Reversible Sensing Technologies Using Upcycled TPEE: Crafting pH and Light Responsive Materials towards Sustainable Monitoring.

Multiresponsive materials with reversible and durable characteristics are indispensable because of their promising applications in environmental change detections. To fabricate multiresponsive materials in mass production, however, complex reactions and impractical situations are often involved. Herein, a dual responsive (light and pH) spiropyran-based smart sensor fabricated by a simple layer-by-layer (LbL) assembly process from upcycled thermoplastic polyester elastomer (TPEE) materials derived from recycled polyethylene terephthalate (r-PET) is proposed. Positively charged chitosan solutions and negatively charged merocyanine-COOH (MC-COOH) solutions are employed in the LbL assembly technique, forming the chitosan-spiropyran deposited TPEE (TPEE-CH-SP) film. Upon UV irradiation, the spiropyran-COOH (SP-COOH) molecules on the TPEE-CH-SP film undergo the ring-opening isomerization, along with an apparent color change from colorless to purple, to transform into the MC-COOH molecules. By further exposing the TPEE-CH-MC film to hydrogen chloride (HCl) and nitric acid (HNO3) vapors, the MC-COOH molecules can be transformed into protonated merocyanine-COOH (MCH-COOH) with the simultaneous color change from purple to yellow.

Alkaline-Responsive, Self-Healable, and Conductive Copolymer Composites with Enhanced Mechanical Properties Tailored for Wearable Tech.

Despite significant advancements, current self-healing materials often suffer from a compromise between mechanical robustness and functional performance, particularly in terms of conductivity and responsiveness to environmental stimuli. Addressing this issue, the research introduces a self-healable and conductive copolymer, poly(ionic liquid-co-acrylic acid) (PIL-co-PAA), synthesized through free radical polymerization, and further optimized by incorporating thermoplastic polyurethane (TPU). This combination leverages the unique properties of each component, especially ion-dipole interactions and hydrogen bonds, resulting in a material that exhibits exceptional self-healing abilities and demonstrates enhanced mechanical properties and electrical conductivity. Moreover, the PIL-co-PAA/TPU films showcase alkaline-responsive behavior, a feature that broadens their applicability in dynamic environments. Through systematic characterization, including thermogravimetric analysis, tensile testing, and electrical properties measurements, the mechanisms behind the improved performance and functionality of these films are elucidated. The conductivities and ultimate tensile strength (σuts) of the PIL-co-PAA/TPU films regain 80% under 8 h healing process. To extend the applications for wearable devices, the self-healing properties of commercial cotton fabrics coated with the self-healable PIL-co-PAA are also investigated, demonstrating both self-healing and electrical properties. This study advances the understanding of self-healable conductive polymers and opens new avenues for their application in wearable technology.

Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D â‰§20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

Temporal and Spatial Variations in Zebrafish Hairy/E(spl) Gene Expression in Response to Mib1-Mediated Notch Signaling During Neurodevelopment.

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. Hairy/E(spl) (HES) genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, mib1ta52b, focusing on changes in the expression of Hairy/E(spl) (her) genes. Our findings reveal significant variability in her gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of Hairy/E(spl) genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using Hairy/E(spl) genes as markers for Notch activity. Additionally, it provides new insights into Mib1's role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders.

A Cortico-Cortical Pathway Targets Inhibitory Interneurons and Modulates Paw Movement during Locomotion in Mice.

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized corticocortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2→non-whisker S1 projections alters the hind paw orientation during locomotion, whereas manipulation of the M1 projection has little effect. Using patch-clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that interneuron-mediated S2-S1 corticocortical interactions are critical for efficient locomotion.SIGNIFICANCE STATEMENT Somatosensory cortex participates in controlling rhythmic movements, such as whisking and walking, but the neural circuitry underlying movement control by somatosensory cortex remains relatively unexplored. We uncover a corticocortical circuit in primary somatosensory cortex that regulates paw orientation during locomotion in mice. We identify neuronal elements that comprise these cortical pathways using pharmacology, behavioral assays, and circuit-mapping methods.

Using a developed co-culture device to evaluate the proliferation of bone marrow stem cells by stimulation with platelet-rich plasma and electromagnetic field.

