NSUN5/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion.

Malignant glioma exhibits immune evasion characterized by highly expressing the immune checkpoint CD47. RNA 5-methylcytosine(m5C) modification plays a pivotal role in tumor pathogenesis. However, the mechanism underlying m5C-modified RNA metabolism remains unclear, as does the contribution of m5C-modified RNA to the glioma immune microenvironment. In this study, we demonstrate that the canonical 28SrRNA methyltransferase NSUN5 down-regulates ß-catenin by promoting the degradation of its mRNA, leading to enhanced phagocytosis of tumor-associated macrophages (TAMs). Specifically, the NSUN5-induced suppression of ß-catenin relies on its methyltransferase activity mediated by cysteine 359 (C359) and is not influenced by its localization in the nucleolus. Intriguingly, NSUN5 directly interacts with and deposits m5C on CTNNB1 caRNA (chromatin-associated RNA). NSUN5-induced recruitment of TET2 to chromatin is independent of its methyltransferase activity. The m5C modification on caRNA is subsequently oxidized into 5-hydroxymethylcytosine (5hmC) by TET2, which is dependent on its binding affinity for Fe2+ and α-KG. Furthermore, NSUN5 enhances the chromatin recruitment of RBFOX2 which acts as a 5hmC-specific reader to recognize and facilitate the degradation of 5hmC caRNA. Notably, hmeRIP-seq analysis reveals numerous mRNA substrates of NSUN5 that potentially undergo this mode of metabolism. In addition, NSUN5 is epigenetically suppressed by DNA methylation and is negatively correlated with IDH1-R132H mutation in glioma patients. Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.

Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide, characterized by persistent respiratory symptoms and airflow limitation. The involvement of C-C motif chemokine ligand 2 (CCL2) in COPD pathogenesis, particularly in macrophage regulation and activation, is poorly understood despite its recognized role in chronic inflammation. Our study aims to elucidate the regulatory role and molecular mechanisms of CCL2 in the pathogenesis of COPD, providing new insights for therapeutic strategies. METHODS: This study focused on the CCL2-CCR2 signaling pathway, exploring its role in COPD pathogenesis using both Ccl2 knockout (KO) mice and pharmacological inhibitors. To dissect the underlying mechanisms, we employed various in vitro and in vivo methods to analyze the secretion patterns and pathogenic effects of CCL2 and its downstream molecular signaling through the CCL2-CCR2 axis. RESULTS: Elevated Ccl2 expression was confirmed in the lungs of COPD mice and was associated with enhanced recruitment and activation of macrophages. Deletion of Ccl2 in knockout mice, as well as treatment with a Ccr2 inhibitor, resulted in protection against CS- and LPS-induced alveolar injury and airway remodeling. Mechanistically, CCL2 was predominantly secreted by bronchial epithelial cells in a process dependent on STAT1 phosphorylation and acted through the CCR2 receptor on macrophages. This interaction activated the PI3K-AKT signaling pathway, which was pivotal for macrophage activation and the secretion of inflammatory cytokines, further influencing the progression of COPD. CONCLUSIONS: The study highlighted the crucial role of CCL2 in mediating inflammatory responses and remodeling in COPD. It enhanced our understanding of COPD's molecular mechanisms, particularly how CCL2's interaction with the CCR2 activates critical signaling pathways. Targeting the CCL2-CCR2 axis emerged as a promising strategy to alleviate COPD pathology.

MFI-11 in Chinese elderly esophageal cancer patients with postoperative adverse outcomes.

