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Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

Lecanemab is a humanized murine IgG1 antibody. Recent Phase 3 clinical trials have demonstrated its ability to reduce brain amyloid-β (Aβ) load and slow cognitive decline in patients with early Alzheimer's disease (AD). However, since its approval, reports on adverse effects (AEs) associated with lecanemab have been limited. To better understand the AEs related to lecanemab and provide guidance for future clinical use, we analyzed lecanemab-associated AEs using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). We extracted all AEs reports from the FAERS database for the period from the first quarter of 2023 to the third quarter of 2024. Using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms, we conducted a comprehensive analysis of lecanemab-related AEs, restricting the analysis to AEs with the role code of primary suspect (PS). A total of 811 AEs reports related to lecanemab used in AD patients and 506 AEs in Non-AD patients were included. The preferred terms (PTs) identified as positive across all four algorithms included headache, Amyloid Related Imaging Abnormalities-oedema/effusion (ARIA-E), chills, Amyloid Related Imaging Abnormalities-haemosiderosis/microhaemorrhage (ARIA-H), fatigue, infusion-related reaction, nausea, pyrexia, pain, influenza like illness, and so on. Among these, ARIA-E, ARIA-H, brain oedema and status epilepticus were associated with Important Medical Events (IMEs) for AD patients, and brain oedema, cerebral haemorrhage, cerebral microhaemorrhage, subdural haematoma, ischaemic stroke, cerebral infarction were associated with IMEs for Non-AD patients. At the system organ class (SOC) level, the highest signal detection for lecanemab was observed in nervous system disorders among AD and Non-AD patients [ROR for AD: 2.42 (2.2-2.65); ROR for Non-AD: 6.97 (6.12-7.95)]. The median time to the occurrence of these AEs was 44 days after administration in AD patients and 30 days for Non-AD patients. This study utilized the FAERS database to evaluate lecanemab-associated AEs in AD and non-AD patients, along with their temporal patterns post-marketing authorization, thereby establishing a foundation for subsequent clinical pharmacovigilance. A biweekly 10 mg/kg was identified as the optimal therapeutic dosage. ARIA emerged as frequent treatment-related AEs, with APOEɛ4 carriers demonstrating heightened susceptibility. This necessitates serial brain MRI surveillance for all patients during treatment, aimed not only at early ARIA detection but also vigilant monitoring of IMEs including cerebral haemorrhage, cerebral microhaemorrhages, subdural haematoma, cerebral edema, ischaemic stroke, and cerebral infarction. While AD patients predominantly exhibited non-specific clinical manifestations, non-AD cohorts showed elevated risks of stroke-related complications. Consequently, dynamic neurological deficit monitoring is indispensable for non-AD populations receiving lecanemab to mitigate adverse outcomes. Finally, comprehensive reassessment of anticoagulant or antiplatelet therapy indications is warranted in both AD and non-AD patients to reduce hemorrhagic risks.

•We examined the relationship between chronic stress and reward processing dynamics.•The PSS score exhibited a U-shaped relationship with cue-N2 amplitudes.•The PSS score exhibited a U-shaped relationship with FRN amplitudes.•Chronic stress showed a U-shaped relationship with the dynamics of reward processing. Despite the potential link between stress-induced reward dysfunctions and the development of mental problems, limited human research has investigated the specific impacts of chronic stress on the dynamics of reward processing. Here we aimed to investigate the relationship between chronic academic stress and the dynamics of reward processing (i.e., reward anticipation and reward consumption) using event-related potential (ERP) technology. Ninety healthy undergraduates who were preparing for the National Postgraduate Entrance Examination (NPEE) participated in the study and completed a two-door reward task, their chronic stress levels were assessed via the Perceived Stress Scale (PSS). The results showed that a lower magnitude of reward elicited more negative amplitudes of cue-N2 during the anticipatory phase, and reward omission elicited more negative amplitudes of FRN compared to reward delivery especially in high reward conditions during the consummatory phase. More importantly, the PSS score exhibited a U-shaped relationship with cue-N2 amplitudes regardless of reward magnitude during the anticipatory phase; and FRN amplitudes toward reward omission in high reward condition during the consummatory phase. These findings suggest that individuals exposed to either low or high levels of chronic stress, as opposed to moderate stress levels, exhibited a heightened reward anticipation, and an augmented violation of expectations or affective response when faced with relatively more negative outcomes.

Numerous studies have consistently demonstrated the presence of the approximate number system (ANS) throughout development. Research has also revealed that visual cues may influence the ANS acuity, which may change with age. However, most studies have drawn conclusions based on performance differences between incongruent and congruent trials, which may be confounded by an individual's ability to inhibit interference. Therefore, to examine the developmental changes of the impact of visual cues on ANS acuity, we utilized congruent trials with varying visual cues. Our sample comprised Chinese children from grade one to grade five. We manipulated the salience of numerical cues (numerical ratio) and visual cues (dot size) in a non-symbolic numerosity comparison task. The results revealed a discernible leap in development from first to third grade and first to fifth grade; however, this upward trajectory did not persist into the transition from third to fifth grade, where no appreciable advancement was observed. Moreover, we observed different effects of visual cues on the dot-comparison task depending on the numerical cues and age. Specifically, visual cues (i.e., dot size) only facilitated ANS acuity in older school-aged children when numerical cues were weakened. The results indicate the presence of two distinct magnitude representational systems—one for the numerical dimension and another for the non-numerical dimension—during development.

Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A simple, rapid, sensitive and specific liquid chromatography–tandem mass spectrometry method to determine the ellagic acid in plasma and tissue samples was developed and validated. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC), and the mass spectrometric detection was achieved using heated electrospray ionization (negative mode) and multiple ion monitoring (m/z 301/229). A sample cleanup with a solid phase extraction (SPE) step prior to the UPLC-MS/MS analysis was also developed. The SPE and UPLC-MS/MS method established here was successfully applied to reveal the pharmacokinetic profiles and tissue distribution of ellagic acid. After oral administration dosing at 50 mg/kg, plasma levels of ellagic acid peaked at about 0.5 h, with Cmax value of 93.6 ng/mL, and the results showed that the ellagic acid was poorly absorbed after oral administration. The pharmacokinetic profile of ellagic acid fitted to a two-compartment model with t1/2α 0.25 h and t1/2β 6.86 h, respectively. Following oral administration, ellagic acid was detected in all examined tissues including kidney, liver, heart, lung and brain et al., and the highest levels were found in kidney and liver.

Industries containing excess acid or alkaline wastewater exacerbate water security. As a semi-crystalline engineering thermoplastic with superior chemical resistance, exceptional mechanical strength, and outstanding thermal stability, polyetheretherketone (PEEK) is a promising candidate for advanced functional membranes in water remediation. Herein, we present a comprehensive overview of recent advances in PEEK materials, encompassing PEEK membrane fabrication, strategies for membrane hydrophilic modification, and applications in wastewater treatment. Specifically, research efforts have focused on membrane preparation methods such as nonsolvent-induced phase separation (NIPS), thermally induced phase separation (TIPS), and chemical-induced crystallization (CIC), which aim to address the critical challenge of forming solvent-resistant PEEK membranes while maintaining membrane performance. Additionally, various hydrophilic modification strategies (pretreatment, co-blending, and post-treatment) for PEEK membranes are discussed to alleviate membrane fouling problems, with in-depth discussions of diverse applications in wastewater treatment (such as the removal and purification of synthetic dyes, organic solvents, natural organic matter removal, and oil–water mixture). The review concludes with an emphasis on the current challenges and potential of PEEK membrane for wastewater treatment.

Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic human-specific LINE-1 (L1Hs) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons-mainly contributed by long genes-than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MeCP2 dysfunction alters their genomic patterns in Rett patients.

Simultaneous imaging of the SPECT tracer 131 I and PET tracer 18 F is important in the diagnosis of high- and low-grade thyroid cancers because high-grade thyroid cancers have high 18 F-FDG and low 131 I uptake, while low-grade thyroid cancers have high 131 I and low 18 F-FDG uptake. In this study, Na 131 I and 18 F-FDG were simultaneously imaged using the Compton-PET system, in vivo. The angular resolution and sensitivity of the Compton camera with 356 keV gamma ray measured using a 133 Ba point source were 12.3° and 2 × 10 −5 , respectively. The spatial resolution and sensitivity of PET were measured with a 22 Na point source. The transaxial and axial spatial resolutions of the PET at the center of the FOV were 1.15 mm and 2.04 mm, respectively. Its sensitivity was 1.2 × 10 −4 . In-vivo images of the 18 F and 131 I isotopes were simultaneously acquired from mice. These showed that 18 F-FDG was active in the heart, brown fat, and brain, while Na 131 I was active in the thyroid, stomach, and bladder. Artifacts were found in the Compton camera images when the activity of 131 I was much lower than that of 18 F. This study demonstrates the potential of simultaneous clinical imaging of 18 F and 131 I.

Rosmarinic acid (RA) is a natural active compound widely found in many plants belonging to the family of Lamiaceae, Boraginaceae, and so on, which has various important bioactivities, including being anti-oxidative, anti-inflammatory, antiviral, etc. Herein, novel hydrophilic magnetic molecularly imprinted polymers (HMMIPs) with a regular core-shell structure were successfully developed using RA as a template molecule, acrylamide (AM) as a functional monomer, N-N ’methylenebisacrylamide (MBA) as a cross-linking agent, and water as the porogen. After a series of characterization and adsorption performance analyses, it was found that HMMIPs are hydrophilic with an adsorption capacity of 8.012 ± 0.54 mg/g, an imprinting factor of 3.64, and a selectivity coefficient of 2.63~2.91. Furthermore, the HMMIPs can be rapidly separated from other components under the influence of external magnetic fields. The HMMIPs were employed for the determination of RA present in the Perilla frutescens and Rosmarinus officinalis aqueous extract with recoveries of 88.2~107.3%. These results indicated that HMMIPs of RA have the benefits of straightforward operation, rapid adsorption, and high selectivity, rendering it an appropriate way for the expedient and selective isolation of RA in an intricate matrix.

Recently, tumor immunotherapy based on immune checkpoint inhibitors (ICI) has been introduced and widely adopted for various tumor types. Nevertheless, tumor immunotherapy has a few drawbacks, including significant uncertainty of outcome, the possibility of severe immune-related adverse events for patients receiving such treatments, and the lack of effective biomarkers to determine the ICI treatments’ responsiveness. DNA methylation profiles were recently identified as an indicator of the tumor immune microenvironment. They serve as a potential hot spot for predicting responses to ICI treatment for their stability and convenience of measurement by liquid biopsy. We demonstrated the possibility of DNA methylation profiles as a predictor for responses to the ICI treatments at the pan-cancer level by analyzing DNA methylation profiles considered responsive and non-responsive to the treatments. An SVM model was built based on this differential analysis in the pan-cancer levels. The performance of the model was then assessed both at the pan-cancer level and in specific tumor types. It was also compared to the existing gene expression profile-based method. DNA methylation profiles were shown to be predictable for the responses to the ICI treatments in the TCGA cases in pan-cancer levels. The proposed SVM model was shown to have high performance in pan-cancer and specific cancer types. This performance was comparable to that of gene expression profile-based one. The combination of the two models had even higher performance, indicating the potential complementarity of the DNA methylation and gene expression profiles in the prediction of ICI treatment responses.