Nonlinear analysis and recognition of epileptic EEG signals in different stages.

It is a hot problem in epilepsy research to detect and predict seizures by EEG signals. Clinically, it is generally observed that there are only sudden abnormal signals during the ictal stage, but there is no significant difference in the EEG signal between the interictal and preictal stages. To solve the problem that preictal signals are difficult to recognize clinically, and then effectively improve the recognition efficiency of epileptic seizures, so, in this paper, some nonlinear methods are comprehensively used to extract the hidden information in the EEG signals in different stages, namely, phase space reconstruction (PSR), Poincaré section (PS), synchroextracting transform (SET) and machine learning for EEG signal analysis. Firstly, PSR based on C-C method is used, and the results show that there are different diffuse attractor trajectories of the signals in different stages. Secondly, the confidence ellipse (CE) is constructed by using the scatter diagram of the corresponding trajectory on PS, and the aspect ratio and area of the ellipse are calculated. The results show that there is an interesting transitional phenomenon in preictal stage. To recognize ictal and preictal signals, time-frequency (TF) spectrums which are processed by SET are fed into the convolutional neural networks (CNN) classifier. The accuracy of recognize ictal and preictal signals reaches 99.7% and 93.7% respectively. To summarize, our results based on nonlinear method provide new research ideas for seizures detection and prediction.

Discovery Small-Molecule p300 Inhibitors Derived from a Newly Developed Indazolone-Focused DNA-Encoded Library.

The DNA-encoded library (DEL) is a robust tool for chemical biology and drug discovery. In this study, we developed a DNA-compatible light-promoted reaction that is highly efficient and plate-compatible for DEL construction based on the formation of the indazolone scaffold. Employing this high-efficiency approach, we constructed a DEL featuring an indazolone core, which enabled the identification of a novel series of ligands specifically targeting E1A-binding protein (p300) after DEL selection. Taken together, our findings underscore the feasibility of light-promoted reactions in DEL synthesis and unveil promising avenues for developing p300-targeting inhibitors.

Interlayer Potassium Single-Atom-Coordinated g-C3N4 for Significantly Boosted Visible Light Photocatalytic H2 Production.

In recent years, graphitic carbon nitride (g-C3N4) has attracted considerable attention because it includes earth-abundant carbon and nitrogen elements and exhibits good chemical and thermal stability owing to the strong covalent interaction in its conjugated layer structure. However, bulk g-C3N4 has some disadvantages of low specific surface area, poor light absorption, rapid recombination of photogenerated charge carriers, and insufficient active sites, which hinder its practical applications. In this study, we design and synthesize potassium single-atom (K SAs)-doped g-C3N4 porous nanosheets (CM-KX, where X represents the mass of KHP added) via supramolecular self-assembling and chemical cross-linking copolymerization strategies. The results show that the utilization of supramolecules as precursors can produce g-C3N4 nanosheets with reduced thickness, increased surface area, and abundant mesopores. In addition, the intercalation of K atoms within the g-C3N4 nitrogen pots through the formation of K-N bonds results in the reduction of the band gap and expansion of the visible-light absorption range. The optimized K-doped CM-K12 nanosheets achieve a specific surface area of 127 m2 g-1, which is 11.4 times larger than that of the pristine g-C3N4 nanosheets. Furthermore, the optimal CM-K12 sample exhibits the maximum H2 production rate of 127.78 µmol h-1 under visible light (λ ≥ 420 nm), which is nearly 23 times higher than that of bare g-C3N4. This significant improvement of photocatalytic activity is attributed to the synergistic effects of the mesoporous structure and K SAs doping, which effectively increase the specific surface area, improve the visible-light absorption capacity, and facilitate the separation and transfer of photogenerated electron-hole pairs. Besides, the optimal sample shows good chemical stability for 20 h in the recycling experiments. Density functional theory calculations confirm that the introduction of K SAs significantly boosts the adsorption energy for water and decreases the activation energy barrier for the reduction of water to hydrogen.

Molecular insight into T cell exhaustion in hepatocellular carcinoma.

Hepatocellular carcinoma is one of the leading causes of cancer-related mortality globally. The emergence of immunotherapy has been shown to be a promising therapeutic approach for hepatocellular carcinoma in recent years. It has been well known that T cell plays a key role in current immunotherapy. However, sustained exposure to antigenic stimulation within the tumor microenvironment may lead to T cell exhaustion, which may cause treatment ineffectiveness. Therefore, reversing T cell exhaustion has been an important issue for the clinical application of immunotherapy, and a comprehensive understanding of the intricacies surrounding T cell exhaustion and its underlying mechanisms is imperative for devising strategies to overcome the T cell exhaustion during treatment. In this review, we summarized the reported drivers of T cell exhaustion in hepatocellular carcinoma and delineate potential ways to reverse it. Additionally, we discussed the interplay among metabolic plasticity, epigenetic regulation, and transcriptional factors in exhausted T cells in hepatocellular carcinoma, and their implication for future clinical applications.

