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Arsenic and perfluorooctane sulfonate (PFOS) are widely distributed pollutants in the soil environment and could coexist as mixture, but little studies have been reported about their combined toxicity to terrestrial invertebrates. In the present work, we exposed earthworm Eisenia fetida to sub-lethal levels of arsenate (As(V)), PFOS, and their mixture for 30 days. Multiple biomarker responses and bioaccumulation of the two toxicants in the organisms were analyzed to assess the joint toxicity of As(V) and PFOS. Bioaccumulation analysis results demonstrated that the coexistence of As(V) and PFOS in soil could increase the bioavailability of As(V) while decreasing the bioavailability of PFOS. As the level of exposure increased, significant variations were observed in all of the biomarkers analyzed, indicating growth inhibition and oxidative damage. The multiple biomarker responses were summarized by using the Integrated Biomarker Response (IBR) index, and significant dose–response relationships were found in treatments of As(V), PFOS and As(V)/PFOS mixture. Then the toxic interaction between As(V) and PFOS was assessed by combining IBR and two mixture toxicity indices, Effect Addition Index (EAI) and Concentration Addition Index (CAI). Results showed that the joint toxicity of As(V) and PFOS depended on the exposure concentration of As(V). The combined pollution of PFOS with lower concentration of As(V) led to synergistic interaction at the whole range of effect levels, while that with higher concentration of As(V) resulted in the toxicity interaction changing from antagonism to synergism as the effect level increased. As(V) was the main toxicant that caused adverse effects on earthworm biomarkers and affected the joint toxicity of As(V)/PFOS mixture. This study, for the first time, provides valuable toxicological data for the risk evaluation of combined toxicity of As(V) and PFOS in the soil environment. Moreover, this work indicates that the integration of IBR index and EAI/CAI could be an effective and practical method for the characterization of toxicity interaction within binary mixture systems.

Identification of exact causative genes is important for in silico drug repositioning based on drug-gene-disease relationships. However, the complex polygenic etiology of the autism spectrum disorder (ASD) is a challenge in the identification of etiological genes. The network-based core gene identification method can effectively use the interactions between genes and accurately identify the pathogenic genes of ASD. We developed a novel network-based drug repositioning framework that contains three steps: network-specific core gene (NCG) identification, potential therapeutic drug repositioning, and candidate drug validation. First, through the analysis of transcriptome data for 178 brain tissues, gene network analysis identified 365 NCGs in 18 coexpression modules that were significantly correlated with ASD. Second, we evaluated two proposed drug repositioning methods. In one novel approach (dtGSEA), we used the NCGs to probe drug-gene interaction data and identified 35 candidate drugs. In another approach, we compared NCG expression patterns with drug-induced transcriptome data from the Connectivity Map database and found 46 candidate drugs. Third, we validated the candidate drugs using an in-house mental diseases and compounds knowledge graph (MCKG) that contained 7509 compounds, 505 mental diseases, and 123,890 edges. We found a total of 42 candidate drugs that were associated with mental illness, among which 10 drugs (baclofen, sulpiride, estradiol, entinostat, everolimus, fluvoxamine, curcumin, calcitriol, metronidazole, and zinc) were postulated to be associated with ASD. This study proposes a powerful network-based drug repositioning framework and also provides candidate drugs as well as potential drug targets for the subsequent development of ASD therapeutic drugs.

The present study was designed to examine the relationship between dispositional mindfulness and suicide risk in undergraduates, and it further explored the potential mediating role of alexithymia in this relationship. A total of 2,633 undergraduates completed the Mindful Attention Awareness Scale (MAAS), the Suicidal Behaviors Questionnaire – Revised (SBQ-R), and the 20-item Toronto Alexithymia Scale (TAS-20). The results indicate that mindfulness and suicide risk were negatively correlated, and alexithymia partially mediated the relationship between mindfulness and suicide risk only in the female undergraduates. Moreover, only the difficulty in identifying feelings (DIF) factor of alexithymia mediated the relationship between mindfulness and suicide risk in the female undergraduates. These findings contribute to the potential mechanism that explains the relationship between mindfulness and suicide risk. Furthermore, it is possible to implement mindfulness in the suicide intervention of alexithymic individuals.

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for the treatment of various cancers. These novel treatments effectively target key mediators of immune checkpoint pathways. Currently, ICIs primarily consist of monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite the notable efficacy of ICIs in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present as autoimmune-like or inflammatory conditions. IrAEs have the potential to affect multiple organ systems, with cutaneous toxicities being the most commonly observed. Although cutaneous irAEs are typically of low-grade severity and can usually be managed effectively, there are cases where severe irAEs can become life-threatening. Therefore, early recognition and a comprehensive understanding of the mechanisms underlying cutaneous irAEs are crucial for improving clinical outcomes in cancer patients. However, the precise pathogenesis of cutaneous irAEs remains unclear. This review focuses on the skin manifestations induced by ICIs, the prognosis related to cutaneous irAEs, and the exploration of potential mechanisms involved in cutaneous irAEs.

