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20:4-NAPE induced changes of mechanical sensitivity and DRG neurons excitability are concentration dependent and mediated via NAPE-PLD
Abstract Alterations in the excitability of dorsal root ganglion (DRG) neurons are critical in the pathogenesis of acute and chronic pain. Neurotransmitter release from the terminals of DRG neurons is regulated by cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both activated by anandamide (AEA). In our experiments, the AEA precursor N-arachidonoylphosphatidylethanolamine (20:4-NAPE) was used to study the modulation of nociceptive DRG neurons excitability using K+-evoked Ca2+ transients. Intrathecal administration was used to evaluate in vivo effects. Application of 20:4-NAPE at lower concentrations (10 nM − 1 µM) decreased the excitability of DRG neurons, whereas the higher (10 µM) increased it. Both effects of 20:4-NAPE were blocked by the N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. Similarly, lower concentrations of externally applied AEA (1 nM − 10 nM) inhibited DRG neurons, whereas higher concentration (100 nM) did not change it. High AEA concentration (10 µM) evoked Ca2+ transients dependent on TRPV1 activation in separate experiments. Inhibition of the CB1 receptor by PF514273 (400 nM) prevented the 20:4-NAPE- and AEA-induced inhibition, whereas TRPV1 inhibition by SB366791 (1 µM) prevented the increased DRG neuron excitability. In behavioral tests, lower 20:4-NAPE concentration caused hyposensitivity, while higher evoked mechanical allodynia. Intrathecal LEI-401 prevented both in vivo effects of 20:4-NAPE. These results highlight anti- and pro-nociceptive effects of 20:4-NAPE mediated by CB1 and TRPV1 in concentration-dependent manner. Our study underscores the complexity of endocannabinoid signaling in pain transmission modulation and highlights 20:4-NAPE as a potential therapeutic target, offering new insights for developing analgesic strategies.
Methylome and transcriptome analyses reveal HLA-DMB’s contribution to periodontitis development
Background Periodontitis is a typical oral disease. Polymorphonuclear neutrophils (PMNs) are crucial immune cells in periodontal tissues, relating to infection, inflammation, and innate immunity. We herein aimed to explore important periodontitis PMN related genes. Methods Periodontitis and control samples were downloaded from Gene Expression Omnibus database, including GSE173082 (methylation data, n=72), GSE10334 (n=127), GSE43525 (n=23), GSE16134 (n=134). Differential expression analysis and differential methylation analysis was employed to find candidate genes. Receiver operating characteristic analysis was performed to evaluate the diagnostic value of the hub gene. The functional pathways were determined by gene set enrichment analysis. Using CIBERSORT software, the immune cell infiltration landscape of periodontitis tissue was explored. The mRNA and protein levels of target gene in clinical tissue samples were determined employing RT-qPCR and western blotting. All statistical analyses were conducted in R software. Results After integrating DNA methylation with transcriptome profiles, GRASP, HLA-DMB, HLA-DMA, CAB39, NCOA2 and TLE4 were identified as candidate genes in periodontitis PMNs. HLA-DMB showed the highest correlation with core DNA methyltransferase DNMT3B (p < 0.05). Between high and low HLA-DMB expression samples, multiple immune related pathways were enriched, and differential immune cell infiltration was observed (p < 0.05). HLA-DMB exhibited significantly higher expressions in both public database and clinical tissue samples (p < 0.05). HLA-DMB was a diagnostic marker for periodontitis (GSE43525 AUC=0.777 and GSE16134 AUC=0.783). Conclusions Significantly higher HLA-DMB expression was noticed in PMNs of periodontitis, which probably contributed to the development of periodontitis. HLA-DMB is a promising diagnostic marker for periodontitis.
