Characterization of chemical constituents and metabolites in rat plasma after oral administration of Ainsliaea fragrans Champ by using UHPLC-QTOF-MS/MS.

Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.

Rhein-chitosan in situ hydrogel promotes wound healing in diabetic mice.

Chronic inflammation and infection often lead to delayed healing in skin wounds of patients with diabetes, presenting a significant challenge in clinical wound repair. In an effort to tackle this issue, we explored the utilization of the natural compounds Rhein and chitosan in the creation of a crosslinked in situ gel. Developed as Rhein-chitosan in situ hydrogel (CS-Rh gel), this formulation has the ability to gel at body temperature, making it suitable for irregular wounds of varying shapes. Our experimental investigations have demonstrated its excellent biocompatibility, controlled release of Rhein, biodegradability, anti-inflammatory properties, antibacterial effect, as well as its ability to enhance keratinocyte proliferation and migration. Furthermore, in vivo studies have confirmed that CS-Rh gel can effectively mitigate tissue inflammation, promote collagen deposition, and significantly accelerate wound healing in diabetic mice within a short timeframe of two weeks. Consequently, this innovative approach holds promise as a viable therapeutic strategy for supporting the healing of diabetic wounds in a clinical setting.

Two New Compounds Based on Bi-Capped Keggin Polyoxoanions and Cu-Bpy Cations Contain Both CuII and CuI Complexes: Synthesis, Characterization and Properties.

Two inorganic-organic hybrid complexes based on bi-capped Keggin-type cluster, {([CuII(2,2'-bpy)2]2[PMoVI8VV2VIV2O40(VIVO)2])[CuI(2,2'-bpy)]}∙2H2O (1) and {[CuII(2,2'-bpy)2]2[SiMoVI8.5MoV2.5VIVO40(VIVO)2]}[CuI0.5(2,2'-bpy)(H2O)0.5] (2) (bpy = bipyridine), had been hydrothermally synthesized and structurally characterized by elemental analysis, FT-IR, TGA, PXRD and X-ray single-crystal diffraction analysis. Compound 1 consists of a novel 1-D chain structure constructed from [CuI(2,2'-bpy)]+ unit linking bi-supported POMs anion {[CuII(2,2'-bpy)2]2[PMoVI8VV2VIV2O40(VIVO)2]}-. Compound 2 is a bi-capped Keggin cluster bi-supported Cu-bpy complex. The main highlights of the two compounds are that Cu-bpy cations contain both CuI and CuII complexes. Furthermore, the fluorescence properties, the catalytic properties, and the photocatalytic performance of compounds 1 and 2 have been assessed, and the results show that both compounds are active for styrene epoxidation and degradation and adsorption of Methylene blue (MB), Rhodamine B (RhB) and mixed aqueous solutions.

Early Childhood Diet in Relation to Toddler Nighttime Sleep Duration Trajectories.

The objective of this study was to evaluate whether dietary habits at age 2 associate with sleep duration trajectories through age 5 in children from north and central Appalachia. A total of 559 children from the Center for Oral Health Research in Appalachia (COHRA) cohort 2 were followed via caregiver phone interviews up to six times between ages 2 and 5. Exposures included data from the year 2 interview: sleep habits, household and demographic characteristics, meal patterns and consumption frequencies of fruits, vegetables, water, juice, milk, and soda. Sleep duration trajectories were identified using group-based trajectory models from ages 2 to 5. Three distinct nightly sleep duration trajectories were identified: short, increasing duration (4.5% of the study population); steady, 9 h of sleep (37.3%); and longer, slightly decreasing sleep duration (58.2%). Using multinomial logistic models that accounted for confounders, children with consistent meal patterns (i.e., meals and snacks at same time every day) and with higher fruit and vegetable consumption were more likely to follow the longer duration sleep trajectory compared to the steady sleep trajectory. In contrast, children who drank milk more frequently at age 2 were less likely to be in the longer duration sleep trajectory than the steady sleep trajectory.

Cryptotanshinone Induces Necroptosis Through Ca2+ Release and ROS Production in vitro and in vivo.

