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RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids. RAD51D deletion impaired the homologous recombination (HR) function and induced G2/M phase arrest, whereas concurrent TP53 deletion mitigated G0/G1 phase arrest and boosted DNA replication when combined with RAD51D mutation. The co-deletion of TP53 and RAD51D downregulated cilia assembly, development, and motility, but upregulated multiple HGSOC-associated pathways, including the IL-17 signaling pathway. IL-17A treatment significantly improved cell viability. TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening.

Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1β. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment.

Creation of bio-multifunctional wound dressings with potent hemostatic, antibacterial, anti-inflammatory, and angiogenesis features for bolstering the healing of full-thickness wounds is sought after for clinical applications. We created bio-multifunctional composite sponges by coupling alginate and chitosan with Sargassum pallidum polysaccharides through electrostatic interactions, calcium ion (Ca2+) crosslinking, and lyophilization. Alginate/chitosan (AC) sponges with different concentrations of Sargassum pallidum polysaccharides were obtained and termed AC, ACS—1%, ACS—2.5%, and ACS—5%. ACS—1% and ACS—2.5% sponges exhibited uniform porosity, high water vapor transmission rate, high water absorption, as well as good hemostatic and antibacterial abilities. ACS—2.5% sponges facilitated wound closure and promoted angiogenesis and re-epithelialization in the dermis. These data suggest that ACS sponges containing a certain amount of Sargassum pallidum polysaccharides could be employed for treatment of full-thickness skin wounds.

A tubular permanent-magnet linear generator is suitable for direct drive wave energy conversion owing to its simple structure, easy maintenance and high efficiency. In this study, a novel Gramme winding tubular permanent-magnet linear generator (GW) is designed to increase power density. First, the structure of the Gramme winding and concentrated winding tubular permanent-magnet linear generator is introduced and the operation principle of the generator is analysed. Second, the initial parameters of GW are determined based on the similar overall dimensions to those of the concentrated winding tubular permanent-magnet linear generator. Third, the air gap flux density, external characteristics, voltage regulation, output power, and loss of the two generators are compared. Finally, the DC load capacities of the two generators are compared based on a three-phase full-control bridge rectifying circuit. The results show that the GW has a higher power density than the latter.

Synaptic devices with bipolar analog resistive switching behavior are the building blocks for memristor-based neuromorphic computing. In this work, a fully complementary metal-oxide semiconductor (CMOS)-compatible, forming-free, and non-filamentary memristive device (Pd/Al2O3/TaOx/Ta) with bipolar analog switching behavior is reported as an artificial synapse for neuromorphic computing. Synaptic functions, including long-term potentiation/depression, paired-pulse facilitation (PPF), and spike-timing-dependent plasticity (STDP), are implemented based on this device; the switching energy is around 50 pJ per spike. Furthermore, for applications in artificial neural networks (ANN), determined target conductance states with little deviation (