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Background: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. Objective: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. Methods: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. Results: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. Conclusion: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer's disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD.Objective: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD.Methods: Methylation levels were obtained from 222 participants (101 AD, 72 MCI, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity.Results: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7 1040077, CNR1 88166293, CX3CR1 39322324, LRRK2 40618505, LRRK2 40618493, NGFR 49496745, TARDBP 11070956, TARDBP 11070840 area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7 1040077 and CX3CR1 39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively).Conclusion: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD. [ABSTRACT FROM AUTHOR]

The abrasive flow precision machining technology was used to carry out numerical simulation and experimental research for the special-shaped deep holes. A large-eddy simulation method was used to numerically analyze the titanium alloy shaped hole parts, and related experimental studies were conducted to reveal the creation mechanism of the surface of the abrasive flow machining special-shaped curved surfaces. The study finds that: the effects of dynamic pressure, velocity, the pressure of abrasive particles on wall surfaces and the effects wall shear force on wall surfaces were revealed through numerical analysis of precision machining of abrasive flow. The vortex position distribution and the cause of the vortex as well as the interaction relationship between the vortex and the abrasive particles in the flow directional sections of the special-shaped section holes were obtained; After precision machining by abrasive flow, the surface roughness of special-shaped curved surfaces improves from Ra=7.136 µm, Rz=40.103 µm to Ra=1.822 µm, Rz=8.964 µm respectively. The protrusions and spheroidization on the inner surfaces of the shaped holes are removed, and the surface quality is significantly improved. The vortex greatly improves the surface quality of the special-shaped curved surfaces. [ABSTRACT FROM AUTHOR]

Abstract Angkor temples in Cambodia, an icon of Khmer civilization, display the ancient culture by bas-relief on the sandstone surface of different temples, which are being destroyed by physical, chemical and biological processes for more than a thousand years. To investigate the bio-erosion of temple sandstone at the Royal Palace of Angkor Thom and Beng Mealea in Cambodia, Next Generation Sequencing (NGS) Illumina sequencing technology based on 16S rRNA gene was performed on samples of biofilm and exfoliated sandstone materials to identify the microbial community composition. After quality filtering the raw data, 678,115 quality reads were obtained for bacterial 16S rRNA gene from a total of 13 samples with high Goods coverage and satisfactory rarefaction curves. Higher bacterial diversity was detected in exfoliated sandstone materials than the biofilms, but the lowest in the lower layers of the biofilm than the top layers. At the phylum level, 4 phyla, namely Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi, were the most common and dominant bacterial groups in these samples with each contributing to greater than 3.7% of the total abundance. Both Firmicutes and Gemmatimonadetes were the dominant phyla detected only in exfoliated materials, while Cyanobacteria, Chloroflexi, and unassigned bacteria were more abundant in the biofilms. Hierarchical cluster analysis at the genus level showed that the distribution of bacterial community composition between exfoliated materials and biofilms was significantly different. The microbiota of Beng Mealea and the Royal Palace was different, especially for the biofilm samples. The correlation of environmental factors and bacterial community structure suggested that the nitrification process was more active at Ben Mealea, which might contribute to biodeterioration. This analysis of microbiota in these biofilms and sandstone exfoliation materials provides further information on the responsible microorganisms involved in geobiochemical processes at Angkor monuments and preservation strategies under tropical climate conditions. Graphical abstract Image 1 Highlights • NGS Illumina sequencing of biofilm and exfoliated sandstone materials at Ben Mealea and the Royal Palace. • Microbiota of the Beng Mealea and the Royal Palace was different, especially for the biofilm samples. • Higher bacterial diversity in exfoliated sandstone than biofilms. • Lowest diversity in the bottom layer of the biofilm comparing with the upper layers. • Nitrification process was more active at Ben Mealea than the Royal Palace. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders. [Display omitted] • Patients with multiple sclerosis exhibit prominent bone marrow myelopoiesis • Autoreactive T cells migrate into the bone marrow via the CXCL12-CXCR4 axis • Autoreactive T cells augment bone marrow myelopoiesis • Bone marrow output of myeloid cells exacerbates CNS inflammatory injury Autoreactive T cells migrate into the bone marrow and skew hematopoietic stem and progenitor cells toward myeloid lineages that augment inflammatory brain injury, suggesting the restriction of bone marrow myelopoiesis as a potential therapy for multiple sclerosis. [ABSTRACT FROM AUTHOR]

