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Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths, posing a serious threat to women′s health worldwide. At present, although the prognosis of some patients with breast cancer has improved, the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis. CD36 is a multiligand transmembrane glycoprotein expressed on various cell types. In recent years, studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells; promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues; regulate the function of Treg cells, CD8+ T cells, DCs, and other immune cells, and thus promote tumor development. In addition, CD36 is also associated with breast cancer stem cells, metastasis-initiating cells, and breast drug resistant cells. Therefore, CD36 could be an important potential therapeutic target for breast cancer.

Introduction: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown. Objectives: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. Methods: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hit model of MV after acid aspiration-induced lung injury in mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered. Results: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacological inhibition or knockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca2+ influx and ATP release in lung epithelial cells. Conclusions: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novel strategy for the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.

Oligopeptide (AYAPE, AYP) has been isolated from Isochrysis Zhanjiangensis and it has been proven to have good biological activity potential, but its structural characteristics and structure-activity are not yet very clear. As an oligopeptide of five amino acids, the structural characteristics of AYP are the key factors of its activity. Therefore, through evaluating the antioxidant mechanism and stress degree of AYP in different cells, the active action sites were analyzed to explain the antioxidant structure activity relationship of AYP. The results indicate that under oxidative stress, 50 μM AYP can restore 78.53 % of cell viability. AYP through NF-κB and MAPK signaling pathways inhibit inflammation and cell apoptosis. And then, it activates Nrf2/Keap1 pathway, promotes Nrf2 nuclear transfer, and increases the expression of antioxidant enzymes, thus exerting antioxidant effects. In addition, in order to further explore the structure activity relationship of AYP, quantum mechanics and molecular docking were combined for analysis. The results showed that tyrosine, alanine, proline, and glutamic acid contained in AYP can all contribute to antioxidant activity, and the key amino acids that mainly play an antioxidant role are tyrosine and alanine. Therefore, this study provides a new idea for the rational design of marine oligopeptides based on the activity mechanism in the application of food and health products.

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.

Low temperatures pose a significant threat to plant growth and development. Studies have shown that aquaporins (AQPs), as the main functional proteins on the cell membrane regulating water ingress and egress, play a vital role in maintaining dynamic water balance when plants face cold stress. Catalpa bungei, an important timber and ornamental tree species, has its cultivation range significantly limited by its poor cold tolerance. However, no study has been found aiming to identify its aquaporin gene family. This study aims to fill this gap using two C. bungei cultivars with differing cold tolerance as experimental material: “Qiuza 1”, which is less cold-tolerant, and “Qiuza 2”, which is more cold-tolerant. The plants were subjected to low-temperature stress at 4 °C for 24 h. Using high-throughput molecular sequencing technology, a transcriptome sequencing of the leaves was performed at 0, 6, 12, and 18 h of cold stress. Fifteen candidate aquaporin genes in C. bungei (CbAQP) were identified. Phylogenetic analysis showed that the CbAQP gene family is divided into five subfamilies: 5 PIPs, 4 TIPs, 3 NIPs, 2 SIPs, and 1 XIP. By analyzing AQPs related to cold stress in other plants and the expression patterns of CbAQP genes, 12 CbAQP genes related to cold stress were identified. The genes that responded positively include CbPIP2;5, CbPIP1;2, CbTIP4;1, and CbNIP2;1. The results provide a foundation for further analysis of the biological functions of candidate CbAQP genes related to cold tolerance and offer theoretical support for improving seedling quality, cold-resistant genetic breeding, and expanding its distribution range.

