Deep learning enables accurate brain tissue microstructure analysis based on clinically feasible diffusion magnetic resonance imaging.

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Bioinspired micro/nanomotor with visible light energy-dependent forward, reverse, reciprocating, and spinning schooling motion.

In nature, microorganisms could sense the intensity of the incident visible light and exhibit bidirectional (positive or negative) phototaxis. However, it is still challenging to achieve the similar biomimetic phototaxis for the artificial micro/nanomotor (MNM) counterparts with the size from a few nanometers to a few micrometers. In this work, we report a fuel-free carbon nitride (C3N4)/polypyrrole nanoparticle (PPyNP)-based smart MNM operating in water, whose behavior resembles that of the phototactic microorganism. The MNM moves toward the visible light source under low illumination and away from it under high irradiation, which relies on the competitive interplay between the light-induced self-diffusiophoresis and self-thermophoresis mechanisms concurrently integrated into the MNM. Interestingly, the competition between these two mechanisms leads to a collective bidirectional phototaxis of an ensemble of MNMs under uniform illuminations and a spinning schooling behavior under a nonuniform light, both of which can be finely controllable by visible light energy. Our results provide important insights into the design of the artificial counterpart of the phototactic microorganism with sophisticated motion behaviors for diverse applications.

[Difference in Brain Age Between Alzheimer's Disease and Mild Cognitive Impairment].

Objective To investigate the brain age differences between Alzheimer's disease(AD)and mild cognitive impairment(MCI)patients,and further explore the correlations between brain age gap(BAG)and clinical features.Methods The clinical data and radiologic findings of 132 probable AD and AD-derived MCI patients diagnosed at Beijing Tiantan Hospital,Capital Medical University from December 2018 to July 2021 were retrospectively analyzed.According to the diagnostic criteria for AD and MCI,the patients were assigned into AD and MCI groups.In addition,156 volunteers without neurological diseases and other severe diseases were recruited as the control group.The general data,Montreal cognitive assessment(MoCA)score,and mini-mental state examination(MMSE)score were compared among the three groups.The deep learning-based brain age prediction model was employed to calculate the BAGs of the three groups.Spearman correlation analysis was conducted to explore the correlations between BAG and clinical features.Results The 132 patients included 106 patients in the AD group and 26 patients in the MCI group.The MoCA and MMSE scores followed an ascending trend of AD group

Atomically Dispersed FeN2 P2 Motif with High Activity and Stability for Oxygen Reduction Reaction Over the Entire pH Range.

The past decade has witnessed the great potential of Fe-based single-atom electrocatalysis in catalyzing oxygen reduction reaction (ORR). However, it remains a grand challenge to substantially improve their intrinsic activity and long-term stability in acidic electrolytes. Herein, we report a facile chemical vapor deposition strategy, by which high-density Fe atoms (3.97 wt%) are coordinated with square-planar para-positioned nitrogen and phosphorus atoms in a hierarchical carbon framework. The as-crafted atomically dispersed Fe catalyst (denoted Fe-SA/PNC) manifests an outstanding activity towards ORR over the entire pH range. Specifically, the half-wave potential of 0.92 V, 0.83 V, and 0.86 V vs. reversible hydrogen electrode (RHE) are attained in alkaline, neutral, and acidic electrolytes, respectively, representing the high performance among reported catalysts to date. Furthermore, after 30,000 durability cycles, the Fe-SA/PNC remains to be stable with no visible performance decay when tested in 0.1 M KOH and 0.5 M H2 SO4 , and only a minor negative shift of 40 mV detected in 0.1 M HClO4 , significantly outperforming commercial Pt/C counterpart. The coordination motif of Fe-SA/PNC is validated by density functional theory (DFT) calculations. This work provides atomic-level insight into improving the activity and stability of non-noble metal ORR catalysts, opening up an avenue to craft the desired single-atom electrocatalysts.

Pilot study of a novel nanobody 68 Ga-NODAGA-SNA006 for instant PET imaging of CD8+ T cells.

