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Global warming has led to an increase in the frequency of cold extremes, causing significant economic losses in aquaculture, particularly in subtropical regions. Milkfish (Chanos chanos) holds significant importance in aquaculture within subtropical Asian regions. Despite milkfish's ability to tolerate varying salinity levels, frequent cold snaps associated with extreme weather events have caused substantial mortality. Understanding the molecular and cellular mechanisms underlying cold stress-induced cell death is crucial for developing effective strategies to mitigate such losses. Given the pivotal role of the liver in fish physiology, we established a primary milkfish hepatocyte culture demonstrating robust proliferation and expressing a unique marker leptin A. The molecular characterization of cold-treated hepatocytes at 18 °C showed that the mRNA levels of superoxide dismutase (sod1) and catalase (cat), responsible for neutralizing reactive oxygen species (ROS), were downregulated in freshwater (FW) conditions, while cat expression was upregulated in seawater (SW) conditions. This differential modulation of ROS signaling implies distinct responses in FW and SW, leading to higher ROS levels and increased cell death in FW condition compared to those in SW. Transcriptomic analysis of liver tissues from milkfish reared in FW or SW, with or without cold stress, revealed distinct gene expression patterns. Although cold stress affected a common set of genes in both FW and SW conditions, SW-specific cold responsive genes are associated with metabolic pathways while FW-specific genes were linked to cell proliferation pathways. Notably, gene set enrichment analysis highlighted the downregulation of cytochrome-related genes, a major source of ROS production, in response to cold stress in SW. In summary, our study unveils an insightful mechanism whereby the salinity of SW counteracts cold stress-induced ROS signaling, emphasizing the feasibility and practicality of preconditioning fish in SW as a preventive measure against cold stress-induced mortality., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Z-DNA, a left-handed helical form of DNA, plays a significant role in genomic stability and gene regulation. Its formation, associated with high GC content and repetitive sequences, is linked to genomic instability, potentially leading to large-scale deletions and contributing to phenotypic diversity and evolutionary adaptation., Results: In this study, we analyzed the density of Z-DNA-prone motifs of 154 avian genomes using the non-B DNA Motif Search Tool (nBMST). Our findings indicate a higher prevalence of Z-DNA motifs in promoter regions across all avian species compared to other genomic regions. A negative correlation was observed between Z-DNA density and developmental time in birds, suggesting that species with shorter developmental periods tend to have higher Z-DNA densities. This relationship implies that Z-DNA may influence the timing and regulation of development in avian species. Furthermore, Z-DNA density showed associations with traits such as body mass, egg mass, and genome size, highlighting the complex interactions between genome architecture and phenotypic characteristics. Gene Ontology (GO) analysis revealed that Z-DNA motifs are enriched in genes involved in nucleic acid binding, kinase activity, and translation regulation, suggesting a role in fine-tuning gene expression essential for cellular functions and responses to environmental changes. Additionally, the potential of Z-DNA to drive genomic instability and facilitate adaptive evolution underscores its importance in shaping phenotypic diversity., Conclusions: This study emphasizes the role of Z-DNA as a dynamic genomic element contributing to gene regulation, genomic stability, and phenotypic diversity in avian species. Future research should experimentally validate these associations and explore the molecular mechanisms by which Z-DNA influences avian biology., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The objective of this study was to explore the potential of machine-learning techniques in the automatic identification and classification of brain metastases from a radiomic perspective, aiming to improve the accuracy of tumor volume assessment for radiotherapy. By using various machine-learning algorithms, including random forest, support vector machine, gradient boosting machine, XGBoost, decision tree, artificial neural network, k-nearest neighbors, LightGBM, and CatBoost algorithms, a stacking ensemble model was developed to classify gross tumor volume (GTV), brainstem, and normal brain tissue based on radiomic features. Multiple evaluation metrics, including the specificity, sensitivity, negative predictive value, positive predictive value, accuracy, Matthews correlation coefficient, and the Youden index, were used to assess the model's performance. The stacked ensemble model integrated the strengths of the nine base models and consistently outperformed individual base models in classifying GTV (area under the curve [AUC] = 0.928), brainstem (AUC = 0.932), and normal brain tissue (AUC = 0.942). Among the base models, the support vector machine model demonstrated the best performance in the three classifications (AUC = 0.922, 0.909, and 0.928). The higher performance of the stacked ensemble model highlighted the low performance of other models, including the decision tree (AUC = 0.709, 0.706, 0.804) and k-nearest neighbors (AUC = 0.721, 0.663, 0.729) models in certain contexts, such as when faced with high-dimensional feature spaces. While machine learning shows significant promise in medical image analysis, relying solely on a single model may lead to suboptimal results. By combining the strengths of various algorithms, the stacking ensemble model offers a better solution for the classification of brain metastases based on radiomic features., Competing Interests: Declarations Ethics approval and consent to participate According to the ethical guide-lines of the Helsinki Declaration and was approved by the institutional review board of Jiang-xi Cancer Hospital. Written informed consents were obtained from all patients prior to treatment. Informed consent forms were signed by all patients. The study was performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Jiang-xi Cancer Hospital (ethics number:2023KY082). Consent for publication Consent for publication is not applicable in this study, because there is not any individual person’s data. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Environmental contamination from oil spills and industrial wastewater poses long-term risks to ecosystems and human health. Amyloid fibrils' superior stiffness and stability, outstanding biocompatibility and biodegradability, versatile functional groups, and high specific surface area make them promising sustainable adsorbents. This study is aimed at examining the application of three-dimensional polysaccharide-modified whey protein amyloid fibril (WPIAF) aerogels in oil/water separation and emulsion separation. The WPIAF aerogel was first synthesized through the salting out method coupled with lyophilization, then modified using carboxymethyl cellulose (CMC) or chitosan (CS). Our results showed that WPIAF aerogels exhibited increased mechanical properties and surface hydrophobicity after polysaccharide modification. The CS-modified WPIAF aerogels showed better oil adsorption capacities, oil adsorption capability, and reusability than WPIAF aerogel and CMC-modified WPIAF aerogels. Furthermore, the applicability of polysaccharide-modified WPIAF aerogels in a continuous oil/water separation system was demonstrated. Finally, the separation efficiencies of polysaccharide-modified WPIAF aerogels were determined to be over 90 % in various emulsion systems, and the possible separation mechanism was further investigated. This study provides a nice example of applying amyloid-based aerogels for oil/water separation and emulsion separation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the cerebral or carotid arteries. CCI may lead to progressive cognitive impairment that is considered as a prelude to neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair in ischemic cerebrovascular diseases, primarily by differentiating into endothelial cells (ECs) or through paracrine effects. However, the clinical transplantation of stem cell therapies remains limited. In this study, we investigated the effects of EPC-derived conditioned medium (EPC-CM) on the impaired vasculature and neurological function in a rodent model of CCI and the mechanism involved., Methods: EPC-CM was analyzed by cytokine array to identify key factors involved in angiogenesis and cellular senescence. The effects and mechanism of the candidate factors in the EPC-CM were validated in vitro using oxygen-glucose deprivation (OGD)-injured ECs and EPCs. The therapeutic effects of EPC-CM and the identified key factor were further examined in a rat model of CCI, which was induced by bilateral internal carotid artery ligation (BICAL). EPC-CM was administered via intracisternal injection one week post BICAL. The cerebral microvasculature and neurobehavior of the rats were examined three weeks after BICAL., Results: Macrophage migration inhibitory factor (MIF) was identified as a key factor in the EPC-CM. Recombinant MIF protein promoted angiogenesis and prevented senescence in the injured EPCs and ECs. The effect was similar to that of the EPC-CM. These therapeutic effects were diminished when the EPC-CM was co-treated with MIF-specific antibody (Ab). Additionally, the vascular, motor, and cognitive improvements observed in the BICAL rats treated with EPC-CM were abolished by co-treated with MIF Ab. Furthermore, we found MIF promoted angiogenesis and anti-senescence via activating the AKT pathway. Inhibition of the AKT pathway diminished the protective effects of MIF in the in vitro study., Conclusions: We demonstrated that EPC-CM protected the brain from chronic ischemic injury and promoted functional recovery through MIF-mediated AKT pathway. These findings suggest EPC-CM holds potential as a novel cell-free therapeutic approach for treating CCI through the actions of MIF., Competing Interests: Declarations Ethics approval and consent to participate This animal experiments were conducted in accordance with the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) and was approved by the Institutional Animal Care and Use Committee of National Taiwan University (Approval no. IACUC-20180430, date of approval: 08/01/2019). The EPCs were collected from fresh human umbilical cord blood and was approved by the Institutional Review Board of National Taiwan University Hospital, Taipei, Taiwan (Study title: Platform establishment, validation, and biomarkers study in cerebrovascular diseases: using pediatric moyamoya disease as a pilot. Approval no. IRB-201204074RIC, date of approval: 07/04/2012; Study title: The pathophysiology of indirect revascularization in chronic cerebral ischemia-induced tauopathy: an in vitro, in vivo and clinical study. Approval no. IRB-202012174RIND, date of approval: 01/19/2021). All patients gave written informed consent for participation in the study and the use of samples. Consent for publication All the authors approved this manuscript to be published in the Journal Stem Cell Research & Therapy. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

