Search

Abstract Background Neuropsychiatric symptoms (NPS) are prevalent in cognitively impaired individuals including Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI). Whereas several studies have reported the associations between NPS with AD pathologic biomarkers and cerebral small vessel disease (SVD), but it remains unknown whether AD pathology and SVD contribute to different sub-syndromes independently or aggravate same symptoms synergistically. Method We included 445 cognitively impaired individuals (including 316 MCI and 129 AD) with neuropsychiatric, cerebrospinal fluid (CSF) biomarkers (Aβ42, p-tau, and t-tau) and multi-model MRI data. Psychiatric symptoms were accessed by using the Neuropsychiatric Inventory (NPI). Visual assessment of SVD (white matter hyperintensity, microbleed, perivascular space, lacune) on MRI images was performed by experienced radiologist. Linear regression analyses were conducted to test the association between neuropsychiatric symptoms with AD pathology and CSVD burden after adjustment for age, sex, education, apolipoprotein E (APOE) ε4 carrier status, and clinical diagnosis. Results The NPI total scores were related to microbleed (estimate 2.424; 95% CI [0.749, 4.099]; P =0.005). Considering the sub-syndromes, the hyperactivity was associated with microbleed (estimate 0.925; 95% CI [0.115, 1.735]; P =0.025), whereas the affective symptoms were correlated to CSF level of Aβ42 (estimate -0.006; 95% CI [-0.011, -0.002]; P =0.005). Furthermore, we found the apathy sub-syndrome was associated with CSF t-tau/Aβ42 (estimate 0.636; 95% CI [0.078, 1.194]; P =0.041) and microbleed (estimate 0.693; 95% CI [0.046, 1.340]; P =0.036). In addition, we found a significant interactive effect between CSF t-tau/Aβ42 and microbleed (estimate 0.993; 95% CI [0.360, 1.626]; P =0.019) on severity of apathy sub-syndrome. Conclusion Our study showed that CSF Aβ42 was associated with affective symptoms, but microbleed was correlated with hyperactivity and apathy, suggesting the effect of AD pathology and SVD on different neuropsychiatric sub-syndromes.

Soft adhesive systems (SASs), which consist of a soft adhesive layer and/or soft adherends, have been extensively applied in advanced fields such as biomedicine, flexible electronics, and soft robotics. Understanding the fatigue failure of SASs is crucial for ensuring their structural safety and functional stability, as they are often subjected to fatigue loading. This paper systematically reviews the fatigue failure of SASs, aiming to provide a comprehensive understanding and contribute to the study of fatigue failure mechanisms and lifetime prediction of SASs. The review starts by introducing classical research methods for fatigue failure of adhesive systems, with a focus on total fatigue lifetime and fatigue crack growth (FCG). After summarizing the complexity of fatigue failure in SASs, it provides an overview of fatigue research for the three types of SASs: “soft interface”, “soft adherend”, and “soft-soft” adhesive systems. Then, the relations between the fatigue failure and energy dissipation of various SASs are specifically discussed noting that significant energy dissipation accompanying the cyclic deformation of SASs during fatigue loading can substantially affect the final fatigue failure of SASs. Finally, the current unresolved issues and challenges in this field are presented.

In order to reduce carbon emissions and consume a large amount of low-quality solid waste, CFBFA-RM-CS has been developed by utilising the synergistic effect of circulating fluidised bed fly ash (CFBFA), red mud (RM) and calcium carbide slag (CS).The solidification mechanism of the ternary paste was studied from both macroscopic mechanical properties and microscopic experiments including XRD, FTIR, TG-DTG, SEM-EDS tests. The results showed that the main hydration products of CFBFA-CS-RM pastes were AFt and C/N-A-S-H, and the generation of hemialuminate and monoaluminate depended on the contents of RM and CS. The highest strength of the pastes was achieved when the hydration produced just the amount of AFt and the gel products that did not cause cracking.Ca(OH)2 is the main reactant that triggers pozzolanic reaction in CFBFA and solidification of RM. The 3d strengths of both CFBFA and CFBFA-CS pastes were less than 0.4 MPa, and cracking problems occurred，which were solved by the addition of RM, and the early strength of the pastes was significantly improved.

