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2.
Autism ; : 13623613241286683, 2024 Oct 05.
Article de Anglais | MEDLINE | ID: mdl-39367736

RÉSUMÉ

LAY ABSTRACT: Parenting can be challenging for any parent, particularly for those parenting autistic children. Research has shown that being kind, accepting, and mindful toward oneself during suffering, a concept known as self-compassion, can help enhance mental health. However, it is not fully understood how self-compassion benefits parenting experiences for parents of autistic children. Therefore, we conducted a study involving 178 parents of autistic children and 178 of autistic children to explore the associations between self-compassion, mental health, and parenting experiences. We found that parents of autistic children reported less self-compassion compared to parents of non-autistic children. For both groups of parents, self-compassion was linked to lower levels of ill-being and parenting stress, as well as higher levels of well-being and parenting competence. In parents of non-autistic children, both ill-being and well-being played a mediating role in the relationship between self-compassion and parenting experiences. However, in parents of autistic children, only well-being was found to mediate this relationship. These findings emphasize the importance of self-compassion and well-being in improving parenting experiences for parents of autistic children.

3.
Ecol Evol ; 14(10): e70380, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39355107

RÉSUMÉ

While floral signaling plays a central role in the reproductive success of all animal-pollinated plants, it may also attract herbivores eager to feed on flowers. False nectaries with glossy surfaces reflecting incident light may produce signals that attract floral visitors guiding their movements to and within the flower. Whether false nectaries also attract herbivores that lower the reproductive success of natural populations requires attention. In this study, we focus on Parnassia wightiana, a subalpine species with a whorl of staminodes that act as false nectaries attracting bees, flies, and herbivorous beetles. We tested the functions of staminodes using controlled manipulative experiments under field and lab conditions. We found a significant decrease in pollinator visits, and subsequent seed set, in flowers in which we removed staminodes or staminode apices confirming the function of these organs. In our natural populations, we found that a beetle, Nonarthra variabilis (Alticinae; Chrysomelidae), chews first on staminode apices, then it eats the entire staminodes and other flower parts, but rarely feeds on ovaries. Additional experiments suggested these beetles preferred staminodes to ovaries. Our results suggest this is a case of selective florivory, in which staminodes play a dual role, attracting pollinators and herbivores at the same time causing the attractive dilemma. Although selective florivory by beetles did not directly damage fruits, it influenced plant-pollinator interactions, decreasing reproductive success in plant populations. Our study highlights the importance of plant-pollinator-herbivore interactions in selecting floral traits.

4.
Int J Mol Sci ; 25(17)2024 Aug 31.
Article de Anglais | MEDLINE | ID: mdl-39273427

RÉSUMÉ

Stenotaphrum secundatum is an excellent shade-tolerant warm-season turfgrass. Its poor cold resistance severely limits its promotion and application in temperate regions. Mining cold resistance genes is highly important for the cultivation of cold-resistant Stenotaphrum secundatum. Although there have been many reports on the role of the Shaker potassium channel family under abiotic stress, such as drought and salt stress, there is still a lack of research on their role in cold resistance. In this study, the transcriptome database of Stenotaphrum secundatum was aligned with the whole genome of Setaria italica, and eight members of the Shaker potassium channel family in Stenotaphrum secundatum were identified and named SsKAT1.1, SsKAT1.2, SsKAT2.1, SsKAT2.2, SsAKT1.1, SsAKT2.1, SsAKT2.2, and SsKOR1. The KAT3-like gene, KOR2 homologous gene, and part of the AKT-type weakly inwardly rectifying channel have not been identified in the Stenotaphrum secundatum transcriptome database. A bioinformatics analysis revealed that the potassium channels of Stenotaphrum secundatum are highly conserved in terms of protein structure but have more homologous members in the same group than those of other species. Among the three species of Oryza sativa, Arabidopsis thaliana, and Setaria italica, the potassium channel of Stenotaphrum secundatum is more closely related to the potassium channel of Setaria italica, which is consistent with the taxonomic results of these species belonging to Paniceae. Subcellular location experiments demonstrate that SsKAT1.1 is a plasma membrane protein. The expression of SsKAT1.1 reversed the growth defect of the potassium absorption-deficient yeast strain R5421 under a low potassium supply, indicating that SsKAT1.1 is a functional potassium channel. The transformation of SsKAT1.1 into the cold-sensitive yeast strain INVSC1 increased the cold resistance of the yeast, indicating that SsKAT1.1 confers cold resistance. The transformation of SsKAT1.1 into the salt-sensitive yeast strain G19 increased the resistance of yeast to salt, indicating that SsKAT1.1 is involved in salt tolerance. These results suggest that the manipulation of SsKAT1.1 will improve the cold and salt stress resistance of Stenotaphrum secundatum.


