SMAX1 potentiates phytochrome B-mediated hypocotyl thermomorphogenesis.

Plant thermosensors help optimize plant development and architecture for ambient temperatures, and morphogenic adaptation to warm temperatures has been extensively studied in recent years. Phytochrome B (phyB)-mediated thermosensing and the gene regulatory networks governing thermomorphogenic responses are well understood at the molecular level. However, it is unknown how plants manage their responsiveness to fluctuating temperatures in inducing thermomorphogenic behaviors. Here, we demonstrate that SUPPRESSOR OF MAX2 1 (SMAX1), known as a karrikin signaling repressor, enhances the thermosensitivity of hypocotyl morphogenesis in Arabidopsis thaliana. Hypocotyl thermomorphogenesis was largely disrupted in SMAX1-deficient mutants. SMAX1 interacts with phyB to alleviate its suppressive effects on the transcription factor activity of PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), promoting hypocotyl thermomorphogenesis. Interestingly, the SMAX1 protein is slowly destabilized at warm temperatures, preventing hypocotyl overgrowth. Our findings indicate that the thermodynamic control of SMAX1 abundance serves as a molecular gatekeeper for phyB function in thermosensitizing PIF4-mediated hypocotyl morphogenesis.

The two clock proteins CCA1 and LHY activate VIN3 transcription during vernalization through the vernalization-responsive cis-element.

Vernalization, a long-term cold-mediated acquisition of flowering competence, is critically regulated by VERNALIZATION INSENSITIVE 3 (VIN3), a gene induced by vernalization in Arabidopsis. Although the function of VIN3 has been extensively studied, how VIN3 expression itself is upregulated by long-term cold is not well understood. In this study, we identified a vernalization-responsive cis-element in the VIN3 promoter, VREVIN3, composed of a G-box and an evening element (EE). Mutations in either the G-box or the EE prevented VIN3 expression from being fully induced upon vernalization, leading to defects in the vernalization response. We determined that the core clock proteins CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and LATE-ELONGATED HYPOCOTYL (LHY) associate with the EE of VREVIN3, both in vitro and in vivo. In a cca1 lhy double mutant background harboring a functional FRIGIDA allele, long-term cold-mediated VIN3 induction and acceleration of flowering were impaired, especially under mild cold conditions such as at 12°C. During prolonged cold exposure, oscillations of CCA1/LHY transcripts were altered, while CCA1 abundance increased at dusk, coinciding with the diurnal peak of VIN3 transcripts. We propose that modulation of the clock proteins CCA1 and LHY participates in the systems involved in sensing long-term cold for the activation of VIN3 transcription.

AT-specific DNA visualization revisits the directionality of bacteriophage λ DNA ejection.

In this study, we specifically visualized DNA molecules at their AT base pairs after in vitro phage ejection. Our AT-specific visualization revealed that either end of the DNA molecule could be ejected first with a nearly 50% probability. This observation challenges the generally accepted theory of Last In First Out (LIFO), which states that the end of the phage λ DNA that enters the capsid last during phage packaging is the first to be ejected, and that both ends of the DNA are unable to move within the extremely condensed phage capsid. To support our observations, we conducted computer simulations that revealed that both ends of the DNA molecule are randomized, resulting in the observed near 50% probability. Additionally, we found that the length of the ejected DNA by LIFO was consistently longer than that by First In First Out (FIFO) during in vitro phage ejection. Our simulations attributed this difference in length to the stiffness difference of the remaining DNA within the phage capsid. In conclusion, this study demonstrates that a DNA molecule within an extremely dense phage capsid exhibits a degree of mobility, allowing it to switch ends during ejection.

Thiiranes: Intelligent Molecules for S-Persulfidation.

This study presents a global strategy for the transsulfuration of intracellular thiols (RSH) to persulfides (RSSH). Thiiranes comprising fluorenyl/diphenyl and malonate ester moieties directly convert intercellular RSH to low-molecular-weight RSSH in cells. The efficiency of transsulfuration is determined by counting the number of olefins produced as byproducts, providing ratiometric signals for the corresponding persulfide production. Specifically, the direct and rapid protein S-persulfidation by thiirane is validated. Thiiranes are expected to play a crucial role in the study of sulfur signaling.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Mapping the immune cell landscape of severe atopic dermatitis by single-cell RNA-seq.

