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To better define roles that astrocytes and microglia play in Alzheimer’s disease (AD), we used single-nuclei RNA-sequencing to comprehensively characterise transcriptomes in astrocyte and microglia nuclei selectively enriched during isolation post-mortem from neuropathologically defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in both the astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid or pTau expression. The differentially expressed genes were distinct between with the two cell types and pathologies, although common (but cell-type specific) gene sets were enriched with both pathologies in each cell type. Astrocytes showed enrichment for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, inflammation and proteostasis were enriched in microglia and perivascular macrophages with greater tissue amyloid, but IL1-related pathway enrichment was found specifically in association with pTau. We also found distinguishable sub-clusters in the astrocytes and microglia characterised by transcriptional signatures related to either homeostatic functions or disease pathology. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.

Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescent reporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate that GenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-cell level to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in the plasma membrane of single cells, resolves repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease. Stretch-activated ion channel Piezo1 contribures to mechanotransduction in many tissues, but its output is mostly measured indirectly. Here, the authors introduce GenEPi, a fluorescent reporter for directly visualizing Piezo1 activation-dependent calcium influx.

To better define roles that astrocytes and microglia play in Alzheimers disease (AD), we used single-nuclei RNA sequencing to comprehensively characterize transcriptomes in astrocyte and microglia nuclei isolated post mortem from neuropathologically-defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid and pTau expression. Astrocytes were enriched for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, proteostasis and autophagy were highly enriched in microglia and perivascular macrophages. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD. Competing Interest Statement PMM has received consultancy fees from Roche, Adelphi Communications, Celgene, Neurodiem and Medscape. He has received honoraria or speakers fees from Novartis and Biogen and has received research or educational funds from Biogen, Novartis and GlaxoSmithKline. Footnotes * The author list was incomplete in the first posted version and the author order now has been altered to reflect the original intent.

An infectious disease is the most apprehensive problem in aquaculture as it can lead to high mortality in aquatic organisms and massive economic loss. Even though significant progress has been accomplished in therapeutic, prevention, and diagnostic using several potential technologies, more robust inventions and breakthroughs should be achieved to control the spread of infectious diseases. MicroRNA (miRNA) is an endogenous small non-coding RNA that post-transcriptionally regulates the protein-coding genes. It involves various biological regulatory mechanisms in organisms such as cell differentiation, proliferation, immune responses, development, apoptosis, and others. Furthermore, an miRNA also acts as a mediator to either regulate host responses or enhance the replication of diseases during infection. Therefore, the emergence of miRNAs could be potential candidates for the establishment of diagnostic tools for numerous infectious diseases. Interestingly, studies have revealed that miRNAs can be used as biomarkers and biosensors to detect diseases, and can also be used to design vaccines to attenuate pathogens. This review provides an overview of miRNA biogenesis and specifically focuses on its regulation during infection in aquatic organisms, especially on the host immune responses and how miRNAs enhance the replication of pathogens in the organism. In addition to that, we explored the potential applications, including diagnostic methods and treatments, that can be employed in the aquaculture industry.

Individuals burdened with socioeconomic disadvantages, including food insecurity, are often exposed to circumstances that may increase the likelihood of smoking, which may in turn affect the respiratory health of others in the household, particularly children. Yet, the role of these factors in perpetuating tobacco use within households remains underexplored. Therefore, this study attempts to determine the association between household food security and socioeconomic status with paternal smoking in Malaysia. This study utilised data from the South East Asian Nutrition Surveys (SEANUTS II) Malaysia, which involved 2,687 children aged 0.5–12.9 years, recruited through multistage cluster sampling. Although the study recruited children as participants, the present analysis draws on paternal and household information, including food security, socioeconomic status, and paternal smoking, as reported through parent/guardian-reported questionnaires. Multivariate binary logistic regression was used to determine factors associated with paternal smoking habits. Overall, forty-three percent of fathers were reported as smokers. Younger fathers (aged <30.0 years) had twice the odds of smoking [aOR: 2.032 (95%CI 1.301–3.173)] compared to their older counterparts (aged >49.9 years). Fathers from low socioeconomic status households, particularly, those with extremely low household income [aOR: 2.606 (95%CI 1.711–3.968)] and without formal education/completed primary education [aOR: 2.604 (95%CI 1.710–3.966)], had double the odds of smoking than their counterparts. Self-employed/other occupation fathers [aOR: 1.343 (95%CI 1.056–1.709)] and families from food-insecure households [aOR: 1.251 (95%CI 1.053–1.487)] were found to have higher odds of smoking. In conclusion, household food insecurity and socioeconomic status, including age, occupation, household income, and education level were significantly associated with paternal smoking status. Authorities should customise interventions to mitigate socioeconomic barriers and create equitable access to quit-smoking resources. This is important for lowering smoking prevalence and safeguarding children’s health.

