Using blood transcriptome analysis for Alzheimer's disease diagnosis and patient stratification.

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA-sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co-expression network analysis (WGCNA) and deconvolution analysis identified AD-associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD-associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell-type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. HIGHLIGHTS: We comprehensively analyze the blood transcriptomes of a well-characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease. Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers. Immune-associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease.

Derivation of Kokumi γ-Glutamyl Peptides and Volatile Aroma Compounds from Fermented Cereal Processing By-Products for Reducing Bitterness of Plant-Based Ingredients.

Current food production methods and consumption behaviours are unsustainable and contribute to environmental harm. One example is food waste-around 38% of food produced is wasted each year. Here, we show that two common food waste products, wheat bran and brewer's spent grain, can successfully be upcycled via miso fermentation. During the fermentation process, kokumi γ-glutamyl peptides, known to increase mouthfulness, are produced; these include γ-ECG (oxidized), γ-EVG, γ-EV, γ-EE, γ-EF, and γ-EL. The profiles of kokumi peptides and volatile aroma compounds are correlated with koji substrate, pH, and enzymatic activity, offering straightforward parameters that can be manipulated to increase the abundance of kokumi peptides during the fermentation process. Correlation analysis demonstrates that some volatile aroma compounds, such as fatty acid ethyl esters, are correlated with kokumi peptide abundance and may be responsible for fatty, greasy, and buttery aromas. Consumer sensory analysis conveys that the bitter taste of vegetables, such as that in endives, can be dampened when miso extract containing kokumi peptides is added. This suggests that kokumi peptides, along with aroma volatile compounds, can enhance the overall flavour of plant-based products. This study opens new opportunities for cereal processing by-product upcycling via fermentation, ultimately having the potential to promote a plant-based diet.

The TOR-dependent phosphoproteome and regulation of cellular protein synthesis.

Cell growth is orchestrated by a number of interlinking cellular processes. Components of the TOR pathway have been proposed as potential regulators of cell growth, but little is known about their immediate effects on protein synthesis in response to TOR-dependent growth inhibition. Here, we present a resource providing an in-depth characterisation of Schizosaccharomyces pombe phosphoproteome in relation to changes observed in global cellular protein synthesis upon TOR inhibition. We find that after TOR inhibition, the rate of protein synthesis is rapidly reduced and that notable phosphorylation changes are observed in proteins involved in a range of cellular processes. We show that this reduction in protein synthesis rates upon TOR inhibition is not dependent on S6K activity, but is partially dependent on the S. pombe homologue of eIF4G, Tif471. Our study demonstrates the impact of TOR-dependent phospho-regulation on the rate of protein synthesis and establishes a foundational resource for further investigation of additional TOR-regulated targets both in fission yeast and other eukaryotes.

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase.

The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause a fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. To identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play key roles in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine-N7 methyltransferase nsp14, and the nsp16 2'-O-methyltransferase with its activating cofactor, nsp10. We performed an in vitro high-throughput screen for inhibitors of nsp14 using a custom compound library of over 5000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified four compounds as potential inhibitors of nsp14, all of which also showed antiviral capacity in a cell-based model of SARS-CoV-2 infection. Three of the four compounds also exhibited synergistic effects on viral replication with remdesivir.

A cross-region analysis of commercial food waste recycling behaviour.

To tackle the crisis associated with the rising commercial food waste generation, it is imperative to comprehend how corporates' recycling behaviour is influenced by different industry structures and economies. This study aims to fill in the information gap that various factors might be affecting corporates' recycling behaviour in two different economies due to environmental inequality by comparing upper-middle-income region (Malaysia) and high-income region (Hong Kong), respectively. A questionnaire survey regarding food waste management according to the Theory of Planned Behaviour was conducted with representatives coming from diverse industries of the hotel, food and beverage, and property management. The questionnaire responses were evaluated based on quantitative structural equation modelling and correlation analysis. The analysis results showed that the model fit the data well, explaining 78% of the variance in recycling behaviour. The findings demonstrated that the most substantial factor on individual's recycling intention by Malaysian commercial food waste generators was perceived behavioural control, and logistics and management incentives. Subjective norms demonstrated significant and adverse effects on the behaviour of food waste recycling. The variable of administrative incentives and corporate support presented strong positive correlations with moral attitudes as well as logistics and management incentives. Hotel industries from both Hong Kong and Malaysia have a higher acceptance level on human resources regarding food waste recycling. In comparison, food and beverage industries from both regions have a lower acceptance level. These findings could enrich our knowledge of the concerns in establishing regional policy strategies to encourage economic behavioural changes for sustainable development.

