Search

Plasmonic absorption of light can create significant local heat and has become a promising tool for rapid temperature regulation in diverse fields, from biomedical technology to optoelectronics. Current plasmonic heating usually relies on specially designed nanomaterials randomly distributed in the space and barely provides uniform temperature regulation in a wide field. Herein, we report a rapid temperature regulation strategy on a plain gold-coated glass slip using a plasmonic scattering microscopy, which can be referred to as wide-field plasmonic thermal microscopy (W-PTM). We calibrated the W-PTM by monitoring the phase transition of the temperature-sensitive polymer solutions, showing that it can provide a temperature regulation range of 33-80 °C. Moreover, the W-PTM provides imaging capability, thus allowing the statistical analysis of the phase-transitioned polymeric nanoparticles. Finally, we demonstrated that W-PTM can be used for noninvasive and local regulation of the transient receptor potential vanilloid 1 (TRPV1) ion channels in the living cells, which can be monitored by simultaneous fluorescence imaging of the calcium influx. With the nondestructive local temperature-regulating and concurrent fluorescence imaging capability, we anticipate that W-PTM can be a powerful tool to study cellular activities associated with cellular membrane temperature changes.

Emerging studies reported that gut microbiota and fecal metabolites take part in major depressive disorder (MDD) pathogenesis. However, the conclusions based on a single depressive animal model seem inconsistent or even controversial.Multiple depression rat models, including chronic unpredictable mild stress, chronic restraint stress, social defeat, and learned helplessness, were used. Then, the 16S ribosomal RNA gene sequencing and liquid chromatography-mass spectrometry analysis determined the alteration of gut microbiota and fecal metabolites.The results of sucrose preference test and forced swimming test suggested that each model successfully established depression-like behavior. A total of 179 discriminative amplicon sequence variants (ASVs) were identified among four models. The overall discriminative ASVs mainly belonged to the family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae. Moreover, the fecal metabolomic analysis identified 468 differential expressed metabolites. Among all the differential metabolites, 11 specific pathways significantly altered, which were mainly belonged to lipid and amino acid metabolism. Finally, co-occurrence network analysis suggested that target differential metabolites were associated with discriminative ASVs mainly assigned to family taxon Lachnospiraceae, Muribaculaceae, and Oscillospiraceae.The heterogeneity of MDD in humans cannot be totally imitated by animal models.In multiple depression models, the alterations of family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae with the dysbiosis of lipid and amino acid metabolism were gut microbiota and fecal metabolome features. The findings of our research may help us to have a comprehensive understanding of gut microbiota and fecal metabolome in depression.

Rapid point-of-care (POC) diagnosis of bacterial infection diseases provides clinical benefits of prompt initiation of antimicrobial therapy and reduction of the overuse/misuse of unnecessary antibiotics for nonbacterial infections. We present here a POC compatible method for rapid bacterial infection detection in 10 min. We use a large-volume solution scattering imaging (LVSi) system with low magnifications (1-2×) to visualize bacteria in clinical samples, thus eliminating the need for culture-based isolation and enrichment. We tracked multiple intrinsic phenotypic features of individual cells in a short video. By clustering these features with a simple machine learning algorithm, we can differentiate

The spread of network attacks is extremely harmful, which poses a great threat to the assets and reputation of firms. Therefore, making a scientific information security strategy is an important task for the continued and stable development of the firms. This paper develops the SIR model of hacker intrusion propagation and then analyzes the evolution trend of hacker intrusion propagation and the conditions of strategy transfer. The research shows that when immune failure and strategy transfer are not considered, the threshold of hacker intrusion propagation is negatively correlated with the probability of invasion, whereas it is positively correlated with the probability of defense success and the externality during outsourcing. In the case of immune failure, there will always be infected firms in the network, where the threshold of hacker intrusion propagation is affected by the proportion of the infected state and the probability of immune failure. When immune failure and strategy transfer occur simultaneously if the externality is positive and high, information security outsourcing can improve firms’ security benefits; if the externality is negative, the firms should stop cooperating with the managed security service provider (MSSP).

Single-molecule detection can push beyond ensemble averages and reveal the statistical distributions of molecular properties. Measuring the binding kinetics of single proteins also represents one of the critical and challenging tasks in protein analysis. Here, we report total internal reflection-based evanescent scattering microscopy with label-free single-protein detection capability. Total internal reflection is employed to excite the evanescent field to enhance light-analyte interaction and reduce environmental noise. As a result, the system provides wide-field imaging capability and allows excitation and observation using one objective. In addition, this system quantifies protein binding kinetics by simultaneously counting the binding of individual molecules and recording their binding sites with nanometer precision, providing a digital method to measure binding kinetics with high spatiotemporal resolution. This approach does not employ specially designed microspheres or nanomaterials and may pave a way for label-free single-protein analysis in conventional microscopy.

