Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Association of Cardiovascular Health with Cognitive Function in US Older Adults: A Population-Based Cross-Sectional Study.

INTRODUCTION: Promoting cardiovascular health (CVH) by Life's Simple 7 is associated with better cognitive function. In 2022, the American Heart Association (AHA) prompted Life's Essential 8 (LE8) to strengthen CVH assessment. This study investigated the association between the new CVH metrics assessed by LE8 and cognitive function, thus providing evidence for implementing LE8 in the primordial prevention of cognitive impairment. METHODS: 2,050 participants aged 60 and older from National Health and Nutrition Examination Survey 2011-2014 were included. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The overall and domain-specific cognitive function z-score was created. CVH score was calculated following AHA's advisory. The multivariable linear regression model estimated the associations. RESULTS: The CVH score assessed by LE8 was independently, positively, and linearly associated with the overall cognitive function. A per-10 point increase in CVH was associated with higher overall cognitive z-scores (ß, 0.06; 95% confidence interval [CI], 0.03, 0.09), and participants with moderate (ß, -0.14; 95% CI, -0.22, -0.05) and low CVH (ß, -0.27; 95% CI, -0.37, -0.16) had lower overall cognitive z-scores compared to participants with high CVH. Similar patterns of associations were observed between CVH of AFT and DSST. Components of CVH were further associated with different domain-specific cognitive functions. CONCLUSION: Maintaining an ideal CVH improves cognitive function in older adults. Ideal adherence to individual components of LE8 was associated with improved overall and domain-specific cognitive functions. Therefore, promoting CVH according to LE8 might benefit cognitive function in the elderly.

Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.

OBJECTIVE: The study aimed to evaluate, using a network meta-analysis, the effects of different transcranial magnetic stimulation (TMS) modalities on improving cognitive function after stroke. METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, Google Scholar, CNKI, and Wanfang databases were conducted to collect randomized controlled clinical studies on the use of TMS to improve cognitive function in stroke patients, published from the time of database construction to November 2023. RESULTS: A total of 29 studies and 2123 patients were included, comprising five interventions: high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), intermittent theta rhythm stimulation (iTBS), sham stimulation (SS), and conventional rehabilitation therapy (CRT). A reticulated meta-analysis showed that the rankings of different TMS intervention modalities in terms of the Montreal Cognitive Assessment (MoCA) scores, Mini-Mental State Examination scores (MMSE), and Modified Barthel Index (MBI) scores were: HF-rTMS > LF-rTMS > iTBS > SS > CRT; the rankings of different TMS intervention modalities in terms of the event-related potential P300. amplitude scores were HF-rTMS > LF-rTMS > iTBS > CRT > SS; the rankings of different TMS intervention modalities in terms of the P300 latency scores were: iTBS > HF-rTMS > LF-rTMS > SS > CRT. Subgroup analyses of secondary outcome indicators showed that HF-rTMS significantly improved Rivermead Behavior Memory Test scores and Functional Independence Measurement-Cognitive scores. CONCLUSIONS: High-frequency TMS stimulation has a better overall effect on improving cognitive functions and activities of daily living, such as attention and memory in stroke patients.

Multi-view feature representation and fusion for drug-drug interactions prediction.

BACKGROUND: Drug-drug interactions (DDIs) prediction is vital for pharmacology and clinical application to avoid adverse drug reactions on patients. It is challenging because DDIs are related to multiple factors, such as genes, drug molecular structure, diseases, biological processes, side effects, etc. It is a crucial technology for Knowledge graph to present multi-relation among entities. Recently some existing graph-based computation models have been proposed for DDIs prediction and get good performance. However, there are still some challenges in the knowledge graph representation, which can extract rich latent features from drug knowledge graph (KG). RESULTS: In this work, we propose a novel multi-view feature representation and fusion (MuFRF) architecture to realize DDIs prediction. It consists of two views of feature representation and a multi-level latent feature fusion. For the feature representation from the graph view and KG view, we use graph isomorphism network to map drug molecular structures and use RotatE to implement the vector representation on bio-medical knowledge graph, respectively. We design concatenate-level and scalar-level strategies in the multi-level latent feature fusion to capture latent features from drug molecular structure information and semantic features from bio-medical KG. And the multi-head attention mechanism achieves the optimization of features on binary and multi-class classification tasks. We evaluate our proposed method based on two open datasets in the experiments. Experiments indicate that MuFRF outperforms the classic and state-of-the-art models. CONCLUSIONS: Our proposed model can fully exploit and integrate the latent feature from the drug molecular structure graph (graph view) and rich bio-medical knowledge graph (KG view). We find that a multi-view feature representation and fusion model can accurately predict DDIs. It may contribute to providing with some guidance for research and validation for discovering novel DDIs.

