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Background: The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. Methods: A model of bleomycin-induced pulmonary fibrosis was established, followed by treatment with bortezomib. Tissue samples were collected for analysis of immune cell subsets and functional assessment by flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors, as well as the characteristics of cell populations. Results: Here, we observed that the expression of CXCL16 and CXCR6 was elevated in the lung tissue of a pulmonary fibrosis model. In the context of pulmonary fibrosis or TGF-β1 stimulation in vitro, macrophages exhibited an M2-polarized phenotype and secreted more CXCL16 than those of the control group. Moreover, flow cytometry revealed increased expression levels of CD69 and CXCR6 in pulmonary CD4 T cells during fibrosis progression. The administration of bortezomib alleviated bleomycin-induced pulmonary fibrosis, accompanied by reduced ratio of M2-polarized macrophages and decreased accumulation of CD4 T cells expressing CXCR6. Conclusions: Our findings provide insights into the key immune players involved in bleomycin-induced pulmonary fibrosis and offer preclinical evidence supporting the repurposing strategy and combination approaches to reduce lung fibrosis. [ABSTRACT FROM AUTHOR]

Aims: Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis. Methods: We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period. Results: Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable. Conclusions: Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the clinical and radiographic outcomes and arthroscopic findings after high tibial osteotomy (HTO) between neutral and classic targeted coronal alignments in patients with medial meniscus posterior root tears (MMPRTs). Methods: Ninety-eight patients with MMPRT were prospectively enrolled in the final cohort and randomized into two groups. Fifty-two patients with the targeted alignment through the Fujisawa point (60–62.5% of the entire tibial plateau width measured from the medial side) during HTO were included in group A, whereas 46 patients with the targeted alignment through the point at 50–55% of the tibial plateau width were included in group B. The clinical and radiographic outcomes and second-look arthroscopic findings were statistically compared for comprehensive assessments. Results: After a mean follow-up of 37.1 months, we found no significant differences between the two groups regarding the final Lysholm (p = 0.205) and Hospital for Special Surgery scores (p = 0.084). However, we only observed significant differences between the two groups in terms of the final hip–knee–ankle angle, weight-bearing line ratio, and medial proximal tibial angle (p < 0.001). Second-look arthroscopy did not reveal a significant difference in meniscal healing rate (p = 0.786). Conclusions: Performing HTO with the aim to achieve neutral alignment leads to similar clinical outcomes in patients with MMPRT compared to classic alignment. Although subsequent research is required, the current study provides clinical evidence for the safety and efficacy of the new targeted alignment during HTO, which may avoid long-term complications associated with overcorrection when using the traditional technique. [ABSTRACT FROM AUTHOR]

Accelerated brain aging (ABA) intricately links with age-associated neurodegenerative and neuropsychiatric diseases, emphasizing the critical need for a nuanced exploration of heterogeneous ABA patterns. This investigation leveraged data from the UK Biobank (UKB) for a comprehensive analysis, utilizing structural magnetic resonance imaging (sMRI), diffusion magnetic resonance imaging (dMRI), and resting-state functional magnetic resonance imaging (rsfMRI) from 31,621 participants. Pre-processing employed tools from the FMRIB Software Library (FSL, version 5.0.10), FreeSurfer, DTIFIT, and MELODIC, seamlessly integrated into the UKB imaging processing pipeline. The Lasso algorithm was employed for brain-age prediction, utilizing derived phenotypes obtained from brain imaging data. Subpopulations of accelerated brain aging (ABA) and resilient brain aging (RBA) were delineated based on the error between actual age and predicted brain age. The ABA subgroup comprised 1949 subjects (experimental group), while the RBA subgroup comprised 3203 subjects (control group). Semi-supervised heterogeneity through discriminant analysis (HYDRA) refined and characterized the ABA subgroups based on distinctive neuroimaging features. HYDRA systematically stratified ABA subjects into three subtypes: SubGroup 2 exhibited extensive gray-matter atrophy, distinctive white-matter patterns, and unique connectivity features, displaying lower cognitive performance; SubGroup 3 demonstrated minimal atrophy, superior cognitive performance, and higher physical activity; and SubGroup 1 occupied an intermediate position. This investigation underscores pronounced structural and functional heterogeneity in ABA, revealing three subtypes and paving the way for personalized neuroprotective treatments for age-related neurological, neuropsychiatric, and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S‐nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine‐turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR‐regulated Na+/K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR‐biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt‐induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR‐mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+/K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+/K+ homeostasis. Summary Statement: Salinity increases brassinosteroid (BR)‐biosynthesis genes expression and endogenous BR in mangrove Kandelia obovata. BR enhances the activity and gene expression of S‐nitrosoglutathione reductase that negatively regulates nitric oxide signaling and reactive oxygen species level, while, BR regulates antioxidant enzymes and Na+/K+ homeostasis. [ABSTRACT FROM AUTHOR]

In the realm of cognitive science, the phenomenon of "successful cognitive aging" stands as a hallmark of individuals who exhibit cognitive abilities surpassing those of their age-matched counterparts. However, it is paramount to underscore a significant gap in the current research, which is marked by a paucity of comprehensive inquiries that deploy substantial sample sizes to methodically investigate the cerebral biomarkers and contributory elements underpinning this cognitive success. It is within this context that our present study emerges, harnessing data derived from the UK Biobank. In this study, a highly selective cohort of 1060 individuals aged 65 and above was meticulously curated from a larger pool of 17,072 subjects. The selection process was guided by their striking cognitive resilience, ascertained via rigorous evaluation encompassing both generic and specific cognitive assessments, compared to their peers within the same age stratum. Notably, the cognitive abilities of the chosen participants closely aligned with the cognitive acumen commonly observed in middle-aged individuals. Our study leveraged a comprehensive array of neuroimaging-derived metrics, obtained from three Tesla MRI scans (T1-weighted images, dMRI, and resting-state fMRI). The metrics included image-derived phenotypes (IDPs) that addressed grey matter morphology, the strength of brain network connectivity, and the microstructural attributes of white matter. Statistical analyses were performed employing ANOVA, Mann–Whitney U tests, and chi-square tests to evaluate the distinctive aspects of IDPs pertinent to the domain of successful cognitive aging. Furthermore, these analyses aimed to elucidate lifestyle practices that potentially underpin the maintenance of cognitive acumen throughout the aging process. Our findings unveiled a robust and compelling association between heightened cognitive aptitude and the integrity of white matter structures within the brain. Furthermore, individuals who exhibited successful cognitive aging demonstrated markedly enhanced activity in the cerebral regions responsible for auditory perception, voluntary motor control, memory retention, and emotional regulation. These advantageous cognitive attributes were mirrored in the health-related lifestyle choices of the surveyed cohort, characterized by elevated educational attainment, a lower incidence of smoking, and a penchant for moderate alcohol consumption. Moreover, they displayed superior grip strength and enhanced walking speeds. Collectively, these findings furnish valuable insights into the multifaceted determinants of successful cognitive aging, encompassing both neurobiological constituents and lifestyle practices. Such comprehensive comprehension significantly contributes to the broader discourse on aging, thereby establishing a solid foundation for the formulation of targeted interventions aimed at fostering cognitive well-being among aging populations. [ABSTRACT FROM AUTHOR]