PURPOSE: Positron emission tomography (PET) with specific diagnostic probes for quantifying CD8+ T cells has emerged as a powerful technique for monitoring the immune response. However, most CD8+ T cell radiotracers are based on antibodies or antibody fragments, which are slowly cleared from circulation. Herein, we aimed to develop and assess 68 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8+ T cells. METHODS: A novel nanobody without a hexahistidine (His6) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with 68 Ga. The PET imaging profiles of 68 Ga-NODAGA-SNA006 were evaluated in BALB/c MC38-CD8+/CD8- tumour models and cynomolgus monkeys. Three volunteers with lung cancer underwent whole-body PET/CT imaging after 68 Ga-NODAGA-SNA006 administration. The biodistribution, pharmacokinetics and dosimetry of patients were also investigated. In addition, combined with immunohistochemistry (IHC), the quantitative performance of the tracer for monitoring CD8 expression was evaluated in BALB/c MC38-CD8+/CD8- and human subjects. RESULTS: 68 Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/µmol. 68 Ga-NODAGA-SNA006 exhibited specific uptake in MC38-CD8+ xenografts tumours, CD8-rich tissues (such as the spleen) in monkeys and CD8+ tumour lesions in patients within 1 h. Fast washout from circulation was observed in three volunteers (t1/2 < 20 min). A preliminary quantitative linear relationship (R2 = 0.9668, p < 0.0001 for xenografts and R2 = 0.7924, p = 0.0013 for lung patients) appeared between 68 Ga-NODAGA-SNA006 uptake and CD8 expression. 68 Ga-NODAGA-SNA006 was well tolerated by all patients. CONCLUSION: 68 Ga-NODAGA-SNA006 PET imaging can instantly quantify CD8 expression with an ideal safety profile and is expected to be important for dynamically tracking CD8+ T cells and monitoring immune responses for individualised cancer immunotherapy. TRIAL REGISTRATION: NCT05126927 (19 November 2021, retrospectively registered).

Visible Light-Driven Micromotor with Incident-Angle-Controlled Motion and Dynamic Collective Behavior.

Light-driven micromotor has become one of the research focuses in the past decade, and its motion behavior is usually controlled by light intensity, polarization, and light wavelength. Herein, the light incident angle is utilized to control the motion behavior of silica/Au/pentacene (SiO2/Au/PEN) spherical Janus micromotor. Under tilted irradiation, a single micromotor shows positive phototactic moving behavior without the addition of external chemical fuels, which relies on the photocatalytic reactions and the self-electrophoresis mechanism. Interestingly, when the incident light is tuned to the vertical angle, the SiO2/Au/PEN micromotor stops moving. Similarly, a number of SiO2/Au/PEN micromotors exhibit the same "on-off" motion change, which is dependent on the light incident angle. More interestingly, the "on-off" motion of the SiO2/Au/PEN microparticles under vertical light irradiation results in the formation of the agglomeration with position and size precisely controlled by light. In addition, the resulting aggregation exhibits light-controlled dynamic migration behavior. The incident angle control thus opens up new opportunities for the motion control of the micromotors for diverse applications.

Clinical-radiological dissociation in a patient with nitrous oxide-induced subacute combined degeneration: a case report.

BACKGROUND: Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD. CASE PRESENTATION: We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation. CONCLUSIONS: Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

Evaluation of cadmium hyperaccumulation and tolerance potential of Myriophyllum aquaticum.

Enrichment of the hyperaccumulator bank is important for phytoremediation, and studying new hyperaccumulators has become a research hotspot. In this study, cadmium (Cd), the main representative factor of heavy-metal-polluted water, was the research object, and the Cd bioenrichment ability and tolerance of Myriophyllum aquaticum were studied for the first time. The experiment was conducted for 28 days by establishing experimental groups with different Cd concentrations (0, 10, 20, 40, 80, and 160 mg/L). The results show that M. aquaticum is a new Cd hyperaccumulator. There was no notable damage in the 40 mg/L Cd treatment group, and the Cd enrichment ability of M. aquaticum reached 17,970 ± 1020.01 mg/kg, while the bioconcentration factor (BCF) reached 449.25. At the same time, the antioxidant system (superoxide dismutase (SOD) and peroxidase (POD)) and proline (Pro) levels of M. aquaticum maintained normal plant physiology, but there were physiological anomalies in M. aquaticum at high concentrations and under long-term treatment. The results show that M. aquaticum has a high Cd bioenrichment ability and tolerance in water and can be used for phytoremediation of river water polluted by Cd.

The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy.

Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (ß2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express ß2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.

Study on the gelling properties of egg white/surfactant system by different heating intensities.

