Metformin induces pyroptosis in leptin receptor-defective hepatocytes via overactivation of the AMPK axis.

Metformin is the biguanide of hepatic insulin sensitizer for patients with non-alcohol fatty liver disease (NAFLD). Findings regarding its efficacy in restoring blood lipids and liver histology have been contradictory. In this study, we explore metformin's preventive effects on NAFLD in leptin-insensitive individuals. We used liver tissue, serum exosomes and isolated hepatocytes from high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats and leptin receptor (Lepr) knockout rats to investigate the correlation between hepatic Lepr defective and liver damage caused by metformin. Through immunostaining, RT-PCR and glucose uptake monitoring, we showed that metformin treatment activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream cytochrome C oxidase (CCO). This leads to overactivation of glucose catabolism-related genes, excessive energy repertoire consumption, and subsequent hepatocyte pyroptosis. Single-cell RNA sequencing further confirmed the hyper-activation of glucose catabolism after metformin treatment. Altogether, we showed that functional Lepr is necessary for metformin treatment to be effective, and that long-term metformin treatment might promote NAFLD progression in leptin-insensitive individuals. This provides important insight into the clinical application of metformin.

Insights into Circulating Tumor Cell Clusters: A Barometer for Treatment Effects and Prognosis for Prostate Cancer Patients.

Prostate cancer (PCa) exhibits high cellular heterogeneity across patients. Therefore, there is an urgent need for more real-time and accurate detection methods, in both prognosis and treatment in clinical settings. Circulating tumor cell (CTC) clusters, a population of tumor cells and non-malignant cells in the blood of patients with tumors, are a promising non-invasive tool for screening PCa progression and identifying potential benefit groups. CTC clusters are associated with tumor metastasis and possess stem-like characteristics, which are likely attributable to epithelial-mesenchymal transition (EMT). Additionally, these biological properties of CTC clusters, particularly androgen receptor V7, have indicated the potential to reflect curative effects, guide treatment modalities, and predict prognosis in PCa patients. Here, we discuss the role of CTC clusters in the mechanisms underlying PCa metastasis and clinical applications, with the aim of informing more appropriate clinical decisions, and ultimately, improving the overall survival of PCa patients.

Assessing COVID-19 Vaccine Hesitancy, Confidence, and Public Engagement: A Global Social Listening Study.

BACKGROUND: Monitoring public confidence and hesitancy is crucial for the COVID-19 vaccine rollout. Social media listening (infoveillance) can not only monitor public attitudes on COVID-19 vaccines but also assess the dissemination of and public engagement with these opinions. OBJECTIVE: This study aims to assess global hesitancy, confidence, and public engagement toward COVID-19 vaccination. METHODS: We collected posts mentioning the COVID-19 vaccine between June and July 2020 on Twitter from New York (United States), London (United Kingdom), Mumbai (India), and Sao Paulo (Brazil), and Sina Weibo posts from Beijing (China). In total, we manually coded 12,886 posts from the five global metropolises with high COVID-19 burdens, and after assessment, 7032 posts were included in the analysis. We manually double-coded these posts using a coding framework developed according to the World Health Organization's Confidence, Complacency, and Convenience model of vaccine hesitancy, and conducted engagement analysis to investigate public communication about COVID-19 vaccines on social media. RESULTS: Among social media users, 36.4% (571/1568) in New York, 51.3% (738/1440) in London, 67.3% (144/214) in Sao Paulo, 69.8% (726/1040) in Mumbai, and 76.8% (2128/2770) in Beijing indicated that they intended to accept a COVID-19 vaccination. With a high perceived risk of getting COVID-19, more tweeters in New York and London expressed a lack of confidence in vaccine safety, distrust in governments and experts, and widespread misinformation or rumors. Tweeters from Mumbai, Sao Paulo, and Beijing worried more about vaccine production and supply, whereas tweeters from New York and London had more concerns about vaccine distribution and inequity. Negative tweets expressing lack of vaccine confidence and misinformation or rumors had more followers and attracted more public engagement online. CONCLUSIONS: COVID-19 vaccine hesitancy is prevalent worldwide, and negative tweets attract higher engagement on social media. It is urgent to develop an effective vaccine campaign that boosts public confidence and addresses hesitancy for COVID-19 vaccine rollouts.

Confidence, Acceptance and Willingness to Pay for the COVID-19 Vaccine among Migrants in Shanghai, China: A Cross-Sectional Study.

Understanding the public's attitude towards COVID-19 vaccination and their acceptance could help facilitate the COVID-19 rollout. This study aimed to assess the acceptance and willingness to pay (WTP) for the COVID-19 vaccine among migrants in Shanghai, China. A cross-sectional study was conducted among 2126 migrants in Shanghai for the period 1-20 November 2020. Convenience sampling was used to recruit respondents in workplaces with large numbers of migrant workers. Multivariable (ordered) logistic regressions were used to examine factors associated with acceptance and WTP of the COVID-19 vaccine. Most (89.1%) migrants would accept COVID-19 vaccination. Over 90.0% perceived the COVID-19 vaccine as important, while only 75.0% and 77.7% perceived vaccines safe and effective. Socio-demographic factors were not significantly associated with vaccine acceptance, but confidence in the importance (OR 8.71, 95% CI 5.89-12.89), safety (OR 1.80, 95% CI 1.24-2.61) and effectiveness (OR 2.66, 95% CI 1.83-3.87) of COVID-19 vaccine was significantly positively associated with vaccine acceptance. The top reasons for vaccine hesitancy were lack of vaccine information and confidence. The proportion of those definitely willing to get the COVID-19 vaccine was 20% lower if paid by themselves than free vaccination. Migrants were willing to pay a median amount of USD 46 for the COVID-19 vaccine. Results show that a high acceptance of the COVID-19 vaccine was universal among migrants in Shanghai. Concerns about vaccine safety, effectiveness and high costs of the COVID-19 vaccine may hinder their uptake. Effective health communication to build confidence in the COVID-19 vaccine and subsidies toward the costs of these vaccines are needed to improve uptake.