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19 pages, 2622 KB  
Article
Three-Compartment Pharmacokinetics of Inhaled and Injected Sinapine Thiocyanate Manifest Prolonged Retention and Its Therapeutics in Acute Lung Injury
by Zixin Li, Caifen Wang, Huipeng Xu, Qian Wu, Ningning Peng, Lu Zhang, Hui Wang, Li Wu, Zegeng Li, Qinjun Yang and Jiwen Zhang
Pharmaceutics 2025, 17(7), 909; https://doi.org/10.3390/pharmaceutics17070909 - 14 Jul 2025
Viewed by 541
Abstract
Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and [...] Read more.
Background: Acute lung injury (ALI) is driven by inflammatory cascades and reactive oxygen species (ROS) generation, with the progression to severe cases markedly increasing mortality. Sinapine thiocyanate (ST), a bioactive natural compound isolated from Sinapis Semen Albae (SSA), demonstrates both anti-inflammatory and antioxidant pharmacological activities. However, no monotherapeutic formulation of ST has been developed to date. A dry powder inhaler (DPI) enables targeted pulmonary drug delivery with excellent stability profiles and high inhalation efficiency. Methods: ST was purified and prepared as inhalable dry powder particles via an antisolvent crystallization technique. The therapeutic mechanisms of ST against ALI were elucidated by network pharmacology and pharmacokinetic analyses, with the therapeutic efficacy of the ST DPI in ALI mitigation being validated using LPS-induced rat models. Results: The ST DPI showed ideal aerodynamic characteristics. Notably, ST exhibited a three-compartment (triexponential) pharmacokinetic profile following both intravenous tail vein injection and inhalation administration. Furthermore, the inhaled formulation displayed a prolonged systemic residence time, which confers therapeutic advantages for pulmonary disease management. Furthermore, the inhalation administration of ST demonstrated a 2.7-fold increase in AUC compared with oral gavage, with a corresponding enhancement in systemic exposure. The ST DPI formulation demonstrated significant therapeutic efficacy against ALI in rats by downregulating inflammatory cytokines and modulating oxidative stress levels, mechanistically achieved through the MAPK-mediated regulation of cellular apoptosis via a positive feedback loop. Conclusions: The unique triexponential plasma level profiles of an ST DPI provide a promising pharmacokinetics-based therapeutic strategy for ALI, leveraging its marked efficacy in attenuating inflammation, oxidative stress, and pulmonary injury. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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20 pages, 1214 KB  
Article
Minor Salivary Gland Biopsy in the Differential Diagnosis of Sicca Syndrome: A Monocentric Cohort Analysis
by Elisa Fiorentini, Pamela Bernardini, Dorilda Zeka, Marco Capassoni, Luca Novelli, Annarita Palomba, Lorenzo Tofani, Laura Cometi and Serena Guiducci
Int. J. Mol. Sci. 2025, 26(13), 6463; https://doi.org/10.3390/ijms26136463 - 4 Jul 2025
Viewed by 565
Abstract
Sicca syndrome is a common condition that draws the attention of rheumatologists, and is frequently related to Sjögren’s disease (SjD). This study analyzed 164 patients with sicca syndrome (clinically suspected for SjD) who underwent minor salivary gland biopsy (mSGB). Patients completed the Xerostomia [...] Read more.
