Bioinspired, vertically stacked, and perovskite nanocrystal-enhanced CMOS imaging sensors for resolving UV spectral signatures.

Imaging and identifying target signatures and biomedical markers in the ultraviolet (UV) spectrum is broadly important to medical imaging, military target tracking, remote sensing, and industrial automation. However, current silicon-based imaging sensors are fundamentally limited because of the rapid absorption and attenuation of UV light, hindering their ability to resolve UV spectral signatures. Here, we present a bioinspired imaging sensor capable of wavelength-resolved imaging in the UV range. Inspired by the UV-sensitive visual system of the Papilio xuthus butterfly, the sensor monolithically combines vertically stacked photodiodes and perovskite nanocrystals. This imaging design combines two complementary UV detection mechanisms: The nanocrystal layer converts a portion of UV signals into visible fluorescence, detected by the photodiode array, while the remaining UV light is detected by the top photodiode. Our label-free UV fluorescence imaging data from aromatic amino acids and cancer/normal cells enables real-time differentiation of these biomedical materials with 99% confidence.

Fluorescence-guided surgical system using holographic display: from phantom studies to canine patients.

Significance: Holographic display technology is a promising area of research that can lead to significant advancements in cancer surgery. We present the benefits of combining bioinspired multispectral imaging technology with holographic goggles for fluorescence-guided cancer surgery. Through a series of experiments with 43D-printed phantoms, small animal models of cancer, and surgeries on canine patients with head and neck cancer, we showcase the advantages of this holistic approach. Aim: The aim of our study is to demonstrate the feasibility and potential benefits of utilizing holographic display for fluorescence-guided surgery through a series of experiments involving 3D-printed phantoms and canine patients with head and neck cancer. Approach: We explore the integration of a bioinspired camera with a mixed reality headset to project fluorescent images as holograms onto a see-through display, and we demonstrate the potential benefits of this technology through benchtop and in vivo animal studies. Results: Our complete imaging and holographic display system showcased improved delineation of fluorescent targets in phantoms compared with the 2D monitor display approach and easy integration into the veterinarian surgical workflow. Conclusions: Based on our findings, it is evident that our comprehensive approach, which combines a bioinspired multispectral imaging sensor with holographic goggles, holds promise in enhancing the presentation of fluorescent information to surgeons during intraoperative scenarios while minimizing disruptions.

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery.

Significance: Fluorescently guided minimally invasive surgery is improving patient outcomes and disease-free survival, but biomarker variability hinders complete tumor resection with single molecular probes. To overcome this, we developed a bioinspired endoscopic system that images multiple tumor-targeted probes, quantifies volumetric ratios in cancer models, and detects tumors in ex vivo samples. Aim: We present a new rigid endoscopic imaging system (EIS) that can capture color images while simultaneously resolving two near-infrared (NIR) probes. Approach: Our optimized EIS integrates a hexa-chromatic image sensor, a rigid endoscope optimized for NIR-color imaging, and a custom illumination fiber bundle. Results: Our optimized EIS achieves a 60% improvement in NIR spatial resolution when compared to a leading FDA-approved endoscope. Ratio-metric imaging of two tumor-targeted probes is demonstrated in vials and animal models of breast cancer. Clinical data gathered from fluorescently tagged lung cancer samples on the operating room's back table demonstrate a high tumor-to-background ratio and consistency with the vial experiments. Conclusions: We investigate key engineering breakthroughs for the single-chip endoscopic system, which can capture and distinguish numerous tumor-targeting fluorophores. As the molecular imaging field shifts toward a multi-tumor targeted probe methodology, our imaging instrument can aid in assessing these concepts during surgical procedures.

Angle of polarization calibration for omnidirectional polarization cameras.