BACKGROUND: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. METHODS: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. RESULTS: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. CONCLUSION: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Spatial transcriptomic analysis of tumour-immune cell interactions in melanoma arising from congenital melanocytic nevus.

BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.

Development and Analysis of an Origami-Based Elastomeric Actuator and Soft Gripper Control with Machine Learning and EMG Sensors.

This study investigates the characteristics of a novel origami-based, elastomeric actuator and a soft gripper, which are controlled by hand gestures that are recognized through machine learning algorithms. The lightweight paper-elastomer structure employed in this research exhibits distinct actuation features in four key areas: (1) It requires approximately 20% less pressure for the same bending amplitude compared to pneumatic network actuators (Pneu-Net) of equivalent weight, and even less pressure compared to other actuators with non-linear bending behavior; (2) The control of the device is examined by validating the relationship between pressure and the bending angle, as well as the interaction force and pressure at a fixed bending angle; (3) A soft robotic gripper comprising three actuators is designed. Enveloping and pinch grasping experiments are conducted on various shapes, which demonstrate the gripper's potential in handling a wide range of objects for numerous applications; and (4) A gesture recognition algorithm is developed to control the gripper using electromyogram (EMG) signals from the user's muscles.

Scannable Dual-Focus Metalens with Hybrid Phase.

Metalenses with two foci in the longitudinal or transverse direction, called bifocal or dual-focus metalenses, are promising building blocks in tomography techniques, data storage, and optical tweezers. For practical applications, relative movement between the beam and specimen is required, and beam scanning is highly desirable for high-speed operation without vibration. However, dual-focus metalenses employ a hyperbolic phase that experiences off-axis aberrations, which is not suitable for beam scanning. Here, we demonstrated a scannable dual-focus metalens by employing a new phase called "hybrid phase". The hybrid phase consists of a hyperbolic phase inside and a quadratic phase outside to reduce off-axis aberrations while maintaining a high numerical aperture. We show that the two foci of the scannable dual-focus metalens move together without severe distortion for incident angles of up to 2.5°. Our design easily extends to the case of multifocusing, which is essential for various applications ranging from imaging to manipulation.

Environmentally adaptive reshaping of plant photomorphogenesis by karrikin and strigolactone signaling.

Coordinated morphogenic adaptation of growing plants is critical for their survival and propagation under fluctuating environments. Plant morphogenic responses to light and warm temperatures, termed photomorphogenesis and thermomorphogenesis, respectively, have been extensively studied in recent decades. During photomorphogenesis, plants actively reshape their growth and developmental patterns to cope with changes in light regimes. Accordingly, photomorphogenesis is closely associated with diverse growth hormonal cues. Notably, accumulating evidence indicates that light-directed morphogenesis is profoundly affected by two recently identified phytochemicals, karrikins (KARs) and strigolactones (SLs). KARs and SLs are structurally related butenolides acting as signaling molecules during a variety of developmental steps, including seed germination. Their receptors and signaling mediators have been identified, and associated working mechanisms have been explored using gene-deficient mutants in various plant species. Of particular interest is that the KAR and SL signaling pathways play important roles in environmental responses, among which their linkages with photomorphogenesis are most comprehensively studied during seedling establishment. In this review, we focus on how the phytochemical and light signals converge on the optimization of morphogenic fitness. We also discuss molecular mechanisms underlying the signaling crosstalks with an aim of developing potential ways to improve crop productivity under climate changes.

The effects of defects on the transport mechanisms of lithium ions in organic ionic plastic crystals.