MG53, a member of the tripartite motif (TRIM) protein family, plays an essential role in cell membrane repair and promotes cell survival. Recent studies show that systemic delivery of recombinant human MG53 (rhMG53) protein markedly attenuates tissue injury/inflammation, and facilitates healing. This study was performed to test whether intravenous administration of rhMG53 protein would decrease the lesion size in a clinically relevant large animal model of traumatic brain injury (TBI).Yorkshire swine (40-45 kg; n = 5/group) were subjected to controlled cortical impact TBI and randomized to either: (1) rhMG53 protein (2 mg/kg, intravenous) or (2) normal saline control. Hemodynamics, intracranial pressure, and brain oxygenation were monitored for 7 hours. Brains were then harvested and sectioned into 5-mm slices and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size. Blood-brain barrier permeability of MG53 in the brain was determined by Western blot and immunohistochemistry. Bcl-2 and phospho-GSK β levels were measured as makers of prosurvival pathway activation.Hemodynamic parameters were similar in both groups, but the lesion size in the rhMG53-treated group (2,517 ± 525.4 mm 3 ) was significantly ( p0.05) smaller than the control group (3,646 ± 740.1 mm 3 ). In the treated animals, rhMG53 was detected in the regions surrounding the TBI, but it was absent in the saline-treated control animals. Bcl-2 and phospho-GSK β levels in the brains were upregulated in the rhMG53-treated animals.Intravenously administered rhMG53 localizes to the injured areas of the brain, with the treated animals demonstrating a significant attenuation in the brain lesion size following TBI.

Purpose: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with poor prognosis. Conventional chemotherapeutics are generally able to shrink the tumor mass, but often fail to completely eradicate cancer stem–like cells (CSCs) that are responsible for high risk of relapse and frequent metastases. In this study, we examined thermal sensibility of CSCs, developed an approach that enabled concurrent elimination of both the bulk of cancer cells and CSCs, and investigated the underlying mechanism.Experimental Design: We designed a platform consisting of gold nanoparticle-coated porous silicon microparticle (AuPSM) that was also loaded with docetaxel micelles (mDTXs) to enable concurrent killing of the bulk of cancer cells by released mDTX and CSCs by mild hyperthermia upon stimulation of AuPSM with near infrared. In addition, we examined the role of heat shock proteins in sensitizing CSC killing. Finally, we applied mDTX-loaded AuPSM to treat mice with SUM159 and 4T1 orthotopic tumors and evaluated tumor growth and tumor metastasis.Results: MDA-MB-231 and SUM159 TNBC cells treated with mDTX-loaded AuPSM and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. Mechanistically, DTX treatment suppressed expression of heat shock protein 27 in cancer cells including the CSCs, rendering cells sensitive to mild hyperthermia.Conclusions: Our results indicate that chemotherapy sensitizes CSC to mild hyperthermia. We have developed an effective therapeutic approach to eliminate therapy-resistant cells in TNBC. Clin Cancer Res; 24(19); 4900–12. ©2018 AACR.

Supplementary Data Supplementary Methods Fig. S1. Increased CD44+CD24-ESA+ cell subpopulation in (A) SUM159 and (B) MDA-MB-231 cells after docetaxel treatment. *, p< 0.05; **, p< 0.01 (compared to untreatment controls). Analysis of apoptotic (C) SUM159 and (D) MDA-MB-231 cells 24 hours after cells were treated with DTX for 8 hours followed by hyperthermia at 43ï,°C for 5 min. *, p< 0.05; **, p< 0.01. The mean and standard deviations were calculated from three replicates. Fig. S2. NIR-triggered heat generation by AuPSMs. (A) Different efficiency on heat generation by different size Au particles in PSM. (B) Photothermal effect is stable and can be repeated for multiple cycles with the 20 nm Au particles in PSM. - Fig. S3. Quantitative RT-PCR analysis of heat shock protein expression in three ALDH1-positive breast cancer cell lines. (A) HSP27, HSP70 and HSP90 mRNA levels in ALDH1-positive MDA-MB-231 cells. (B) Dose-dependent killing of murine 4T1 cells treated with increasing concentrations of DTX for 72 hours. (C) HSP25 (murine homologue of human HSP27), HSP70 and HSP90 mRNA levels in ALDH1-positive 4T1 cells. (D) Dose-dependent killing of drug resistant MDA-MB-231/MDR cells treated with increasing concentrations of DTX for 72 hours. (E) HSP27, HSP70 and HSP90 mRNA levels in ALDH1-positive MDA-MB-231/MDR cells. All cells were treated with DTX for 8 hours followed by mild hyperthermia at 43ï,°C for 5 min.

