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Abstract Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

To study the seed dormancy and germination mechanism of Xanthoceras sorbifolium, the seeds of four cultivars [‘Putong’(PT),‘Qihong’(QH), ‘Wofeng’(WF) and‘Woshi’(WS)] were stored at -20 ℃ for different periods (30, 60, 90, 120, 150 d). The seed germination indexes were determined in each treatment, and the changes of reserve substance and hormone content were also analyzed in three stages including before storage, after storage, and 7 days of germination. The results were as follows: (1) Cold storage could significantly promote the germination rate and germination potential of small seeds (PT, QH). The best treatment was cold storage for 60 d, and the germination rate was up to 48.3% and 58.3%, respectively. The effects of cold storage on large seeds (WF and WS) was lower than that of small seeds. (2) The kernel oil content, seed shell thickness (SST) in four cultivar seeds all decreased significantly during periods of cold storage and germination, especially in 3-7 days of germination, the oil content and SST (except WS cultivar) decreased notably. However, water content in kernels increased rapidly within 1-3 days of germination and then slowly increased to the peak value on the 7th day. The contents of soluble sugar in kernels increased significantly at the 3-4 days of germination. (3) Cold storage increased GA/ABA and tHor/ABA ratios in small seeds (PT, QH), promoted oil degradation, made seed shell thinning and break seed dormancy. In conclusion, the main factors leading to dormancy in X. sorbifolium seeds are larger in size, higher shell thickness and more hardness, physiological post-ripening, and belongs to comprehensive dormancy type. Cold storage at -20 ℃ for 60 d can improve the germination rate of PT, QH and WF seeds, reduces dormancy degree, while the cold storage time of WS seeds needs prolonging to 150 d. The method using -20 ℃ storage with wet sand germination is a rapid and simple method to promote X. sorbifolium seeds germination. This study provides a reference for the promotion of superior varieties and the research on the seed breaking dormancy mechanism in X. sorbifolium.

Background: Obesity and sarcopenia are both viewed as pathological body composition issues and indicators of compromised nutritional status. The aim of this study was to evaluate the effects of sarcopenic obesity on short- and long-term clinical outcomes. Methods: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Sarcopenia is defined by European Working Group on Sarcopenia in Older People (EWGSOP2) and obesity is defined by the body mass index (BMI). To identify the independent predictors of postoperative complications and overall survival, we performed univariate and multivariate logistic and Cox regression analyses. Results: In a total of 508 cases, 372 (73.2%) cases were diagnosed with non-sarcopenia, 112 (22.0%) with non-obese sarcopenia, and 24 (4.7%) with sarcopenic obesity. In the multivariate logistic regression, both of non-obese sarcopenia (OR = 2.305, 95% CI = 1.444–3.679, P < 0.001) and sarcopenic obesity (OR = 2.589, 95% CI = 1.088–6.156, P = 0.031) were independent risk factors for postoperative complications. In the multivariate Cox analysis, only non-obese sarcopenia (HR = 2.614, 95% CI = 1.882–3.631, P < 0.001) was independent risk factor for overall survival. Conclusions: Sarcopenic obesity serves as an independent risk factor for postoperative complications, but not for overall survival. [ABSTRACT FROM AUTHOR]

Utilizing hydrophone arrays for detecting underwater acoustic communication (UWAC) signals leverages spatial information to enhance detection efficiency and expand the perceptual range. This study redefines the task of UWAC signal detection as an object detection problem within the frequency–azimuth (FRAZ) spectrum. Employing Faster R-CNN as a signal detector, the proposed method facilitates the joint prediction of UWAC signals, including estimates of the number of sources, modulation type, frequency band, and direction of arrival (DOA). The proposed method extracts precise frequency and DOA features of the signals without requiring prior knowledge of the number of signals or frequency bands. Instead, it extracts these features jointly during training and applies them to perform joint predictions during testing. Numerical studies demonstrate that the proposed method consistently outperforms existing techniques across all signal-to-noise ratios (SNRs), particularly excelling in low SNRs. It achieves a detection F1 score of 0.96 at an SNR of −15 dB. We further verified its performance under varying modulation types, numbers of sources, grating lobe interference, strong signal interference, and array structure parameters. Furthermore, the practicality and robustness of our approach were evaluated in lake-based UWAC experiments, and the model trained solely on simulated signals performed competitively in the trials. [ABSTRACT FROM AUTHOR]