Sunflowers are widely cultivated as a cash crop in the Inner Mongolia Autonomous Region, China. However, due to the lack of efficient resource utilization techniques, most of the sunflower stalks are discarded. In the Hetao irrigation area, the problem of desertification has prompted the limited use of sunflower straw to construct physical sand barriers for windbreaks and sand stabilization. In response to this, this study focuses on synthesizing a cellulose ether sand-fixing material using sunflower straw, the primary agricultural waste in Denkou County, Hetao irrigation district. This material enhances the effective adhesion between sand grains, reduces porosity among loose sand grains, and inhibits sand grain movement. The findings from this study conclusively demonstrate that the sand-fixing materials under investigation meet international standards for mechanical properties. They effectively transform loose, unconnected sand grains into a state with strong adhesion properties.

This paper proposes an unmanned surface vehicles (USVs) formation control method based on distributed average tracking (DAT) with different relative information measurement scale factors. Firstly, the DAT algorithm is designed in the controller to control the time when the system reaches stability. Then, the relative position information of adjacent USVs is measured by installing distance sensors and direction sensors on each USV, and different scale factors are used to control the formation of USVs, and improve the stability and robustness of its control system. Finally, the effectiveness of the method proposed in this paper is verified by numerical simulation experiments.

Pine wilt disease, caused by Bursaphelenchus xylophilus, is a highly destructive and contagious forest affliction. Often termed the “cancer” of pine trees, it severely impacts the growth of Masson pine (Pinus massoniana). Previous studies have demonstrated that ectopic expression of the PmACRE1 gene from P. massoniana in Arabidopsis thaliana notably enhances resistance to pine wilt nematode infection. To further elucidate the transcriptional regulation and protein interactions of the PmACRE1 in P. massoniana in response to pine wilt nematode infection, we cloned a 1984 bp promoter fragment of the PmACRE1 gene, a transient expression vector was constructed by fusing this promoter with the reporter GFP gene, which successfully activated the GFP expression. DNA pull-down assays identified PmMYB8 as a trans-acting factor regulating PmACRE1 gene expression. Subsequently, we found that the PmACRE1 protein interacts with several proteins, including the ATP synthase CF1 α subunit, ATP synthase CF1 β subunit, extracellular calcium-sensing receptor (PmCAS), caffeoyl-CoA 3-O-methyltransferase (PmCCoAOMT), glutathione peroxidase, NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase 1, cinnamyl alcohol dehydrogenase, auxin response factor 16, and dehydrin 1 protein. Bimolecular fluorescence complementation (BiFC) assays confirmed the interactions between PmACRE1 and PmCCoAOMT, as well as PmCAS proteins in vitro. These findings provide preliminary insights into the regulatory role of PmACRE1 in P. massoniana’s defense against pine wilt nematode infection.

Abstract Revealing the energy transfer (ET) process from excitons to rare earth ions in halide perovskites has great guiding value for designing optoelectronic materials. Here, the multiple ET channels in multi‐exciton emissive Sb3+/Nd3+ co‐doped Cs2ZrCl6 are explored to comprehend the ET processes. Förster–Dexter ET theory reveals that the sensitizer concentration rather than the overlap integral of the spectra plays the leading function in the comparison of the ET efficiency among multiple ET channels from the host self‐trapped excitons (STEs) and dopant triplet STEs to Nd3+ ions. Besides, Sb3+/Nd3+ co‐doped Cs2ZrCl6 enables varied color delivery and has great potential as anti‐counterfeiting material. Under X‐ray irradiation, Sb3+/Nd3+ co‐doped Cs2ZrCl6 presents a high light yield of ≈13300 photons MeV−1 and promising X‐ray imaging ability. This work provides new insight for investigating the ET efficiency among multiple ET processes and presents great potentiality of multi‐exciton emissive perovskites in the fields of anti‐counterfeiting and X‐ray imaging.