X-linked retinoschisis (XLRS) is an inherited retinal disorder with severe retinoschisis and visual impairments. Multiomics approaches integrate single-cell RNA-sequencing (scRNA-seq) and spatiotemporal transcriptomics (ST) offering potential for dissecting transcriptional networks and revealing cell-cell interactions involved in biomolecular pathomechanisms. Herein, a multimodal approach is demonstrated combining high-throughput scRNA-seq and ST to elucidate XLRS-specific transcriptomic signatures in two XLRS-like models with retinal splitting phenotypes, including genetically engineered (Rs1 emR209C ) mice and patient-derived retinal organoids harboring the same patient-specific p.R209C mutation. Through multiomics transcriptomic analysis, the endoplasmic reticulum (ER) stress/eukryotic initiation factor 2 (eIF2) signaling, mTOR pathway, and the regulation of eIF4 and p70S6K pathways are identified as chronically enriched and highly conserved disease pathways between two XLRS-like models. Western blots and proteomics analysis validate the occurrence of unfolded protein responses, chronic eIF2α signaling activation, and chronic ER stress-induced apoptosis. Furthermore, therapeutic targeting of the chronic ER stress/eIF2α pathway activation synergistically enhances the efficacy of AAV-mediated RS1 gene delivery, ultimately improving bipolar cell integrity, postsynaptic transmission, disorganized retinal architecture, and electrophysiological responses. Collectively, the complex transcriptomic signatures obtained from Rs1 emR209C mice and patient-derived retinal organoids using the multiomics approach provide opportunities to unravel potential therapeutic targets for incurable retinal diseases, such as XLRS., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) activity in depression is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate how hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviours, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons using behavioural analyses, microdialysis coupled with mass spectrometry and electrophysiological recordings. Moreover, 5-HT2CR modulated the neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction by influencing intracellular Ca2+ release, as determined by fibre photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON with the specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP abolished 5-HT2CR inhibition-induced depressive-like behaviours, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviours in the presence of a 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviours and highlight hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioural consequences of 5-HT2CR inhibition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Greenberger-Horne-Zeilinger (GHZ) states, also known as two-component Schrödinger cats, play vital roles in the foundation of quantum physics and the potential quantum applications. Enlargement in size and coherent control of GHZ states are both crucial for harnessing entanglement in advanced computational tasks with practical advantages, which unfortunately pose tremendous challenges as GHZ states are vulnerable to noise. Here we propose a general strategy for creating, preserving, and manipulating large-scale GHZ entanglement, and demonstrate a series of experiments underlined by high-fidelity digital quantum circuits. For initialization, we employ a scalable protocol to create genuinely entangled GHZ states with up to 60 qubits, almost doubling the previous size record. For protection, we take a different perspective on discrete time crystals (DTCs), originally for exploring exotic nonequilibrium quantum matters, and embed a GHZ state into the eigenstates of a tailor-made cat scar DTC to extend its lifetime. For manipulation, we switch the DTC eigenstates with in-situ quantum gates to modify the effectiveness of the GHZ protection. Our findings establish a viable path towards coherent operations on large-scale entanglement, and further highlight superconducting processors as a promising platform to explore nonequilibrium quantum matters and emerging applications., (© 2024. The Author(s).)

