Multidisciplinary assessment and interventions for childhood auditory processing disorder (APD) and listening difficulties (LiD).

Purpose: Auditory processing disorder (APD) has been studied in both research and clinic settings, but the relation between the two has not been addressed. In a longitudinal research study (SICLiD), we found that children with clinically normal audiometry who had caregiver-reported listening difficulties (LiD), with or without clinically assessed APD, performed poorly on both listening and cognitive tests. Specific questions asked here were, for the children with LiD, what other neurodevelopmental clinical conditions were identified, what interventions were used by different clinical providers, and how clinical practice was predicted by research results. Methods: Study setting was a large, research-led, tertiary pediatric hospital. Electronic medical records of 74 children aged 6-13 years, recruited into SICLiD and assigned to an LiD group based on a validated and reliable caregiver report (ECLiPS), were independently reviewed. Focus was on clinical assessments and interventions following appointments provided in the Hospital Divisions of Audiology, Occupational Therapy, Psychology (Developmental and Behavioral Pediatrics), and Speech-Language Pathology (SLP), prior to participation in SICLiD. Descriptive statistics on clinical encounters, identified conditions, and interventions were compared with quantitative, standardized performance on SICLiD assessments of listening and cognitive function. SICLiD z-scores were compared for participants with and without each clinical condition using univariate and logistic prediction analyses. Results: Most (86%) of the children with LiD had been evaluated by at least one clinical service. Overall, 24 assessment categories related to LiD, including APD, were identified. Most common conditions were attention (32%), language (28%), hearing (18%), anxiety (16%), and autism spectrum (6%) disorders. Performance on SICLiD measures varied significantly between providers, conditions, and interventions. Significant relationships between SICLiD and clinical conditions were mostly caregiver-reported items from the ECLiPS or the Children's Communication Checklist (CCC-2). Other significant correlations were scarce, but included the SCAN composite score, which predicted clinical language and attention, but not other auditory abilities or APD. SICLiD data combined with caregiver reports provided reliable predictions of all clinical conditions except APD. Conclusions: The variety of disciplines, assessments, conditions and interventions revealed here supports previous studies showing that LiD and APD are multifaceted problems of neurodevelopment. Comparisons between clinical- and research-based assessments suggest a diagnostic path that prioritizes caregiver reports and selected psychometric tests for screening and diagnostic purposes.

Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

Advancing Precise Syphilis Diagnosis: A Nontreponemal IgM Antibody-Based Model for Latent Syphilis Staging.

Purpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies. Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer-Lemeshow χ2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model's stability. Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer-Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model's robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer-Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model. Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.

Historical sedimentary and evolutionary characteristics of POPs and EDCs in typical regions of the three Gorges reservoir, China.

The historical sedimentary and evolutionary characteristics of persistent organic pollutants and endocrine disruptors in typical regions of the Three Gorges Reservoir are scarcely studied. Herein, the 96-year data on contaminated sediment history were reconstructed using Caesium 137 isotope dating. Polychlorinated biphenyl concentrations in the involved sediment cores ranged from non-detected (ND) to 11.39 ng/g. The concentrations of polycyclic aromatic hydrocarbons ranged from ND to 2075.20 ng/g and peaked in the 1970s owing to natural, agricultural and human activities. Further, phthalate esters (PAEs) and heavy metals (HMs) were detected at concentrations ranging from ND to 589.2 ng/g and 12.10-93.67 µg/g, respectively, with highest values recorded in the 1980s owing to rapid industrialisation and insufficient management during China's early reform and development stages. PAE and HM concentrations have increased in recent years, suggesting the need to focus on industrial and agricultural activities that have caused this impact. Although current pollutant concentrations in sediments do not pose a risk to the aquatic ecosystem, they should be continuously monitored.

Frailty management in older patients: a best practice implementation project.

