FBXL18 is required for ovarian cancer cell proliferation and migration through activating AKT signaling.

BACKGROUND: F-box and leucine-rich repeat protein 18 (FBXL18) is an F-box protein that functions as an E3-ubiquitin ligase, and it plays pivotal roles in multiple disease processes. However, its role and underlying mechanism in ovarian cancer (OC) are still unknown. We investigated the impact and mechanism of FBXL18 in OC cell growth and tumorigenesis. METHODS: Silent interfering RNAs and overexpression plasmids were employed to knock down and overexpress FBXL18 in OC cells (A2780 and OVCAR3). CCK-8, colony formation, cell migration, and nude mouse xenograft assays were used to assess the effect of FBXL18 on OC cell proliferation and migration. Western blotting and co-immunoprecipitation followed by ubiquitination assays were performed to detect the mechanism of the FBXL18/AKT axis in OC. RESULTS: FBXL18 knockdown inhibited OC cell proliferation and migration, whereas FBXL18 overexpression showed the opposite results. Phosphorylated-AKT (S473) protein expression was increased by FBXL18 overexpression and markedly decreased after phosphorylated-AKT inhibitor (MK-2206) treatment. Co-immunoprecipitation assays demonstrated that FBXL18 strongly interacted with AKT in OC cells. Ubiquitination assays revealed that FBXL18 promoted K63-linked AKT ubiquitination to activate AKT. MK-2206 treatment reversed the increase in proliferation and migration of OC cells induced by FBXL18 overexpression. CONCLUSIONS: FBXL18 promoted OC cell proliferation and migration and facilitated OC tumorigenesis. Mechanically, FBXL18 interacted with AKT and promoted K63-linked ubiquitination of AKT to activate AKT in OC cells. Our study revealed that the FBXL18/AKT axis plays a crucial role in the OC process, indicating that FBXL18 may be a valuable target for OC diagnosis and treatment.

A Periosteum-Bioinspired Electrospun Janus Membrane with Antibacterial and Osteogenic Dual Function.

For a guided bone regeneration membrane, it is critical to possess osteogenic capability while inhibiting infection caused by bacteria. Inspired by the bilayer structure of the native periosteum, an electrospun Janus membrane with osteogenic and antibacterial dual-function is fabricated for guided bone regeneration. Hydrophilic moxifloxacin (MXF) and hydrophobic icariin (ICA) are loaded in the nanofibers made of a mixture of polycaprolactone and gelatin at the top and bottom layers, respectively, leading to the opposing hydrophilic/hydrophobic properties of the bilayer Janus membranes. The as-obtained Janus membrane exhibits excellent physical properties (tensile strength > 6.0 MPa) and robust biocompatibility, indicating the immense potential as a suitable replacement for the native periosteum. The membrane has a superior surface morphology and outstanding degradation performance in vitro. Besides, the rapid release of MXF and the slow release of ICA can meet the different needs of drug release rates. Only ≈30% ICA is released from the as-obtained Janus membrane after 21 d while almost 80% MXF is released. Mimicking the bilayer structure of the native periosteum, the electrospun Janus membrane containing ICA and MXF exhibits excellent comprehensive properties, which provides a promising strategy for preparing multifunctional scaffolds for tissue engineering.

The Latest Sensor Detection Methods for per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFASs) have emerged as a prominent environmental pollutant in recent years, primarily due to their tendency to accumulate and magnify in both the environment and living organisms. The entry of PFASs into the environment can have detrimental effects on human health. Hence, it is crucial to actively monitor and detect the presence of PFASs. The current standard detection method of PFAS is the combination of chromatography and mass spectrometry. However, this requires expensive instruments, extra sample pretreatment steps, complicated operation and long analysis time. As a result, new methods that do not rely on chromatography and mass spectrometry have been developed and applied. These alternative methods mainly include optical and electrochemical sensor methods, which offer great potential in terms of real-time field detection, instrument miniaturization, shorter analysis time, and reduced detection cost. This review provides a summary of recent advancements in PFAS detection sensors. We categorize and explain the principles and mechanisms of these sensors, and compare their limits of detection and sensitivity. Finally, we discuss the future challenges and improvements needed for PFAS sensors, such as field application, commercialization, and other related issues.