BACKGROUNDS: Bone marrow stem cell can differentiate to osteoblast by growth factors, pulsed low-intensity ultrasound and electric magnetic field. In the research, bone marrow stem cells were cultured; bone marrow stem cells in culture can be stimulated by platelet-rich plasma and electric field. METHODS: The culture well of the co-cultivation device has a radius of 7.5 mm and a depth of 7 mm. It is divided into two sub-chambers separated by a 3 mm high and 1 mm wide barrier. The bone marrow stem cells were seeded at a density of 2 × 104 cells and the medium volume was 120µl. Platelet-rich plasma (PRP) or platelet-poor plasma (PPP) was added to the other sub-chamber at a volume of 10µl. The bone marrow stem cells were subjected to different electric fields (0 ~ 1 V/cm) at a frequency of 70 kHz for 60 min. RESULTS: The highest osteogenic capacity of bone marrow stem cells was achieved by addition of PRP to electric field stimulation (0.25 V/cm) resulted in a proliferation rate of 599.78%. In electric field stimulation (0.75 V/cm) with PPP, the proliferation rate was only 10.46%. CONCLUSIONS: Bone marrow stem cell with PRP in the co-culture device combined with electric field at 0.25 V/cm strength significantly promoted the growth of bone marrow stem cells.

Identification of the Time Period during Which BMP Signaling Regulates Proliferation of Neural Progenitor Cells in Zebrafish.

Bone morphogenetic protein (BMP) signaling regulates neural induction, neuronal specification, and neuronal differentiation. However, the role of BMP signaling in neural progenitors remains unclear. This is because interruption of BMP signaling before or during neural induction causes severe effects on subsequent neural developmental processes. To examine the role of BMP signaling in the development of neural progenitors in zebrafish, we bypassed the effect of BMP signaling on neural induction and suppressed BMP signaling at different time points during gastrulation using a temporally controlled transgenic line carrying a dominant-negative form of Bmp receptor type 1aa and a chemical inhibitor of BMP signaling, DMH1. Inhibiting BMP signaling from 8 hpf could bypass BMP regulation on neural induction, induce the number of proliferating neural progenitors, and reduce the number of neuronal precursors. Inhibiting BMP signaling upregulates the expression of the Notch downstream gene hairy/E(spl)-related 2 (her2). Inhibiting Notch signaling or knocking down the Her2 function reduced neural progenitor proliferation, whereas inactivating BMP signaling in Notch-Her2 deficient background restored the number of proliferating neural progenitors. These results reveal the time window for the proliferation of neural progenitors during zebrafish development and a fine balance between BMP and Notch signaling in regulating the proliferation of neural progenitor cells.

Group IV THz large area emitter based on GeSn alloy.

THz photoconductive emitters based on III-V materials have demonstrated excellent THz radiation properties, enabling many unique applications. However, the incompatibility with the complementary-metal-oxide-semiconductor (CMOS) foundry fabrication process and the challenging growth condition hampers THz photoconductive emitters from large-scale production. To address this limitation, we proposed the GeSn alloy as the photoconductive material candidate through the CMOS-compatible epitaxy instrument. The GeSn photoconductor features a 518 cm2/V-s mobility and a 7187 cm-1 absorption coefficient at the wavelength of 1560 nm, resulting in sufficiently ultrafast photocurrent generation for THz radiation. As a result, the GeSn THz emitter provides over a bandwidth of 2 THz and a 40 dB signal-to-noise ratio, which shows its potential in realizing mass-producible, cost-effective THz integrated systems with CMOS technology.

Efficacy and cost-effectiveness analysis of post-acute care for elderly patients with hip fractures.

BACKGROUND/PURPOSE: Hip fractures are associated with physical dysfunction, and poor quality of life in the elderly. Post-acute care (PAC) would facilitate functional recovery in patients with hip fractures after surgeries. Taiwan has proposed a nationwide PAC program for hip fractures since 2017, but little has been known about its effectiveness. Therefore, this study aimed to evaluate the efficacy and cost-effectiveness of the PAC program for hip fracture patients in Taiwan. METHODS: This was a prospective study. Patients aged ≥ 65 years with hip fractures after surgeries were recruited and divided into home-based, hospital-based, and control groups. Outcome measures included pain, physical function (sit-to-stand test, Barthel Index [BI], and Harris hip score [HHS]), and quality of life (EuroQol instrument [EQ-5D]). Direct medical and non-medical costs were recorded. Cost-effectiveness ratio (CER) was calculated as the amount of New Taiwanese Dollars (NTDs) paid per BI and EQ-5D unit improvement. RESULTS: Forty-one patients participated in this study, with 17, 12, and 12 in the home-based, hospital-based, and control groups, respectively. The home-based group showed significant improvements in BI and HHS compared to the controls (p = 0.018 and p = 0.029, respectively). The hospital-based group demonstrated significant improvement in EQ-5D compared to the controls (p = 0.015). The home-based PAC program demonstrated the best CER for BI (NTD 554) and EQ-5D (NTD 41948). CONCLUSION: Both PAC programs would significantly improve the physical function and quality of life in patients with hip fractures. However, the home-based PAC provided the best CER for BI and EQ-5D.