Sicca syndrome is a common condition that draws the attention of rheumatologists, and is frequently related to Sjögren’s disease (SjD). This study analyzed 164 patients with sicca syndrome (clinically suspected for SjD) who underwent minor salivary gland biopsy (mSGB). Patients completed the Xerostomia Inventory (XI) and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires to assess Patient-Reported Outcome Measures (PROMs), and biopsies were graded using the Chisholm and Mason system. Patients were classified as seropositive (SSA, SSB, Ro52, Ro60 positive) or seronegative, and also divided into three groups by age. Positive biopsies (60.37%) were more common in older patients (61–80) and associated with confirmed SjD, more severe xerostomia, and stronger lymphocytic infiltrates. Among these, 37.37% were seropositive, showing higher disease activity, hypergammaglobulinemia, and elevated IgG. Seronegative patients had a heavier symptom burden, confirmed by the PROMs, and more fibrosis and fatty replacement in biopsies. Age-stratified analysis showed younger patients (18–40) were more affected by ocular dryness, while older patients had worse xerostomia and more severe histological and ultrasound changes. Younger individuals had higher IgG/IgA, more anemia, and reduced C3. Hydroxychloroquine was used more in younger and seropositive groups; older patients used more topical therapies. These results highlight mSGB’s diagnostic value, especially in seronegative cases, and stress the importance of combining clinical, histological, imaging, and patient-reported outcomes for optimal care. Full article
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14 pages, 2140 KB  
Article
Comprehensive Clinical, Serological, and Molecular Biomarker Profiling of Primary Sjögren’s Syndrome: A Single-Center Cohort Study in Northeastern Romania
by Alexandru Lodba, Codrina Ancuta, Diana Tatarciuc, Magda Ecaterina Antohe, Ana Maria Fatu, Luciana-Oana Lodba and Cristina Iordache
Int. J. Mol. Sci. 2025, 26(13), 6327; https://doi.org/10.3390/ijms26136327 - 30 Jun 2025
Viewed by 414
Abstract
Primary Sjögren’s syndrome (pSS) exhibits considerable clinical and immunological heterogeneity, complicating personalized management. We aimed to delineate the demographic, functional, serological, histopathological, and therapeutic features of a Romanian pSS cohort and to identify biomarker–treatment correlations that could inform patient-oriented strategies. Thirty-two patients meeting [...] Read more.
Primary Sjögren’s syndrome (pSS) exhibits considerable clinical and immunological heterogeneity, complicating personalized management. We aimed to delineate the demographic, functional, serological, histopathological, and therapeutic features of a Romanian pSS cohort and to identify biomarker–treatment correlations that could inform patient-oriented strategies. Thirty-two patients meeting the 2016 ACR/EULAR classification criteria for pSS were retrospectively analyzed. Data collected included demographics, autoantibody profiles (Anti-Ro/SSA, Anti-La/SSB, ANA, RF, Anti-CCP), immunoglobulin levels, complement consumption (C3/C4), minor salivary gland biopsy (focus score), salivary flow tests, and systemic inflammation markers (CRP). Pearson correlation matrices were constructed to explore the associations between serological markers and prescribed therapies. The cohort was predominantly female (87.5%) with a mean age of 52.8 ± 9.9 years. Seropositivity rates were 50% for Anti-Ro/SSA, 77% for Anti-La/SSB, and 40% for ANA. Clinically significant glandular dysfunction was evident in 65% of patients (unstimulated flow ≤ 0.1 mL/min), and all biopsies demonstrated focus scores > 1. Methotrexate use correlated strongly with Anti-Ro/SSA and Anti-La/SSB positivity (p ≤ 0.05), indicating its targeted application in seropositive sub-phenotypes. Conclusion: These findings underscore the immunologic and clinical diversity of pSS and support a biomarker-driven, multidisciplinary framework for personalized treatment. Larger prospective and multicenter studies are warranted to validate these correlations and to refine precision medicine approaches in pSS. Full article
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10 pages, 268 KB  
Article
Pediatric Sjögren’s Syndrome: Focus on Ocular Involvement and Diagnostic Challenges
by Emanuela Del Giudice, Maria Carmela Saturno, Maria Grazia Fiorino, Danilo Iannetta, Luca Spadea, Vanessa Martucci, Alessia Marcellino, Mariateresa Sanseviero, Angela Mauro, Sandra Cinzia Carlesimo, Nicola Nante, Giovanni Guarducci, Leopoldo Spadea, Riccardo Lubrano and Maria Pia Paroli
Medicina 2025, 61(7), 1128; https://doi.org/10.3390/medicina61071128 - 23 Jun 2025
Viewed by 489
Abstract
Background and Objectives: Pediatric Sjögren’s syndrome is a rare autoimmune disease with a heterogeneous clinical expression and limited pediatric-specific diagnostic criteria. Ocular involvement often represents an early manifestation, yet it may go unrecognized in children due to poor symptom reporting and the [...] Read more.