Background: Severe asthma, which differs significantly from typical asthma, involves specific molecular biomarkers that enhance our understanding and diagnostic capabilities. The objective of this study is to assess the biological processes underlying severe asthma and to detect key molecular biomarkers., Methods: We used Weighted Gene Co-Expression Network Analysis (WGCNA) to detect hub genes in the GSE143303 dataset and indicated their functions and regulatory mechanisms using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) annotations. In the GSE147878 dataset, we used Gene Set Enrichment Analysis (GSEA) to determine the regulatory directions of gene sets. We detected differentially expressed genes in the GSE143303 and GSE64913 datasets, constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and validated the model using the GSE147878 dataset and real-time quantitative PCR (RT-qPCR) to confirm the molecular biomarkers., Results: Using WGCNA, we discovered modules that were strongly correlated with clinical features, specifically the purple module ( r  = 0.53) and the midnight blue module ( r  = -0.65). The hub genes within these modules were enriched in pathways related to mitochondrial function and oxidative phosphorylation. GSEA in the GSE147878 dataset revealed significant enrichment of upregulated gene sets associated with oxidative phosphorylation and downregulated gene sets related to asthma. We discovered 12 commonly regulated genes in the GSE143303 and GSE64913 datasets and developed a LASSO regression model. The model corresponding to lambda.min selected nine genes, including TFCP2L1, KRT6A, FCER1A, and CCL5, which demonstrated predictive value. These genes were significantly upregulated or under expressed in severe asthma, as validated by RT-qPCR., Conclusion: Mitochondrial abnormalities affecting oxidative phosphorylation play a critical role in severe asthma. Key molecular biomarkers like TFCP2L1, KRT6A, FCER1A, and CCL5, are essential for detecting severe asthma. This research significantly enhances the understanding and diagnosis of severe asthma.

Colorectal cancer (CRC) is one of the primary contributors to cancer-related fatalities, with up to 80% of advanced CRC cases exhibiting mutations in the p53 gene. Unfortunately, the development of new compounds targeting mutant p53 is quite limited. The anticancer effects of Dehydroepiandrosterone (DHEA) on various cancers have been reported. However, the suppressive effect of DHEA on CRC cells harboring wild-type or mutant p53 gene remains controversial. This study emphasized revealing the suppressive mechanism and the effect of DHEA on CRC cell tumorigenesis in the presence of wild-type or mutant p53 gene. We demonstrate that DHEA causes CRC cell death and cell cycle arrest in a dose and time-dependent manner. Notably, DHEA exhibits similar inhibitory effects on CRC cells regardless of the p53 gene status. Further study reveals that DHEA induces endoplasmic reticulum (ER) stress and triggers PERK/eIF2/ATF4/CHOP UPR signaling pathway to activate autophagy followed by apoptosis, which was confirmed by suppression of 4-phenylbutyric acid (an ER stress inhibitor) or knockdown either ATF4 or CHOP. DHEA-induced apoptosis was attenuated by silencing ATG5 gene in either p53 +/+ or p53 -/- CRC cells, indicating autophagy regulation of apoptosis. Furthermore, DHEA treatment accompanied by bafilomycin A1 (a blocker of autophagosome degradation) leads to the accumulation of ATF4, CHOP, DR5, and p21 levels in CRC cells, implying that the degradative autophagy machinery regulates these four molecules. Consistently, DHEA demonstrates its inhibitory effect by suppressing CRC tumor formation in vivo . Altogether, we provide compelling evidence that DHEA is a potential therapeutic candidate for CRC patient treatment regardless of the p53 status through ER stress-PERK-autophagy-apoptosis axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nguyen, Ko, Tsai, Cheng, Tran, Doan, Hsiao, Chang, Liu, Hong and Huang.)

Background: Recent magnetic resonance imaging (MRI) studies have established that brain iron accumulation might accelerate cognitive decline in Alzheimer's disease (AD) patients. Both normal aging and AD are associated with cerebral atrophy in specific regions. However, no studies have investigated aging- and AD-selective iron deposition-related cognitive changes during normal aging. Here, we applied quantitative susceptibility mapping (QSM) to detect iron levels in cortical signature regions and assessed the relationships among iron, atrophy, and cognitive changes in older adults., Methods: In this Taizhou Imaging Study, 770 older adults (mean age 62.0 ± 4.93 years, 57.5% women) underwent brain MRI to measure brain iron and atrophy, of whom 219 underwent neuropsychological tests nearly every 12 months for up to a mean follow-up of 2.68 years. Global cognition was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Domain-specific cognitive scores were obtained from MoCA subscore components. Regional analyses were performed for cortical regions and 2 signature regions where atrophy affected by aging and AD only: Aging (AG) -specific and AD signature meta-ROIs. The QSM and cortical morphometry means of the above ROIs were also computed., Results: Significant associations were found between QSM levels and cognitive scores. In particular, after adjusting for cortical thickness of regions of interest (ROIs), participants in the upper tertile of the cortical and AG-specific signature QSM exhibited worse ZMMSE than did those in the lower tertile [ β = -0.104, p = 0.026; β = -0.118, p = 0.021, respectively]. Longitudinal analysis suggested that QSM values in all ROIs might predict decline in ZMoCA and key domains such as attention and visuospatial function (all p < 0.05). Furthermore, iron levels were negatively correlated with classic MRI markers of cortical atrophy (cortical thickness, gray matter volume, and local gyrification index) in total, AG-specific signature and AD signature regions (all p < 0.05)., Conclusion: AG- and AD-selective iron deposition was associated with atrophy and cognitive decline in elderly people, highlighting its potential as a neuroimaging marker for cognitive aging., (© 2024. The Author(s).)

Background/purpose: Mesenchymal stem cells exhibit therapeutic efficacy for brain injury. This study examined the effect of mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) on alleviating symptoms of Parkinson's disease (PD)., Materials and Methods: SHED were isolated to examine the biosafety and bioavailability of stem cells derived from human exfoliated deciduous teeth-derived conditioned medium (SHED-CM) for the alleviation of PD symptoms in a 6-hydroxydopamine (6-OHDA)-induced PD zebrafish model., Results: SHED-CM administration did not induce neurological, skin or muscle toxicity in control zebrafish at any dose, and estrogen equivalent testing showed no chronic toxicants. Induction of PD with 6-OHDA suppressed zebra SHED-CM was administered to zebrafish treated with 6-OHDA to induce PD symptoms. Similar to nomifensine, a drug with proven anti-PD potential, SHED-CM repaired the motor deficiencies in the zebrafish PD model., Conclusion: Our results indicate the biosafety of SHED-CM and its therapeutic potential in treating PD in a zebrafish model., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: The lifelong administration of immunosuppressants remains the largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model., Methods: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term antilymphocyte serum (ALS) and cyclosporine A (CsA). Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis., Results: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared with the control (group 1). However, in group 4, FBLT combined with short-term ALS/CsA, median composite tissue allograft survival time (266 days) was significantly prolonged compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) ( P < 0.01). Group 4 also showed a significant increase in regulatory T cells ( P = 0.04) and transforming growth factor-β1 levels ( P = 0.02), and a trend toward a decrease in interleukin-1β levels ( P = 0.03) at 16 weeks after transplantation as compared with control (group 1)., Conclusions: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and antiinflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival., Clinical Relevance Statement: Full-spectrum light therapy could be a potential strategy to increase vascularized composite allotransplant survival., (Copyright © 2023 by the American Society of Plastic Surgeons.)

