Dual Effect Research Articles

Model multifactor analysis of soil heavy metal pollution on plant germination in Southeast Chengdu, China: Based on redundancy analysis, factor detector, and XGBoost-SHAP

This study assessed the levels of soil heavy metal pollution in agricultural land in southeastern Chengdu and its effects on the germination stage of higher plants. Through extensive soil sampling and laboratory analyses, 15 soil environmental factors were measured, including soil density, porosity, pH, field moisture capacity (FMC), calcium carbonate (CaCO3), and heavy metals such as arsenic (As) and cadmium (Cd). Acute toxicity tests were performed on sorghum (Sorghum bicolor) and Brassica napus (Brassica napus var. napus). The results of the geo-accumulation index (Igeo) and enrichment factor (EF) analyses indicate a higher risk of pollution and enrichment of As and Cd in the study area, with relatively lower risks for other heavy metals. Additionally, the current soil heavy metal concentrations inhibited the growth of sorghum and Brassica napus shoots and roots during the germination stage. Redundancy analysis (RDA), factor detector, and XGBoost-SHAP models identified the As, Cd, FMC, and CaCO3 contents, soil density, and porosity as the primary factors influencing plant growth. Among these factors, FMC, porosity, and Cd were found to promote plant growth, whereas soil density and As demonstrated inhibitory effects. CaCO3 had a dual effect, initially promoting growth but later inhibiting it as its concentration increased. Further analysis revealed that Brassica napus is more sensitive to soil environmental factors than sorghum, particularly to Cd and As, while sorghum has greater tolerance. Moreover, roots were found to be more sensitive than shoots to soil environmental factors, with roots being influenced primarily by physical factors such as FMC and soil density, whereas shoots were affected primarily by chemical factors such as As and Cd.This study addresses the significant lack of data regarding the impact of soil heavy metal concentrations on plant growth in southeastern Chengdu, providing a scientific basis for regional environmental monitoring, soil remediation, and plant cultivation optimization.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, and QTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 μM, 28.27 ± 1.52 μM, and 22.93 ± 1.63 μM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 μM). This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Electrodeposition on laser induced graphene dual conductive substrate as a free-standing electrode for asymmetric supercapacitors

Herein, combing laser-induced graphene (LIG) obtained by laser scribing on polyethersulfone (PES) films with carbon cloth (CC) forming novel dual conductive networks can cause the well-designed electrode materials possessing strong electric conductivity in favor of electron transferring. The free-standing NiCo/L-CC@PES-IG or Fe/L-CC@PES-IG have been prepared through laser scribing and electrodeposition processes at mild conditions. Fe/L-CC@PES-IG exhibits a high areal specific capacitance of 1544 mF cm−2 at a current density of 1 mA cm−2, which matches well with NiCo/L-CC@PES-IG (1840 mF cm−2). It is worth mentioning that the capacitance retention of NiCo/L-CC@PES-IG can reach 80 % at 10 mA cm−2, ca. 16 times that of NiCo/L-CC-IG (only 5 %) just adding small amount PES, which indicate that the dual conductive network synergistic effect of the external conductive graphene and the internal CC. The asymmetric supercapacitor (ASC) device is constructed using NiCo/L-CC@PES-IG as a positive electrode and Fe/L-CC@PES-IG as a negative electrode, which delivers a high areal energy density of 381 μWh cm−2 at the areal power density of 825.8 μW cm−2. This work provides a unique insight into the design of hybrid supercapacitor assembled with matching positive and negative electrodes, which will achieve the desired superhigh performance.

Detecting and attributing the impact of human activities on grassland aboveground biomass in China's Loess Plateau

Human activities significantly influence grassland ecosystem functions, particularly plant biomass. However, the direction and magnitude of these effects remain insufficiently explored. Herein, we quantitively assessed both the positive and negative effects of various human activities on grassland aboveground biomass (AGB) in China's Loess Plateau from 2000 to 2022. The results indicated that the magnitudes of positive effects increased by 0.29 g m−2 per year, whereas the negative effects decreased by 0.31 g m−2 per year. Spatially, 32 % of the grasslands experienced significant positive effects, whereas the rest grasslands faced negative effects. Notably, only 20 % of the areas with negative effects showed worsening trends mainly due to ecological restoration, sustainable agriculture, and population migration. Agricultural production activities and population changes emerged as dominant factors, with some activities, like livestock farming, exhibiting dual effects (i.e., positive and negative effects) on AGB. These findings underscore the complexity of human activities in affecting the grassland production function and highlight the necessity for balanced management strategies to sustain grassland productivity and resilience.

