Point-of-Sale Marketing in Recreational Marijuana Dispensaries Around California Schools.

PurposeAfter marijuana commercialization, the presence of recreational marijuana dispensaries (RMDs) was rapidly increasing. The point-of-sale marketing poses concerns about children's exposure. This study examined advertising and promotions that potentially appeal to children and access restrictions in RMDs around California schools.MethodsThis was a cross-sectional and observational study conducted from June to September 2018. Trained fieldworkers audited retail environments in 163 RMDs in closest proximity to 333 randomly sampled public schools in California.ResultsAbout 44% of schools had RMDs located within 3 miles. Regarding interior marketing, 74% of RMDs had at least one instance of child-appealing products, packages, paraphernalia, or advertisements. RMDs closer to a school had a higher proportion with interior child-appealing marketing. More than three fourths of RMDs had generic promotional activities; particularly, 28% violated the free-sample ban. Regarding exterior marketing, only 2% of RMDs had those appealing to children. More than 60% of RMDs had exterior signs indicative of marijuana. Approximately, one-third had generic advertisements, and 13% had advertisements bigger than 1,600 square inches. Regarding access restrictions, almost all RMDs complied with age verification, but 84% had no age limit signs, and only 40% had security personnel.ConclusionsDespite minimal point-of-sale marketing practices appealing to children on the exterior of RMDs around California schools, such practices were abundant on the interior. Marketing practices not specifically appealing to children were also common on both the interior and exterior of RMDs. Dispensaries' violation of age verification law, lack of security personnel, and presence of child-appealing marketing should be continuously monitored and prevented

Altering nodes types in controlling complex networks

Controlling a complex network towards a desired state is of great importance in many applications. A network can be controlled by inputting suitable external signals into some selected nodes, which are called driver nodes. Previous works found there exist two control modes in dense networks: distributed and centralized modes. For networks with the distributed mode, most of the nodes can be act as driver nodes; and those with the centralized mode, most of the nodes never be the driver nodes. Here we present an efficient algorithm to change the control type of nodes, from input nodes to redundant nodes, which is done by reversing edges of the network. We conclude four possible cases when reversing an edge and show the control mode can be changed by reversing very few in-edges of driver nodes. We evaluate the performance of our algorithm on both synthetic and real networks. The experimental results show that the control mode of a network can be easily changed by reversing a few elaborately selected edges, and the number of possible driver nodes is dramatically decreased. Our methods provide the ability to design the desired control modes of the network for different control scenarios, which may be used in many application regions

In Vitro Exploration of ACAT Contributions to Lipid Droplet Formation During Adipogenesis

As adipose tissue is the major cholesterol storage organ and most of the intracellular cholesterol is distributed to lipid droplets (LDs), cholesterol homeostasis may have a role in the regulation of adipocyte size and function. ACATs catalyze the formation of cholesteryl ester (CE) from free cholesterol to modulate the cholesterol balance. Despite the well-documented role of ACATs in hypercholesterolemia, their role in LD development during adipogenesis remains elusive. Here, we identify ACATs as regulators of de novo lipogenesis and LD formation in murine 3T3-L1 adipocytes. Pharmacological inhibition of ACAT activity suppressed intracellular cholesterol and CE levels, and reduced expression of genes involved in cholesterol uptake and efflux. ACAT inhibition resulted in decreased de novo lipogenesis, as demonstrated by reduced maturation of SREBP1 and SREBP1-downstream lipogenic gene expression. Consistent with this observation, knockdown of either ACAT isoform reduced total adipocyte lipid content by approximately 40%. These results demonstrate that ACATs are required for storage ability of lipids and cholesterol in adipocytes

The shift of percent excess mortality from zero-COVID policy to living-with-COVID policy in Singapore, South Korea, Australia, New Zealand and Hong Kong SAR

IntroductionWith the economic recession and pandemic fatigue, milder viral variants and higher vaccine coverage along the time lay the basis for lifting anti-COVID policies to restore COVID-19 normalcy. However, when and how to adjust the anti-COVID policies remain under debate in many countries.MethodsIn this study, four countries (Singapore, South Korea, Australia, and New Zealand) and one region (Hong Kong SAR), that have shifted from the zero-COVID (ZC) policy to or close to the living-with-COVID (LWC) during or after the Omicron outbreak, were selected as research objects. All-cause mortality data were collected for these objects from 2009 to 2019. The expected mortality was estimated by a simple linear regression method. Excess mortality over time was calculated as the difference between the expected mortality and the observed mortality. Finally, percent excess mortality (PEM) was calculated as the excess mortality divided by the expected mortality.ResultsIn the examined four countries, PEM fluctuated around 0% and was lower than 10% most of the time under the ZC policy before 2022. After shifting to the LWC policy, all the examined countries increased the PEM. Briefly, countries with high population density (Singapore and South Korea) experienced an average PEM of 20–40% during the first half of 2022, and followed by a lower average PEM of 15–18% during the second half of 2022. For countries with low population density under the LWC policy, Australia experienced an average PEM of 39.85% during the first half of 2022, while New Zealand was the only country in our analysis that achieved no more than 10% in average PEM all the time. On the contrary, Hong Kong SAR under their ZC policy attained an average PEM of 71.14% during the first half of 2022, while its average PEM decreased to 9.19% in the second half of 2022 with LWC-like policy.ConclusionPEM under different policies within each country/region overtime demonstrated that the mortality burden caused by COVID-19 had been reduced overtime. Moreover, anti-COVID policies are suggested to control the excess mortality to achieve as low as 10% in PEM

Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds

Integration of multi-omics and clinical treatment data reveals bladder cancer therapeutic vulnerability gene combinations and prognostic risks

BackgroundBladder cancer (BCa) is a common malignancy of the urinary tract. Due to the high heterogeneity of BCa, patients have poor prognosis and treatment outcomes. Immunotherapy has changed the clinical treatment landscape for many advanced malignancies, opening new avenues for the precise treatment of malignancies. However, effective predictors and models to guide clinical treatment and predict immunotherapeutic outcomes are still lacking.MethodsWe downloaded BCa sample data from The Cancer Genome Atlas to identify anti-PD-L1 immunotherapy-related genes through an immunotherapy dataset and used machine learning algorithms to build a new PD-L1 multidimensional regulatory index (PMRI) based on these genes. PMRI-related column-line graphs were constructed to provide quantitative tools for clinical practice. We analyzed the clinical characteristics, tumor immune microenvironment, chemotherapy response, and immunotherapy response of patients based on PMRI system. Further, we performed function validation of classical PMRI genes and their correlation with PD-L1 in BCa cells and screening of potential small-molecule drugs targeting PMRI core target proteins through molecular docking.ResultsPMRI, which consists of four anti-PD-L1 immunotherapy-associated genes (IGF2BP3, P4HB, RAC3, and CLK2), is a reliable predictor of survival in patients with BCa and has been validated using multiple external datasets. We found higher levels of immune cell infiltration and better responses to immunotherapy and cisplatin chemotherapy in the high PMRI group than in the low PMRI group, which can also be used to predict immune efficacy in a variety of solid tumors other than BCa. Knockdown of IGF2BP3 inhibited BCa cell proliferation and migration, and IGF2BP3 was positively correlated with PD-L1 expression. We performed molecular docking prediction for each of the core proteins comprising PMRI and identified 16 small-molecule drugs with the highest affinity to the target proteins.ConclusionsOur PD-L1 multidimensional expression regulation model based on anti-PD-L1 immunotherapy-related genes can accurately assess the prognosis of patients with BCa and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical management of intermediate and advanced BCa

Advances in research on spexin-mediated regulation of reproductive function in vertebrates

Spexin (SPX, NPQ) is a 14-amino acid neuroactive peptide identified using bioinformatics. This amino acid sequence of the mature spexin peptide has been highly conserved during species evolution and is widely distributed in the central nervous system and peripheral tissues and organs. Therefore, spexin may play a role in various biological functions. Spexin, the cognate ligand for GALR2/3, acting as a neuromodulator or endocrine signaling factor, can inhibit reproductive performance. However, controversies and gaps in knowledge persist regarding spexin-mediated regulation of animal reproductive functions. This review focuses on the hypothalamic-pituitary-gonadal axis and provides a comprehensive overview of the impact of spexin on reproduction. Through this review, we aim to enhance understanding and obtain in-depth insights into the regulation of reproduction by spexin peptides, thereby providing a scientific basis for future investigations into the molecular mechanisms underlying the influence of spexin on reproductive function. Such investigations hold potential benefits for optimizing farming practices in livestock, poultry, and fish industries

Preliminary Findings of the High Quantity of Microplastics in Faeces of Hong Kong Residents

Microplastics are recognised as a ubiquitous and hazardous pollutant worldwide. These small-sized particles have been detected in human faeces collected from a number of cities, providing evidence of human ingestion of microplastics and their presence in the gastrointestinal tract. Here, using Raman spectroscopy, we identified an average of 50 particles g−1 (20.4–138.9 particles g−1 wet weight) in faeces collected from a healthy cohort in Hong Kong. This quantity was about five times higher than the values reported in other places in Asia and Europe. Polystyrene was the most abundant polymer type found in the faeces, followed by polypropylene and polyethylene. These particles were primarily fragments, but about two-thirds of the detected polyethylene terephthalate were fibres. More than 88% of the microplastics were smaller than 300 µm in size. Our study provides the first data on the faecal level, and thus the extent of ingestion, of microplastics in Hong Kong’s population. This timely assessment is crucial and supports the recently estimated ingestion rate of microplastics by Hong Kong residents through seafood consumption, which is one of the highest worldwide. These findings may be applicable to other coastal populations in South China with similar eating habits