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Foam ceramics were prepared by using 80 wt.% sand shale, 8 wt.% coal fly ash, 8 wt.% steel slag and 4 wt.% magnesite as raw materials and 0.3 wt.% SiC as foam agent. Effects of firing temperature and holding time on performance and phases of foam ceramics were investigated. Grey system theory was used to explore the correlation between pore structure parameters and thermal conductivity. The foam ceramics sintered at 1160 °C for 50 min exhibit the optimal comprehensive properties: bulk density of 0.651 g/cm3, flexural strength of 4.75 MPa, total porosity of 73.58%, closed porosity of 54.16%, and thermal conductivity of 0.081 W/(m·K). The Micro-CT results show that the pores with the average pore volume of 1.083 mm3 are relatively independent and uniform; and the pore wall thickness presents a normal distribution, which is conducive to improving the properties. Among the pore structure parameters, the fractal dimension has the greatest correlation with the thermal conductivity of foam ceramics.

ABSTRACTNumerous studies have described the notable impact of gut microbiota on the brain in Alzheimer’s disease (AD) via the gut – brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p

Text classification is widely studied in natural language processing (NLP). Deep learning models, including large pre-trained models like BERT and DistilBERT, have achieved impressive results in text classification tasks. However, these models’ robustness against adversarial attacks remains an area of concern. To address this concern, we propose three data augmentation methods to improve the robustness of such pre-trained models. We evaluated our methods on four text classification datasets by fine-tuning DistilBERT on the augmented datasets and exposing the resulting models to adversarial attacks to evaluate their robustness. In addition to enhancing the robustness, our proposed methods can improve the accuracy and F1-score on three datasets. We also conducted comparison experiments with two existing data augmentation methods. We found that one of our proposed methods demonstrates a similar improvement in terms of performance, but all demonstrate a superior robustness improvement.

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the LAMC3 gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.470G > A and c.4030 + 1G > A) of the LAMC3 gene in a Chinese female with childhood-onset seizures. Cranial magnetic resonance imaging was normal. Functional experiments confirmed that both variant sites caused premature truncation of the laminin γ3 chain. Bioinformatics analysis predicted 10 genes interacted with LAMC3 with an interaction score of 0.4 (P value = 1.0e–16). The proteins encoded by these genes were mainly located in the basement membrane and extracellular matrix component. Furthermore, the biological processes and molecular functions from gene ontology analysis indicated that laminin γ3 chain and related proteins played an important role in structural support and cellular processes through protein-containing complex binding and signaling receptor binding. KEGG pathway enrichment predicted that the LAMC3 gene variant was most likely to participate in the occurrence and development of OCCM through extracellular matrix receptor interaction and PI3K-Akt signaling pathway.

Abstract Lead‐free halide double perovskite (HDP) nanocrystals are considered as one of the most promising alternatives to the lead halide perovskite nanocrystals due to their unique characteristics of nontoxicity, robust intrinsic thermodynamic stability, rich and tunable optoelectronic properties. Although lead‐free HDP variants with highly efficient emission are synthesized and characterized, the photoluminescent (PL) properties of colloidal HDP nanocrystals still have enormous challenges for application in light‐emitting diode (LED) devices due to their intrinsic and surface defects, indirect band, and disallowable optical transitions. Herein, recent progress on the synthetic strategies, ligands passivation, and metal doping/alloying for boosting efficiency and stability of HDP nanocrystals is comprehensive summarized. It begins by introducing the crystalline structure, electronic structure, and PL mechanism of lead‐free HDPs. Next, the limiting factors on PL properties and origins of instability are analyzed, followed by highlighting the effects of synthesis strategies, ligands passivation, and metal doping/alloying on the PL properties and stability of the HDPs. Then, their preliminary applications for LED devices are emphasized. Finally, the challenges and prospects concerning the development of highly efficient and stable HDP nanocrystals‐based LED devices in the future are proposed.

Ethanol-responsive movement disorders are a group of movement disorders of which clinical manifestation could receive significant improvement after ethanol intake, including essential tremor, myoclonus-dystonia, and some other hyperkinesia. Emerging evidence supports that the sensitivity of these conditions to ethanol might be attributed to similar anatomical targets and pathophysiologic mechanisms. Cerebellum and cerebellum-related networks play a critical role in these diseases. Suppression of inhibitory neurotransmission and hyper-excitability of these regions are the key points for pathogenesis. GABA pathways, the main inhibitory system involved in these regions, were firstly linked to the pathogenesis of these diseases, and GABAA receptors and GABAB receptors play critical roles in ethanol responsiveness. Moreover, impairment of low-voltage-activated calcium channels, which were considered as a contributor to oscillation activity of the nervous system, also participates in the sensitivity of ethanol in relevant disease. Glutamate transporters and receptors that are closely associated with GABA pathways are the action sites for ethanol as well. Accordingly, alternative medicines aiming at these shared mechanisms appeared subsequently to mimic ethanol-like effects with less liability, and some of them have achieved positive effects on different diseases with well-tolerance. However, more clinical trials with a large sample and long-term follow-ups are needed for pragmatic use of these medicines, and further investigations on mechanisms will continue to deepen the understanding of these diseases and also accelerate the discovery of ideal treatment.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson’s disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson’s disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach’s Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860–0.935, p

