Chemokines and lymphocyte homing in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4ß7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-ß, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-ß receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.

Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren's syndrome.

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Liquid Metal Actuators: A Comparative Analysis of Surface Tension Controlled Actuation.

Liquid metals, with their unique combination of electrical and mechanical properties, offer great opportunities for actuation based on surface tension modulation. Thanks to the scaling laws of surface tension, which can be electrochemically controlled at low voltages, liquid metal actuators stand out from other soft actuators for their remarkable characteristics such as high contractile strain rates and higher work densities at smaller length scales. This review summarizes the principles of liquid metal actuators and discusses their performance as well as theoretical pathways toward higher performances. The objective is to provide a comparative analysis of the ongoing development of liquid metal actuators. The design principles of the liquid metal actuators are analyzed, including low-level elemental principles (kinematics and electrochemistry), mid-level structural principles (reversibility, integrity, and scalability), and high-level functionalities. A wide range of practical use cases of liquid metal actuators from robotic locomotion and object manipulation to logic and computation is reviewed. From an energy perspective, strategies are compared for coupling the liquid metal actuators with an energy source toward fully untethered robots. The review concludes by offering a roadmap of future research directions of liquid metal actuators.

A bibliometric analysis of primary Sjögren's syndrome-associated lymphoma from 1991 to 2022.

Background: Patients with primary Sjögren's syndrome (pSS) take a higher risk of developing lymphoma, which is the most frequent cause of death in pSS. Based on this situation, the number of publications focusing on pSS-associated lymphoma has been growing. Nevertheless, the extent, range, and nature of available research in this field have not been systematically summarized. This study aimed to map the literature available on pSS-associated lymphoma and identify global hotspots and trends. Methods: Papers on pSS and lymphoma published from 1991 to 2022 were searched from the Web of Science Core Collection. Microsoft Excel, SPSS Statistics, VOSviewer, and CiteSpace software were used to analyze and visualize the quantity and citations of publications, and the global research hotspots and trends of pSS-associated lymphoma. Results: 629 publications from 50 countries/regions and 538 institutions were included in this study. From 1991 to 2022, the cumulative publications steadily increased. The USA ranked first in the number of publications (n = 118, 18.76 %), followed by Italy (n = 94, 14.94 %) and France (n = 73, 11.61 %). Udine University (n = 29) and Salvatore De Vita (n = 39) were the most prolific affiliation and author, respectively. Claudio Vitali was the most frequently cited author (n = 335). In total, the most frequently occurring keywords were clustered into four well-defined groups. The first group of keywords pointed to the clinical assessment and treatment of pSS-associated lymphoma. The second group highlighted the pathogenesis. The third group identified the predictors and prognosis of pSS-associated Lymphoma, while the fourth group focused on interstitial lung disease and pulmonary lymphoma in patients with pSS. Currently, the hot keywords include consensus, disease activity, and pathogenesis. Ultrasonography, mucosa-associated lymphoid tissue (MALT) lymphoma, and epidemiology are the emerging research trends in pSS-associated lymphoma. Conclusion: Research on pSS-associated lymphoma is burgeoning. Despite clinical assessment, treatment and pathogenesis, researchers also showed great interest in the predictors, prognosis, and pulmonary manifestations of pSS-associated lymphoma. Current research of pSS-associated lymphoma mainly focuses on consensus, disease activity, and pathogenesis, while the emerging research trends in pSS are pointing to ultrasonography, MALT lymphoma and epidemiology.

Anti-SSA/SSB-negative primary Sjögren's syndrome showing different clinical phenotypes: a retrospective study of 934 cases.

BACKGROUND: Currently, only a few studies have described the general characteristics of patients with primary Sjögren's syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample. METHODS: Data from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis. RESULTS: Overall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95). CONCLUSION: Approximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

Knowledge mapping of autophagy in osteoarthritis from 2004 to 2022: A bibliometric analysis.

