Biosimilars: navigating the regulatory maze across two worlds.

The impending loss of market exclusivity for established biologic products creates a lucrative market opportunity for biosimilars. However, complex and variable regulatory requirements between regions present challenges to developers. Understanding the regulatory differences between two major markets, Europe and China, will expedite entry into these key markets.

A novel ferroptosis-related gene signature to predict overall survival in patients with osteosarcoma.

OBJECTIVES: Ferroptosis plays vital roles in the pathogenesis of various malignant tumors. However, knowledge on roles of ferroptosis in osteosarcoma remains scarce. In the present study, a comprehensive bioinformatics analysis was performed aiming to identify ferroptosis-related genes (FRGs), construct a FRGs-based model predicting overall survival (OS), and assess the impact of these FRGs on the migration and invasion of osteosarcoma cells. METHODS: Initially, data regarding differentially expressed FRGs were obtained from the GSE160881 dataset. Prognostic significance and possible biological functions of these differentially expressed FRGs were comprehensively and systematically explored adopting a series of bioinformatics methods. The impact of cystathionine ß-synthase (CBS) on migration and invasion of osteosarcoma cells were assessed using transwell assays. RESULTS: A total of 50 FRGs were differentially expressed. Four FRGs including G6PD, VEGFA, CBS, and HMOX1 were used to construct a model predicting OS in osteosarcoma patients. In the training cohort, patients with high risk had significantly poorer OS than those with low risk, which was also demonstrated in validation cohorts (GSE16091 and GSE39058). Furthermore, we established a clinically useful nomogram predicting OS using the four FRGs mentioned above. Risk scores were significantly associated with the proportion of tumor-infiltrating immune cells. Additionally, we used the Cytoscape software to identify hub FRGs, and found that TP53, HMOX1, SLC7A11, HRAS, VEGFA, and TXNRD1 were hub FRGs. By performing in vitro cell culture experiments, we demonstrated that invasion and migration capability of Saos2 and HOS cells were significantly weakened after CBS knock down. CONCLUSIONS: In conclusion, gene signatures based on four FRGs were reliable in predicting OS in patients with osteosarcoma. Findings from this study will enable a better understanding of the prognostic significance of FRGs and tumor immunity in osteosarcoma.

Development and Validation of Novel Prognostic Models for Immune-Related Genes in Osteosarcoma.

Immunotherapy has shown excellent therapeutic effects on various malignant tumors; however, to date, immunotherapy for osteosarcoma is still suboptimal. In this study, we performed comprehensive bioinformatic analysis of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs). Datasets of differentially expressed IRGs were extracted from the GEO database (GSE16088). The functions and prognostic values of these differentially expressed IRGs were systematically investigated using a series of bioinformatics methods. In addition, CCK8 and plate clone formation assays were used to explore the effect of PGF on osteosarcoma cells, and twenty-nine differentially expressed IRGs were identified, of which 95 were upregulated and 34 were downregulated. Next, PPI was established for Identifying Hub genes and biology networks by Cytoscape. Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model. Compared with the low-risk patients in the training cohort (GSE39058) and TARGET validation cohorts, high-risk patients had poorer OS and RFS. Using these identified IRGs, we used OS and RFS prediction nomograms to generate a clinical utility model. The risk scores of the two prediction models were associated with the infiltration proportions of some TIICs, and the activation of memory CD4 T-cells was associated with OS and RFS. CD86 was associated with CTLA4 and CD28 and influenced the infiltration of different TIICs. In vitro experiments showed that the knockdown of PGF inhibited the proliferation and viability of osteosarcoma cells. In conclusion, these findings help us better understand the prognostic roles of IRGs and TIICs in osteosarcoma, and CD86 and PGF may serve as specific immune targets.

Ultra-high capacity for three-dimensional optical data storage inside transparent fluorescent tape: erratum.

In Opt. Lett.45, 1535 (2020)OPLEDP0146-959210.1364/OL.387278, there was an error regarding the corresponding author assignment. That error is corrected here.

Zn2+ responsive fluorescence enhancement for optical data storage.

In this paper, we put forward a new application in optical data storage (ODS) of tetraphenylethene (TPE)-doped photopolymer, which has an aggregation-induced emission attribute. The photopolymer host reacted with the excitation light at the focal point of a high numerical-aperture lens to enhance the fluorescence intensity mainly because of the function of the ${{\rm Zn}^{2 + }}$Zn2+ ion. We recorded data inside the photopolymer matrix by using this property and had distinct fluorescence intensity contrast between the photochemical regions and other regions. This attribute paves a new way for superresolution ODS and opens the way to exploring the possibility of utilizing TPE-doped photopolymers as chemical sensors in the future.

Ultra-high capacity for three-dimensional optical data storage inside transparent fluorescent tape.

In this Letter, we show an ultralarge capacity for three-dimensional optical data storage inside transparent fluorescent tape using the two-photon absorption photo-bleaching method. We can obtain transparent fluorescent tape by means of the simple dip method. We successfully demonstrate recording and reading of six layers of binary data bits with lateral separation of 2 µm and longitudinal layer separation of 3 µm. Thus, this result leads to a storage density of approximately ${80}\;{{\rm Gbits/cm}^3}$80Gbits/cm3. Therefore, we can realize authentic ultrahigh capacity optical data storage using long transparent fluorescent tape in the future, like magnetic tape, and fundamentally solve the data explosion disaster.

Surgical results and prognostic factors following percutaneous full endoscopic posterior decompression for thoracic myelopathy caused by ossification of the ligamentum flavum.