Sujet(s)
Canaux potassiques de la superfamille Shaker , Canaux potassiques de la superfamille Shaker/métabolisme , Canaux potassiques de la superfamille Shaker/génétique , Régulation de l'expression des gènes végétaux , Protéines végétales/génétique , Protéines végétales/métabolisme , Poaceae/génétique , Poaceae/métabolisme , Basse température , Phylogenèse , Transcriptome , Arabidopsis/génétique , Arabidopsis/métabolisme , Famille multigénique
5.
ACS Appl Mater Interfaces ; 16(39): 53252-53260, 2024 Oct 02.
Article de Anglais | MEDLINE | ID: mdl-39298517

RÉSUMÉ

Fog collection is a promising solution for mitigating the urgent water shortage around the world. Despite the delicate design of various bionic fog harvesting surfaces with prowess to enable fast fog capture and programmed water transport, achieving sustainable and efficient fog collection by regulating the macroscale surface refreshment efficacy remains rarely concerned yet is effective. Here, we proposed a bioinspired structural design to achieve significant improvement on the surface refreshment efficacy to 46.47%, nearly 5 times larger than that of conventional design. Specifically, we constructed superhydrophilic vein-like microchannels on a superhydrophobic brass surface by using laser texture technology and hydrothermal treatment. Our microchannel design acts as a "highway" for synergically transporting and converging the collected fog droplets, as well as rapidly refreshing large surface area for the subsequent fog collection, reminiscent of the leaf veins responsible for the persistent mass transport between plant tissues. The practical implementation also convinced our design of a maximum water collection efficiency of up to 506.67 mg cm-2 h-1 and a long-term performance stability within a 10 h test. Our design is generic to most of the fog harvesting materials, showing great application potential for efficient atmospheric fog collection.

6.
ACS Appl Mater Interfaces ; 16(40): 54272-54281, 2024 Oct 09.
Article de Anglais | MEDLINE | ID: mdl-39329282

RÉSUMÉ

The inverted perovskite solar cells (PSCs) are gaining increasing attention recently for their unprecedented advantages, such as better integration with tandem and flexible designs, negligible hysteresis, good operational stability, and compatibility with commercially scalable fabrication approaches. Nickel oxide (NiOx) films prepared by magnetron sputtering technology exhibit excellent scalability and reproducibility, which could well meet the requirements of the large-scale production of inverted PSCs. However, NiOx prepared by vacuum methods generally has fewer surface hydroxyl groups, deteriorating the wettability and damaging the interface contact with the perovskite. Particularly, the Ni3+ defects on the NiOx surface could lead to unfavorable redox reactions with organic cations in the perovskite under high temperatures, promoting the rapid degradation of the perovskite. Thus, surface regulation of sputtered NiOx is imperative for high-performance PSCs. Herein, 4-(trifluoromethyl) phenylcarbamate hydrochloride (TFFA) was used to regulate the surface properties of sputtered NiOx. The strongly electronegative F ions in TFFA passivated the Ni3+ defects on the NiOx surface, suppressed unfavorable interface reactions, and improved charge recombination. The polar ammonium functional group was used to adjust the surface energy of NiOx, thereby improving the wettability and optimizing the crystallization kinetics of the perovskite. As a result, the power conversion efficiency (PCE) of PSCs reached 22.76%, which was among the highest PCEs reported for sputtered NiOx-based inverted PSCs to date. Moreover, the unencapsulated target devices exhibited better stability, maintaining over 85% of the initial PCE after aging for approximately 1200 h in a N2 environment. Our achievements pointed out a practical strategy for enhancing the performance of sputtered NiOx-based inverted PSCs, which could potentially accelerate the development and application of large-area PSCs.