The cognitive reserve (CR) hypothesis is reinforced by negative moderating effects, suggesting that those with higher CR are less reliant on brain structure for cognitive function. Previous research on CR's moderating effects yielded inconsistent results, motivating our 3 studies using UK Biobank data. Study I examined five CR proxies' moderating effects on global, lobar, and regional brain-cognition models; study II extended study I by using a larger sample size; and study III investigated age-related moderating effects on the hippocampal regions. In study I, most moderating effects were negative and none survived the multiple comparison correction, but study II identified 13 global-level models with significant negative moderating effects that survived correction. Study III showed age influenced CR proxies' moderating effects in hippocampal regions. Our findings suggest that the effects of CR proxies on brain integrity and cognition varied depending on the proxy used, brain integrity indicators, cognitive domain, and age group. This study offers significant insights regarding the importance of CR for brain integrity and cognitive outcomes. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans) is an opportunistic pathogen increasingly causing candidiasis worldwide. This study aims to investigate the pattern of systemic immune responses triggered by C. albicans with disease associated variation of Sap2, identifying the novel evasion strategies utilized by clinical isolates. Specifically, a variation in clinical isolates is identified at nucleotide position 817 (G to T). This homozygous variation causes the 273rd amino acid exchange from valine to leucine, close to the proteolytic activation center of Sap2. The mutant (Sap2‐273L) generated from SC5314 (Sap2‐273V) background carrying the V273L variation within Sap2 displays higher pathogenicity. In comparison to mice infected with Sap2‐273V strain, mice infected with Sap2‐273L exhibit less complement activation indicated by less serum C3a generation and weaker C3b deposition in the kidney. This inhibitory effect is mainly achieved by Sap2273L‐mediated stronger degradation of C3 and C3b. Furthermore, mice infected with Sap2‐273L strain exhibit more macrophage phenotype switching from M0 to M2‐like and more TGF‐β release which further influences T cell responses, generating an immunosuppressed cellular microenvironment characterized by more Tregs and exhausted T cell formation. In summary, the disease‐associated sequence variation of Sap2 enhances pathogenicity by complement evasion and M2‐like phenotype switching, promoting a more efficient immunosuppressed microenvironment. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) poses a significant threat to the safety of residents in long-term care facilities, and the staff of long-term care facilities are essential in the care and prevention of major infectious diseases and therefore require good health literacy to ensure the health of residents. The main objective of this study was to examine the health literacy of staff in long-term care facilities and analyze the factors associated with their COVID-19 health literacy in Taiwan to provide a basis for the response mechanism to emerging infectious diseases. Methods: A cross-sectional survey with a structured questionnaire by a convenience sample method and to assess the COVID-19 health literacy of caregivers working in long-term care facilities in this study. The COVID-19 health literacy scale was a self-administered scale designed to combine the concept of "health literacy" with the 3 levels and 5 stages of preventive medicine. A total of 385 workers from 10 long-term care facilities were surveyed as the study sample, and the validated questionnaires were statistically analyzed using SPSS version 22.0 statistical software. A multivariate logistic regression model was used to establish the associated factors of the COVID-19 health literacy level. Results: Overall, the mean COVID-19 health literacy score was 88.7 ± 10.4 (range: 58–105). Using a quartile scale, 92 (23.9%) of the study participants had low health literacy (health literacy score < 82), 190 (49.3%) had average health literacy (health literacy score 82–98), and the remaining 103 (26.8%) had good health literacy (health literacy score 99–105). Statistical analysis revealed significant differences (p < 0.05) in the COVID-19 health literacy score by demographic variables (education, job category, number of daily service users, and training related to infectious disease prevention and control) of the study population. The logistic regression analysis of the COVID-19 health literacy level (> 82 vs. ≤82) showed a significant difference in the study sample by gender (male vs. female, OR = 2.46, 95% CI = 1.15–5.26), job category (nurse practitioner vs. caregiver, OR = 7.25, 95% CI = 2.46–21.44), monthly service hours (> 160 h vs. 40–79 h, OR = 0.044, 95% CI = 0.07–0.97), experience caring for confirmed COVID-19 patients (yes vs. no, OR = 0.13, 95% CI = 0.02–0.98), and training related to infectious disease prevention and control (yes vs. no, OR = 2.8, 95% CI = 1.52–5.15). Conclusions: This study recommends that facilities provide immediate updated COVID-19 information to staff, especially frontline caregivers, and specifically enhance COVID-19 infection control education training for all facility staff to eliminate health literacy disparities. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) plays a major etiological role in the increasing number of patients with head and neck squamous cell carcinoma (HNSCC). This study aimed at exploring the relationship between HPV infection and prognosis in patients with hypopharyngeal carcinoma (HPSCC). We retrospectively analyzed 108 consecutive patients diagnosed with HPSCC from 2015 to 2018. Real-time fluorescent quantitative PCR and P16 immunohistochemistry were used to detect HPV infection in tissues of patients with hypopharyngeal carcinoma. The numbers of CD8, CD4 and Foxp3 cells in tumor parenchyma were obtained by immunohistochemical counting. Finally, the analysis was performed according to the clinicopathological variables and prognosis of the patients. Among 108 patients with HPSCC, 18 cases were detected by qPCR, and 16 subtypes accounted for the majority (77.8%). Kaplan–Meier analysis showed that HPV16+, higher CD8+, higher CD4+ and higher FoxP3+ TIL infiltration was strongly associated with superior three-year disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Univariate analysis showed that HPV and CD4+ TIL had higher predictive value for prognosis. HPV16 infection is significantly related to tumor immune infiltrating cells (TILs). [ABSTRACT FROM AUTHOR]

Natural colorants, mostly of plant and fungal origins, offer advantages over chemically synthetic colorants in terms of alleviating environmental pollution and promoting human health. The market value of natural colorants has been increasing significantly across the globe. Due to the ease of artificially culturing most fungi in the laboratory and in industrial settings, fungi have emerged as the organisms of choice for producing many natural colorants. Indeed, there is a wide variety of colorful fungi and a diversity in the structure and bioactivity of fungal colorants. Such broad diversities have spurred significant research efforts in fungi to search for natural alternatives to synthetic colorants. Here, we review recent research on the genetic and environmental factors influencing the production of three major types of natural fungal colorants: carotenoids, melanins, and polyketide-derived colorants. We highlight how molecular genetic studies and environmental condition manipulations are helping to overcome some of the challenges associated with value-added and large-scale productions of these colorants. We finish by discussing potential future trends, including synthetic biology approaches, in the commercial production of fungal colorants. [ABSTRACT FROM AUTHOR]

