Methylseleninic acid inhibits human glioma growth in vitro and in vivo by triggering ROS-dependent oxidative damage and apoptosis.

Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.

Finite element biomechanical analysis of 3D printed intervertebral fusion cage in osteoporotic population.

OBJECTIVE: To study the biomechanical characteristics of each tissue structure when using different 3D printing Cage in osteoporotic patients undergoing interbody fusion. METHODS: A finite element model of the lumbar spine was reconstructed and validated with regarding a range of motion and intervertebral disc pressure from previous in vitro studies. Cage and pedicle screws were implanted and part of the lamina, spinous process, and facet joints were removed in the L4/5 segment of the validated mode to simulate interbody fusion. A 280 N follower load and 7.5 N·m moment were applied to different postoperative models and intact osteoporotic model to simulate lumbar motion. The biomechanical characteristics of different models were evaluated by calculating and analyzing the range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment. RESULTS: After rigid fixation, the range of motion of the fixed segment of model A-C decreased significantly, which was much smaller than that of the osteoporotic model. And with the increase of the axial area of the interbody fusion cages, the fixed segment of model A-C tended to be more stable. The range of motion and intradiscal pressure of the spinal models with different interbody fusion cages were higher than those of the complete osteoporosis model, but there was no significant difference between the postoperative models. On the other hand, the L5 upper endplate stress and screw-rod system stress of model A-C show a decreasing trend in different directions of motion. The stress of the endplate is the highest during flexion, which can reach 40.5 MPa (model A). The difference in endplate stress between models A-C was the largest during lateral bending. The endplate stress of models A and B was 150.5% and 140.9% of that of model C, respectively. The stress of the screw-rod system was the highest during lateral bending (model A, 102.0 MPa), which was 108.4%, 102.4%, 110.4%, 114.2% of model B and 158.5%, 110.1%, 115.8%, 125.4% of model C in flexion, extension, lateral bending, and rotation, respectively. CONCLUSIONS: For people with osteoporosis, no matter what type of cage is used, good immediate stability can be achieved after surgery. Larger cage sizes provide better fixation without significantly increasing ROM and IDP in adjacent segments, which may contribute to the development of ASD. In addition, larger cage sizes can disperse endplate stress and reduce stress concentration, which is of positive significance in preventing cage subsidence after operation. The cage and screw rod system establish a stress conduction pathway on the spine, and a larger cage greatly enhances the stress-bearing capacity of the front column, which can better distribute the stress of the posterior spine structure and the stress borne by the posterior screw rod system, reduce the stress concentration phenomenon of the nail rod system, and avoid exceeding the yield strength of the material, resulting in the risk of future instrument failure.

The environmental impact assessment of China's ecological migration from a social-ecological perspective.

When accounting for the social-ecological impact of an ecological restoration program, both objective environmental contexts and people's subjective perceptions are required. While this kind of environmental impact assessment lacks a comprehensive perspective. We use the difference-in-differences model to evaluate the effect of the greenness of the landscape after ecological migration in the Qilian Mountains in China; and analysis of variance and fixed effects models are used to evaluate the effects of such ecological restoration programs on local people's perceptions. The results show that the ecological migration program in the Qilian Mountains has been successful at not only significantly improving remotely sensed greenness at the landscape scale, but also at enhancing immigrants' environmental perceptions. These findings demonstrate the environmental impacts of ecological migration from a social-ecological perspective, and can provide methodological implications for landscape planning to support a better understanding of ecological restoration programs in the drylands.

A bibliometric and visualization analysis of global research status and frontiers on autophagy in cardiomyopathies from 2004 to 2023.

BACKGROUND: Autophagy is intimately associated with the development of cardiomyopathy, and has received widespread attention in recent years. However, no relevant bibliometric analysis is reported at present. In order to summarize the research status of autophagy in cardiomyopathy and provide direction for future research, we conducted a comprehensive, detailed, and multidimensional bibliometric analysis of the literature published in this field from 2004 to 2023. METHODS: All literatures related autophagy in cardiomyopathy from 2004 to 2023 were collected from the Web of Science Core Collection (WOSCC), and annual papers, global publication trends and proportion charts were analyzed and plotted using Graphpad price v8.0.2. In addition, CtieSpace (6.2.4R (64 bit) Advanced Edition) and VOSviewer (1.6.18 Edition) were used to analyze and visualize these data. RESULTS: 2279 papers about autophagy in cardiomyopathy were accessed in the WoSCC over the last 20 years, comprising literatures from 70 countries and regions, 2208 institutions, and 10,810 authors. China contributes 56.32% of the total publications, substantially surpassing other countries, while the U.S. is ranked first in frequency of citations. Among the top 10 authors, 6 are from China and 4 are from the United States. Air Force Military Medical University was the institution with the highest number of publications; while journal of molecular and cellular cardiology (62 articles, 2.71% of the total) was the journal with the highest number of papers published in the field. Clustering of co-cited references and temporal clustering analysis showed that ferroptosis, hydrogen sulfide mitophagy, lipid peroxidation, oxidative stress, and SIRT-1 are hot topics and trends in the field. The principal keywords are oxidative stress, heart and heart-failure. CONCLUSION: The research on autophagy in cardiomyopathy is in the developmental stage. This represents the first bibliometric analysis of autophagy in cardiomyopathy , revealing the current research hotspots and future research directions in this field.

Chloroplast genomes of Eriobotrya elliptica and an unknown wild loquat "YN-1".

The chloroplast genomes of wild loquat can help to determine their place in the history of evolution. Here, we sequenced and assembled two novel wild loquat's chloroplast genomes, one is Eriobotrya elliptica, and the other is an unidentified wild loquat, which we named "YN-1". Their sizes are 159,471 bp and 159,399 bp, respectively. We also assembled a cultivated loquat named 'JFZ', its chloroplast genome size is 159,156 bp. A comparative study was conducted with six distinct species of loquats, including five wild loquats and one cultivated loquat. The results showed that both E. elliptica and "YN-1" have 127 genes, one gene more than E. fragrans, which is psbK. Regions trnF-GAA-ndhJ, petG-trnP-UGG, and rpl32-trnL-UAG were found to exhibit high variability. It was discovered that there was a positive selection on rpl22 and rps12. RNA editing analysis found several chilling stress-specific RNA editing sites, especially in rpl2 gene. Phylogenetic analysis results showed that "YN-1" is closely related to E. elliptica, E. obovata and E. henryi.

Preparation, characterization, and application of gallic acid-mediated photodynamic chitosan-nanocellulose-based films.

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e-12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products.

Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial.

OBJECTIVES: Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy. MATERIALS AND METHODS: CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel. RESULTS: A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.6 months (95 % confidence interval [CI], 8.2-12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5-13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76-1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3-4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (< 10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (≥ 10 mg/L) CRP levels. There was no association with treatment arm. CONCLUSION: Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy. CLINICAL REGISTRATION: NCT03626545.