7.
ACS Appl Mater Interfaces ; 16(40): 54456-54466, 2024 Oct 09.
Article de Anglais | MEDLINE | ID: mdl-39344047

RÉSUMÉ

Recent studies have revealed that the integration of metal nanoparticles (NPs) with photocatalysts allows the metal NPs to serve as cocatalysts, significantly enhancing reactant efficiency near nanostructures through the surface plasmon resonance (SPR) effect. On this basis, we synthesized highly reactive FePt quantum dots (FePt QDs) with tailored configurations, manipulating the Pt coordination environment and combining FePt QDs with ultrathin two-dimensional nickel metal-organic layer (Ni-MOL) nanosheets. X-ray absorption fine spectroscopy (XAFS) confirmed the distinctive Pt-Fe configuration after photoactivation. The optimized loading amount of FePt QDs led to a hydrogen evolution reaction (HER) yield of 113 mmol·g-1·h-1 after activation, with the catalyst remaining stable over five cycles. The improved reaction efficiency stemmed from Pt coordination adjustments and a localized SPR effect, supported by ultraviolet-visible (UV-vis), infrared (IR), Raman, and XAFS characterizations. A comparative analysis was conducted with Ni-MOL deposited with platinum NPs, further underscoring the distinct advantages of FePt QDs and corroborating by density functional theory (DFT) calculations, which revealed favorable d-band center properties. These findings offer a promising avenue for the development of highly efficient and stable nanoalloy photocatalysts.

8.
Adv Sci (Weinh) ; : e2403219, 2024 Sep 23.
Article de Anglais | MEDLINE | ID: mdl-39308241

RÉSUMÉ

The continuous imbalance of the diabetic wound microenvironment is an important cause of chronic nonhealing, which manifests as a vicious cycle between excessive accumulation of reactive oxygen species (ROS) and abnormal healing. Regulating the microenvironment by suppressing wound inflammation, oxidative stress, and bacterial infection is a key challenge in treating diabetic wounds. In this study, ROS-responsive hydrogels are developed composed of silk fibroin methacrylated (SFMA), modified collagen type III (rCol3MA), and lipid nanoparticles (LNPs). The newly designed hydrogel system demonstrated stable physicochemical properties and excellent biocompatibility. Moreover, the release of antimicrobial peptide (AMP) and puerarin (PUE) demonstrated remarkable efficacy in eradicating bacteria, regulating inflammatory responses, and modulating vascular functions. This multifunctional hydrogel is a simple and efficient approach for the treatment of chronic diabetic infected wounds and holds tremendous potential for future clinical applications.

9.
Front Microbiol ; 15: 1448539, 2024.
Article de Anglais | MEDLINE | ID: mdl-39323878

RÉSUMÉ

Selenium (Se) is a vital trace element integral to numerous biological processes in both plants and animals, with significant impacts on soil health and ecosystem stability. This review explores how soil microorganisms facilitate Se transformations through reduction, oxidation, methylation, and demethylation processes, thereby influencing the bioavailability and ecological functions of Se. The microbial reduction of Se compounds, particularly the conversion of selenate and selenite to elemental Se nanoparticles (SeNPs), enhances Se assimilation by plants and impacts soil productivity. Key microbial taxa, including bacteria such as Pseudomonas and Bacillus, exhibit diverse mechanisms for Se reduction and play a substantial role in the global Se cycle. Understanding these microbial processes is essential for advancing soil management practices and improving ecosystem health. This review underscores the intricate interactions between Se and soil microorganisms, emphasizing their significance in maintaining ecological balance and promoting sustainable agricultural practices.