INTRODUCTION: Frailty in older adults can lead to a gradual decline in organ function. Without timely diagnosis and intervention, this condition can progress rapidly, increasing the risk of disability and mortality. OBJECTIVES: The aim of this project was to implement evidence-based practices for managing frailty in the medical ward to prevent disability in older patients. METHODS: This project was conceptually informed by the JBI Evidence Implementation Framework. This framework uses an audit and feedback approach and a pre- and post-test design to measure baseline compliance, develop implementation strategies responsive to gaps in compliance, and conduct a final evaluation to measure changes in compliance. JBI PACES and JBI GRiP situational analysis software were used to support data collection and implementation planning. Ten audit criteria were used with a sample of 30 patients in a regional teaching hospital in southern Taiwan. RESULTS: The baseline audit showed poor compliance, with rates below 30% for all ten audit criteria. Through strategies such as professional training and education, the implementation of evidence-based care guidelines, and interdisciplinary consensus-building, the follow-up audit revealed an increase in compliance to over 90% for each audit criterion. CONCLUSIONS: Frailty management strategies based on evidence-based audit criteria were implemented and routinely measured. The most effective strategies for improving compliance included the development of a training course, a digitized assessment tool, team meetings, interdisciplinary collaboration, communication, and consensus-building. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A225.

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

DNA Damage-Sensitized metal phenolic nanosynergists potentiate Low-Power phototherapy for osteosarcoma therapy.

Non-invasive and efficient photodynamic therapy (PDT) holds great promise to circumvent resistance to traditional osteosarcoma (OS) treatments. Nevertheless, high-power PDT applied in OS often induces photothermogenesis, resulting in normal cells rupture, sustained inflammation and irreversible vascular damage. Despite its relative safety, low-power PDT fails to induce severe DNA damage for insufficient reactive oxygen species (ROS) production. Herein, a non-ROS-dependent DNA damage-sensitizing strategy is introduced in low-power PDT to amplify the therapeutic efficiency of OS, where higher apoptosis is achieved with low laser power. Inspired by the outstanding DNA damage performance of tannic acid (TA), TA-based metal phenolic networks (MPNs) are engineered to encapsulate hydrophobic photosensitizer (purpurin 18) to act as DNA damage-sensitized nanosynergists (TCP NPs). Specially, under low-power laser irradiation, the TCP NPs can boost ROS instantly to trigger mitochondrial dysfunction simultaneously with upregulation of DNA damage levels triggered by TA to reinforce PDT sensitization, evoking potent antitumor effects. In addition, TCP NPs exhibit long-term retention in tumor, greatly benefiting sustained antitumor performances. Overall, this study sheds new light on promoting the sensitivity of low-power PDT by strengthening DNA damage levels and will benefits advanced OS therapy.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Uni4Eye++: A General Masked Image Modeling Multi-modal Pre-training Framework for Ophthalmic Image Classification and Segmentation.

A large-scale labeled dataset is a key factor for the success of supervised deep learning in most ophthalmic image analysis scenarios. However, limited annotated data is very common in ophthalmic image analysis, since manual annotation is time-consuming and labor-intensive. Self-supervised learning (SSL) methods bring huge opportunities for better utilizing unlabeled data, as they do not require massive annotations. To utilize as many unlabeled ophthalmic images as possible, it is necessary to break the dimension barrier, simultaneously making use of both 2D and 3D images as well as alleviating the issue of catastrophic forgetting. In this paper, we propose a universal self-supervised Transformer framework named Uni4Eye++ to discover the intrinsic image characteristic and capture domain-specific feature embedding in ophthalmic images. Uni4Eye++ can serve as a global feature extractor, which builds its basis on a Masked Image Modeling task with a Vision Transformer architecture. On the basis of our previous work Uni4Eye, we further employ an image entropy guided masking strategy to reconstruct more-informative patches and a dynamic head generator module to alleviate modality confusion. We evaluate the performance of our pre-trained Uni4Eye++ encoder by fine-tuning it on multiple downstream ophthalmic image classification and segmentation tasks. The superiority of Uni4Eye++ is successfully established through comparisons to other state-of-the-art SSL pre-training methods. Our code is available at Github1.