Two year comparative outcomes of drug coated balloons in long versus short femoropopliteal lesions
Effects of repeated gravity changes during parabolic flight: Evidence of the need to assist space tourists to outer space
In the era of space tourism, walking in the steps of Neil Armstrong has never been more real. Future space tourists will have to face the harshness of the environment, especially the travel, and adapt quickly for their own safety. This issue raises both the question of preparation and the impact of such a journey on novice populations who have not been selected for their physical and cognitive abilities. The objectives of the study are (1) to investigate the impact of space travel on psychophysiological and sensory responses during a parabolic flight experience; (2) to assess recovery from this experience one week later; and (3) to evaluate the relevance of high parasympathetic functioning at baseline as a biomarker of adaptation. Seventeen healthy participants were enrolled in the 79th ESA Parabolic Flight Campaign on board the Airbus A310. Psychological, physiological, and sensory responses were measured at different times from the day before the 3h-flight (baseline) to one week after the flight (recovery). Labels were allocated to two groups according to their parasympathetic functioning at baseline: high parasympathetic (HP) profile and low parasympathetic (LP) profile. At the psychological level, those with an HP profile have a higher coping acceptation and a higher level of interoceptive awareness than the LP profile, except for sleep quality. At the physiological and exteroceptive level, they have a higher heart rate variability, preserved identification of odors and a predisposition to a more adaptive postural response postflight. Nevertheless, postural stability is affected in both profiles, particularly during visual deprivation, while their heart rate variability is increased in both linear and non-linear components. Nevertheless, our results reveal that the recovery constitutes a critical period. Flyers have a decrease of interoceptive awareness and emotions, especially the HP profile. Although the LP profile reported a better subjective sleep quality, both profiles decreased their sleep quality. These results raise the question of the risks that may be induced by space tourism. They highlight two major outcomes: (1) travel of future space tourists does not seem to be at risk as long as the individuals are qualified and fit for the flight and adaptation may be improved by targeting parasympathetic functioning; (2) level of experience has no impact on the psychophysiological and sensory responses. The results highlight the need to monitor the crews over several days and/or to include in the preparation a module allowing them to be prepared for the postflight period and the return to life on Earth. Beyond this, these results contribute to enriching our knowledge of the human challenge of confronting space travel constraints.
Treatment outcomes and predictors of success for multidrug resistant tuberculosis MDR TB in Ugandan regional referral hospitals
Abstract Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis caused by strains resistant to both isoniazid and rifampicin, the most critical first-line drugs. Managing MDR-TB presents substantial challenges due to prolonged and costly treatment regimens, which are less effective than those for drug-susceptible TB. These difficulties are further exacerbated in low-resource settings by inadequate healthcare infrastructure, limited diagnostic capacity, and suboptimal access to treatment. Uganda, a high-burden TB country, faces persistent challenges in meeting national MDR-TB treatment targets, with high mortality rates and unfavourable outcomes. This study evaluated the treatment outcomes and factors associated with success among MDR-TB patients in regional referral hospitals. Of the 293 registered patients, 284 were included in the analysis, with a median age of 38 years (IQR: 30–45) and a predominance of male patients (65.1%). Overall, 68.7% of patients achieved successful treatment outcomes, while 31.3% experienced unfavourable outcomes. Multivariate analysis identified weight at treatment initiation (41–49 kg) as significantly associated with poor outcomes. These findings highlight a treatment success rate below national targets, with persistent high mortality and treatment failure in several regions. Addressing these challenges requires the development of innovative therapies and personalized care strategies to improve MDR-TB management in Uganda.