The aim of this study was to elucidate the different effects and difference mechanism of gelling properties among egg white (EW) treated with different heating intensities and the composite addition of rhamnolipid and soybean lecithin. Particle size analyzer, potentiometric analyzer, surface hydrophobicity method, and Fourier transform infrared spectroscopy techniques were used to determine the physicochemical properties and molecular structure, respectively. Low-field nuclear magnetic resonance, magnetic resonance imaging, texture profile analysis, and scanning electron microscopy techniques were used to analyze the gelling properties and gel structure, respectively. And we illuminate the different mechanisms in the gelling properties of the EW with various treatments and key internal factors that play important roles in improving gelling properties by establishing the link between the gelling properties and relevant characteristics by mixed effects model and visual network analysis. The results indicate raising the content of rhamnolipid decreased the migration of immobilized water in the EW gel and the free water content. At the heating intensities of 55 °C/3.5, 65 °C/2.5, and 67 °C/1.5 min, with an increase in rhamnolipid, the gel's cohesiveness, gumminess, and chewiness gradually increased. The mixed effects model indicated that heating intensities and composite ratios have a 2-way interaction on zeta potential, the relaxation time of bound water (T21), the content of bound water (P21), the content of immobilized water (P22), and fractal dimension (df) attributes (P < 0.05). The visual network analysis showed that the protein solubility, the relaxation time of immobilized water (T22), surface hydrophobicity, zeta potential, average particle size (d43) and the relaxation time of free water (T23) are critical contributors to the different gelling properties of EW subjected to various treatments and the improvement of gelling properties. This study will provide theoretical guidance for the development of egg white products and the expansion of egg white's application scope in the egg product processing industry.

A Light-Powered Micropump with Dynamic Collective Behavior for Reparation.

Inspired by the collective behaviors of active systems in nature, the collective behavior of micromotors has attracted more and more attention in recent years. However, little attention has been paid to the collective behavior of the immobilized micromotor, i.e., the micropump. In this paper, a unique pentacene-based micropump is reported, which demonstrates dynamic collective behavior activated by white light irradiation. The light irradiation may generate the photochemical reactions between pentacene and water, leading to the electroosmotic flow. As a result, this micropump is capable of pumping the surrounding solution inward along the substrate surface based on the electroosmosis mechanism. Intriguingly, the inward pumping causes the agglomeration of the tracer particles on the surface of the micropump. In addition, the aggregation can migrate following the change in the light irradiation position between two adjacent micropumps. Based on the aggregating and migrating behaviors of this pentacene-based micropump, we have achieved the conductivity restoration of the cracked circuit.

Clinical and neuroimaging association between neuropsychiatric symptoms and nutritional status across the Alzheimer's disease continuum: a longitudinal cohort study.

OBJECTIVES: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer's disease (AD) continuum. DESIGN: A longitudinal, observational cohort study. SETTING: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. PARTICIPANTS: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months' follow-up. MEASUREMENTS: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. RESULTS: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (ß = -1.317, P = 0.003), affective symptoms (ß = -1.887, P < 0.001), and appetite/eating disorders (ß = -1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (ß = -0.048), affective symptoms (ß = -0.181), and appetite/eating disorders (ß = -0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. CONCLUSIONS: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

Mediation of Regional Cerebral Blood Flow in the Relationship between Specific Gut Microbiota and Cognition in Vascular Cognitive Impairment.

BACKGROUND: Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular mechanisms involved remain unclear. OBJECTIVE: To investigate the gut microbiota associated with VCI and examine the mediating effects of regional cerebral blood flow (CBF) to explore potential therapeutic targets for VCI. METHODS: This prospective study enrolled patients with VCI (n = 16) and healthy controls (n = 18) from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1 and June 30, 2022. The gut microbiota composition and diversity were determined by 16 S ribosomal RNA gene sequencing. The association between gut microbiota and Montreal Cognitive Assessment (MoCA) scores was determined using Spearman's correlation analysis. Regional CBF was calculated using pseudo-continuous arterial spin labeling. The mediating effects of regional CBF on the relationship between specific gut microbiota and cognition in VCI were investigated using mediation analysis. RESULTS: Compared to healthy controls, patients with VCI had significantly greater abundance of Bifidobacterium, Veillonella, R uminococcus gnavus , Fusobacterium, and Erysipelatoclostridium and smaller abundance of Collinsella. The abundance of Ruminococcus gnavus was negatively associated with MoCA scores in patients with VCI, with the CBF in the left hypothalamus, right hypothalamus, and left amygdala accounting for 63.96%, 48.22%, and 36.51%, respectively, of this association after adjusting for confounders. CONCLUSIONS: Ruminococcus gnavus is associated with cognition in VCI, which is strongly mediated by CBF in the bilateral hypothalamus and left amygdala. These findings highlight the potential regulatory roles of nutrition and metabolism-related areas of the brain in VCI.

