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Traditionally, the surface charge number (SCN) of permanently charged soils/clay minerals is believed to be unaffected by environmental pH. However, recent studies have revealed the occurrence of polarization-induced covalent bonding between H+ and the surface O atoms of permanently charged clay minerals. This discovery challenges the traditional notions of "permanently charged soil" and "permanently charged clay mineral". The purpose of this study is to confirm that there are no true "permanently charged clay" or "permanently charged soil". In this study, the SCNs of two permanently charged clay minerals, two variably charged clay minerals, five permanently charged soils (temperate soils), and four variably charged soils (tropical or subtropical soils) were measured at different pH values using the universal determination method of SCN. The results showed that: (1) The SCNs of the permanently/variably charged soils and clay minerals decreased significantly with decreasing pH; (2) the SCN of montmorillonite decreased less with decreasing pH than the SCNs of variably charged minerals, whereas the SCN of illite decreased to nearly the same extent, indicating strong polarization-induced covalent bonding between H+ and the surface O atoms of illite; (3) the SCNs of permanently charged soils decreased to a similar extent as those of variably charged soils with decreasing pH. This study demonstrated that the concepts, "permanently charged clay mineral" or "permanently charged soil", are questionable because of the polarization-induced covalent bonding between H+ and the surface O atoms of clay minerals. [ABSTRACT FROM AUTHOR]

Music serves as a prevalent emotional regulation tool among young people. However, the correlational and causal relationships between music use, emotion regulation ability, and emotional symptoms remain unclear. This study aimed to investigate the associations and causal relationships between healthy and unhealthy music use, emotion regulation ability, and emotional symptoms, including alexithymia, depression, and anxiety. This study included 16,588 college students nationwide in China. All participants were assessed online with the Healthy‐Unhealthy Music Scale (HUMS), the Regulatory Emotional Self‐Efficacy Scale (RESE), the Toronto Alexithymia Scale (TAS‐20), and the 10‐item Kessler Psychological Stress Scale (K10) using a cluster convenience sampling method. We applied a regularized partial correlation network (RPCN) and Bayesian network to analyze the network characteristics of the outcomes. In the RPCN analysis, healthy music use showed the second strongest expected influence (one‐step) and correlated positively with emotion regulation self‐efficacy while inversely correlating with externally oriented thinking of alexithymia and depression. The Bayesian network indicated that healthy music use was located downstream of the network, positively predicted by managing anger‐irritation and expressing positive affect in emotion regulation self‐efficacy. In contrast, unhealthy music use in the RPCN displayed the strongest bridge strength and bridge expected influence (one‐step). It negatively correlated with expressing positive affect in emotion regulation self‐efficacy and positively correlated with alexithymia, anxiety, and depression. The Bayesian network highlighted that unhealthy music use was positively affected by anxiety, depression, and difficulty identifying feelings. In addition, managing despondency‐distress influences difficulty identifying feelings through depression, subsequently affecting unhealthy music use and, finally, influencing externally oriented thinking. This study provides a novel framework for understanding the role of emotion regulation self‐efficacy and alexithymia in the relationship between music use and emotional symptoms. Emotion regulation and mental health may benefit from music‐based interventions and therapies informed by the findings of this study. [ABSTRACT FROM AUTHOR]

Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The concurrent use of ritonavir, a potent CYP3A4 inhibitor, can lead to significant drug interactions. Using physiologically based pharmacokinetic (PBPK) modeling and simulation, this study examines the effects of different dosing regimens of ritonavir on the pharmacokinetics of these opioids. The findings reveal that co-administration of ritonavir significantly increases the exposure of fentanyl analogs, with over a 10-fold increase in the exposure of alfentanil and sufentanil when given with ritonavir. Conversely, the effect of ritonavir on fentanyl exposure is modest, likely due to additional metabolism pathways. Additionally, the study demonstrates that the steady-state exposure of hydrocodone and its active metabolite hydromorphone can be increased by up to 87% and 95%, respectively, with concurrent use of ritonavir. The extended-release formulation of hydrocodone is particularly affected. These insights from PBPK modeling provide valuable guidance for optimizing opioid dosing and minimizing the risk of toxicity when used in combination with ritonavir-containing prescriptions. [ABSTRACT FROM AUTHOR]