Accurately diagnosing of Alzheimer's disease (AD) and its early stages is critical for prompt treatment or potential intervention to delay the the disease's progression. Convolutional neural networks (CNNs) models have shown promising results in structural MRI (sMRI)-based diagnosis, but their performance, particularly for 3D models, is constrained by the lack of labeled training samples. To address the overfitting problem brought on by the insufficient training sample size, we propose a three-round learning strategy that combines transfer learning with generative adversarial learning. In the first round, a 3D Deep Convolutional Generative Adversarial Networks (DCGAN) model was trained with all available sMRI data to learn the common feature of sMRI through unsupervised generative adversarial learning. The second round involved transferring and fine-tuning, and the pre-trained discriminator (D) of the DCGAN learned more specific features for the classification task between AD and cognitively normal (CN). In the final round, the weights learned in the AD versus CN classification task were transferred to the MCI diagnosis. By highlighting brain regions with high prediction weights using 3D Grad-CAM, we further enhanced the model's interpretability. The proposed model achieved accuracies of 92.8%, 78.1%, and 76.4% in the classifications of AD versus CN, AD versus MCI, and MCI versus CN, respectively. The experimental results show that our proposed model avoids overfitting brought on by a paucity of sMRI data and enables the early detection of AD. [ABSTRACT FROM AUTHOR]

Machine learning (ML) has transformed neuroimaging research by enabling accurate predictions and feature extraction from large datasets. In this study, we investigate the application of six ML algorithms (Lasso, relevance vector regression, support vector regression, extreme gradient boosting, category boost, and multilayer perceptron) to predict brain age for middle-aged and older adults, which is a crucial area of research in neuroimaging. Despite the plethora of proposed ML models, there is no clear consensus on how to achieve better performance in brain age prediction for this population. Our study stands out by evaluating the impact of both ML algorithms and image modalities on brain age prediction performance using a large cohort of cognitively normal adults aged 44.6 to 82.3 years old (N = 27,842) with six image modalities. We found that the predictive performance of brain age is more reliant on the image modalities used than the ML algorithms employed. Specifically, our study highlights the superior performance of T1-weighted MRI and diffusion-weighted imaging and demonstrates that multi-modality-based brain age prediction significantly enhances performance compared to unimodality. Moreover, we identified Lasso as the most accurate ML algorithm for predicting brain age, achieving the lowest mean absolute error in both single-modality and multi-modality predictions. Additionally, Lasso also ranked highest in a comprehensive evaluation of the relationship between BrainAGE and the five frequently mentioned BrainAGE-related factors. Notably, our study also shows that ensemble learning outperforms Lasso when computational efficiency is not a concern. Overall, our study provides valuable insights into the development of accurate and reliable brain age prediction models for middle-aged and older adults, with significant implications for clinical practice and neuroimaging research. Our findings highlight the importance of image modality selection and emphasize Lasso as a promising ML algorithm for brain age prediction. [ABSTRACT FROM AUTHOR]

The neuroscience community has developed many convolutional neural networks (CNNs) for the early detection of Alzheimer's disease (AD). Population graphs are thought of as non-linear structures that capture the relationships between individual subjects represented as nodes, which allows for the simultaneous integration of imaging and non-imaging information as well as individual subjects' features. Graph convolutional networks (GCNs) generalize convolution operations to accommodate non-Euclidean data and aid in the mining of topological information from the population graph for a disease classification task. However, few studies have examined how GCNs' input properties affect AD-staging performance. Therefore, we conducted three experiments in this work. Experiment 1 examined how the inclusion of demographic information in the edge-assigning function affects the classification of AD versus cognitive normal (CN). Experiment 2 was designed to examine the effects of adding various neuropsychological tests to the edge-assigning function on the mild cognitive impairment (MCI) classification. Experiment 3 studied the impact of the edge assignment function. The best result was obtained in Experiment 2 on multi-class classification (AD, MCI, and CN). We applied a novel framework for the diagnosis of AD that integrated CNNs and GCNs into a unified network, taking advantage of the excellent feature extraction capabilities of CNNs and population-graph processing capabilities of GCNs. To learn high-level anatomical features, DenseNet was used; a set of population graphs was represented with nodes defined by imaging features and edge weights determined by different combinations of imaging or/and non-imaging information, and the generated graphs were then fed to the GCNs for classification. Both binary classification and multi-class classification showed improved performance, with an accuracy of 91.6% for AD versus CN, 91.2% for AD versus MCI, 96.8% for MCI versus CN, and 89.4% for multi-class classification. The population graph's imaging features and edge-assigning functions can both significantly affect classification accuracy. [ABSTRACT FROM AUTHOR]

In recent years, the rapid development of artificial intelligence has promoted the widespread application of convolutional neural networks (CNNs) in neuroimaging analysis. Although three-dimensional (3D) CNNs can utilize the spatial information in 3D volumes, there are still some challenges related to high-dimensional features and potential overfitting issues. To overcome these problems, patch-based CNNs have been used, which are beneficial for model generalization. However, it is unclear how the choice of a patchwise sampling strategy affects the performance of the Alzheimer's Disease (AD) classification. To this end, the present work investigates the impact of a patchwise sampling strategy for 3D CNN based AD classification. A 3D framework cascaded by two-stage subnetworks was used for AD classification. The patch-level subnetworks learned feature representations from local image patches, and the subject-level subnetwork combined discriminative feature representations from all patch-level subnetworks to generate a classification score at the subject level. Experiments were conducted to determine the effect of patch partitioning methods, the effect of patch size, and interactions between patch size and training set size for AD classification. With the same data size and identical network structure, the 3D CNN model trained with 48 × 48 × 48 cubic image patches showed the best performance in AD classification (ACC = 89.6%). The model trained with hippocampus-centered, region of interest (ROI)-based image patches showed suboptimal performance. If the pathological features are concentrated only in some regions affected by the disease, the empirically predefined ROI patches might be the right choice. The better performance of cubic image patches compared with cuboidal image patches is likely related to the pathological distribution of AD. The image patch size and training sample size together have a complex influence on the performance of the classification. The size of the image patches should be determined based on the size of the training sample to compensate for noisy labels and the problem of the curse of dimensionality. The conclusions of the present study can serve as a reference for the researchers who wish to develop a superior 3D patch-based CNN model with an appropriate patch sampling strategy. [ABSTRACT FROM AUTHOR]

Due to the negative environmental and health effects of synthetic colorants, pigments of natural origins of plants and microbes constitute an abundant source for the food, cosmetic, textile, and pharmaceutical industries. The demands for natural alternatives, which involve natural colorants and natural biological processes for their production, have been growing rapidly in recent decades. Fungi contain some of the most prolific pigment producers, and they excel in bioavailability, yield, cost-effectiveness, and ease of large-scale cell culture as well as downstream processing. In contrast, pigments from plants are often limited by seasonal and geographic factors. Here, we delineate the taxonomy of pigmented fungi and fungal pigments, with a focus on the biosynthesis of four major categories of pigments: carotenoids, melanins, polyketides, and azaphilones. The molecular mechanisms and metabolic bases governing fungal pigment biosynthesis are discussed. Furthermore, we summarize the environmental factors that are known to impact the synthesis of different fungal pigments. Most of the environmental factors that enhance fungal pigment production are related to stresses. Finally, we highlight the challenges facing fungal pigment utilization and future trends of fungal pigment development. This integrated review will facilitate further exploitations of pigmented fungi and fungal pigments for broad applications. [ABSTRACT FROM AUTHOR]

Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Non-textbook outcome (non-TO) represents a new prognostic evaluation index for surgical oncology. The present study aimed to develop new nomograms based on non-TO to predict the mortality and recurrence rate in patients with esophageal squamous cell cancer (ESCC) after minimally invasive esophagectomy (MIE). Methods: The study involved a retrospective analysis of 613 ESCC patients, from the prospectively maintained database from January 2011 to December 2018. All the included ESCC patients underwent MIE, and they were randomly (1:1) assigned to the training cohort (307 patients) and the validation cohort (306 patients). Kaplan–Meier survival analysis was used to analyze the differences recorded between overall survival (OS) and disease-free survival (DFS). In the case of the training cohort, the nomograms based on non-TO were developed using Cox regression, and the performance of these nomograms was calibrated and evaluated in the validation cohort. Results: Significant differences were recorded for 5-year OS and DFS between non-TO and TO groups (p < 0.05). Multivariate cox analysis revealed that non-TO, intraoperative bleeding, T stage, and N stage acted as independent risk factors that affected OS and DFS (p < 0.05). The results for multivariate regression were used to build non-TO-based nomograms to predict OS and DFS of patients with ESCC, the t-AUC curve analysis showed that the nomograms predicting OS and DFS were more accurate as compared to TNM staging, during the follow-up period in the training cohort and validation cohort. Further, the nomogram score was used to divide ESCC patients into low-, middle-, and high-risk groups and significant differences were recorded for OS and DFS between these three groups (p < 0.001). Conclusions: Non-TO was identified as an independent prognostic factor for ESCC patients. The nomograms based on non-TO could availably predict OS and DFS in ESCC patients after MIE. [ABSTRACT FROM AUTHOR]

This study assessed patient satisfaction and its associated factors among male drug-using inmates utilizing a prison detention clinic in Taiwan. A cross-sectional design and structured questionnaire were employed to recruit 580 drug-using inmates into the study. The Patient Satisfaction Questionnaire Short Form (PSQ-18), developed by the RAND Corporation, was used as the basis for the short scale of patient satisfaction, and the research data were analyzed using the SPSS for Windows 20.0 statistical software package. The results showed that the research subjects had low patient satisfaction in all the factors assessed compared with the scale's general norms. Among the original seven satisfaction subscales in this study, the highest score was for the financial aspects, and the lowest was for the amount of time spent with doctors. This study also investigated satisfaction with medical lab exams and the pharmacy at the prison's clinic, and the satisfaction scores were higher than the original seven subscales. In multiple logistic regression analyses, the final model indicated that the inmates undergoing observed rehabilitation (OR = 13.837, 95% CI = 2.736-69.983) were more likely satisfied with prison detention clinic c than those serving prison sentences. Those inmates with custodial deposits (high vs. low; OR = 1.813, 95% CI = 1.038-3.168), and meet their physical health needs (met vs. unmet; OR = 4.872, 95% CI = 2.054-11.560) had significant correlated with detention clinic care satisfactory level. Although there is only one study setting cannot give a generalizability for people who are incarcerated in Taiwan, this study highlights that the prison authorities should scrutinize factors associated with detention clinic care satisfaction, such as the type of inmate, economic status in the prison, self-reported health status, and their physical health needs, to increase the level of patient satisfaction. [ABSTRACT FROM AUTHOR]

This research evaluates the effects of performance benchmarking for public utilities using the Australian experience, providing empirical support for the significance of mechanism design in implementing revenue-cap regulation. We estimate the efficiency and productivity of Australian electricity distribution providers by utilizing the meta-frontier framework with panel data covering the period from 2007 to 2021. Our findings indicate that introducing benchmarking has facilitated technological progress and reduced efficiency gaps among companies. However, there is no statistically significant difference in the average efficiency between the periods before and after the reform, potentially due to strategic behavior exhibited by network service providers. • The average efficiency levels of AustralianDNSP in period of before- and after- 2012 reform are 0.9230 and 0.9280 respectively. • The introduction of benchmarking technique in 2012 promoted the technological progress. • The strategical behaviors of network service providers has led to no statistically significant improvement in efficiency. • We divide Australian DNSPs′ inefficiency in the two sub-periods into cost gap inefficiency and management inefficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • Single-stage PD/A-HAP process was successfully started up for the first time. • Effective nitrogen and phosphorus removal was achieved in the PD/A-HAP system. • Reconciling biomass and HAP growth is essential for effective mass transfer. • Biofilm-encapsulated HAP granular sludge exhibits superior settleability. In this study, hydroxyapatite (HAP) crystallization was introduced into a partial denitrification/Anammox (PD/A) process to develop PD/A-HAP granules and achieve simultaneous removal of nitrogen and phosphorus from wastewater. During the formation of PD/A-HAP granules, an unbalanced relationship between the biomass growth and phosphorus crystallization was observed, which resulted in a mass transfer inhibition inside the system. PD and Anammox activities were both impacted by the impeded nutrient contact, and PD process was revealed to be more susceptible to inhibition. Through the regulation of COD and NO 3 –-N, a dynamic balance between microbial proliferation and phosphorus crystallization was achieved. As a result, high nitrogen removal efficiency (NRE) was attained at 97.8±1.2 % in the final stage of operation, accompanied by a phosphorus removal efficiency (PRE) of 59.4±2.9 %. Furthermore, the recovered phosphorus was transformed into HAP crystals and encapsulated by the PD/A biomass to form granules, which greatly promoted the settling performance of the sludge. This study underlines the importance of reconciling biomass and HAP growth for a strengthened PD/A granular sludge and an enhanced nitrogen removal system. The constructed PD/A-HAP process will expand the application of PD/A with its ability to remove phosphorus while efficiently removing nitrogen. [ABSTRACT FROM AUTHOR]

The design of Junction Termination Extension (JTE) is an important step for meeting the reliability requirement of SiC PiN diode radiation detectors. For early evaluation, Technology Computer Aided Design (TCAD) software is often used to simulate the electronic property of detectors with different JTE parameters. But it is time consuming, which need 1 h or even longer for one case. Here, a TCAD augmented Machine Learning (ML) method based on the fully connected Neural Network (NN) algorithm is proposed to predict the breakdown performance quickly with different parameters of Spatial Modulation (SM) JTE. Utilized ∼5000 datum generated by TCAD simulation, the ML model could be established and achieve good prediction of breakdown voltage and location within a few seconds. As a semi-supervised learning model, its prediction accuracy of breakdown location is higher than 89.4 % and the determination coefficient R 2 of breakdown voltage could be up to 0.97 compared with TCAD simulations. Moreover, this model could give the relationship curve of breakdown voltages and doping concentration, which is useful to choose an ideal structure with a wide implantation dose window. Based on this ML prediction model, the design cycle of SiC PiN diode radiation detectors could be reduced significantly. [ABSTRACT FROM AUTHOR]