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients.

AIMS: Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. METHODS: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. RESULTS: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. CONCLUSIONS: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.

Multiomics Reveals Biological Mechanisms Linking Macroscale Structural Covariance Network Dysfunction With Neuropsychiatric Symptoms Across the Alzheimer's Disease Continuum.

BACKGROUND: The highly heterogeneity of neuropsychiatric symptoms (NPSs) hinder further exploration of their role in neurobiological mechanisms and Alzheimer's disease (AD). We aimed to delineate NPS patterns based on brain macroscale connectomics to understand the biological mechanisms of NPSs on the AD continuum. METHODS: We constructed Regional Radiomics Similarity Networks (R2SN) for 550 participants (AD with NPSs [AD-NPS, n=376], AD without NPSs [AD-nNPS, n=111], and normal controls [n=63]) from CIBL study. We identified R2SN connections associated with NPSs, and then cluster distinct subtypes of AD-NPS. An independent dataset (n=189) and internal validation were performed to assess the robustness of the NPS subtypes. Subsequent multiomics analysis were performed to assess the distinct clinical phenotype and biological mechanisms in each NPS subtype. RESULTS: AD-NPS patients were clustered into severe (n=187), moderate (n=87), and mild NPS (n=102) subtypes, each exhibiting distinct brain network dysfunction patterns. A high level of consistency in clustering NPS was internally and externally validated. Severe and moderate NPSs showed significant cognitive impairment, increased plasma p-Tau181 levels, extensive decreased brain volume and cortical thickness, and accelerated cognitive decline. Gene set enrichment analysis (GSEA) revealed enrichment of differentially expressed genes in ion transport and synaptic transmission with variations for each NPS subtype. Genome-wide association studies (GWAS) analysis defined the specific gene loci for each subtype of AD-NPS (i.e, logical memory), aligning with clinical manifestations and progression patterns. CONCLUSIONS: This study identified and validated three distinct NPS subtypes, underscoring the role of NPSs in neurobiological mechanisms and progression of the AD continuum.

Scale-dependent power law properties in hashtag usage time series of Weibo.

We analyze the time series of hashtag numbers of social media data. We observe that the usage distribution of hashtags is characterized by a fat-tailed distribution with a size-dependent power law exponent and we find that there is a clear dependency between the growth rate distributions of hashtags and size of hashtags usage. We propose a generalized random multiplicative process model with a theory that explains the size dependency of the fat-tailed distribution. Numerical simulations show that our model reproduces these size-dependent properties nicely. We expect that our model is useful for understanding the mechanism of fat-tailed distributions in various fields of science and technology.

Enzymatic response and antibiotic resistance gene regulation by microbial fuel cells to resist sulfamethoxazole.

Microbial fuel cells (MFCs) are a promising and sustainable technology which can generate electricity and treat antibiotic wastewater simultaneously. However, the antibiotic resistance genes (ARGs) induced by antibiotics in MFCs increase risks to ecosystems and human health. In this study, the activities of enzymes and regulation genes related to ARGs in MFCs spiked with sulfamethoxazole (SMX) were evaluated to explore the induction mechanism of ARGs. Under lower doses of SMX (10 mg/L and 20 mg/L SMX in this study), microorganisms tend to up regulate catalase and RpoS regulon to induce sul1, sul3 and intI1. The microorganisms exposed to higher doses of SMX (30 mg/L and 40 mg/L SMX in this study) tend to up regulate superoxide dismutase and SOS response to generate sul2 and sulA. Moreover, the exposure concentrations of SMX had no significant effect on the electricity production of MFCs. This work suggested that the ARGs in MFCs might be inhibited by affecting enzymatic activities and regulatory genes according to the antibiotic concentration without affecting the electricity production.