Abstract Objective This study investigated cerebral small vessel disease (CSVD) damage patterns in early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD) and their effects on cognitive function. Methods This study included 93 participants, 45 AD patients (14 EOAD and 31 LOAD), and 48 normal controls (13 YNC and 35 ONC) from the ADNI database. All participants had diffusion tensor imaging data; some had amyloid PET and plasma p‐tau181 data. The study used peak width of skeletonized mean diffusivity (PSMD) to measure CSVD severity and compared PSMD between patients and age‐matched controls. The effect of age on the relationship between PSMD and cognition was also examined. The study also repeated the analysis in amyloid‐positive AD patients and amyloid‐negative controls in another independent database (31 EOAD and 38 LOAD), and the merged database. Results EOAD and LOAD showed similar cognitive function and disease severity. PSMD was validated as a reliable correlate of cognitive function. In the ADNI database, PSMD was significantly higher for LOAD and showed a tendency to increase for EOAD; in the independent and merged databases, PSMD was significantly higher for both LOAD and EOAD. The impact of PSMD on cognitive function was notably greater in the younger group (YNC and EOAD) than in the older group (ONC and LOAD), as supported by the ADNI and merged databases. Interpretation EOAD has less CSVD burden than LOAD, but has a greater impact on cognition. Proactive cerebrovascular prevention strategies may have potential clinical value for younger older adults with cognitive decline.

Curcumin possesses a wide spectrum of liver cancer inhibition effects, yet it has chemical instability and poor metabolic properties as a drug candidate. To alleviate these problems, a series of new mono-carbonyl curcumin derivatives G1–G7 were designed, synthesized, and evaluated by in vitro and in vivo studies. Compound G2 was found to be the most potent derivative (IC50 = 15.39 μM) compared to curcumin (IC50 = 40.56 μM) by anti-proliferation assay. Subsequently, molecular docking, wound healing, transwell, JC-1 staining, and Western blotting experiments were performed, and it was found that compound G2 could suppress cell migration and induce cell apoptosis by inhibiting the phosphorylation of AKT and affecting the expression of apoptosis-related proteins. Moreover, the HepG2 cell xenograft model and H&E staining results confirmed that compound G2 was more effective than curcumin in inhibiting tumor growth. Hence, G2 is a promising leading compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.

In interference cancellation, the null at the angle of arrival (AoA) of interference can suppress interference. However, due to the large spacing between array elements and the periodicity of the array, some small nulls at the angles of noninterference are formed inevitably. When the AoA of the desired signal is in these small nulls, they impair the effectiveness of interference cancellation by attenuating the desired signal. This paper proposes the concept of a side null to represent these nulls in the noninterference direction. And the cancellation ratio of the desired signal (SCR) is deduced to quantitatively characterize the side null. The spatial noncooperative interference cancellation model based on the main-auxiliary antenna array is established. Based on this, the SCR is derived to evaluate the amount of desired signal attenuation. Then the simulation, respectively, in two-dimensional plane and three-dimensional space, describes the side null visually. Moreover, the method of side null reduction is discussed by modulation of the array. Finally, the existence of side null and its influence on interference cancellation are verified through the experiments. The results of the simulation and experiment are in good agreement, and both support the theoretical analysis.

In this study, we exposed adult male crayfish (Procambarus clarkii) to different concentrations of diclofenac (DCF) for 96 h. In the meantime, we investigated the alternations of hepatopancreatic pathology, molecular regulation and intestinal microbiota of P. clarkii exposed to DCF. The results demonstrated DCF led to histological changes including epithelium vacuolization and tubule lumen dilatation in the hepatopancreas. Transcriptome sequencing analysis showed that 642 and 586 genes were differentially expressed in the hepatopancreas of P. clarkii exposed to 1 and 10 mg/L DCF, respectively. DCF could affect the functions of antioxidation, immunity and metabolism of hepatopancreas by inducing the abnormal expressions of immune- and redox-related genes. GO enrichment results demonstrated that 10 mg/L DCF exposure could modulate the processes of molting, amino sugar metabolism, protein hydrolysis and intracellular protein translocation of P. clarkii. Additionally, the abundances of bacterial families including Shewanellaceae, Bacteroidaceae, Vibrionaceae, Erysipelotrichaceae, Aeromonadaceae, Moraxellaceae, etc. in the intestine were significantly changed after DCF exposure, and the disruption of intestinal flora might further cause abnormal intestinal metabolism in P. clarkii. This study provides novel mechanistic insights into the toxic effects of anti-inflammatory drugs on aquatic crustaceans.