This study examined the effectiveness of interactive electronic picture (IEP) books during immersive reading, impact on mental health education, and integrating gaming elements in educational settings. The mixed-methods experiment combined quantitative data from surveys with qualitative insights from in-depth interviews. The findings revealed that males have higher levels of immersion during interactive reading. This study contributes to digital learning by providing empirical evidence on the benefits of integrating interactive technology into education as well as emphasizing IEP books' potential to revolutionize mental health education and the importance of considering gender differences when designing educational tools. [ABSTRACT FROM AUTHOR]

Industry 4.0 can enhance the operational efficiency of the supply chain, but the current research mainly focuses on analytics and smart things. Many companies integrate their organizations more closely with data by adopting Industry 4.0, but this study found that some companies have changed their leadership, organizational, and customer relationships through the adoption of CPS. Industry 4.0 is a socio-technical system that should be explored in terms of management practices, employee feedback, and the cause-and-effect relationship between them. This study proposes a modeling framework using the Su-field analysis of TRIZ method (Theory of Inventive Problem Solving) and applies the Partial Least Squares Structural Equation Modeling (PLS-SEM) method to investigate the relationship between leadership, organizational culture, and service management in the Taiwan industry. The results show that the data analysis, CPS, IoT, and intelligent technologies of Industry 4.0 can facilitate connections within the value chain and increase agility in response to environmental changes. Companies must have a good organizational culture and provide the right incentives to gain the organizational commitment of their employees to implement Industry 4.0.

The neutrophil is the major phagocyte and the final effector cell of the innate immunity, with a primary role in the clearance of extracellular pathogens. Using the broad array of cytokines, extracellular traps, and effector molecules as the humoral arm, neutrophils play a crucial role in the host defense against pathogen infections. On the other hand, the pathogen has the capacity to overcome neutrophil-mediated host defense to establish infection causing human disease. Pathogens, such as S. aureus, have the potential to thwart neutrophil chemotaxis and phagocytosis and thereby succeed in evading killing by neutrophils. Furthermore, S. aureus surviving within neutrophils promotes neutrophil cytolysis, resulting in the release of host-derived molecules that promote local inflammation. Here, we provide a detailed overview of the mechanisms by which neutrophils kill the extracellular pathogens and how pathogens evade neutrophils degradation. This review will provide insights that might be useful for the development of novel therapies against infections caused by antibiotic resistant pathogens.

Gene-specific, age-dependent regulations are common at the transcriptional and translational levels, while protein transport into organelles is generally thought to be constitutive. Here we report a new level of differential age-dependent regulation and show that chloroplast proteins are divided into three age-selective groups: group I proteins have a higher import efficiency into younger chloroplasts, import of group II proteins is nearly independent of chloroplast age, and group III proteins are preferentially imported into older chloroplasts. The age-selective signal is located within the transit peptide of each protein. A group III protein with its transit peptide replaced by a group I transit peptide failed to complement its own mutation. Two consecutive positive charges define the necessary motif in group III signals for older chloroplast preference. We further show that different members of a gene family often belong to different age-selective groups because of sequence differences in their transit peptides. These results indicate that organelle-targeting signal peptides are part of cells' differential age-dependent regulation networks. The sequence diversity of some organelle-targeting peptides is not a result of the lack of selection pressure but has evolved to mediate regulation. [ABSTRACT FROM AUTHOR]

An Arabidopsis thaliana mutant defective in chloroplast protein import was isolated and the mutant locus, cia5, identified by map-based cloning. ClA5 is a 21-kD integral membrane protein in the chloroplast inner envelope membrane with four predicted transmembrane domains, similar to another potential chloroplast inner membrane protein-conducting channel, At Tic20, and the mitochondrial inner membrane counterparts Tim17, Tim22, and Tim23. cia5 null mutants were albino and accumulated unprocessed precursor proteins, cia5 mutant chloroplasts were normal in targeting and binding of precursors to the chloroplast surface but were defective in protein translocation across the inner envelope membrane. Expression levels of ClA5 were comparable to those of major translocon components, such as At Tic110 and At Toc75, except during germination, at which stage At Tic20 was expressed at its highest level. A double mutant of cia5 At tic20-l had the same phenotype as the At tic20-l single mutant, suggesting that ClA5 and At Tic20 function similarly in chloroplast biogenesis, with At Tic20 functioning earlier in development. We renamed ClA5 as Arabidopsis Tic21 (At Tic21) and propose that it functions as part of the inner membrane protein-conducting channel and may be more important for later stages of leaf development [ABSTRACT FROM AUTHOR]

