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Adhesive Photoinitiator Constructs Polymer Jackets on Enzymes: Direct, Release‐Free Cytosolic Delivery
ABSTRACT Enzyme therapeutics require both catalytic activity and efficient cytosolic delivery—yet protective encapsulation typically compromises enzymatic function, while achieving cellular uptake without lysosomal degradation remains challenging. We address this with a rationally designed supramolecular adhesive photoinitiator ( Gu CD⊃BP‐SH) that unifies surface adhesion, radical initiation, and membrane translocation within a single host‐guest architecture. Guanidinium (Gu + ) motifs on a cyclodextrin scaffold ( Gu CD) enable non‐covalent adhesion to protein surfaces at carboxylate‐rich regions; the cyclodextrin cavity hosts a thiol‐benzophenone guest (BP‐SH) whose photoactivation (365 nm, 60 mW cm −2 for 30 min) initiates localized grafting‐from polymerization, constructing a semi‐permeable polymer jacket. Applied to β ‐galactosidase, this yields sub‐100 nm multi‐enzyme nanoassemblies (containing ∼10 enzymes per particle) retaining ∼30% catalytic activity with exceptional proteolytic resistance: 86% activity retained versus 25% for unprotected enzyme after Proteinase K challenge. The incorporated Gu + motifs enable efficient, energy‐independent cytosolic delivery via membrane translocation, with 91% of cells showing catalytic activity compared to 5% with non‐jacketed enzyme. This modular strategy confers protection and cell‐penetrating capability onto native biomacromolecules while maintaining catalytic function, eliminating the need for enzyme release—a persistent bottleneck in therapeutic delivery.
Evaluation of depression, anxiety, and stress levels during the internship clinical training process of dentistry students
Pyridine Into Pyrrole Transformation Induced Within the Confinement of the Macrocycle
ABSTRACT The pyridine contracted to form the pyrrole ring. This transformation belongs to a unique class of reactions with the fundamental characteristic of the cleavage of the aromatic structure. By investigating the unusual coordination chemistry of N‐confused pyriporphyrin with silver and gold ions, we observed this process and obtained several complexes that exhibited remarkable reactivity. This includes the reversible cleavage of C–O bonds and the selective demetallation of the outer metal ion.
Efficacy of vaginal 17β-estradiol on the urinary storage symptoms in postmenopausal women: a randomized double-blind, placebo-controlled study
Bedtime procrastination as the missing link between chronotype and insomnia
A school-based respect-for-life program integrating deceased organ donation awareness in South Korea: a post-class mixed-methods evaluation
Small RNA sequencing analysis identified miR159a as a novel candidate for activity in plant-derived nanovesicles from limon, hassaku, and sudachi
Abstract Owing to their safety, plant-derived nanovesicles (PDNVs), particularly those derived from edible plants, are expected to be natural delivery carriers for microRNAs (miRNAs). Among PDNVs, Citrus limon -derived extracellular vesicle-like nanovesicles have been shown to exert antitumor effects. We previously reported that PDNVs derived from C. limon L. exert selective inhibitory effects on the proliferation of p53-inactivated colon cancer cells. However, miRNAs in C. limon L .-derived nanovesicles have not yet been identified, and it remains unclear which miRNAs are contained in these PDNVs. We herein extracted PDNVs from C. limon L. , C. hassaku , and C. sudachi and identified and compared the miRNAs present within them via next-generation sequencing. A total of 158 miRNAs were identified, of which 109 were known miRNAs and 49 were novel miRNAs. Comparisons of miRNAs expressed by C. limon L ., C. hassaku , and C. sudachi revealed 77 miRNAs that were commonly expressed. Among all the libraries, miR159a had the highest number of reads, and the same result was obtained when it was converted to TPM. The present results raise the possibility that miR159a could be involved in the biological properties of citrus‑derived nanovesicles, given that it was the most abundantly expressed miRNA.
Impact of the defined Oligo-MM12 microbiota on intestinal colonisation and dissemination of Listeria monocytogenes
Abstract Listeria monocytogenes is a foodborne pathogen of global concern, particularly for immunocompromised individuals at risk of severe disease. In mice, infection outcomes are strongly influenced by host immunity and gut microbiome composition. The Oligo-MM 12 defined microbiota mouse model, containing a simplified community of 12 bacterial strains, offers a controlled system to study L. monocytogenes pathogenesis and microbiome interactions. Defined or reduced-complexity microbiota models are increasingly used to investigate colonisation resistance and identify protective taxa. In this study, we compared Oligo-MM 12 mice with conventionally raised Specific Pathogen Free (SPF) mice to assess how microbiome complexity shapes infection. This allowed us to explore how microbiome complexity affects resistance to L. monocytogenes . We performed an in vivo infection study to assess host responses and pathogen-related outcomes, alongside an ex vivo fermentation assay that simulated the murine distal colon, to monitor microbial dynamics. Building on our earlier work, we now demonstrate that in vivo, Oligo-MM 12 mice showed significantly higher L. monocytogenes shedding in faeces during infection, whereas SPF mice progressively reduced L. monocytogenes levels. Despite this, L. monocytogenes dissemination to internal organs after three days of infection was similar in both models. Alterations to gut Prevotella , Akkermansia and Blautia species following L. monocytogenes infection were noteworthy. Ex vivo fermentation mirrored in vivo patterns, validating the Oligo-MM 12 system for mechanistic studies. Together, these results highlight the importance of microbiome complexity in modulating infection outcomes and establish a foundation for identifying protective taxa and mechanisms of colonization resistance.
Correction to “pH‐Dependent Packing Mode Variations and Chirality Inversion in Short Peptide Self‐Assembly”
Effectiveness of exercise prehabilitation before anterior cruciate ligament reconstruction on functional outcomes – a single-blinded randomized controlled trial
Abstract Objective: To compare the effectiveness of an individually tailored, adaptive, guided, structured and criteria-based preoperative rehabilitation program (IG) to a structured, non-guided, self-administered home training program (CG) in individuals after an anterior cruciate ligament (ACL) rupture. Methods: We enrolled participants 16 to 60 years with a unilateral ACL rupture, scheduled for reconstruction using a hamstring or quadriceps tendon autograft. They were assessor-blinded 1:1 block-randomized to the IG or the CG. Self-reported knee function, assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), was the primary outcome. Secondary outcomes included functional measures (range of motion, muscle strength, functional limb asymmetries, and hopping ability) as well as self-reported psychological readiness to return to sport. Parameters were assessed at up to seven time points: anamnesis in the hospital, 1 to 7 days before the surgery, on the day of surgery, 30, 60, 90, and 180 days post-surgery. Intention-to-treat based linear mixed models were calculated using the change scores since anamnesis. Results: Of 114 enrolled participants (mean age = 31.03, SD = 10.30 years; 53% females), 58 participants discontinued intervention or dropped out. The IG (KOOS score anamnesis: 46.04, 95% confidence interval = [45.07 to 47.02]; pre-reconstruction: 58.52, [57.51 to 59.54]) demonstrated a more pronounced preoperative improvement in the KOOS score compared to the CG (51.01, [50.10 to 51.92]; 59.18, [58.40 to 59.96]). The interaction (group*time) of the KOOS sum score differed for the change score to the surgery day ( p = 0.039) and to 60 days postoperative ( p = 0.039). Conclusion: The individually tailored preoperative rehabilitation program may improve perceived knee function more than self-guided training. Caution and future research are needed as the effects were small. Trial registration : German Register of Clinical Trials, DRKSID: DRKS00030312, Date of registration in DRKS 26.09.2022.
Hypnotic and sleep-promoting effects of Limosilactobacillus reuteri LM1063 on pentobarbital-induced sleep and electroencephalogram analysis in mice
Abstract Sleep disturbances are an increasing health concern, and limitations associated with long-term use of conventional hypnotics have prompted interest in alternative approaches that support sleep health. Growing evidence suggests that the gut–brain axis contributes to sleep regulation; however, the effects of probiotics on objective sleep parameters and their underlying mechanisms remain incompletely understood and may vary across probiotic strains. The present study investigated the sleep – modulating effects of a selected probiotic strain, Limosilactobacillus reuteri LM1063 (LM1063), using murine models. Sleep latency and duration were assessed using a pentobarbital-induced sleep test, and sleep architecture was evaluated by electroencephalogram (EEG) recordings, including rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. To explore potential mechanisms, neurochemical analyses focusing on key neurotransmitters, including gamma-aminobutyric acid (GABA) and serotonin, were conducted. Administration of LM1063 significantly shortened sleep latency and prolonged sleep duration in mice. EEG analysis revealed shifts in overall sleep architecture toward a sleep-favorable state without disruption of normal sleep organization. These sleep-related changes were accompanied by modulation of GABAergic and serotonergic neurochemical pathways. In conclusion, LM1063 exerts strain-specific sleep-modulating effects through neurochemical mechanisms associated with the gut–brain axis. By integrating behavioral sleep assessment, electrophysiological analysis, and neurochemical profiling, this study provides mechanistic insight supporting the potential translational application of microbiome-targeted approaches for promoting sleep health.