Enzyme-Mimic Activities of RuCo Bimetallic Nanosheets for Inflammatory Bowel Disease Treatment
Effects of sensory room intervention on autonomic function in healthy adults: A pilot randomized controlled trial
Sensory rooms are those equipped with various visual, auditory, and other sensory items that can be adjusted according to user preferences. Although several studies have reported the effectiveness of sensory rooms, their physiological effects remain unclear. This pilot study aims to investigate the effect of sensory rooms on vagal function, mood states, and attentional functions. Thirty-nine healthy young adults were randomly divided into the sensory room intervention (SRI) and sedentary activity (SA) groups, and given a 30-minute intervention. The SRI group spent time in a dimly lit room with beaded cushions and aroma oils. The SA group engaged in activities such as handicrafts and puzzles. We compared changes in respiratory sinus arrhythmia (RSA) at rest, RSA variability during discomfort sensory stimulation, mood states, and attentional functions between the groups, both before and after the intervention. As a result, 1) SRI significantly increased RSA compared with SA. 2) It also reduced the variability of RSA in response to specific sensory stimuli compared with SA. 3) However, no significant differences existed in negative mood or attentional function between the groups. The results suggest that sensory rooms might contribute to the sensory modulation, including that of the autonomic nervous system. Further investigation with larger samples in clinical settings, particularly among individuals with sensory modulation issues and mental illness, is necessary to confirm and generalize these findings.
Mechanical, workability, economic and environmental properties of concrete with limestone calcined clay cement and recycled aggregates
Abstract Limestone calcined clay cement (LC3) and recycled aggregates (RAs) are important innovations in civil engineering, offering solutions to the industry’s energy and carbon challenges. However, limited research on their combined use has hindered widespread application. This study systematically evaluates LC3-based concrete with both coarse and fine RAs, using material testing, cost analysis and carbon footprint assessments to examine the effects of water-to-binder ratio, metakaolin-limestone powder synergy, RA content and particle quality on workability, compressive strength, elastic modulus, splitting-tensile strength, unit cost and environmental impact, while establishing clear quantitative relationships. Key findings include: (i) Using up to 50% metakaolin-limestone powder by mass, 30% coarse RA and 20% recycled sand by volume results in minimal reductions in 28-day strength and elastic modulus. However, exceeding 70%, 50% and 40%, respectively, leads to significant mechanical deterioration. (ii) LC3 concrete has 4-15% lower strength than Portland cement concrete at 14 days due to slower pozzolanic reactions, but strength levels equalize by 28 days. Similarly, recycled aggregate concrete shows lower early-age strength, with extended curing further highlighting performance differences, likely due to the residual mortar on recycled particles. (iii) Lifecycle analysis confirms that replacing 50% of the binder with metakaolin-limestone powder reduces carbon emissions by 29.9% and costs by 12.4% for strength-equivalent concrete. In contrast, RAs offer only modest sustainability benefits, with 20% recycled sand and 30% coarse RA increasing emissions by 5.4% and 2.8%, respectively, while keeping costs stable. (iv) The quality of RA particles plays a key role in their sustainable application. Additionally, transportation distance significantly affects the circular benefits of RA use but has a limited impact on the sustainability of metakaolin-limestone powder.
Power shift in the transformation and upgrading of the service sector—Empirical evidence from China
In recent years, as the global economy has entered the “service economy” period, improving the service industry’s total factor productivity, realizing high-quality development, and better playing its supportive role in the real economy and its function of improving people’s well-being have become the top priorities for its development. The service industry is growing fast, yet its production and operations are putting pressure on the environment. For this reason, this paper incorporates environmental constraints into the analysis of the transformation and upgrading of the service industry to decompose and analyze the sources of green growth of the service industry. We find that: first, the level of green technology efficiency in the service industry is low, there is a downward trend, and the green technology efficiency gap widens significantly across provinces. Secondly, GTFP in the service sector is declining in general, with large inter-provincial differences, and the obstacle to growth lies in the deterioration of green technical efficiency, while the driving force for growth lies in green technological progress. Thirdly, labor productivity in the service sector has improved considerably, but all at the cost of high inputs, and the growth contribution of green total factor productivity and its constituent factors is negative, and the whole is still in the input factor-driven stage. Finally, the factors affecting GTFP in services are multifaceted, mainly involving structural, environmental regulatory, economic, social and institutional factors. This paper offers a theoretical foundation for further promoting the transformation and upgrading of the service industry to attract jade.
