Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions.

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

VIOLET: Visual Analytics for Explainable Quantum Neural Networks.

With the rapid development of Quantum Machine Learning, quantum neural networks (QNN) have experienced great advancement in the past few years, harnessing the advantages of quantum computing to significantly speed up classical machine learning tasks. Despite their increasing popularity, the quantum neural network is quite counter-intuitive and difficult to understand, due to their unique quantum-specific layers (e.g., data encoding and measurement) in their architecture. It prevents QNN users and researchers from effectively understanding its inner workings and exploring the model training status. To fill the research gap, we propose VIOLET, a novel visual analytics approach to improve the explainability of quantum neural networks. Guided by the design requirements distilled from the interviews with domain experts and the literature survey, we developed three visualization views: the Encoder View unveils the process of converting classical input data into quantum states, the Ansatz View reveals the temporal evolution of quantum states in the training process, and the Feature View displays the features a QNN has learned after the training process. Two novel visual designs, i.e., satellite chart and augmented heatmap, are proposed to visually explain the variational parameters and quantum circuit measurements respectively. We evaluate VIOLET through two case studies and in-depth interviews with 12 domain experts. The results demonstrate the effectiveness and usability of VIOLET in helping QNN users and developers intuitively understand and explore quantum neural networks.

In Vivo Imaging of γ-Glutamyl Transferase in Cardiovascular Diseases with a Photoacoustic Probe.

In this work, a photoacoustic (PA) probe, HDS-GGT, was developed for the in vivo imaging of cardiovascular diseases by monitoring the γ-glutamyl transferase (GGT) dynamics. HDS-GGT exhibited a stable PA signal with auxiliary absorbance and NIRF variation after the trigger by GGT. In all three modalities of absorbance, NIRF, and PA, HDS-GGT could quantitatively reflect the GGT level. In PA modality, HDS-GGT indicated the practical advantages including high sensitivity, high stability, and high specificity. In living oxidized low-density lipoprotein-induced RAW264.7 cells, HDS-GGT indicated proper capability for imaging the plaques by visualizing the GGT dynamics. Moreover, during imaging in living model mice, HDS-GGT was achieved to distinguish the plaques from healthy blood vessels via a multiview PA presentation. HDS-GGT could also suggest the severity of plaques in the extracted aorta from the model mice, which was consistent with the histological staining results. The information herein might be useful for future investigations on cardiovascular diseases.

Promoting In Vivo NIR-II Fluorescent Imaging for Lipid in Lipid Metabolism Diseases Diagnosis.

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.

Association between body roundness index and risk of ultrasound-defined non-alcoholic fatty liver disease.

Objectives: While several indicators have been studied, the association of body roundness index (BRI) with non-alcoholic fatty liver disease (NAFLD) remains unclear. We aimed to explore the association between BRI and ultrasound-defined NAFLD. Methods: The sample dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2017-2018. The diagnosis of NAFLD was determined based on the controlled attenuated parameter (CAP≥248 dB/m) score of liver ultrasound transient elastography (LUTE). Participants with excessive alcohol use and viral hepatitis were excluded. To delve deeper into the relationship, Multivariable logistic regression with adjustment for confounding variables and smoothing curve analysis was used to investigate the association and nonlinear relationships between BRI and NAFLD. Results: Among 4210 individuals aged 20 years or older included in the study, 28.2 % had NAFLD. Compared to the first tertile, BRI notably increased the risk of NAFLD 3.53-fold [95 % confidence interval (CI) = 2.73-4.57] in the second tertile and 7.00-fold (95%CI = 5.29-9.27) in the third tertile after adjusting for multiple covariates (P for trend <0.001). Furthermore, when BRI was treated as a continuous variable, one unit of increment in BRI was associated with 41 % higher odds of NAFLD [adjusted odds ratio (aOR) = 1.41; 95%CI = 1.34-1.48; P < 0.001]. The associations of BRI with NAFLD persisted in all subgroup analyses. A smoothing curve fitting demonstrated that the relationship between BRI and NAFLD was a nonlinear connection. The risk of NAFLD increased significantly when BRI was lower than 4.82, after which the curve showed a modest ascent. Conclusion: Higher BRI was consistently associated with an increased risk of NAFLD in US adults. BRI is a risk factor for NAFLD, and there is an imperative to give more attention to lowering the BRI.

Effect of Short Bouts of Vigorous Stair Climbing on Cardiorespiratory Fitness in Women with Overweight and Obesity: A Pilot Feasibility Study.