10.
ACS Omega ; 9(34): 36341-36352, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39220523

RÉSUMÉ

Petroleum can be generated by thermal cracking of organic matter within sediments, and the organic matter within sediments plays the dominant role in determining oil and gas generation. Organic matter within sediments is characterized by various sources, such as sapropelic organic matter from algal, microbial, and planktonic organisms and humic organic matter from higher plants. Paleo-productivity, terrestrial influx, and depositional environments could obviously influence the enrichment processes of the organic matter within sediments. Organic and elemental geochemical proxies can investigate the sedimentary process and reflect the enrichment characteristics of organic matter. In this study, hydrocarbon source rocks from the Shuixigou Group were collected from the Taibei Sag of the Turpan-Hami Basin, rock-eval pyrolysis was conducted, and stable carbon isotope composition of organic carbon and major and trace element distributions were measured. Based on this, the type and maturation of organic matter, paleo-productivity, terrestrial influx, and depositional paleo-environments were investigated. The results show that the Jurassic hydrocarbon source rocks are characterized by type III kerogen and are in the oil-window stage of maturation. The depositional paleo-environments of hydrocarbon source rocks in different formations are not remarkably different. The water bodies have freshwater oxidizing environments, and the paleo-climatic characteristics are warm and humid. However, the paleo-productivity of samples from the lower Jurassic Sangonghe Formation is higher than samples from other formations. Overall, the organic matter enrichment in Jurassic hydrocarbon source rocks of the Turpan-Hami Basin could be mutually controlled by the paleo-productivity and depositional paleo-environments. The results of this study could provide theoretical insight into deep petroleum exploration and resource evaluation in the Turpan-Hami Basin.

11.
Macromol Rapid Commun ; : e2400553, 2024 Sep 03.
Article de Anglais | MEDLINE | ID: mdl-39225663

RÉSUMÉ

Durable functionalization on polypropylene (PP) surfaces is always a key problem to besolved. Coatings with low surface energy peel off easily especially under extreme conditions, owing to their weak adhesion. In this paper, side groups of both polyhedral oligomeric silsesquioxane (POSS) and alkane are grafted to polypentafluorophenyl methacrylate (PFP), and then PP blends with these side-group modified PFP are obtained through a melt-blending process. It is found that POSS can result in surface segregation and provide hydrophobicity in blends. Microfibers are formed because of the orientation effect during the tensile testing, which furtherly promotes mechanical strength. Significantly, alkaneside-groups can be entangled with PP segments, which brings about cross linking. Therefore, with crosslinking and synchronous orientation of POSS, the elongation at the break of blends is greatly increased up to 974%. The final blend demonstrates quite durable hydrophobicity under many extreme conditions, such as repeated tape peeling, ultrasonic washing, strong friction, and soaking in strong acid (pH = 1), strong alkali (pH = 14) and alcohol. The heat and UV resistance of the blend are also obviously improved. This study will develop anovel and facile strategy to endow PP with durable hydrophobicity as well as greatly enhanced mechanical properties.

12.
Hum Genomics ; 18(1): 104, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39289776

RÉSUMÉ

BACKGROUND: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. OBJECTIVES: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. RESULTS: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. CONCLUSIONS: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.


Sujet(s)
Allèles , Génétique des populations , Sélection génétique , Humains , Adaptation biologique/génétique , Chine , Peuples d'Asie de l'Est/génétique , Ethnies/génétique , Variation génétique , Haplotypes , Polymorphisme de nucléotide simple
13.
ChemSusChem ; : e202401454, 2024 Sep 20.
Article de Anglais | MEDLINE | ID: mdl-39302821

RÉSUMÉ

Two-dimensional (2D) conjugated metal-organic frameworks (c-MOFs) are promising materials for supercapacitor (SC) electrodes due to their high electrochemically accessible surface area coupled with superior electrical conductivity compared to traditional MOFs. Here, porous and non-porous HHB-Cu (HHB=hexahydroxybenzene), derived through surfactant-assisted synthesis, are studied as representative 2D c-MOF models, showing different reversible redox reactions with Na+ and Li+ in aqueous and organic electrolytes, respectively. We deployed these redox activities to design negative electrodes for hybrid SCs (HSCs), combining the battery-like property of HHB-Cu as negative electrode and the high capacitance and robust cyclic stability of activated carbon (AC) as positive electrode. In organic electrolyte, porous HHB-Cu-based HSC achieves a maximum cell specific capacity (Cs) of 22.1 mAhg-1 at 0.1 Ag-1, specific energy (Es) of 15.55 Whkg-1 at specific power (Ps) of 70.49 Wkg-1, and 77% cyclic stability after 3000 gravimetric charge-discharge (GCD) cycles at 1 Ag-1 (calculated on the mass of both electrode materials). In the aqueous electrolyte, porous HHB-Cu-based HSC displays a Cs of 13.9 mAhg-1 at 0.1 Ag-1, Es of 6.13 Whkg-1 at 44.05 Wkg-1, and 72.3% Cs retention after 3000 GCD cycles. The non-porous sample shows lower Es performance but better rate capability compared to the porous one.

