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Abstract The role of mitochondria peptides in the spreading of glioblastoma remains poorly understood. In this study, we investigated the mechanism underlying intracranial glioblastoma progression. Our findings demonstrate that the mitochondria-derived peptide, humanin, plays a significant role in enhancing glioblastoma progression through the intratumoral activation of the integrin alpha V (ITGAV)–TGF beta (TGFβ) signaling axis. In glioblastoma tissues, humanin showed a significant upregulation in the tumor area compared to the corresponding normal region. Utilizing multiple in vitro pharmacological and genetic approaches, we observed that humanin activates the ITGAV pathway, leading to cellular attachment and filopodia formation. This process aids the subsequent migration and invasion of attached glioblastoma cells through intracellular TGFβR signaling activation. In addition, our in vivo orthotopic glioblastoma model provides further support for the pro-tumoral function of humanin. We observed a correlation between poor survival and aggressive invasiveness in the humanin-treated group, with noticeable tumor protrusions and induced angiogenesis compared to the control. Intriguingly, the in vivo effect of humanin on glioblastoma was significantly reduced by the treatment of TGFBR1 inhibitor. To strengthen these findings, public database analysis revealed a significant association between genes in the ITGAV–TGFβR axis and poor prognosis in glioblastoma patients. These results collectively highlight humanin as a pro-tumoral factor, making it a promising biological target for treating glioblastoma.

This study utilised remote sensing data and ArcGIS 10.8 software to evaluate changes in land use and land cover (LULC) and their effects on land surface temperature (LST) in Hai Duong Province, Vietnam, from 1992 to 2022. Landsat satellite data were pre-processed and classified using supervised methods for the years 1992, 2010, and 2022. In 1992, vegetation cover accounted for 57.89% of land cover, increasing to 84.49% in 2010, but then decreasing again to 66.67% in 2022. In contrast, the built-up area consistently increased, from 2.88% in 1992 to 29.35% in 2022, as most of the barren land present in 1992 became built-up area in 2022. The LST values were calculated from the thermal bands for the years 1992, 2010, and 2022 and ranged from 16.09°C to 34.27°C, 17.04°C to 36.74°C, and 11.03°C to 28.44°C, respectively. In addition, the Normalized Difference Vegetation Index (NDVI) values were calculated using the near-infrared band and the red band, with values ranging from -0.40 to 0.70 over the study period. A linear regression analysis indicated a shift in the correlation between NDVI and LST from positive to negative. This study highlights the significant transformation that occurred in Hai Duong Province due to rapid population density increases, urban growth and infrastructure development, leading to a decline in greenery. These LULC changes can cause severe environmental damage. These research findings will assist policymakers in formulating management strategies and sustainable land-use plans to minimize potential harm and promote sustainable development in the area.

Xây dựng một hệ thống sản xuất trải qua nhiều quá trình như: lập kế hoạch, thiết kế, mô phỏng, thử nghiệm và triển khai thực tế. Trong đó, quá trình quan trọng nhất trước khi triển khai xây dựng nhà máy hoặc phân xưởng là mô phỏng hệ thống để kiểm tra toàn bộ hệ thống sản xuất. Mô phỏng hệ thống sản xuất có thể kiểm tra và tối ưu hóa quá trình kiểm soát mà không cần phải có phần cứng vật lý. Bài báo tập trung nghiên cứu và thực hiện mô phỏng qui trình sản xuất pin lithium-ion trên phần mềm Tecnomatix Plant Simulation. Bằng cách sử dụng công cụ phân tích nút thắt cổ chai (Bottleneck analyzer), các điểm nghẽn trong hệ thống sản xuất đã được xác định. Từ đó, nghiên cứu đã để xuất các biện pháp cải tiến hệ thống sản xuất bằng cách sử dụng hệ thống kéo Kanban tránh những lãng phí có thể xảy ra, đồng thời trực quan hóa và hợp lí hóa qui trình sản xuất.