Mirroring public ideologies and value systems in legislative discourse, stance not only functions as a powerful instrument for legislators to balance legal values and stakeholders' interests but also acts as a valuable reference for individuals to understand legislative texts. This study conducts a corpus-driven analysis of stance expressions in legislative discourse. Using three self-compiled corpora that incorporate data protection laws from the United States, the European Union, and China, we apply Hyland's stance model to contrastively analyse evidence of hedging, boosting, self-mention, and attitude markers across these jurisdictions and eventually propose a specialised research model of stance in law. This study unveils the nature of modesty and sufficient discursive space of data protection laws, as well as legislative values and public ideologies conveyed by different jurisdictions within the broader socio-legal cultural context. Besides uncovering the legal constructiveness of data protection laws, the results also suggest that the overall representation of stance in data protection legislation aligns with its performance in legislative discourse, which showcases a legislative tendency to achieve an overtly neutral appearance through covert stance expressions. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsDiscussionThe study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis.The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study.Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes.TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease. [ABSTRACT FROM AUTHOR]

The advancement of laser-induced graphene (LIG) technology has streamlined the fabrications of flexible graphene devices. However, the ultrafast kinetics triggered by laser irradiation generates intrinsic amorphous characteristics, leading to high resistivity and compromised performance in electronic devices. Healing graphene defects in specific patterns is technologically challenging by conventional methods. Herein, we report the rapid rectification of LIG's topological defects by flash Joule heating in milliseconds (referred to as F-LIG), whilst preserving its overall structure and porosity. The F-LIG exhibits a decreased ID/IG ratio from 0.84 – 0.33 and increased crystalline domain from Raman analysis, coupled with a 5-fold surge in conductivity. Pair distribution function and atomic-resolution imaging delineate a broader-range order of F-LIG with a shorter C-C bond of 1.425 Å. The improved crystallinity and conductivity of F-LIG with excellent flexibility enables its utilization in high-performance soft electronics and low-voltage disinfections. Notably, our F-LIG/polydimethylsiloxane strain sensor exhibits a gauge factor of 129.3 within 10% strain, which outperforms pristine LIG by 800%, showcasing significant potential for human-machine interfaces. Laser-induced graphene (LIG) can be obtained via a practically convenient approach, but its amorphous characteristics limit its applications. Here, the authors report a flash Joule heating strategy to improve the crystalline quality and conductivity of LIG, leading to strain sensors with enhanced sensitivity. [ABSTRACT FROM AUTHOR]

Background: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD)., Methods: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects., Results: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures., Conclusions: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

"The EU Artificial Intelligence Act: Regulating Subliminal AI Systems" by Rostam J. Neuwirth explores the need for regulation in the field of Artificial Intelligence (AI) to address legal and ethical concerns. The book focuses on the specific challenge of regulating subliminal techniques used by AI systems. It examines the proposed EU Artificial Intelligence Act (AIA) and its objective, scope, and context. The book also delves into the psychology of subliminal messages and the potential negative effects they can have. It concludes by emphasizing the importance of global collaboration and a binding legal framework for regulating AI systems. This book provides valuable insights for researchers, policymakers, and legal professionals interested in understanding and addressing the impact of AI on society. [Extracted from the article]