Chemical Space Profiling of SARS-CoV-2 PLpro Using DNA-Encoded Focused Libraries.

DNA-encoded library (DEL) technology is gaining attention for its rapid construction and deconvolution capabilities. Our study explored a novel strategy using rational DELs tailored for the SARS-CoV-2 papain-like protease, which revealed new fragments. Structural changes post-DEL screening mimic traditional medicinal chemistry lead optimization. We unveiled unique aromatic structures offering an alternative optimization path. Notably, we identified superior binding fragments targeting the BL2 groove. Derivative 16 emerged as the most promising by exhibiting IC50 values of 0.25 µM. Derivative 6, which features an aromatic fragment capped with a naphthalene moiety, showed IC50 values of 2.91 µM. Molecular modeling revealed hydrogen bond interactions with Lys157 residue and potential covalent interactions with nearby amino acid residues. This research underscored DEL's potential for fragment-based drug discovery against SARS-CoV-2 protease.

Endoscopic endonasal surgery of Rathke's cleft cysts-- preoperative imaging evaluation, personalized removal and multilevel sellar floor reconstruction.

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of endoscopic endonasal surgery (EES) for Rathke's cleft cysts (RCCs) and the advantages of detailed preoperative imaging evaluation, intraoperative personalized removal and multilevel sellar floor reconstruction. METHODS: The clinical data of 43 patients with RCCs who were treated by EES in the neurosurgery department of affiliated hospital of Jiangnan University and Wuxi No.2 People's Hospital from January 2018 to January 2023 were retrospectively analyzed. The effectiveness of EES for RCCs was analyzed by imaging information, surgical procedures, symptom improvement and complications. RESULTS: All 43 RCCs were completely removed by EES, and all clinical symptoms improved to varying degrees. Postoperative relief of headache was achieved in 23 out of 26 patients (88.5 %); there was improvement in 10 out of 13 patients with visual field disorders (76.9 %) and in 8 out of 10 patients with endocrine abnormalities (80 %). New hormonal deficiency was discovered in 7 of all the patients postoperatively. There were 8 patients with postoperative diabetes insipidus and 1 patient with cerebrospinal fluid leakage. The incidence of new hormonal dysfunction and postoperative DI in expanded EES (33.3 %, 33.3 %) was higher than it in conventional EES (4 %, 8 %) (P < 0.05). The average follow-up time was 29.1 ± 14.8 months, and there were no deaths or infections. Three patients presented with cyst recurrence on MRI. CONCLUSIONS: The clinical manifestations and imaging characteristics of RCCs are variable, and a detailed preoperative review of the imaging is helpful for the development of surgical plans. RCCs can be treated more safely and thoroughly with less trauma and complications by intraoperative personalized removal and multilevel sellar floor reconstruction. The high incidence of new hormonal dysfunction and postoperative DI may be related to the disturbance of the pituitary stalk. EES has unique advantages and high clinical application value for the treatment of RCCs.

Rhodium-Promoted C-H Activation/Annulation between DNA-Linked Terminal Alkyne and Aromatic Acid: A Finding from the Selection Outcomes.

Inspired by previous selection outcomes, we investigated and developed a rhodium-promoted C-H activation/annulation reaction of DNA-linked terminal alkynes and aromatic acids. This reaction exhibits excellent efficiency with high conversions and a broad substrate scope. Most importantly, the unique DEL-compatible conditions provide a better scenario for yielding an isocoumarin scaffold compared to conventional organic reaction conditions, and this newly developed on-DNA method has confirmed its feasibility in preparing DNA-encoded libraries.

Intracellular self-aggregation of biomimetic Fe3O4 nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer.