Hepatitis B virus X protein promotes MAN1B1 expression by enhancing stability of GRP78 via TRIM25 to facilitate hepatocarcinogenesis.

BACKGROUND: GRP78 has been implicated in hepatocarcinogenesis. However, the clinical relevance, biological functions and related regulatory mechanisms of GRP78 in hepatitis B virus (HBV)-associated hepatoma carcinoma (HCC) remain elusive. METHODS: The association between GRP78 expression and HBV-related HCC was investigated. The effects of HBV X protein (HBX) on GRP78 and MAN1B1 expression, biological functions of GRP78 and MAN1B1 in HBX-mediated HCC cells and mechanisms related to TRIM25 on GRP78 upregulation to induce MAN1B1 expression in HBX-related HCC cells were examined. RESULTS: GRP78 expression was correlated with poor prognosis in HBV-positive HCC. HBX increased MAN1B1 protein expression depending on GRP78, and HBX enhanced the levels of MAN1B1 to promote proliferation, migration and PI3-K/mTOR signalling pathway activation in HCC cells. GRP78 activates Smad4 via its interaction with Smad4 to increase MAN1B1 expression in HBX-expressing HCC cells. TRIM25 enhanced the stability of GRP78 by inhibiting its ubiquitination. HBX binds to GRP78 and TRIM25 and accelerates their interaction of GRP78 and TRIM25, leading to an increase in GRP78 expression. CONCLUSIONS: HBX enhances the stability of GRP78 through TRIM25 to increase the expression of MAN1B1 to facilitate tumorigenesis, and we provide new insights into the molecular mechanisms underlying HBV-induced malignancy.

Integrating network pharmacology and experimental verification to explore the mechanisms of salidroside against myocardial fibrosis.

Myocardial fibrosis (MF) is the manifestation of a variety of cardiovascular diseases. Salidroside (SAL) has been proved to have a certain effect on anti-fibrosis in various organs. However, the mechanism of SAL in the treatment of MF remains unclear. Network pharmacology showed that there were 1228 SAL-related target genes and 2793 MF-related target genes. The intersection of these genes resulted in 271 drug-disease interactions, and 15 core active targets were filtered from protein-protein interaction mapping. The top 20 Gene ontology biological processes analysis showed that the involved processes were close to the pathogenesis of MF. Among the top 20 enriched KEGG pathways, Wnt/ß-catenin and TGF-ß1/Smad3 signaling pathways were identified. In vivo, MI rats exhibited thinning of the myocardial region and the formation of fibrous scars, the expression of smad3 and ß-catenin were increased. After SAL treatment, there was a significant reduction in collagen area and a decrease in the ratio of collagen type I to type III. The expression of smad3 and ß-catenin was suppressed and positively correlated with the dosage of SAL. SAL may contribute to the progression of MF through the TGF-ß1/Smad3 and Wnt/ß-catenin signaling pathways.

Triglyceride-glucose index for predicting repeat revascularization and in-stent restenosis in patients with chronic coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index, a reliable surrogate indicator of insulin resistance, is independently associated with coronary artery disease of various clinical manifestations. This study aimed to investigate the prognostic value of the TyG index in predicting repeat revascularization and in-stent restenosis (ISR) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 1414 participants were enrolled and divided into groups according to the tertiles of the TyG index. The primary endpoint was a composite of PCI complications, including repeat revascularization and ISR. The associations between the TyG index and the primary endpoint were assessed by multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). RESULTS: Over a median follow-up of 60 months, 548 (38.76%) patients had experienced at least one primary endpoint event. The follow-up incidence of the primary endpoint increased with the TyG index tertiles. After adjusting for potential confounders, the TyG index was independently associated with the primary endpoint in CCS patients (HR, 1.191; 95% CI 1.038-1.367; P = 0.013). Additionally, the highest tertile of the TyG group was correlated with a 1.319-fold risk of the primary endpoint compared with the lowest tertile of the TyG group (HR, 1.319; 95% CI 1.063-1.637; P = 0.012). Furthermore, a linear and dose-response relationship was observed between the TyG index and the primary endpoint (non-linear P = 0.373, P overall = 0.035). CONCLUSIONS: An increased TyG index was associated with elevated risk for long-term PCI complications, including repeat revascularization and ISR. Our study suggested that the TyG index could be a potent predictor in evaluating the prognosis of CCS patients undergoing PCI.