The COVID-19 pandemic has affected various industries in different ways depending on their type of business. We attempt to understand the impact of the pandemic on the performance of 26 major container carriers. To capture performance differences before and during the pandemic, we collect data the years 2019 and 2020. Further, we divide carriers' business processes into two stages, i.e., asset acquisitions and transport operations. We employ relevant data envelopment analysis (DEA) models to this effect. The mean efficiency score in 2020 was higher than in 2019. Overall, container carriers increased their performance during the COVID-19 pandemic. However, seven companies showed lower efficiency in 2020. Similarly, eight companies were efficient in their operations but not in asset acquisition decisions. Our results show that firm strategy is important in coping with external shocks. The contribution of the paper is in measuring the impact of external shocks, such as the COVID-19 pandemic, on the performance of container carriers, both in regard of their acquisitions and their operations. [ABSTRACT FROM AUTHOR]

In construction, risk is inherent in each project, and success involves meeting defined objectives beyond budget and schedule. Factors vary for infrastructure projects, and their correlation with performance must be studied. In the case of public–private partnership (PPP) transportation, the level of complexity is higher due to more involved parties. Risks and success factors in PPP projects affect each other, which may lead to project failure. Recognizing the critical risk factors (CRFs) and critical success factors (CSFs) is indispensable to ensure the success of PPP infrastructure project implementation. However, the existing research on the PPP risk and success relationship has not gone into sufficient detail, and more support to address the existing gaps in the body of knowledge and literature is necessary. Therefore, in response to the missing area in the public–private partnership transportation industry, this paper analyzed the correlation between PPP risks and success factors. It identified, explored, and categorized various risk and success factors by combining a literature review, expert panel interviews, and a questionnaire survey among both the public and private sectors, a win–win principle. The data collected were analyzed using the structural equation modeling (SEM) approach and relative significance. Results show the relationship between risk and success factors, their influence on PPPs, and the most important factors, known as CRFs and CSFs, with high loading factors (LF > 0.5) and high relative importance (NMS > 0.5). The top five CRFs include "Contract quality (incomplete, conflicting)", "Staff expertise and experience", "Financial market risk", "Conflicting objectives and expectations", and "Inefficient feasibility study". The top five CSFs were found as "Appropriate risk allocation and risk-sharing", "Strong financial capacity and capability of the private sector", "Government providing guarantees", "Employment of professional advisors", and "Realistic assessment of the cost and benefits". This study advances the understanding of risk and success factors in PPPs and contributes to the theoretical foundations, which will benefit not only public management, policy consultants, and investors but also academics interested in studying PPP transportation projects. [ABSTRACT FROM AUTHOR]

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferondriving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between social and psychological factors and the risk of cognitive impairment following acute ischemic stroke. Materials and methods: A prospective study was conducted at Shanghai Tenth People’s Hospital from June 2021 to July 2022. The study focused on social and psychological factors, which were assessed using the Social Support Rating Scale (SSRS), Self-Perceived Burden Scale (SPBS), and Hamilton Depression Scale (HAMD) within 3 days after admission to the hospital. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3 months post-stroke. Logistic hierarchical regression models were used to examine the association between these three indicators and cognitive impairment following a stroke. Results: Among these patients, cognitive function was assessed in 211 cases at the 3-month follow-up after the initial stroke event. At 3 months post-stroke, 118 (55.9%) of the participants experienced cognitive impairment, while 93(44.1%) did not. The scores on the SPBS and HAMD showed significant associations with cognitive impairment at 3 months after stroke. The scores of SPBS [scores: 30~39 vs.<20 points, odds ratio (OR)=2.993 (1.135–7.896); scores: ≥40 vs.<20points, OR=7.382 (1.117–48.799); P=0.043] and the HAMD [scores: >7 vs.≤7 points, OR=3.287(1.362~7.936); P=0.008]. There were no significant associations observed between SSRS and PSCI. Conclusion: Early screening for depressive symptoms and focusing on selfperceived burden can be beneficial for decision support for clinicians and improve cognitive function recovery at the 3-month mark post-stroke. [ABSTRACT FROM AUTHOR]

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