The impact of the COVID 19 pandemic on myopia prevalence in 5 year old Israeli children
A phase division-based multi-segment foot model for estimating dynamic foot arch stiffness during walking
The arch of the human foot plays a significant role in bearing weight and keeping gait balance. Previous studies mainly focus on the foot arch stiffness at the static or quasi-dynamic state of a particular foot shape. The variation of the linear arch stiffness across the entire walking gait has rarely been reported. This work presents a phase division-based multi-segment foot model that considers plantar aponeurosis’s tension force for calculating the dynamics of the medial longitudinal arch. Kinematics and ground reaction forces of 10 healthy young adults during walking are recorded and analyzed. The stiffness changes of the foot arch throughout the stance phase are calculated. The experimental results show that the foot arch experiences a stiff-compliant-stiff-compliant transition during a single stance phase, including an extremely low stiffness during the plantar contact phase. By comparing the foot arch stiffness results with those from previous studies, the accuracy of the proposed model is indirectly validated. This study presents a new approach to explore the variation of the linear stiffness of the foot arch across the entire stance phase during walking. The proposed multi-segment foot model provides a new method for solving foot dynamics that can be used for wearable sensing and assistive design and applications.
A statistical estimation of fractional order cryptosporidiosis epidemic model
Adjuvant chemotherapy compared with observation in patients with resected biliary tract cancer: A systematic review and meta-analysis of randomized controlled trials
Objectives Several randomized controlled trials compared adjuvant systemic chemotherapy with observation in patients with resected biliary tract cancer (BTC) have yielded inconsistent outcomes. In order to assess the efficacy of adjuvant therapy in these patients, we conducted this systematic review and meta-analysis. Methods We conducted a thorough search in various databases, which included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts, ESMO Abstracts and ClinicalTrials.gov. All relevant randomized controlled trials investigating the adjuvant chemotherapy compared with observation in resected biliary tract cancer were identified. The primary outcome of interest was overall survival (OS), while secondary outcome was relapse-free survival (RFS). Statistical analyses were conducted using Review Manager 5.3. Additionally, publication bias was evaluated using Egger’s test in Stata 12.0. Results A total of 5 randomized controlled trials, involving 1406 patients, were included in this analysis. Compared with observation, adjuvant chemotherapy improved RFS [HR 0.84 (0.73-0.96), p=0.01] (I2=0%, p=0.89) but not OS [HR 0.89 (0.77-1.03), p=0.12] (I2=51%, p=0.09) in the entire population after BTC resection. Subgroup analyses revealed that adjuvant chemotherapy did improve both OS [HR 0.76 (0.62-0.93), p=0.009] (I2=7%, p=0.37) and RFS [HR 0.74 (0.58-0.95), p=0.02] (I2=0%, p=0.39) in patients with lymph node positivity. Furthermore, patients receiving oral fluoropyrimidine monotherapy showed benefit from the adjuvant therapy, with longer OS [HR 0.78 (0.65-0.94), p=0.009] (I2=2%, p=0.31) and RFS [HR 0.81 (0.68-0.95), p=0.01] (I2=0%, p=0.95). Conclusions To conclude, adjuvant chemotherapy have the potential to offer advantages in patients with resected BTC. Specifically, patients demonstrating positive lymph node status have a higher likelihood of benefiting from adjuvant therapy. Our analysis supports the current standard of care of adjuvant fluoropyrimidine. However, the recommendation of oral fluoropyrimidine monotherapy as the preferred option is not definitive, as it is based on limited studies. Further validation of these outcomes is necessary by conducting extensive randomized controlled trials.