Polarization cameras quantify one of the fundamental properties of light and capture intrinsic properties of the imaged environment that are otherwise omitted by color sensors. Many polarization applications, such as underwater geolocalization and sky-based polarization compass, require simultaneous imaging of the entire radial optical field with omnidirectional lenses. However, the reconstructed angle of polarization captured with omnidirectional lenses has a radial offset due to redirection of the light rays within these lenses. In this paper, we describe a calibration method for correcting angle of polarization images captured with omnidirectional lenses. Our calibration method reduces the variance of reconstructed angle of polarization from 76.2 ∘ to 4.1 ∘. Example images collected both on an optical bench and in nature, demonstrate the improved accuracy of the reconstructed angle of polarization with our calibration method. The improved accuracy in the angle of polarization images will aid the development of polarization-based applications with omnidirectional lenses.

Protease-activated indocyanine green nanoprobes for intraoperative NIR fluorescence imaging of primary tumors.

Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.

Decoupling channel count from field of view and spatial resolution in single-sensor imaging systems for fluorescence image-guided surgery.

Significance: Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important. Aim: Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff. Approach: In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer. Results: We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making. Conclusions: These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.

Hexachromatic bioinspired camera for image-guided cancer surgery.

Cancer affects one in three people worldwide. Surgery remains the primary curative option for localized cancers, but good prognoses require complete removal of primary tumors and timely recognition of metastases. To expand surgical capabilities and enhance patient outcomes, we developed a six-channel color/near-infrared image sensor inspired by the mantis shrimp visual system that enabled near-infrared fluorescence image guidance during surgery. The mantis shrimp's unique eye, which maximizes the number of photons contributing to and the amount of information contained in each glimpse of its surroundings, is recapitulated in our single-chip imaging system that integrates arrays of vertically stacked silicon photodetectors and pixelated spectral filters. To provide information about tumor location unavailable from a single instrument, we tuned three color channels to permit an intuitive perspective of the surgical procedure and three near-infrared channels to permit multifunctional imaging of optical probes highlighting cancerous tissue. In nude athymic mice bearing human prostate tumors, our image sensor enabled simultaneous detection of two tumor-targeted fluorophores, distinguishing diseased from healthy tissue in an estimated 92% of cases. It also permitted extraction of near-infrared structured illumination enabling the mapping of the three-dimensional topography of tumors and surgical sites to within 1.2-mm error. In the operating room, during surgical resection in 18 patients with breast cancer, our image sensor further enabled sentinel lymph node mapping using clinically approved near-infrared fluorophores. The flexibility and performance afforded by this simple and compact architecture highlights the benefits of biologically inspired sensors in image-guided surgery.

Short-term Effect of Air Pollution on Tuberculosis Based on Kriged Data: A Time-series Analysis.

Tuberculosis (TB) has a very high mortality rate worldwide. However, only a few studies have examined the associations between short-term exposure to air pollution and TB incidence. Our objectives were to estimate associations between short-term exposure to air pollutants and TB incidence in Wuhan city, China, during the 2015-2016 period. We applied a generalized additive model to access the short-term association of air pollution with TB. Daily exposure to each air pollutant in Wuhan was determined using ordinary kriging. The air pollutants included in the analysis were particulate matter (PM) with an aerodynamic diameter less than or equal to 2.5 micrometers (PM2.5), PM with an aerodynamic diameter less than or equal to 10 micrometers (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ground-level ozone (O3). Daily incident cases of TB were obtained from the Hubei Provincial Center for Disease Control and Prevention (Hubei CDC). Both single- and multiple-pollutant models were used to examine the associations between air pollution and TB. Seasonal variation was assessed by splitting the all-year data into warm (May-October) and cold (November-April) seasons. In the single-pollutant model, for a 10 µg/m3 increase in PM2.5, PM10, and O3 at lag 7, the associated TB risk increased by 17.03% (95% CI: 6.39, 28.74), 11.08% (95% CI: 6.39, 28.74), and 16.15% (95% CI: 1.88, 32.42), respectively. In the multi-pollutant model, the effect of PM2.5 on TB remained statistically significant, while the effects of other pollutants were attenuated. The seasonal analysis showed that there was not much difference regarding the impact of air pollution on TB between the warm season and the cold season. Our study reveals that the mechanism linking air pollution and TB is still complex. Further research is warranted to explore the interaction of air pollution and TB.

