CADD-based discovery of novel oligomeric modulators of PKM2 with antitumor activity in aggressive human glioblastoma models by Maia Cabrera, Romina Armando, Ian Czarnowski, Patricio Chinestrad, Ramiro Blanco, Alejandra Zinni, Daniel Gómez, Diego L. Mengual Gómez, Pablo Lorenzano Menna

“…These effects were directly linked to their inhibition of PKM2 enzymatic activity, validating the proposed mechanism of action in their rational design. ADMET studies further highlighted their strong potential as lead PKM2 inhibitors for GBM treatment.Molecular dynamics (MD) simulations and post-MD analyses, including Dynamic Cross-Correlation Maps (DCCM), Probability Density Function (PDF), and Free Energy Landscape (FEL), confirmed the stability of the protein-ligand interactions and highlighted critical residues at the dimer-dimer interface. …”
Get full text

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery by Massimo Nunes, Mare Vlok, Amy Proal, Douglas B. Kell, Etheresia Pretorius

“…ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes. …”
Get full text

SCO and BRICS in an emerging multipolar world order by D. V. Malyshev

“…The author concludes that although the SCO member countries have managed to create a solid legal framework and effective mechanisms of interaction, there are contradictions and even clashes between them on a number of issues. …”
Get full text

Photometric Determination of Unresolved Main-sequence Binaries in the Pleiades: Binary Fraction and Mass-ratio Distribution by Rongrong Liu, Zhengyi Shao, Lu Li

“…The variations of f _b and q with ${{ \mathcal M }}_{1}$ reveal a complex binary distribution within the Pleiades, which might be attributed to a combination of primordial binary formation mechanisms, dynamical interactions, and the observational limit of photometric binaries imposed by ${q}_{{\rm{lim}}}({{ \mathcal M }}_{1})$ .…”
Get full text

Human neural stem cell–derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway by Jiayi Wang, Mengke Zhao, Dong Fu, Meina Wang, Chao Han, Zhongyue Lv, Liang Wang, Jing Liu

“…However, the precise mechanisms underlying the efficacy and safety of human neural stem cell–derived extracellular vesicles remain unclear, presenting challenges for clinical translation. …”
Get full text

Analysis of the Influence of Groundwater Level Fluctuation on Karst Soil Cave Collapse by Xuejun Chen, Mingming Xue, Yu Song

“…These laws elucidate the change of water-gas pressure in different initial water level fluctuations and reveal the collapse mechanism of water level fluctuations. It will provide essential theoretical support for further research on the action law of hydrodynamic factors on karst collapse and a scientific and reasonable basis for urban groundwater pumping control, karst and roadbed collapse prevention and prediction.…”
Get full text

Design, Molecular Docking, Synthesis, Characterization and Preliminary Evaluation of Novel 1,3,4-Oxadiazole Derivatives as Cyclin-Dependent Kinase 2 Inhibitors by Yousef Sabah Ali, Monther Faisal Mahdi, Basma Monjid Abd Razik, Talal Aburjai

“…The findings of the cytotoxicity investigation and molecular docking analysis of these final derivatives (5a-5g) demonstrated a strong correlation, indicating the importance of a comprehensive pharmacological study to comprehend the anti-cancer mechanisms of these newly synthesized compounds fully. …”
Get full text

A Spatial–Temporal Difference Aggregation Network for Gaofen-2 Multitemporal Image in Cropland Change Area by Chuang Liu, Liyang Bao, Zhiqi Zhang

“…Furthermore, the serious imbalance between the cropland change area and the nonchange area makes it difficult to focus on the real change area in the cropland under these interferences. …”
Get full text

Role of exercise on ncRNAs and exosomal ncRNAs in preventing neurodegenerative diseases: a narrative review by Shangwu Liu, Runhong Zhang, Jamal Hallajzadeh

“…However, more research is needed to fully understand the underlying mechanisms and to further explore the potential of exercise-induced ncRNA signatures as biomarkers and therapeutic targets for neurodegenerative disorders.…”
Get full text

Advancing precision therapy for colorectal cancer: Developing clinical indications for multi-target kinase inhibitor BPR1J481 using patient-derived xenograft models by Ya-Chu Tang, Jing-Jim Ou, Shu-Ching Hsu, Chih-Hsiang Huang, Li-Mei Lin, Hsin-Huei Chang, Yi-Hsin Wang, Zih-Ting Huang, Manwu Sun, Ko-Jiunn Liu, Yi-Mei Hung, Chi-Yun Lai, Chuan Shih, Chiung-Tong Chen, Jang-Yang Chang, Hsing-Pang Hsieh, Weir-Torn Jiaang, Ching-Chuan Kuo