Organic ionic plastic crystals (OIPCs) consist of molecular ions of which interactions are strong enough to maintain crystalline order but are weak enough to allow the rotations of the molecular ions at sufficiently high temperatures. When defects such as Schottky vacancies and grain boundaries are introduced into OIPCs, the defects facilitate the transport of dopants such as Li+ ions, for which OIPCs are considered as strong candidates for solid electrolytes. The transport mechanism of dopant ions in OIPCs with defects, however, remains elusive at a molecular level partly because it is hard in experiments to track the dopant ions and control the types of defects systematically. In this work, we perform molecular dynamics simulations for 1,3-dimethylimidazolium hexafluorophosphate ([MMIM][PF6]) OIPCs with Li+ ions doped and show that the transport mechanism of Li+ ions depends on the types and concentrations of defects. A high concentration of Schottky vacancies enhance the overall ion conduction, but decrease the transference number. The transference numbers of Li+ ions in [MMIM][PF6] with grain boundaries are similar to that in [MMIM][PF6] with 0.78 mol% point vacancies. We also find that the transport of ions in OIPCs is strongly heterogeneous and the time scales of the dynamic heterogeneity of the ions are sensitive to the types of defects.

The effects of the shape of a capsid on the ejection rate of a single polymer chain through a nanopore.

The shape of a viral capsid affects the equilibrium conformation of DNA inside the capsid: the equilibrium DNA conformation inside a spherical capsid is a concentric spool while the equilibrium conformation inside an elongated capsid is a twisted toroid. The conformation of DNA, jammed inside the capsid due to high internal pressure, influences the ejection kinetics of the DNA from the capsid. Therefore, one would expect that the DNA ejection kinetics would be subject to the shape of the viral capsid. The effects of the capsid shape on the ejection, however, remain elusive partly due to a plethora of viral capsid shapes. In this work, we perform Langevin dynamics simulations for the ejection of a polymer chain from three different types of viral capsids: (1) spherical, (2) cubic, and (3) cuboid capsids. We find that the ejection rate of the polymer chain from the spherical capsid is much faster than that from either cubic or cuboid capsids. The polymer chain in the spherical capsid may undergo collective rotational relaxation more readily such that the polymer chain becomes more mobile inside the spherical capsid, which enhances the ejection kinetics. On the other hand, a threading motion is dominant inside cubic and cuboid capsids. We also find that the effects of the collective rotational motion become more significant for a more rigid chain inside a capsid.

SMAX1 Integrates Karrikin and Light Signals into GA-Mediated Hypocotyl Growth during Seedling Establishment.

Morphogenic adaptation of young seedlings to light environments is a critical developmental process that ensures plant survival and propagation, as they emerge from the soil. Photomorphogenic responses are facilitated by a network of light and growth hormonal signals, such as auxin and gibberellic acid (GA). Karrikins (KARs), a group of butenolide compounds produced from burning plant materials in wildfires, are known to stimulate seed germination in fire-prone plant species. Notably, recent studies support that they also regulate seedling growth, while underlying molecular mechanisms have been unexplored yet. Here, we demonstrate that SUPPRESSOR OF MAX2 1 (SMAX1), a negative regulator of KAR signaling, integrates light and KAR signals into GA-DELLA pathways that regulate hypocotyl growth during seedling establishment. We found that SMAX1 facilitates degradation of DELLA proteins in the hypocotyls. Interestingly, light induces the accumulation of SMAX1 proteins, and SMAX1-mediated degradation of DELLA is elevated in seedling establishment during the dark-to-light transition. Our observations indicate that SMAX1-mediated integration of light and KAR signals into GA pathways elaborately modulates seedling establishment.

Phytochrome B Conveys Low Ambient Temperature Cues to the Ethylene-Mediated Leaf Senescence in Arabidopsis.