A study on the impact of icon structural features in human-computer interface on visual search efficiency.

This article, from the perspective of structural features, focuses on in-car user interface icons and explores the impact of different icon structural features on visual search efficiency. Initially, we categorised the icons into four groups based on structural features: individual structure icons (ISI), enclosed structure icons (ESI), horizontal structure icons (HSI) and vertical structure icons (VSI). Subsequently, we conducted a visual search experiment with structure as the sole variable, recording participants' behaviours and eye-tracking data. Finally, data analysis was conducted using methods including analysis of variance and logistic regression. The results indicate that differences in icon structural features significantly affect visual search efficiency, showcasing significant intergroup differences. HSI exhibit the highest visual search efficiency, while ESI show the lowest efficiency. ISI have shorter response times but the lowest matching accuracy. VSI only perform better than ESI. These findings hold significant implications for optimising icon design and enhancing visual search efficiency.

Visual search efficiency of icons is crucial for human-computer interaction. We investigated how the structural features of icons influence visual search efficiency. Horizontal icons are most effective, enclosed icons the least. Individual icons are quick but less accurate. Vertical icons outperform enclosed ones. Structural features should be considered in design.

Synthesis of metal-free benzimidazole-based catalysts and its application in CO2 cycloaddition.

Ionic polymers functionalized with hydroxyl, carboxyl, and amino groups can enhance the catalytic activity of catalysts. However, the straightforward preparation of bifunctional ionic polymers containing abundant ionic active sites and hydrogen bond donors remains challenging. In this study, a series of porous ionic polymers (BZIs) containing different hydrogen bond donors (-NH2, -OH, -COOH) were prepared through a simple one-pot Friedel-Crafts alkylation using benzimidazole derivatives and benzyl bromide. The structures and properties of BZIs were characterized by various techniques such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, solid-state nuclear magnetic resonance, and scanning electron microscopy. Among the prepared catalysts (BZI-NH2, BZI-OH, and BZI-COOH), BZI-NH2 exhibited the highest catalytic activity and recyclability, achieving a yield of 97% in the CO2 cycloaddition. The synergistic effect of Br-, hydrogen bond donors (-NH-, -NH2), and N+ in BZI-NH2 was found to contribute to its superior catalytic performance. DFT calculations were employed to study the effect of hydrogen bonds, Br-, and N+ in BZI-NH2 and BZI-OH on the CO2 cycloaddition. Using BZI-NH2 as an example, a mechanism was proposed for the synergistic effect between amino groups and bromide ions in catalyzing the CO2 cycloaddition reaction.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

OBJECTIVE: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. METHODS: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. RESULTS: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. CONCLUSIONS: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.

Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

Characteristics of demersal fish community structure during summer hypoxia in the Pearl River Estuary, China.

In recent decades, hypoxic areas have rapidly expanded worldwide in estuaries and coastal zones. The Pearl River Estuary (PRE), one of China's largest estuaries, experiences frequent seasonal hypoxia due to intense human activities and eutrophication. However, the ecological effects of hypoxia in the PRE, particularly on fish communities, remain unclear. To explore these effects, we collected fish community and environmental data in July 2021 during the summer hypoxia development period. The results revealed that bottom-layer dissolved oxygen (DO) in the PRE ranged from 0.08 to 5.71 mg/L, with extensive hypoxic zones (DO ≤ 2 mg/L) observed. Hypoxia has varied effects on fish community composition, distribution, species, and functional diversity in the PRE. A total of 104 fish species were collected in this study, with approximately 30 species (28.6%) exclusively found in hypoxic areas. Species responses to hypoxia varied: species such as Sardinella zunasi, Coilia mystus, and Nuchequula nuchalis were sensitive, while Decapterus maruadsi, Siganus fuscescens, and Lagocephalus spadiceus showed higher tolerance. Within the hypoxia area, dissolved oxygen was the main limiting factor for fish community diversity. Functional diversity (FDiv) decreased with higher dissolved oxygen levels, indicating a potential shift in the functional traits and ecological roles of fish species in response to changing oxygen conditions. Further analysis demonstrated that dissolved oxygen had a significantly stronger effect on fish community structure at hypoxic sites than in the whole PRE. Moreover, other environmental variables also had significant effects on the fish community structure and interacted with dissolved oxygen in the hypoxia area. These findings suggest that maintaining sufficient dissolved oxygen levels is essential for sustaining fish communities and ecosystem health in the PRE. This study provides novel insights into the effects of hypoxia on fish communities in estuarine ecosystems and has significant implications for the ecological health and management of the PRE.