Modulation of Performance, Plasma Constituents, Small Intestinal Morphology, and Cecum Microbiota in Growing Geese by Dietary Citric Acid Supplementation.

To investigate the efficiency and optimum inclusion level of CA in growing geese diets on performance, plasma constituents, and intestinal health, 240 healthy female geese at the age of 28d were randomly allotted six treatment diets incorporated with 0, 0.8, 1.6, 2.4, 3.2, and 4% CA. Each treatment group consisted of five replicates and eight birds per replicate. The findings demonstrated that 3.2% CA supplementation resulted in improved growth performance (ADG, ADFI, and FBW) (p = 0.001), and geese who received CA also showed lower body fat contents (p < 0.05) than the control group. Moreover, geese from the 2.4% and 3.2% CA group had the highest plasma glutathione peroxidase and insulin-like growth factor 1 levels compared to the other groups (p < 0.05). A microbial diversity analysis of the cecum conducted by 16S rDNA sequencing revealed that 3.2% CA supplementation showed a significantly higher abundance of beneficial bacteria (Muribaculaceae, CHKCI001, Erysipelotricha-ceae_UCG_003, and UCG_009) (p < 0.05) and a lower abundance of harmful bacteria (Atopobiaceae, Streptococcus, Acinetobacter, Pseudomonas, and Alistipes) (p < 0.10). Collectively, our results revealed that dietary supplementation with 3.2% CA had several benefits on the performance and physiological health of growing geese by promoting nutrients metabolism, improving antioxidant capacity, and modulating cecum microbiota.

Integrating Bioactive Graded Hydrogel with Radially Aligned Nanofibers to Dynamically Manipulate Wound Healing Process.

Skin wound healing is a complex process that requires appropriate treatment and management. Using a single scaffold to dynamically manipulate angiogenesis, cell migration and proliferation, and tissue reconstruction during skin wound healing is a great challenge. We developed a hybrid scaffold platform that integrates the spatiotemporal delivery of bioactive cues with topographical cues to dynamically manipulate the wound-healing process. The scaffold comprised gelatin methacryloyl hydrogels and electrospun poly(ε-caprolactone)/gelatin nanofibers. The hydrogels had graded cross-linking densities and were loaded with two different functional bioactive peptides. The nanofibers comprised a radially aligned nanofiber array layer and a layer of random fibers. During the early stages of wound healing, the KLTWQELYQLKYKGI peptide, which mimics vascular endothelial growth factor, was released from the inner layer of the hydrogel to accelerate angiogenesis. During the later stages of wound healing, the IKVAVS peptide, which promotes cell migration, synergized with the radially aligned nanofiber membrane to promote cell migration, while the nanofiber membrane also supported further cell proliferation. In an in vivo rat skin wound-healing model, the hybrid scaffold significantly accelerated wound healing and collagen deposition, and the ratio of type I to type III collagen at the wound site resembled that of normal skin. The prepared scaffold dynamically regulated the skin tissue regeneration process in stages to achieve rapid wound repair with clinical application potential, providing a strategy for skin wound repair.

Slc26a1 is not essential for spermatogenesis and male fertility in mice.

Thousands of genes are expressed in the testis of mice. However, the details about their roles during spermatogenesis have not been well-clarified for most genes. The purpose of this study was to examine the effect of Slc26a1 deficiency on mouse spermatogenesis and male fertility. Slc26a1-knockout (KO) mice were generated using CRISPR/Cas9 technology on C57BL/6J background. We found no obvious differences between Slc26a1-KO and Slc26a1-WT mice in fertility tests, testicular weight, sperm concentrations, or morphology. Histological analysis found that Slc26a1-KO mouse testes had normal germ cell types and mature sperm. These findings indicated that Slc26a1 was dispensable for male fertility in mice. Our results may save time and resources by allowing other researchers to focus on genes that are more meaningful for fertility studies. We also found that mRNAs of two Slc26a family members (Slc26a5 and Slc26a11) were expressed on higher mean levels in Slc26a1-KO total mouse testes, compared to Slc26a1-WT mice. This effect was not found in mouse GC-1 and GC-2 germ cell lines with the Slc26a1 gene transiently knocked down. This result may indicate that a gene compensation phenomenon was present in the testes of Slc26a1-KO mice.