Concrete-filled steel tubular pile (CFSTP) consists of an exterior steel tube filled with core concrete. The cooperation of the steel and concrete results in the sound performance of the pile, giving the CFSTP distinct structural advantages for the coastal pile-supported wharf. The wharf pile bears the horizontal load caused by the vessels' berthing, and the vertical and moment load from the wharf as well as the vehicles and equipment on it. However, the mechanical behavior of the CFSTP under combined loads has yet to be systematically investigated, restricting the extensive applications in the wharf accordingly. To address the issue, this paper developed the comprehensive finite element models of the CFSTP under the coupled horizontal-vertical and horizontal-moment loads. Based on these models, parametric analyses are first conducted to reveal the vertical and moment load impacts on the lateral deformation and bearing capacity of the CFSTP. Then, the mechanisms of the vertical and moment load effects are clarified from the perspective of the composite action between the steel and concrete. Furthermore, the formulas quantifying these effects on the critical horizontal load of the CFSTP are established. The findings contribute to the rational design for the CFSTP subjected to combined loads. • Developing FE model of concrete-filled steel tubular pile under combined loads. • Exposing the influence of vertical and moment loads on pile lateral performance. • Revealing the mechanism of vertical and moment load effects. • Establishing formulas quantifying coupling effect of vertical and moment loads. [ABSTRACT FROM AUTHOR]

The dynamic cone penetration test (DCPT) is a common method for assessing the physical and mechanical properties of cohesionless soils. However, current formulas might not be suitable for carbonate granular soil because of its unique engineering properties. In this study, a series of DCPTs were conducted on carbonate granular soil in the field and laboratory using a light dynamic penetrometer (LDP). The results show that for a given relative density, the dynamic cone penetration resistance of carbonate granular soil increases with the mean diameter as well as the coefficient of uniformity, and it is greater than that of quartz granular soil with a similar gradation. Moreover, the relationship between the dynamic cone penetration resistance and relative density of carbonate granular soil, considering the particle size and gradation effect, is established for the LDP. The feasibility of this relationship is verified using the model test results of two other sets of carbonate sands. [ABSTRACT FROM AUTHOR]

Rationale: Characterizing the functional mechanism of quality control marker (Q‐marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug‐related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q‐marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine‐related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti‐DM mechanism of Cortex Phellodendri. Methods: An ultra‐high‐performance liquid chromatography‐coupled time‐of‐flight mass spectrometry (UHPLC/Q‐TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. Results: A total of 19 phellodendrine‐related metabolites were screened out in rats for the first time. Among them, M4, M5, M9, and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites (M4, M5, and M12) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP‐PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. Conclusion: The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti‐DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM. [ABSTRACT FROM AUTHOR]

Along with definite clinical effects, traditional Chinese medicine (TCM) has increasingly gained worldwide attention. Quality control marker (Q-marker) is always used to confirm the primary effects of herbs or TCM. Thus, the characterization of the metabolism features and subsequently induced effects are essential to reveal the functional consequences. In this work, a strategy by integrating metabolite profiling of a Q-marker and network pharmacology was proposed and applied to explore the potential function of herbs, and prim-O-glucosylcimifugin, the Q-marker of Radix Saposhnikoviae, was used as an example. As a result, 35 metabolites were characterized in rats' plasma, urine, feces, heart, liver, spleen, lung, kidney, and brain. Among them, M13/M17/M20/M23/M24/M28 were the primary metabolites, and 23 metabolites were reported for the first time. It was found that major metabolic pathways of prim-O-glucosylcimifugin were hydroxylation, dehydrogenation, hydrogenation and glucuronidation. In addition to the above metabolic reactions, methylation, hydrogenation, glycosylation, isomerization, sulfation, and other S-conjunctions were found in prim-O-glucosylcimifugin for the first time. Meanwhile, targets of prim-O-glucosylcimifugin and its major metabolites targeted additional 125 targets with functions of MAPK signaling pathway, proteoglycans in cancer, pathways in cancer, bladder cancer, colorectal cancer, serotonergic synapse and natural killer cell-mediated cytotoxicity. Among them, the depression of inflammation by MAPK signaling pathway might be the core mechanism for prim-O-glucosylcimifugin to treat respiratory tract infections. The above results provided vital information for understanding the metabolism and functional mechanism of prim-O-glucosylcimifugin in the treatment of respiratory tract infections, and a new insight for revealing the pharmacological mechanism of the complex system was also provided. [ABSTRACT FROM AUTHOR]

Invasion and metastasis are the main causes of colorectal cancer (CRC)‐related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1‐driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p‐paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p‐paxillin, MMP‐2, and vimentin was enhanced in SphK1‐overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E‐cadherin was suppressed in SphK1‐overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1‐overexpressed CRC cells, indicated that SphK1‐driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation. [ABSTRACT FROM AUTHOR]

Background: Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial–mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Methods: Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. Results: ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. Conclusion: ARHGAP10 inhibits the epithelial–mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a heterogeneous disease with different subtypes. Studying AD subtypes from brain structure, neuropathology, and cognition are of great importance for AD heterogeneity research. Starting from the study of constructing AD subtypes based on the features of T1-weighted structural magnetic resonance imaging, this paper introduces the major connections between the subtype definition and analysis strategies, including brain region-based subtype definition, and their demographic, neuropathological, and neuropsychological characteristics. The advantages and existing problems are analyzed, and reasonable improvement schemes are prospected. Overall, this review offers a more comprehensive view in the field of atrophy subtype in AD, along with their advantages, challenges, and future prospects, and provide a basis for improving individualized AD diagnosis. [ABSTRACT FROM AUTHOR]

