51 research outputs found
Ferroelectrically tunable topological phase transition in InSe thin films
Materials with ferroelectrically switchable topological properties are of
interest for both fundamental physics and practical applications. Using
first-principles calculations, we find that stacking ferroelectric
-InSe monolayers into a bilayer leads to polarization-dependent
band structures, which yields polarization-dependent topological properties.
Specifically, we find that the states with interlayer ferroelectric couplings
are quantum spin Hall insulators, while those with antiferroelectric
polarizations are normal insulators. We further find that InSe trilayer
and quadlayer exhibit nontrivial band topology as long as in the structure the
ferroelectric InSe bilayer is antiferroelectrically coupled to
InSe monolayers or other ferroelectric InSe bilayer. Otherwise
the system is topologically trivial. The reason is that near the Fermi level
the band structure of the ferroelectric InSe bilayer has to be
maintained for the nontrivial band topology. This feature can be used to design
nontrivial band topology for the thicker films by a proper combination of the
interlayer polarization couplings. The topological properties can be
ferroelectrically tunable using the dipole locking effect. Our study reveals
switchable band topology in a family of natural ferroelectrics, which provide a
platform for designing new functional devices.Comment: 12 pages, 12 figure
Patterns and Determinants of Antibiotic Use Behaviors among Rural Community Residents in Eastern China
Inappropriate antibiotic use may lead to antibiotic resistance, which has become a serious global crisis. Addressing suboptimal antibiotic use in the general population can play a significant role in the fight against antimicrobial resistance. This study aims to describe antibiotic use and sources of acquisition, and to identify factors influencing antibiotic access among rural community residents in Eastern China. A cross-sectional survey was conducted from July to August 2020, and 1494 participants from two villages in Eastern China were enrolled. Information was obtained using face-to-face interviews with a structured electronic questionnaire. Chi-squared and multinominal logistic regression analysis were used to explore possible determinants. In total, 1379 participants were eligible for the analysis. In the past 12 months, nearly half the respondents had taken any antibiotic (48.4%), and this proportion varied across marital status and age group. Two thirds of them (59.9%) obtained antibiotics from medical facilities with a prescription when they last took antibiotics, while 17.7% and 22.4% chose retail pharmacies and other sources, respectively. Multinominal analysis found that a higher proportion obtained antibiotics outside medical facilities among those aged 15 to 44 years, unmarried, non-white collar workers, with more years of education, lower annual household income per capita and lower levels of antibiotic knowledge. The antibiotic use behavior of rural community residents in Eastern China remains suboptimal. Antibiotic use and access behaviors need to be further addressed. Effective antibiotic stewardship in non-medical facility sources and training programs targeted for rural Chinese is warranted in future
Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis Survivors
Patients surviving a septic episode exhibit persistent immune impairment and increased mortality due to enhanced vulnerability to infections. In the present study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis, we addressed the hypothesis that altered vagus nerve activity contributes to immune impairment in sepsis survivors. CLP-surviving mice exhibited less TNFα in serum following administration of LPS, a surrogate for an infectious challenge, than control-operated (control) mice. To evaluate the role of the vagus nerve in the diminished response to LPS, mice were subjected to bilateral subdiaphragmatic vagotomy at 2 weeks post-CLP. CLP-surviving vagotomized mice exhibited increased serum and tissue TNFα levels in response to LPS-challenge compared to CLP-surviving, non-vagotomized mice. Moreover, vagus nerve stimulation in control mice diminished the LPS-induced TNFα responses while having no effect in CLP mice, suggesting constitutive activation of vagus nerve signaling in CLP-survivors. The percentage of splenic CD4+ ChAT-EGFP+ T cells that relay vagus signals to macrophages was increased in CLP-survivors compared to control mice, and vagotomy in CLP-survivors resulted in a reduced percentage of ChAT-EGFP+ cells. Moreover, CD4 knockout CLP-surviving mice exhibited an enhanced LPS-induced TNFα response compared to wild-type mice, supporting a functional role for CD4+ ChAT+ T cells in mediating inhibition of LPS-induced TNFα responses in CLP-survivors. Blockade of the cholinergic anti-inflammatory pathway with methyllcaconitine, an α7 nicotinic acetylcholine receptor antagonist, restored LPS-induced TNFα responses in CLP-survivors. Our study demonstrates that the vagus nerve is constitutively active in CLP-survivors and contributes to the immune impairment
Anabolic Actions of Fibroblast Growth Factor 2 on Bone Formation are medicated by Acting Transcription Factor 4 and by Modulation of the Wnt Signaling pathway
Our previous studies showed that fibroblast growth factor 2 (FGF2) intermittent treatment stimulates osteoblast differentiation and bone formation. However, the detailed mechanism(s) is not fully defined. We hypothesize that anabolic actions of FGF2 in bone are mediated in part by activating transcription factor 4 (ATF4) and by the Wnt signaling pathway. ATF4 is essential for osteoblasts differentiation. The first aim of the study was to examine the ability of FGF2 to increase ATF4 expression in osteoblasts. We demonstrated that FGF2 positively regulates ATF4 expression in osteoblasts, suggesting that impaired osteoblast differentiation and bone formation in Fgf2-/- mice may be partially due to reduced ATF4 expression. ^ The second aim was to investigate whether ATF4 is a mediator of the impaired anabolic response to parathyroid hormone (PTH) in Fgf2-/- mice. PTH is currently the only available anabolic agent for the treatment of osteoporosis in the U.S. In vitro and in vivo data have shown that increased ATF4 expression by PTH was attenuated by FGF2 ablation, indicating that reduced ATF4 expression may result in decreased osteoblast differentiation, and possibly contribute to the impaired stimulation of PTH on bone formation in Fgf2-/- mice. ^ Wnt signaling is particularly important for bone homeostasis. The third & fourth aims were to explore modulation of the Wnt/β-Catenin signaling in osteoblasts both in the absence of endogenous FGF2 and in the presence of exogenous FGF2. We observed that FGF2 deletion results in profound changes in expression of ligand Wnt10b, receptor lipoprotein receptor-related protein 6 and β-Catenin during osteoblast differentiation. FGF2 modulation of Wnt/β-Catenin signaling may be through kinase glycogen synthase kinase-3, a negative regulator of Wnt/β-Catenin pathway as well as Dickkopf 2, which plays a role in terminal osteoblast differentiation. Addition of exogenous FGF2 promoted β-Catenin nuclear accumulation and partially rescued decreased mineralization in Fgf2-/- bone marrow stromal cell cultures. These data demonstrate a role of endogenous FGF2 in bone formation through Wnt signaling. These results will advance our understanding of cross-talk between FGF2 and Wnt/β-Catenin signaling in bone biology. Our studies may offer insights and suggest new approaches for the treatment of bone diseases with low bone formation.