Background: Glymphatic dysfunction may contribute to the accumulation of Alzheimer's disease (AD) pathologies. Conversely, AD pathologic change might also cause neuroinflammation and aggravate glymphatic dysfunction, forming a loop that accelerates AD progression. In vivo validations are needed to confirm their relationships. Methods: In this study, we included 144 cognitively normal participants with AD pathological biomarker data (baseline CSF Aβ1–42, T-Tau, P-Tau181; plasma P-Tau181 at baseline and at least one follow-up) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Each subject had completed structural MRI scans. Among them, 117 subjects have available neuroinflammatory biomarker (soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and 123 subjects have completed two times [18F]-florbetapir PET. The enlarged PVS (EPVS) visual rating scores in basal ganglia (BG) and centrum semiovale (CS) were assessed on T1-weighted images to reflect glymphatic dysfunction. Intracranial volume and white matter hyperintensities (WMH) volume were also calculated for further analysis. We performed stepwise linear regression models and mediation analyses to estimate the association between EPVS severity, sTREM2, and AD biomarkers. Results: CS-EPVS degree was associated with CSF sTREM2, annual change of plasma P-tau181 and total WMH volume, whereas BG-EPVS severity was associated with age, gender and intracranial volume. The sTREM2 mediated the association between CSF P-tau181 and CS-EPVS. Conclusion: Impaired glymphatic dysfunction could contribute to the accumulation of pathological tau protein. The association between tauopathy and glymphatic dysfunction was mediated by the microglia inflammatory process. These findings may provide evidence for novel treatment strategies of anti-neuroinflammation therapy in the early stage.

Abstract Background The neuropathological hallmarks of Alzheimer’s disease (AD) are amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The amyloid cascade theory is the leading hypothesis of AD pathology. Aβ deposition precedes the aggregation of tau pathology and Aβ pathology precipitates tau pathology. Evidence also indicates the reciprocal interactions between amyloid and tau pathology. However, the detailed relationship between amyloid and tau pathology in AD remains elusive. Metformin might have a positive effect on cognitive impairments. However, whether metformin can reduce AD-related pathologies is still unconclusive. Methods Brain extracts containing tau aggregates were unilaterally injected into the hippocampus and the overlying cerebral cortex of 9-month-old APPswe/PS1DE9 (APP/PS1) mice and age-matched wild-type (WT) mice. Metformin was administrated in the drinking water for 2 months. Aβ pathology, tau pathology, plaque-associated microgliosis, and autophagy marker were analyzed by immunohistochemical staining and immunofluorescence analysis 2 months after injection of proteopathic tau seeds. The effects of metformin on both pathologies were explored. Results We observed tau aggregates in dystrophic neurites surrounding Aβ plaques (NP tau) in the bilateral hippocampi and cortices of tau-injected APP/PS1 mice but not WT mice. Aβ plaques promoted the aggregation of NP tau pathology. Injection of proteopathic tau seeds exacerbated Aβ deposits and decreased the number of microglia around Aβ plaques in the hippocampus and cortex of APP/PS1 mice. Metformin ameliorated the microglial autophagy impairment, increased the number of microglia around Aβ plaques, promoted the phagocytosis of NP tau, and reduced Aβ load and NP tau pathology in APP/PS1 mice. Conclusion These findings indicate the existence of the crosstalk between amyloid and NP tau pathology. Metformin promoted the phagocytosis of pathological Aβ and tau proteins by enhancing microglial autophagy capability. It reduced Aβ deposits and limited the spreading of NP tau pathology in APP/PS1 mice, which exerts a beneficial effect on both pathologies.

Pyridinones have been adopted as an important block in medicinal chemistry that could serve as hydrogen bond donors and acceptors. With the help of feasible synthesis routes via established condensation reactions, the physicochemical properties of such a scaffold could be manipulated by adjustment of polarity, lipophilicity, and hydrogen bonding, and eventually lead to its wide application in fragment-based drug design, biomolecular mimetics, and kinase hinge-binding motifs. In addition, most pyridinone derivatives exhibit various biological activities ranging from antitumor, antimicrobial, anti-inflammatory, and anticoagulant to cardiotonic effects. This review focuses on recent contributions of pyridinone cores to medicinal chemistry, and addresses the structural features and structure–activity relationships (SARs) of each drug-like molecule. These advancements contribute to an in-depth understanding of the potential of this biologically enriched scaffold and expedite the development of its new applications in drug discovery.