Impact of Ambient Temperature and Relative Humidity on the Incidence of Hand-Foot-Mouth Disease in Wuhan, China.

Background: Few studies have previously explored the relationship between hand, foot, and mouth disease (HFMD) and meteorological factors with the effect modification of air pollution, and these studies had inconsistent findings. We therefore applied a time-series analysis assessing the effects of temperature and humidity on the incidence of HFMD in Wuhan, China to deepen our understanding of the relationship between meteorological factors and the risk of HFMD. Methods: Daily HFMD cases were retrieved from Hubei Provincial Center for Disease Control and Prevention from 1 February 2013 to 31 January 2017. Daily meteorological data including 24 h average temperature, relative humidity, wind velocity, and atmospheric pressure were obtained from Hubei Meteorological Bureau. Data on Air pollution was collected from 10 national air-monitoring stations in Wuhan city. We adopted a distributed lag non-linear model (DLNM) combined with Poisson regression and time-series analysis to estimate the effects of temperature and relative humidity on the incidence HFMD. Results: We found that the association between temperature and HFMD incidence was non-linear, exhibiting an approximate "M" shape with two peaks occurring at 2.3 °C (RR = 1.760, 95% CI: 1.218-2.542) and 27.9 °C (RR = 1.945, 95% CI: 1.570-2.408), respectively. We observed an inverted "V" shape between relative humidity and HFMD. The risk of HFMD reached a maximum value at a relative humidity of 89.2% (RR = 1.553, 95% CI: 1.322-1.824). The largest delayed cumulative effects occurred at lag 6 for temperature and lag 13 for relative humidity. Conclusions: The non-linear relationship between meteorological factors and the incidence of HFMD on different lag days could be used in the early targeted warning system of infectious diseases, reducing the possible outbreaks and burdens of HFMD among sensitive populations.

The association between short-term exposure to ambient air pollution and the incidence of mumps in Wuhan, China: A time-series study.

BACKGROUND: Previous studies have estimated the association between meteorological factors and mumps outbreaks without assessing the influence of air pollution. In this research, we explored the effects of short-term exposure to air pollution on the incidence of mumps. METHODS: Our time-series analysis was conducted using data collected in Wuhan, China from 2015 to 2017. Daily number of mumps cases was obtained from Disease Reporting System in Hubei Provincial Center for Disease Control and Prevention. Data on air pollution was obtained from 10 national air quality monitoring stations, including nitrogen dioxide (NO2), sulfur dioxide (SO2), ground-level ozone (O3), particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10), and particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5). Daily meteorological data including temperature and relative humidity were obtained from Hubei Meteorological Bureau. We performed a Poisson regression in generalized additive models (GAM) to explore the association between the incidence of mumps and exposure to air pollution. RESULTS: We observed that the effects of air pollutants were statistically significant mainly in two periods, lag 0 to lag 5 and lag 20 to lag 25, with the strongest effects appearing at lag 2 and lag 23. The cumulative effects were stronger than single-day lag effects. The stratified analysis showed the effect of pollutants during the hot season was stronger than that during the cold season, especially for NO2 and SO2. CONCLUSIONS: We found that exposure to NO2 and SO2 was significantly associated with higher risk of developing mumps. Our findings could help deepen the understanding of how air pollution exposure affects the incidence of mumps.

The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses.

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 µg/m3 increment in SO2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.

Ground Level PM2.5 Estimates over China Using Satellite-Based Geographically Weighted Regression (GWR) Models Are Improved by Including NO2 and Enhanced Vegetation Index (EVI).

