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Wuzhuyu decoction (WZYD) is a well-known classic traditional Chinese medicine prescription and has been widely used to treat headache, nausea, vomiting, insomnia, etc. However, little published information is available about its safety. Our aim was to investigate the acute and subacute oral toxicity of WZYD extract in rats following the technical guidelines from China's National Medical Products Administration (NMPA) for single and repeated doses toxicity studies of drugs. Acute oral toxicity was assessed in rats via oral administration of WZYD extract at 4 g/kg three times within a day followed by a 14-day observation period. To evaluate the subacute toxicity, rats were orally administered with WZYD extract at doses of 0, 0.44, 1.33, and 4 g/kg for 28 days. The items examined included clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and histopathology. After the rats were administered with 12 g/kg (3 × 4 g/kg) WZYD extract, no mortality and toxic effects were observed during the observation period. In the subacute toxicity study, WZYD extract did not cause any significant treatment-related abnormality in each examined item of rats, so the no observed adverse effect level (NOAEL) of WZYD extract for 28 days orally administered to rats is considered to be 4 g/kg, which is approximately 80-fold of its clinical proposed dosage. [ABSTRACT FROM AUTHOR]

Hypergolic ignition of H2O2 and MEA-NaBH4 by off-center collision of their droplets was experimentally studied, focusing on the characteristics and mechanism of droplet mixing, droplet heating and evaporation, and gas-phase ignition. The whole collision ignition process was divided into five stages, which were compared, respectively, with that of head-on collision. Under the condition of a slightly off-center collision (for cases where B < 0.35), H2O2 droplets penetrate MEA-NaBH4 droplets after the collision and coalesce with it, but the internal H2O2 drop inside the MEA-NaBH4 droplet does not form a stable sphere. Instead, it rotates and expands inside the mixed droplet. With B increasing to 0.59, the droplets no longer coalesce after collision but separate away, forming satellite droplets. In such cases, multi-ignition mode is observed. When B increases to a certain extent, specifically, 0.85, a grazing collision is observed such that no mass transfer exists during the interaction of droplets, which leads to ignition failure. A theoretical model quantifying droplet swelling rate was established to calculate the volume change of the droplet. It was found that the swelling can be attributed to the flash boiling of superheated internal H2O2 fluid. Meanwhile, the ignition delay time was found to linearly decrease with B at various Wes until the extent where the chemical reaction takes over control, leading to an almost constant time delay defined as RDT. Additionally, the regime of ignition modes corresponding to different droplet mixing features is summarized in the We-B parametric space. [ABSTRACT FROM AUTHOR]

Objective To investigate the allelic mutations of kdr and ace-1 in Anopheles gambiae s. l., providing a scientific basis for mosquito-borne disease prevention and control in the region. Methods Mosquitoes were collected from six villages in two malaria-prone areas, Est-mono (Ogou koulidé, Kepssi, Igbomedji) and Anié (Kolocopé, Bana, Afolé). All mosquitoes were used for DNA extraction, species identification, and genotyping of kdr and ace-1. Results An. coluzzii and An. gambiae, two closely related species within the An. gambiae complex, were identified across six collection sites, with An. gambiae being predominant, constituting approximately 96.53% of the samples. Among all mosquito samples detected, high-frequency mutations were observed at the kdr 1014 locus in the An. gambiae complex, with mutation frequencies reaching 100.0% in Ogou koulidé, Bana, and Afolé, 97.5% in Kepssi and Igbomedji, and 91.1% in Kolocopé district. The allelic frequency of 1014F ranged from 85.5% to 100%. Mutation frequency of An. coluzzii 1014 locus in all three regions was 100%, with an allelic frequency of 1014F ranging from 90% to 100%, indicating a high rate of homozygosity. The kdr 1575 mutation frequency in An. gambiae ranged from 6.6% to 24.3%, with the allelic frequency of 1575Y ranging from 3.2% to 12.2%, all detected mutations were heterozygous, and no mutations were detected at the 1575 locus in An. coluzzii. Mutations at the ace-1 G119 locus were also observed in the An. gambiae complex, with mutation frequencies in An. gambiae ranging from 8.8% to 15% and the allelic frequency of 119S from 4.4% to 7.5%. In An. coluzzii, mutation frequencies ranged from 0 to 20.0%, with an allelic frequency of 119S from 0 to 10%, and all detected 119S mutations were heterozygous. Conclusions The high frequencies of the Anopheles gambiae kdr mutation observed suggest that malaria mosquito vectors in Togo may have developed a high level of resistance to pyrethroid insecticides and possibly a moderate resistance to organophosphorus or carbamate insecticides. This indicates that local vector management authorities should prioritize insecticide resistance issues in future malaria vector control and resistance management planning, and conduct regular monitoring. [ABSTRACT FROM AUTHOR]

Artemisinin-hydroxychloroquine sulfate tablets (AH) are regarded as a relatively inexpensive and novel combination therapy for the treatment of various forms of malaria, particularly aminoquinoline drugs-resistant strains of Plasmodium falciparum. Our aim was to conduct acute and subacute oral toxicity studies in non-rodents to obtain more nonclinical data on the safety of AH. Acute toxicity evaluation was performed in beagle dogs at single doses of 230, 530, 790, 1180, 2660, and 5000 mg/kg. Beagle dogs at doses of 0, 56, 84, and 126 mg/kg were used to assess subacute toxicity for 14 days. The approximate lethal dose range for acute oral administration of AH in dogs is found to be 790–1180 mg/kg, and toxic symptoms prior to death include gait instability, limb weakness, mental fatigue, tachypnea, and convulsion. Repeated doses of AH in dogs caused vomiting, soft feces, decreased activity, anorexia, and splenic red pulp vacuolation. Of note, AH could reduce body weight gain and prolong the QTc interval of individual dogs. Therefore, the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of oral administration of AH for 14 days in dogs are determined to be 84 mg/kg and 126 mg/kg, respectively. [ABSTRACT FROM AUTHOR]