Insights into the impact of hepatitis B virus on hepatic stellate cell activation.

During chronic hepatitis B virus (HBV) infection, hepatic fibrosis is a serious pathological condition caused by virus-induced liver damage. The activation of hepatic stellate cells (HSCs) is a central event in the occurrence and progression of liver fibrosis. Although accumulating evidence has shown that HBV directly stimulates HSC activation, whether the virus infects and replicates in HSCs remains controversial. Inflammation is one of the obvious characteristics of chronic HBV infection, and it has been demonstrated that persistent inflammation has a predominant role in triggering and maintaining liver fibrosis. In particular, the regulation of HSC activation by HBV-related hepatocytes via various inflammatory modulators, including TGF-ß and CTGF, in a paracrine manner has been reported. In addition to these inflammation-related molecules, several inflammatory cells are essential for the progression of HBV-associated liver fibrosis. Monocytes, macrophages, Th17 cells, NK cells, as well as NKT cells, participate in the modulation of HBV-related liver fibrosis by interacting with HSCs. This review summarizes current findings on the effects of HBV and the relevant molecular mechanisms involved in HSC activation. Because HSC activation is essential for liver fibrosis, targeting HSCs is an attractive therapeutic strategy to prevent and reverse hepatic fibrosis induced by HBV infection. Video abstract.

The telehealth program of occupational therapy among older people: an up-to-date scoping review.

BACKGROUND: The average life expectancy of older people is increasing, and most seniors desire to age at home and are capable of living independently. Occupational therapy (OT) is client-centered and uses patients' meaningful activities, or occupations, as treatment methods, thus playing an important role in later adulthood. Telemedicine removes the constraints of time and space, and the combination of OT and telemedicine can greatly improve medical efficiency and clinical effectiveness. AIMS: The purpose of this scoping review was to examine the scope and effectiveness of telehealth OT for older people. METHODS: This scoping review was conducted following the methodological framework proposed by Arksey and O'Malley. We searched the literature in five databases following the PICOS (Population, Intervention, Comparison, Outcome, Study design) guideline, from inception to April 2022. Two trained reviewers independently retrieved, screened, and extracted data, and used a descriptive synthesizing approach to summarize the results. RESULTS: The initial search yielded 1249 studies from databases and manual searches, of which 20 were eligible and were included in the final review. A thematic analysis revealed five main themes related to telehealth OT: occupational assessment, occupational intervention, rehabilitation counseling, caregiver support, and activity monitoring. CONCLUSIONS: Telehealth OT has been used widely for older people, focusing primarily on occupational assessment and intervention provided conveniently for occupational therapists and older clients. In addition, telehealth OT can monitor patients' activities and provide rehabilitation counseling and health education for the elderly and their caregivers, thus improving the security of their home life and the efficacy of OT. During the COVID-19 pandemic, telehealth will be an effective alternative to face-to-face modalities.

Regulation of epithelial-mesenchymal transition by protein lysine acetylation.