Neurotoxicity of fine and ultrafine particulate matter: A comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework.

Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.

Adsorption-driven reverse osmosis separation of ethanol/water using zeolite nanosheets.

Developing more energy-efficient and cost-effective membrane processes for the separation of ethanol and water represents a strategically important direction to facilitate the production of renewable biofuels. In this study, by employing state-of-the-art molecular simulations, the potential of zeolite nanosheets as reverse osmosis (RO) membranes in ethanol/water separation is investigated. These materials are predicted to offer unprecedentedly high fluxes and more importantly, the ethanol-to-water separation factor can be as large as approximately 800 if the structure is meticulously selected. The separation achieved herein can in fact be considered counter-intuitive as the membrane allows the larger ethanol molecules to permeate through while blocking smaller water molecules. Further investigations reveal that the observed selectivity is strongly correlated with the adsorption selectivity of the bulk materials, suggesting an adsorption-driven mechanism. Promising candidates also appear to have the largest cavity diameter of approximately 6 Å, a size that can be commensurate with the dimensions of ethanol to facilitate its adsorption. The hydrophilicity on the membrane surfaces is as well found to play a non-negligible role. Overall, this study demonstrates the great promise of zeolite nanosheets as RO membranes for extracting anhydrous ethanol from its aqueous mixture and provides guidance toward the selection of promising membrane candidates.

Tailoring parameters for QM/MM simulations: accurate modeling of adsorption and catalysis in zirconium-based metal-organic frameworks.

Quantum mechanics/molecular mechanics (QM/MM) simulations offer an efficient way to model reactions occurring in complex environments. This study introduces a specialized set of charge and Lennard-Jones parameters tailored for electrostatically embedded QM/MM calculations, aiming to accurately model both adsorption processes and catalytic reactions in zirconium-based metal-organic frameworks (Zr-MOFs). To validate our approach, we compare adsorption energies derived from QM/MM simulations against experimental results and Monte Carlo simulation outcomes. The developed parameters showcase the ability of QM/MM simulations to represent long-range electrostatic and van der Waals interactions faithfully. This capability is evidenced by the prediction of adsorption energies with a low root mean square error of 1.1 kcal mol-1 across a wide range of adsorbates. The practical applicability of our QM/MM model is further illustrated through the study of glucose isomerization and epimerization reactions catalyzed by two structurally distinct Zr-MOF catalysts, UiO-66 and MOF-808. Our QM/MM calculations closely align with experimental activation energies. Importantly, the parameter set introduced here is compatible with the widely used universal force field (UFF). Moreover, we thoroughly explore how the size of the cluster model and the choice of density functional theory (DFT) methodologies influence the simulation outcomes. This work provides an accurate and computationally efficient framework for modeling complex catalytic reactions within Zr-MOFs, contributing valuable insights into their mechanistic behaviors and facilitating further advancements in this dynamic area of research.

Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

A case of herpes zoster secondary to monkeypox in a young man.

A 19-year-old young man presented with prodromal symptoms including fever and sore throat, followed by the development of scattered rashes in the perianal and penile regions. Monkeypox (MPX) was confirmed using polymerase chain reaction (PCR) of lesions. On the third day after complete resolution of the initial rash, the patient developed a new rash, which was diagnosed as secondary herpes zoster (HZ). Therefore, clinicians should not only focus on the accurate diagnosis of monkeypox, but also be alert to secondary herpes zoster.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.