Scalable Synthesis of Photoluminescent Single-Chain Nanoparticles by Electrostatic-Mediated Intramolecular Crosslinking.

We report the large-scale synthesis of photoluminescent single-chain nanoparticles (SCNPs) by electrostatic-mediated intramolecular crosslinking in a concentrated solution of 40 mg mL-1 by continuous addition of the free radical initiator. Poly(vinyl benzyl chloride) was charged by quaternization with vinyl-imidazolium for the intramolecular crosslinking by using 2,2-dimethoxy-2-phenylacetophenone (DMAP) as the radical initiator. Under the electrostatic repulsion thus interchain isolation, the intrachain crosslinking experiences the transition from coil through pearl-necklace to globular state. The SCNPs demonstrate strong photoluminescence in the visible range when the non-emissive units are confined thereby. Composition and microstructure of the SCNPs are tunable. The photoluminescent tadpole-like Janus SCNP can be used to selectively illuminate interfacial membranes while stabilizing the emulsions.

Audiogenic Seizures in the Fmr1 Knock-Out Mouse Are Induced by Fmr1 Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Hyperactive circuits are hypothesized to underlie dysfunction in a number of brain regions in patients with FXS and Fmr1 KO mice, and the AGS may be a result of this. But the specific cell types and brain regions underlying AGSs in the Fmr1 KO are unknown. We used conditional deletion or expression of Fmr1 in different cell populations to determine whether Fmr1 deletion in those cells was sufficient or necessary, respectively, for the AGS phenotype in males. Our data indicate that Fmr1 deletion in glutamatergic neurons that express vesicular glutamate transporter 2 (VGlut2) and are located in subcortical brain regions is sufficient and necessary to cause AGSs. Furthermore, the deletion of Fmr1 in glutamatergic neurons of the inferior colliculus is necessary for AGSs. When we demonstrate necessity, we show that Fmr1 expression in either the larger population of VGlut2-expressing glutamatergic neurons or the smaller population of inferior collicular glutamatergic neurons-in an otherwise Fmr1 KO mouse-eliminates AGSs. Therefore, targeting these neuronal populations in FXS and autism may be part of a therapeutic strategy to alleviate sensory hypersensitivity.SIGNIFICANCE STATEMENT Sensory hypersensitivity in fragile X syndrome (FXS) and autism patients significantly interferes with quality of life. Audiogenic seizures (AGSs) are arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knockout-and may be considered a model of sensory hypersensitivity in FXS. We provide the clearest and most precise genetic evidence to date for the cell types and brain regions involved in causing AGSs in the Fmr1 knockout and, more broadly, for any mouse mutant. The expression of Fmr1 in these same cell types in an otherwise Fmr1 knockout eliminates AGSs indicating possible cellular targets for alleviating sensory hypersensitivity in FXS and other forms of autism.

Regulatory mechanisms of B cell responses and the implication in B cell-related diseases.

Terminally differentiated B cell, the plasma cell, is the sole cell type capable of producing antibodies in our body. Over the past 30 years, the identification of many key molecules controlling B cell activation and differentiation has elucidated the molecular pathways for generating antibody-producing plasma cells. Several types of regulation modulating the functions of the important key molecules in B cell activation and differentiation add other layers of complexity in shaping B cell responses following antigen exposure in the absence or presence of T cell help. Further understanding of the mechanisms contributing to the proper activation and differentiation of B cells into antibody-secreting plasma cells may enable us to develop new strategies for managing antibody humoral responses during health and disease. Herein, we reviewed the effect of different types of regulation, including transcriptional regulation, post-transcriptional regulation and epigenetic regulation, on B cell activation, and on mounting memory B cell and antibody responses. We also discussed the link between the dysregulation of the abovementioned regulatory mechanisms and B cell-related disorders.

Welding Silver Nanowire Junctions for Transparent Conducting Films by a Rapid Electroplating Method.