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs., Competing Interests: Declaration of competing interest None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

There are currently over forty degenerative diseases that are correlated with abnormal accumulation of peptide/protein aggregates in the human body, such as Alzheimer's disease. Due to their unique physiochemical properties (e.g., small size, large surface-to-volume ratio, and facile surface modification), silver nanoparticles (AgNPs) have been considered potential substrates for designing inhibitors against amyloid fibrillogenesis. Metal polyphenolic network (MPN) that combines the characteristics of organic and inorganic components has been used to suppress amyloid fibril formation. This study is aimed at investigating the effects of MPN-coated AgNPs (MPN-AgNPs) on the in vitro amyloid fibrillogenesis of hen lysozyme (HEWL). The two types of MPN-AgNPs (Zn/MPN-AgNPs and Co/MPN-AgNPs) were synthesized through chemical reduction and metal chelation, and their particle sizes were determined to be in the range of 40-60 nm. The characterization of MPN-AgNPs by ζ-potential and transmission electron microscopy showed that the MPN-AgNPs had negative surface charge and spherical-shaped morphology. Furthermore, the elemental analysis demonstrated that the MPN was uniformly coated on the surface of AgNPs. The thioflavin T fluorescence results revealed that the Co/MPN-AgNPs showed a better percent of inhibition compared to Zn/MPN-AgNPs and TA-AgNPs. The kinetics data of amyloid fibril formation in the presence of MPN-AgNPs were analyzed using the sigmoidal curve, showing that the MPN-AgNPs reduced fibril growth rate and prolonged lag time. Our findings also demonstrated that MPN-AgNPs could effectively suppress HEWL aggregation upon binding to aggregation-prone regions. The quenching of intrinsic fluorescence of HEWL by MPN-AgNPs was found to be a static type. Moreover, the fluorescence quenching data were analyzed using the modified Stern-Volmer equation to determine the number of binding sites. Notably, our findings indicated that the binding between HEWL and MPN-AgNPs was mainly governed by hydrophobic interaction. This work offers an excellent example of utilizing MPN-based materials as anti-aggregating/anti-fibrillogenic nano-drugs for the treatment of amyloidosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hsiao-Hua Yu reports financial support was provided by National Science and Technology Council. Shih-Hwa Chiou reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, NAA10, encodes the enzyme NAA10, as the catalytic subunit for the N-terminal acetyltransferase A (NatA) complex, including the accessory protein, NAA15. The first human disease directly involving NAA10 was discovered in 2011, and it was named Ogden syndrome (OS), after the location of the first affected family residing in Ogden, Utah, USA. Since that time, other variants have been found in NAA10 and NAA15 . Here we describe the generation of 31 iPSC lines, with 16 from females and 15 from males. This cohort includes CRISPR-mediated correction to the wild-type genotype in 4 male lines, along with editing one female line to generate homozygous wild-type or mutant clones. Following the monoclonalizaiton and screening for X-chromosome activation status in female lines, 3 additional pairs of female lines, in which either the wild type allele is on the active X chromosome (Xa) or the pathogenic variant allele is on Xa, have been generated. Subsets of this cohort have been successfully used to make cardiomyocytes and neural progenitor cells (NPCs). These cell lines are made available to the community via the NYSCF Repository., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Transcatheter arterial embolization (TAE) is an effective alternative to nonoperative management (NOM) to improve the spleen salvage rate for patients with blunt splenic injuries (BSIs), but it is not always available at some institutions. Moreover, laparoscopy has also been used to diagnose and treat trauma, including BSIs., Methods: We present our 11-year experience in performing laparoscopic surgery for spleen salvage in patients with severe BSIs when TAE is infeasible. The outcomes of laparoscopic surgery or TAE for spleen salvage in hemodynamically stable patients with severe BSIs were compared., Results: Fifty-six patients underwent interventions for severe BSIs during this period. Twenty patients underwent laparoscopic surgery, and 36 underwent TAE. There were no significant differences in demographics, preoperative conditions, or clinical characteristics (all p > 0.05). In the laparoscopic surgery group, 15 patients (75 %) underwent laparoscopic splenorrhaphy for spleen salvage surgery, and five (25 %) required splenectomy. No complications requiring intervention were observed in the laparoscopic surgery group, whereas three patients in the TAE group required a late splenectomy for splenic abscess. No significant differences were detected in the splenic preservation rate, complication rate, or length of hospital stay between the groups (all p > 0.05)., Conclusion: Laparoscopy is feasible and safe for managing hemodynamically stable patients with severe BSIs, and the outcomes are comparable to those of TAE. When TAE is infeasible, laparoscopy can be considered an alternative to increase the spleen salvage rate., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Absolute quantity imaging of biomolecules on a single cell level is critical for measurement assurance in biosciences and bioindustries. While infrared (IR) transmission microscopy is a powerful label-free imaging modality capable of chemical quantification, its applicability to hydrated biological samples remains challenging due to the strong IR absorption by water. Traditional IR imaging of hydrated cells relies on powerful light sources, such as synchrotrons, to mitigate the light absorption by water. However, we overcome this challenge by applying a solvent absorption compensation (SAC) technique to a home-built benchtop IR microscope based on an external-cavity quantum cascade laser. SAC-IR microscopy adjusts the incident light using a pair of polarizers to precompensate the IR absorption by water while retaining the full dynamic range. Integrating the IR absorbance over a cell yields the total mass of biomolecules per cell. We monitor the total mass of the biomolecules of live fibroblast cells over 12 h, demonstrating promise for advancing our understanding of the biomolecular processes occurring in live cells on the single-cell level.

