DOPE - CAS 4004-05-1

Osteosarcoma (OS) is the most common bone cancer with a high risk of metastasis, high growth rate, and poor prognosis. Honokiol (HNK) is a general ingredient of traditional Chinese medicine, with a potential anti-tumor effect. However, HNK is insoluble in water and lacks drug targeting, which limits its clinical application. To improve the OS therapeutic effect of HNK, we used HNK-loaded liposomes modified with hyaluronic acid-phospholipid conjugates (HA-DOPE) to treat OS based on the HA interaction with CD44. The HNK-loaded liposomes were prepared via thin-film hydration and sonication. HA-DOPE was used to combine the HNK-loaded liposomes (HA-DOPE@Lips/HNK) via sonication and co-extrusion. HA-DOPE@Lips/HNK were characterized with respect to size, zeta potential, polymer dispersity index (PDI), and stability, and transmission electron microscopy was performed. Cellular uptake, cell viability, cell apoptosis, cell cycle, and mitochondrial activity were utilized to evaluate the antitumor effect in vitro. The biodistribution, xenograft tumor growth inhibition, and safety of HA-DOPE@Lips/HNK were evaluated in 143B OS xenograft mice in vivo. The particle size, PDI, and zeta potential of HA-DOPE@Lips/HNK were 146.20±0.26 nm, 0.20±0.01, and -38.45±0.98 mV, respectively. The encapsulation rate and drug loading were 80.14±0.32% and 3.78±0.09%, respectively. HA-DOPE@Lips/HNK could inhibit cell proliferation, cause apoptosis, block the cell cycle and disrupt mitochondrial activity. HA-DOPE@Lips/HNK specially delivered the drug into the tumor and inhibited tumor growth, and showed no obvious toxicity to normal tissues. HA-DOPE@Lips/HNK could deliver HNK into the tumor site and had a good antitumor ability in vitro and in vivo. In addition, HA-DOPE@Lips/HNK increased the antitumor effects of HNK. Thus, it provides a promising nanocarrier to improve drug delivery in OS therapy.

Testing individuals for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen causing the coronavirus disease 2019 (COVID-19), is crucial for curtailing transmission chains. Moreover, rapidly testing many potentially infected individuals is often a limiting factor in controlling COVID-19 outbreaks. Hence, pooling strategies, wherein individuals are grouped and tested simultaneously, are employed. Here, we present a novel pooling strategy that builds on the Bayesian D-optimal experimental design criterion. Our strategy, called DOPE (D-Optimal Pooling Experimental design), is built on a novel Bayesian formulation of pooling. DOPE defines optimal pooled tests as those maximizing the mutual information between data and infection states. We estimate said mutual information via Monte-Carlo sampling and employ a discrete optimization heuristic to maximize it. We compare DOPE to other, commonly used pooling strategies, as well as to individual testing. DOPE dominates the other strategies as it yields lower error rates while utilizing fewer tests. We show that DOPE maintains this dominance for a variety of infection prevalence values. DOPE has several additional advantages over common pooling strategies: it provides posterior distributions of the probability of infection rather than only binary classification outcomes; it naturally incorporates prior information of infection probabilities and test error rates; and finally, it can be easily extended to include other, newly discovered information regarding COVID-19. DOPE can substantially improve accuracy and throughput over current pooling strategies. Hence, DOPE can facilitate rapid testing and aid the efforts of combating COVID-19 and other future pandemics.

Recent reports have highlighted the emergence of 'wasp dope' as an issue of concern, but epidemiological evidence is lacking. Wasp dope is a crystalline substance created by electrifying pyrethroid-containing insecticides (e.g. wasp sprays) that may give users a methamphetamine-like 'rush'. This paper describes wasp dope use and correlates of use in a sample of people who use drugs (PWUD) in Appalachian Kentucky, a region that has been an epicenter of opioid use and related harms in the United States. Respondent-driven sampling and targeted street outreach were used to recruit PWUD. Eligibility criteria included being aged at least 18 years, residing in one of five Appalachian Kentucky counties, and having either used opioids or injected any drug to get high in the prior 30 days. Interviewer-administered surveys queried participants' (n = 278) recent (past 6 months) wasp dope use, other substance use and demographic characteristics. Prevalence ratios (PR) were estimated using generalized estimating equations assuming a Poisson outcome distribution in a cross-sectional analysis. Recent wasp dope use was reported by 16.1% of participants. Men and people who recently experienced homelessness and transportation difficulties were twice or more as likely to have used wasp dope compared with their counterparts [PR = 2.08, 95% confidence interval (CI) = 1.11, 3.87, PR = 2.78, 95% CI = 1.64, 4.72 and PR = 2.01, 95% CI = 1.06-3.81, respectively]. While wasp dope use was associated with injection drug use and using opioids and other substances to get high in unadjusted analyses, the factor most strongly associated with wasp dope use was methamphetamine use (PR = 17.23, 95% CI = 2.57, 115.61), specifically methamphetamine injection (PR = 4.47, 95% CI = 1.56, 12.78). Among people who use drugs in rural Kentucky, USA, more than one in six people surveyed reported using wasp dope in the past 6 months, nearing the percentage using cocaine/crack (20%) and fentanyl/carfentanil (25%). Wasp dope use was higher among men and strongly associated with homelessness, transportation access, methamphetamine use and injection drug use.