Leaf senescence is an active developmental process that is tightly regulated through extensive transcriptional and metabolic reprogramming events, which underlie controlled degradation and relocation of nutrients from aged or metabolically inactive leaves to young organs. The onset of leaf senescence is coordinately modulated by intrinsic aging programs and environmental conditions, such as prolonged darkness and temperature extremes. Seedlings growing under light deprivation, as often experienced in severe shading or night darkening, exhibit an accelerated senescing process, which is mediated by a complex signaling network that includes sugar starvation responses and light signaling events via the phytochrome B (phyB)-PHYTOCHROME-INTERACTING FACTOR (PIF) signaling routes. Notably, recent studies indicate that nonstressful ambient temperatures profoundly influence the onset and progression of leaf senescence in darkness, presumably mediated by the phyB-PIF4 signaling pathways. However, it is not fully understood how temperature signals regulate leaf senescence at the molecular level. Here, we demonstrated that low ambient temperatures repress the nuclear export of phyB and the nuclear phyB suppresses the transcriptional activation activity of ethylene signaling mediator ETHYLENE INSENSITIVE3 (EIN3), thus delaying leaf senescence. Accordingly, leaf senescence was insensitive to low ambient temperatures in transgenic plants overexpressing a constitutively nuclear phyB form, as observed in ein3 eil1 mutants. In contrast, leaf senescence was significantly promoted in phyB-deficient mutants under identical temperature conditions. Our data indicate that phyB coordinately integrates light and temperature cues into the EIN3-mediated ethylene signaling pathway that regulates leaf senescence under light deprivation, which would enhance plant fitness under fluctuating natural environments.

iRegNet: an integrative Regulatory Network analysis tool for Arabidopsis thaliana.

Gene expression is delicately controlled via multilayered genetic and/or epigenetic regulatory mechanisms. Rapid development of the high-throughput sequencing (HTS) technology and its derivative methods including chromatin immunoprecipitation sequencing (ChIP-seq) and DNA affinity purification sequencing (DAP-seq) have generated a large volume of data on DNA-protein interactions (DPIs) and histone modifications on a genome-wide scale. However, the ability to comprehensively retrieve empirically validated upstream regulatory networks of genes of interest (GOIs) and genomic regions of interest (ROIs) remains limited. Here, we present integrative Regulatory Network (iRegNet), a web application that analyzes the upstream regulatory network for user-queried GOIs or ROIs in the Arabidopsis (Arabidopsis thaliana) genome. iRegNet covers the largest empirically proven DNA-binding profiles of Arabidopsis transcription factors (TFs) and non-TF proteins, and histone modifications obtained from all currently available Arabidopsis ChIP-seq and DAP-seq data. iRegNet not only catalogs upstream regulomes and epigenetic chromatin states for single-query gene/genomic region but also suggests significantly overrepresented upstream genetic regulators and epigenetic chromatin states of user-submitted multiple query genes/genomic regions. Furthermore, gene-to-gene coexpression index and protein-protein interaction information were also integrated into iRegNet for a more reliable identification of upstream regulators and realistic regulatory networks. Thus, iRegNet will help discover upstream regulators as well as molecular regulatory networks of GOI(s) and/or ROI(s), and is freely available at http://chromatindynamics.snu.ac.kr:8082/iRegNet_main.

Surface Wettability Prediction Using Image Analysis and an Artificial Neural Network.

In this study, a wettability-predicting method that uses an artificial neural network (ANN) by learning from digital images of the actual surface structures was developed. Polyester film surfaces were treated with oxygen plasma to realize various nanostructured surfaces. Surface structural characteristics from SEM images were quantified in a multifaceted way using a box-counting algorithm, a gray-level co-occurrence matrix algorithm, and binary image analysis. An ANN model that can predict wettability from surface structures was developed using the quantified surface structure and the resulting wettability as learning data. Furthermore, a surface with an optimal nanostructure to achieve superhydrophobicity was suggested by considering extracted surface structural parameters that significantly affect the surface wettability.

Effects of alkali ion dopants on the transport mechanisms and the thermal stabilities of imidazolium-based organic ionic plastic crystals.