BACKGROUND: Frailty becomes more pronounced with advancing age, tightly intertwined with adverse clinical outcomes. Across diverse medical disciplines, frailty is now universally recognized as not only a risk factor but also a predictive indicator for unfavorable clinical prognosis. METHODS: This study was a retrospective cohort study that included clinical data from patients (aged ≥ 65 years) with esophageal cancer treated surgically at the First Affiliated Hospital of Anhui Medical University in 2021. For each patient, we calculated their 11-index modified frailty index(mFI-11) scores and categorized the patients into a frailty group (mFI-11hign) and a non-frailty group (mFI-11low) based on the optimal grouping cutoff value of 0.27 from a previous study. The primary study index was the incidence of postoperative pulmonary infection, arrhythmia, anastomotic fistula, chylothorax, and electrolyte disturbance complications. Secondary study indicators included postoperative ICU stay, total hospitalization time, readmission rate within 30 days of discharge, and mortality within 30 days after surgery. We performed univariate and multivariate analyses to assess the association between mFI-11 and adverse outcomes as well as postoperative complications. RESULTS: Five hundred and fifteen patients were included, including 64.9% (334/515) in the non-frailty group and 35.1% (181/515) in the frailty group. Comparing postoperative complication rates between the two groups revealed lower incidences of postoperative anastomotic fistula (21.5% vs. 4.5%), chylothorax (16.0% vs. 2.1%), cardiac arrhythmia (61.9% vs. 9.9%), pulmonary infections (85.1% vs. 26.6%), and electrolyte disturbance (84.5% vs. 15.0%) in patients of the non-frailty group was lower than that in the frailty group (p < 0.05). mFI-11 showed better prognostic results in predicting postoperative complications. anastomotic fistula (area under the ROC curve AUROC = 0.707), chylothorax (area under the ROC curve AUROC = 0.744), pulmonary infection (area under the ROC curve AUROC = 0.767), arrhythmia (area under the ROC curve AUROC = 0.793), electrolyte disturbance (area under the ROC curve AUROC = 0.832), and admission to ICU (area under the ROC curve AUROC = 0.700). CONCLUSION: Preoperative frail elderly patients with esophageal cancer have a high rate of postoperative complications. mFI-11 can be used as an objective indicator for identifying elderly patients at risk for esophageal cancer.

Embracing beauty through leftward movements: An ERP study on metaphorical association between hand actions and aesthetic judgments.

In this study, we examined the metaphorical association between aesthetic judgments of faces and horizontal hand movements as well as their cognitive neural mechanisms using a joint categorical response task. In the "aesthetic-action" metaphorical representation situation, participants were asked to classify beautiful/ugly faces by moving the mouse to the left or the right. The results showed that the joint categorization condition "judge beautiful-move mouse left, judge ugly-move mouse right" had a shorter reaction time than the "judge beautiful-move mouse right, judge ugly-move mouse left" condition, which was accompanied by larger amplitudes of the early component N170, EPN, and the late component P300. Combining the behavioral and event-related potentials (ERPs) results, the present study demonstrated a metaphorical association between horizontal hand actions and aesthetic judgments. It suggested that horizontal hand actions can affect the speed of aesthetic judgments by influencing processing fluency, emotional arousal level, categorization motivation, and attentional resources. These findings provide new perspectives to better understand the cognitive process of aesthetic judgments and provide a basis for applying embodied cognition and metaphor theory to the field of aesthetic psychology.

Understanding tightened muscle in knee osteoarthritis and the impacts of Fu's subcutaneous needling: A pilot trial with shear-wave elastography and near-infrared spectroscopy.

BACKGROUND: Given the scarce reports on the interplay between Fu's subcutaneous needling (FSN), tightened muscle, and therapeutic effects, we developed a clinical research protocol to synchronously collect data on clinical efficacy and muscle characteristics in patients with knee osteoarthritis, exploring the mechanism of FSN action. The primary aim was to assess the feasibility and safety of this protocol, guiding future trials and their sample size calculations. METHODS: In this prospective, single-blind, self-controlled study, 19 patients with early to mid-stage unilateral knee osteoarthritis underwent FSN therapy on both knees over 1 week (4 sessions, every other day). We measured local elastic modulus, muscle thickness, blood flow volume, and oxygen consumption rate of bilateral vastus lateralis muscles using shear-wave elastography and near-infrared spectroscopy (NIRS) before and after the first and fourth treatments. Additionally, real-time NIRS indicators (oxygenated hemoglobin [O2Hb], deoxyhemoglobin [HHb], total hemoglobin [THb], and tissue saturation index [TSI]) were recorded during these treatments. Pain intensity (visual analogue scale [VAS]), functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and active range of motion were evaluated before these treatments. RESULTS: All 19 participants completed the trial without serious adverse events. After 3 FSN treatments, significant changes were observed in VAS and WOMAC scores (VAS: P < .001; WOMAC: P < .001), and knee flexion (P < .001) and external rotation (P = .02), except for internal rotation. No meaningful significant differences were observed in muscle characteristics at baseline or between pre- and post-treatment periods. NIRS results during treatments indicated significant increases in local O2Hb and THb post-FSN therapy (First treatment: O2Hb: P = .005; THb: P = .006. Fourth treatment: O2Hb: P = .002; THb: P = .004); however, no significant increases were observed for HHb (First treatment: P = .06; Fourth treatment: P = .28). No linear correlation was found between therapeutic effects and changes in tightened muscle indices. CONCLUSION: FSN reduces pain and improves joint function in knee osteoarthritis, while also enhancing blood flow and oxygenation in the vastus lateralis muscle of the affected side. Further revisions of this protocol are warranted based on our insights.