Aedes aegypti control in breeding sites through an insecticidal coating with dual effect: Laboratory trials and safety assessment.

Ground water tanks are known to be preferred Aedes aegypti oviposition places providing opportunities for adult and larvae control. Therefore, a dual-effect insecticidal coating (IC) (alphacypermethrin/ pyriproxyfen) with a slow-release mechanism and safe for users could be applied within Aedes spp. breeding sites, representing a promising option. Bioassays were designed to determine the mortality and sterilizing effects on gravid mosquitoes exposed to IC. The effect of inhibition of emergence was evaluated in eggs, larvae and pupae exposed in different containers. For the water safety assessment concentrations of active ingredients were determined by reverse phase high performance liquid chromatography (RP-HPLC) and the health risk was calculated. The IC applied to the interior walls of water-holding containers showed efficacy against Ae. aegypti in terms of high gravid-female mortality (81% at 24 h, p < 0.01), sterilizing effect (inhibition of oviposition by 63%, p < 0.01) and emergence inhibition (100% in eggs, L3 and L4; 97% in pupae). The offspring rate was reduced [only 0.15 (38/250) new adults emerged per exposed gravid females as against 11.90 per unexposed female (2976/250) at baseline]. Emergence inhibition was recorded up to 12 months and adult mortality >80% up to 6 months. The use of water stored in treated containers, either for washing or drinking, is not expected to pose a health risk to users. IC applied to domestic water containers has dual and complementary action that reduces Ae. aegypti densities (immature and adult stages). This represents baseline information for a cluster randomized efficacy trial in Colombia.

Dual winding slot area allocation ratio effect on torque and suspension performance of BPMSMs

Dual winding slot area allocation ratio effect on torque and suspension performance of BPMSMs

In Situ Preparation of MnO2 on the Catechol/Silane-Coated Polypropylene Nonwoven Fabrics for Effective Removal of Cationic Dyes.

Previous studies have confirmed that MnOx removes heavy metal ions and organic pollutants from water with dual effects of adsorption and oxidation coupling, significantly improving the ability to remove impurities. Nanometal oxides have a highly reactive surface but tend to agglomerate during preparation and are challenging to recycle after use. A common method is to combine nano-MnO2 with Fe3O4 to prepare magnetic materials for easy recycling. Our previous research has confirmed that catechol (CA) and (3-aminopropyl) triethoxysilane (KH550) can be co-deposited on the surface of polypropylene nonwovens to form a stable CK coating under alkaline conditions. In addition, the coating has many active groups, including hydroxyl groups, amino groups, etc. This study further investigates the secondary reactivity of CK coatings. The coordination of catechol groups and metal ions was used to anchor manganese ions to the coating. Meanwhile, the hydroxyl and amino groups were used to reduce manganese ions to Mn4+ in situ to prepare PP-(CK-MnO2). We found that the sample had an excellent decolorization effect on cationic dyes but was limited to anionic dyes. The decolorization mechanism of cationic dyes was further discussed. The results showed that the decolorization of cationic dyes had a dual effect of adsorption and oxidative degradation. Under acidic conditions, its oxidation properties were enhanced. It can be used as a highly effective decolorizing agent for cationic dyes, and the decolorization behavior is consistent with the first-order kinetics. As the pH increases, its oxidation properties gradually decrease. Although the electrostatic adsorption effect was enhanced, the overall decolorization performance was significantly reduced. Recycling experiments have proved that it can maintain >90% removal rate after five cycles. This study also demonstrated that the CK coating has dopamine-like properties, which can coordinate with metal ions to prepare metal-organic hybrid materials.

Cytokine modulation in pelvic organ prolapse and urinary incontinence: from molecular insights to therapeutic targets.