The topological Weyl semimetals with peculiar band structure exhibit novel nonlinear optical enhancement phenomena even for light at optical wavelengths. While many intriguing nonlinear optical effects were constantly uncovered in type-I semimetals, few experimental works focused on basic nonlinear optical properties in type-II Weyl semimetals. Here we perform a fundamental static and time-resolved second harmonic generation (SHG) on the three dimensional Type-II Weyl semimetal candidate $\beta$-WP$_2$. Although $\beta$-WP$_2$ exhibits extremely high conductivity and an extraordinarily large mean free path, the second harmonic generation is unscreened by conduction electrons, we observed rather strong SHG response compared to non-topological polar metals and archetypal ferroelectric insulators. Additionally, our time-resolved SHG experiment traces ultrafast symmetry switching and reveals that polar metal $\beta$-WP$_2$ tends to form inversion symmetric metastable state after photo-excitation. Intense femtosecond laser pulse could optically drive symmetry switching and tune nonlinear optical response on ultrafast timescales although the interlayer coupling of $\beta$-WP$_2$ is very strong. Our work is illuminating for the polar metal nonlinear optics and potential ultrafast topological optoelectronic applications., Comment: 8 pages, 5 figures

The circuit origins of aggression in autism spectrum disorder remain undefined. Here we reportTac1-expressing glutamatergic neurons in ventrolateral division of ventromedial hypothalamus (VMHvl) drive intermale aggression. Aggression is increased due to increases ofUbe3agene dosage in the VMHvl neurons when modeling autism due to maternal 15q11-13 triplication. Targeted deletion of increasedUbe3acopies in VMHvl reverses the elevated aggression adult mice. VMHvl neurons form excitatory synapses onto hypothalamic arcuate nucleus AgRP/NPY neurons through a NRXN1-CBLN1-GluD1 transsynaptic complex and UBE3A impairs this synapse by decreasingCbln1gene expression. Exciting AgRP/NPY arcuate neurons leads to feedback inhibition of VMHvl neurons and inhibits aggression. Asymptomatic increases of UBE3A synergize with a heterozygous deficiency of presynapticNrxn1or postsynapticGrid1(both ASD genes) to increase aggression. Targeted deletions ofGrid1in arcuate AgRP neurons impairs the VMHvl to AgRP/NPY neuron excitatory synapses while increasing aggression. Chemogenetic/optogenetic activation of arcuate AgRP/NPY neurons inhibits VMHvl neurons and represses aggression. These data reveal that multiple autism genes converge to regulate the VMHvl-arcuate AgRP/NPY glutamatergic synapse. The hypothalamic circuitry implicated by these data suggest impaired excitation of AgRP/NPY feedback inhibitory neurons may explain the increased aggression behavior found in genetic forms of autism.One Sentence SummaryA feedback circuit in the hypothalamus that inhibits aggression is impaired by converging autism genetic defects.

As a class of randomized learner model, stochastic configuration networks (SCNs) have been successfully applied in a few data analytics tasks. Given the industrial big data modeling tasks, however, the original SCNs potentially lead to excessive training time. To this end, this paper extends SCNs to a hybrid parallel version, termed HPSCNs. In the hybrid parallel learning algorithm, two SCNs are synchronously constructed. The difference between the two of them is that one employs a point-incremental algorithm, and another one adopts a block-incremental algorithm. Moreover, a data parallel method is established based on a dynamic block strategy to accelerate the establishment of candidate node pool for each SCN. Additionally, this paper proposes an adaptive hyperparameter adjustment method, which allows the hyperparameters in the supervisory mechanism to be automatically adjusted along with the learning process. Comparative experiments are first conducted through four large-scale benchmark datasets, followed by the fully discussion on the algorithm parameters. Finally, a practical industrial application case is made, where a grinding particle size soft sensor is developed based on HPSCN, showing the effectiveness of the proposed algorithm.

Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant-induced lung injury. MG53 is a vital component of cell membrane repair and lung protection. Here, we show that mice with ablation of MG53 are more susceptible to NM-induced lung injury than the wild-type mice. Treatment of wild-type mice with exogenous recombinant human MG53 (rhMG53) protein ameliorates NM-induced lung injury by restoring arterial blood oxygen level, by improving dynamic lung compliance and by reducing airway resistance. Exposure of lung epithelial and endothelial cells to NM leads to intracellular oxidative stress that compromises the intrinsic cell membrane repair function of MG53. Exogenous rhMG53 protein applied to the culture medium protects lung epithelial and endothelial cells from NM-induced membrane injury and oxidative stress, and enhances survival of the cells. Additionally, we show that loss of MG53 leads to increased vulnerability of macrophages to vesicant-induced cell death. Overall, these findings support the therapeutic potential of rhMG53 to counteract vesicant-induced lung injury.

Kidney fibrosis is associated with the progression of acute kidney injury to chronic kidney disease. MG53, a cell membrane repair protein, has been shown to protect against injury to kidney epithelial cells and acute kidney injury. Here, we evaluated the role of MG53 in modulation of kidney fibrosis in aging mice and in mice with unilateral ureteral obstruction (UUO) a known model of progressive kidney fibrosis. Mice with ablation of MG53 developed more interstitial fibrosis with age than MG53-intact mice of the same age. Similarly, in the absence of MG53, kidney fibrosis was exaggerated compared to mice with intact MG53 in the obstructed kidney compared to the contralateral unobstructed kidney or the kidneys of sham operated mice. The ureteral obstructed kidneys from MG53 deficient mice also showed significantly more inflammation than ureteral obstructed kidneys from MG53 intact mice. In vitro experiments demonstrated that MG53 could enter the nuclei of proximal tubular epithelial cells and directly interact with the p65 component of transcription factor NF-κB, providing a possible explanation of enhanced inflammation in the absence of MG53. To test this, enhanced MG53 expression through engineered cells or direct recombinant protein delivery was given to mice subject to UUO. This reduced NF-κB activation and inflammation and attenuated kidney fibrosis. Thus, MG53 may have a therapeutic role in treating chronic kidney inflammation and thereby provide protection against fibrosis that leads to the chronic kidney disease phenotype.

Exosome analysis is a promising tool for clinical and biological research applications. However, detection and biomarker quantification of exosomes is technically challenging because they are small and highly heterogeneous. Here, we report an optical approach for imaging exosomes and quantifying their protein markers without labels using plasmonic scattering microscopy (PSM). PSM can provide improved spatial resolution and distortion-free image compared to conventional surface plasmon resonance (SPR) microscopy, with the signal-to-noise ratio similar to objective coupled surface plasmon resonance (SPR) microscopy, and millimeter-scale field of view as a prism-coupled SPR system, thus allowing exosome size distribution analysis with high throughput. In addition, PSM retains the high specificity and surface sensitivity of the SPR sensors and thus allows selection of exosomes from extracellular vesicles with antibody-modified sensor surfaces and

Cloud contamination is a common phenomenon in the optical remote sensing field, which limits their application in land surface studies and causes the waste of satellite images. This letter presents a new framework for removing thin clouds from visible images based on multiscale dark channel prior (MDCP). The cloud removal of cloudy images (target images) is carried out with the assistance of a different temporal cloudless image (reference image) from the perspective view of multiscale transform (MST). In order to make it more suitable for the application of thin cloud removal, two improvements are made to this traditional fusion method. For one thing, a dark channel prior module is integrated into the low-frequency component of the target image in the framework of MST. For another, we choose the weighted average for high-frequency components and sparse representation (SR) for low-frequency components as fusion rules. After the fusion process, the modified Laplacian sharpening whose model is optimized is carried out. The performance of MDCP was evaluated with both simulated and real cloudy images. Experimental results show that the proposed MDCP has a good performance.

At present, virtual reality technology is still in its infancy in the medical field in China, and the application ratio of virtual reality technology in medical education and medical treatment is relatively low. Based on the structure of the human stomach, this study integrates virtual reality technology, sensing technology, big data technology, and cloud computing technology to form a new form of medical education with an online website platform for data storage and analysis and offline VR glasses for physical operation. The project has established a model of the morphological structure and physiological processes of the human stomach in basic medicine, a model of the pathological tissue structure and pathophysiological processes in basic medicine, a model of the pharmacological processes and clinical pharmacology in basic medicine, and a model of the integrated treatment of the human stomach in clinical medicine for medical students at the university, as well as a model of the integrated treatment of preoperative discussions in clinical medicine and a model of the integrated treatment of doctor-patient communication in clinical medicine for clinicians at the hospital. It also established a model of integrated clinical medicine preoperative discussion and treatment, a model of integrated clinical medicine doctor-patient communication, and integrated clinical medicine general health treatment. The model has effectively improved the quality and efficiency of medical education, updated the concept of medical education, facilitated the formulation of surgical plans and the reduction of surgical risks as well as provided experimental materials for scientific research, and can be further developed into a three-dimensional structure of the human circulatory system and the major systems of the human body in the future.