Background: Autophagy in osteoarthritis (OA) has become an active area of research with substantial value and potential. Nevertheless, few bibliometric studies have systematically analyzed the available research in the field. The main goal of this study was to map the available literature on the role of autophagy in OA and identify global research hotspots and trends. Methods: The Web of Science Core Collection and Scopus databases were interrogated for studies of autophagy in OA published between 2004 and 2022. Microsoft Excel, VOSviewer and CiteSpace software were used to analyze and visualize the number of publications and associated citations, and reveal global research hotspots and trends in the autophagy in OA field. Results: 732 outputs published by 329 institutions from 55 countries/regions were included in this study. From 2004 to 2022, the number of publications increased. China produced the most publications (n=456), prior to the USA (n=115), South Korea (n=33), and Japan (n=27). Scripps Research Institute (n=26) was the most productive institution. Martin Lotz (n=30) was the highest output author, while Caramés B (n=302) was the highest output author. Osteoarthritis and Cartilage was the most prolific and most co-cited journal. Currently, the autophagy in OA research hotspots include chondrocyte, transforming growth factor beta 1 (TGF-ß1), inflammatory response, stress, and mitophagy. The emerging research trends in this field are AMPK, macrophage, senescence, apoptosis, tougu xiaotong capsule (TXC), green tea extract, rapamycin, and dexamethasone. Novel drugs targeting specific molecule such as TGF-ß and AMPK have shown therapeutic potential but are still in the preclinical stage of development. Conclusions: Research on the role of autophagy in OA is flourishing. Martin Lotz, Beatriz Caramés, and Osteoarthritis and Cartilage have made outstanding contributions to the field. Prior studies of OA autophagy mainly focused on mechanisms underlying OA and autophagy, including AMPK, macrophages, TGF-ß1, inflammatory response, stress, and mitophagy. Emerging research trends, however, are centered around the relationship between autophagy, apoptosis, and senescence, as well as drug candidates such as TXC and green tea extract. The development of new targeted drugs that enhance or restore autophagic activity is a promising strategy for the treatment of OA.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.

Reconfigurable Electrical Networks within a Conductive Hydrogel Composite.

Soft materials that exhibit compliance, programmability, and reconfigurability can have a transformative impact as electronic skin for applications in wearable electronics/soft robotics. There has been significant progress in soft conductive materials; however, achieving electrically controlled and reversible changes in conductivity and circuit connectivity remains challenging. To overcome this limitation, a soft material architecture with reconfigurable conductive networks of silver flakes embedded within a hydrogel matrix is presented. The conductive networks can be reversibly created/disconnected through various stimuli, including current, humidity, or temperature. Such stimuli affect electrical connectivity of the hydrogel by controlling its water content, which can be modulated by evaporation under ambient conditions (passive dehydration), evaporation through electrical Joule heating (active dehydration), or absorption of additional water (rehydration). The resulting change in electrical conductivity is reversible and repeatable, endowing the composite with on-demand reconfigurable conductivity. To highlight this material's unique properties, it is shown that conductive traces can be reconfigured after severe damage and revert to lower conductivity after rehydration. Additionally, a quadruped robot is demonstrated that can respond to stimuli by changing direction following exposure to excess water, thereby achieving reprogrammable locomotion behaviors.

Anti-SSA/SSB-negative primary Sjögren's syndrome showing different clinical phenotypes: a retrospective study of 934 cases

Abstract Background Currently, only a few studies have described the general characteristics of patients with primary Sjögren's syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample. Methods Data from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis. Results Overall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95). Conclusion Approximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

Research on Herbal Therapies for Osteoarthritis in 2004-2022: A Web of Science-Based Cross-Sectional Bibliometric Analysis.

