“Reporting on the latest research in epilepsy, a neurological disorder marked by recurrent seizures, experts have delved into the bio-physical mechanisms of epileptic seizures. By analyzing spontaneous and stimulation-induced seizures from patients with focal epilepsy, they isolated the slow-varying direct current (Sv DC) component, a frequency range often overlooked in electroencephalography. This component, which accounts for a high energy proportion in both ictal and interictal states, showed spatially dynamic changes and a moderate correlation with high-frequency activity. Notably, interictal Sv DC fluctuations were more pronounced in electrodes within the epileptogenic zone, suggesting its potential as a marker for epileptogenic localization. The temporal variability of the Sv DC signal also demonstrates potential as an early indicator of seizure development. This research provides a comprehensive framework for understanding epileptic networks and guiding diagnosis and therapy.”
Abstract:BackgroundEpilepsy is a neurological disorder characterized by recurrent seizures due to hyperexcitable neuronal network activity. The manifestations vary widely, ranging from subtle sensory disturbances to profound alterations of consciousness, depending on which brain regions are affected and their underlying etiology. Exploring the bio-physical mechanisms of epileptic seizures holds significant for predicting and controlling the disease.MethodsWe analyzed 45 spontaneous seizures recorded from 24 patients with focal epilepsy, as well as stimulation-induced seizures from 2 additional patients. A second-order Butterworth low-pass filter isolated the slow-varying direct current (Sv DC) component (0.01–0.5 Hz), a frequency range often overlooked in electroencephalography. The energy ratio of the Sv DC component was calculated by dividing its total energy by the total signal energy during seizures and over a 1-hour period including the seizure, enabling comparison between ictal and interictal states.ResultsThe Sv DC component exhibited spatially dynamic changes during both ictal and interictal periods and showed a moderate correlation with high-frequency activity. Moreover, it accounted for a high energy proportion in both periods, with seizure data showing that 80.82% of leads had ≥ 60% Sv DC energy. Notably, interictal Sv DC fluctuations were more pronounced in electrodes located within the epileptogenic zone, suggesting its potential as a marker for epileptogenic localization. Furthermore, the temporal variability of the Sv DC signal, reflected in its dispersion, demonstrates potential as an early indicator of seizure development.ConclusionsThe Sv DC component may reflect local voltage differences likely linked to ion channel activity, potentially contributing to seizure initiation. Combined analysis of Sv DC with low- and high-frequency components offers a comprehensive framework for understanding epileptic networks and guiding diagnosis and therapy.
Keywords:epilepsy;Epileptic seizures;Slow-varying direct current (Sv DC) field;Local voltage difference;Epileptogenic zone
“In the field of acute liver injury (ALI) research, experts have identified a molecular mechanism that initiates and sustains liver regeneration through muscle-liver crosstalk via the FGF6-FGFBP1/FGF5 axis, providing a potential therapeutic target and treatment strategy for ALI.”
Yue-Jie Xu, Cai-Zhi Liu, Ying Chen, Lan-Xin Li, Bo Xu, Ling-Xin You, Mei-Yao Meng, Xin Li, Hong Zhang, Qiu-Rong Ding, Rong Zhang, Xin-Ran Ma, Xiao-Hua Chen, Cheng Hu
Abstract:BackgroundAcute liver injury (ALI) requires rapid hepatic regeneration to avert fatal liver failure. As key mechanisms, systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process. Skeletal muscle, as a major metabolic organ system, undergoes significant remodeling during ALI. However, its specific regulatory contributions remain largely uncharacterized.MethodsPartial (2/3) hepatectomy and acetaminophen were used to induce ALI in male mice. RNA-sequencing(RNA-seq), assay for transposase-accessible chromatin by sequencing (ATAC-seq), chromatin immunoprecipitation, luciferase assay, Western blotting, TUNEL assay, immunohistochemistry, and phase separation assays were performed to reveal the transcriptional axis involved. Serum fibroblast growth factor binding protein 1 (FGFBP1) protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.ResultsIntegrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid (GC) signaling-mediated regulation of fibroblast growth factor 6 (FGF6) in skeletal muscle metabolism. Muscle-specific knockdown of GC receptor (GR) exacerbates ALI and suppresses liver regeneration. Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration, with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown. Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling. Moreover, FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid–liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane. Circulating FGFBP1 subsequently interacts with hepatic fibroblast growth factor 5 (FGF5) through LLPS mechanisms to regulate liver regeneration.ConclusionOur results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis, providing a potential therapeutic target and treatment strategy for ALI.