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

The microclimate environment can be conveniently controlled with accuracy by plant incubators, in which the cuttings propagation method can efficiently enhance seedling production. To ensure air flow evenly throughout the incubator, the scientific design of the air inlet is crucial. This study utilized a computational fluid dynamics (CFD) model to simulate the airflow patterns in a culture layer under different air inlet conditions. Furthermore, the optimal design parameters were determined by way of response surface methodology (RSM) and the Non-dominated Sorting Genetic Algorithm-II (NSGA-II). Adopting the optimal parameters, a prototype was manufactured, and a cuttings experiment was carried out with apple cuttings in the incubator. The results showed that the optimal air inlet radius is 90 mm, the optimal air inlet height is 188 mm, and the optimal uniform flow plate hole diameter is 13 mm. Meanwhile, the apple cuttings were able to root. Therefore, this incubator with optimal parameters can be used for cuttings. The study provides a methodological and theoretical basis for the future optimizing of air inlet parameters and promoting cuttings rooting.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile–Ile–Ala–Val–Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.

The corrosion of reinforced concrete (RC) is one of the most serious durability problems in civil engineering structures, and the corrosion detection of internal reinforcements is an important basis for structural durability assessment. In this paper, the appropriate frequency required to cause excitation signals in the specimen is first analyzed by means of frequency dispersion curves. Subsequently, the effectiveness of five damage indexes (DIs) is discussed using random corrosion in finite elements. Finally, guided ultrasonic wave (GUW) tests are conducted on reinforcement and RC specimens at different corrosion degrees, and the test results are verified using a theoretical corrosion model. The results show that the larger the covered thickness is at the same frequency, the higher the modal order of the GUW in the frequency dispersion curve is, and the smaller the group velocity is. The SAD is the most sensitive to the corrosion state of the reinforcement compared with the other DIs, and it shows a linear increasing trend with the increase in the corrosion degree of the reinforcement. The SAD values of the RC specimens showed a three-stage change with the increase in the corrosion time, and the time until the appearance of corrosion cracks was increased with the increase in the covered thickness. It can be seen that increasing the covered thickness is an effective method to delay the time until the appearance of corrosion cracks in RC specimens.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Large numbers of studies have focused on the long non-coding RNA (lncRNA) that plays essential roles in the progression of osteosarcoma. Nevertheless, the functions and underlying mechanisms of LncRNA NDRG1 in osteosarcoma remain unknown. Methods Differentially expressed lncRNAs between osteosarcoma and adjacent normal tissues were identified through RNA sequencing. The role of LncRNA NDRG1 in osteosarcoma proliferation and metastasis were investigated through in vitro and in vivo functional experiments. The interaction between LncRNA NDRG1 and miR-96-5p was verified through bioinformatic analysis and luciferase reporter assay. Regulation relationship between LncRNA NDRG1 and miR-96-5p was further evaluated by the rescue experiments. Additionally, the changes in the expression of epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were verified by Western blot. Results LncRNA NDRG1 was up-regulated in osteosarcoma cell lines and tissues and the expression of LncRNA NDRG1 was correlated with the overall survival of osteosarcoma patients. Functional experiments exhibited that LncRNA NDRG1 aggravated osteosarcoma proliferation and migration in vitro; meanwhile, animals experiments showed that LncRNA NDRG1 promoted osteosarcoma growth and metastasis in vivo. Mechanistically, LncRNA NDRG1 was found to aggravate osteosarcoma progression and regulate the PI3K/AKT pathway by sponging miR-96-5p. Conclusions LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p. Therefore, LncRNA NDRG1 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.

Abstract Background P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co‐test for detecting high‐grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high‐throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. Methods P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A‐knockout) standards. Since 2018, 24 100‐women (HPV‐positive/‐negative, Pap‐normal/‐abnormal) have been enrolled nationwide for two‐tier validation work. In cross‐sectional studies, age‐ and viral genotype‐dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut‐offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2‐year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV‐positive Pap‐normal, Pap‐abnormal biopsy‐negative and biopsy‐confirmed LSIL. Results P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A‐positive ratio was 13.9 ± 1.8% among HPV‐negative NILM women and peaked at the ages of 40–49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV‐negative: 17.7 ± 5.0–21.4 ± 7.2%; HPV‐positive: 18.0 ± 5.2–20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV‐combined double‐cut‐off‐ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co‐test. The p16INK4A‐abnormal situation was an independent HSIL+ risk factor for 2‐year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3–7.2). Conclusions FCM‐based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk‐stratification‐based interventions.

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.