A dual-band omnidirectional circularly polarized (CP) antenna using composite right/left-handed (CRLH) transmission line (TL) with miniaturized size is presented. The antenna consists of a circular radiation patch and a circular ground connected by three copper shorting vias, on which three rectangular slits are etched. Two sets of opposite branches are arranged in sequence around the radiation patch and ground to widen the impedance bandwidth (BW). The zeroth-order resonance (ZOR) structure by CRLH-TL and meandering technology allow miniaturization of the antenna, and rectangular slits realize wide low axial-ratio (AR) performance in the azimuth plane. The dual-band antenna is fabricated and measured. The overall size of the antenna prototype is only 0.208λL × 0.208λL × 0.026λL, where λL is the free-space wavelength at the center working frequency of the low band. The BW in the lower band has a range of 2.39 GHz to 2.42 GHz, equivalent to 1.25%, and that of the upper band has a range of 5.6 GHz to 6.0 GHz, equivalent to 6.90%. The AR bandwidth (ARBW) has ranges of 1.9 GHz to 2.6 GHz at 2.4 GHz, approximately 29.2%, and 4.6 GHz to 7.3 GHz at 5.8 GHz, equivalent to 46.6%. The overlap BW covers the two frequencies of unmanned aerial vehicle (UAV) image transmission, 2.4 GHz and 5.8 GHz in China.

Background and ObjectiveHearing loss (HL) is one of the modifiable risk factors for Alzheimer's disease (AD). However, the underlying mechanism behind HL in AD remains elusive. A possible mechanism is cognitive load hypothesis, which postulates that over-processing of degraded auditory signals in the auditory cortex leads to deficits in other cognitive functions. Given mild cognitive impairment (MCI) is a prodromal stage of AD, untangling the association between HL and MCI might provide insights for potential mechanism behind HL.MethodsWe included 85 cognitively normal (CN) subjects with no hearing loss (NHL), 24 CN with HL, 103 mild cognitive impairment (MCI) patients with NHL, and 23 MCI with HL from the ADNI database. All subjects underwent resting-state functional MRI and neuropsychological scale assessments. Fractional amplitude of low-frequency fluctuation (fALFF) was used to reflect spontaneous brain activity. The mixed-effects analysis was applied to explore the interactive effects between HL and cognitive status (GRF corrected, voxel p-value

The construction of a new shield tunnel near an existing operating tunnel poses a great risk to the existing tunnel structure due to the continuous encryption of the rail transit network. This study investigated the safety status of an existing metro tunnel in close proximity to new shield tunnels following construction. A fuzzy comprehensive assessment model (hierarchical fuzzy comprehensive evaluation model) based on an analytic hierarchy process was proposed to assess the risks of the existing tunnel structure. The threshold of indicators in the existing tunnel structure risk assessment system was determined based on the tunnel function and structure security. Then, we described the membership vector determination method, weight vector determination method, and comprehensive evaluation vector processing method. Taking a project case in China as the research object, the quantitative analysis of the established evaluation system was carried out, and the intuitive risk assessment results were obtained. The hierarchical fuzzy comprehensive evaluation model can be employed as a decision-making tool for newly built shield tunnels passing through the existing tunnels, which can provide guidance for tunnel maintenance and guarantee.

Background: Anosognosia is a significant symptom in patients with mild cognitive impairment (MCI) while the underlying neurological mechanism behind it is still unclear.Methods: A total of 121 subjects were included and classified into three groups, including 39 normal controls (NCs), 42 individuals with MCI without anosognosia (MCI-NA), and 40 individuals with MCI with anosognosia (MCI-A), based on their everyday cognition (ECog) questionnaire (discrepancy score). Resting-state functional MRIs were acquired from all the subjects, and the static amplitudes of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance were investigated to evaluate the intrinsic functional network strength and stability, respectively, and both were corrected by age, sex, education, and gray matter volume. Eventually, correlation analyses were conducted to explore the relationship between brain activity changes and cognitive status in all the subjects.Results: No significant difference was found between MCI-A and MCI-NA (P > 0.05) in cognitive ability. Regarding intrinsic brain activity, MCI-A had increased sALFF and dALFF variance in the anterior cingulate cortex (ACC) relative to MCI-NA, as well as decreased sALFF and dALFF variance in the precuneus relative to MCI-NA and controls. Moreover, MCI-A had decreased sALFF in the inferior temporal gyrus (ITG) and paracentral lobule (PCL) compared to MCI-NA. Among all the subjects, correlation analyses showed that the sALFF and dALFF variance in the precuneus was related to the Ecog discrepancy score (r = 0.232 and 0.235, respectively), immediate story recall (r = 0.200 and 0.277, respectively), and delayed story recall (r = 0.255 and 0.298, respectively).Conclusion: Alterations of intrinsic brain activation in the ACC and precuneus seem to be associated with the anosognosia symptom in patients with MCI.