• BML-111 inhibits migration and angiogenesis in Td-EC by modulating MMP2/9-TIMP1. • BML-111 inhibits migration and angiogenesis in Td-EC by decreasing the production of HIF-1α and COX-2. • BML-111 inhibits Td-EC permeability through the stabilization of VE-cadherin/β-catenin- dependent adherent junctions and TRPC1 pathway. Tumor angiogenesis plays a vital role in carcinogenesis, cancer progression, and metastasis. Lipoxin A 4 (LXA 4) is an endogenously-produced family of effective anti-inflammatory with a potent inhibitory effect on angiogenesis. However, BML-111, a LXA 4 agonist, its governing tumor-derived endothelial cells (Td-EC) mechanisms remain unknown. In the present study, we utilized VEGF or CoCl 2 to mimic tumor microenvironment in vitro to study the effect of BML-111 on angiogenesis and permeability of Td-EC, and preliminarily explore its specific mechanism. Data suggested that BML-111 inhibited viability, migration and angiogenesis in VEGF or CoCl 2 -treated Td-EC by modulating MMP2/9-TIMP1, and decreasing the production of HIF-1α and COX-2 level. In addition, we observed that BML-111 inhibited Td-EC permeability induced by VEGF or CoCl 2 , through the stabilization of VE-cadherin/β-catenin-dependent adherens junctions and TRPC1 pathway. Nevertheless, these effects could be blocked by BOC-2 which was the specific inhibitor of FPR2/ALX (the receptor of LXA 4).These results suggest that BML-111 may have inhibitory effects on VEGF or CoCl 2 -induced migration, angiogenesis and permeability in tumor-derived endothelial cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • High-strength anammox granules as inoculation to initiate the PD-anammox process. • A synergistic PD-anammox relationship achieved efficient nitrite conversion. • High anammox microbial abundance (∼23 %) contributed to the stability of PD-anammox. • Thauera was enriched in the system as PD functional bacteria (7.6 % in abundance). Partial denitrification (PD) is an effective approach to supply nitrite for the anaerobic ammonium oxidation (anammox) reaction, and the PD-anammox process can achieve nearly 100 % nitrogen removal when denitratation, denitritation and anammox processes are well balanced. However, most of the previous studies initiated the PD-anammox process by a mixed inoculation of denitrification and anammox sludges, leading to low anammox bacteria abundance and a risk of unstable operation in the long-term. To address this, this study used high-strength anammox granules as seed sludge for rapid PD-anammox process start-up. During the continuous operation, nitrogen removal efficiencies of 97.6 ± 1.6 % and 91.0 ± 2.0 % were attained under influent conditions of 159.4 ± 3.4 mg N/L and 78.1 ± 3.5 mg N/L, respectively. In addition, the nitrite conversion rate of the sludge reached 5.34 ± 0.37 g N/g VSS/d during the operation, and the anammox activity was stable at 0.27–0.41 g N/g VSS/d, indicating a synergistic PD-anammox relationship. Furthermore, PD bacteria were efficiently enriched in the reactor within a short period of time, with Thauera accounting for 7.6 % of the relative abundance. Notably, the abundances of dominating anammox bacteria, Ca. Brocadia and Ca. Kuenenia were 16.6 % and 4.9 %, respectively, which were among the highest of the reported PD-anammox processes. High anammox microbial abundance is conducive to ensuring the dominance and stability of the anammox reaction, enabling efficient nitrite conversion and nitrogen removal throughout the continuous operation. Finally, nitrogen removal pathways based on mass balance were proposed to clarify the fate of different nitrogen compounds in the PD-anammox system. [ABSTRACT FROM AUTHOR]

As a subsoil for many offshore structures, marine coral sand can encounter various impact loads, resulting in particle fragmentation. The "fractal theory" is an excellent method to quantify particle fragmentation. However, the relationship between the fractal dimension and relative breakage as well as its influencing factors are somewhat limited for coral sand under impact loads. Therefore, this paper systematically investigates the fractal behavior of a classic type of coral sand in the South China Sea through a series of impact load experiments. The experiment results show that the gradation curve of the coral sand under impact loading exhibits evident fractal characteristics after fragmentation, with the fractal dimension increasing with increasing fragmentation. And the ultimate fractal dimension is independent of the particle size and uniformity coefficient. Therefore, taking the ultimate fractal dimension as an ultimate state of particle fragmentation, a relative breakage index based on the relationship between the original, current, and ultimate fractal dimensions is proposed. These results can support more efficient and accurate predictions of particle fragmentation, thus promoting the safer design and construction of offshore engineering in coral sand. • Particle gradation after fragmentation appears evident fractal characteristics. • Fractal dimension increases with original particle size and uniformity coefficient. • Fractal dimension tends to a unique ultimate value with increasing fragmentation. • Breakage index based on original, current and ultimate fractal dimension is proposed. [ABSTRACT FROM AUTHOR]

The combination of partial denitrification (PD) and anaerobic ammonium oxidation (anammox) is a novel and promising nitrogen removal process. Regulating the synergistic reaction between denitrifiers and anammox bacteria (AnAOB) is the key to achieving stable and efficient PD-anammox performance. In this study, 10 mg/L of hydroxylamine (NH 2 OH) was considered to efficiently promote the bacterial activity, microbial energy flow, and the synergy of functional microflora. As a result, the nitrogen removal rate (NRR) significantly increased from 0.05 to 0.30 g N/L/d in parallel with an increase in the nitrogen loading rate (NLR) from 0.10 to 0.40 g N/L/d. However, the dual-edged effect of NH 2 OH was also confirmed. The long-term presence of NH 2 OH caused overgrowth of complete-denitrifying bacteria and decreased the NRR to 0.11 g N/L/d. Additionally, NH 2 OH enhanced nitrous oxide (N 2 O) emissions via chemical pathways as well as enhanced denitrification Fortunately, the inhibition caused by NH 2 OH was reversible by stopping the dosing, the reactor restored to stable operation with an NRR of 0.27 g N/L/d. Analysis of metabolic intensity and pathways revealed the effecting process and mechanism of NH 2 OH on the PD-anammox system. This study verified the dual-edged effects and mechanisms of NH 2 OH, therefore proving a theoretical basis and technical reference for the application of PD-anammox. [Display omitted] • Dual-edged effects and mechanisms of NH 2 OH were confirmed in the PD-anammox system. • NH 2 OH promoted microbial energy flow, and the synergy of AnAOB and denitrifiers. • Long-term presence of NH 2 OH caused overgrowth of complete-denitrifying bacteria. • NH 2 OH increased N 2 O through chemical reactions as well as enhanced denitrification. • The inhibition caused by NH 2 OH was reversible by stopping the dosing. [ABSTRACT FROM AUTHOR]

The carbonate sand could encounter impact loads causing particle breakage. To study the evolution of particle size distribution (PSD) in breakage state, a series of impact load tests were conducted on carbonate sands. From the results of uniformly graded samples, it is obtained that the fractal dimension and active breakage probability, which is equal to the mass percentage of new particle groups generated from crushing, are the functions of input energy as well as initial mean diameter. An "evolution function" of PSD in breakage state for the uniformly graded sample is established according to the fractal theory, with fractal dimension and active breakage probability as parameters. Based on the evolution functions of multiple uniform graded groups, an "assembly matrix" is proposed and used to describe the PSD evolution for non-uniformly graded sample in breakage state. The test results of non-uniformly graded samples show that this method is feasible. An "evolution function "of particle size distribution (PSD) for uniformly graded carbonate sand under impact load is established from fractal theory, with active breakage probability and fractal dimension as parameters. Based on multiple sets of evolution functions, an "assembly matrix "is proposed to describe the PSD evolution for non-uniformly graded sample. Unlabelled Image • Proposing the concept of "active breakage probability" p B. • p B and fractal dimension D relate to input energy and initial mean diameter. • Establishing PSD evolution function for uniformly graded sample with p B , D. • Calculating PSD of non-uniformly graded sample from that of uniformly graded sample. [ABSTRACT FROM AUTHOR]