Minimally invasive surgery (MIS) has shown satisfactory surgical results for the treatment of thoracic myelopathy (TM) caused by ossification of the ligamentum flavum (OLF). This study investigated the prognostic factors following MIS and was based on the retrospective analysis of OLF patients who underwent percutaneous full endoscopic posterior decompression (PEPD). Thirty single-segment OLF patients with an average age of 60.4 years were treated with PEPD under local anaesthesia. Clinical data were collected from the medical and operative records. The surgical results were assessed by the recovery rate (RR) calculated from the modified Japanese Orthopaedic Association (mJOA) score. Correlations between the RR and various factors were analysed. Patients' neurological status improved from a preoperative mJOA score of 6.0 ± 1.3 to a postoperative mJOA score of 8.5 ± 2.0 (P < 0.001) at an average follow-up of 21.3 months. The average RR was 53.8%. Dural tears in two patients (6.7%, 2/30) were the only observed complications. Multiple linear regression analysis showed that a longer duration of preoperative symptoms and the presence of a high intramedullary signal on T2-weighted MRI (T2HIS) were significantly associated with poor surgical results. PEPD is feasible for the treatment of TM patients with a particular type of OLF. Patients without T2HIS could achieve a good recovery if they received PEPD early.

Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma.

INTRODUCTION: Long non-coding RNA MEG3 (lncRNA MEG3) has been showed to involve in a variety of cancers. However, the association between lncRNA MEG3 expression level and the prognosis of osteosarcoma is still unclear. METHODS: The expression levels of lncRNA MEG3 in osteosarcoma tissues and adjacent non-tumor tissues were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Our findings showed that expression of lncRNA MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non-tumor tissues. The expression of lncRNA MEG3 was associated with clinical stage and distant metastasis (P<0.05). Kaplan-Meier analysis showed that patients with low lncRNA MEG3 expression had a shorter overall survival (log-rank test, P<0.05). Furthermore, multivariate analysis revealed that decreased expression of lncRNA MEG3, advanced clinical stage and distant metastasis were all independent predictors to overall survival of osteosarcoma patients. CONCLUSIONS: Downregulation of lncRNA MEG3 was associated with poor overall survival of osteosarcoma. LncRNA MEG3 could be a useful biomarker for progression and prognosis of osteosarcoma.

MACC1 is involved in the regulation of proliferation, colony formation, invasion ability, cell cycle distribution, apoptosis and tumorigenicity by altering Akt signaling pathway in human osteosarcoma.

There is mounting evidence that metastasis-associated in colon cancer-1 (MACC1) plays pivotal roles in development and progression of many tumors, particularly in osteosarcoma (OS). However, its precise roles and molecular mechanisms remain to be delineated in OS. In the current study, we found that the levels of MACC1 mRNA and protein in four OS cell lines (MG-63, HOS, SaOS-2 and U2OS) were significantly higher than that in hFOB1.19 osteoblast (P < 0.05). The vector pcDNA-MACC1 contributed to the increase of MACC1 level in MG-63 cells, whereas MACC1 siRNA evoked the decrease of MACC1 level in U2OS cells. In addition, MACC1 downregualtion caused the inhibition of cell proliferation in vitro, colony formation, invasion and tumor growth in vivo, arrested cell cycle in G0/G1 phase and induced cell apoptosis in U2OS cells, and reversed effects were observed in MG-63 cells by MACC1 upregulation. Most notably, MACC1 depletion markedly inactivated Akt signaling pathway in U2OS cells, conversely, MACC1 upregulation evidently activated Akt signaling pathway in MG-63 cells. Collectively, our data presented herein suggest that biological implications triggered by MACC1 may be tightly associated with the status of Akt signaling pathway in OS.

[Posterior open-door laminoplasty combined with lateral mass plate fixation in the treatment of ossification of the posterior longitudinal ligament of the cervical spine].

OBJECTIVE: To evaluate the clinical effect of posterior decompression and open-door laminoplasty combined with lateral mass plate fixation in the treatment of ossification of the posterior longitudinal ligament of the cervical spine (OPLL). METHODS: A total of 41 OPLL patients in our hospital, with differing extents of spinal compression, were analyzed retrospectively. All cases underwent a posterior open-door laminoplasty operation, and lateral mass plate fixation. The Japanese Orthopedic Association ( JOA) score was adopted to evaluate nerve function. RESULTS: All cases were followed up for 12 to 16 (14±2.0) months. The postoperative JOA score was increased 4.8 points compared with the preoperative. CONCLUSION: Posterior open-door laminoplasty combined with lateral mass plate fixation for ossification of the posterior longitudinal ligament of the cervical spine possesses the advantages of extensive applicability, simplicity and safety, and strong stability. It is an efficient and reliable method for ossification of the posterior longitudinal ligament.

[Properties comparing and evolutionary analysis of MEF2 of Homo sapiens based on bioinformatic methods].

As one of the members of MADS family, MEF2 group is important in regulating development. Analytical tools of NCBI, ExPASy, CBS, CDD, and SABLE were adopted to analyze the properties of human MEF2 proteins, and evolutionary tree was built according to the result of correlative sequence alignments. The results showed that there are various forms of MEF2 in human body, and there are some differences in the physicochemical characteristics. Relatively more phosphorylation sites are found and the main glycosylation sites are N-glycosylation sites. All MEF2 proteins of human contain MADS domain, and most contain MEF2 domain and HJURP_C domain. Their secondary structures contain three dominant states: helix, sheet and coil, their tertiary structures are similar. The phylogenetic tree result shows that MEF2B may be original because of its difference of sequences and evolutional relation.