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The spread of drug-resistant Plasmodium strains is diminishing the effectiveness of current antimalarials, highlighting the importance of discovering new therapeutics with novel targets. A screen of the Jumpstarter library against P. falciparum identified W482 with a pyrimidine-2,4-diamine scaffold. Structure-activity relationships reveal the importance of the pyrimidine core and its endocyclic nitrogen, while alternative amines are tolerated in the 4-position. Bulky and hydrophobic carboxamides or substituted phenyl ureas display the most potent antiplasmodial activity. Resistance selection and whole genome sequencing reveal an amplification of the gene encoding the ABCI3 transporter protein W482-resistant parasites. W482 is found to exhibit greater activity against parasites with reduced expression of ABCI3, confirming that resistance is related to the transporter. W482 arrests asexual parasites at the ring to trophozoite transition stage and exhibits a fast-killing profile with a lag phase of 24 h. Improving the antiparasitic activity alongside metabolic stability and solubility remains a challenge in the future development of the pyrimidine-2,4-diamine class.

Electrocatalytic CO₂ reduction (ECO₂R) to high-value chemicals is a promising method to upcycle emitted CO₂, but it is also a fascinating scientific challenge. Catalyst materials, as well as cell configurations, play a pivotal role in the efficacy and efficiency of the ECO₂R reaction, which also dictates reaction pathways and product selectivity. In this work, we employ the isotopological Zr- and Ce-based UiO-67 metal-organic frameworks (MOFs) that contain Pd species in a zero-gap gas diffusion cathode electrode configuration, where the water content, i.e., relative humidity (RH) level, in the CO₂ gas stream can be varied. We show that only UiO-67-based MOFs containing Pd embedded in their pores can produce syngas, while the product selectivity can be controlled by varying the RH levels in the gas stream. The pristine MOFs (precatalysts) undergo chemical and structural transformation during the ECO₂R reaction, forming the active catalysts toward CO₂ electroreduction to syngas. Our work highlights the effect of water content on the selectivity during ECO₂R, but also the need for predictive catalyst design for effective electroreduction of CO₂ to high-value chemicals.

Current intravesical therapies for bladder cancer after resection are limited by poor tissue penetration, off-target effects, and insufficient efficacy. To address these challenges, this study designs a thermo-responsive hydrogel (PNH) that encapsulates chitosan (CS)-coated Fe/Mn bimetallic nanozymes (FMCC) together with cholesterol oxidase (ChOx). FMCC displays multiple enzyme-mimicking activities, including peroxidase (POD), catalase (CAT), and glutathione oxidase (GSHox). ChOx amplifies this catalytic cascade, enhancing reactive oxygen species (ROS) production and inducing ferroptosis-mediated tumor cell death. The CS coating improves mucosal adhesion and tissue permeability, thereby facilitating intravesical delivery. Upon near-infrared (NIR) irradiation, FMCC generates heat that liquefies the hydrogel, enabling spatiotemporally controlled drug release and providing mild photothermal therapy (MPTT). This photothermal effect acts synergistically with ferroptosis induction and immune modulation, concurrently minimizing damage to normal tissues. In parallel, ChOx disrupts cholesterol-rich membrane rafts and promotes pro-inflammatory M1 macrophage polarization. Released Mn²⁺ ions further potentiate immune activation by stimulating the cGAS-STING pathway, driving IFN-β and IL-6 secretion, dendritic cell maturation, and T cell infiltration. Together, this nanozyme-hydrogel system integrates tissue penetration, metabolic disruption, and immune stimulation, representing a promising strategy for localized bladder cancer therapy.

Porcine epidemic diarrhea virus (PEDV) causes acute, highly contagious enteric disease in pigs, leading to severe economic losses, particularly due to high mortality in suckling piglets. Currently, no specific antiviral drugs are available. In this study, we evaluated the anti-PEDV potential of celastrol, a natural triterpenoid derived from Tripterygium wilfordii, in Vero E6 cells. We found that celastrol significantly inhibited PEDV replication in a dose-dependent manner, primarily targeting the postentry stage of the viral life cycle. Network pharmacology analysis highlighted apoptosis as a key signaling pathway, and mechanistic studies revealed that celastrol enhanced PEDV-induced reactive oxygen species (ROS) accumulation, which triggered apoptosis and suppressed viral RNA synthesis, protein expression, and progeny production. Importantly, inhibition of ROS abolished celastrol’s antiviral activity, confirming a ROS-dependent mechanism. Furthermore, celastrol demonstrated inhibitory effects against porcine deltacoronavirus (PDCoV) and porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. These findings suggest celastrol as a promising candidate for the prevention and control of PED and other swine viral infections.