Background: We examined the effect of 4 weeks of a brief vigorous stair climbing exercise on cardiorespiratory fitness (CRF) and body composition in women with overweight or obesity. Methods: Twenty-six participants (age, 25.4±4.9 years; body mass index [BMI], 25.3±1.8 kg/m2) were randomly assigned to either a stair climbing exercise group (n=13) or a non-exercising control group (n=13). The stair climbing exercise group performed 20 sessions (supervised, five sessions/week over 4 weeks) of brief intermittent stair climbing exercise consisting of a 3-minute warm-up followed by three bouts of 20 seconds of stair climbing (≥80% of age-predicted maximum heart rate) interspersed with 2-minute recovery periods (total exercise duration=10 minutes/session). Peak oxygen uptake (VO2peak) was measured using a graded maximal treadmill test with the use of a standard open-circuit spirometry technique. Body composition was assessed with bioelectrical impedance analysis. Results: All participants, except one who dropped out due to coronavirus disease 2019 (COVID-19) infection, completed the study with 100% attendance rates. There were significant interaction effects (group×time) on body weight, BMI, waist circumference, and CRF such that the stair climbing exercise group had significant (P≤0.01) reductions in body weight (66.5±4.6 to 65.2±4.6 kg), BMI (24.8±1.2 to 24.4±1.1 kg/m2), and waist circumference (78.0±3.7 to 76.5±4.1 cm) and improvements in VO2peak (31.6±2.5 to 34.9±2.6 mL/kg/min) compared with controls. Conclusion: Short bouts of vigorous stair climbing is a feasible and time-efficient exercise strategy for improving CRF in previously sedentary, young women with overweight and obesity.

Near-infrared imaging of hepatocellular carcinoma and its medicinal treatment with a γ-glutamyl transpeptidase-monitoring fluorescence probe.

Herein, the Near-infrared imaging of hepatocellular carcinoma (HCC) and its medicinal treatment was achieved with a γ-glutamyl transpeptidase (GGT)-monitoring fluorescence probe KYZ-GGT which consisted of the typical recognition group γ-glutamyl and the structurally modified signal reporting group hemicyanine-thioxanthene. Compared with the recently reported probes, KYZ-GGT suggested practical and steady capability for monitoring the GGT level in the cellular, xenograft, induced as well as medicinal treatment HCC models. It realized the mitochondrial targeting intracellular imaging to reflect the GGT dynamics in the induction or medicinal treatment of HCC. In the xenograft and induced model mice with multiple factors, KYZ-GGT showed stable performance for visualizing the HCC status. In the medicinal treatment of the long-period-induced HCC model mice verified by the serum indexes and histopathological analysis, KYZ-GGT successfully imaged the medicinal treatment process of HCC with two marketed drugs (Sorafenib and Lenvatinib) respectively, with an applicative penetration depth. The information here was meaningful for investigating effective medicinal strategies for overcoming HCC.

Imaging Investigation of Hepatocellular Carcinoma Progress via Monitoring γ-Glutamyltranspeptidase Level with a Near-Infrared Fluorescence/Photoacoustic Bimodal Probe.

Hepatocellular carcinoma (HCC) is one of the main principal causes of cancer death, and the late definite diagnosis limits therapeutic approaches in time. The early diagnosis of HCC is essential, and the previous investigations on the biomarkers inferred that the γ-glutamyltranspeptidase (GGT) level could indicate the HCC process. Herein, a near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal probe, CySO3-GGT, was developed for monitoring the GGT level and thus to image the HCC process. After the in-solution tests, the bimodal response was convinced. The various HCC processes were imaged by CySO3-GGT at the cellular level. Then, the CCl4-induced HCC (both induction and treatment) and the subcutaneous and orthotopic xenograft mice models were selected. All throughout the tests, CySO3-GGT achieved NIRF and PA bimodal imaging of the HCC process. In particular, CySO3-GGT could effectively realize 3D imaging of the HCC nodule by visualizing the boundary between the tumor and the normal tissue. The information here might offer significant guidance for the dynamic monitoring of HCC in the near future.

Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.

DiffSeer: Difference-Based Dynamic Weighted Graph Visualization.

Existing dynamic weighted graph visualization approaches rely on users' mental comparison to perceive temporal evolution of dynamic weighted graphs, hindering users from effectively analyzing changes across multiple timeslices. We propose DiffSeer, a novel approach for dynamic weighted graph visualization by explicitly visualizing the differences of graph structures (e.g., edge weight differences) between adjacent timeslices. Specifically, we present a novel nested matrix design that overviews the graph structure differences over a time period as well as shows graph structure details in the timeslices of user interest. By collectively considering the overall temporal evolution and structure details in each timeslice, an optimization-based node reordering strategy is developed to group nodes with similar evolution patterns and highlight interesting graph structure details in each timeslice. We conducted two case studies on real-world graph datasets and in-depth interviews with 12 target users to evaluate DiffSeer. The results demonstrate its effectiveness in visualizing dynamic weighted graphs.