Tuan Vu,1 Heinz Wiendl,2 Masahisa Katsuno,3 Stephen W Reddel,4 James F Howard Jr5 1Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA; 2Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany; 3Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 4Department of Neurology, Concord Hospital, University of Sydney, Sydney, NSW, Australia; 5Department of Neurology, The University of North Carolina, Chapel Hill, NC, USACorrespondence: Tuan Vu, Department of Neurology, University of South Florida Morsani College of Medicine, 13220 USF Laurel Drive, Tampa, FL, 33612, USA, Tel +1 813 396 2955, Email tvu6@usf.eduAbstract: The terminal complement C5 inhibitor ravulizumab was engineered from the humanized monoclonal antibody eculizumab to have an extended half-life and duration of action. It binds to human terminal complement protein C5, inhibiting its cleavage into C5a and C5b, thus preventing the cascade of events that lead to architectural destruction of the postsynaptic neuromuscular junction membrane by the membrane attack complex, and consequent muscle weakness in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG). The 26-week randomized, placebo-controlled period (RCP) of the phase 3 CHAMPION MG study demonstrated the rapid efficacy of ravulizumab in reducing MG symptoms. Weight-based dosing of ravulizumab every 8 weeks provided sustained efficacy, in terms of patient-reported (Myasthenia Gravis–Activities of Daily Living) and clinician-reported (Quantitative Myasthenia Gravis) endpoints in patients with anti-AChR antibody-positive gMG. Pharmacokinetic and pharmacodynamic analyses showed therapeutic serum ravulizumab concentrations (> 175 μg/mL) were achieved immediately after the first dose and were maintained throughout 26 weeks, irrespective of patient body weight; inhibition of serum free C5 was immediate, complete (< 0.5 μg/mL), and sustained in all patients. Interim results from the open-label extension (OLE) showed that after 60 weeks, efficacy was maintained in patients continuing on ravulizumab. Rapid and sustained improvements in efficacy, similar to those seen in patients initiating ravulizumab in the RCP, were observed after initiation of ravulizumab treatment in patients who switched from placebo in the RCP to ravulizumab in the OLE. The findings from the RCP and OLE support ravulizumab’s favorable safety profile. In conclusion, ravulizumab has a simple weight-based administration and long dosing interval. Its targeted mechanism of action without generalized immunosuppression is reflected in its rapid onset of symptom improvement, sustained efficacy and good safety profile in the treatment of patients with anti-AChR antibody-positive gMG.Plain Language Summary: Ravulizumab in anti-AChR antibody-positive gMGRavulizumab was engineered from eculizumab to have an extended half-life and longer duration of action. It binds to terminal complement protein C5 to inhibit anti-AChR antibody-mediated activation of terminal complement and destruction of the neuromuscular junction.Pharmacokinetic/pharmacodynamic analyses support a simple weight-based administration and long dosing interval and show that therapeutic ravulizumab concentrations and complete inhibition of C5 were achieved immediately after the first dose.The 26-week randomized placebo-controlled period (RCP) of the CHAMPION MG study in patients with anti-AChR antibody-positive gMG showed that ravulizumab has rapid and sustained efficacy with good safety and tolerability across a broad range of patients.Ravulizumab’s efficacy, safety, and tolerability were confirmed in interim analyses of the open-label extension study (including data for up to 60 weeks from the RCP baseline): efficacy was maintained in patients remaining on ravulizumab; rapid and sustained efficacy was established in patients switching from placebo to ravulizumab.Keywords: acetylcholine receptor antibody, complement, membrane attack complex, monoclonal antibody, terminal complement complex

Deforestation in the tropics continues inexorably with severe implications for biodiversity conservation, climate regulation and ecosystem services. This study investigated variation in forest cover in Thua Thien Hue province, Vietnam, using the Landsat Thematic Mapper and Operational Land Imager satellite images over the period 1989–2021. Imageries were classified using the maximum likelihood classification technique for the years 1989, 2006, and 2021 and were evaluated for accuracy using the kappa coefficient for each year. Furthermore, forest cover losses and gains were evaluated using the Normalized Difference Vegetation Index and Soil Adjusted Vegetation Index, which were compared with the output of the supervised classification. Results showed that the forest cover of Thua Thien Hue province has drastically declined over the years. The forest cover, which was estimated at 68.88% (3461.46 km2) of the total land area in 1989, increased to 69.04% (3469.51 km2) in 2006 and subsequently decreased to 57.55% (2891.81 km2) in 2021. Severely reduced forest cover is often associated with the expansion of agriculture on the forest edge; other contributing factors include logging, illegal production land, and forest fires. Overall, our results show the necessity of forest management, rational land-use planning policy, and increased community awareness of conservation and sustainable development of forest resources in the study area in the future.

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

ObjectiveTo examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting.MethodsProspective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health.ResultsAmong 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score 10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q₃ 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression.ConclusionsDespite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.

Glioblastoma stem-cell derived mesenchymal cells become reliant on iron but vulnerable to ferroptosis and within patients of heterogeneous glioblastoma multiforme prognosis for those with high iron uptake is poorer than other subtypes.

Background: Potassium (K) is an essential macronutrient, improves rice yield and contributes to salt stress tolerance. This study determined the best potassium (K) application level on yield formation and the saline resistance capability of rice under salinity field conditions of central Vietnam. Methods: Experiments were comprised of five K fertilizer application rates (0, 25, 50, 75 and 100 kg K2O/ha) and two rice varieties, viz, OM8104 and MNR3 for two growing seasons of 2021 and 2022. All treatments were arranged in a split-plot design with 3 replicates in Duy Vinh commune, Duy Xuyen district, Quang Nam province. Result: Potassium application affected the number of panicles per unit area, filled grain per panicle and actual grain yield of both rice varieties in both seasons under saline condition. Application of 50 kg K2O/ha reduced the soil salinity over the monitoring periods compared to the other K rates. EC values of soil were significantly higher during the hot season than the wet season showing high temperature effects. Application of 50 kg K2O/ha also accumulated maximum dry matter at different crop stages and produced the highest rice yield with 7.57 and 5.25 tons/ha for OM8104 and 7.35 and 5.18 tons/ha for MNR3 in both wet and hot seasons respectively. The harvest index could not affect significantly by K application irrespective of seasons and varieties. These increases in actual grain yields using 50 kg K2O/ha were attributed to increased filled grains per panicle, accumulation of high K+ content and K+/Na+ ratios in rice varieties in both seasons under saline field condition. [ABSTRACT FROM AUTHOR]

We explored how notions of oppression manifest in the identities of 16 multiracial college students. We were guided by two research questions: (a) How does racial oppression affect multiracial students' identities? and (b) Is that racial oppression tied to traditional manifestations of racism, monoracism, or both? Findings demonstrate that racial oppression is influential, yet there are difficulties in identifying racial oppression that targets multiracial people. This study highlights the need for more education on monoracism as a unique and connected form of oppression and on racial asymmetries within multiraciality.