Search

Abstract Background Methionine (Met) is the only sulfur-containing amino acid among animal essential amino acids, and methionine deficiency (MD) causes tissue damage and cell death in animals. The common modes of cell death include apoptosis, autophagy, pyroptosis, necroptosis. However, the studies about the major modes of cell death caused by MD have not been reported, which worth further study. Methods Primary hepatocytes from grass carp were isolated and treated with different doses of Met (0, 0.5, 1, 1.5, 2, 2.5 mmol/L) to examine the expression of apoptosis, pyroptosis, autophagy and necroptosis-related proteins. Based on this, we subsequently modeled pyroptosis using lipopolysaccharides and nigericin sodium salt, then autophagy inhibitors chloroquine (CQ), AMP-activated protein kinase (AMPK) inhibitors compound C (CC) and reactive oxygen species (ROS) scavengers N-acetyl-L-cysteine (NAC) were further used to examine the expression of proteins related to pyroptosis, autophagy and AMPK pathway in MD-treated cells respectively. Results MD up-regulated B-cell lymphoma protein 2 (Bax), microtubule-associated protein 1 light chain 3 II (LC3 II), and down-regulated the protein expression levels of B-cell lymphoma-2 (Bcl-2), sequestosome 1 (p62), cleaved-caspase-1, cleaved-interleukin (IL)-1β, and receptor-interacting protein kinase (RIP) 1 in hepatocytes, while it did not significantly affect RIP3. In addition, MD significantly increased the protein expression of liver kinase B1 (LKB1), p-AMPK, and Unc-51-like kinase 1 (ULK1) without significant effect on p-target of rapamycin. Subsequently, the use of CQ increased the protein expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved-caspase-1, and cleaved-IL-1β inhibited by MD; the use of CC significantly decreased the protein expression of MD-induced LC3 II and increased the protein expression of MD-suppressed p62; then the use of NAC decreased the MD-induced p-AMPK protein expression. Conclusion MD promoted autophagy and apoptosis, but inhibited pyroptosis and necroptosis. MD inhibited pyroptosis may be related regarding the promotion of autophagy. MD activated AMPK by inducing ROS production which in turn promoted autophagy. These results could provide partial theoretical basis for the possible mechanisms of Met in ensuring the normal structure and function of animal organs. Furthermore, ferroptosis is closely related to redox states, it is worth investigating whether MD affects ferroptosis in hepatocytes.

Abstract Exposure to PM2.5, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3′-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health.

Abstract Background Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

The object detection of synthetic aperture radar (SAR) ships holds significant promise for water traffic monitoring, ship search and rescue, and maritime warning tasks. Regrettably, most of the existing SAR ship object detection is limited to the fully supervised paradigm, exhibiting a firm reliance on data labels, and inherent challenges such as multiscale ship feature disparities and indistinct small-sized ships also make SAR ship detection difficult. To address these, we propose a scale-mixing enhanced and dual consistency guided semisupervised object detection (SMDC-SSOD) method. Specifically, this method is based on the teacher–student framework and primarily comprises three core components: cross-scale feature mixing (CSFM) scheme, scale change consistency guidance (SCCG) strategy, and proposal consistency guidance (PCG) strategy, which can efficiently conduct end-to-end semisupervised learning from limited data labeling, achieving low-cost and high-performance ship perception. CSFM scheme includes interpyramid and intrapyramid feature cross-scale mixings, which can improve the network's adaptability for multiscale ship characteristics and increase focus on small-sized ships. SCCG strategy leverages variations in confidence scores at different scales to select valuable pseudolabels, providing more precise guidance for the student network. PCG strategy further reflects the positioning quality of pseudolabels through the proposal consistency generated by the student network, guiding it to make high-quality predictions. The experimental results on the publicly available HRSID, BBox-SSDD, and SAR-Ship-Dataset demonstrate that SMDC-SSOD can accurately detect SAR ships with an extremely low data annotation rate (below 10%) and achieve optimal detection performance compared to state-of-the-art methods.

Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer, but the drugs currently used for its treatment are less than ideal. Tilapia oligopeptides have a wide range of biological activities and are potential sources of new drugs. In this study, the role and mechanism of TBP-1 (Ser-Val-Val-Ala-Ile), an oligopeptide from tilapia, on inflammation and endothelial-mesenchymal transition (EMT) in HCC was investigated using the LPS-induced RAW264.7 inflammation model and the transforming growth factor (TGF)-β1-induced HCC EMT model. The results showed that TBP-1 could effectively inhibit inflammatory response. Moreover, in TGF-β1-induced human hepatocellular carcinoma (HepG2) cells, 100 μM TBP-1 significantly reduced the secretion of N-cadherin (54.2 ± 10.6 %), Vimentin (47.0 ± 9.4 %) and Snail (76.0 ± 9.0 %), increased the secretion of E-cadherin (56.0 ± 16.3 %), inhibited cell metastasis, and participated in the regulatory mechanisms of TGF-β/Smad and non-TGF-β/Smad mediated EMT. TBP-1 may be a potentially valuable inhibitor of HCC.