Background and Objectives: Pediatric Sjögren’s syndrome is a rare autoimmune disease with a heterogeneous clinical expression and limited pediatric-specific diagnostic criteria. Ocular involvement often represents an early manifestation, yet it may go unrecognized in children due to poor symptom reporting and the underuse of objective diagnostic tools. This retrospective study evaluated six pediatric patients with Sjögren’s syndrome, integrating systemic and ocular findings with a focus on early immunological and clinical markers. Materials and Methods: All patients underwent ophthalmological assessments, including tear break-up time, Schirmer’s test, and slit-lamp examination. Results: Tear break-up time values consistently indicated tear film instability (mean RE 7.4 ± 2.5 s; LE 7.7 ± 2.3 s), while Schirmer’s test showed greater variability. Slit-lamp examination revealed inhomogeneous tear films in all patients and blepharitis in 66.7%, consistent with Meibomian gland dysfunction. Systemic features included arthralgia, Raynaud’s phenomenon, fatigue, and frequent seropositivity for ANA and anti-SSA/Ro antibodies. Minor salivary gland biopsy confirmed lymphoepithelial sialadenitis in all cases. Conclusions: These findings highlight the importance of combining laboratory and clinical markers with ophthalmological parameters to support an early diagnosis of Sjögren’s syndrome in pediatric patients. Integrating TBUT and slit-lamp evaluation with serological and histopathological data may enhance diagnostic accuracy and guide timely, targeted intervention to prevent long-term complications. Full article
(This article belongs to the Section Pediatrics)
16 pages, 269 KB  
Article
The Role of Anti-SSB/La Antibodies as Predictors of Decreased Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) in Primary Sjögren Disease
by Simona Caraiola, Laura Voicu, Daniela Opriș-Belinski, Claudia Oana Cobilinschi, Magda Ileana Pârvu, Ion Andrei Ion, Daniela Ștefana Gologanu and Răzvan Adrian Ionescu
Int. J. Mol. Sci. 2025, 26(12), 5867; https://doi.org/10.3390/ijms26125867 - 19 Jun 2025
Viewed by 1125
Abstract
Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity [...] Read more.
Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article
20 pages, 5483 KB  
Article
Evolution of Pore Structure and Fractal Characteristics in Transitional Shale Reservoirs: Case Study of Shanxi Formation, Eastern Ordos Basin
by Yifan Gu, Xu Wu, Yuqiang Jiang, Quanzhong Guan, Dazhong Dong and Hongzhan Zhuang
Fractal Fract. 2025, 9(6), 335; https://doi.org/10.3390/fractalfract9060335 - 23 May 2025
Viewed by 472
Abstract
The fractal dimension quantitatively describes the complexity of the shale pore structure and serves as a powerful tool for characterizing the evolution of shale reservoirs. Thermal simulation experiments were conducted on the low-maturity transitional shale from the Shanxi Formation in the Ordos Basin. [...] Read more.