This paper aims to report South East Asian Nutrition Surveys (SEANUTS) II Malaysia data on nutritional status, dietary intake and nutritional biomarkers of children aged 6 months to 12 years. Cross-sectional survey conducted in 2019-2020. Multistage cluster sampling conducted in Central, Northern, Southern and East Coast regions of Peninsular Malaysia. 2989 children aged 0·5-12·9 years. Prevalences of stunting, thinness, overweight and obesity among children aged 0·5-12·9 years were 8·9 %, 6·7 %, 9·2 % and 8·8 %, respectively. Among children below 5 years old, 11·4 % were underweight, 13·8 % had stunting and 6·2 % had wasting. Data on nutritional biomarkers showed that a small proportion of children aged 4-12 years had Fe (2·9 %) and vitamin A deficiencies (3·1 %). Prevalence of anaemia was distinctly different between children below 4 years old (40·3 %) and those aged 4 years and above (3·0 %). One-fourth of children (25·1 %) had vitamin D insufficiency, which was twice as prevalent in girls (35·2 % . boys: 15·6 %). The majority of children did not meet the recommended dietary intake for Ca (79·4 %) and vitamin D (94·8 %). Data from SEANUTS II Malaysia confirmed that triple burden of malnutrition coexist among children in Peninsular Malaysia, with higher prevalence of overnutrition than undernutrition. Anaemia is highly prevalent among children below 4 years old, while vitamin D insufficiency is more prevalent among girls. Low intakes of dietary Ca and vitamin D are also of concern. These findings provide policymakers with useful and evidence-based data to formulate strategies that address the nutritional issues of Malaysian children.

Coexisting forms of malnutrition (CFM), defined as multiple forms of malnutrition within the same child (individual-level), pose a greater risk to children than individual forms of malnutrition. This study aimed to determine the prevalence and factors associated with individual-level CFM among children aged 0.5-12.9 years in Peninsular Malaysia. Between May 2019 and March 2020, a total of 2989 children were recruited for the SEANUTS II Malaysia study; after excluding 16 with implausible anthropometric data, 2973 were analysed. CFM prevalence was 6.8%, with the coexistence of underweight and stunting most common (5.2%). Associated factors included younger age (0.5 to 4.9 years; adjusted odds ratio [aOR] = 1.58; 95% CI 1.01-2.48), low birth weight (< 2.5 kg; aOR = 2.12; 95% CI 1.25-3.59), Malay ethnicity (aOR = 2.58; 95% CI 1.47-4.50) and maternal height < 150 cm (aOR = 2.30; 95% CI 1.29-4.10). CFM affects approximately one in 15 children in Peninsular Malaysia and is associated with several childhood and maternal factors. As the impact of CFM on affected children is more severe than that of standalone malnutrition, interventions and policies should focus on improving child and maternal nutrition to effectively mitigate this problem in the region.

We present Chirpy Cardinal, an open-domain social chatbot. Aiming to be both informative and conversational, our bot chats with users in an authentic, emotionally intelligent way. By integrating controlled neural generation with scaffolded, hand-written dialogue, we let both the user and bot take turns driving the conversation, producing an engaging and socially fluent experience. Deployed in the fourth iteration of the Alexa Prize Socialbot Grand Challenge, Chirpy Cardinal handled thousands of conversations per day, placing second out of nine bots with an average user rating of 3.58/5.