Total Tau Protein Mediates the Association of Ischemic Cerebrovascular Disease with Cognitive Decline.

Background: Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized. Objective: To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition. Methods: A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers. Results: ICVD was associated with higher total-tau (t-tau) (p = 2.828×10-2) and poorer cognition (CM-MMSE: p = 1.539×10-5, MoCA-b: p = 4.552×10-6). Additionally, no discernible correlation surfaced between ICVD and amyloid-ß (Aß) 42 (p = 6.910×10-1) or phosphorylated tau (p-tau) (p = 4.324×10-1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%). Conclusions: These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline.

ANU-ADRI scores, tau pathology, and cognition in non-demented adults: the CABLE study.

BACKGROUND: It has been reported that the risk of Alzheimer's disease (AD) could be predicted by the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) scores. However, among non-demented Chinese adults, the correlations of ANU-ADRI scores with cerebrospinal fluid (CSF) core biomarkers and cognition remain unclear. METHODS: Individuals from the Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study were grouped into three groups (low/intermediate/high risk groups) based on their ANU-ADRI scores. The multiple linear regression models were conducted to investigate the correlations of ANU-ADRI scores with several biomarkers of AD pathology. Mediation model and structural equation model (SEM) were conducted to investigate the mediators of the correlation between ANU-ADRI scores and cognition. RESULTS: A total of 1078 non-demented elders were included in our study, with a mean age of 62.58 (standard deviation [SD] 10.06) years as well as a female proportion of 44.16% (n = 476). ANU-ADRI scores were found to be significantly related with MMSE (ß = -0.264, P < 0.001) and MoCA (ß = -0.393, P < 0.001), as well as CSF t-tau (ß = 0.236, P < 0.001), p-tau (ß = 0.183, P < 0.001), and t-tau/Aß42 (ß = 0.094, P = 0.005). Mediation analyses indicated that the relationships of ANU-ADRI scores with cognitive scores were mediated by CSF t-tau or p-tau (mediating proportions ranging from 4.45% to 10.50%). SEM did not reveal that ANU-ADRI scores affected cognition by tau-related pathology and level of CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2). CONCLUSION: ANU-ADRI scores were associated with cognition and tau pathology. We also revealed a potential pathological mechanism underlying the impact of ANU-ADRI scores on cognition.

Analysis of the differences in physicochemical properties, volatile compounds, and microbial community structure of pit mud in different time spaces.

Pit mud (PM) is among the key factors determining the quality of Nongxiangxing baijiu, a Chinese liquor. Microorganisms present inside PM are crucial for the unique taste and flavor of this liquor. In this study, headspace solid-phase microextraction was used in combination with gas chromatography and high-throughput sequencing to determine the volatile compounds and microbial community structure of 10- and 40-year PM samples from different spaces. The basic physicochemical properties of the PM were also determined. LEfSe and RDA were used to systematically study the PM in different time spaces. The physicochemical properties and ester content of the 40-year PM were higher than those of the 10-year PM, but the spatial distribution of the two years PM samples exhibited no consistency, except in terms of pH, available phosphorus content, and ester content. In all samples, 29 phyla, 276 families, and 540 genera of bacteria, including four dominant phyla and 20 dominant genera, as well as eight phyla, 24 families, and 34 genera of archaea, including four dominant phyla and seven dominant genera, were identified. The LEfSe analysis yielded 18 differential bacteria and five differential archaea. According to the RDA, the physicochemical properties and ethyl caproate, ethyl octanoate, hexanoic acid, and octanoic acid positively correlated with the differential microorganisms of the 40-year PM, whereas negatively correlated with the differential microorganisms of the 10-year PM. Thus, we inferred that Caproiciproducens, norank_f__Caloramatoraceae, and Methanobrevibacter play a dominant and indispensable role in the PM. This study systematically unveils the differences that affect the quality of PM in different time spaces and offers a theoretical basis for improving the declining PM, promoting PM aging, maintaining cellars, and cultivating an artificial PM at a later stage.