Pelvic organ prolapse (POP) and urinary incontinence (UI) are common disorders that significantly impact women's quality of life. Studies have demonstrated that cytokines, including pro- and anti-inflammatory immune mediators, play a role in illness genesis and progression. Research on the inflammatory milieu of the pelvic floor has shown that POP patients have increased inflammation in vaginal tissues. This evidence revealed that significant changes in the inflammatory milieu of the pelvic floor are an aspect of the pathogenesis of POP. POP patients exhibit increased levels of inflammatory cytokines (IL-1, TNF, IFN, and others) in the front vaginal wall, which may alter collagen metabolism and contribute to POP. Studies indicate that cytokines such as IL-6, IL-10, and TGF, which are involved in inflammation, remodelling, and repair, have dual effects on POP and UI. They can promote tissue healing and regeneration but also exacerbate inflammation and fibrosis, contributing to the progression of these conditions. Understanding the dual roles of these cytokines could help us improve the vaginal microenvironment of women and treat POP and UI. Given the considerable changes in these cytokines, this review addresses studies published between 2000 and 2024 on the molecular mechanisms by which pro- and anti-inflammatory cytokines affect women with POP and UI. Furthermore, we explain novel therapeutic strategies for cytokine regulation, emphasizing the possibility of personalized treatments that address the underlying inflammatory milieu of the vagina in POP and UI patients. This thorough analysis aims to establish a foundation for future research and clinical applications, ultimately improving patient outcomes via designed cytokine-based therapies.

Influence of Urban Morphologies on the Effective Mean Age of Air at Pedestrian Level and Mass Transport Within Urban Canopy Layer

This study adapted the mean age of air, a time scale widely utilized in evaluating indoor ventilation, to assess the impact of building layouts on urban ventilation capacity. To distinguish it from its applications in enclosed indoor environments, the adapted index was termed the effective mean age of air (τ¯E). Based on an experimentally validated method, computational fluid dynamic (CFD) simulations were performed for parametric studies on four generic parameters that describe urban morphologies, including building height, building density, and variations in the heights or frontal areas of adjacent buildings. At the breathing level (z = 1.7 m), the results indicated three distinct distribution patterns of insufficiently ventilated areas: within recirculation zones behind buildings, in the downstream sections of the main road, or within recirculation zones near lateral facades. The spatial heterogeneity of ventilation capacity was emphasized through the statistical distributions of τ¯E. In most cases, convective transport dominates the purging process for the whole canopy zone, while turbulent transport prevails for the pedestrian zone. Additionally, comparisons with a reference case simulating an open area highlighted the dual effects of buildings on urban ventilation, notably through the enhanced dilution promoted by the helical flows between buildings. This study also serves as a preliminary CFD practice utilizing τ¯E with the homogenous emission method, and demonstrates its capability for assessing urban ventilation potential in urban planning.

Abstract 4124070: Dual-action Nanomatrix Coated Stent for Improving Endothelialization while Suppressing Restenosis and Inflammation

Introduction: The most common cause of cardiovascular disease (CVD) is atherosclerosis. The progression of atherosclerosis is characterized by endothelial cell dysfunction, proliferation of smooth muscle cell proliferation, and plaques which lead to progressive arterial stenosis. Bare metal stents (BMS) were developed to hinder stenosis, but re-stenosis has been observed following deployment. Drug-eluting stents (DES) have been developed to mitigate this, by releasing anti-proliferative drugs to suppress smooth muscle cell proliferation. However, these drugs also suppress endothelial growth. To address this, we are developing and evaluating a dual action nanomatrix coated stent comprised of a nitric oxide (NO) releasing peptide amphiphile (PA) and everolimus-encapsulated liposomes to improve endothelial proliferation and suppressing smooth muscle cell proliferation and inflammation. Materials and Methods: The nanomatrix coating contains a PA generated via solid phase peptide synthesis consisting of a nitric oxide donor and a cell adhesive ligand. The everolimus-encapsulated liposomes were prepared with DPPC, DOTAP, DSPE-PEG, and cholesterol via thin film rehydration, followed by encapsulation with everolimus. TEM was performed on liposomes to assess their stability. The release kinetics were evaluated via UV-vis of samples containing released everolimus. To evaluate the dual effect of the nanomatrix coating on metabolism, NO and everolimus were used to treat endothelial and smooth muscle cells, and an MTT assay was done. Results and Discussion: TEM showed that liposomes maintained stability over time. It was found that 60% of everolimus was released by day 30. The MTT assay showed that NO with everolimus increased endothelial cell metabolic activity and maintained or lowered smooth muscle cell activity compared to everolimus alone. Conclusions: Everolimus-encapsulated liposomes have potential as an effective delivery method of everolimus. NO and everolimus have a synergistic effect of improving endothelial function and suppressing smooth muscle cells.

