TPST2-mediated receptor tyrosine sulfation enhances leukocidin cytotoxicity and S. aureus infection

BackgroundAn essential fact underlying the severity of Staphylococcus aureus (S. aureus) infection is the bicomponent leukocidins released by the pathogen to target and lyse host phagocytes through specific binding cell membrane receptors. However, little is known about the impact of post-transcriptional modification of receptors on the leukocidin binding.MethodIn this study, we used small interfering RNA library (Horizon/Dharmacon) to screen potential genes that affect leukocidin binding on receptors. The cell permeability was investigated through flow cytometry measuring the internalization of 4′,6-diamidino-2-phenylindole. Expression of C5a anaphylatoxin chemotactic receptor 1 (C5aR1), sulfated C5aR1 in, and binding of 6x-His–tagged Hemolysin C (HlgC) and Panton-Valentine leukocidin (PVL) slow-component to THP-1 cell lines was detected and analyzed via flow cytometry. Bacterial burden and Survival analysis experiment was conducted in WT and myeloid TPST-cko C57BL/6N mice.ResultsAfter short hairpin RNA (shRNA) knockdown of TPST2 gene in THP-1, HL-60, and RAW264.7, the cytotoxicity of HlgAB, HlgCB, and Panton–Valentine leukocidin on THP-1 or HL-60 cells was decreased significantly, and the cytotoxicity of HlgAB on RAW264.7 cells was also decreased significantly. Knockdown of TPST2 did not affect the C5aR1 expression but downregulated cell surface C5aR1 tyrosine sulfation on THP-1. In addition, we found that the binding of HlgC and LukS-PV on cell surface receptor C5aR1 was impaired in C5aR1+TPST2− and C5aR1−TPST2− cells. Phagocyte knockout of TPST2 protects mice from S. aureus infection and improves the survival of mice infected with S. aureus.ConclusionThese results indicate that phagocyte TPST2 mediates the bicomponent leukocidin cytotoxicity by promoting cell membrane receptor sulfation modification that facilitates its binding to leukocidin S component

Short-term prediction of PV output based on weather classification and SSA-ELM

In this paper, according to the power output characteristics of distributed photovoltaic users, the SSA-ELM (Sparrow Search Algorithm - Extreme Learning Machine) model based on weather type division is proposed for photovoltaic power day ahead prediction. Because the solar panel power generation sequence of photovoltaic users contains high frequency fluctuations, in this paper we use the power sequence convergence effect to make cluster prediction on all photovoltaic panels to reduce the randomness of distributed photovoltaic. The prediction accuracy is further improved by dividing weather types. The historical data of distributed PV users in a region of Gansu province is used for modeling verification, and the results show that the prediction error of the proposed method is lower. In bad weather, the root mean square error is at least 0.02 less than the comparison model, and the average annual accuracy rate is 93.2%, which proves the applicability of the proposed method in different output types

Tunable terahertz photodetector using ferroelectric-integrated graphene plasmonics for portable spectrometer

Terahertz (THz) detector has great potential for use in imaging, spectroscopy, and communications due to its fascinating interactions between radiation and matter. However, current THz detection devices have limitations in sensitivity, operating frequency range, and bulky footprint. While recent ferroelectric-integrated graphene plasmonic devices show promise in overcoming these limitations, they are not yet extended to the THz range. Here, we propose a wavelength-sensitive terahertz detector that uses a single layer graphene integrated onto the ferroelectric thin film with patterned polarization domains. This device works at room temperature, with high responsivity and detectivity by coupling graphene plasmons with THz frequencies through spatial modulation of carrier behaviors using ferroelectric polarization, without requiring additional local electrodes. By reconfiguring an interweaving squared ferroelectric domain array with alternating upward and downward polarizations to highly confine graphene surface plasmon polaritons, our device achieves an ultrahigh responsivity of 1717 A W-1 and a normalized detectivity of 1.07*10^13 Jones at a resonance frequency of 6.30 THz and a 0.3 V bias voltage. We also show that the device makes possible for spectrum reconstruction application of portable spectrometer combining the mathematical algorithms.Comment: 17 pages, 5 figure

Combination of plant metabolites hinders starch digestion and glucose absorption while facilitating insulin sensitivity to diabetes

IntroductionDiabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications.MethodsTo overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity.ResultsThe results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM.DiscussionThe results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity

The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study.

BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire. DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings

A Secure and Verifiable Outsourced Access Control Scheme in Fog-Cloud Computing

With the rapid development of big data and Internet of things (IOT), the number of networking devices and data volume are increasing dramatically. Fog computing, which extends cloud computing to the edge of the network can effectively solve the bottleneck problems of data transmission and data storage. However, security and privacy challenges are also arising in the fog-cloud computing environment. Ciphertext-policy attribute-based encryption (CP-ABE) can be adopted to realize data access control in fog-cloud computing systems. In this paper, we propose a verifiable outsourced multi-authority access control scheme, named VO-MAACS. In our construction, most encryption and decryption computations are outsourced to fog devices and the computation results can be verified by using our verification method. Meanwhile, to address the revocation issue, we design an efficient user and attribute revocation method for it. Finally, analysis and simulation results show that our scheme is both secure and highly efficient

ECT2 Increases the stability of EGFR and Tumorigenicity by Inhibiting Grb2 Ubiquitination in Pancreatic Cancer

The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is associated with the invasion and metastasis of tumor cells. Epithelial cell transforming 2 (ECT2) is a guanine nucleotide exchange factor (GEF) of the Rho family of GTPases. It has also been reported that upregulation of ECT2 in pancreatic cancer, but the role and mechanism of ECT2 have not been previously determined. We found that ECT2 was significantly elevated in PDAC tissues and cells, correlated with more advanced AJCC stage, distant metastases, and overall survival of patients with PDAC. Inhibition and overexpression tests showed that ECT2 promoted proliferation, migration and invasion in vitro, and promoted tumor growth and metastasis in vivo. We determined that ECT2 was involved in the post-translational regulation of Grb2. ECT2 inhibited the degradation of Grb2 through deubiquitination. Furthermore, knockdown of ECT2 downregulated EGFR levels by accelerating EGFR degradation. EGF stimulation facilitated the formation of ECT2-Grb2 complex. Overall, our findings indicated that ECT2 could be used as a promising new therapeutic candidate for PDAC

River Bars and Vegetation Dynamics in Response to Upstream Damming: A Case Study of the Middle Yangtze River

Investigating river bars and their vegetation dynamics in response to upstream damming is important for riverine flood management and ecological assessment. However, our mechanical understanding of the damming-induced changes in river bar and vegetation, such as bar area, morphology, and leaf area index (LAI), remains limited for large river systems. Leveraging satellite images and in situ observed hydrogeomorphic data from, we improve a machine learning-based LAI inversion model to quantify variations in river bar morphology, vegetation distribution, and LAI in the Middle Yangtze River (MYR) following the operation of the Three Gorges Dam (TGD). Then we analyze the mechanisms controlling the bar and vegetation dynamics based on high-resolution river cross-sectional profiles as well as daily discharge, water levels, and sediment in both the pre- and post-TGD periods. Our results indicate that the river bar area decreased by approximately 10% from 2003 to 2020, while the vegetation area and average LAI of these bars increased by >50% and >20%, respectively. Moreover, the plant community on most river bars tended to expand from the bar tail to the bar head and from the edge to the center. The main factor driving vegetation expansion in the MYR after the TGD’s operation was the reduction in bar submergence frequency (by 55%), along with a slight bar erosion. Further analysis revealed that the standard deviation of annual discharge decreased by approximately 37%, and the frequency of vegetation-erosive flow decreased by approximately 74%. Our data highlight the potential impact of large dams downstream flow regimes and vegetation encroachement. Such findings further the understanding of the biogeomorphological impacts of large dams on the river bar vegetation and have important implications for riverine plant flux estimatin, flood management and ecological restoration in dammed river systems