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder frequently accompanied by cognitive impairment. Contributing factors such as modern lifestyle, genetic predisposition, and gene environmental interactions have been postulated, but the pathogenesis remains unclear. In this study, we attempt to investigate the potential mechanisms and interventions underlying T2DM-induced cognitive deficits from the brain–gut axis perspective. A combined analysis of the brain transcriptome, plasma metabolome, and gut microbiota in db/db mice with cognitive decline was conducted. Transcriptome analysis identified 222 upregulated gene sets and 85 downregulated gene sets, mainly related to mitochondrial respiratory, glycolytic, and inflammation. In metabolomic analysis, a total of 75 significantly altered metabolites were identified, correlated with disturbances of glucose, lipid, bile acid, and steroid metabolism under disease state. Gut microbiota analysis suggested that the species abundance and diversity of db/db mice were significantly increased, with 23 significantly altered genus detected. Using the multi-omics integration, significant correlations among key genes (n = 33), metabolites (n = 41), and bacterial genera (n = 21) were identified. Our findings suggest that disturbed circulation and brain energy metabolism, especially mitochondrial-related disturbances, may contribute to cognitive impairment in db/db mice. This study provides novel insights into the functional interactions among the brain, circulating metabolites, and gut microbiota.

ZrO2 whiskers have been synthesized by a facile molten salt method using ZrOCl2 · 8 H2O and Na3PO4 · 12 H2O as the zirconium source and molten salt, respectively. Differential thermal and thermogravimetric analyses, X-ray diffraction analysis, field emission scanning electron microscope and transmission electron microscope were employed to characterize the heating process of the precursor mixture, phase composition of the as-synthesized ZrO2 whiskers and the effect of reaction temperature on the synthesis of ZrO2 whiskers. The results show that the ZrO2 whiskers synthesized at 900 °C have an average aspect ratio of 30 and preferentially grow along [010] direction. The formation of sodium zirconium phosphate [Na9-4xZrx(PO4)3] (x = 1, 2) and the reaction temperature play an important role in the growth of ZrO2 whiskers. This work also suggests an effective route for mass production of high quality ZrO2 whiskers.

Abstract Background Mild cognitive impairment is an early stage of Alzheimer’s disease. Increasing evidence has indicated that cognitive training could improve cognitive abilities of MCI patients in multiple cognitive domains, making it a promising therapeutic approach for MCI. However, the effect of long-time training has not been widely explored. It is also necessary to evaluate the extent how it could reduce the convertion rate from MCI to AD. Methods/design The SIMPLE study is a multicenter, randomized, single-blind prospective clinical trial assessing the effects of computerized cognitive training on different cognitive domains in MCI patients. It is carried out in 7 centers in China. The study population includes patients aged 50–85, and they are randomly allocated to the training or control group. The primary outcome is to compare the conversion rate of MCI within 36-month follow-up. Structural and functional MRI will be used to interpret the effect of cognitive training. The cognitive training comprises a variety of games related with cognitive domains such as attention, memory, visualspatial ability and executive function. We cautiously set 50% reduction in the rate of conversion as estimated effect. With 80–90% statistical power and 12% as the overall probability of conversion within the study period, 600–800 patients are finally required in the study. The first patent has been recruited in April 2017. Discussion Previous studies suggested the benefit of cognitive training for MCI, but neither long-time nor Chinese culture were investigated. The SIMPLE designs and utilizes an improved computerized cognitive training approach and assesses its effects on MCI progress. In addition, neural activities explaining the effects on cognition function changes will be revealed, which could in turn to imply more useful therapeutic approaches. Trial registration ClinicalTrials.gov Identifier: NCT03119051.

Abstract Introduction Alzheimer's disease (AD) is an age‐related neurodegenerative disorder. One of the pathological features of AD is neuronal loss in brain regions associated with cognition, particularly the hippocampus. An enriched environment (EE) can facilitate neuronal plasticity and improve behaviors such as emotion, motor function, and cognition in AD. Methods After APP/PS1 mice were exposed to EE at an early stage (2 months of age), elevated plus maze performance and contextual fear conditioning were tested, and neurogenesis and the extent of activation in the hippocampus were observed. Results The results showed that, compared with that in the mice that experienced a standard environment, the cognition of the mice exposed to EE, as measured by contextual fear conditioning, was not statistically significant. However, based on their performance in the elevated plus maze, the index was increased in the mice, especially the APP/PS1 mice, exposed to EE. Consistent with the behavioral changes, the APP/PS1 mice exposed to EE showed an increased number of c‐Fos‐positive neurons and elevated neurogenesis in the dentate gyrus (DG) area. In addition, the activation of newborn neurons did not occur in the other three groups. Conclusions These results indicate that the activation of newborn neurons may participate in the improvement of behavioral performance in APP/PS1 mice after EE.

Although anomalies in the topological architecture of whole-brain connectivity have been found to be associated with Alzheimer's disease (AD), our understanding about the progression of AD in a functional connectivity (FC) perspective is still rudimentary and few study has explored the function-structure relations in brain networks of AD patients. By using resting-state functional MRI (fMRI), this study firstly investigated organizational alternations in FC networks in 12 AD patients, 15 amnestic mild cognitive impairment (aMCI) patients, and 14 age-matched healthy aging subjects and found that all three groups exhibit economical small-world network properties. Nonetheless, we found a decline of the optimal architecture in the progression of AD, represented by a more localized modular organization with less efficient local information transfer. Our results also show that aMCI forms a boundary between normal aging and AD and represents a functional continuum between healthy aging and the earliest signs of dementia. Moreover, we revealed a dissociated relationship between the overall FC and structural connectivity (SC) in AD patients. In this study, diffusion tensor imaging tractography was used to map the structural network of the same individuals. The decreased FC-SC coupling may be indicative of more stringent and less dynamic brain function in AD patients. Our findings provided insightful implications for understanding the pathophysiological mechanisms of brain dysfunctions in aMCI and AD patients and demonstrated that functional disorders can be characterized by multimodal neuroimaging-based metrics.

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer's disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case-control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim