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Neuroinflammation plays a key role in Alzheimer's disease (AD) and related neurodegenerative disorders. Chronic activation of astrocytes and microglia fuels neuronal damage via cytokine secretion, oxidative stress, and proteolysis. However, glial inflammatory regulation remains poorly understood. Using chemoproteomics, we identified CK2, particularly the brain-enriched catalytic subunit CK2α2, as a key driver of astrocytic inflammation. CK2 enhances NF-κB activity by phosphorylating NF-κB S529 and IκBα S32, promoting pro-inflammatory gene expression. CK2 inhibition via genetic or chemical approaches dampens inflammation, including IL-6 and IL-8 expression in an acute neuroinflammation mouse model. CK2α2 is upregulated in AD postmortem tissues and patient-derived astrocytes. AD astrocytes exhibit a hyperinflammatory state that can be attenuated by CK2 inhibition. Overexpression of CK2α2 in cortical organoids mimics AD pathology, whereas CK2 inhibition using the potent, selective, and brain-penetrant probe TAL606 rescues inflammatory markers in transgenic AD mice. These findings position CK2 as a central regulator of neuroinflammation and a promising therapeutic target for AD and related disorders.

Patients undergoing major abdominal surgery received restrictive or liberal intravenous fluids during surgery and up to 24 hours thereafter. The restrictive regimen did not improve disability-free survival and resulted in increased acute kidney injury.

Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacillus crispatus , Lactobacillus gasseri , Lactobacillus iners , and Lactobacillus jensenii . These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alternatives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the effectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the beneficial effects of lactobacilli derivatives (i.e. surface-active molecules) with anti-biofilm, antioxidant, pathogen-inhibition, and immunomodulation activities in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health.

Purpose – The purpose of this paper is to explore attitudes of consumers who engage with brands through Facebook “likes”. It explores the extent to which these brands are self-expressive and examines the relationship between brand “liking” and brand outcomes. Brand outcomes include brand love and advocacy, where advocacy incorporates WOM and brand acceptance. Design/methodology/approach – Findings are presented from a survey of Facebook users who engage with a brand by “liking” it. Findings – Brands “liked” are expressive of the inner or social self. The study identifies a positive relationship between the self-expressive nature of brands “liked” and brand love. Consumers who engage with inner self-expressive brands are more likely to offer WOM for that brand. By contrast, consumers who engage with socially self-expressive brands are more likely to accept wrongdoing from a brand. Research limitations/implications – The research is exploratory and is limited to consumers who are engaged with a brand through “liking” it on the Facebook social network. Practical implications – The study offers suggestions for managers seeking to enhance brand engagement through Facebook “liking”, and to encourage positive brand outcomes (such as WOM) among consumers already engaged with a brand on Facebook. Originality/value – This paper provides new insights into consumer brand engagement evidenced through Facebook “liking”. It charts the relationship between “liked” self-expressive brands and brand love. Distinctions are drawn between brand outcomes among consumers who “like” for socially self-expressive reasons, and consumers who are brand engaged by “liking” to express their inner selves.

Mentioning products or brands on Facebook enables individuals to display an ideal self to others through a form of virtual conspicuous consumption. Drawing on conspicuous donation behaviour literature, we investigate 'conspicuous virtue signalling' (CVS), as conspicuous consumption on Facebook. CVS occurs when an individual mentions a charity on their Facebook profile. We investigate need for uniqueness (NFU) and attention to social comparison information (ATSCI) as antecedents of two types of CVS-self-oriented (to gain intrinsic benefits) and other-oriented (to impress others). We also explore the relationship between CVS and self-esteem, and offline prosocial (donation to the charity) and unethical (counterfeit purchase) behaviour intentions. Data from two studies, a college survey (N=234) and an adult survey via MTurk (N=296), were analysed using structural equation modelling. Results indicate that NFU predicts both forms of CVS, while ATSCI influences both forms of CVS for adults and other-oriented CVS for students. Self-esteem is enhanced by self-oriented CVS. Self-oriented CVS predicts donation intention whereas other-oriented CVS significantly reduces donation intention for both samples. Furthermore, a significant relationship between CVS and purchase intention of counterfeit luxury goods is revealed. Findings provide insights into conspicuous virtue signalling and the relationship between CVS on Facebook and offline behavioural intentions.

Saved from Desert Sands: Re-Discovering Objects on the Silk Road. Edited by Kelsey Granger and Imre Galambos. Brill, 2024. Pp. xvii + 299. $132; open access.

Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. Of 10 102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

Wild and fantastical animals climb, fly, scamper, and prance across pictorial stone carvings decorating Eastern Han tomb doors in northern Shaanxi. Alongside dragons and other mythical animals, bears felicitously dance, tigers grin opening their mouths to roar, and other wild animals frolic in swirling cloudscapes. While the same animals can be found in Eastern Han tomb reliefs and mortuary art in other regions, their frequency, emphasis on plasticity and movement, and combination with the yunqi 雲氣 motif are unique to the region. Originating in a hybrid style of art that was created during the Mid-Western Han Dynasty (206 BCE–9 CE), their significance was dependent not so much on any individual creature but on their display as an assemblage of shared forms, behaviors, and habitats. This paper explores how Eastern Han patrons and artists in Shanbei reinvigorated such imagery. It argues that on tomb doors through the region, these same wild and fantastical animals have become a key element of compositions meant to pacify the potentially dangerous realms that awaited the deceased in their postmortem ascension to Heaven (tian 天).

Background Carbon utilization and metabolism are fundamental to every living organism for cellular growth. For intracellular human fungal pathogens such as Candida glabrata , an effective metabolic adaptation strategy is often required for survival and pathogenesis. As one of the host defence strategies to combat invading pathogens, phagocytes such as macrophages constantly impose restrictions on pathogens’ access to their preferred carbon source, glucose. Surprisingly, it has been reported that engulfed C. glabrata are able to survive in this harsh microenvironment, further suggesting alternative carbon metabolism as a potential strategy for this opportunistic fungal pathogen to persist in the host. Main text In this review, we discuss alternative carbon metabolism as a metabolic adaptation strategy for the pathogenesis of C. glabrata . As the glyoxylate cycle is an important pathway in the utilization of alternative carbon sources, we also highlight the key metabolic enzymes in the glyoxylate cycle and its necessity for the pathogenesis of C. glabrata . Finally, we explore the transcriptional regulatory network of the glyoxylate cycle. Conclusion Considering evidence from Candida albicans and Saccharomyces cerevisiae , this review summarizes the current knowledge of the glyoxylate cycle as an alternative carbon metabolic pathway of C. glabrata .