The fractal dimension quantitatively describes the complexity of the shale pore structure and serves as a powerful tool for characterizing the evolution of shale reservoirs. Thermal simulation experiments were conducted on the low-maturity transitional shale from the Shanxi Formation in the Ordos Basin. The initial samples consisted mainly of quartz (39.9%) and clay minerals (49.9%) with moderate-to-good hydrocarbon generation potential. Samples from different thermal maturation stages were analyzed through geochemical, mineralogical, and pore structure experiments to reveal the evolution of mineral compositions and pore structure parameters. The fractal dimensions of the pore structure were calculated using both the FHH and capillary bundle models. Correlation coefficients and principal component analysis (PCA) were employed to explore the factors influencing the fractal dimension and its evolutionary patterns during reservoir development. The results indicate that (1) with increasing thermal maturity, the quartz content gradually increases while the contents of clay minerals, carbonate minerals, pyrite, and feldspar decrease. (2) The evolution of porosity follows five stages: a slow decrease (0.78 < Ro < 1.0%), a rapid increase (1.0% < Ro < 2.0%), a relatively stable phase (2.0% < Ro < 2.7%), a rapid rise (2.7% < Ro < 3.2%), and a slow decline (Ro > 3.2%). The evolution of the pore volume (PV) and specific surface area (SSA) indicates that the proportion of pores in the 5–20 nm and 20–60 nm ranges gradually increases while the proportion of pores smaller than 5 nm decreases. (3) The fractal dimension of shale pores (D1, average value 2.61) derived from the FHH model is higher than D2 (average value 2.56). This suggests that the roughness of pore surfaces is greater than the complexity of the internal pore structure at various maturities. The DM distribution range calculated from the capillary bundle model was broad (between 2.47 and 2.94), with an average value of 2.84, higher than D1 and D2. This likely indicates that larger pores have more complex structures. (4) D1 shows a strong correlation with porosity, PV, and SSA and can be used to reflect pore development. D2 correlates well with geochemical parameters (TOC, HI, etc.) and minerals prone to diagenetic alteration (carbonates, feldspar, and pyrite), making it useful for characterizing the changes in components consumed during pore structure evolution. (5) Based on the thermal maturation process of organic matter, mineral composition, diagenesis, and pore structure evolution, an evolutionary model of the fractal dimension for transitional shale was established. Full article
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10 pages, 4683 KB  
Article
Potential Novel Tissue Biomarkers in Salivary Glands of Patients with Sjogren’s Syndrome
by Canan Sadullahoglu, Neslihan Yaprak, Veli Yazısız and İrem Hicran Ozbudak
J. Clin. Med. 2025, 14(7), 2390; https://doi.org/10.3390/jcm14072390 - 31 Mar 2025
Viewed by 843
Abstract
Background/Objectives: Primary Sjogren’s syndrome (pSS) is an autoimmune disease caused by chronic inflammation of the exocrine glands. We aimed to determine the immunohistochemical parameters that may help in the diagnosis of pSS and to determine histopathological markers for the early diagnosis of patients. [...] Read more.
Background/Objectives: Primary Sjogren’s syndrome (pSS) is an autoimmune disease caused by chronic inflammation of the exocrine glands. We aimed to determine the immunohistochemical parameters that may help in the diagnosis of pSS and to determine histopathological markers for the early diagnosis of patients. Methods: Hematoxylin–eosin-stained preparations of salivary gland tissue samples of a control group consisting of 9 healthy patients and 12 patients diagnosed with non-specific chronic sialadenitis (NSCS) and a study group consisting of 39 patients diagnosed with pSS were evaluated. SSA/Ro (TRIM21), SSB/la, BAFF, enolase (ENO1), and MMP-9 antibodies were applied to the samples to assess the presence of staining in the ductal, acini, and inflammation regions. Results: In our study, mild staining with the SSA/Ro (TRIM21) antibody was observed in the ductal areas of all pSS cases, while no staining was detected in the healthy and NSCS cases (p < 0.01). Additionally, stronger staining was identified in the ductal and inflammatory areas of the pSS cases with BAFF compared to the control group. The staining for the ENO1 antibody was higher and more intense in the NSCS and pSS cases compared to those with normal salivary glands, and this difference was found to be statistically significant (p < 0.01). While mild staining was detected in the ductal areas with MMP-9 antibody in most of the NSCS and pSS cases, it was detected in 11% of the healthy cases. Conclusions: Our study suggests that SSA/Ro (TRIM21), ENO1, MMP9, and BAFF can be used to confirm the diagnosis in cases of suspicion. Full article
(This article belongs to the Section Otolaryngology)
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16 pages, 6667 KB  
Article
Nanoscale Pore Evolution of Terrestrial Shale with Thermal Maturation Level Increase Induced by Hydrous Pyrolysis
by Haiyan Hu, Wangpeng Li, Yifan Yang and Shuai Chen
Processes 2025, 13(1), 246; https://doi.org/10.3390/pr13010246 - 16 Jan 2025
Cited by 1 | Viewed by 875
Abstract
A series of terrestrial shale samples with different thermal maturities were subjected to hydrous artificial pyrolysis to study the evolution of terrestrial shale pores. The original shale was obtained from the terrestrial interval of a core sample, the total organic carbon (TOC) content [...] Read more.