“In the field of tumor PANoptosis, a "boiling-bubbling" strategy is developed, introducing its research progress. Expert xx established the NZCB NPs system, which provides solutions to solve highly immunogenic tumor PANoptosis problems, laying a foundation for the construction of nano-catalytic oxidation system.”
Abstract:BackgroundPANoptosis has been identified as a robust inflammatory cell death pathway triggered upon host defense against invaded pathogens such as bacteria and viruses, however, pathogen-free tumor PANoptosis has not been achieved yet. Reactive oxygen and nitrogen species capable of inducing robust and diverse cell death pathways such as pyroptosis, apoptosis, and necroptosis are supposed to be the potential triggers for tumor PANop-tosis by ultrasound (US)-controlled sono-piezodynamic therapy.MethodsS-nitrosothiols (SNO)-zinc peroxide (ZnO2)@cyclic dinucleotide (CDN)@mesoporous tetragonal barium titanate (mtBTO) nanoparticles (NZCB NPs) were synthesized by hydrothermal method with subsequent annealing, in situ growth, and finally surface functionalization. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared spectroscopy, and electron spin resonance were used for materials characterizations. Murine melanoma B16 cells are employed to investigate the in vitro US-initiated tumor PANoptosis by NZCB NPs. In vivo US-initiated tumor PANoptosis was investigated on B16 tumor-bearing C57BL/6J mice.ResultsA "boiling-bubbling" strategy is developed to endow the piezoelectric BTO nanocatalysts, with mesoporous architecture, which enables the encapsulation of the immune-agonist CDN (9.4 wt%) to initiate innate immunity of the host. Then, SNO-functionalized ZnO2 was further employed to cap the mesoporous nanocatalysts, forming multifunctional piezocatalytic NZCB NPs. Under US irradiation, intracellular massive reactive oxygen and nitrogen spe-cies such as superoxide anion radicals, nitric oxide (NO), and peroxynitrite (ONOO−) could be produced from the pie-zoelectric NZCB NPs, which, synergized with CDN-triggered antitumoral immunity, lead to highly immunogenic tumor PANoptosis by NZCB NPs through the tumor microenvironment remodeling. Intratumoral injection of NZCB NPs leads to substantial tumor PANoptosis with immune potentiation, ultimately destroying the tumor xenografts effectively.ConclusionThe present work presents the mesostructure design of piezocatalytic nanomaterials and the crosstalk between oxidative stress and antitumor immunity within the tumor, facilitating promising tumor PANoptosis by nano-catalytic oxidation with high effectiveness and biocompatibility.
“In the field of organ transplantation, a novel CRISPR-based detection platform was developed, establishing a one-pot RPA-CRISPR reaction system and optimizing it for BKV and JCV detection. This platform can simultaneously and rapidly detect BKV and JCV with high sensitivity, providing absolute quantification, which is suitable for viral load detection and conducive to personalized and precise treatment for organ transplant recipients.”
Yu Liu, Jing-Song Xu, Li Cao, Shuang Yang, Tian-Ming Li, Hai-Qian Huang, Jun-Heng Zhang, Xue Zhao, Qian Liu, Shun Li, Min Li, Hua Wang
Abstract:BackgroundOrgan transplantation recipients encounter significant risks from acute or chronic infections that threaten graft survival. BK virus (BKV) and JC virus (JCV) are two prominent opportunistic infection viruses, and they may cause polyomavi-rus-associated nephropathy and graft kidney loss in patients who are in an immunosuppressed state after kidney transplanta-tion. Hence, timely detection and sustained monitoring of the viral load are indispensable. However, the current diagnostic methods remain limited, and the development of new molecular detection technology is extremely urgent.MethodsThe sequences and concentrations of clustered regularly interspaced short palindromic repeats (CRISPR) RNA(crRNA), the concentration of Cas13a, and the primers for recombinase polymerase amplification (RPA) were optimized for BKV and JCV detection. Next, a novel microfluidic dual-droplet chip was designed and fabricated, and it was integrated with CRISPR (ddCRISPR) to simultaneously qualitatively detect BKV and JCV. Subsequently, the ddCRISPR assay was verified using clinical samples. Then, a lateral flow strip combined with CRISPR (LFCRISPR) was developed for the detection of BKV and JCV in resource-limited settings.ResultsA one-pot RPA-CRISPR reaction system was established and optimized for BKV and JCV detection. ddCRISPR can simultaneously and rapidly detect BKV and JCV with high sensitivity (10 copies/ml for BKV and 1 copy/ml for JCV), and provide absolute quantification, which is suitable for viral load detection and conducive to personalized and pre-cise treatment for organ transplant recipients. LFCRISPR simplified the operational process through a simple visual readout, facilitating virus screening after organ transplantation.ConclusionsThese platforms incorporate molecular testing into the transplantation treatment model, thereby reducing costs, prolonging the survival time of the graft, improving the clinical outcomes of postoperative manage-ment in kidney transplantation, and enhancing the patients’ quality of life.