Women with substance use disorders (SUDs) are more inclined to use drugs and relapse for regulating emotions compared to men. This study aimed to explore the effects of group music and imagery in alleviating anxiety, depression, emotion regulation difficulties, and craving for women with methamphetamine use disorder (MUD) in a compulsory rehabilitation context. A total of 90 women with MUD were randomly assigned to the music therapy treatment arm (n = 45) or control treatment arm (n = 45). Participants in the music therapy treatment arm received 12 biweekly sessions of group music and imagery (GrpMI) and those in the control treatment arm received 6 weeks of usual care. Anxiety, depression, emotion regulation difficulties, and craving were assessed at pre-test and post-test. After the intervention, participants in the GrpMI group reported significantly greater improvements than those in the control group for state anxiety (F = 6.27; p =.02; Partial η2 =.13), trait anxiety (F = 4.49; p =.04; Partial η2 =.09), depression (F = 5.48; p =.02; Partial η2 =.11), and craving (F = 4.53; p =.04; Partial η2 =.09). There was no significant difference between groups in emotion regulation difficulties (F =.95, p =.34, Partial η2 =.09). GrpMI significantly decreased depression, anxiety, and craving for women with MUD. Emotion regulation ability may need a longer period of treatment for significant improvement. Future studies could add long-term follow-up and compare the effects of group music therapy in women versus men with SUDs. [ABSTRACT FROM AUTHOR]

This was a single‐center, randomized, open‐label, 2‐formulation, and 2‐cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40 mg) during each study period. Blood samples were collected before and up to 144 hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration‐time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%‐125% equivalence interval for both the fasting and fed tests. Ingesting high‐fat and high‐calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar. [ABSTRACT FROM AUTHOR]

Ecto-5-nucleotidase (CD73) is overexpressed in a variety of cancers and associated with the immunosuppressive tumor microenvironment, making it an attractive target for cancer immunotherapy. Herein, we designed and synthesized a series of novel (pyridazine-3-yl)pyrimidine-2,4(1 H ,3 H )-dione derivatives as CD73 inhibitors. These compounds exhibited remarkable inhibitory activity against CD73 in both enzymatic biochemical and cellular assays. Among them, compound 35j proved to be one of the most potent inhibitors and an uncompetitive inhibitor with no obvious cytotoxicity. This compound showed high metabolic stability in rat liver microsomes and favorable pharmacokinetic profiles in rats ( T 1/2 = 3.37 h, F = 50.24%). Importantly, orally administered 35j significantly inhibited tumor growth in the triple-negative breast cancer 4T1 mouse model (TGI = 73.6%, 50 mg/kg). Immunoassays suggested that 35j remarkably increased the infiltration of positive immune cells, thereby reinvigorating antitumor immunity. These results demonstrate that 35j is a potent CD73 inhibitor worthy of further development.

Background and Aims: In 2021, China implemented a policy to prevent adolescents from excessive online gaming, with the goal of encouraging healthier leisure activities., Methods: Three months after this policy was implemented, we conducted a study involving 430 Chinese adolescents who regularly played online games for over two hours daily before the policy. We collected their responses to the restriction, including their compliance with the policy, engagement in undesirable alternative behaviors (e.g., watching short videos), and engagement in desirable alternative behaviors (e.g., playing sports). We also collected data on individual factors, parental technology interference, and feelings of restriction to use as predictors for behaviors, including those related to violating the restriction or watching short videos., Results: A small percentage of heavy gamers violated the restriction by renting others' game accounts (3%) or using a family member's identity (14%), while 59% of the sample shifted to watching short videos. Heavy gamers who lived in rural areas, spent more time on online games prior to the policy, did not feel restricted from playing online games, and experienced parental technology interference were more likely to violate the restriction. Females or those lacking stable hobbies were more inclined to watch short videos., Conclusions: Although the policy restricted heavy gaming, it has also led to increased short video use. Policymakers could explore alternative approaches, such as developing infrastructure that supports outdoor leisure activities in rural areas, encouraging parents to model responsible technology use behaviors, and guiding adolescents to cultivate positive hobbies in their leisure time.