A series of terrestrial shale samples with different thermal maturities were subjected to hydrous artificial pyrolysis to study the evolution of terrestrial shale pores. The original shale was obtained from the terrestrial interval of a core sample, the total organic carbon (TOC) content was 8.34 wt%, and the vitrinite reflectance (Ro) was 5.31%. The original shale core was cut into eight parts, which were heated at temperatures of 300, 350, 400, 420, 450, 500, 550, and 600 °C to obtain samples with different thermal maturities. The pore size distribution (PSD), pore volume (PV), specific surface area (SSA), and pore types were investigated via CO2 and N2 adsorption tests and field emission scanning electron microscopy (FE-SEM). Many organic matter (OM) pores and mineral pores were observed via FE-SEM with increasing thermal maturity. The total PV and SSA increased until the sample reached 500 °C and then decreased, and the mesopore volume followed this trend. The micropore volume first decreased, increased until the sample reached 500 °C, and then decreased; the macropore volume increased to a peak in the sample pyrolyzed at 420 °C and then remained stable. Pores with sizes ranging from 10 to 30 nm were the predominant contributors to the shale pore volume. The SSA was affected by pores with diameters less than 20 nm, which accounted for approximately 54% of the SSA. The rate of OM conversion influenced pore creation. Full article
(This article belongs to the Special Issue Advances in Enhancing Unconventional Oil/Gas Recovery, 2nd Edition)
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18 pages, 4434 KB  
Article
Fractal Characteristics of Pore Structure of Longmaxi Shales with Different Burial Depths in Southern Sichuan and Its Geological Significance
by Manping Yang, Yanyan Pan, Hongye Feng, Qiang Yan, Yanjun Lu, Wanxin Wang, Yu Qi and Hongjian Zhu
Fractal Fract. 2025, 9(1), 2; https://doi.org/10.3390/fractalfract9010002 - 24 Dec 2024
Cited by 4 | Viewed by 1033
Abstract
Burial depth can significantly impact the pore structure characteristics of shale. The Lower Silurian Longmaxi Shale in the Weiyuan block of the Sichuan Basin is a marine formation that we studied for deep shale gas exploration. We used two groups of Longmaxi samples, [...] Read more.
Burial depth can significantly impact the pore structure characteristics of shale. The Lower Silurian Longmaxi Shale in the Weiyuan block of the Sichuan Basin is a marine formation that we studied for deep shale gas exploration. We used two groups of Longmaxi samples, outcrop shale and middle-deep shale, to investigate the pore structure fractal features at varying burial depths using a combination of mineralogy, organic geochemistry, scanning electron microscopy (SEM), and low-temperature gas (CO2, N2) adsorption. The V-S fractal model was used to determine the fractal dimension (Dc) of micropores, and the FHH fractal model was used to determine the fractal dimension (DN) of mesopores. The findings indicate that the pore morphology of organic matter becomes irregular and more broken as the burial depth increases, as does the content and maturity of organic matter. The pore size of organic matter gradually decreases, the SSA (BET, DR) and PV (BJH, DA) of shale pores increase, the pore structure becomes more complex, and the average shale pore size decreases. According to this study, the organic matter content and its maturity show an increasing trend as burial depth increases. Meanwhile, the organic matter’s pore morphology tends to be irregular, and fracture rates rise, which causes the organic matter’s pore size to gradually decrease. In addition, the SSA (comprising the values assessed by BET and DR techniques) and PV (evaluated by BJH and DA methods) of shale pores grew, suggesting that the pore structure became more complex. Correspondingly, the average pore size of the shale decreased. The fractal dimensions of the micropores (DC), mesoporous surface (DN1), and mesoporous structure (DN2) of outcrop shale are 2.6728~2.7245, 2.5612~2.5838, and 2.7911~2.8042, respectively. The mean values are 2.6987, 2.5725, and 2.7977, respectively. The DC, DN1, and DN2 of middle-deep shale are 2.6221~2.7510, 2.6085~2.6390, and 2.8140~2.8357, respectively, and the mean values are 2.7050, 2.6243, and 2.8277, respectively. As the fractal dimension grows, the shale’s pore structure becomes more intricate, and the heterogeneity increases as the buried depth increases. The fractal dimension has a positive association with the pore structure parameters (SSA, PV), TOC, and Ro and a negative association with the mineral component (quartz, feldspar, clay mineral) contents. Minerals like quartz, feldspar, and clay will slow down the expansion of pores, but when SSA and PV increase, the pore heterogeneity will be greater and the pore structure more complex. Full article
