Applications of Graphene Family Nanomaterials in Regenerative Medicine: Recent Advances, Challenges, and Future Perspectives.

Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis.

First Report of Postharvest Fruit Brown Rot Disease on Navel Orange Caused by Diaporthe sojae in China.

In October 2020, a postharvest fruit brown rot symptom was observed on navel orange (Citrus sinensis Osbeck cv. Newhall) fruits in a local fruit market in Ganzhou, Jiangxi Province, China. The disease incidence increased up to 15% in 40 fruits with a 7-day-long storage at room temperature. The disease symptoms on the infected fruit were circular, light brown to brown, slightly sunken lesions, covered with whitish mycelium mass, and brown rot in the center. To isolate the causal organism, infected fruits were surface sterilized with 1% NaClO solution for 30 sec, and rinsed thrice with sterilized water. Symptomatic tissues at the margins were cut into 5-mm2 pieces, placed on potato dextrose agar (PDA) medium and incubated at 25℃ for 5 days. Thirteen morphologically similar single-spore fungal isolates were obtained from the isolation experiment. Fungal colonies were white, fluffy, cottony texture, reverse buff to light yellow, with black stromata at maturity. Alpha conidia were hyaline, aseptate, ellipsoid to clavate, tapering towards the ends, often biguttulate, and ranged in size from 6.8 to 9.8 µm × 2.7 to 4.5 µm (n=50). Beta conidia were hyaline, aseptate, smooth, straight to sinuous, and with size ranging from 12.1 to 21.3 µm × 0.9 to 2.2 µm (n=50). Morphological features were consistent with those of Diaporthe sojae (Dissanayake et al. 2015). For molecular identification, DNA was extracted from the representative isolate JFRL 03-13, the internal transcribed spacer (ITS) region, beta-tubulin (TUB), calmodulin (CAL), partial translation elongation factor 1-alpha (TEF1-α), and histone H3 (HIS) genes were amplified by using primers ITS1/ITS4, Bt2a/Bt2b, CAL228F/CAL737R, EF1-728F/EF1-986R, and CYLH3F/H3-1b (Udayanga et al. 2015), respectively. The resulting sequences were deposited in GenBank (Accession Nos. OM281710 for ITS, OM289961 for TUB, OM289964 for CAL, OM289963 for TEF1-α, and OM289962 for HIS). BLAST analysis revealed that these sequences were 100% similar to the sequences of ITS (MN816426), TUB (MK941336), CAL (MN894375), TEF1-α (MN894447), HIS (MN894409) published for D. sojae. Phylogenetic analysis was conducted based on the concatenated sequences (ITS, TUB, CAL, TEF1-α, and HIS) by Maximum likelihood analysis (ML) and Bayesian inference (BI) using IQtree v.1.6.11 and MrBayes v.3.2.7 (Guo et al. 2020). The phylogenetic tree showed that the isolate clustered with D. sojae. To confirm pathogenicity, mature and healthy harvested fruits of navel orange (Citrus sinensis Osbeck cv. Newhall) were surface sterilized. Ten fruits were wounded by a sterile scalpel and put a 7-mm-diamter agar plug with 7-day-old mycelium of the isolate JFRL03-13 cultured on PDA at 25°C, noncolonized PDA plugs were used as the control. Inoculated fruits were incubated at 25℃ with 80% relative humidity. After 10 days, the similar symptoms were observed on the inoculated sites and spread on the surface of fruits, whereas the control remained symptomless. The pathogen was re-isolated from the lesions of inoculated fruits and confirmed as D. sojae via morphological and molecular analysis. The assays were repeated twice, fulfilling the Koch's postulates. Although D. sojae is known as the major causative agent of pod and stem blight, and has been reported as an endophyte in the twigs and leaves of citrus (Huang et al. 2015; Santos et al. 2011), but to our knowledge, this is the first report of postharvest fruits brown rot disease on navel orange caused by D. sojae in China. However, further investigation of the specific causes of this disease is necessary to help the local fruit farmers develop effective disease management strategies.

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA­374a/forkhead box O1 signaling axis.

Ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (DDP) resistance in ovarian cancer cells. Ovarian cancer cell viability was assessed by the Cell Counting kit­8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)­374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription­quantitative PCR; the binding ability of miR­374a to FOXO1 was assessed by the dual­luciferase reporter assay; cellular sensitivity to DDP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl­2­like­protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased miR­374a expression levels in A2780 cells. In addition, the viability of A2780/DDP cells in the propofol + DDP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR­374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. Conversely, genetic knockdown of miR­374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, miR­374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. In addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. In conclusion, propofol downregulated miR­374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

[Dynamic monitoring on ovarian function among patients having had cervical squamous cell carcinoma transposition surgery].

UNLABELLED: To investigate the changes in ovarian function and the radiotherapeutic influence on ovarian function on patients with cervical squamous cell carcinoma. METHODS: We retrospectively analyzed 53 cases of cervical cancer patients FIGO staging I B1- II B who had received ovarian transposition surgery at the Maternal and Child Health Hospital of Jiangxi province from January 2009 to June 2012. All the patients included in the study were FIGO staging I B1- II B and had undergone radiation therapy, including 38 staging I B1- II A2 cervical cancer patients receiving chemo-therapy after radical radiotherapy due to the presence of risk factors and other 15 patients with stage II B to radical concurrent chemoradiotherapy ovarian transposition. Ovarian transposition methods would include laparoscopic ovarian transposition and transabdominal ovarian transposition. 15 concurrent patients with stage II B who currently receiving chemo-radiotherapy were under laparoscopic ovarian transposition. Among the 38 radical hysterectomy patients, 31 were having abdominal ovarian transposition, and the remaining 7 cases were laparoscopic. All the 53 patients had undergone radiotherapy. The levels of serum female hormones FSH, LH, E2 were determined to monitor the ovarian endocrine function. RESULTS: According to FIGO staging, 18 cases were stage I B1, 15 cases I B2, 3 cases II A1, 2 cases II A2 and 15 cases II B. Patients' age range was from 28 to 44 years old, with an average of 37.7 years, median age as 38 years. 14 patients (63.6%) were still normal ovarian function after radiotherapy by laparoscopic ovarian transposition, which was 100.0% before radiotherapy. There was a significant difference (P < 0.05)compared with before radiotherapy. After transabdominal ovarian transposition surgery and radiotherapy, normal ovarian function 22 cases (71.0%), and there was a significant difference (P < 0.05) compared with before radiotherapy. No significant difference was found with regard to the proportion of normal ovarian function after radiotherapy between the two groups of patients with laparoscopic and transabdominal ovarian transposition (P > 0.05). CONCLUSION: For the young cervical cancer patients, even with ovarian transposition, ovarian dysfunction was still evident after radiotherapy. There was no significant difference between laparoscopic and transabdominal ovarian transposition.