How energy service companies moderate the impact of industrialization and urbanization on carbon emissions in China?

Energy service companies (ESCOs) have emerged to carry out energy efficiency retrofit projects, playing an essential role in mitigating carbon dioxide (CO2) emissions in China. However, it remains unclear how exactly ESCOs contribute to CO2 mitigation during urbanization and industrialization. We conducted regression analyses on data collected in 29 provinces in China as the first case study to investigate the moderating effect of ESCOs in relationships between urbanization, industrialization, and CO2 emissions. The results indicate that urbanization had a significantly negative influence on CO2 emissions. In contrast, industrialization displayed a statistically significant positive impact on CO2 emissions. ESCOs have a significant moderating effect on the relationship between industrialization, urbanization, and CO2 emissions. The analysis also revealed that ESCOs have a better performance in areas with lower industrialization and greater urbanization. ESCOs may invest more in regions with limited ESCO activities and huge CO2 emission reduction demand, while energy-saving technology innovation should be advocated in regions with sufficient ESCO activities.

Sustainable food waste management towards circular bioeconomy: Policy review, limitations and opportunities.

Research attention is increasingly drawn on constructing a circular bioeconomy and enhancing the value of material flows. Circular bioeconomy aims to achieve sustainable consumption and production with reduction of greenhouse gas emission. This study identifies research gaps on how circular bioeconomy can be achieved through sustainable food waste management by comparing the similarities and differences in concepts of bioeconomy and circular economy, reviewing the benefits and limitations of the existing policies, and evaluating the global situations of food waste and its management on household and commercial basis to promote circular bioeconomy. Future development on food waste management is expected to capitalise on the multi-functionality of products, boundary and allocation in a circular system, and trade-off between food waste and resources. With future technological advances, food waste management in circular bioeconomy policy can facilitate the accomplishment of sustainable development goals.

YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells.

The properties and behaviour of stem cells rely heavily on signaling from the local microenvironment. At the apical end of Drosophila testis, self-renewal and differentiation of germline stem cells (GSCs) are tightly controlled by distinct somatic cells that comprise a specialised stem cell niche known as the hub. The hub maintains GSC homeostasis through adhesion and cell signaling. The Salvador/Warts/Hippo (SWH) pathway, which suppresses the transcriptional co-activator YAP/Yki via a kinase cascade, is a known regulator of stem cell proliferation and differentiation. Here, we show that increasing YAP/Yki expression in the germline, as well as reducing Warts levels, blocks the decrease of GSC numbers observed in aging flies, with only a small increase on their proliferation. An increased expression of YAP/Yki in the germline or a reduction in Warts levels also stymies an age-related reduction in hub cell number, suggesting a bilateral relationship between GSCs and the hub. Conversely, RNAi-based knockdown of YAP/Yki in the germline leads to a significant drop in hub cell number, further suggesting the existence of such a SC-to-niche relationship. All together, our data implicate the SWH pathway in Drosophila GSC maintenance and raise questions about its role in stem cell homeostasis in aging organisms.

Extended theory of planned behaviour for promoting construction waste recycling in Hong Kong.

Changing individual's recycling attitude and behaviour is of utmost importance in achieving sustainable construction and demolition (C&D) waste management, yet it has often been underachieved. To understand the motivations for recycling, this study identifies and prioritizes the key factors that affect C&D waste recycling behaviour of various stakeholders in Hong Kong (i.e., representatives from construction-waste-related organizations, environmental consultants and contractors, and government engineers) in a quantitative manner using statistical tools. Different from traditional C&D waste behavioural determinants studies, this paper utilizes an integrated analytical method through semi-structured interviews and survey questionnaire on the basis of Theory of Planned Behaviour (TPB). Qualitative thematic analysis and quantitative frequency analysis were performed to analyse responses from semi-structured interviews and questionnaires, followed by correlation analysis to quantify the relationships between factors. Results indicated that four key factors: (i) regulatory compliance, (ii) economic incentives, (iii) accreditation scheme, and (iv) logistics and management incentives directly influenced recycling behaviour of individuals. Regulatory compliance was the most determining factor for consultants, contractors, experts, and government officials, whereas economic incentives were of great concern to the public. Under the factor of economic incentives, strong positive relationships were identified between disposal costs and collection and sorting costs, thus increasing waste disposal charging fee may promote recycling behaviour. In comparison, accreditation scheme deserved better recognition to facilitate a closed-loop material flow in the construction industry. These findings help to devise more effective and stakeholder-oriented policy tools to raise awareness and encourage behavioural change towards C&D waste recycling, and assist policy makers to establish regulations and practices for sustainable resource management.