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21 pages, 6695 KB  
Article
Diabase Intrusion-Induced Changes in Shale Pore Structure in Subei Basin: Insights from Mono- and Multifractal Analysis of N2 Adsorption
by Zuxian Hua, Xiaoping Liu, Biao Sun, Tian Liu, Qidong Liu, Hongliang Duan, Shili Liu, Yue Zheng, Wendi Peng and Wenhui Xie
Fractal Fract. 2024, 8(12), 737; https://doi.org/10.3390/fractalfract8120737 - 14 Dec 2024
Viewed by 917
Abstract
Diabase intrusion is a common geological phenomenon in lacustrine shale formations in continental basins in China, which has important effects on the physical and chemical properties of shale oil reservoirs. In this paper, we systematically analyzed the pore structure of diabase-intruded lacustrine shale [...] Read more.
Diabase intrusion is a common geological phenomenon in lacustrine shale formations in continental basins in China, which has important effects on the physical and chemical properties of shale oil reservoirs. In this paper, we systematically analyzed the pore structure of diabase-intruded lacustrine shale in the Gaoyou sag of the Subei Basin using geochemical tests, thin-section observation, argon ion polishing scanning electron microscopy (SEM), low-temperature nitrogen adsorption experiments (LTNA), and other methods combined with monofractal and multifractal theories. The results show that the intrusion metamorphic segments are a diabase zone, hornfels zone, slate zone, and normal shale zone from the intrusion center. The pores of hornfels and slate are mostly oriented and dissolution is obvious. Many microfractures and secondary minerals such as quartz and chlorite are observed. The pore volumes of diabase and hornfels are small, while those of slate and normal shale are larger. The monofractal dimensions D1 and D2 of the intrusion segment show a general trend of decreasing first and then increasing from the intrusion center to the shale zone. The multifractal parameters’ H index decreases gradually from the lower normal shale to the upper metamorphic zone hornfels, while Δα and Rd increase gradually. The total organic carbon (TOC) content of the intrusion zone has little effect on the pore structure, and the fractal characteristics fluctuate weakly, while the vitrinite reflectivity (Ro) value change has a significant impact on the monofractal characteristics of the shale pore. Pore volume also affects the pore heterogeneity; the larger the specific surface area (SSA) and total pore volume (TPV), the lower the pore heterogeneity and the higher the surface roughness and pore connectivity. The diabase intrusion caused three modification mechanisms of mechanical squeezing, the thermal effect, and chemical action on the shale surrounding rocks, resulting in different degrees of pore formation or change. The pore evolution model of the metamorphic belt with the combined action of “mechanical-thermal-chemical” is established, and the influence of diabase intrusion on the pore types and pore size distribution (PSD) of shale reservoirs is quantitatively described, providing a new perspective and method for understanding the impact of diabase intrusion on the characteristics and exploration potential of shale oil reservoirs. Full article
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21 pages, 3698 KB  
Article
Child-Centric Robot Dialogue Systems: Fine-Tuning Large Language Models for Better Utterance Understanding and Interaction
by Da-Young Kim, Hyo Jeong Lym, Hanna Lee, Ye Jun Lee, Juhyun Kim, Min-Gyu Kim and Yunju Baek
Sensors 2024, 24(24), 7939; https://doi.org/10.3390/s24247939 - 12 Dec 2024
Cited by 1 | Viewed by 1772
Abstract
Dialogue systems must understand children’s utterance intentions by considering their unique linguistic characteristics, such as syntactic incompleteness, pronunciation inaccuracies, and creative expressions, to enable natural conversational engagement in child–robot interactions. Even state-of-the-art large language models (LLMs) for language understanding and contextual awareness cannot [...] Read more.