BACKGROUND: Necroptosis is a type of programmed necrosis mediated by receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3), which is morphologically characterized by enlarged organelles, ruptured plasma membrane, and subsequent loss of intracellular contents. Cryptotanshinone (CPT), a diterpene quinone compound extracted from the root of Salvia miltiorrhiza Bunge, has been reported to have significant anticancer activities. However, the detailed mechanism of CPT has not been clearly illustrated. OBJECTIVE: The present study aimed to explore the cell death type and mechanisms of CPT-induced in non-small cell lung cancer (NSCLC) cells. METHODS: The cytotoxicity of CPT on A549 cells was assessed by MTS assay. Ca2+ release and reactive oxygen species (ROS) generation were detected by flow cytometry. The changes in mitochondrial membrane potential (MMP) were observed through JC-1 staining. The expressions of p- RIP1, p-RIP3, p-MLKL, and MAPKs pathway proteins were analyzed by western blotting analysis. The efficacy of CPT in vivo was evaluated by the Lewis lung carcinoma (LLC) xenograft mice model. Blood samples were collected for hematology analysis. ELISA investigated the effects of CPT on tumor necrosis factor α (TNF-α). Hematoxylin and eosin staining (HE) determined the tumor tissues. Proteins' expression of tumor tissues was quantified by western blotting. RESULTS: CPT inhibited the cell viability of A549 cells in a time- and concentration-dependent manner, which was reversed by Necrostatin-1 (Nec-1). In addition, CPT treatment increased the expression of p-RIP1, p-RIP3, p-MLKL, the release of Ca2+, ROS generation, and the MAPKs pathway activated in A549 cells. Moreover, animal experiment results showed that intraperitoneal injection of CPT (15 mg/kg and 30 mg/kg) significantly inhibited tumor growth in C57BL/6 mice without affecting the bodyweight and injuring the organs. CONCLUSION: Our findings suggested that CPT-induced necroptosis via RIP1/RIP3/MLKL signaling pathway both in vitro and in vivo, indicating that CPT may be a promising agent in the treatment of NSCLC.

Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis.

Pyroptosis, a type of programmed cell death (PCD), is characterized by cell swelling with bubbles, and the release of inflammatory cell cytokines. Cucurbitacin B (CuB), extracted from muskmelon pedicel, is a natural bioactive product that could effectively exert anti-tumor activities in lung cancer. However, the exact molecular mechanisms and the direct targets of CuB in non-small cell lung cancer (NSCLC) remain to be discovered. Here, we firstly found that CuB exerted an anti-tumor effect via pyroptosis in NSCLC cells and NSCLC mice models. Next, based on the molecular docking and cellular thermal shift assay (CETSA), we identified that CuB directly bound to Toll-like receptor 4 (TLR4) to activate the NLRP3 inflammasome, which further caused the separation of N- and C-terminals of Gasdermin D (GSDMD) to execute pyroptosis. Moreover, CuB enhanced the mitochondrial reactive oxygen species (ROS), mitochondrial membrane protein Tom20 accumulation, and cytosolic calcium (Ca2+) release, leading to pyroptosis in NSCLC cells. Silencing of TLR4 inhibited CuB-induced pyroptosis and decreased the level of ROS and Ca2+ in A549 cells. In vivo study showed that CuB treatment suppressed lung tumor growth in mice via pyroptosis without dose-dependent manner, and CuB at 0.75 mg/kg had a better anti-tumor effect compared to the Gefitinib group. Taken together, our findings revealed the mechanisms and targets of CuB triggering pyroptosis in NSCLC, thus supporting the notion of developing CuB as a promising therapeutic agent for NSCLC.

The ethyl acetate extraction of Pileostegia tomentella (ZLTE) exerts anti-cancer effects on H1299 cells via ROS-induced canonical apoptosis.