BackgroundApolipoprotein E (APOE) ε2 is a protective genetic factor for Alzheimer’s disease (AD). However, the potential interaction effects between the APOE ε2 allele and disease status on the intrinsic brain activity remain elusive.MethodsWe identified 73 healthy control (HC) with APOE ε3/ε3, 61 mild cognitive impairment (MCI) subjects with APOE ε3/ε3, 24 HC with APOE ε2/ε3, and 10 MCI subjects with APOE ε2/ε3 from the ADNI database. All subjects underwent a resting-state functional MRI and Fluoro-deoxy-glucose positron emission tomography (FDG-PET). We used a fractional amplitude of low-frequency fluctuation (fALFF) to explore the spontaneous brain activity. Based on the mixed-effects analysis, we explored the interaction effects between the APOE ε2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, p < 0.01), followed by post hoc two-sample t-tests (Bonferroni corrected, p < 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities.ResultsThere are no significant differences in gender, age, or education among the four groups. The interaction effect on brain activity was located in the inferior parietal lobule (IPL). Post hoc analysis showed that APOE ε2/ε3 MCI had an increased IPL fALFF than APOE ε3/ε3 MCI. Regarding the APOE ε2 allele effects, we found that ε2 carriers had a decreased fALFF in the transverse temporal gyrus than non-carriers. Also, FDG-PET results showed a lower SUVR of the frontal lobe in APOE ε2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (r = −0.16, p < 0.05).ConclusionAPOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies.

BackgroundActivated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive.MethodsLipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot.ResultsLPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling.ConclusionsIRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

BackgroundSmoking is a modifiable risk factor for Alzheimer’s disease (AD). However, smoking-related effects on intrinsic brain activity in high-risk AD population are still unclear.ObjectiveWe aimed to explore differences in smoking effects on brain function between healthy elderly and amnestic mild cognitive impairment (aMCI) patients using ReHo mapping.MethodsWe identified 64 healthy elderly controls and 116 aMCI patients, including 98 non-smoking and 18 smoking aMCI. Each subject underwent structural and resting-state functional MRI scanning and neuropsychological evaluations. Regional homogeneity (ReHo) mapping was used to assess regional brain synchronization. After correction for age, gender, education, and gray matter volume, we explored the difference of ReHo among groups in a voxel-wise way based on analysis of covariance (ANCOVA), followed by post hoc two-sample analyses (p < 0.05, corrected). Further, we correlated the mean ReHo with neuropsychological scales.ResultsThree groups were well-matched in age, gender, and education. Significant ReHo differences were found among three groups, located in the left supramarginal gyrus (SMG) and left angular gyrus (AG). Specifically, non-smoking aMCI had lower ReHo in SMG and AG than smoking aMCI and controls. By contrast, smoking aMCI had greater AG ReHo than healthy controls (p < 0.05). Across groups, correlation analyses showed that left AG ReHo correlated with MMSE (r = 0.18, p = 0.015), clock drawing test (r = 0.20, p = 0.007), immediate recall (r = 0.36, p < 0.001), delayed recall (r = 0.34, p < 0.001), and auditory verbal learning test (r = 0.20, p = 0.007).ConclusionSmoking might pose compensatory or protective effects on intrinsic brain activity in aMCI patients.