The epithelial-mesenchymal transition (EMT) is a vital driver of tumor progression. It is a well-known and complex trans-differentiation process in which epithelial cells undergo morphogenetic changes with loss of apical-basal polarity, but acquire spindle-shaped mesenchymal phenotypes. Lysine acetylation is a type of protein modification that favors reversibly altering the structure and function of target molecules via the modulation of lysine acetyltransferases (KATs), as well as lysine deacetylases (KDACs). To date, research has found that histones and non-histone proteins can be acetylated to facilitate EMT. Interestingly, histone acetylation is a type of epigenetic regulation that is capable of modulating the acetylation levels of distinct histones at the promoters of EMT-related markers, EMT-inducing transcription factors (EMT-TFs), and EMT-related long non-coding RNAs to control EMT. However, non-histone acetylation is a post-translational modification, and its effect on EMT mainly relies on modulating the acetylation of EMT marker proteins, EMT-TFs, and EMT-related signal transduction molecules. In addition, several inhibitors against KATs and KDACs have been developed, some of which can suppress the development of different cancers by targeting EMT. In this review, we discuss the complex biological roles and molecular mechanisms underlying histone acetylation and non-histone protein acetylation in the control of EMT, highlighting lysine acetylation as potential strategy for the treatment of cancer through the regulation of EMT. Video Abstract.

A Dynamic Convolution Kernel Generation Method Based on Regularized Pattern for Image Super-Resolution.

Image super-resolution aims to reconstruct a high-resolution image from its low-resolution counterparts. Conventional image super-resolution approaches share the same spatial convolution kernel for the whole image in the upscaling modules, which neglect the specificity of content information in different positions of the image. In view of this, this paper proposes a regularized pattern method to represent spatially variant structural features in an image and further exploits a dynamic convolution kernel generation method to match the regularized pattern and improve image reconstruction performance. To be more specific, first, the proposed approach extracts features from low-resolution images using a self-organizing feature mapping network to construct regularized patterns (RP), which describe different contents at different locations. Second, the meta-learning mechanism based on the regularized pattern predicts the weights of the convolution kernels that match the regularized pattern for each different location; therefore, it generates different upscaling functions for images with different content. Extensive experiments are conducted using the benchmark datasets Set5, Set14, B100, Urban100, and Manga109 to demonstrate that the proposed approach outperforms the state-of-the-art super-resolution approaches in terms of both PSNR and SSIM performance.

Focal DETR: Target-Aware Token Design for Transformer-Based Object Detection.

In this paper, we propose a novel target-aware token design for transformer-based object detection. To tackle the target attribute diffusion challenge of transformer-based object detection, we propose two key components in the new target-aware token design mechanism. Firstly, we propose a target-aware sampling module, which forces the sampling patterns to converge inside the target region and obtain its representative encoded features. More specifically, a set of four sampling patterns are designed, including small and large patterns, which focus on the detailed and overall characteristics of a target, respectively, as well as the vertical and horizontal patterns, which handle the object's directional structures. Secondly, we propose a target-aware key-value matrix. This is a unified, learnable, feature-embedding matrix which is directly weighted on the feature map to reduce the interference of non-target regions. With such a new design, we propose a new variant of the transformer-based object-detection model, called Focal DETR, which achieves superior performance over the state-of-the-art transformer-based object-detection models on the COCO object-detection benchmark dataset. Experimental results demonstrate that our Focal DETR achieves a 44.7 AP in the coco2017 test set, which is 2.7 AP and 0.9 AP higher than the DETR and deformable DETR using the same training strategy and the same feature-extraction network.

Explore the gene network regulating the composition of fatty acids in cottonseed.

BACKGROUND: Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. RESULTS: In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5-15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10-60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25-50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. CONCLUSIONS: These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

Combination of TLR agonist and miR146a mimics attenuates ovalbumin-induced asthma.

BACKGROUND: microRNA-146a has been reported to be a regulator in the process of attenuating asthma by inhibiting Toll-like receptor 2 (TLR2) pathway. This study aimed to investigate how miR146a-inhibitor affect the symptom of asthma and the underlying mechanisms. METHODS: Ovalbumin (OVA)-induced allergic asthma mice model was established by intraperitoneal injection with 20 µg of OVA. Total cells and differential inflammatory cells in bronchoalveolar lavage fluid were counted by flow cytometry. The expression levels of molecules and cytokines in TLR2 signaling pathway were detected by Q-PCR and ELISA. RESULTS: miR146a-inhibitor attenuated OVA-induced allergic asthma by increasing Th1 cytokines in OVA-induced allergic asthma model, and the treatment of miR146a-inhibitor can reduce the inflammation caused by asthma, followed by the down-regulation of IL-5 and IL-13 in sorted ILC2. The inhibition of miR-146a significantly reduced symptoms of asthma model with TLR2-related molecules being up-regulated. CONCLUSION: It was found that miR-146a is an important regulator in OVA-induced allergic asthma model, which can relieve symptoms of asthma through regulating TLR2 pathway. These findings provide a theoretical basis for solving asthma in clinical treatment.

