Assessment of drug-drug interaction of dapagliflozin with LCZ696 based on an LC-MS/MS method.

The co-administration of dapagliflozin (DPF) and sacubitril/valsartan (LCZ696) has emerged as a promising therapeutic approach for managing heart failure. Given that DPF and LCZ696 are substrates for P-glycoprotein, there is a plausible potential for drug-drug interactions when administered concomitantly. To investigate the pharmacokinetic changes when these drugs are co-administered, we have established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method capable of simultaneously detecting DPF, LBQ657 (the active metabolite of sacubitril) and valsartan in rat plasma. This method has demonstrated selectivity, sensitivity, and accuracy. Drug-drug interactions were examined by the LC-MS/MS method. The mechanisms were investigated using everted intestinal sac models and Caco-2 cells. The results showed that DPF significantly increased the area under the curve (AUC(0-t)) (3,563.3 ± 651.7 vs. 7,146.5 ± 1,714.9 h µg/L) of LBQ657 (the active metabolite of sacubitril) and the AUC(0-t) (24,022.4 ± 6,774.3 vs. 55,728.3 ± 32,446.3 h µg/L) of valsartan after oral co-administration. Dapagliflozin significantly increased the amount of LBQ657 and valsartan in intestinal sacs by 1- and 1.25-fold at 2.25 h. Caco-2 cell uptake studies confirmed that P-glycoprotein is the transporter involved in this interaction. This finding enhances the understanding of drug-drug interactions in the treatment of heart failure and provides a guidence for clinical therapy.

Functional trait-based phytoplankton biomass and assemblage analyses in the pre-growing season for comprehensive algal bloom risk assessment.

Algal bloom (AB) risk assessment is critical for maintaining ecosystem health and human sustainability. Previous AB risk assessments have focused on the potential occurrence of ABs and related factors in the growing season, whereas their hazards, especially in the pre-growing season, have attracted less attention. Here, we performed a comprehensive AB risk assessment, including water trophic levels, phytoplankton biomass, functional trait-based assemblages, and related environmental factors, in the pre-growing season in Dongting Lake, China. Although mesotrophic water and low phytoplankton biomass suggested low AB potential, toxic taxa, which constituted 13.28% of the phytoplankton biomass, indicated non-negligible AB hazards. NH4+ and water temperature were key factors affecting phytoplankton motility and toxicity. Our study establishes a new paradigm for quantitative AB risk assessment, including both potential AB occurrence and hazards. We emphasize the importance of phytoplankton functional traits for early AB warning and NH4+ reduction for AB control in the pre-growing season.

Bibliometric and visualization analysis of risk management in the doctor-patient relationship: A systematic quantitative literature review.

OBJECTIVES: This paper analyzed the research on risk management in the doctor-patient relationship (DPR) based on a systematic quantitative literature review approach using bibliometric software. It aims to uncover potential information about current research and predict future research hotspots and trends. METHODS: We conducted a comprehensive search for relevant publications in the Scopus database and the Web of Science Core Collection database from January 1, 2000 to December 31, 2023. We analyzed the data using CiteSpace 6.2.R2 and VOSviewer 1.6.19 software to examine the annual number of publications, countries/regions, journals, citations, authors, and keywords in the field. RESULTS: A total of 553 articles and reviews that met the criteria were included in this study. There is an overall upward trend in the number of publications issued; in terms of countries/regions, the United States and the United Kingdom are the largest contributors; Patient Education and Counseling is the most productive journal (17); Physician communication and patient adherence to treatment: a meta-analysis is the most cited article (1637); the field has not yet to form a stable and obvious core team; the analysis of high-frequency keywords revealed four main research directions: the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the keyword burst analysis revealed several shifts in the research hotspots for risk management in the DPR, suggesting that chronic disease management, is a future research direction for the continued development of risk management in the DPR. CONCLUSIONS: The visualization analysis of risk management literature in the DPR using CiteSpace and VOSviewer software provides insights into the current research status and highlights future research directions.

Global disease burden attributed to unsafe sex in 204 countries and territories from 1990 to 2019: results from the Global Burden of Disease Study 2019.

Unsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97-13.52) per 100,000 people and 570.78 (95% UI: 510.24-658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62-9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82-533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90-3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52-119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08-0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51-25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40-44 age group for men and the 35-39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.

Organic Crosslinked Polymer-Derived N/O-Doped Porous Carbons for High-Performance Supercapacitor.

Supercapacitors, as a new type of green electrical energy storage device, are a potential solution to environmental problems created by economic development and the excessive use of fossil energy resources. In this work, nitrogen/oxygen (N/O)-doped porous carbon materials for high-performance supercapacitors are fabricated by calcining and activating an organic crosslinked polymer prepared using polyethylene glycol, hydroxypropyl methylcellulose, and 4,4-diphenylmethane diisocyanate. The porous carbon exhibits a large specific surface area (1589 m2·g-1) and high electrochemical performance, thanks to the network structure and rich N/O content in the organic crosslinked polymer. The optimized porous carbon material (COCLP-4.5), obtained by adjusting the raw material ratio of the organic crosslinked polymer, exhibits a high specific capacitance (522 F·g-1 at 0.5 A·g-1), good rate capability (319 F·g-1 at 20 A·g-1), and outstanding stability (83% retention after 5000 cycles) in a three-electrode system. Furthermore, an energy density of 18.04 Wh·kg-1 is obtained at a power density of 200.0 W·kg-1 in a two-electrode system. This study demonstrates that organic crosslinked polymer-derived porous carbon electrode materials have good energy storage potential.

Characterization of nitrogen-bridged 1,2,4,5-tetrazine-, furazan-, and 1H-tetrazole-based polyheterocyclic compounds: heats of formation, thermal stability, and detonation properties.

The heats of formation (HOFs), thermal stability, and detonation properties for a series of nitrogen-bridged 1,2,4,5-tetrazine-, furazan-, and 1H-tetrazole-based polyheterocyclic compounds (3,6-bis(1H-1,2,3,4-tetrazole-5-ylamino)-1,2,4,5- tetrazine (TST), 3,6-bis(furazan-5-ylamino)-1,2,4,5-tetrazine (FSF), 3,4-bis(1,2,4,5- tetrazine-3-ylamino)-furazan (SFS), 3,4-bis(1H-1,2,3,4-tetrazole-5-ylamino)-furazan (TFT), 1,5-bis(1,2,4,5-tetrazine-3-ylamino)-1H-1,2,3,4-tetrazole (STS), and 1,5-bis(furazan-3-ylamino)-1H-1,2,3,4-tetrazole (FTF) derivatives) were systematically studied by using density functional theory. The results show that the -N(3) or -NHNH(2) group plays a very important role in increasing the HOF values of the derivatives. Among these series, the SFS derivatives have lower energy gaps, while the TFT derivatives have higher ones. Incorporation of the -NH(2) group into the FSF, SFS, STS, or FTF ring is favorable for enhancing its thermal stability, whereas the substitution of the -NHNH(2) group could increase the thermal stability of the TST, SFS, STS, or FTF ring. The calculated detonation properties indicate that the -NO(2) or -NF(2) is very helpful for enhancing the detonation performance for these derivatives. Considering the detonation performance and thermal stability, six derivatives may be regarded as promising candidates of high-energy density materials (HEDMs). These results provide basic information for the molecular design of novel HEDMs.