14.
Curr Microbiol ; 81(10): 336, 2024 Sep 02.
Article de Anglais | MEDLINE | ID: mdl-39223428

RÉSUMÉ

Fatty acids (FAs) participate in extensive physiological activities such as energy metabolism, transcriptional control, and cell signaling. In bacteria, FAs are degraded and utilized through various metabolic pathways, including ß-oxidation. Over the past ten years, significant progress has been made in studying FA oxidation in bacteria, particularly in E. coli, where the processes and roles of FA ß-oxidation have been comprehensively elucidated. Here, we provide an update on the new research achievements in FAs ß-oxidation in bacteria. Using Xanthomonas as an example, we introduce the oxidation process and regulation mechanism of the DSF-family quorum sensing signal. Based on current findings, we propose the specific enzymes required for ß-oxidation of several specific FAs. Finally, we discuss the future outlook on scientific issues that remain to be addressed. This paper supplies theoretical guidance for further study of the FA ß-oxidation pathway with particular emphasis on its connection to the pathogenicity mechanisms of bacteria.


Sujet(s)
Acides gras , Oxydoréduction , Détection du quorum , Transduction du signal , Xanthomonas , Acides gras/métabolisme , Xanthomonas/métabolisme , Xanthomonas/pathogénicité , Xanthomonas/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/génétique , Virulence , Régulation de l'expression des gènes bactériens , Voies et réseaux métaboliques/génétique
15.
Front Immunol ; 15: 1441863, 2024.
Article de Anglais | MEDLINE | ID: mdl-39229266

RÉSUMÉ

This perspective article delves into a novel integration of Yin-Yang theory-an ancient Chinese philosophical cornerstone-with the sophisticated realm of immunology. Given the intricate concepts inherent in immunology, many students find it challenging to comprehend the delicate mechanisms governing immune equilibrium and regulation. Given the deep-rooted understanding of Yin-Yang theory among Chinese students, we advocate for an educational strategy that contextualizes the concept of immune equilibrium within the framework of Yin-Yang, thereby offering a more intuitive and engaging learning experience. This method not only capitalizes on the cultural significance of Yin-Yang, but also corresponds to its principles of equilibrium and harmony, thus mirroring the homeostatic essence of immune responses. This article critically assesses this technique's capacity to bolster immune comprehension amongst Chinese students, while also considering its limitations. Despite these limitations, the fusion of these seemingly divergent fields holds substantial promise for augmenting immunology education, promoting critical thinking, and advancing cross-cultural academic discourse. The amalgamation of age-old philosophical insights with modern scientific exploration prompts a reassessment of educational methodologies within immunology, underscoring a novel pedagogical approach that bridges traditional wisdom with contemporary scientific education.


Sujet(s)
Allergie et immunologie , Yin-yang , Allergie et immunologie/enseignement et éducation , Allergie et immunologie/histoire , Humains , Enseignement , Chine
16.
Article de Anglais | MEDLINE | ID: mdl-39231057

RÉSUMÉ

Knowledge distillation (KD) has shown great potential for transferring knowledge from a complex teacher model to a simple student model in which the heavy learning task can be accomplished efficiently and without losing too much prediction accuracy. Recently, many attempts have been made by applying the KD mechanism to graph representation learning models such as graph neural networks (GNNs) to accelerate the model's inference speed via student models. However, many existing KD-based GNNs utilize multilayer perceptron (MLP) as a universal approximator in the student model to imitate the teacher model's process without considering the graph knowledge from the teacher model. In this work, we provide a KD-based framework on multiscaled GNNs, known as graph framelet, and prove that by adequately utilizing the graph knowledge in a multiscaled manner provided by graph framelet decomposition, the student model is capable of adapting both homophilic and heterophilic graphs and has the potential of alleviating the oversquashing issue with a simple yet effective graph surgery. Furthermore, we show how the graph knowledge supplied by the teacher is learned and digested by the student model via both algebra and geometry. Comprehensive experiments show that our proposed model can generate learning accuracy identical to or even surpass the teacher model while maintaining the high speed of inference.