“…This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. …”
Get full text

Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. by Alexandra Schuetz, Claire Deleage, Irini Sereti, Rungsun Rerknimitr, Nittaya Phanuphak, Yuwadee Phuang-Ngern, Jacob D Estes, Netanya G Sandler, Suchada Sukhumvittaya, Mary Marovich, Surat Jongrakthaitae, Siriwat Akapirat, James L K Fletscher, Eugene Kroon, Robin Dewar, Rapee Trichavaroj, Nitiya Chomchey, Daniel C Douek, Robert J O Connell, Viseth Ngauy, Merlin L Robb, Praphan Phanuphak, Nelson L Michael, Jean-Louis Excler, Jerome H Kim, Mark S de Souza, Jintanat Ananworanich, RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups

“…These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.…”
Get full text

An Investigation of Infrared Small Target Detection by Using the SPT–YOLO Technique by Yongjun Qi, Shaohua Yang, Zhengzheng Jia, Yuanmeng Song, Jie Zhu, Xin Liu, Hongxing Zheng

“…To detect and recognize small-size and submerged complex background targets in infrared images, we combine a dynamic receptive field fusion strategy and a multi-scale feature fusion mechanism to improve the detection performance of small targets significantly. …”
Get full text

Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy by Pei-Pei Liu, Xin-Yue Yu, Qing-Qing Pan, Jia-Jun Ren, Yu-Xuan Han, Kai Zhang, Yan Wang, Yin Huang, Tao Ban

“…Additionally, we tested the cardioprotective effects of two drug candidates in the SCM mouse model and explored their mechanism-of-action in H9c2 cells. Results: Network analysis identified 129 drugs associated with SCM, which were refined to 14 drug candidates based on strong network predictions, proven anti-infective effects, suitability for ICU use, and minimal side effects. …”
Get full text

Nanomaterials: Promising Tools for the Diagnosis and Treatment of Myocardial Infarction by Ge Y, Wu L, Mei S, Wu J

“…We summarize the pathophysiological mechanisms and staging of myocardial infarction. We systematically review the applications of nanomaterials in MI diagnosis, including the detection of biomarkers and imaging techniques, as well as in MI treatment, encompassing anti-inflammatory effects, antioxidant stress, inhibition of fibrosis, promotion of angiogenesis, and cardiac conduction repair. …”
Get full text

Constituer des archives en sexologie francophone : un essai d’autoethnographie by Alain Giami

“…In this perspective, the mechanisms put in place by the institutions that will receive these archives occupy a fundamental place in the constitution, collection and archiving of the documents and they must benefit from the confidence of the archive holders.…”
Get full text

Wet Feeding Promotes Growth without Affecting Hypothalamic Peptide Gene Expression in Growing Broiler Chicks by Tomoya Matsunami, Yuhui Zhang, Yuji Taniguchi, Sei-ichi Hinomoto, Takaoki Saneyasu, Hiroshi Kamisoyama, Kazuhisa Honda

“…From the perspective of animal welfare, freedom from hunger and thirst is an undeniable requirement for the poultry industry. Regulatory mechanisms underlying drinking behavior have not yet been identified in chickens; however, the regulation of osmolality and water intake appears to be closely related. …”
Get full text

An Investigation Towards Resampling Techniques and Classification Algorithms on CM1 NASA PROMISE Dataset for Software Defect Prediction by Agung Fatwanto, Muh Nur Aslam, Rebbecah Ndugi, Muhammad Syafrudin

“…In the context of classification models, ensemble-based algorithms, which extend the decision tree classification mechanism such as Random Forest and eXtreme Gradient Boosting, achieved sufficiently good performance for predicting defective software modules. …”
Get full text

Association of Circulating Neprilysin with BMI, Cardiovascular Health, and Kidney Function in High-Risk Pregnancies: A Pilot Study by Kaltrina Kutllovci Hasani, Azra Kulovic-Sissawo, Adam Saloň, Christina Stern, Karoline Mayer-Pickel, Mila Cervar-Zivkovic, Nandu Goswami, Herbert Fluhr, Ursula Hiden

“…Further research is needed to clarify these mechanisms and their clinical relevance.…”
Get full text

Evaluating Trends in Interior Design Strategies and Their Impact on the Emotional Experience of Older Adults by Lintong Li, Suhua Wang, Noranita Mansor, Athira Azmi, Jialing Xiang

“…The study introduces a dynamic feedback mechanism within the framework of the proposed architectural interior design strategy, highlighting the importance of employing multiple strategies that balance and complement each other in practical applications. …”
Get full text

TGFβ1 Controls PPARγ Expression, Transcriptional Potential, and Activity, in Part, through Smad3 Signaling in Murine Lung Fibroblasts by Allan Ramirez, Erin N. Ballard, Jesse Roman

“…Transforming growth factor β1 (TGFβ1) promotes fibrosis by, among other mechanisms, activating quiescent fibroblasts into myofibroblasts and increasing the expression of extracellular matrices. …”
Get full text