Background: Free flap construction enhances quality of life for head and neck cancer (HNC) patients; however, complications, such as thrombosis and hematoma, threaten flap survival. This study aimed to identify factors influencing flap failure, thrombosis, and hematoma., Methods: A retrospective nested case-control study was conducted on HNC patients who underwent free flap reconstruction at a tertiary medical center between January 2019 and January 2022. All patients received antithrombotic prophylaxis consisting of prostaglandin E1, dextran, aspirin, and dipyridamole. Risk factors were analyzed using multivariate logistic regression., Results: Among 548 flaps analyzed, flap failure, thrombosis, and hematoma rates were 4.74%, 3.83%, and 9.65%, respectively. Risk factors for flap failure included thrombosis (OR 86.42, 95% CI 15.73-474.89), smoking (OR 49.44, 95% CI 1.28->1000), posteromedial thigh (PMT) flap usage (OR 14.05, 95% CI 2.48-79.54), hematoma (OR 9.68, 95% CI 2.35-39.79), and younger age (OR 0.93, 95% CI 0.87-0.99). Thrombosis risk factors included PMT usage (OR 11.45, 95% CI 2.60-50.38) and anastomosis with the superior thyroid vein (SThV) as the recipient vein after multiple reconstructions (OR 7.91, 95% CI 2.06-30.39). Hematoma risk factors included fibula osteocutaneous flap usage (OR 9.22, 95% CI 2.71-31.42), double-flap usage (OR 8.88, 95% CI 1.80-43.81), liver cirrhosis (OR 6.28, 95% CI 1.44-27.47), and postsurgery hypertension (OR 2.77, 95% CI 1.39-5.50), whereas ipsilateral recurrence (OR 0.14, 95% CI 0.03-0.73) and using the external jugular vein (EJV) as the recipient vein (OR 0.22, 95% CI 0.08-0.61) were protective factors., Conclusion: Thrombosis poses a greater risk than hematoma for flap failure. Utilization of the PMT flap and the SThV markedly increased the risk of thrombosis and flap failure. These findings highlight the importance of antithrombotic prophylaxis and the selection of flaps and recipient veins in recurrent HNC patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Chloroplast (cp) genome sequences have been extensively used for phylogenetic and evolutionary analyses, as many have been sequenced in recent years. Identification of Quercus is challenging because many species overlap phenotypically owing to interspecific hybridization, introgression, and incomplete lineage sorting. Therefore, we wanted to gain a better understanding of this genus at the level of the maternally inherited chloroplast genome. Here, we sequenced, assembled, and annotated the cp genomes of the threatened Quercus marlipoensis (160,995 bp) and Q. kingiana (161,167 bp), and mined these genomes for repeat sequences and codon usage bias. Comparative genomic analyses, phylogenomics, and selection pressure analysis were also performed in these two threatened species along with other species of Quercus. We found that the guanine and cytosine content of the two cp genomes were similar. All 131 annotated genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes, had the same order in the two species. A strong A/T bias was detected in the base composition of simple sequence repeats. Among the 59 synonymous codons, the codon usage pattern of the cp genomes in these two species was more inclined toward the A/U ending. Comparative genomic analyses indicated that the cp genomes of Quercus section Ilex are highly conserved. We detected eight highly variable regions that could be used as molecular markers for species identification. The cp genome structure was consistent and different within and among the sections of Quercus. The phylogenetic analysis showed that section Ilex was not monophyletic and was divided into two groups, which were respectively nested with section Cerris and section Cyclobalanopsis. The two threatened species sequenced in this study were grouped into the section Cyclobalanopsis. In conclusion, the analyses of cp genomes of Q. marlipoensis and Q. kingiana promote further study of the taxonomy, phylogeny and evolution of these two threatened species and Quercus., (© 2024. The Author(s).)

Background: Controlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored., Objective: This study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts., Methods: Nutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]-Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t tests were used to compare the apps to national reference data. The reliability across different national contexts was investigated by comparing the Chinese and English versions of MyFitnessPal with the USDA-FNDDS and Taiwan FCD., Results: Across the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from -13.8% to -40.3% (all P<.05). All apps underestimated cholesterol, with errors ranging from -26.3% to -60.3% (all P<.05). COFIT omitted 47% of saturated fat data, and MyFitnessPal-Chinese missed 62% of cholesterol data. The coefficients of variation of beef, chicken, and seafood ranged from 78% to 145%, from 74% to 112%, and from 97% to 124% across MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, respectively, indicating a high variability in saturated fats across different food groups. Similarly, cholesterol variability was consistently high in dairy (71%-118%) and prepackaged foods (84%-118%) across all selected apps. When examining the reliability of MyFitnessPal across different national contexts, errors in MyFitnessPal were consistent across different national FCDs (USDA-FNDSS and Taiwan FCD). Regardless of the FCDs used as a reference, these errors persisted to be statistically significant, indicating that the app's core database is the source of the problems rather than just mismatches or variances in external FCDs., Conclusions: The findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps' reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves., (© Dang Khanh Ngan Ho, Wan-Chun Chiu, Jing-Wen Kao, Hsiang-Tung Tseng, Cheng-Yu Lin, Pin-Hsiang Huang, Yu-Ren Fang, Kuei-Hung Chen, Ting-Ying Su, Chia-Hui Yang, Chih-Yuan Yao, Hsiu-Yueh Su, Pin-Hui Wei, Jung-Su Chang. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

A Mueller matrix polarimetry system at 532 nm wavelength is developed for noninvasive glucose sensing in turbid media such as human's fingertip. The system extracts mean absorbance and anisotropic properties, demonstrated numerically and experimentally with phantom glucose samples. It is found that mean absorbance ( A e ), depolarization index (Δ), and linear dichroism (LD) show linear variation with glucose concentration 100-500 mg/dL. In addition, LightTools simulations indicate proportional scaling of scattering effects with A e , Δ, and LD. Real-world tests on fingertip show a strong correlation between these properties and blood glucose levels with a mean absolute relative deviation (MARD) of 12.56% and a correlation coefficient (R 2 ) of 0.875 in prediction by a neural network (NN) model, highlighting the advantages of Mueller matrix in extracting more parameters related to blood glucose., (© 2024 Wiley‐VCH GmbH.)