“Magnetic particle imaging (MPI), a novel imaging technique with high sensitivity and temporal resolution, is expected to become a mainstream technology for early diagnosis of brain diseases. This review explores its potential applications in brain diseases and discusses the prospects for diagnosis and management.”
Li-Shuang Guo, Yu An, Ze-Yu Zhang, Chen-Bin Ma, Jia-Qian Li, Zhen Dong, Jie Tian, Zhen-Yu Liu, Jian-Gang Liu
Abstract:Brain diseases are characterized by high incidence, disability, and mortality rates. Their elusive nature poses a significant challenge for early diagnosis. Magnetic particle imaging (MPI) is a novel imaging technique with high sensitivity, high temporal resolution, and no ionizing radiation. It relies on the nonlinear magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs), allowing visualization of the spatial concentration distribution of SPIONs in biological tissues. MPI is expected to become a mainstream technology for the early diagnosis of brain diseases, such as cancerous, cerebrovascular, neurodegenerative, and inflammatory diseases. This review provides an overview of the principles of MPI, explores its potential applications in brain diseases, and discusses the prospects for the diagnosis and management of these diseases.
“Recent advances in next-generation sequencing and bioinformatics have driven growing interest in the distinct roles of intratumoral microbiota, particularly intracellular bacteria, during tumor evolution. The present review explores the sources, mechanisms of invasion into cancer cells, and potential survival strategies of intracellular bacteria in neoplasms, highlighting their critical role in cancer development. Expert xx established the xx system, which provides solutions to solve xx problems and lay a foundation for the construction of xx system.”
Abstract:Recent advances in next-generation sequencing and bioinformatics have driven growing interest in the distinct roles of intratumoral microbiota, particularly intracellular bacteria, during tumor evolution. These bacteria increase the like-lihood of metastasis, play important roles in cancer progression, and impact therapy efficiency. The present review explores the sources, mechanisms of invasion into cancer cells, and potential survival strategies of intracellular bacte-ria in neoplasms, highlighting their critical role in cancer development. We also examine the heterogeneity and intri-cate interplay of intratumoral microbial communities with immune and cancer cells, emphasizing their potential roles in modulating host genetics, epigenetics, and immunity. Finally, we discuss novel approaches to targeting intracel-lular bacteria, particularly engineered drug delivery systems, and synthetic biology, which aim to enhance bacterial clearance, reprogram the tumor immune microenvironment, and enhance the efficacy of chemotherapy and immu-notherapy. As a result, this review provides new insights to guide future investigations and support the development of microbiota-based interventions in oncology.
Abstract:Conventional diagnostic and therapeutic approaches in orthopedics are frequently time intensive and associated with elevated rates of diagnostic error, underscoring the urgent need for more efficient tools to improve the cur-rent situation. Recently, artificial intelligence (AI) has been increasingly integrated into orthopedic practice, provid-ing data-driven approaches to support diagnostic and therapeutic processes. With the continuous advancement of AI technologies and their incorporation into routine orthopedic workflows, a comprehensive understanding of AI principles and their clinical applications has become increasingly essential. The review commences with a summary of the core concepts and historical evolution of AI, followed by an examination of machine learning and deep learn-ing frameworks designed for orthopedic clinical and research applications. We then explore various AI-based applica-tions in orthopedics, including image analysis, disease diagnosis, and treatment approaches such as surgical assis-tance, drug development, rehabilitation support, and personalized therapy. These applications are designed to help researchers and clinicians gain a deeper understanding of the current applications of AI in orthopedics. The review also highlights key challenges and limitations that affect the practical use of AI, such as data quality, model generaliz-ability, and clinical validation. Finally, we discuss possible future directions for improving AI technologies and promot-ing their safe and effective integration into orthopedic care.
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”