Lung cancer is the leading cause of cancer death and the most common malignant tumor, the long-term survival of which has stagnated in the past several decades. Pileostegia tomentella Hand. Mazz is a traditional Chinese medicine called "Zhongliuteng" (ZLT) in the pharmacopeia, which has been proved to possess a potent anti-tumor effect on various cancers. In this study, the effects of ZLT N-butanol extraction (ZLTN) and ZLT ethyl acetate extraction (ZLTE) on the viability of non-small cell lung cancer cell (NSCLC) lines H1299 and A549 were evaluated. Here, we firstly reported that ZLTE significantly inhibited H1299 cells growth without affecting the release of lactate dehydrogenase (LDH). In addition, ZLTE induced caspase-dependent apoptosis in a concentration-dependent manner and increased the expression cleaved-PARP and decreased pro-caspase-3, pro-caspase-7, pro-caspase-8, and pro-caspase-9. Moreover, ZLTE increased the level of cellular reactive oxygen species (ROS) in H1299 cells to lead to apoptosis, which was reversed by N-acetyl-cysteine (NAC). Taken together, our results revealed that ZLTE induced caspase-dependent apoptosis via ROS generation, suggesting that ZLTE is a promising herbal medicine for the treatment of NSCLC.

MXP(M = Co/Ni)@carbon core-shell nanoparticles embedded in 3D cross-linked graphene aerogel derived from seaweed biomass for hydrogen evolution reaction.

Low-cost electrocatalysts play an important role in the hydrogen evolution reaction (HER). Particularly, transition metal phosphides (TMPs) are widely applied in the development of HER electrocatalysts. To improve the poor electrochemical reaction kinetics of HER, we introduce a facile way to synthesize carbon core-shell materials containing cobalt phosphide nanoparticles embedded in different graphene aerogels (GAs) (CoP@C-NPs/GA-x (x = 5, 10 and 20)) using seaweed biomass as precursors. The synthesized CoP@C-NPs/GA-5 exhibits efficient catalytic activity with small overpotentials of 120 and 225 mV at current densities of 10 mA cm-2, along with the low Tafel slopes of 57 and 66 mV dec-1, for HER in acidic and alkaline electrolytes, respectively. Compared with carbon aerogel (CA) containing cobalt phosphide nanoparticles (CoP-NPs@CA), the stability of CoP@C-NPs/GA-5 coated with carbon-shells (∼0.8 nm) was significantly improved in acidic electrolytes. We also prepared carbon core-shell materials containing nickel phosphide nanoparticles embedded in GA (Ni2P@C-NPs/GA) to further expand this synthetic route. The graphene-Ni2P@C aerogel shows a similar morphology and better catalytic activity for HER in acidic and alkaline electrolytes. In this work, the robust three-dimensional (3D) GA matrix with abundant open pores and large surface area provides unblocked channels for electrolyte contact and electronic transfer and enables very close contact between the catalyst and electrolyte. The MxP@C core-shell structure prevents the inactivation of MxP NPs during HER processes, and the thin graphene oxide (GO) layers and 3D CA together build up a 3D conductive matrix, which not only adjusts the volume expansion of MxP NPs as well as preventing their aggregation, but also provides a 3D conductive pathway for rapid charge transfer processes. The present synthetic strategy for phosphides via in situ phosphorization with 3D GA can be extended to other novel high-performance catalysts. The simple synthesis and efficient catalytic activity of MXP@C-NPs/GA indicate good application prospects in HER.

Comparative study of modified/non-modified aluminum and silica aerogels for anionic dye adsorption performance.

Developing effective and low-cost adsorbents is of great significance for controlling water contamination. To eliminate anionic water contaminants, four modified/non-modified aluminum (AlHMD, AlOSSD) and silica (SiHMD, SiOSSD) aerogels have been successfully employed. The four as-prepared aerogels were applied as adsorbents for removal of an anionic dye (acid orange 7, AO) from aqueous solution. Compared to silica aerogels, aluminum aerogels showed efficient adsorption performance for anionic water contaminants. The AO maximum adsorption capacity of Al2O3 aerogel is twice as high as that of SiO2 aerogel. The maximum adsorption capacity of aerogels was in the following order: AlHMD > AlOSSD > SiHMD > SiOSSD. Adsorption kinetics and isotherms of AO dye on the four as-prepared aerogels have also been studied. The kinetic data fitted well with the pseudo first-order kinetics model and the adsorption isotherm could be described by the Langmuir model. Adsorption rate of AO dye was mainly governed by film diffusion and intra-particle diffusion. Based on the adsorption mechanism, this work provides an idea for the design of superior adsorbents for anionic water contaminants.