Bilateral trismus associated with oral cancer was commonly occurred in those who had received surgical intervention and radiotherapy. Complete release of bilateral fibrotic tissues followed by free flaps reconstruction was the main current surgical intervention. However, reconstructions of both defects mostly needed to harvest two flaps from different donor sites were time-consuming and increasing morbidities. Herein, we presented three cases who undergone modified reconstructive method by harvesting the anterolateral thigh (ALT) flap and tensor fascia latae (TFL) flap simultaneously from the same donor site. Trismus release was performed including resection of the buccal part and fibrotic tissue, myotomy of the masticatory and medial pterygoid muscles, and bilateral coronoidectomy. Case 1, a 52 years-old man, with severe trismus as the interincisal distance (IID) was about 0 mm. He undergone a combined 12 × 7.5 cm ALT and 11 × 6 cm TFL flap reconstruction from a single-donor thigh. The IID apparently increased to 37 mm after 1-year follow-up. Case 2, a 64 years-old man, went through a combination of 6 × 7 cm ALT and 6 × 6 cm TFL flap reconstruction from unilateral thigh for severe trismus. The IID significantly improved from 10 mm to 30 mm after one and a half-year follow-up. Case 3, a 53 years-old woman, with IID was around 0 mm before the surgery. A combined 9 × 3 cm ALT and 9 × 3 cm TFL flap reconstruction was performed as the IID enhanced to 20 mm after 6 months follow-up. This reconstruction method using ALT and TFL flaps harvested from a single-donor thigh simultaneously could be suitable for patients with bilateral severe trismus., (© 2024 Wiley Periodicals LLC.)

Mercury (Hg) is a toxic element which impacts on biological systems and ecosystems. Because the toxicity of Hg species is highly dependent on their concentration levels and chemical forms, the sensitive identification of the chemical forms of Hg-i.e., Hg speciation-is of major significance in providing meaningful information about the sources of Hg exposure. In this study, a microfluidic-based device made of high-clarity poly(methyl methacrylate) (PMMA) was fabricated. Then, titanium dioxide nanoparticles (nano-TiO 2 s) were attached to the treated channel's interior with the aid of poly(diallyldimethylammonium chloride) (PDADMAC). After coupling the nano-TiO 2 -coated microfluidic-based photocatalyst-assisted reduction device (the nano-TiO 2 -coated microfluidic-based PCARD) with high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), a selective and sensitive, hyphenated system for Hg speciation was established. Validation procedures demonstrated that the method could be satisfactorily applied to the determination of mercury ions (Hg 2+ ) and methylmercury ions (CH 3 Hg + ) in both human urine and water samples. Remarkably, the zeta potential measured clearly indicated that the PDADMAC-capped nano-TiO 2 s with a predominance of positive charges indeed provided a steady force for firm attachment to the negatively charged device channel. The cause of the durability of the nano-TiO 2 -coated microfluidic-based PCARD was clarified thus.

This study introduces an innovative energy harvesting system designed for industrial applications such as fluid pipelines, air conditioning ducts, sewer systems, and subsea oil pipelines. The system integrates magneto-electric flow coupling and utilizes a dynamic vibration absorber (DVA) to mitigate the vibrations induced by fluid flow while simultaneously harvesting energy through magnetic dipole-dipole interactions in a vibration energy harvester (VEH). The theoretical models, based on Hamilton's Principle and the Biot-Savart Law, were validated through comprehensive experiments. The results indicate the superior performance of the small-magnet system over the large-magnet system in both damping and power generation. The study analyzed the frequency response and energy conversion efficiency across different parameters, including the DVA mass, spring constant, and placement location. The experimental findings demonstrated significant vibration reduction and increased voltage output, validating the theoretical model. This research offers new avenues for energy harvesting systems in pipeline infrastructures, potentially enhancing energy efficiency and structural integrity.

End-stage kidney disease (ESKD) presents a significant public health challenge, with hemodialysis (HD) remaining one of the most prevalent kidney replacement therapies. Ensuring the longevity and functionality of arteriovenous accesses is challenging for HD patients. Blood flow sound, which contains valuable information, has often been neglected in the past. However, machine learning offers a new approach, leveraging data non-invasively and learning autonomously to match the experience of healthcare professionas. This study aimed to devise a model for detecting arteriovenous grafts (AVGs) stenosis. A smartphone stethoscope was used to record the sound of AVG blood flow at the arterial and venous sides, with each recording lasting one minute. The sound recordings were transformed into mel spectrograms, and a 14-layer convolutional neural network (CNN) was employed to detect stenosis. The CNN comprised six convolution blocks with 3x3 kernel mapping, batch normalization, and rectified linear unit activation function. We applied contrastive learning to train the pre-training audio neural networks model with unlabeled data through self-supervised learning, followed by fine-tuning. In total, 27,406 dialysis session blood flow sounds were documented, including 180 stenosis blood flow sounds. Our proposed framework demonstrated a significant improvement (p<0.05) over training from scratch and a popular pre-trained audio neural networks (PANNs) model, achieving an accuracy of 0.9279, precision of 0.8462, and recall of 0.8077, compared to previous values of 0.8649, 0.7391, and 0.6538. This study illustrates how contrastive learning with unlabeled blood flow sound data can enhance convolutional neural networks for detecting AVG stenosis in HD patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Glycans are oligosaccharides attached to proteins or lipids and affect their functions, such as drug efficacy, structural contribution, metabolism, immunogenicity, and molecular recognition. Conventional glycosylation analysis has relied on destructive, slow, system-sensitive methods, including enzymatic reactions, chromatography, fluorescence labeling, and mass spectrometry. Herein, we propose quantum cascade laser (QCL) infrared (IR) spectroscopy as a rapid, nondestructive method to quantify glycans and their monosaccharide composition. Previously, we demonstrated high-sensitivity IR spectroscopy of protein solution using solvent absorption compensation (SAC) and double-beam modulation (DBM) techniques. However, the SAC-DBM approach suffered a limited frequency scanning range (<400 cm -1 ) due to the light dispersion by acousto-optic modulators (AOMs). Here, we implemented a mirror-based double-pass AOM in the SAC-DBM scheme and successfully extended the frequency range to (970 to 1840 cm -1 ), which encompasses the vibrational fingerprint of biomolecules. The extended frequency range allowed the simultaneous observation of monosaccharide ring bands (1000 to 1200 cm -1 ) and protein amide bands (1500 to 1700 cm -1 ). We compared the IR spectra of six glycoproteins and two nonglycosylated proteins with the results from intact mass spectrometry. The IR absorbance ratios of the ring band to the amide band of glycoproteins in solutions showed a linear correlation with the ratios of glycan to protein backbone masses. Furthermore, a multivariate analysis produced monosaccharide compositions consistent with the reported database for the glycoproteins, and the monosaccharide compositions were used to improve the predictability of the glycan-protein mass ratio from the IR-absorbance ratio. This nondestructive, high-sensitivity QCL-IR spectroscopy could be used as a standard method to monitor batch-to-batch comparability during drug manufacturing and quantify the glycosylation and monosaccharide composition of new glycoproteins and other glycosylated biosystems.