TriPlan: an interactive visual analytics approach for better tourism route planning.

Abstract: Continuous research and development of novel tourism routes is necessary for tourism service providers to improve the tourist experience and industrial competitiveness. However, the route planning is cumbersome due to the time-consuming, extensive, and costly field study. Most of the existing route planning studies focus on recommending tourism routes for users based on attraction characteristics or tourist behavior features, which are generally unexplainable due to the black-box approaches they use. Other solutions allow users to customize itineraries through an interactive interface but often lack guidance from the aspect of route evaluation or destination image perception. In this paper, we thoroughly discuss the requirements and design tasks with domain experts and propose TriPlan, an interactive visual analytics system that provides intuitive planning guidance for tourism product developers. We design and improve multiple coordinated visualizations to facilitate analysis from the perspectives of overall route pattern and individual destination image. We also develop a hierarchical planning view to display the structural information of a plan. In addition, we introduce an automatic route optimization algorithm and multiple interactions to assist users in optimizing and adjusting the itineraries. Finally, we evaluate the usability and effectiveness of our system through three case studies and quantitative and qualitative interviews with the domain experts on real-world datasets.

Pesticide residues in the pollen and nectar of oilseed rape (Brassica napus L.) and their potential risks to honey bees.

Research evidence suggests that pesticide residues are one of the leading potential causes of the decline in pollinators, especially during vulnerable periods such as foraging in the early springtime. In China, no research quantifies pesticide residues in the nectar and pollen of honey bee colonies during this period or examines the potential risks and toxicity of pesticides to honey bees. Oilseed rape is one of the first and primary bee-attractive plants in most parts of China. Here, we investigated the pesticide residues in the oilseed rape of the years 2017 and 2018 in China. The hazard quotient (HQ) from pollen and nectar and the BeeREX risk assessment were used to evaluate the potential risks of the pesticide residues to honey bees. We detected 48 pesticides in pollen samples and 34 chemicals in nectar samples. The maximum pollen HQ (PHQ) values (contact or oral) ranged from 0.16 to 706,421, and the maximum nectar HQ (NHQ) values (contact or oral) ranged from 0.07 to 185,135. In particular, carbofuran, cyfluthrin, deltamethrin, and fenpropathrin have relatively high PHQ and NHQ values. Our results indicated that further investigation of nearly half of the tested compounds is needed because their PHQ or NHQ values are more than 50. Especially cyfluthrin and carbofuran need advanced tier assessment due to their maximum RQ (risk quotient) values exceeding the level of concern. These results provide valuable guidance for protecting bees and other pollinators in China.

Wireless Self-Powered High-Performance Integrated Nanostructured-Gas-Sensor Network for Future Smart Homes.

The accelerated evolution of communication platforms including Internet of Things (IoT) and the fifth generation (5G) wireless communication network makes it possible to build intelligent gas sensor networks for real-time monitoring chemical safety and personal health. However, this application scenario requires a challenging combination of characteristics of gas sensors including small formfactor, low cost, ultralow power consumption, superior sensitivity, and high intelligence. Herein, self-powered integrated nanostructured-gas-sensor (SINGOR) systems and a wirelessly connected SINGOR network are demonstrated here. The room-temperature operated SINGOR system can be self-driven by indoor light with a Si solar cell, and it features ultrahigh sensitivity to H2, formaldehyde, toluene, and acetone with the record low limits of detection (LOD) of 10, 2, 1, and 1 ppb, respectively. Each SINGOR consisting of an array of nanostructured sensors has the capability of gas pattern recognition and classification. Furthermore, multiple SINGOR systems are wirelessly connected as a sensor network, which has successfully demonstrated flammable gas leakage detection and alarm function. They can also achieve gas leakage localization with satisfactory precision when deployed in one single room. These successes promote the development of using nanostructured-gas-sensor network for wide range applications including smart home/building and future smart city.

Bottom-up de novo design of functional proteins with complex structural features.

De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structures. Here, we used a bottom-up approach to build de novo proteins tailored to accommodate structurally complex functional motifs. We applied the bottom-up strategy to successfully design five folds for four distinct binding motifs, including a bifunctionalized protein with two motifs. Crystal structures confirmed the atomic-level accuracy of the computational designs. These de novo proteins were functional as components of biosensors to monitor antibody responses and as orthogonal ligands to modulate synthetic signaling receptors in engineered mammalian cells. Our work demonstrates the potential of bottom-up approaches to accommodate complex structural motifs, which will be essential to endow de novo proteins with elaborate biochemical functions, such as molecular recognition or catalysis.

Tectoridin inhibits osteoclastogenesis and bone loss in a murine model of ovariectomy-induced osteoporosis.