WITHDRAWN: Diffusion kurtosis imaging (DKI) in characterization in indetermined solitary pulmonary nodules (SPNs): comparison with conventional DWI and quantitative.

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Structure of yeast RAVE bound to a partial V 1 complex.

Vacuolar-type ATPases (V-ATPases) are membrane-embedded proton pumps that acidify intracellular compartments in almost all eukaryotic cells. Homologous with ATP synthases, these multi-subunit enzymes consist of a soluble catalytic V 1 subcomplex and a membrane-embedded proton-translocating V O subcomplex. The V 1 and V O subcomplexes can undergo reversible dissociation to regulate proton pumping, with reassociation of V 1 and V O requiring the protein complex known as RAVE (regulator of the A TPase of v acuoles and e ndosomes). In the yeast Saccharomyces cerevisiae , RAVE consists of subunits Rav1p, Rav2p, and Skp1p. We used electron cryomicroscopy (cryo-EM) to determine a structure of yeast RAVE bound to V 1 . In the structure, RAVE is a L-shaped complex with Rav2p pointing toward the membrane and Skp1p distant from both the membrane and V 1 . Only Rav1p interacts with V 1 , binding to a region of subunit A not found in the corresponding ATP synthase subunit. When bound to RAVE, V 1 is in a rotational state suitable for binding the free V O complex, but it is partially disrupted in the structure, missing five of its 16 subunits. Other than these missing subunits and the conformation of the inhibitory subunit H, the V 1 complex with RAVE appears poised for reassembly with V O .

Utility of C4d Immunohistochemistry in the Diagnosis of Esophageal Pemphigus Vulgaris.

Aims. To assess the utility of C4d immunohistochemistry for esophageal pemphigus vulgaris. Methods and results. We searched for patients with a history of esophageal pemphigus vulgaris who had esophageal biopsies for routine hematoxylin and eosin (H&E) staining. A total of 8 biopsies from 7 patients were available. We also identified 18 non-pemphigus esophageal biopsies for controls. C4d immunohistochemistry was performed on each biopsy. Five of 6 (83%) biopsies with classic pemphigus vulgaris histologic findings were positive for intercellular staining at the basal layer. The negative biopsy was in a patient that had recently received high-dose corticosteroid treatment for a flare. Two biopsies with atypical histologic features for pemphigus vulgaris had negative C4d staining but positive direct immunofluorescence (DIF) studies. Various nonspecific C4d staining patterns were observed in the controls, but none showed the intercellular staining pattern that was observed in pemphigus vulgaris. Conclusions. Suprabasal clefting with acantholysis and "tombstone effect" are described histologic features of pemphigus vulgaris on H&E. However, procedural artifact may mimic these findings. Currently, the gold standard for pemphigus vulgaris is DIF, which is not always available because it cannot routinely be performed on formalin-fixed paraffin embedded tissue. Our study shows that C4d immunohistochemistry may be a useful adjunct in evaluating esophageal pemphigus vulgaris.

Early prediction of drug-resistant epilepsy using clinical and EEG features based on convolutional neural network.

OBJECTIVE: Machine learning utilization in electroencephalogram (EEG) analysis and epilepsy care is fast evolving. Thus, we aim to develop and validate two one-dimensional convolutional neural network (CNN) algorithms for predicting drug-resistant epilepsy (DRE) in patients with newly-diagnosed epilepsy based on EEG and clinical features. METHODS: We included a total of 1010 EEG signal epochs and 15 clinical features from 101 patients with epilepsy. Each patient had 10 epochs of EEG signal data, with each signal recorded for 90 s. The ratio of development set and validation set was 80:20, and ten-fold cross validation was performed. First, a CNN algorithm was used to extract EEG features automatically. Then, Two one-dimensional CNNs were crafted.. Accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, mean square error (MSE) and area under the curve (AUC) were calculated to evaluate the classifiers performance. RESULTS: The clinical-EEG model showed good performance and clinical practical value, with the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.72, 0.82, 0.96, 0.89, 0.83, 32.00, 0.81, respectively, and the accuracy in validation set was 0.84. In the EEG model, the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.59, 0.82, 0.90, 0.86, 0.72, 181.76, 0.76, respectively, and the accuracy in validation set was 0.81. CONCLUSION: We constructed a clinical-EEG model showed good potential for predicting DRE in patients with newly-diagnosed epilepsy, which could help identify patients at high risk of developing DRE at earlier stages.

A detachable interface for stable low-voltage stretchable transistor arrays and high-resolution X-ray imaging.