Objective: The extent, range, and nature of available research in the field of herbal therapies for osteoarthritis (OA) have not been systematically analyzed. This study aimed to map the literature available on herbal therapies for OA and identify global hotspots and trends in this field. Methods: Studies on herbal therapies for OA published between 2004 and 2022 were searched from the Web of Science Core Collection. Microsoft Excel, SPSS Statistics, and CiteSpace software were used to analyze and visualize the quantity and citations of publications, and the research hotspots and trends in research on herbal therapies for OA. Results: A total of 1649 publications mainly from 76 countries/regions and 270 institutions were included in this study. From 2004 to 2022, there is an upward trend in the publications of herbal therapies for OA. China ranked first in the number of publications (n = 568, 34.45%), followed by the USA (n = 353, 21.41%), South Korea (n = 187, 11.34%), Germany (n = 85, 5.15%), and England (n = 79, 4.79%). Kyung Hee University (n = 46), Xianxiang Liu (n = 25), and Evidence-Based Complementary and Alternative Medicine (n = 74) were the most prolific affiliation, author, and journal, respectively. Felson DT (n = 185) and Arthritis and Rheumatism (n = 1173) held the record for the most cited papers by an author and journal, respectively. Currently, the hot keywords in the field of herbal therapies for OA include knee OA, traditional Chinese medicine (TCM), differentiation, rosa canina, inflammation, oxidative stress, stem cell, and regenerative medicine. The emerging research trends in herbal therapies for OA are herbal medicinal product, chronic knee pain, mesenchymal stem cell, and clinical pharmacology. Conclusions: Research on herbal therapies for OA is flourishing, but communication among countries/regions should be strengthened. Current research on herbal therapies for OA mainly focuses on knee OA, TCM, differentiation, rosa canina, inflammation, oxidative stress, stem cell, and regenerative medicine. The research frontiers are herbal medicinal product, chronic knee pain, mesenchymal stem cell, and clinical pharmacology.

Muscle-Inspired Linear Actuators by Electrochemical Oxidation of Liquid Metal Bridges.

Progress in artificial muscles relies on new architectures that combine soft matter with transduction mechanisms for converting controlled stimuli into mechanical work. Liquid metal, in particular eutectic gallium-indium (EGaIn), is promising for creating an artificial muscle since it is intrinsically deformable and capable of generating significant force and shape change through low voltage stimulation. In this work, a muscle-inspired structure for designing liquid metal actuators is presented, where EGaIn droplets are configured with copper pads to linearly contract. By theory and experiments, it is demonstrated that this design enables higher work densities and stress, making it a favorable actuator at smaller length scales. Furthermore, higher frequency (up to 5 Hz) operation is achieved by prestretching an antagonistic pair of actuators, where energy bistability enables fast-switching actuation. Overall, this muscle-inspired architecture shows a unique combination of low voltage operation, higher energy density at smaller scales, structural scalability, and higher frequency actuation.

Liquid Crystal Elastomer with Integrated Soft Thermoelectrics for Shape Memory Actuation and Energy Harvesting.

Liquid crystal elastomers (LCEs) have attracted tremendous interest as actuators for soft robotics due to their mechanical and shape memory properties. However, LCE actuators typically respond to thermal stimulation through active Joule heating and passive cooling, which make them difficult to control. In this work, LCEs are combined with soft, stretchable thermoelectrics to create transducers capable of electrically controlled actuation, active cooling, and thermal-to-electrical energy conversion. The thermoelectric layers are composed of semiconductors embedded within a 3D printed elastomer matrix and wired together with eutectic gallium-indium (EGaIn) liquid metal interconnects. This layer is covered on both sides with LCE, which alternately heats and cools to achieve cyclical bending actuation in response to voltage-controlled Peltier activation. Moreover, the thermoelectric layer can harvest energy from thermal gradients between the two LCE layers through the Seebeck effect, allowing for regenerative energy harvesting. As demonstrations, first, closed-loop control of the transducer is performed to rapidly track a changing actuator position. Second, a soft robotic walker that is capable of walking toward a heat source and harvesting energy is introduced. Lastly, phototropic-inspired autonomous deflection of the limbs toward a heat source is shown, demonstrating an additional method to increase energy recuperation efficiency for soft systems.

Soft actuators by electrochemical oxidation of liquid metal surfaces.

The surface energy of liquid metals can be electrochemically controlled over a wide range of values - from near zero to 500 mJ m-2- using a low voltage potential (∼1 V). This enables the ability to create soft-matter actuators that exhibit a high work density on small scales. We demonstrate that a liquid metal (LM) meniscus wetted between two copper pads can function as an electrochemical soft actuator whose force and shape are controllable by tuning the LM surface energy. Energy minimization models are presented in order to predict the actuator performance as a function of LM droplet and Cu pad dimensions. The results suggest that the electrochemical LM actuator has a unique combination of high work density, biologically-relevant activation frequency, and low operational voltage that stands out from other classes of soft-matter actuators.