Background: Suspected non-Alzheimer disease pathophysiology (SNAP) refers to the subjects who feature negative β-amyloid (Aβ) but positive tau or neurodegeneration biomarkers. It accounts for a quarter of the elderly population and is associated with cognitive decline. However, the underlying pathophysiology is still unclear.Methods: We included 111 non-demented subjects, then classified them into three groups using cerebrospinal fluid (CSF) Aβ 1–42 (A), phosphorylated tau 181 (T), and total tau (N). Specifically, we identified the normal control (NC; subjects with normal biomarkers, A-T-N-), SNAP (subjects with normal amyloid but abnormal tau, A−T+), and predementia Alzheimer’s disease (AD; subjects with abnormal amyloid and tau, A+T+). Then, we used the static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance to reflect the intrinsic functional network strength and stability, respectively. Further, we performed a correlation analysis to explore the possible relationship between intrinsic brain activity changes and cognition.Results: SNAP showed decreased sALFF in left superior frontal gyrus (SFG) while increased sALFF in left insula as compared to NC. Regarding the dynamic metric, SNAP showed a similarly decreased dALFF in the left SFG and left paracentral lobule as compared to NC. By contrast, when compared to NC, predementia AD showed decreased sALFF in left inferior parietal gyrus (IPG) and right precuneus, while increased sALFF in the left insula, with more widely distributed decreased dALFF variance across the frontal, parietal and occipital lobe. When directly compared to SNAP, predementia AD showed decreased sALFF in left middle occipital gyrus and IPG, while showing decreased dALFF variance in the left temporal pole. Further correlation analysis showed that increased sALFF in the insula had a negative correlation with the general cognition in the SNAP group. Besides, sALFF and dALFF variance in the right precuneus negatively correlated with attention in the predementia AD group.Conclusion: SNAP and predementia AD show distinct functional impairment patterns. Specifically, SNAP has functional impairments that are confined to the frontal region, which is usually spared in early-stage AD, while predementia AD exhibits widely distributed functional damage involving the frontal, parietal and occipital cortex.

Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3–6 months.Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3–6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology.Results: In total, 66 patients had PSCI when evaluated 3–6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743–0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725–0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842).Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3–6 months after the onset of minor stroke.

Biomacromolecular folding kinetics involves fast folding events and broad timescales. Current techniques face limitations in either the required time resolution or the observation window. In this study, we developed the TeZla micromixer, integrating Tesla and Zigzag microstructures with a multistage velocity descending strategy. TeZla achieves a significant short mixing dead time (40 µs) and a wide time window covering four orders of magnitude (up to 300 ms). Using this unique micromixer, we explored the folding landscape of c-Myc G4 and its noncanonical-G4 derivatives with different loop lengths or G-vacancy sites. Our findings revealed that c-Myc can bypass folding intermediates and directly adopt a G4 structure in the cation-deficient buffer. Moreover, we found that the loop length and specific G-vacancy site could affect the folding pathway and significantly slow down the folding rates. These results were also cross-validated with real-time NMR and circular dichroism. In conclusion, TeZla represents a versatile tool for studying biomolecular folding kinetics, and our findings may ultimately contribute to the design of drugs targeting G4 structures. [ABSTRACT FROM AUTHOR]

Abstract Background In the context of a gradual increase in aging, improving the mental health of the elderly is particularly vital for coping with aging. Leveraging data from the 2020 China Family Panel Studies, this study rigorously examines the influence of short video on the mental health of the elderly. Methods We use a multiple linear regression model to investigate the influence of short video usage on the mental health of the elderly. To address endogeneity concerns, this study employs two-stage least squares and propensity score matching to estimate the impact of short video usage on the mental health of the elderly. Results The empirical analysis reveals a substantive and statistically significant enhancement in the mental health of elderly people attributable to the use of short videos. To ensure the reliability and robustness of our estimations, a comprehensive battery of robustness tests is conducted, all of which consistently support the conclusion of a positive association between short video usage and improved mental health among the elderly. Furthermore, the results of the heterogeneity analysis suggest that short videos have less of an impact on elderly males and individuals with higher levels of education. The results of the mechanism analysis indicate that the use of short videos can enhance the mental health of elderly individuals by positively impacting the intergenerational relationships between them and their children, as well as their leisure consumption habits. Conclusions This study can provide policy inspiration for the government to improve the mental health of the elderly and achieve active aging.