Talc as a natural mineral catalyst for the one pot-three component synthesis of benzo[f]chromene, dihydropyrano[3,2-c]chromene, and tetrahydrobenzo[b]pyran derivatives under different conditions
From responsibility to value: ESG and long-term corporate value
Although a large body of literature has explored the relationship between ESG and firm value, the findings are inconsistent and most studies have focused on mature Western markets, with relatively little research on ESG practices and value creation effects in emerging markets, especially in transition economies such as China. This paper analyzes the correlation between ESG performance and firms’ long-term value using data from 4,185 listed companies in China’s A-share market from 2017–2022. We find that good ESG practices can significantly enhance firms’ future cash flows, long-term value and market competitiveness. The results suggest that ESG increases long-term firm value by reducing weighted average cost and increasing return on invested capital. The effects of firms’ HHI index, nature of property rights and ISO 9001 system certification on the relationship are further investigated and it is found that Lerner’s index acts as a mediating variable to enable ESG performance to affect firms’ long-term value by enhancing their market pricing power and competitiveness. This paper serves as an important reference for corporate managers to integrate ESG concepts into strategic planning for sustainable development and long-term value growth, helping enterprises implement ESG strategies for long-term corporate success and sustainable development.
Comparison of self-reported and job-exposure matrix assessed workplace inhalant exposures and their association with obstructive airways disease
Abstract Chronic obstructive pulmonary diseases (COPD) are major public health concerns, with occupational exposure to vapors, gases, dusts, and fumes (VGDF) often overlooked as risk factors. This study investigates discrepancies between self-reported and Job-Exposure Matrix (JEM)-assessed exposures in chronic airway obstruction (AO), highlighting the importance of robust assessment methods. Data from the Hamburg City Health Study (2016–2020) were analyzed, contrasting self-reported VGDF exposure with Airborne Chemical Exposure (ACE) JEM assessments. COPD definition followed GOLD (Global Initiative for Chronic Obstructive Lung Disease) and GLI (The Global Lung Function Initiative) criteria for an AO. Inter-rater reliability was calculated using Cohen’s Kappa. Logistic regression models analyzed VGDF-AO associations, adjusting for confounders. Among 4,811 participants assessed with GOLD criteria, 3,545 met GLI criteria; inter-rater reliability between self-reported and JEM-based exposure was modest (Kappa = 0.29). Awareness of exposure varied between skill levels. Self-reported VGDF exposure was associated with GLI-defined AO (OR 1.48, 95% CI: 1.11–1.96), but not with GOLD-defined AO. JEM assessments did not show an association for either criterion. Discrepancies exist between self-reported and JEM-assessed VGDF exposures, as well as between GOLD and GLI criteria. Enhanced assessment strategies are needed to accurately assess occupational health risks related to COPD.
Retraction: 3D craniofacial registration using thin-plate spline transform and cylindrical surface projection
Development and validation of a novel model for patients with soft tissue sarcoma who received neoadjuvant chemotherapy
Influence of discrete fracture network on the performance of enhanced geothermal system considering thermal-hydraulic-mechanical multi-physical field coupling
The long-term circulation of cold water within the deep heat reservoir in enhanced geothermal system (EGS) involves dynamic evolution of thermal-hydraulic-mechanical (THM) fields. The characteristics of discrete fracture network (DFN) in the reservoir also affect the thermal performance of EGS. In this paper, the influence of the DFN on the performance of EGS considering THM multi-physical field couple was numerically investigated. The effect of water property change and cold tension stress with temperature was considered. The influence of DFN characteristics (fracture density, fracture aperture, angle between fracture and well connection line and fracture pattern) was discussed. Results indicate that the effect of considering water property change on the Darcy velocity is larger than considering the stress field. Considering water property change and stress field both lead to a larger Darcy velocity of the fracture water and make the temperature field drop faster. With the increase of fracture density, the production Darcy’s velocity increases gradually and the difference in thermal recovery efficiency is significant. Fracture aperture has a greater influence on the temperature field of the whole DFN reservoir than fracture density. The larger the fracture aperture, it will take away the heat energy from the heat reservoir faster. The smaller the angle between fracture and well connection line, the smaller the flow resistance of the working fluid, and the larger the equivalent permeability of the reservoir DFN system. The differences in the seepage field are small for the same range of statistical characteristics and parameter values for the DFN patterns. The DFN system with uniform fracture distribution should be selected for a better EGS reservoir, and the angle between the direction of the main fracture group and the direction of the well connection line should be at a certain acute angle.