Aim: To construct a recombinant adenovirus that can simultaneously express both antisense ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AdoMetDC) and detect its inhibitory effect on the intracellular polyamine pool and colorectal cancer cell growth. Methods: A205-bp cDNA of AdoMetDC was reverse-inserted into recombinant pAdTrack-ODCas vectors and recombined with pAdEasy-1 vectors in AdEasy-1 cells. Positive clones were selected and transfected into the packaging cell HEK293 after they were linearized by PacI. Green fluorescent protein expression was used to monitor the process of adenovirus packaging. The ODC and AdoMetDC protein levels were identified by western blotting, and intracellular polyamine content was detected by reverse-phase high performance liquid chromatography. A viable cell count was used to determine the growth of HT-29 cells with or without exogenous polyamine. Results: Sequencing confirmed that AdoMetDC cDNA was successfully ligated into the pAdTrack-ODCas vector. GFP expression in 293 cells during virus packing and amplification was observed by fluorescence microscopy. Western blotting demonstrated that both ODC and AdoMetDC were downregulated by Ad-ODC-AdoMetDCas, and consequently 3 kinds of polyamine (putrescine, spermidine and spermine) were reduced to very low levels. HT-29 cell growth was significantly inhibited as compared with control conditions, and growth arrest was not reversed by exogenous putrescine. Conclusion: The successfully constructed recombinant adenovirus, Ad-ODC-AdoMetDCas, blocked polyamine synthesis and has therapeutic potential for treating colorectal cancer in vitro. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the association between obesity and orbital fat expansion in proptosis of thyroid eye disease. Methods This observational study retrospectively enrolled 87 participants who received orbital fat decompression surgery for thyroid eye disease. Primary outcome measures included average body mass index (BMI) and the proportion of the study sample with overweight and obesity, compared with the general Taiwanese population. Secondary outcome measures included the association of obesity with proptosis severity, removed fat volume, and thyroid status. Results The average BMI (25.59 ± 4.36 kg/m2) of the study sample was significantly higher than that in the general population of Taiwan (24.5 kg/m2; P = 0.012). Participants with overweight (19.52 ± 3.52 mm) and obesity (21.25 ± 3.76 mm) exhibited significantly more severe proptosis than participants without overweight (18.05 ± 3.37 mm) and without obesity (18.09 ± 3.02 mm; P = 0.029 and P

Compares the effect of various experimental factors on the photoisomerization of nitrobenzaldehyde. Light source; Light energy; Exposure time; Light path distance; Concentration of nitrobenzaldehyde.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with memory loss and cognitive decline. Neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein are one of the pathological hallmarks of several neurodegenerative diseases including AD. Heat shock protein family B (small) member 1 (HSPB1) is a molecular chaperone that promotes the correct folding of other proteins in response to environmental stress. Nuclear factor erythroid 2-like 2 (NRF2), a redox-regulated transcription factor, is the master regulator of the cellular response to excess reactive oxygen species. Tropomyosin-related kinase B (TRKB) is a membrane-bound receptor that, upon binding brain-derived neurotrophic factor (BDNF), phosphorylates itself to initiate downstream signaling for neuronal survival and axonal growth. In this study, four natural flavones such as 7,8-dihydroxyflavone (7,8-DHF), wogonin, quercetin, and apigenin were evaluated for Tau aggregation inhibitory activity and neuroprotection in SH-SY5Y neuroblastoma. Among the tested flavones, 7,8-DHF, quercetin, and apigenin reduced Tau aggregation, oxidative stress, and caspase-1 activity as well as improved neurite outgrowth in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. Treatments with 7,8-DHF, quercetin, and apigenin rescued the reduced HSPB1 and NRF2 and activated TRKB-mediated extracellular signal-regulated kinase (ERK) signaling to upregulate cAMP-response element binding protein (CREB) and its downstream antiapoptotic BCL2 apoptosis regulator (BCL2). Knockdown of TRKB attenuated the neuroprotective effects of these three flavones. Our results suggest 7,8-DHF, quercetin, and apigenin targeting HSPB1, NRF2, and TRKB to reduce Tau aggregation and protect cells against Tau neurotoxicity and may provide new treatment strategies for AD.

Removal of a paint layer of 2024 aluminum alloy was studied using a nanosecond fiber pulsed laser with a maximum power of 30 W and the influence of laser cleaning energy density on the surface integrity of the substrate was explored. The cleaning energy density threshold of the paint layer is 17.69 J / c m 2 and the damage energy density threshold is 24.77 J / c m 2 . The optimum cleanliness and surface integrity of laser cleaning were obtained when the energy density was 21.23 J / c m 2 . Microhardness and Young's modulus of the surface after laser cleaning were improved by 6% and 25%, respectively. The mechanical properties of the surface of the substrate after laser cleaning were significantly improved, which is an advantage for this high-quality non-destructive cleaning technology of the aircraft skin surface paint layer.