Osteoporosis is a systemic disease that typically affects older adults and that remains a major threat to global public health owing to its high morbidity and mortality rates. In those with osteoporosis, excess osteoclast (OC)-mediated resorption of bone tissue can lead to an imbalance in normal bone metabolism resulting in the onset of diseases including postmenopausal osteoporosis (PMOP). In the present study, we found that the natural Belamcanda chinensis (L.) DC derivative tectoridin can reduce bone loss in ovariectomized mice. TRAP staining further revealed that tectoridin suppresses OC differentiation in a dose-dependent fashion, and qPCR analyses indicated that this compound also dose-dependently inhibits the RANKL-induced upregulation of OC marker genes including Trap, Ctsk, ATP60, DC-Stamp, c-Fos, and NFATc1 in bone marrow macrophages (BMMs). Tectoridin treatment further suppressed actin ring formation and in vitro bone resorption as determined via F-actin staining and scanning electron microscopy. At the mechanistic level, we found that tectoridin was capable of inhibiting osteoclastogenesis at least in part owing to its ability to interfere with NF-κB pathway activation. In addition, we confirmed that tectoridin was able to protect against in vivo estrogen-deficiency-associated bone loss. Together, these results suggest that tectoridin can inhibit osteoclastogenesis and OC functionality in the context of PMOP at least in part via modulating RANKL-induced NF-κB signaling.

Upregulation of miR-92a contributes to blocking goblet cell metaplasia by targeting MUC5AC in asthma.

As a chronic airway disease, asthma has two characteristics, tissue remodeling and airway inflammation. This research focused on miR-92a to explore how it works in asthma. We revealed that the expressions of miR-92a were decreased in both serum and lung tissues from ovalbumin-induced asthma mouse. Bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and dual luciferase assay revealed that miR-92a targets MUC5AC, which was linked to mucus hypersecretion in the pulmonary tracts. By injecting miR-92a-mimics into the trachea, both the airway hyper-reactivity and airway inflammation can be alleviated in an asthma mouse model which is induced by ovalbumin. Moreover, the goblet cell phenotype of asthmatic mice is significantly reduced by the action of miR-92a. Furthermore, miR-92a blocked interleukin (IL)-13-induced MUC5AC luciferase activity in 16HBE. Together, upregulation of miR-92a expression in asthmatic mice plays a role in blocking goblet cell metaplasia by targeting MUC5AC, and thus in the treatment of chronic airway diseases, miR-92a can prevent epithelial remodeling, which is a reasonable method.

De novo protein design enables the precise induction of RSV-neutralizing antibodies.

De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo-designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused preexisting antibody responses toward defined neutralization epitopes. Overall, our design approach opens the possibility of targeting specific epitopes for the development of vaccines and therapeutic antibodies and, more generally, will be applicable to the design of de novo proteins displaying complex functional motifs.

Continuous-wave and pulsed 1,066-nm Nd:Gd0.69Y0.3TaO4 laser directly pumped by a 879-nm laser diode.

We demonstrated an 879-nm-diode-pumped Nd:Gd0.69Y0.3TaO4 laser in continuous-wave-(CW), pulse-pumped, pulse-reflection-mode Q-switched, and cavity-dumped burst-mode Q-switched operations for the first time. A maximum output power of 9.3 W at 1,066 nm was obtained in the CW operation with a slope efficiency of ~48%. The slope efficiency reached the value of ~68% in the pulse-pumped operation. A peak power of 150 kW and pulse width of 3.4 ns were obtained in the cavity-dumped burst-mode Q-switched operation at a Q-switching repetition rate of 20 kHz.

Emodin suppresses cadmium-induced osteoporosis by inhibiting osteoclast formation.

Environmental level of cadmium (Cd) exposure can induce bone loss. Emodin, a naturally compound found in Asian herbal medicines, could influence osteoblast/osteoclast differentiation. However, the effects of emodin on Cd-induced bone damage are not clarified. The aim of this study was to investigate the role of emodin on Cd-induced osteoporosis. Sprague-Dawley male rats were divided into three groups which were given 0mg/L, 50mg Cd/L and 50mg Cd/L plus emodin (50mg/kg body weight). Bone histological investigation, microCT analysis, metabolic biomarker determination and immunohistochemical staining were performed at the 12th week. The bone mass and bone microstructure index of rats treated with Cd were obviously lower than in control. Cd markedly enhanced the osteoclast formation compared with control. Emodin significantly abolished the Cd-induced bone microstructure damage (p<0.05), osteoclast formation and increase of tartrate-resistant acid phosphatase 5b level (p<0.05). Our data further showed that emodin attenuated the Cd-induced inhibition of osteoprotegerin expression and stimulation of receptor activator for nuclear factor-κ B ligand expression. Our data show that emodin suppresses the Cd-induced osteoporosis by inhibiting osteoclast formation.