The Impaired Bone Anabolic Effect of PTH in the Absence of Endogenous FGF2 is Partially Due to Reduced ATF4 Expression
Parathyroid hormone (PTH) is currently the only approved anabolic agent for osteoporosis pharmacotherapy in the USA. However, the molecular and cellular mechanisms underlying which intermittent PTH stimulates bone formation are not fully established.
Activating transcription factor 4 (ATF4) was recently identified to be a downstream target of PTH signaling in osteoblasts and FGF2 is able to rapidly increase ATF4 mRNA and protein expression in osteoblasts. Furthermore, ATF4 expression is markedly reduced in Fgf2−/− osteoblasts. In addition, FGF2 is required for the anabolic action of PTH on bone formation. Therefore, we hypothesize that the impaired anabolic effect of PTH in Fgf2−/− mice is partially due to reduced ATF4 expression. To test this hypothesis, we examined the ability of PTH to increase ATF4 expression in vitro and in vivo. In vitro data showed that PTH induced a significant increase in ATF4 mRNA expression as early as 15 min in Fgf2+/+ primary bone marrow stromal cells (BMSCs) but not in Fgf2−/− BMSCs. In vivo data showed that treatment with PTH (1–34) (40 μg/kg/d) treatment for 2 weeks in 21–23 months female mice increased lumbar vertebrae bone mineral density in Fgf2+/+ (13.8% increase). In contrast there was a 2.1% decrease in Fgf2−/− mice. Interestingly, basal ATF4 mRNA expression in tibiae was significantly lower in Fgf2−/− mice (46% decrease) compared to Fgf2+/+ mice. PTH treatment increased ATF4 mRNA by 97% (p\u3c 0.05) in Fgf2+/+ compared to 8% (p = 0.57) in Fgf2−/− mice. Immunohistochemistry of vertebrae showed less ATF4 staining in Fgf2−/− tissue, and treatment with PTH increased ATF4 staining in Fgf2+/+ but the increase was attenuated in Fgf2−/− tissue.
In summary, reduced ATF4 expression may result in decreased osteoblast differentiation, and possibly contribute to the impaired stimulation of PTH on bone formation in Fgf2−/− mice
FGF2 crosstalk with Wnt signaling in mediating the anabolic action of PTH on bone formation
The mechanisms of the anabolic effect of parathyroid hormone (PTH) in bone are not fully defined. The bone anabolic effects of PTH require fibroblast growth factor 2 (FGF2) as well as Wnt signaling and FGF2 modulates Wnt signaling in osteoblasts. In vivo PTH administration differentially modulated Wnt signaling in bones of wild type (WT) and in mice that Fgf2 was knocked out (Fgf2KO). PTH increased Wnt10b mRNA and protein in WT but not in KO mice. Wnt antagonist SOST mRNA and protein was significantly higher in KO group. However, PTH decreased Sost mRNA significantly in WT as well as in Fgf2KO mice, but to a lesser extent in Fgf2KO. Dickhopf 2 (DKK2) is critical for osteoblast mineralization. PTH increased Dkk2 mRNA in WT mice but the response was impaired in Fgf2KO mice. PTH significantly increased Lrp5 mRNA and phosphorylation of Lrp6 in WT but the increase was markedly attenuated in Fgf2KO mice. PTH increased β-catenin expression and Wnt/β-catenin transcriptional activity significantly in WT but not in Fgf2KO mice. These data suggest that the impaired bone anabolic response to PTH in Fgf2KO mice is partially mediated by attenuated Wnt signaling. Keywords: PTH, FGF2, Wnt signaling, Bon
Cloud-enabled privacy-preserving collaborative learning for mobile sensing
In this paper, we consider the design of a system in which Internet-connected mobile users contribute sensor data as training samples, and collaborate on building a model for classification tasks such as activity or context recognition. Constructing the model can naturally be performed by a ser-vice running in the cloud, but users may be more inclined to contribute training samples if the privacy of these data could be ensured. Thus, in this paper, we focus on privacy-preserving collaborative learning for the mobile setting, which addresses several competing challenges not previ-ously considered in the literature: supporting complex clas-sification methods like support vector machines, respecting mobile computing and communication constraints, and en-abling user-determined privacy levels. Our approach, Pickle, ensures classification accuracy even in the presence of sig-nificantly perturbed training samples, is robust to methods that attempt to infer the original data or poison the model, and imposes minimal costs. We validate these claims using a user study, many real-world datasets and two different im-plementations of Pickle
- …