Dialogue systems must understand children’s utterance intentions by considering their unique linguistic characteristics, such as syntactic incompleteness, pronunciation inaccuracies, and creative expressions, to enable natural conversational engagement in child–robot interactions. Even state-of-the-art large language models (LLMs) for language understanding and contextual awareness cannot comprehend children’s intent as accurately as humans because of their distinctive features. An LLM-based dialogue system should acquire the manner by which humans understand children’s speech to enhance its intention reasoning performance in verbal interactions with children. To this end, we propose a fine-tuning methodology that utilizes the LLM–human judgment discrepancy and interactive response data. The former data represent cases in which the LLM and human judgments of the contextual appropriateness of a child’s answer to a robot’s question diverge. The latter data involve robot responses suitable for children’s utterance intentions, generated by the LLM. We developed a fine-tuned dialogue system using these datasets to achieve human-like interpretations of children’s utterances and to respond adaptively. Our system was evaluated through human assessment using the Robotic Social Attributes Scale (RoSAS) and Sensibleness and Specificity Average (SSA) metrics. Consequently, it supports the effective interpretation of children’s utterance intentions and enables natural verbal interactions, even in cases with syntactic incompleteness and mispronunciations. Full article
(This article belongs to the Special Issue Challenges in Human-Robot Interactions for Social Robotics)
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11 pages, 3337 KB  
Article
Involvement of ATF6 in Octreotide-Induced Endothelial Barrier Enhancement
by Saikat Fakir and Nektarios Barabutis
Pharmaceuticals 2024, 17(12), 1604; https://doi.org/10.3390/ph17121604 - 28 Nov 2024
Cited by 6 | Viewed by 1298
Abstract
Background/Objectives: Endothelial hyperpermeability is the hallmark of severe disease, including sepsis and acute respiratory syndrome (ARDS). The development of medical countermeasures to treat the corresponding illness is of utmost importance. Synthetic somatostatin analogs (SSA) are FDA-approved drugs prescribed in patients with neuroendocrine [...] Read more.
Background/Objectives: Endothelial hyperpermeability is the hallmark of severe disease, including sepsis and acute respiratory syndrome (ARDS). The development of medical countermeasures to treat the corresponding illness is of utmost importance. Synthetic somatostatin analogs (SSA) are FDA-approved drugs prescribed in patients with neuroendocrine tumors, and they act via growth hormone (GH) suppression. Preclinical investigations suggest that Octreotide (OCT) alleviates Lipopolysaccharide (LPS)-induced injury. The aim of the study is to investigate the involvement of activating transcription factor 6 (ATF6) in the protective effects of OCT in endothelial dysfunction. To the best of our knowledge, the available information on that topic is limited. Methods: Human lung microvascular endothelial cells (HULEC-5a) and bovine pulmonary artery endothelial cells (BPAEC) which expressed elevated levels of ATF6 due to AA147 were exposed to OCT or vehicle. Protein expression, endothelial permeability, and reactive oxygen species (ROS) generation were assessed utilizing Western blot analysis, Fluorescein isothiocyanate (FITC)-Dextran assay, and Dichlorofluorescein diacetate measurements, respectively. Results: Our observations suggest that ATF6 activation significantly improves OCT-induced endothelial barrier enhancement. This combination led to increased expression of binding immunoglobulin protein (BiP) and glucose-regulated protein 94 (Grp94), which are downstream unfolded protein response (UPR) targets. Moreover, ATF6 activation prior to OCT treatment resulted in decreased activation of myosin light chain 2 (MLC2) and cofilin; and reduced reactive oxygen species (ROS) generation. ATF6 activation enhanced the anti-inflammatory effects of OCT, as reflected in the suppression of transducer and activator of transcription (STAT) 1, STAT3, and P38 phosphorylation. Conclusions: Our findings suggest that ATF6 activation prior to OCT treatment enhances the beneficial effects of OCT in the endothelium. Full article
(This article belongs to the Section Pharmacology)
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11 pages, 225 KB  
Article
Clinical Characteristics of Distinct Subgroups of Patients with Primary Sjögren’s Syndrome Classified by Serological Profiles: A Comparison Study
by Erdal Bodakçi
J. Pers. Med. 2024, 14(9), 967; https://doi.org/10.3390/jpm14090967 - 12 Sep 2024
Cited by 3 | Viewed by 1688
Abstract
Sjögren’s syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. [...] Read more.