A simple electrochemical method is developed in this study to weld the contact points in silver nanowire (AgNW) thin films. The AgNW thin film is first fabricated by spray coating and then submerged in a silver plating solution. By applying electrical potential over the AgNW thin films, silver ions in the plating solution are reduced into silver nanoparticles preferentially over nanowires and solder the nanomesh structures. Due to the large current density between silver nanowires, nanoparticles generated in the electroplating reaction mainly appeared at the junction. The electroplated AgNW network not only shows better conductivity with a negligible loss of transmittance, but also exhibit much better mechanical strength in the bending test.

Stability Analysis of Printed Liquid Elbows.

In this study, a theoretical model was developed to analyze the stability of liquid elbow patterns and validated by experiments. An exemplar system of ethylene glycol continuously deposited on polyethylene terephthalate (PET) was used to study the effects of printing parameters on bulge formation near the elbow corners. In the elbow region, because of the capillary pressure differences, liquids flowed into the concave elbow corner and formed bulges easily after being printed. However, the bulge formation disappeared when the elbow angle is >90°. A simple model based on surface energy analysis was proposed to explain the bulging phenomenon and can successfully predict bulge sizes at steady state. A stability diagram was also calculated to map out the stable regimes. With the guidance of the stability diagram, stable elbow lines without any bulges can be printed with various angles by controlling the thickness of liquids. In summary, this stabilization strategy in this study is effective to maintain the fidelity of printed liquid patterns and provides useful guidelines for printed electronic applications.

Surgical outcome of atypical subtrochanteric and femoral fracture related to bisphosphonates use in osteoporotic patients with or without teriparatide treatment.

BACKGROUND: Atypical subtrochanteric fracture and femoral fracture have been considered to be rare complications related to long-term bisphosphonates use. A reduced bone turnover rate may lead to delayed bone healing. Limited data have revealed that teriparatide treatment may reverse the effect of bisphosphonates and be effective in bone healing. METHODS: We reviewed patients with atypical subtrochanteric and femoral fracture related to bisphosphonates use between January 2008 and December 2014. Thirteen female patients were enrolled. Radiographic findings were compatible with the characteristics of atypical fracture. Surgical intervention was performed for all, and teriparatide use was advised postoperatively. Outcome measures included perioperative results, and clinical and radiographic outcome. RESULTS: Of the 13 female patients enrolled, 10 had subtrochanteric and 6 had proximal femoral fracture; 3 had bilateral fractures. The mean age of the patients at surgery was 70.15±6.36 years. Most fractures (68.8%) presented prodromal thigh pain. All patients were treated with an intramedullary fixation system without severe complications. The patients were divided into 2 groups based on whether they had received treatment with teriparatide or not. The mean time to bone union was 4.4 months in the teriparatide-treated group, and 6.2 months in the non-teriparatide-treated group (p=0.116). Six patients (75%) in the teriparatide-treated group and 4 (50%) in the non-teriparatide-treated group (p= 0.3) achieved bone union within 6 months. The means of the modified Harris Hip Score and Numerical Rating Scale were significantly better in the teriparatide-treated group at postoperative 6 months. Seven patients had the same ability to walk at the 1-year follow-up as they did before the atypical fracture. CONCLUSIONS: Teriparatide treatment in patients with atypical fracture may help in fracture healing, hip function recovery, and pain relief in this reduced bone turnover patient group.

The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells.

Epigenetic mechanisms, including histone modifications, have emerged as important factors influencing cell fate determination. The functional role of H3K4 methylation, however, remains largely unclear in the maintenance and differentiation of hematopoietic stem cells (HSCs)/hematopoietic progenitor cells (HPCs). Here we show that DPY30, a shared core subunit of the SET1/MLL family methyltransferase complexes and a facilitator of their H3K4 methylation activity, is important for ex vivo proliferation and differentiation of human CD34(+) HPCs. DPY30 promotes HPC proliferation by directly regulating the expression of genes critical for cell proliferation. Interestingly, while DPY30 knockdown in HPCs impaired their differentiation into the myelomonocytic lineage, it potently promoted hemoglobin production and affected the kinetics of their differentiation into the erythroid lineage. In an in vivo model, we show that morpholino-mediated dpy30 knockdown resulted in severe defects in the development of the zebrafish hematopoietic system, which could be partially rescued by coinjection of dpy30 messenger RNA. Taken together, our results establish a critical role of DPY30 in the proliferation and appropriate differentiation of hematopoietic progenitor cells and in animal hematopoiesis. Finally, we also demonstrate a crucial role of DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines.