Various dopant alkali ions have been introduced into organic ionic plastic crystals (OIPCs) in order to design solid electrolytes with the desired thermal stability and ionic conductivity. We performed extensive molecular dynamics simulations to investigate at the molecular level how dopant alkali ions affect the rotational and the translational diffusion of ions and the thermal stability of OIPCs. We introduced lithium (Li+), sodium (Na+), and potassium (K+) ions as dopants into 1-methyl-3-methylimidazolium hexafluorophosphate ([MMIM][PF6]) OIPCs at the molecular level. We found that as smaller alkali ions are doped, larger domains of the crystals are disrupted. This makes it harder for OIPCs doped with smaller alkali ions to maintain their crystal structure such that the melting temperature of OIPCs decreases and phase transitions between rotator phases change. The size of dopant alkali ions also affects the rotational diffusion of matrix ions of [MMIM]+ and PF6-: the rotational diffusion of matrix ions near Li+ ions becomes more heterogeneous and facilitated than those near other kinds of alkali ions. We also find that alkali ions of different kinds diffuse translationally in OIPCs via different transport mechanisms: while the Li+ ion undergoes continuous (anion-associated) diffusion through an amorphous region, the K+ ion hops between neighbor lattice sites. To investigate the effects of the relative size between matrix cations and dopant ions on translational diffusions, we also simulate OIPCs with longer alkyl chains such as 1-ethyl-3-methylimidazolium hexafluorophosphate ([EMIM][PF6]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) crystals. We find that as the size of imidazolium cations increases, the hopping diffusion of the K+ ion becomes suppressed and the K+ ion is more likely to diffuse through amorphous domains.

The effects of polarization on the rotational diffusion of ions in organic ionic plastic crystals.

Organic ionic plastic crystals (OIPCs), which consist of organic molecular ions, are considered excellent candidates for solid electrolytes due to their high ionic conductivity in solid phases. Molecular ions undergo either rotational or conformational relaxation at certain temperatures in OIPCs. There have been molecular simulations to understand the rotational motion. The polarizability of ions was, however, often ignored in simulations due to the high computational cost. Since the polarizability may affect the translational diffusion, the ionic conductivity, and the phase transition of ionic liquids, it should be of interest to investigate how the polarizability would affect the rotational diffusion of ions in solid phases. In this work, we perform extensive atomistic molecular dynamics simulations for two different kinds of OIPCs, 1-methyl-3-methylimidazolium hexafluorophosphate ([MMIM][PF6]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]). We employ various simulation models for ions by turning on and off the polarization in their interaction potentials. We find that the polarizability hardly affects the density, the crystalline structure, and the phase transition of both OIPCs. However, a certain rotational motion, especially the rotational diffusion of PF6 - in [MMIM][PF6] OIPCs, is enhanced by a factor of up to four when the polarizability is turned on. The PF6 - in [MMIM][PF6] OIPCs undergoes rotational hopping motions more significantly due to polarizability. We find that the rotational diffusion of a certain ion can be enhanced only when the polarization results in a significant change in the dipole moment of the neighboring ions around the ion.

Chlorogenic Acid as a Positive Regulator in LPS-PG-Induced Inflammation via TLR4/MyD88-Mediated NF-κB and PI3K/MAPK Signaling Cascades in Human Gingival Fibroblasts.

Gingival inflammation is one of the main causes that can be related to various periodontal diseases. Human gingival fibroblast (HGF) is the major constituent in periodontal connective tissue and secretes various inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), upon lipopolysaccharide stimulation. This study is aimed at investigating the anti-inflammatory mechanism of chlorogenic acid (CGA) on Porphyromonas gingivalis LPS- (LPS-PG-) stimulated HGF-1 cells. The concentration of NO and PGE2, as well as their responsible enzymes, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), was analyzed by Griess reaction, ELISA, and western blot analysis. LPS-PG sharply elevated the production and protein expression of inflammatory mediators, which were significantly attenuated by CGA treatment in a dose-dependent manner. CGA treatment also suppressed activation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) and nuclear factor- (NF-) κB in LPS-PG-stimulated HGF-1 cells. Furthermore, LPS-PG-induced phosphorylation of extracellular regulated kinase (ERK) and Akt was abolished by CGA treatment, while c-Jun N-terminal kinase (JNK) and p38 did not have any effect. Consequently, these results suggest that CGA ameliorates LPS-PG-induced inflammatory responses by attenuating TLR4/MyD88-mediated NF-κB, phosphoinositide-3-kinase (PI3K)/Akt, and MAPK signaling pathways in HGF-1 cells.