GhFAD2-3 is required for anther development in Gossypium hirsutum.

BACKGROUND: In higher plants, the FAD2 gene encodes the microsomal oleate Δ12-desaturase, one of the key enzymes essential for the biosynthesis of the polyunsaturated lipids that serve many important functions in plant development and stress responses. FAD2 catalyzes the first step, in the biosynthesis of the polyunsaturated fatty acids (PUFAs) found in the cell membrane and cell wall, and it is thus of great importance to investigate the regulatory role of FAD2 in anther development. RESULTS: We reported the molecular characterization of the cotton (Gossypium hirsutum) GhFAD2 gene family and the essential role of GhFAD2-3 in cotton anther development. G. hirsutum contains four pairs of homoeologous FAD2 genes (GhFAD2-1 to GhFAD2-4). GhFAD2-3 is ubiquitously and relatively highly expressed in all analyzed tissues, particularly in anthers. Specific inhibition of GhFAD2-3 using the RNA interference approach resulted in male sterility due to impaired anther development at the stages from meiosis to maturation. The cellular phenotypic abnormality observed at the meiosis stage of the GhFAD2-3 silenced plant (fad2-3) coincides with the significant reduction of C18:2 in anthers at the same stage. Compared with that of the wild type (WT), the content of C18:1 was 41.48%, which increased by 5 fold in the fad2-3 anther at the pollen maturation stage. Moreover, the ratio of monounsaturated to polyunsaturated fatty acid was 5.43 in fad2-3 anther, which was much higher than that of the WT (only 0.39). Through compositional analysis of anthers cuticle and transcriptome data, we demonstrated it was unfavorable to the development of anther by regulating GhFAD2-3 expression level to increase the oleic acid content. CONCLUSIONS: Our work demonstrated the importance of C18:2 and/or C18:3 in the development of the pollen exine and anther cuticle in cotton and provided clue for further investigation of the physiological significance of the fatty acid composition for plant growth and development.

Online Workload Allocation via Fog-Fog-Cloud Cooperation to Reduce IoT Task Service Delay.

Fog computing has recently emerged as an extension of cloud computing in providing high-performance computing services for delay-sensitive Internet of Things (IoT) applications. By offloading tasks to a geographically proximal fog computing server instead of a remote cloud, the delay performance can be greatly improved. However, some IoT applications may still experience considerable delays, including queuing and computation delays, when huge amounts of tasks instantaneously feed into a resource-limited fog node. Accordingly, the cooperation among geographically close fog nodes and the cloud center is desired in fog computing with the ever-increasing computational demands from IoT applications. This paper investigates a workload allocation scheme in an IoT-fog-cloud cooperation system for reducing task service delay, aiming at satisfying as many as possible delay-sensitive IoT applications' quality of service (QoS) requirements. To this end, we first formulate the workload allocation problem in an IoT-edge-cloud cooperation system, which suggests optimal workload allocation among local fog node, neighboring fog node, and the cloud center to minimize task service delay. Then, the stability of the IoT-fog-cloud queueing system is theoretically analyzed with Lyapunov drift plus penalty theory. Based on the analytical results, we propose a delay-aware online workload allocation and scheduling (DAOWA) algorithm to achieve the goal of reducing long-term average task serve delay. Theoretical analysis and simulations have been conducted to demonstrate the efficiency of the proposal in task serve delay reduction and IoT-fog-cloud queueing system stability.

Magnified Image Spatial Spectrum (MISS) microscopy for nanometer and millisecond scale label-free imaging.

Label-free imaging of rapidly moving, sub-diffraction sized structures has important applications in both biology and material science, as it removes the limitations associated with fluorescence tagging. However, unlabeled nanoscale particles in suspension are difficult to image due to their transparency and fast Brownian motion. Here we describe a novel interferometric imaging technique referred to as Magnified Image Spatial Spectrum (MISS) microscopy, which overcomes these challenges. The MISS microscope provides quantitative phase information and enables dynamic light scattering investigations with an overall optical path length sensitivity of 0.95 nm at 833 frames per second acquisition rate. Using spatiotemporal filtering, we find that the sensitivity can be further pushed down to 10-3-10-2 nm. We demonstrate the instrument's capability through colloidal nanoparticle sizing down to 20 nm diameter and measurements of live neuron membrane dynamics. MISS microscopy is implemented as an upgrade module to an existing microscope, which converts it into a powerful light scattering instrument. Thus, we anticipate that MISS will be adopted broadly for both material and life sciences applications.

