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Enantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts

Correction: Metabolite changes during developmental transitions in Adonis amurensis Regel et Radde flowers: Insights from HPLC-MS analysis

Research on the extrusion characteristics for the geometry of materials in material extrusion process using heating syringe

Mechanism of Unexpected <i>In-Trans</i> Post-PKS Polyketide Reduction in Cochliodone Biosynthesis

Human sensory-like neuron surfaceome analysis

Acral and triggerable pain is a hallmark of diseases involving small nerve fiber impairment, yet the underlying cellular mechanisms remain elusive. A key role is attributed to pain-related proteins located within the neuronal plasma membrane of nociceptive neurons. To explore this, we employed human induced pluripotent stem cell-derived sensory-like neurons and enriched their surface proteins by biotinylation. Samples from three independent cell differentiations were analyzed via liquid chromatography tandem mass spectrometry. Detected proteins were categorized by cellular location and function, followed by generating an interaction network for deregulated surface proteins. Gene expression of selected proteins was quantified using real-time PCR. A comparative analysis was performed between a patient with Fabry disease (FD) and a healthy control, which we used as model system. We successfully extracted surfaceome proteins from human sensory-like neurons, revealing deregulation of 48 surface proteins in FD-derived neurons. Among the candidates with potential involvement in pain pathophysiology were CACNA2D3, GPM6A, EGFR, and ABCA7. Despite the lack of gene expression differences in these candidates, the interaction network indicated compromised neuronal network integrity. Our approach successfully enabled the extraction and comprehensive analysis of the surfaceome from human sensory-like neurons, establishing a novel methodological framework for investigating human sensory-like neuron biology and cellular disease mechanisms.

An efficient fire detection algorithm based on Mamba space state linear attention

Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors

Occludin is a key component of tight junctions. Reduced occludin expression has been linked to cancer progression in individual tumor types, but a comprehensive and standardized analysis across human tumor types is lacking. To study the prevalence and clinical relevance of occludin expression in cancer, a tissue microarray containing 16,870 samples from 148 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Occludin immunostaining was observed in 10,746 (76.6%) of 14,017 analyzable tumors, including 18.9% with weak, 16.2% with moderate, and 41.6% with strong staining intensity. Occludin positivity was found in 134 of 148 tumor categories and was most frequent in adenocarcinomas (37.5-100%) and neuroendocrine neoplasms (67.9-100%), less common in squamous cell carcinomas (23.8-93%) and in malignant mesotheliomas (up to 48.1%), and rare in Non-Hodgkin’s lymphomas (1-2%) and most mesenchymal tumors. Reduced occludin staining was linked to adverse tumor features in several tumor types, including colorectal adenocarcinoma (advanced pT stage, p &lt; 0.0001; L1 status, p = 0.0384; absence of microsatellite instability, p &lt; 0.0001), pancreatic adenocarcinoma (advanced pT stage, p = 0.005), clear cell renal cell carcinoma (high ISUP grade, p &lt; 0.0001; advanced pT stage, p &lt; 0.0001; high UICC stage, p &lt; 0.0001; distant metastasis, p = 0.0422; shortened overall or recurrence-free survival, p ≤ 0.0116), papillary renal cell carcinoma (high pT stage, p &lt; 0.0001; high UICC stage, p = 0.0228; distant metastasis, p = 0.0338; shortened recurrence-free survival, p = 0.006), and serous high-grade ovarian cancer (advanced pT stage, p = 0.0133). Occludin staining was unrelated to parameters of tumor aggressiveness in breast, gastric, endometrial, and thyroidal cancer. Our data demonstrate significant levels of occludin expression in many different tumor entities and identify reduced occludin expression as a potentially useful prognostic feature in several tumor entities.

Equivalent elastic model of splitting grouting reinforcement in weak strata

Molecularly Responsive Aptamer-Functionalized Hydrogel for Continuous Plasmonic Biomonitoring

A study on the evolution of original sites of fortifications from the perspective of Historic Urban Landscape: Cases of Paris, Beijing, and Moscow

The Historic Urban Landscape theory underscores the importance of historical stratification processes in shaping the overall value of urban heritage. Building on this perspective, this study examines the stratification and evolution of the original sites of fortifications in Paris, Beijing, and Moscow, three global cities. First, historical research is conducted to identify the key moments of significant changes and their contextual backgrounds in these cities’ original sites of fortifications. Second, quantitative analysis is applied to calculate the changes in functional proportions across different periods. The findings reveal that, although the timing of major transformations varies among the three cities, all have undergone three distinct stages: demolition and planning, development and construction, and reflection and renewal. This evolutionary process is closely tied to the urbanization trajectories of each city, with the driving forces exhibiting notable commonalities and patterns.

Therapeutic effects of lomerizine on vasculopathy in Fabry disease

Dynamics of DNA Repair by Class-II Photolyases via a Unified Electron-Transfer Bifurcating Mechanism

Cranial morphology reveals a lack of phylogenetic signal and rapid adaptive radiation in the bat genus Molossus (Chiroptera: Molossidae)

The 16 species of Molossus (Chiroptera: Molossidae) are distributed throughout the Neotropical region and can be classified into two groups: one consisting of morphologically similar yet phylogenetically divergent species, and another of morphologically distinct but closely related species. This dynamic has led to frequent revisions in the systematics and taxonomy of this genus. This study aimed to analyze patterns of diversification in cranial shape and size within Molossus species using geometric morphometrics (GM), integrating genetic and morphological data. A total of 299 specimens from ten Molossus species widely distributed across the Neotropics were examined, focusing on cranial size, shape diversity, and evolution, and correlating these findings with mitochondrial DNA-based phylogenetic data. Integrated morphometric and phylogenetic analyses revealed a complex evolutionary history within Molossus, with most speciation events occurring during the Pleistocene, suggesting a recent rapid adaptive radiation. GM analyses demonstrated patterns of divergence in cranial size with shape conservatism, and these traits were not significantly related to phylogeny. The data indicate that phylogenetic relationships have limited influence on cranial morphology due to the lack of a strong phylogenetic signal, suggesting that ecological factors, such as diet and habitat, have played central roles in the diversification of Molossus.

An innovative model based on machine learning and fuzzy logic for tracking lower limb exercises in stroke patients

Abstract Rehabilitation after a stroke is vital for regaining functional abilities. However, a shortage of rehabilitation professionals leads to many patients with severe disabilities. Traditional rehabilitation methods can be time-consuming and hard to measure for progress. This study introduces an innovative machine learning (ML) approach for lower limb rehabilitation in stroke patients. The proposed methodology integrates two models: a fuzzy logic rule-based system and a K-Nearest Neighbor(K-NN) machine learning model. The rule-based model utilizes the Fugl-Meyer Assessment to evaluate lower limb angles during exercises using a camera without human intervention. The hybrid fuzzy logic-based ML model continuously tracks the desired angle, counts exercise repetitions, and provides real-time feedback on patient progress. Furthermore, it measures the Range of Motion (ROM) for each repetition, presenting a graphical visualization of ROMs for ten repetitions simultaneously. The model facilitates real-time evaluation of rehabilitation progress by clinicians, with the lowest observed error rate of $$0.34^\circ$$ of angle measurement. The K-NN model assesses rehabilitation exercise accuracy levels, presenting results graphically, with machine learning accuracy rates of $$97\%$$ , $$92\%$$ , and $$91\%$$ for hip flexion, hip external rotation, and knee extension rehabilitation exercises. Model training utilized data from 30 experienced physical therapists at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, garnering positive evaluations from rehabilitation doctors. The proposed ML-based models offer real-time and prerecorded video capabilities, enabling telerehabilitation applications. This research highlights the potential of ML-based methodologies in stroke rehabilitation to enhance accuracy, efficiency, and patient outcomes.

Correction: Creating a diagnostic assessment model for autism spectrum disorder by differentiating lexicogrammatical choices through machine learning

Dynamical diversity of FWM-induced pulsating solitons in an ultrafast fiber laser

A qPCR assay for the detection of Phytophthora abietivora, an emerging pathogen on fir species cultivated as Christmas trees