17.
Article de Anglais | MEDLINE | ID: mdl-39255181

RÉSUMÉ

We introduce HiSC4D, a novel Human-centered interaction and 4D Scene Capture method, aimed at accurately and efficiently creating a dynamic digital world, containing large-scale indoor-outdoor scenes, diverse human motions, rich human-human interactions, and human-environment interactions. By utilizing body-mounted IMUs and a head-mounted LiDAR, HiSC4D can capture egocentric human motions in unconstrained space without the need for external devices and pre-built maps. This affords great flexibility and accessibility for human-centered interaction and 4D scene capturing in various environments. Taking into account that IMUs can capture human spatially unrestricted poses but are prone to drifting for long-period using, and while LiDAR is stable for global localization but rough for local positions and orientations, HiSC4D employs a joint optimization method, harmonizing all sensors and utilizing environment cues, yielding promising results for long-term capture in large scenes. To promote research of egocentric human interaction in large scenes and facilitate downstream tasks, we also present a dataset, containing 8 sequences in 4 large scenes (200 to 5,000 m2 ), providing 36k frames of accurate 4D human motions with SMPL annotations and dynamic scenes, 31k frames of cropped human point clouds, and scene mesh of the environment. A variety of scenarios, such as the basketball gym and commercial street, alongside challenging human motions, such as daily greeting, one-on-one basketball playing, and tour guiding, demonstrate the effectiveness and the generalization ability of HiSC4D. The dataset and code will be publicly available for research purposes.

18.
J Forensic Sci ; 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39233350

RÉSUMÉ

Diester diterpenoid alkaloids (DDAs) are the main active ingredients of herbaceous perennial plants Aconitum. DDAs possess cardiotoxic and neurotoxic properties. Although most deaths caused by DDA poisoning are accidental, a few instances of suicide and homicide have been reported. Presented is a case of an acute aconitine (AC) poisoning following the ingestion of approximately 50 mL of homemade medicinal liquor. We described the clinical manifestations after poisoning and detailed postmortem changes, and detected the concentrations of AC and hypaconitine (HA) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The decedent experienced a burning sensation in the gastrointestinal tract after poisoning, followed by flushing and paralysis of the face and limbs, and severe cardiac arrhythmia. An autopsy revealed cyanosis of the lips and nail beds; conjunctival hemorrhage in both eyes; pulmonary edema; tissue hemorrhage and congestion in multiple organs; and inflammatory cell infiltration in the stomach, duodenum, pancreas, and cardiac muscle. The concentrations of AC and HA were as follows: cardiac blood, 38.4 ng/mL and 7.1 ng/mL; pericardial fluid, 7.3 ng/mL and 41 ng/mL; urine, 28.1 ng/mL and 574 ng/mL; bile, 38.5 ng/mL and 108 ng/mL; gastric contents, 0.06 mg and 0.56 mg; liver tissue, 10.7 ng/g and 109.6 ng/g; and medicinal liquor, 0.568 mg/mL and 0.664 mg/mL, respectively. The clinical manifestations, anatomy findings, and quantitative data on the concentrations of AC and HA in body fluids and tissues will aid forensic investigations of deaths caused by acute AC poisoning.

19.
J Med Chem ; 67(17): 14820-14839, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39140772

RÉSUMÉ

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.


Sujet(s)
Conception de médicament , Récepteur du peptide-1 similaire au glucagon , Récepteur du peptide-1 similaire au glucagon/agonistes , Récepteur du peptide-1 similaire au glucagon/métabolisme , Animaux , Humains , Souris , Relation structure-activité , Mâle , Hypoglycémiants/pharmacologie , Hypoglycémiants/synthèse chimique , Hypoglycémiants/composition chimique , Hypoglycémiants/pharmacocinétique , Hypoglycémiants/usage thérapeutique , Diabète de type 2/traitement médicamenteux , Diabète de type 2/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Récepteurs au glucagon/agonistes , Récepteurs au glucagon/métabolisme
20.
Cancer Res ; 2024 Aug 09.
Article de Anglais | MEDLINE | ID: mdl-39120588

RÉSUMÉ

Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.

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