Sjögren’s syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren’s syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren’s syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud’s phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
21 pages, 14878 KB  
Article
Reservoir Characteristics of Marine–Continental Transitional Taiyuan Formation Shale and Its Influence on Methane Adsorption Capacity: A Case Study in Southern North China Basin
by Wei Jiang and Yang Hu
Appl. Sci. 2024, 14(15), 6577; https://doi.org/10.3390/app14156577 - 27 Jul 2024
Viewed by 944
Abstract
To further study the reservoir characteristics and adsorption capacity of the Taiyuan Formation shale in the South North China Basin (SNCB), the pore structure and adsorption capacity of shale are discussed using various analysis tests, including elemental geochemistry, organic geochemistry, mineral composition, low-temperature [...] Read more.
To further study the reservoir characteristics and adsorption capacity of the Taiyuan Formation shale in the South North China Basin (SNCB), the pore structure and adsorption capacity of shale are discussed using various analysis tests, including elemental geochemistry, organic geochemistry, mineral composition, low-temperature nitrogen adsorption (LTNA), and methane adsorption experiments. The results indicate that the Taiyuan Formation shale formed in a poor oxygen and anaerobic sedimentary environment in still water. The average value of total organic carbon (TOC) content is 2.37%. The organic matter type mainly consists of type III kerogen. The vitinite reflectance (Ro) ranges from 3.11% to 3.50%. The clay mineral content varies greatly, averaging at 40.7%, while the quartz content averages at 37.7%. The Taiyuan Formation shale mainly develops interparticle (InterP) pores, followed by organic pores, intraparticle (IntraP) pores, solution pores, and microfractures. BET specific surface area (SSA) is between 9.47 m2/g and 22.14 m2/g, while pore volume (PV) ranges from 0.0098 cm3/g to 0.022 cm3/g, indicating favorable conditions for shale gas storage. According to the results of the CH4 adsorption experiment, Langmuir volume from Taiyuan Formation shales exhibits 1.35~4.30 cm3/g, indicating excellent adsorption capacity. TOC content shows a positive correlation with both Langmuir volume and BET SSA from Taiyuan Formation shales, suggesting that TOC plays a crucial role in controlling microscopic pores and gas adsorption capacity. Organic matter enhances the shale adsorption capacity by providing abundant pore SSA. Due to formation compaction, the pore size of clay minerals decreases, leading to an increase in pore SSA, while kaolinite exhibits weak hydrophilic ability. Consequently, with the increase in clay minerals and kaolinite content, the shale adsorption capacity is enhanced to a certain extent. However, an increase in the carbonate mineral content may result in a decrease in the proportion of clay minerals, therefore reducing the CH4 adsorption capacity of shale. Full article
(This article belongs to the Special Issue Advances in Unconventional Natural Gas: Exploration and Development)
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19 pages, 1786 KB  
Review
Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases
by Ranjeet Singh Mahla, Esther L. Jones and Lynn B. Dustin
Int. J. Mol. Sci. 2024, 25(14), 7705; https://doi.org/10.3390/ijms25147705 - 14 Jul 2024
Cited by 1 | Viewed by 3299
Abstract
The Ro60/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including [...] Read more.
The Ro60/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including YRNAs (for the ‘y’ in ‘cytoplasmic’), retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal toll-like receptors (TLRs) and cytoplasmic RNA sensors, which typically sense pathogen-associated molecular patterns, and mount the first line of defence against invading pathogens. However, the recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases, including Sjögren’s disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for anti-drug antibody responses among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mechanisms of autoimmune conditions. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome 3.0)
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