Dysregulation of cholesterol metabolism underlies neurodegenerative disease and is increasingly implicated in neuroinflammatory diseases, such as multiple sclerosis (MS). Cytochrome P450 family 7 subfamily B member 1 (CYP7B1) is a key enzyme in alternative cholesterol metabolism. A recessive mutation in the gene CYP7B1 is known to cause a neurodegenerative disease, hereditary spastic paraplegia type 5 and oxysterol accumulation. However, the role of CYP7B1 in neuroinflammation has been little revealed. In this study, we induced experimental autoimmune encephalomyelitis (EAE), as a murine model of MS, using CYP7B1 homozygous knockout (KO) mice. We found that CYP7B1 deficiency can significantly attenuate EAE severity. CYP7B1 deficiency is sufficient to reduce leukocyte infiltration into the central nervous system, suppress proliferation of pathogenic CD4 + T cells, and decrease myeloid cell activation during EAE. Additionally, live-animal imaging targeting translocator protein expression, an outer mitochondrial membrane protein biomarker of neuroinflammation, showed that CYP7B1 deficiency results in suppressed neuroinflammation. Using human monocyte-derived microglia-like cellular disease model and primary microglia of CYP7B1 KO mice, we also found that activation of microglia of CYP7B1 deficiency was impaired. These cumulative results suggest that CYP7B1 can regulate neuroinflammation, thus providing potential new targets for therapeutic intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Multiple sclerosis (MS) and Cerebral Small Vessel Disease (CSVD) exhibit some similarities in Magnetic resonance imaging (MRI), potentially leading to misdiagnosis and delaying effective treatment windows. It is unclear whether CSVD can be detected with Paramagnetic Rim Lesions (PRL), which is special in MS., Objective: We aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD., Methods: In this retrospective study, 49 MS and 104 CSVD patients underwent 3.0 T Magnetic resonance imaging (MRI). Visual assessment of 37 MS patients and 89 CSVD patients with or without lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), central vein sign (CVS), and PRL. The distribution and number of PRL were then counted., Results: Our study found that PRL was detected in over half of the MS patients but was entirely absent in CSVD patients (78.38 vs. 0%, p  < 0.0001), and PRL showed high specificity with good sensitivity in discriminating between MS and CSVD (sensitivity: 78.38%, specificity: 100%, AUC: 0.96)., Conclusion: Paramagnetic Rim Lesions is a special imaging feature in MS, absent in CSVD. Detection of PRL can be very helpful in the clinical management of MS and CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Zhang, Li, Guo, Chen, Chen, Li, Wang, Chen and Fu.)

Advanced age and apolipoprotein E ( APOE ) ε4 allele are both associated with increased risk of the Alzheimer's disease (AD). However, the extent of the joint contribution of APOE ε4 allele and age on the brain white matter integrity, cognition and their relationship are unclear. We assessed the age-related variation differences of major cognitions in 846 non-demented elderly, and brain major white matter tracts in an MRI sub-cohort of 111 individuals between ε4 carriers and noncarriers. We found that: (i) carriers showed a steeper age-related decline after age 50 in general mental status, attention, language, and executive function and performed worse than noncarriers at almost all ages; (ii) main effect of age on anterior fibers, but main effect of APOE ε 4 on posterior fibers, and the interactive effect of them existed on anterior and posterior fibers; (iii) carriers showed an accelerated age-related integrity reduction of these fibers compared to noncarriers who had a slight decrease but not significant; and (iv) significant associations of the higher white matter integrity with better multi-cognitive performance in old ε4 carriers. Overall, combining APOE status with age may be useful in assessing possible mechanisms of disease development in AD.

The object of this study was to estimate the sorption property of active silica derived from fly ash after separation of silica and aluminum. The specific surface area of active silica enlarged to 115 m(2)/g was compared with the original fly ash (4 m(2)/g). Field emission scanning electron microscopy displayed the active silica, which looked like a honeycomb or curly layer with many lamellae that formed many mesopores. The uptake kinetics indicated that the residual concentration of Pb(2+) in the aqueous solution decreased rapidly from the initial 1.25 mg/L to less than 10 μg/L within 45 min. The removal efficiency of Pb(2+) on active silica was pH dependent. The increase in pH value promoted Pb(2+) removal because the negative surface provided more electrostatic attraction sites. A stepwise non-linear isotherm was obtained because the lamellae of active silica provided a heterogeneous surface with various kinds of active sites. The maximum sorption amount of Pb on active silica was more than 90 mg/g, which was better than some pristine-activated carbon.