Retraction Note: Management of uterine leiomyoma and adenomyosis: role of hysteroscopy in diagnosis and norethindrone in the treatment
Analysis of factors associated with cervical cancer and precancerous lesions
Abstract To investigate factors influencing cervical cancer and precancerous lesions by collecting and analyzing clinical data and pathological results from 2,998 patients undergoing cervical biopsy; Pathological results and clinical data of 2,998 patients who underwent cervical biopsy at the gynecology outpatient clinic of a tertiary hospital in Hangzhou (January 2022–January 2023) were collected. Univariate analysis and multivariate unconditional logistic regression models were used to analyze relevant influencing factors; The results of univariate and multivariate analyses showed that cervical lesions were related to Human Papillomavirus (HPV) infection and the number of deliveries ( P < 0.05) but were not related to age, number of pregnancies, number of abortions, use of condoms for contraception, and smoking ( P > 0.05); Cervical cancer and precancerous lesions are associated with HPV infection and number of deliveries. It is imperative to implement a series of prevention and treatment measures to inhibit the onset and progression of cervical diseases, thereby reducing their incidence and mortality rates.
Stereospecific Assembly of Triply Chiral Pseudopeptidic Cages Through Dynamic Dual Chirality Transfer
ABSTRACT A stereospecific transmission of chiral information within tripodal pseudopeptidic cages has been observed from dynamic constitutional co‐operation of reversible orthogonal processes: imine bond and metal coordination. The chiral centers from the phenylalanine amino acid moieties induce a specific chirality into the formed octahedral Fe(II) complex and into the helical twist of the macrobicycle, as confirmed by NMR, circular dichroism, X‐ray diffraction of single crystals, and theoretical calculations. Instead, when a configurationally stable Ru(II) complex is employed, the dynamic imine exchange efficiently selects the corresponding matched‐combination of the same chiral elements, leading after reduction to a water‐soluble homochiral stable macrobicyclic pseudopeptide Ru(II) complex with appealing chemical and photophysical properties. Overall, our study demonstrates how subtle structural factors from a chiral effector in a reversible dynamic system rule the generation and selection of subsequent chiral elements with high fidelity and complete stereocontrol.
Adaptive multi-feature fusion architecture with optimized learning for high-fidelity brain tumor classification in MRI
Abstract Brain gliomas represent one of the most aggressive cancers worldwide and remain difficult to diagnose accurately at an early stage. Although computer-aided diagnostic (CAD) approaches have progressed notably in recent years, distinguishing between high-grade glioma (HG-G), low-grade glioma (LG-G), and healthy brain tissue on magnetic resonance images is still a major challenge. To address this issue, we propose a multi-stage framework designed to push the boundaries of current classification methods. The framework begins with a preprocessing phase that integrates Adaptive Gamma Correction (AGC) for improved contrast adjustment with a Denoising Convolutional Neural Network (DnCNN) for noise removal. Feature extraction is then carried out from three representative layers across three fine-tuned transfer learning CNNs (TRCNNs), where each model is optimized by a different algorithm. These deep representations are combined with handcrafted texture measures based on the Gray-Level Co-occurrence Matrix (GLCM), producing nine unique CNN–GLCM Fused Feature (CGFF) sets. The resulting hybrid descriptors are evaluated using several strong classifiers such as Random Forest (RF), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Support Vector Machine (SVM), along with a stacked ensemble to reinforce stability and robustness. Performance significance was verified through the Friedman statistical test, with p < 0.05, confirming the reliability of the improvements. The framework achieved 99.05% accuracy, 98.99% recall, 99.52% specificity, 99.08% positive predictive value (PPV), and 99.54% negative predictive value (NPV), consistently surpassed state-of-the-art (SOTA) methods across all reported metrics.
Incomplete reputation information and punishment in indirect reciprocity
Distinct functional profiles of oral neutrophils in molar incisor pattern periodontitis, generalized periodontitis and periodontal health
InFoRM: a unified inverse and forward model for sensorimotor control
Abstract Sensorimotor control models traditionally consist of two types of internal models: inverse models, which compute the motor commands needed to reach a desired movement goal, and forward models, which predict the resulting sensory feedback. These models are usually considered separate entities, but it is unclear whether such separation exists in the nervous system. Additionally, maintaining separate networks may be more computationally expensive. Therefore, we investigated whether these functions could be executed within a single neural circuit: an inverse-forward-recognition model (InFoRM). We implemented InFoRM using neural networks and compared their ability to reproduce cyclic reaching movements with that of control architectures based on classical, separated inverse and forward models. Desired movement trajectories were represented by recorded three-dimensional kinematics, while efferent (muscle activation) and afferent (muscle length and velocity) signals were obtained through inverse dynamics. Our findings show that InFoRM significantly outperforms control architectures across various conditions, while requiring fewer resources. The network is also able to morph to untrained movement directions, generating motor commands and predicted feedback that had not been learned. These findings demonstrate the computational advantages of integrating inverse and forward processes within a single neural network, suggesting that such unified sensorimotor models may be worthwhile to explore further.