Purpose: Because of increasing wealth inequality, China has been confronted with resentment against the rich (referred to hereafter as RAR or Choufu in Chinese), which is a growing concern owing to its potential to foment social conflict. Drawing on social comparison and deonance theories, this paper aims to provide theoretical insights into RAR within the Chinese context and to develop an RAR scale. Following spillover theory, the attitudinal and behavioral outcomes of RAR in organizational settings will be explored. Design/methodology/approach: This research consists of two studies. Study 1 conceptualizes RAR and develops an RAR scale by using three separate samples. Exploratory and confirmatory factor analyses are conducted to establish scale reliability and validity. Study 2 uses hierarchical linear regression analysis to test whether employees' RAR attitude spills over from the societal to the organizational setting. Findings: Results suggest that RAR can be conceptualized as two distinct but related dimensions – emotional RAR and moral RAR. These two forms spill over to the workplace, influencing employees' work attitudes and behaviors. Emotional RAR relates negatively to life satisfaction and prosocial organizational behaviors and positively to unethical organizational behaviors. Moral RAR relates negatively to pay satisfaction and positively to prosocial behaviors. Practical implications: This research suggests that RAR has spillover effects from societal to organizational settings and demonstrates that a more robust understanding of employees' workplace experience requires acknowledging social experiences, such as conflicts beyond the workplace. Originality/value: This research contributes to the conflict management literature by exploring RAR as a negative attitude that serves to potentially ignite social conflict. It not only develops a theory-grounded, conceptual RAR model and a reliable RAR scale but also for the first time explores RAR attitudinal and behavioral outcomes beyond the social domain. This study serves as a meaningful touchstone for future research to incorporate social attitudes into organizational behavior research. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. TNBC currently lacks a transplantation model that is suitable for clinical simulations of the tumor microenvironment. Intraductal injection of tumor cells into the mammary duct could mimic the occurrence and development of breast cancer. Herein, we injected 4T1 cells into the mammary ducts of BALB/C mice to build a preclinical model of TNBC and optimized the related construction method to observe the occurrence and spontaneous metastasis of tumors. We compared the effects of different cell numbers on tumorigenesis rates, times to tumorigenesis, and metastases to determine the optimal number of cells for modelling. We demonstrated that 4T1-MIND model mice injected with 20,000 cells revealed a suitable tumor formation rate and time, thus indicating a potential treatment time window after distant metastasis. We also injected 20,000 cells directly into the breast fat pad or breast duct for parallel comparison. The results still showed that the 4T1-MIND model provides sufficient treatment time for lung metastases in mice and that it is a more reliable model for early tumor development. The 4T1-MIND model requires continuous improvement and optimization. A suitable and optimized model for translational research and studies on the microenvironment in TNBC should be developed. [ABSTRACT FROM AUTHOR]

Transfer-matrix methods have been routinely used to calculate the transmission and reflection spectra of electromagnetic waves propagating through a photonic crystal slab. In this article we show that the intrinsic lattice symmetries within a photonic crystal can be used to reduce numerical computations of the electromagnetic problem. We have employed this lattice-symmetry enhanced transfer-matrix method to handle two-dimensional photonic crystal slabs of square and triangular lattices and three-dimensional layer-by-layer photonic crystal slabs. The calculated transmission spectra agree excellently with the photonic band structures in predicting the photonic band gap positions, indicating the accuracy and efficiency of this proposed approach. [ABSTRACT FROM AUTHOR]

Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the contribution of the inflammatory response to STSLS, the precise mechanism underlying STSLS development remains elusive. Here, we use a murine model to demonstrate that caspase-1 activity is critical for STSLS development. Furthermore, we show that inflammasome activation by S. suis is mainly dependent on NLRP3 but not on NLRP1, AIM2 or NLRC4. The important role of NLRP3 activation in STSLS is further confirmed in vivo with the NLRP3 inhibitor MCC950 and nlrp3-knockout mice. By comparison of WT strain with isogenic strains with mutation of various virulence genes for inflammasome activation, Suilysin is essential for inflammasome activation, which is dependent on the membrane perforation activity to cause cytosolic K+ efflux. Moreover, the mutant strain msly (P353L) expressing mutagenic SLY without hemolytic activity was unable to activate the inflammasome and does not cause STSLS. In summary, we demonstrate that the high membrane perforation activity of the epidemic strain induces a high level of NLRP3 inflammasome activation, which is essential for the development of the cytokine storm and multi-organ dysfunction in STSLS and suggests NLRP3 inflammasome as an attractive target for the treatment of STSLS. [ABSTRACT FROM AUTHOR]

Background: Physical exercises have been shown to be a surprisingly effective strategy to take advantage of the brain's natural capacity for plasticity, and prevent brain degeneration in mouse histological studies. In vivo magnetic resonance microscopy (MRM) provides highly resolved anatomical images and allows quantitative assessment of brain atrophy in the aged mouse model.Objective: The aim of the present study was to investigate, through the effects of 10 weeks voluntary wheel running, the mouse's brain atrophy.Methods: Sixteen C57BL/6J mice, aged 21 months, were randomized to the exercise or sedentary group. Each mouse was scanned in a 7.0-T MRM scanner at two time points: 22 months old baseline and a follow-up three months later. Multi-atlas based brain segmentation approach was used to obtain volumes of 39 brain regions.Results: The results showed that mice in the exercise group had less brain atrophy compared with the mice in the sedentary group.Conclusions: The results provide new insights into exercise induced brain plasticity in aged animals. [ABSTRACT FROM AUTHOR]

Abstract Food safety regulations for food contact materials (FCM) usually rely on the assessment of chemical migration in order to reduce human exposure to chemical residues that could leach from the FCM into the food. In this field, there is a need for non-targeted analytical tools which can identify unknown or unexpected leachable residues, and therefore avoid unwanted human exposure. In this study, a method based on high performance liquid chromatography coupled to hybrid quadrupole time of flight mass spectrometry (HPLC-QTOF-MS) was developed and optimized to investigate leachable residues from 30 reusable plastic bottles. Firstly, a method was validated for the targeted analysis of the 11 bisphenol analogues. None of the bisphenols were detected in the food simulants (ethanol/water; 50:50 v/v), indicating that all tested bottles are free of BPA, and that bisphenol analogues were not applied as BPA replacement in bottle manufacture. The effect of post-acquisition data processing parameters on the feature extraction in non-targeted analysis was then systematically investigated. Several parameters significantly reduced the number of correct identifications of some target trace residues, which confirms that data post-processing has to be carefully optimized to decrease the risk of false negatives. The optimized method was effectively applied to the 30 bottle samples, and monomethyl terephthalate was identified at trace level in food simulants in contact with Tritan™ bottles (migration rate of 0.054 ± 0.002–0.53 ± 0.021 µg cm−2 per 10 days at 40 °C). This method can therefore be applied to study the leachable residues from other FCMs and offer some novel information for human risk assessments. Graphical abstract fx1 Highlights • A method based on HPLC-QTOF-MS was optimized to study food contact materials. • The targeted analysis of 11 bisphenol analogues in simulants was validated. • Post-acquisition data processing parameters influence the non-targeted identification of residues. • Monomethyl terephthalate was identified in food simulants in contact with Tritan™ bottles. [ABSTRACT FROM AUTHOR]