Challenges associated with stretchable optoelectronic devices, such as pixel size, power consumption and stability, severely brock their realization in high-resolution digital imaging. Herein, we develop a universal detachable interface technique that allows uniform, damage-free and reproducible integration of micropatterned stretchable electrodes for pixel-dense intrinsically stretchable organic transistor arrays. Benefiting from the ideal heterocontact and short channel length (2 µm) in our transistors, switching current ratio exceeding 106, device density of 41,000 transistors/cm2, operational voltage down to 5 V and excellent stability are simultaneously achieved. The resultant stretchable transistor-based image sensors exhibit ultrasensitive X-ray detection and high-resolution imaging capability. A megapixel image is demonstrated, which is unprecedented for stretchable direct-conversion X-ray detectors. These results forge a bright future for the stretchable photonic integration toward next-generation visualization equipment.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Green Printing for Scalable Organic Photovoltaic Modules by Controlling the Gradient Marangoni Flow.

Despite the rapid development in the performances of organic solar cells (OSCs), high-performance OSC modules based on green printing are still limited. The severe Coffee-ring effect (CRE) is considered to be the primary reason for the nonuniform distribution of active layer films. To solve this key printing problem, the cosolvent strategy is presented to deposit the active layer films. The guest solvent Mesitylene with a higher boiling point and a lower surface tension is incorporated into the host solvent o-XY to optimize the rheological properties, such as surface tension and viscosity of the active layer solutions. And the synergistic effect of inward Marangoni flow generation and solution thickening caused by the cosolvent strategy can effectively restrain CRE, resulting in highly homogeneous large-area active layer films. In addition, the optimized crystallization and phase separation of active layer films effectively accelerate the charge transport and exciton dissociation of devices. Consequently, based on PM6:BTP-eC9 system, the device prepared with the co-solvent strategy shows the a power conversion efficiency of 17.80%. Moreover, as the effective area scales to 1 and 16.94 cm2, the recorded performances are altered to 16.71% and 14.58%. This study provides a universal pathway for the development of green-printed high-efficiency organic photovoltaics.

Early identification of Parkinson's disease with anxiety based on combined clinical and MRI features.

Objective: To identify cortical and subcortical volume, thickness and cortical area features and the networks they constituted related to anxiety in Parkinson's disease (PD) using structural magnetic resonance imaging (sMRI), and to integrate multimodal features based on machine learning to identify PD-related anxiety. Methods: A total of 219 patients with PD were retrospectively enrolled in the study. 291 sMRI features including cortical volume, subcortical volume, cortical thickness, and cortical area, as well as 17 clinical features, were extracted. Graph theory analysis was used to explore structural networks. A support vector machine (SVM) combination model, which used both sMRI and clinical features to identify participants with PD-related anxiety, was developed and evaluated. The performance of SVM models were evaluated. The mean impact value (MIV) of the feature importance evaluation algorithm was used to rank the relative importance of sMRI features and clinical features within the model. Results: 17 significant sMRI variables associated with PD-related anxiety was used to build a brain structural network. And seven sMRI and 5 clinical features with statistically significant differences were incorporated into the SVM model. The comprehensive model achieved higher performance than clinical features or sMRI features did alone, with an accuracy of 0.88, a precision of 0.86, a sensitivity of 0.81, an F1-Score of 0.83, a macro-average of 0.85, a weighted-average of 0.92, an AUC of 0.88, and a result of 10-fold cross-validation of 0.91 in test set. The sMRI feature right medialorbitofrontal thickness had the highest impact on the prediction model. Conclusion: We identified the brain structural features and networks related to anxiety in PD, and developed and internally validated a comprehensive model with multimodal features in identifying.

Autocatalytic degradation of Cu-EDTA in the Calcite/PMS system: Singlet oxygen and Cu(III).

The simultaneous removal of heavy metal complexes (HMCs) and heavy metal ions presents a significant challenge in treating wastewater. To address this, we propose a Calcite/Peroxymonosulfate (Calcite/PMS) system aimed at simultaneously decomplexing Cu-EDTA and removing Cu ions. Calcite/PMS system could achieve 99.5 % Cu-EDTA decomplexation and 61.9 % Cu ions removal within 60 min under initial conditions of Cu-EDTA (10 mg/L), Calcite (3 g/L), and PMS (2 mM). Singlet oxygen (1O2) emerged as the predominant reactive species responsible for Cu-EDTA decomplexation, which selectively targeted the N-C bonds in the Cu-EDTA structure to produce intermediates with lower biotoxicity than EDTA. Interestingly, solid phase Cu(III) (≡Cu(III)) promoted the generation of superoxide radicals (O2•-) with a contribution of up to 72.8 %. Subsequently, nascent ≡Cu(III) and O2•- accelerated the degradation of intermediates. Besides, coexisting organic substances inhibited Cu-EDTA decomplexation, whereas inorganic ions had a weak impact. After five cycles of use, the Calcite/PMS system retained 99.3 % efficiency in decomplexing Cu-EDTA. This investigation provides valuable insights into using calcite to remove HMCs and enhances our comprehension of the decomplexation intermediates accelerating HMCs degradation.