We report the misuse of a novel synthetic glucocorticoid, 9α-fluoro-6α-methylprednisolone (9F6MP) for the first time in camel racing and, to the best of our knowledge, human or other animal sports. During routine post-race drug testing of cameline plasma samples using liquid chromatography-tandem mass spectrometry we encountered an unknown peak with the same selected reaction monitoring traces as a dexamethasone formate adduct but at a different retention time. The product ion mass spectrum of the unknown peak in negative ion mode was identical to dexamethasone. However, significant differences were observed in positive ion mode. Based on mass spectral analysis, we postulated the unknown peak to be a 6-methyl-16-nor isomer of dexamethasone. Following the procurement of a commercial 9F6MP reference material, the unknown peak was successfully identified as this substance. Interestingly, previous research predicted a high potential for glucocorticoid and anti-inflammatory activity for 9F6MP. However, the therapeutic use of 9F6MP in camels has not been approved by any authorities, and any toxicities and side-effects potentially caused by 9F6MP have not been thoroughly evaluated. Therefore, the misuse of 9F6MP should be strictly controlled for the sake of animal welfare and the integrity of camel racing. The information described in this case report will be beneficial for other anti-doping laboratories in both human and animal sports for the purpose of doping control.

Photocatalytic overall water splitting (POWS), as a promising technology for large-scale solar hydrogen production, has propelled the development of advanced photocatalysts. Z-scheme heterojunctions are believed to be ideal candidates for efficient POWS due to the reconcilable benefits of broad solar spectrum absorption and sufficient redox potentials. POWS by Z-scheme heterojunctions involves multiple-step charge transfer processes happening at the interfaces, thereby making interfacial manipulation crucial to improving the photocatalytic performance. This review delves into the intricate details of interfacial manipulation in Z-scheme heterojunctions with an emphasis on the semiconductor-semiconductor interfaces and the semiconductor-water interfaces. First, the basic charge transfer processes are explored at the interfaces, and then summarize and explore the effective manipulation strategies to promote the interfacial charge transfer processes for enhanced POWS performance. Further, the advanced characterization techniques are introduced for understanding these interfacial processes. Finally, the current challenges and future directions are provided for the development of efficient Z-scheme heterojunctions for POWS.

In this study, we assess the feasibility of wastewater sampling from manholes as a potential monitoring tool for performance and image-enhancing drugs (PIEDs) at local gyms and general sports centers in Denmark. Wastewater samples from two gyms and two sports centers were analyzed using two LC-MS-based analytical methods (UPLC-MS/MS and UPLC-TOF-MS) to detect the presence of PIEDs. Samples were collected at 3-h intervals during the opening hours on three selected days of the week for each location. The study showed the presence of anabolic agents such as oxandrolone, stanozolol, and ostarine in wastewater sampled from the gyms. All three compounds are class C drugs in the United States, and likewise, illegal to sell and possess in Denmark. Other PIEDs, such as aromatase inhibitors and psychoactive drugs, were detected in several samples from both gyms and sports centers. However, gyms showed a higher occurrence of PIEDs, whereas general sports centers showed a lower occurrence. Although it cannot be used as a traditional prevalence measure, wastewater sampling from manholes is a useful tool for studying the occurrence of PIEDs among recreational athletes at specific locations or events. Wastewater analysis may be used as an easy and cost-effective tool to complement both preventive and control measures, such as information campaigns, surveys, or personal testing. However, not all locations are suitable for manhole sampling, and it is necessary to consider the legal, ethical, and practical aspects before using wastewater analysis to monitor communities or specific populations.

Methyldienolone, a synthetic anabolic androgenic steroid (AAS), has been banned in sports by the World Anti-Doping Agency (WADA) because of its performance-enhancing properties. This study aimed to investigate the main metabolites using in vitro incubation with human liver microsomes (HLM) and to detect them through liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for doping control purposes. A total of six groups of Phase I metabolites, including 17-epimerization, hydroxylation, C3-keto reduction, 18-nor modifications, reduction, and demethylation, as well as five different Phase II metabolites, such as glucuronide conjugates, were characterized, indicating extensive metabolism by HLM. Structural characterization of these metabolites was improved through derivatization with methoxylamine and hydroxylamine, which enabled their detection with higher sensitivity by LC-HRMS. These novel metabolites provide new insights into the metabolism of methyldienolone and may contribute to antidoping analysis. The synthesis of reference materials is necessary to confirm the structure of the proposed metabolites in the future.