Separation and determination of peptide metabolite of Bacillus licheniformis in a microbial fuel cell by high-speed capillary micellar electrokinetic chromatography.

A method using high-speed capillary micellar electrokinetic chromatography and a microbial fuel cell was applied to determine the metabolite of the peptides released by Bacillus licheniformis. Two peptides, l-carnosine and l-alanyl-l-glutamine were used as the substrate to feed Bacillus licheniformis in a microbial fuel cell. The metabolism process of the bacterium was monitored by analyzing the voltage outputs of the microbial fuel cell. A home-made spontaneous injection device was applied to perform high-speed capillary micellar electrokinetic chromatography. Under the optimized conditions, tryptophan, glycine, valine, tyrosine and the two peptides could be rapidly separated within 2.5 min with micellar electrokinetic chromatography mode. Then the method was applied to analyze the solutions sampled from the microbial fuel cell. After 92 h running, valine, as the metabolite, was successfully detected with concentration 3.90 × 10-5 M. The results demonstrated that Bacillus licheniformis could convert l-carnosine and l-alanyl-l-glutamine into valine. The method employed in this work was proved to have great potential in analysis of metabolites, such as amino acids, for microorganisms.

Separation and detection of amino acid metabolites of Escherichia coli in microbial fuel cell with CE.

In this work, CE-LIF was employed to investigate the amino acid metabolites produced by Escherichia coli (E. coli) in microbial fuel cell (MFC). Two peptides, l-carnosine and l-alanyl-glycine, together with six amino acids, cystine, alanine, lysine, methionine, tyrosine, arginine were separated and detected in advance by a CE-LIF system coupled with a homemade spontaneous injection device. The injection device was devised to alleviate the effect of electrical discrimination for analytes during sample injection. All analytes could be completely separated within 8 min with detection limits of 20-300 nmol/L. Then this method was applied to analyze the substrate solution containing amino acid metabolites produced by E. coli. l-carnosine, l-alanyl-glycine, and cystine were used as the carbon, nitrogen, and sulfur source for the E. coli culture in the MFC to investigate the amino acid metabolites during metabolism. Two MFCs were used to compare the activity of metabolism of the bacteria. In the sample collected at the running time 200 h of MFC, the amino acid methionine was discovered as the metabolite with the concentrations 23.3 µg/L.

Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion.

Malignant pleural effusion (MPE) is associated with a poor prognosis in lung cancer. Currently, no effective cure exists for MPE. Chloroquine (CQ) has been demonstrated to induce vascular normalization and inhibit tumor growth. The aim of this study was to assess whether CQ affects MPE. The xenografts mice were divided into normal saline (NS), CQ, or bevacizumab (BE) group. Tumor growth and microvascular density (MVD) were monitored. We explored the effect of CQ on the proliferation, survival, and proangiogenic signaling of tumor cells in vitro. We further evaluated the effects of CQ on the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). A chicken chorioallantoic membrane (CAM) model was used to elucidate the effects of CQ on angiogenesis. Finally, an MPE mouse model were treated by CQ, BE, or NS. The volume of pleural effusion, tumor foci, and MVD was evaluated. CQ therapy group exhibited decreased tumor volume, tumor weight, and MVD in the mouse xenografts. CQ inhibited the proliferation of the tumor cells. However, the expression of vascular endothelial growth factor was not affected. Additionally, CQ inhibited the proliferation, migration, and tube formation of HUVECs and also restrained angiogenesis in the CAM. Western blot showed that CQ might suppress angiogenesis by downregulating p-Akt, Jagged1, and Ang2 in HUVECs. In MPE mice, the volume of the pleural effusion, the number of pleural tumor foci, and the MVD were significantly reduced in the CQ group. Our work demonstrated that CQ played the role of an efficient treatment for MPE.