TMOD-01. EGFR AMPLIFICATION ACCOMPANIES ADAPTATION TO MITOGEN-INDUCED DEFECTIVE MITOSIS IN PDGFA

Abstract Using a newly described in vitro murine model of GBM [Bohm et al., Neuro-Oncol 2020 and Omairi et al., Neuro-Oncol 2023] in which P53 null neural progenitor cells (NPCs) divide abnormally and evolve a GBM-like genome during exposure to Platelet-Derived Growth Factor-AA (PDGFA), we asked how a brain-abundant mitogen could transform NPCs. By analyzing gene and protein expression over time, we found that PDGFA fails to induce the transcription of kinetochore and spindle assembly checkpoint genes, while simultaneously driving NPCs to enter mitosis. These dual effects caused chromosome miss-segregation in continuously dividing NPCs; moreover, they occurred in both WT and null NPCs, although only null cells survived defective mitosis. These surviving cells gradually expanded in PDGFA accumulating both random and clonal chromosomal re-arrangements. Transcriptome analysis of NPCs in PDGFA revealed significant under-expression of Foxm1, the major regulator of kinetochore transcription, together with over-expression and phosphorylation of the immediate early response gene, FOS. Analysis of signalling downstream of PDGFRα identified the Ras-MAPK pathway, especially ERK, as responsible for FOS activation. As surviving null cells gradually expanded, they accumulated random and recurrent chromosomal rearrangements. Expansion and subsequent PDGFA-independent proliferation and tumorigenicity were associated with re-expression of Foxm1 and kinetochore proteins, and accompanied by over-expression of Egfr, an RTK-signature that defines human GBM. By stimulating proliferation without setting the stage for error-free mitosis, exposure to PDGFA transforms p53 null NPCs and generates Egfr amplified GBM-like cancer cells.

A Gendered Double Movement? Income Security and Family Policy Dynamics Over Three Decades

Over the past decades, social policy in OECD countries has experienced significant shifts in family and income security policies. This article investigates these changes from a feminist political economy perspective and argues how they give rise to a gendered double movement. The double movement results from increased (re)commodification combined with rising individualisation, which has a dual effect: it releases women from familial duties while simultaneously commodifying female labour. By integrating the concepts of familisation, individualisation, decommodification and (re)commodification, this analysis examines data from 17 OECD countries between 1985 and 2010 regarding three aspects: the extent of shifts towards individualisation and (re)commodification in welfare states, the identification of distinct welfare state types based on these dimensions, and their consistency over time. The findings show a trend towards increased (re)commodifying policies from 1985 to 1995 and a rise in individualising policies from the late 1990s. By using a cluster analysis with a longitudinal perspective based on four dimensions, six different types of welfare states can be identified, highlighting both stability and shifts. Notably, shifts mostly occur in the same direction, moving towards an optional familialistic/individualistic flexicurity, which combines strong familising and individualising family policies with de- and (re)commodifying income security policies.

Anthropogenic Factor as a Relief-forming Factor of the Coastal Zone of the Black Sea Coast of the Krasnodar Territory (On the Example of the Tuapse-Adler Coastline)

The ever-increasing technogenic and anthropogenic load on the seacoasts, which significantly affects natural coastal processes, is increasingly beginning to act as a determining relief-forming factor. Hydraulic structures erected in the coastal zone have a dual effect on the natural coastal processes. On the one hand, they themselves are an artificially created relief, and on the other hand, the structures being erected have a significant effect on natural coastal processes. The example of the coastal section between Tuapse and Adler, located within the Black Sea coast of Krasnodar Territory, which experiences enormous technogenic and anthropogenic load on the coast, shows the need to identify anthropogenic coastal dynamic systems as an independent relief-forming factor. At the same time, an assessment should be made of both the processes occurring within the system and its impact on the natural processes occurring in the adjacent coastal areas.