Nanomedicines based on ferroptosis may be effective strategies for cancer therapy due to their unique inducing mechanism. However, the challenges, including non-target distribution, poor accumulation and retention of nanomedicine, have a profound impact on the effectiveness of drug delivery. Here, we developed cancer cell membrane (CCM)-coated Fe3O4 nanoparticles (NPs) modified with supramolecular precursors and loaded with sulfasalazine (SAS) for breast cancer therapy. Benefiting from the coating of the CCM, these NPs can be specifically recognized and internalized by tumor cells rapidly after being administered and form aggregates via the host-guest interaction between adamantane (ADA) and cyclodextrins (CD), which in turn effectively reduces the exocytosis of tumor cells and prolongs the retention time. In vitro and in vivo studies showed that Fe3O4 NPs possessed effective cellular uptake and precise specific accumulation in tumor cells and tissues through CCM-targeted supramolecular in situ aggregation, demonstrating enhanced ferroptosis-inducing therapy of breast cancer. Overall, this work provided a supramolecular biomimetic platform to achieve targeted delivery of Fe3O4 NPs with high efficiency and precise self-assembly for improved cancer therapy.

A Vancomycin-Templated DNA-Encoded Library for Combating Drug-Resistant Bacteria.

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Excitation generated preferential binding sites for ethane on porous carbon-copper porphyrin sorbents: ethane/ethylene adsorptive separation improved by light.

Energy-efficient separation of C2H6/C2H4 is a great challenge, for which adsorptive separation is very promising. C2H6-selective adsorption has big implications, while the design of C2H6-sorbents with ideal adsorption capability, particularly with the C2H6/C2H4-selectivity exceeded 2.0, is still challenging. Instead of the current strategies such as chemical modification or pore space modulation, we propose a new methodology for the design of C2H6-sorbents. With a Cu-TCPP [TCPP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin] framework dispersed onto a microporous carbon and a hierarchical-pore carbon, two composite sorbents are fabricated. The composite sorbents exhibit enhanced C2H6-selective adsorption capabilities with visible light, particularly the composite sorbent based on the hierarchical-pore carbon, whose C2H6 and C2H4 adsorption capacities (0 °C, 1 bar) are targetedly increased by 27% and only 1.8% with visible light, and therefore, an C2H6-selectivity (C2H6/C2H4 = 10/90, v/v) of 4.8 can be realized. With visible light, the adsorption force of the C2H6 molecule can be asymmetrically enhanced by the excitation enriched electron density over the adsorption sites formed via the close interaction between the Cu-TCPP and the carbon layer, whereas that of the C2H4 molecule is symmetrically altered and the forces cancelled each other out. This strategy may open up a new route for energy-efficient adsorptive separation of C2H6/C2H4 with light.

The Effect of Unhealthy Food Packaging Information Boundaries on Consumer Purchasing Intentions.

Existing studies have examined unhealthy food packaging information, mainly focusing on aspects such as the content, color, and text, whilst paying less attention to the boundaries of information. This paper investigates unhealthy foods through three experiments, revealing that the presence (vs. absence) of packaging information boundaries on unhealthy foods has a negative impact on consumers' purchasing intentions (p = 0.040) (Experiment 1). The feeling of constraint mediates this effect (ß = -0.078, CI: [-0.1911, -0.0111]) (Experiment 2). Additionally, consumers with an independent self-construal exhibit reduced purchasing intentions when unhealthy food packaging information boundaries are present (vs. absent) (p < 0.001), whereas those with an interdependent self-construal show increased purchasing intentions under the same conditions (p = 0.024) (Experiment 3). This paper reveals the psychological mechanism and boundary conditions of unhealthy food packaging information boundaries affecting consumers' purchasing intention and provides practical inspiration for government policy-making related to unhealthy food packaging.

Discovery and Optimization of WDR5 Inhibitors via Cascade Deoxyribonucleic Acid-Encoded Library Selection Approach.

The DNA-encoded library (DEL) is a powerful hit generation tool for chemical biology and drug discovery; however, the optimization of DEL hits remained a daunting challenge for the medicinal chemistry community. In this study, hit compounds targeting the WIN binding domain of WDR5 were discovered by the initial three-cycle linear DEL selection, and their potency was further enhanced by a cascade DEL selection from the focused DEL designed based on the original first run DEL hits. As expected, these new compounds from the second run of focused DEL were more potent WDR5 inhibitors in the protein binding assay confirmed by the off-DNA synthesis. Interestingly, selected inhibitors exhibited good antiproliferative activity in two human acute leukemia cell lines. Taken together, this new cascade DEL selection strategy may have tremendous potential for finding high-affinity leads against WDR5 and provide opportunities to explore and optimize inhibitors for other targets.

The immunomodulatory effects of mesenchymal stem cell-derived extracellular vesicles in Alzheimer's disease.

Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer's disease following Aß amyloid deposition and tau protein hyperphosphorylation, activated in the central nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer's disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer's disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer's disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer's disease by targeting neuroinflammation.