This paper takes "situational simulation hospital practice and testing" as the teaching content, gamification as the innovative breakthrough point, and mobile learning as the goal, organically combines games and medicine, establishes a new student-centered learning model, and develops a mobile learning product in line with the development trend of "Internet + education." The mobile learning products conform to the development trend of "Internet+education," integrate game elements (such as problem situations, challenges, role-playing, instant evaluation, etc.) into teaching, provide learners with rewards, challenges, and success experiences that are lacking in the real world, create a variety of pleasant learning situations that are conducive to the input experience, make learners "learn in entertainment, learn in It is dedicated to serving medical students and medical workers, providing learners with an adaptive, fragmented and gamified mobile learning environment, realizing an innovative attempt to achieve student-centered and education 4.0, providing them with a new mode of hospital teaching experience by conducting "situational simulation of hospital practice and testing" on mobile terminals for teaching content, etc. The system is designed and finally implemented through the teaching content of "simulated hospital practice and test" on mobile terminals, which is a new attempt in the modern medical teaching field of gamified mobile learning.

Multiplexed protein detection is critical for improving the drug and biomarker screening efficiency. Here, we show that multiplexed protein detection and parallel protein interaction analysis can be realized by evanescent scattering microscopy (ESM). ESM enables binding kinetics measurement with label-free digital single-molecule counting. We implemented an automatic single-molecule counting strategy with high temporal resolution to precisely determine the binding time, which improves the counting efficiency and accuracy. We show that digital single-molecule counting can recognize proteins with different molecular weights, thus making it possible to monitor the protein binding processes in the solution by real-time tracking of the numbers of free and bound proteins landing on the sensor surface. Furthermore, we show that this strategy can simultaneously analyze the kinetics of two different protein interaction processes on the surface and in the solution. This work may pave a way to investigate complicated protein interactions, such as the competition of biomarker-antibody binding in biofluids with biomarker-protein binding on the cellular membrane.

Bullying is a repetitive ofefensive behavior intended to harm and with asymmetric power. School bullying is a special bullying behavior in which students are the mainparticipants. It has varying degrees of negativ Impact on the adolescents involved. In recent years, school bullying incidents have emerged one after another, and have received extensive attention from researchers. Research on school bullying has gradually been enriched. This paper reviews previous studies on bullying behavior in schools, and explores and summarizes the factors that lead to bullying behavior in adolescents from four main aspects: personal, family, school, and social environment, as well as some intervention methods for these influencing factors, hoping to provide theoretical support for establishing more effective intervention and prevention measures. Bullying is a repetitive ofefensive behavior intended to harm and with asymmetric power. School bullying is a special bullying behavior in which students are the mainparticipants. It has varying degrees of negativ Impact on the adolescents involved. In recent years, school bullying incidents have emerged one after another, and have received extensive attention from researchers. Research on school bullying has gradually been enriched. This paper reviews previous studies on bullying behavior in schools, and explores and summarizes the factors that lead to bullying behavior in adolescents from four main aspects: personal, family, school, and social environment, as well as some intervention methods for these influencing factors, hoping to provide theoretical support for establishing more effective intervention and prevention measures.

Conflict is an inevitable social phenomenon and the analysis of it can effectively resolve disputes, improve the position of decision makers (DMs), forecast compromise solutions as well. At present, the Graph Model for Conflict Resolution (GMCR), a completely non-quantitative decision support system (DSS) based on DM’s ordinal preference information, is constructed to combat conflict analysis complicated by multiple participant or multiple criteria or both. The purpose of the study is to introduce an overview of GMCR in conflict analyzing through bibliometrics. In order to achieve this goal, a systematic review of articles in leading journals of Web of Science Core Collection (WoSCC) during 1987–2019 is posed, referring to the distribution of countries, institutions, authors, subjects and journals, research topics and hotspots exploration as well as frontiers prediction, by utilizing VOSviewer and CiteSpace. The contributions of this study are not only providing a handy method to grasp generalized scientific research situation, but also demonstrating status quo and emerging trends of GMCR for researchers and everyone who interested in.