Emerging species of the Phytophthora genus are among the most important threats to global plant biodiversity, horticulture and trade. For instance, Phytophthora root rot (PRR) of Christmas trees, mainly Fraser (Abies fraseri) and balsam (Abies balsamea) firs, is responsible for an average of 10% of the observed diseased trees in plantations. Diagnosing PRR involves isolation followed by morphological and molecular identification of the causal agents. However, these methods are rarely adapted to larger scale monitoring such as in situ detection. For these applications, molecular detection of environmental DNA (eDNA) provides the fast and high-throughput results needed. Phytophthora abietivora was associated with PRR in firs (Abies spp.) cultivated as Christmas trees in the province of Québec (Canada). This study focused on developing a sensitive and specific qPCR assay targeting P. abietivora and validating its efficiency on DNA extracted from soil and roots. A set of primers and probe was designed for this assay, and parameters such as the limit of detection (LOD95%) and limit of quantification (LOQ) were measured. The assay was tested on DNA obtained from healthy-looking and PRR symptomatic Fraser and balsam firs. The assay was shown to be semi-specific because it cross-reacted with P. europaea and three other phylogenetically close species, but deemed specific in the context of PRR of firs. The LOD95% was estimated at 10 copies per reaction (Cq of 35.7) and the LOQ to 33 P. abietivora oospores per gram of soil. Out of 488 DNA samples from soil, 68 were positive for P. abietivora from which 42 (61.7%) were from PRR symptomatic trees. Only a slight overlap (3 out of 7 samples) was observed with previously obtained baiting results. This assay will be useful for rapid diagnostics of P. abietivora infected trees and as a prospecting tool to better characterize the natural distribution and dissemination of the disease.

An ACE2-Fc decoy produced in glycoengineered plants neutralizes ancestral and newly emerging SARS-CoV-2 variants and demonstrates therapeutic efficacy in hamsters

Abstract Newly emerging SARS-CoV-2 variants of concern (VOCs) continue to drive COVID-19 waves and are typically associated with immune escape and increased resistance to current therapeutics including monoclonal antibodies. By contrast, VOCs still display strong binding to the host cell receptor ACE2. Consistent with these properties, we have now found that a soluble ACE2-Fc decoy produced in glycoengineered plants effectively neutralizes different SARS-CoV-2 isolates and exhibits even increased potency against VOCs as compared to an ancestral virus strain. In a golden Syrian hamster model, therapeutic intranasal delivery of ACE2-Fc effectively reduced weight loss and SARS-CoV-2 replication in the lungs when administered 24 h post-inoculation. This protective effect was not observed upon treatment of the infected animals with a non-binding ACE2-Fc mutant, demonstrating that the plant-derived ACE2-Fc decoy interferes specifically with the attachment of the virus to host cells. The results obtained provide support for further development of decoy-based antiviral approaches by plant molecular pharming.

Anodized Aluminum Oxide Membrane Ionic Memristors

Improvements in health-related quality of life are maintained long-term in patients prescribed medicinal cannabis in Australia: The QUEST Initiative 12-month follow-up observational study

Aims Since 2016, more than one million new patients with chronic health conditions have been prescribed medicinal cannabis in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, depression, and motor function in a large real-world sample of patients prescribed medicinal cannabis. We previously found all patient-reported outcomes improved in the first 3-months and hypothesised that improvements would be maintained to 12-months. Methods The QUEST Initiative, a multicentre prospective study, recruited adult patients with any chronic health condition newly prescribed medicinal cannabis oil between November 2020 and December 2021. Participants identified by 114 clinicians across Australia completed validated questionnaires at baseline, then 2-weeks titration, and 1-,2-,3-,5-,7-,9- and 12-months follow-up. Results Of 2744 consenting participants who completed baseline assessments, 2353 also completed at least one follow-up questionnaire and were included in analyses, with completion rates declining to 778/2353 (38%) at 12-months. Ages ranged between 18–97 years (mean 50.4y; SD = 15.4), 62.8% were female. Chronic conditions commonly treated included musculoskeletal pain (n = 896/2353; 38.1%), neuropathic pain (n = 547/2353; 23.2%), insomnia (n = 546/2353; 23.2%), anxiety (n = 520/2353; 22.1%), and mixed depressive and anxiety disorder (n = 263/2353; 11.2%). Clinically meaningful improvements were observed in HRQL: EQ-5D-5L index (d = 0.52) and QLQ-C30 summary scores (d = 0.91), PROMIS fatigue (d = 0.51) and sleep disturbance (d = 0.76). Participants diagnosed with chronic pain experienced clinically meaningful improvement in scores on QLQ-C30 pain (d = 0.5), PROMIS pain intensity (d = 0.76), and PROMIS pain interference (d = 0.76). There was significant improvement in DASS anxiety (d = 0.69) and DASS depression (d = 0.65) for those with anxiety or depressive conditions, but no motor function improvements observed for participants with movement disorders. All observed improvements were statistically significant. Conclusions Statistically significant and clinically meaningful improvements in overall HRQL, fatigue, and sleep disturbance were maintained over 12-months in patients prescribed medical cannabis for chronic health conditions. Anxiety, depression, insomnia, and pain also improved over time for those with corresponding health conditions. Study registration Australian New Zealand Clinical Trials Registry: ACTRN12621000063819