Methotrexate-Loaded Chitosan Oligosaccharide-ES2 for Targeted Cancer Therapy.

Cancer presents a significant health threat, necessitating the development of more precise, efficient, and less damaging treatment approaches. To address this challenge, we employed the 1-ethyl-(3-dimethyl aminopropyl) carbodiimide/N-hydroxy succinimide (EDC/NHS) catalytic system and utilized quaternized chitosan oligosaccharide (HTCOSC) as a drug carrier to construct a nanoparticle delivery system termed HTCOSC-cRGD-ES2-MTX (CREM). This system specifically targets integrin αvß3 on tumor cell surfaces and enables simultaneous loading of the antiangiogenic agent ES2 (IVRRADRAAVP) and the chemotherapy drug methotrexate (MTX). Due to its amphiphilic properties, CREM self-assembles into nanoparticles in aqueous solution, exhibiting an average diameter of 179.47 nm. Comparative studies demonstrated that CREM, in contrast to free ES2 and MTX-free nanoparticles (CRE), significantly suppressed the proliferation of EAhy926 endothelial cells and B16 melanoma cells in vitro, resulting in inhibition rates of 71.18 and 82.25%, respectively. Furthermore, CREM exhibited a hemolysis rate below 2%, indicating excellent in vitro antiangiogenic and antitumor activity as well as favorable blood compatibility. Additionally, both CRE and CREM demonstrated favorable tumor targeting capabilities through the specific binding action of cyclic RGD (cRGD) to integrin αvß3. Further in vivo investigations revealed that CREM induced apoptosis in tumor cells via the mitochondrial apoptotic pathway and reduced the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), thereby inhibiting tumor angiogenesis. This potent antitumor effect was evident through a tumor suppression rate of 80.19%. Importantly, histopathological staining (HE staining) demonstrated the absence of significant toxic side effects of CREM on various organs compared to MTX. In conclusion, the CREM nano drug delivery system synergistically enhances the therapeutic efficacy of antiangiogenic drugs and chemotherapeutic agents, thus offering a novel targeted approach for cancer treatment.

Li Promoting Long Afterglow Organic Light-Emitting Transistor for Memory Optocoupler Module.

The artificial brain is conceived as advanced intelligence technology, capable to emulate in-memory processes occurring in the human brain by integrating synaptic devices. Within this context, improving the functionality of synaptic transistors to increase information processing density in neuromorphic chips is a major challenge in this field. In this article, Li-ion migration promoting long afterglow organic light-emitting transistors, which display exceptional postsynaptic brightness of 7000 cd m-2 under low operational voltages of 10 V is presented. The postsynaptic current of 0.1 mA operating as a built-in threshold switch is implemented as a firing point in these devices. The setting-condition-triggered long afterglow is employed to drive the photoisomerization process of photochromic molecules that mimic neurotransmitter transfer in the human brain for realizing a key memory rule, that is, the transition from long-term memory to permanent memory. The combination of setting-condition-triggered long afterglow with photodiode amplifiers is also processed to emulate the human responding action after the setting-training process. Overall, the successful integration in neuromorphic computing comprising stimulus judgment, photon emission, transition, and encoding,  to emulate the complicated decision tree of the human brain is demonstrated.

Biomimetic nanocluster photoreceptors for adaptative circular polarization vision.

Nanoclusters with atomically precise structures and discrete energy levels are considered as nanoscale semiconductors for artificial intelligence. However, nanocluster electronic engineering and optoelectronic behavior have remained obscure and unexplored. Hence, we create nanocluster photoreceptors inspired by mantis shrimp visual systems to satisfy the needs of compact but multi-task vision hardware and explore the photo-induced electronic transport. Wafer-scale arrayed photoreceptors are constructed by a nanocluster-conjugated molecule heterostructure. Nanoclusters perform as an in-sensor charge reservoir to tune the conductance levels of artificial photoreceptors by a light valve mechanism. A ligand-assisted charge transfer process takes place at nanocluster interface and it features an integration of spectral-dependent visual adaptation and circular polarization recognition. This approach is further employed for developing concisely structured, multi-task, and compact artificial visual systems and provides valuable guidelines for nanocluster neuromorphic devices.