Background: The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments., Objective: This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics., Method: We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions., Results: Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis., Discussion: Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration., Competing Interests: The author(s) have no conflicts of interest relevant to this article., (© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Coronavirus disease-2019 (COVID-19) has caused continuous effects on the global public, especially for susceptible and vulnerable populations like pregnant women. COVID-19-related studies and publications have shown blowout development, making it challenging to identify development trends and hot areas by using traditional review methods for such massive data. Aimed to perform a bibliometric analysis to explore the status and hotspots of COVID-19 in obstetrics. An online search was conducted in the Web of Science Core Collection (WOSCC) database from January 01, 2020 to November 31, 2022, using the following search expression: (((TS= ("COVID 19" OR "coronavirus 2019" OR "coronavirus disease 2019" OR "SARS-CoV-2" OR "2019-nCoV" OR "2019 novel coronavirus" OR "SARS coronavirus 2" OR "Severe Acute Respiratory Syndrome Coronavirus-2" OR "SARS-COV2")) AND TS= ("obstetric*" OR "pregnancy*" OR "pregnant" OR "parturition*" OR "puerperium"))). VOSviewer version 1.6.18, CiteSpace version 6.1.R6, R version 4.2.0, and Rstudio were used for the bibliometric and visualization analyses. 4144 articles were included in further analysis, including authors, titles, number of citations, countries, and author affiliations. The United States has contributed the most significant publications with the leading position. "Sahin, Dilek" has the largest output, and "Khalil, Asma" was the most influential author with the highest citations. Keywords of "Cov," "Experience," and "Neonate" with the highest frequency, and "Systematic Review" might be the new research hotspots and frontiers. The top 3 concerned genes included ACE2, CRP, and IL6. The new research hotspot is gradually shifting from the COVID-19 mechanism and its related clinical research to reviewing treatment options for pregnant women. This research uniquely delves into specific genes related to COVID-19's effects on obstetrics, a focus that has not been previously explored in other reviews. Our research enables clinicians and researchers to summarize the overall point of view of the existing literature and obtain more accurate conclusions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs., Methods: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs., Results: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway)., Conclusions: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF)., Methods: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56., Results: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated., Conclusion: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

In this study, attention deficit hyperactivity disorder (ADHD), a childhood neurodevelopmental disorder, is being studied alongside its comorbidity, conduct disorder (CD), a behavioral disorder. Because ADHD and CD share commonalities, distinguishing them is difficult, thus increasing the risk of misdiagnosis. It is crucial that these two conditions are not mistakenly identified as the same because the treatment plan varies depending on whether the patient has CD or ADHD. Hence, this study proposes an electroencephalogram (EEG)-based deep learning system known as ADHD/CD-NET that is capable of objectively distinguishing ADHD, ADHD + CD, and CD. The 12-channel EEG signals were first segmented and converted into channel-wise continuous wavelet transform (CWT) correlation matrices. The resulting matrices were then used to train the convolutional neural network (CNN) model, and the model's performance was evaluated using 10-fold cross-validation. Gradient-weighted class activation mapping (Grad-CAM) was also used to provide explanations for the prediction result made by the 'black box' CNN model. Internal private dataset (45 ADHD, 62 ADHD + CD and 16 CD) and external public dataset (61 ADHD and 60 healthy controls) were used to evaluate ADHD/CD-NET. As a result, ADHD/CD-NET achieved classification accuracy, sensitivity, specificity, and precision of 93.70%, 90.83%, 95.35% and 91.85% for the internal evaluation, and 98.19%, 98.36%, 98.03% and 98.06% for the external evaluation. Grad-CAM also identified significant channels that contributed to the diagnosis outcome. Therefore, ADHD/CD-NET can perform temporal localization and choose significant EEG channels for diagnosis, thus providing objective analysis for mental health professionals and clinicians to consider when making a diagnosis., Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-10028-2., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Ischemia-reperfusion injury (IRI) is a cause of acute kidney injury in patients after renal transplantation and leads to high morbidity and mortality. Damaged kidney resident cells release cytokines and chemokines, which rapidly recruit leukocytes. Fibronectin (FN-1) contributes to immune cell migration, adhesion and growth in inflamed tissues. CCAAT/enhancer-binding protein delta is responsive to inflammatory cytokines and stresses and plays functional roles in cell motility, extracellular matrix production and immune responses. We found that the expression of CCAAT/enhancer-binding protein delta was increased in renal epithelial cells in IRI mice compared with sham mice. Following IRI, the colocalization of FN-1 with the macrophage marker F4/80 was increased in renal injury model wild-type mice but was significantly attenuated in Cebpd-deficient mice. Inactivation of CEBPD can repress hypoxia-induced FN-1 expression in HK-2 cells. Moreover, the inactivation of CEBPD and FN-1 also reduces macrophage accumulation in HK-2 cells. These findings suggest that the involvement of CEBPD in macrophage accumulation through the activation of FN-1 expression and the inhibition of CEBPD can protect against renal IRI., (© 2024. The Author(s).)

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H 2 ) in their synthesis. Using CVD growth of MoSe 2 as an example, this study illustrates the role of a H 2 -free environment during temperature ramping in suppressing the reduction of MoO 3 , which promotes effective vaporization and selenization of the Mo precursor to form MoSe 2 monolayers with excellent crystal quality. As-synthesized MoSe 2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm 2 /(V·s) with an on-off ratio of 7 × 10 7 . This approach can be extended to other TMDs, such as WSe 2 , MoTe 2 , and MoSe 2 /WSe 2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Supported ionic liquid membranes (SILMs), owing to their capacities in harnessing physicochemical properties of ionic liquid for exceptional CO 2 solubility, have emerged as a promising platform for CO 2 extraction. Despite great achievements, existing SILMs suffer from poor structural and performance stability under high-pressure or long-term operations, significantly limiting their applications. Herein, a one-step and in situ interfacial polymerization strategy is proposed to elaborate a thin, mechanically-robust, and highly-permeable polyamide armor on the SILMs to effectively protect ionic liquid within porous supports, allowing for intensifying the overall stability of SILMs without compromising CO 2 separation performance. The armored SILMs have a profound increase of breakthrough pressure by 105% compared to conventional counterparts without armor, and display high and stable operating pressure exceeding that of most SILMs previously reported. It is further demonstrated that the armored SILMs exhibit ultrahigh ideal CO 2 /N 2 selectivity of about 200 and excellent CO 2 permeation of 78 barrers upon over 150 h operation, as opposed to the full failure of CO 2 separation performance within 36 h using conventional SILMs. The design concept of armor provides a flexible and additional dimension in developing high-performance and durable SILMs, pushing the practical application of ionic liquids in separation processes., (© 2024 Wiley‐VCH GmbH.)