CSIG-17. ADHESION GPCR BAI1/ADGRB1 CAN BLOCK IGF1R-MEDIATED GROWTH SIGNALLING, INCREASE RADIOSENSITIVITY AND AUGMENT SURVIVAL IN MEDULLOBLASTOMA

Abstract Medulloblastoma (MB) is an aggressive pediatric brain tumors and increased knowledge about the disease mechanisms is needed to develop new therapeutic approaches. Brain-specific Angiogenesis Inhibitor 1 (BAI1/ADGRB1) is an adhesion GPCR receptor and tumor suppressor epigenetically silenced in MB. Our prior studies showed that BAI1 can bind the MDM2 E3 ubiquitin ligase and relocate it to the cell membrane, thereby preventing it from degrading p53 in the nucleus (Zhu et al, Cancer Cell, 2018). Whether other MDM2 targets are affected by this relocation that may be functionally important in MB development is unknown. We hypothesized that BAI1-mediated relocation of MDM2 might destabilize cell surface oncogenic receptors and found that BAI1 stimulates IGF1R poly-ubiquitination and degradation. Mechanistically, BAI1 fosters MDM2-IGF1R interaction through beta-arrestins, adaptor proteins connecting MDM2 to IGF1R. Epigenetic reactivation of BAI1 expression suppressed Stat3 and Akt signaling, and radio-sensitized MB cells, leading to significantly improved survival in orthotopic MB xenograft models in mice regardless of tumor p53 mutation status. These findings are important as they demonstrate that BAI1 has dual anti-tumor effects in MB through MDM2 membrane re-localization, stabilizing p53 and blocking IGF1R signaling. They further suggest that epigenetic targeting of BAI1 is a promising therapeutic approach for clinical translation.

Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation.

Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival.

Dual effects of DLG5 (disks large homolog 5 gene) modulation on chemotherapy-induced thrombocytopenia and nausea/vomiting via the hippo signalling pathway.

The CAPEOX (combination of oxaliplatin and capecitabine) chemotherapy protocol is widely used for colorectal cancer treatment, but it can lead to chemotherapy-induced adverse effects (CRAEs). To uncover the mechanisms and potential biomarkers for CRAE susceptibility, we performed whole-genome sequencing on normal colorectal tissue (CRT) before adjuvant chemotherapy. This is followed by in vivo and in vitro verifications for selected gene and CRAE pair. Our analysis revealed specific germline mutations linked to Grade 2 (or higher) chemotherapy-induced thrombocytopenia (CIT) and nausea/vomiting (CINV). Notably, both CRAEs were associated with mutations in the DLG5 gene. We found that DLG5 mutations related to CIT were associated with increased gene expression, while those associated with CINV were linked to suppressed gene expression, as indicated by the Genotype-Tissue Expression (GTEX) database. In megakaryocytes, overexpression of human DLG5 suppressed the hippo signalling pathway and induced YAP expression. In zebrafish, overexpression of human DLG5 not only reduced platelet production but also inhibited thrombus formation. Subsequent qPCR analysis revealed that DLG5 overexpression affected genes involved in cytoskeleton formation and alpha-granule formation, which could impact the normal generation of proplatelets. We identified a series of germline mutations associated with susceptibility to CIT and CINV. Of particular interest, we demonstrated that induced and suppressed DLG5 expression is respectively related to CIT and CINV. These findings shed light on the involvement of the hippo signalling pathway and DLG5 in the development of CRAEs, providing valuable insights into potential targets for therapeutic interventions.

Bipolar Membranes With Controlled, Microscale 3D Junctions Enhance the Rates of Water Dissociation and Formation

AbstractA soft lithographic method is developed for making bipolar membranes (BPMs) with catalytic junctions formed from arrays of vertically oriented microscale cylinders. The membranes are cast from reusable polydimethylsiloxane (PDMS) molds made from silicon masters, which are fabricated on 2″ to 4″ wafer scales by nanosphere lithography. High‐aspect‐ratio junctions are made on a length scale similar to the thickness of optimized catalyst layers for water dissociation, creating a platform for probing the dual effects of catalysis and local electric field at the microscale BPM junction. Optimized polymer materials and nanoscale metal oxide catalysts are used in this study. 3D BPMs are tested under reverse and forward bias conditions, exhibiting superior performance relative to their 2D counterparts. Under forward bias in H2‐O2 fuel cells, 3D BPMs achieve a current density of 1500 mA cm−2, ≈7 times higher than 2D membranes made from the same materials.