Linking Microbial Functional Gene Abundance and Daqu Extracellular Enzyme Activity: Implications for Carbon Metabolism during Fermentation.

Daqu is the starter of Baijiu, it provides the microbes and enzymes necessary for fermentation. Studies have already established carbohydrate metabolism as the primary functional module in Daqu fermentation. The present study investigated the changes in microbial functions and the relationship between carbohydrate metabolism-related functional genes and extracellular enzyme activity during the Daqu fermentation. Amplicon sequencing identified 38 bacterial and 10 fungal phyla in Daqu samples, while shotgun metagenomic sequencing classified and annotated 40.66% of the individual features, of which 40.48% were prokaryotes. KEGG annotation showed that the pathways related to metabolites were less in the early fermentation stage, but higher in the middle and late stages. The functional genes related to pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and propanoate metabolism were relatively high in the early and late stages of fermentation, while that for start and cross metabolism was relatively low. The study also found that amino sugar and nucleoside sugar metabolism were dominant in the middle stage of fermentation. Finally, the correlation network analysis showed that amylase activity positively correlated with many carbon metabolism-related pathways, while liquefaction activity negatively correlated with these pathways. In conclusion, the present study provides a theoretical basis for improving and stabilizing the quality of Daqu.

Correlation: Between Autochthonous Microbial Diversity and Volatile Metabolites During the Fermentation of Nongxiang Daqu.

Daqu is an important saccharifying and fermenting agent. It provides various microorganisms and enzymes for the fermentation of Baijiu and plays a vital role in the formation of Baijiu flavor. However, it is difficult to obtain information on microbial growth and metabolism in time for Daqu production. Therefore, the "Qu Xiang" obtained by smelling is an important index in the traditional production process to evaluate the microbial fermentation in the process of Daqu-making, "Qu Xiang" mainly represents the volatile flavor compounds in Daqu. The microbial diversity and volatile metabolites on 0, 6, 16, and 29 days of the fermentation process were measured using high-throughput sequencing and gas chromatography-mass spectrometry. Significant differences were found in the composition of the microbial community. Pseudomonas, Weissella, Bacillus, and Pelomonas were the main bacterial genera. Alternaria, Rhizopus, and Pichia are the main fungal genera. A total of 32 differential volatile metabolites were detected in samples at four time points using differential metabolic analysis. The correspondence of prevailing microorganisms with differential metabolites distinguished by Spearman correlation and two-way orthogonal partial least square analysis show that Saccharopolyspora exhibited a significant connection for the 12 differential metabolites. A significant positive correlation was observed between Rhizomucor and 13 different metabolites. These findings further understanding of the metabolism of microorganisms in Daqu fermentation and also help to control the microorganisms in the Daqu-making process, to obtain more stable Baijiu products.

Application of hyperspectral technology in detection of agricultural products and food: A Review.

Food is the foundation of human survival. With the development and progress of society, people increasingly focus on the problems of food quality and safety, which is closely related to human's health. Thus, the whole industrial chain from farmland to dining table need to be strictly controlled. Traditional detection methods are time-consuming, laborious, and destructive. In recent years, hyperspectral technology has been more and more applied to food safety and quality detection, because the technology can achieve rapid and nondestructive detection of food, and the requirement to experimental condition is low; operability is strong. In this paper, hyperspectral imaging technology was briefly introduced, and its application in agricultural products and food detection in recent years was systematically summarized, and the key points in the research process were deeply discussed. This work lays a solid foundation for the peers to the following in-depth research and application of this technology.

Research Progress of the Functional Role of ACK1 in Breast Cancer.

ACK1 is a nonreceptor tyrosine kinase with a unique structure, which is tightly related to the biological behavior of tumors. Previous studies have demonstrated that ACK1 was involved with multiple signaling pathways of tumor progression. Its crucial role in tumor cell proliferation, apoptosis, invasion, and metastasis was tightly related to the prognosis and clinicopathology of cancer. ACK1 has a unique way of regulating cellular pathways, different from other nonreceptor tyrosine kinases. As an oncogenic kinase, recent studies have shown that ACK1 plays a critical regulatory role in the initiation and progression of tumors. In this review, we will be summarizing the structural characteristics, activation, and regulation of ACK1 in breast cancer, aiming to deeply understand the functional and mechanistic role of ACK1 and provide novel therapeutic strategies for breast cancer treatment.

Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks.

NME1 (also known as NM23-H1) was the first identified tumor metastasis suppressor, which has been reported to link with genomic stability maintenance and cancer. However its underlying mechanisms are still not fully understood. Here we find that NME1 is required for non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Mechanistically, NME1 re-localizes to DNA damage sites in a Ku-XRCC4-dependent manner, and regulates downstream LIG4 recruitment and end joining efficiency. Furthermore, we show that the 3'-5' exonuclease activity of NME1 is critical for its function in NHEJ. Taken together, our findings identify NME1 as a novel NHEJ factor, and reveal how this metastasis suppressor promotes genome stability.

Current Advances in Molecular Basis and Mechanisms Regulating Leaf Morphology in Rice.

Yield is majorly affected by photosynthetic efficiency. Leaves are essential structure for photosynthesis and their morphology especially size and shape in a plant canopy can affect the rate of transpiration, carbon fixation and photosynthesis. Leaf rolling and size are considered key agronomic traits in plant architecture that can subsidize yield parameters. In last era, a number of genes controlling leaf morphology have been molecularly characterized. Despite of several findings, our understanding toward molecular mechanism of leaf rolling and size are under-developed. Here, we proposed a model to apprehend the physiological basis of different genes organized in a complex fashion and govern the final phenotype of leaf morphology. According to this leaf rolling is mainly controlled by regulation of bulliform cells by SRL1, ROC5, OsRRK1, SLL2, CLD1, OsZHD1/2, and NRL1, structure and processes of sclerenchyma cells by SLL1 and SRL2, leaf polarity by ADL1, RFS and cuticle formation by CFL1, and CLD1. Many of above mentioned and several other genes interact in a complex manner in order to sustain cellular integrity and homeostasis for optimum leaf rolling. While, leaf size is synchronized by multifarious interaction of PLA1, PLA2, OsGASR1, and OsEXPA8 in cell division, NAL1, NAL9, NRL1, NRL2 in regulation of number of veins, OsCOW1, OsPIN1, OsARF19, OsOFP2, D1 and GID in regulation of phytohormones and HDT702 in epigenetic aspects. In this review, we curtailed recent advances engrossing regulation and functions of those genes that directly or indirectly can distress leaf rolling or size by encoding different types of proteins and genic expression. Moreover, this effort could be used further to develop comprehensive learning and directing our molecular breeding of rice.

OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response.

O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR).

Systematic review on Epstein-Barr virus (EBV) DNA in diagnosis of nasopharyngeal carcinoma in Asian populations.

OBJECTIVE: To conduct a meta-analysis to investigate the value of EBV DNA in diagnosis of nasopharyngeal cancer (NPC) in Asian populations, and provide important evidence for screening. METHODS: Prospective or respective case-control or cohort studies regarding the detection role of EBV DNA for NPC were included in our study. We conducted a comprehensive literature search in PubMed, EMBASE, and the Chinese Biomedical Database (CBM database between January 1980 and March 2012. RESULTS: A total of 18 studies with 1492 NPC cases and 2641 health controls were included. Almost of the included studies were conducted in China, and only one other conducted in Thailand. The overall results demonstrated that the pooled sensitivity, specificity, positive likelihood (+ LR) and negative likelihood (-LR) were 0.73 (0.71-0.75), 0.89 (0.88-0.90), 8.84 (5.65-13.84) and 0.19(0.11-0.32), respectively. The overall EBV DNA detection showed the largest area of 0.932 under the summary receiver operator curve (SROC). The accuracy of detection by plasma for NPC (0.86) was higher than in serum (0.81), with largest areas under the SROC of 0.97 and 0.91, respectively. CONCLUSION: Our results demonstrated the EBV DNA detection in plasma or serum has high sensitivity and specificity in diagnosis of NPC, especially in Chinese populations with a high risk of cancer.