Accelerated Sedimentation Velocity Assessment for Nanowires Stabilized in a Non-Newtonian Fluid.

In this work, the long-term stability of titanium oxide nanowire suspensions was accessed by an accelerated sedimentation with centrifugal forces. Titanium oxide (TiO2) nanoparticle (NP) and nanowire (NW) dispersions were prepared, and their sizes were carefully characterized. To replace the time-consuming visual observation, sedimentation velocities of the TiO2 NP and NW suspensions were measured using an analytical centrifuge. For an aqueous TiO2 NP suspension, the measured sedimentation velocities were linearly dependent on the relative centrifugal forces (RCF), as predicted by the classical Stokes law. A similar linear relationship was also found in the case of TiO2 NW aqueous suspensions. However, NWs preferred to settle parallel to the centrifugal direction under high RCF because of the lower flow resistance along the long axis. Thus, the extrapolated sedimentation velocity under regular gravity can be overestimated. Finally, a stable TiO2 NW suspension was formulated with a shear thinning fluid and showed great stability for weeks using visual observation. A theoretical analysis was deduced with rheological shear-thinning parameters to describe the nonlinear power-law dependence between the measured sedimentation velocities and RCF. The good agreement between the theoretical predictions and measurements suggested that the sedimentation velocity can be properly extrapolated to regular gravity. In summary, this accelerated assessment on a theoretical basis can yield quantitative information about long-term stability within a short time (a few hours) and can be further extended to other suspension systems.

ß-adrenergic signaling inhibits Gq-dependent protein kinase D activation by preventing protein kinase D translocation.

RATIONALE: Both ß-adrenergic receptor (ß-AR) and Gq-coupled receptor (GqR) agonist-driven signaling play key roles in the events, leading up to and during cardiac dysfunction. How these stimuli interact at the level of protein kinase D (PKD), a nodal point in cardiac hypertrophic signaling, remains unclear. OBJECTIVE: To assess the spatiotemporal dynamics of PKD activation in response to ß-AR signaling alone and on coactivation with GqR-agonists. This will test our hypothesis that compartmentalized PKD signaling reconciles disparate findings of PKA facilitation and inhibition of PKD activation. METHODS AND RESULTS: We report on the spatial and temporal profiles of PKD activation using green fluorescent protein-tagged PKD (wildtype or mutant S427E) and targeted fluorescence resonance energy transfer-based biosensors (D-kinase activity reporters) in adult cardiomyocytes. We find that ß-AR/PKA signaling drives local nuclear activation of PKD, without preceding sarcolemmal translocation. We also discover pronounced interference of ß-AR/cAMP/PKA signaling on GqR-induced translocation and activation of PKD throughout the cardiomyocyte. We attribute these effects to direct, PKA-dependent phosphorylation of PKD-S427. We also show that phosphomimetic substitution of S427 likewise impedes GqR-induced PKD translocation and activation. In neonatal myocytes, S427E inhibits GqR-evoked cell growth and expression of hypertrophic markers. Finally, we show altered S427 phosphorylation in transverse aortic constriction-induced hypertrophy. CONCLUSIONS: ß-AR signaling triggers local nuclear signaling and inhibits GqR-mediated PKD activation by preventing its intracellular translocation. PKA-dependent phosphorylation of PKD-S427 fine-tunes the PKD responsiveness to GqR-agonists, serving as a key integration point for ß-adrenergic and Gq-coupled stimuli.

The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice.

The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contributions of the constitutively expressed SmeYZ efflux pump to drug resistance, virulence-related characteristics, and virulence were evaluated. S. maltophilia KJ is a clinical isolate of multidrug resistance. The smeYZ isogenic deletion mutant, KJΔYZ, was constructed by a gene replacement strategy. The antimicrobial susceptibility, virulence-related physiological characteristics, susceptibility to human serum and neutrophils, and in vivo virulence between KJ and KJΔYZ were comparatively assessed. The SmeYZ efflux pump contributed resistance to aminoglycosides and trimethoprim-sulfamethoxazole. Inactivation of smeYZ resulted in attenuation of oxidative stress susceptibility, swimming, flagella formation, biofilm formation, and secreted protease activity. Furthermore, loss of SmeYZ increased susceptibility to human serum and neutrophils and decreased in vivo virulence in a murine model. These findings suggest the possibility of attenuation of the resistance and virulence of S. maltophilia with inhibitors of the SmeYZ efflux pump.