The development of deep generative models has inspired various facial image editing methods, but many of them are difficult to be directly applied to video editing due to various challenges ranging from imposing 3D constraints, preserving identity consistency, ensuring temporal coherence, etc. To address these challenges, we propose a new framework operating on the StyleGAN2 latent space for identity-aware and shape-aware edit propagation on face videos. In order to reduce the difficulties of maintaining the identity, keeping the original 3D motion, and avoiding shape distortions, we disentangle the StyleGAN2 latent vectors of human face video frames to decouple the appearance, shape, expression, and motion from identity. An edit encoding module is used to map a sequence of image frames to continuous latent codes with 3D parametric control and is trained in a self-supervised manner with identity loss and triple shape losses. Our model supports propagation of edits in various forms: I. direct appearance editing on a specific keyframe, II. implicit editing of face shape via a given reference image, and III. existing latent-based semantic edits. Experiments show that our method works well for various forms of videos in the wild and outperforms an animation-based approach and the recent deep generative techniques.

Background: The potential of biodegradable magnesium (Mg) skin staple has recently garnered widespread attention due to their biodegradability and biocompatibility rather than traditional stainless steel staples, the most commonly used in current clinical practice. The aim of this study is to evaluate the safety and mechanical properties of a novel biodegradable Mg skin staple., Methods: A prototype of Mg skin staple was designed using a novel ZK60 Mg alloy. The mechanical properties of the staple were evaluated using a universal testing machine. The cytotoxicity of the staple was examined in vitro and the efficacy of the staple in wound closure was assessed in New Zealand rabbits for one and three weeks, respectively., Results: The tensile strength of this Mg alloy is 258.4 MPa with 6.9% elongation. The treatment of HaCaT and L929 cells with the staple extract resulted in over 95% cell viability, indicating no cytotoxicity. In vivo, no tissue irritation was observed. No difference was found in wound healing between the Mg skin staple and the stainless steel staple after one and three weeks in the cutting wound on the back of rabbits. Some Mg skin staples spontaneously dislodged from the skin within three weeks, while others were easily removed., Conclusion: Our results confirm the safety, biocompatibility, and functionality of the novel Mg skin staple in wound closure. The efficacy of the staple in wound closure was demonstrated to be as effectively as conventional staples, with the added benefit of decreased long-term retention of skin staples in the wounds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Drugs that can treat one disease may either be detrimental or beneficial toward another due to possible cross-interactions. Therefore, care in choosing a suitable drug for patients with multiple diseases is crucial in successful patient management. This study explores several currently available ophthalmic drugs used to treat common ocular diseases to understand how they can affect the amyloidogenesis of a transforming growth factor β-induced protein (TGFBIp) peptide fragment found in abundance in the corneal protein aggregation deposits of lattice corneal dystrophy (LCD) patients. Results from this study provided supporting evidence that some drugs intended to treat other diseases can enhance or inhibit fibrillar aggregation of TGFBIp peptide, which may have potential implication of affecting the disease progression of LCD by either worsening or ameliorating it. Comparisons of the different properties of ophthalmic compounds explored in this study may also provide some guidance for future design of drugs geared toward the treatment of LCD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Efficient hydrogen generation from water splitting underpins chemistry to realize hydrogen economy. The electrocatalytic activity can be effectively modified by two-dimensional (2D) heterostructures, which offer great flexibility. Furthermore, they are useful in enhancing the exposure of the active sites for the hydrogen evolution reaction. Although the 1T-metallic phase of the transition metal dichalcogenides (TMDs) is important for the hydrogen evolution reaction (HER) catalyst, its practical application has not yet been much utilized because of the lack of stability of the 1T phase. Here, we introduce a novel approach to create a 1T-WS 2 /1T-WSe 2 heterostructure using a low-temperature plasma-assisted chemical vapor reaction (PACVR), namely plasma-assisted sulfurization and plasma-assisted selenization processes. This heterostructure exhibits superior electrocatalytic performance due to the presence of the metallic 1T phase and the beneficial synergistic effect at the interface, which is attributed to the transfer of electrons from the underlying WS 2 layer to the overlying WSe 2 layer. The WS 2 /WSe 2 heterostructure catalyst demonstrates remarkable performance in the HER as evidenced by its small Tafel slope of 57 mV dec -1 and exceptional durability. The usage of plasma helps in replacing the top S atoms with Se atoms, and this ion bombardment also increases the roughness of the thin film, thus adding another factor to enhance the HER performance. This plasma-synthesized low-temperature metallic-phase heterostructure brings out a novel method for the discovery of other catalysts.

Gene knock-in in mammalian cells usually uses homology-directed repair (HDR) mechanism to integrate exogenous DNA template into the target genome site. However, HDR efficiency is often low, and the co-localization of exogenous DNA template and target genome site is one of the key limiting factors. To improve the efficiency of HDR mediated by CRISPR/Cas9 system, our team and previous studies fused different adaptor proteins with SpCas9 protein and expressed them. By using their characteristics of binding to specific DNA sequences, many different CRISPR/SpCas9 donor adapter gene editing systems were constructed. In this study, we used them to knock-in eGFP gene at the 3'-end of the terminal exon of GAPDH and ACTB genes in HEK293T cells to facilitate a comparison and optimization of these systems. We utilized an optimized donor DNA template design method, validated the knock-in accuracy via PCR and Sanger sequencing, and assessed the efficiency using flow cytometry. The results showed that the fusion of yGal4BD, hGal4BD, hLacI, hTHAP11 as well as N57 and other adaptor proteins with the C-terminus of SpCas9 protein had no significant effect on its activity. At the GAPDH site, the donor adapter systems of SpCas9 fused with yGal4BD, hGal4BD, hLacI and hTHAP11 significantly improved the knock-in efficiency. At the ACTB site, SpCas9 fused with yGal4BD and hGal4BD significantly improved the knock-in efficiency. Furthermore, increasing the number of BS in the donor DNA template was beneficial to enhance the knock-in efficiency mediated by SpCas9-hTHAP11 system. In conclusion, this study compares and optimizes multiple CRISPR/Cas9 donor adapter gene editing systems, providing valuable insights for future gene editing applications.

Background: Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process., Methods: Databases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α., Results: The expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth., Conclusion: These findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation., (© 2024. The Author(s).)