Dual effects of mefenamic acid on the IKs molecular complex.

Mutations in both KCNQ1 and KCNE1, which together form the cardiac IKs current, are associated with inherited conditions such as long and short QT syndromes. Mefenamic acid, a non-steroidal anti-inflammatory drug, is an IKs potentiator and may be utilised as an archetype to design therapeutically useful IKs agonists. However, here we show that mefenamic acid can also act as an IKs inhibitor, and our data reveal its dual effects on KCNQ1/KCNE1 channels. Effects of mefenamic acid on wild type (WT) and mutant KCNQ1/KCNE1 channels expressed in tsA201 cells were studied using whole cell patch clamp. Molecular dynamics simulations were used to determine trajectory clustering. Mefenamic acid inhibits WT IKs at high concentrations while preserving some attributes of current potentiation. Inhibitory actions of mefenamic acid are unmasked at lower drug concentrations by KCNE1 and KCNQ1 mutations in the mefenamic acid binding pocket, at the extracellular end of KCNE1 and in the KCNQ1 S6 helix. Mefenamic acid does not inhibit KCNQ1 in the absence of KCNE1 but inhibits IKs current in a concentration-dependent manner in the mutant channels. Inhibition involves modulation of pore kinetics and/or voltage sensor domain-pore coupling in WT and in the KCNE1 E43C mutant. This work highlights the importance of structural motifs at the extracellular inter-subunit interface of KCNQ1 and KCNE1 channels, and their interactions, in determining the nature of drug effects on the IKs channel complex and has important implications for treating patients with specific long QT mutations.

Unpacking the association between social media use and support for unlawful behaviors in protests: a study in Hong Kong

PurposeExisting research has shown the role of social media in facilitating general protest participation. However, there is a noticeable gap in understanding the dynamics related to explicitly unlawful behaviors during protests, which have become increasingly prominent in recent times. Drawing upon the communication mediation model (O-S-O-R model), this study proposes a moderated mediation model to delineate specific mechanisms under which social media use influences individuals' support for unlawful behaviors in protests.Design/methodology/approachA survey of 1,121 Hong Kong residents was conducted in the context of the 2019 Hong Kong Anti-Extradition Law Amendment Bill Movement to test the theoretical model.FindingsObtaining political information on social media has a dual effect on support for unlawful behaviors in protests. On one hand, social media use increases individuals' political knowledge, which is reinforced by frequent political discussions on social media. This enhanced political knowledge tends to reduce the likelihood of supporting unlawful behaviors in protests. On the other hand, acquiring political information on social media can also generate increased anger toward politics, potentially leading to a more supportive attitude toward unlawful behaviors in protests.Originality/valueThis study contributes to the expanding field of research on digital activism by revealing the intricate mechanisms by which social media usage shapes support for unlawful behaviors in protests. It also expands our understanding of explicit unlawful behaviors within protests as a distinct form of political behavior.

CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model.

Heterotopic ossification (HO) in Achilles tendon often arises due to endochondral ossification during the healing process following trauma. Retinoic acid receptor γ (RARγ) plays a critical role in this phenomenon. This study aims to elucidate the therapeutic effects of CD1530, an RARγ selective agonist, along with the contributing cells, in Achilles tendon healing, utilizing a cell lineage tracing system. Local injection of CD1530 facilitated histological tendon healing by inhibiting chondrification in a mouse Achilles rupture model. Resident Scleraxis (Scx)+ cells in Achilles tendon were not found to be actively involved in HO or tendon healing following injury. Instead, these processes were primarily driven by tendon stem/progenitor cells (TSPC)-like cells. Furthermore, an in vitro assay revealed that CD1530 attenuated inflammation in injured Achilles tendon-derived tendon fibroblasts (iATF) and inhibited the chondrogenesis of iATF. This dual effect suggests the potential of CD1530 in effectively modulating the healing environment during tendon healing. Together, the present study demonstrated that the local administration of CD1530 accelerated tendon healing by modulating the healing environment, including reducing chondrification via targeting TSPC-like cells in a mouse Achilles tendon rupture model. These results suggest that CD1530 may have the potential to be a novel tendon therapy that offers benefits via the inhibition of chondrogenesis.