Attached microalgae cultivation could simplify the microalgae harvest process and reduce its associated cost, which has attracted much attention recently. In this paper, the reactor patterns, advantages, microalgae biomass productivity, influencing factors and the microalgae physicochemical properties in the attached microalgae cultivation was summarized to show the sketch of this novel microalgae cultivation. It was concluded that the attached microalgae cultivation is advantageous in achieving less water and space consumption, higher water treatment potential and higher biomass productivity compared with the traditional suspended microalgae cultivation. The accumulation of the attached microalgae biomass showed a linear increase with culture time with the largest productivity up to 20.7 g m −2 d −1 . Chlorella and Scenedesmus were the top two species that have been studied in attached culture system. Cellulose acetate/nitrate membrane, polycarbonate membrane and cotton were the most popular materials used owing to their high hydrophilicity and wide availability. Flow rate, nutrients, light, CO 2 and other factors could affect the attached microalgae productivity and the physicochemical property in a way different from the suspended microalgae, which were described in detail in this review. At last, some technical bottlenecks and the corresponding solvents in the attached microalgae were suggested. [ABSTRACT FROM AUTHOR]

The small-world architecture has gained considerable attention in anatomical brain connectivity studies. However, how to adequately quantify small-worldness in diffusion networks has remained a problem. We addressed the limits of small-world measures and defined new metric indices: the small-world efficiency (SWE) and the small-world angle (SWA), both based on the tradeoff between high global and local efficiency. To confirm the validity of the new indices, we examined the behavior of SWE and SWA of networks based on the Watts-Strogatz model as well as the diffusion tensor imaging (DTI) data from 75 healthy old subjects (aged 50-70). We found that SWE could classify the subjects into different age groups, and was correlated with individual performance on the WAIS-IV test. Moreover, to evaluate the sensitivity of the proposed measures to network, two network attack strategies were applied. Our results indicate that the new indices outperform their predecessors in the analysis of DTI data. [ABSTRACT FROM AUTHOR]

Microalgae are promising feedstocks for food, feed, fuel, fertilizers, fine chemicals and other value-added products, and are considered of great potential in wastewater treatment. Convenient acquisition of the cultivated microalgal biomass or easy separation of microalgae from the treated effluents, however, are the prerequisites of these applications. Biomass harvesting and dewatering in traditional suspended cultivation systems are costly and energy intensive, since volumes of liquid medium needs to be separated from the obtained diluted microalgal biomass. Attached systems can effectively overcome such limitations by introducing substratum into the liquid medium for microalgae attachment, and the attached biomass with magnitudes higher solid content can be collected via simple and straightforward harvesting methods such as mechanical scraping. As an emerging field with less than ten years of research history, systematic information on microalgae attachment and attached systems for biomass production and wastewater treatment has not been thoroughly reviewed. This review, therefore, analyzed the two-step mechanisms of microalgae attachment, discussed the influencing factors of attached microalgal growth including properties of substratum, properties of microalgal cells, turbulence of liquid medium, frequency of biomass harvesting, etc., and their possible impacts on microalgal biofilm formation and biomass production in attached systems. Classification of attached microalgal systems based on different criteria such as substratum orientation, relative position of microalgal cells and the culturing medium, system scales and culturing medium, was summarized. Performances of attached microalgal systems for biomass production and wastewater treatment were evaluated, with commonly used parameters identified and compared as well. Recommendations for future theoretical research and practical applications were also addressed in the manuscript. This review could offer much useful information on microalgal attachment and attached systems for biomass production and wastewater treatment, and may serve as guidance for future studies in related fields. [ABSTRACT FROM AUTHOR]

β‑elemene (β‑ELE) is a natural compound extracted from Curcuma zedoaria Roscoe that has shown promise as a novel anticancer drug to treat malignant tumors. Recent studies have demonstrated that β‑ELE can reverse the drug resistance of tumor cells. To the best of our knowledge, there are no reports concerning the reversal of erlotinib resistance by β‑ELE in human non‑small cell lung cancer (NSCLC) cells. Therefore, the present study investigated the effects of β‑ELE on erlotinib‑resistant human NSCLC A549/ER cells in vitro and its possible mechanism of action. The sensitivity of A549/ER cells to erlotinib, the cytotoxicity of β‑ELE on the growth of A549/ER cells and the effects of β‑ELE on the reversal of drug resistance in A549/ER cells were determined by MTT assay. The cell apoptosis rate, cell cycle phase distribution and intracellular rhodamine 123 (Rh123) fluorescence intensity were detected by flow cytometry. The expression level of P‑glycoprotein (P‑gp) was detected by western blotting. A549/ER cells had a stable drug‑resistance to erlotinib. β‑ELE inhibited the proliferation of A549/ER cells in a time‑ and dose‑dependent manner, enhanced the sensitivity of A549/ER cells to erlotinib and reversed the drug resistance in A549/ER cells. Treatment with 15 μg/ml β‑ELE combined with 10 μmol/l erlotinib caused an increased rate of cell apoptosis and G0/G1 phase arrest. Furthermore, β‑ELE reduced the efflux of Rh123 from A549/ER cells, increased the intracellular accumulation of Rh123 and decreased the expression of P‑gp. The results of the present study indicated that β‑ELE could reverse drug resistance in erlotinib‑resistant human NSCLC A549/ER cells in vitro through a mechanism that may involve the decreased expression of P‑gp, inhibition of P‑gp dependent drug efflux and the increased intracellular concentration of anticancer drugs. [ABSTRACT FROM AUTHOR]

Abstract: In the last ten years, Chinese outward direct investment (CODI) has undergone dramatic development. It has become increasingly important on the global stage. This paper attempts to integrate the guanxi concept into the Uppsala internationalisation process model to explain CODI motivation, location choice and knowledge acquisition channels. It reveals that Chinese investment in Germany is mainly driven by the desire to explore markets and to search for strategic resources. It favours location rich in network resources. Guanxi acts as an important channel of knowledge acquisition, but it is not as important as contractual linkage because of the limited professional and industry‐related knowledge in the local Chinese community. Chinese capitalism has been shaped into a hybrid form that incorporates both modern corporate management and traditional guanxi utilisation. Research which ignores or overemphasises the role of guanxi could lead to an incorrect understanding. [ABSTRACT FROM AUTHOR]

With advantages of high load-bearing and construction efficiency, concrete-filled steel tubular (CFST) pile has been increasingly adopted in the constructions of the sea-crossing bridge, offshore wind farm and port. The mechanism of the outer steel tube effect on the CFST pile has not been comprehensively studied, which may limit the further extensive applications accordingly. This study systematically investigates the structural behavior on one classic type CFST rock-socketed pile under lateral loading through the finite element analysis, from the pile member behavior to the cross-sectional confinement effect between the constitutive components. The influence of the steel tube on the lateral displacement, critical load, and pile-soil interaction is analyzed. The mechanism of the composite action between the outer steel tube and core concrete throughout the full-loading history has been investigated to clarify the confinement effect of the steel tube to the core concrete. The parametric studies have been conducted to study the relationship between this confinement effect and the cross-sectional steel ratio. The findings may promote more efficient design and construction of the CFST pile under lateral load. • Developing comprehensive finite element models of the CFST rock-socketed pile. • Exposing the influence of the steel tube on the pile structural behaviors. • Revealing the mechanism of the steel tube reinforce effect. • Relationship between the steel tube reinforce effect and steel ratio was established. [ABSTRACT FROM AUTHOR]