences in some blood cell analyses, T-lymphocyte counts, and comprehensive biochemical indicators, no factors had a significant effect on clinical typing and the presence or absence of symptoms. CT findings and CT scores reflect disease stage and pathological changes and correlate moderately with laboratory tests, making them of good value for disease diagnosis and monitoring.Key MessagesPaediatric patients infected with B.1.617.2 variant have a milder clinical and imaging presentation than adults and are similar to the prototype infection.CT findings and scores which reflect disease stages and pathological changes.There is a correlation between chest CT and laboratory tests, which can be useful for the diagnosis and follow-up of the disease.

Enrichment Characteristics of Macerals during Triboelectrostatic Separation in the View of Surface Microstructure, Pore distribution, and Typical Electrical Parameters.

Vitrinite and inertinite, respectively, are the reactive and inert macerals for coal liquefaction, which could be effectively enriched in triboelectrostatic separation specialized in particle processing. Inertinite has a higher specific surface area and more pores than vitrinite and a more balanced mesopores distribution, while the mesopores in vitrinite are mainly focused in the 4 nm × 7 nm range. As for electrical properties, inertinite has a higher relative dielectric constant than vitrinite in all granularities, while its resistivity is only higher than vitrinite in the <74 µm fraction, which means inertinite and vitrinite tend to have negative and positive charges, respectively, in their mutual friction, but inertinite (<74 µm) has a stronger ability to maintain surface charge. During triboelectrostatic separation, the 105 µm × 150 µm fraction of clean coal has the highest vitrinite content, whereas inertinite tends to concentrate at tailings <74 µm under the co-effect of separation granularity limit and electrical characteristics of macerals; this conclusion has a certain guiding significance to maceral separation.

An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.

BACKGROUND: Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra-epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole-genome bisulfite sequencing (WGBS-seq), oxidative WGBS, RNA-seq, and external histone modifications profiling data. RESULTS: In the development and progression of CC, there were genome-wide hypo-methylation and hypo-hydroxymethylation, accompanied by local hyper-methylation and hyper-hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region-associated genes both enriched in Hippo and other cancer-related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated-associated genes (DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP, and PAPSS2) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs. CONCLUSION: Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated-associated genes can be used as the potential epigenetic biomarkers in CC prognosis.

White Matter Structural Network Analysis to Differentiate Alzheimer's Disease and Subcortical Ischemic Vascular Dementia.

To explore the evaluation of white matter structural network analysis in the differentiation of Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD), 67 participants [31 AD patients, 19 SIVD patients, and 19 normal control (NC)] were enrolled in this study. Each participant underwent 3.0T MRI scanning. Diffusion tensor imaging (DTI) data were analyzed by graph theory (GRETNA toolbox). Statistical analyses of global parameters [gamma, sigma, lambda, global shortest path length (Lp), global efficiency (Eg), and local efficiency (Eloc)] and nodal parameters [betweenness centrality (BC)] were obtained. Network-based statistical analysis (NBS) was employed to analyze the group differences of structural connections. The diagnosis efficiency of nodal BC in identifying different types of dementia was assessed by receiver operating characteristic (ROC) analysis. There were no significant differences of gender and years of education among the groups. There were no significant differences of sigma and gamma in AD vs. NC and SIVD vs. NC, whereas the Eg values of AD and SIVD were statistically decreased, and the lambda values were increased. The BC of the frontal cortex, left superior parietal gyrus, and left precuneus in AD patients were obviously reduced, while the BC of the prefrontal and subcortical regions were decreased in SIVD patients, compared with NC. SIVD patients had decreased structural connections in the frontal, prefrontal, and subcortical regions, while AD patients had decreased structural connections in the temporal and occipital regions and increased structural connections in the frontal and prefrontal regions. The highest area under curve (AUC) of BC was 0.946 in the right putamen for AD vs. SIVD. White matter structural network analysis may be a potential and promising method, and the topological changes of the network, especially the BC change in the right putamen, were valuable in differentiating AD and SIVD patients.