Highly accurate data on the spatial distribution of ambient fine particulate matter (<2.5 µm: PM2.5) is currently quite limited in China. By introducing NO2 and Enhanced Vegetation Index (EVI) into the Geographically Weighted Regression (GWR) model, a newly developed GWR model combined with a fused Aerosol Optical Depth (AOD) product and meteorological parameters could explain approximately 87% of the variability in the corresponding PM2.5 mass concentrations. There existed obvious increase in the estimation accuracy against the original GWR model without NO2 and EVI, where cross-validation R² increased from 0.77 to 0.87. Both models tended to overestimate when measurement is low and underestimate when high, where the exact boundary value depended greatly on the dependent variable. There was still severe PM2.5 pollution in many residential areas until 2015; however, policy-driven energy conservation and emission reduction not only reduced the severity of PM2.5 pollution but also its spatial range, to a certain extent, from 2014 to 2015. The accuracy of satellite-derived PM2.5 still has limitations for regions with insufficient ground monitoring stations and desert areas. Generally, the use of NO2 and EVI in GWR models could more effectively estimate PM2.5 at the national scale than previous GWR models. The results in this study could provide a reasonable reference for assessing health impacts, and could be used to examine the effectiveness of emission control strategies under implementation in China.

Real-Time Estimation of Satellite-Derived PM2.5 Based on a Semi-Physical Geographically Weighted Regression Model.

The real-time estimation of ambient particulate matter with diameter no greater than 2.5 µm (PM2.5) is currently quite limited in China. A semi-physical geographically weighted regression (GWR) model was adopted to estimate PM2.5 mass concentrations at national scale using the Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth product fused by the Dark Target (DT) and Deep Blue (DB) algorithms, combined with meteorological parameters. The fitting results could explain over 80% of the variability in the corresponding PM2.5 mass concentrations, and the estimation tends to overestimate when measurement is low and tends to underestimate when measurement is high. Based on World Health Organization standards, results indicate that most regions in China suffered severe PM2.5 pollution during winter. Seasonal average mass concentrations of PM2.5 predicted by the model indicate that residential regions, namely Jing-Jin-Ji Region and Central China, were faced with challenge from fine particles. Moreover, estimation deviation caused primarily by the spatially uneven distribution of monitoring sites and the changes of elevation in a relatively small region has been discussed. In summary, real-time PM2.5 was estimated effectively by the satellite-based semi-physical GWR model, and the results could provide reasonable references for assessing health impacts and offer guidance on air quality management in China.

Characteristics of Fine Particles in an Urban Atmosphere-Relationships with Meteorological Parameters and Trace Gases.

Atmospheric fine particles (diameter < 1 µm) attract a growing global health concern and have increased in urban areas that have a strong link to nucleation, traffic emissions, and industrial emissions. To reveal the characteristics of fine particles in an industrial city of a developing country, two-year measurements of particle number size distribution (15.1 nm-661 nm), meteorological parameters, and trace gases were made in the city of Wuhan located in central China from June 2012 to May 2014. The annual average particle number concentrations in the nucleation mode (15.1 nm-30 nm), Aitken mode (30 nm-100 nm), and accumulation mode (100 nm-661 nm) reached 4923 cm(-3), 12193 cm(-3) and 4801 cm(-3), respectively. Based on Pearson coefficients between particle number concentrations and meteorological parameters, precipitation and temperature both had significantly negative relationships with particle number concentrations, whereas atmospheric pressure was positively correlated with the particle number concentrations. The diurnal variation of number concentration in nucleation mode particles correlated closely with photochemical processes in all four seasons. At the same time, distinct growth of particles from nucleation mode to Aitken mode was only found in spring, summer, and autumn. The two peaks of Aitken mode and accumulation mode particles in morning and evening corresponded obviously to traffic exhaust emissions peaks. A phenomenon of "repeated, short-lived" nucleation events have been created to explain the durability of high particle concentrations, which was instigated by exogenous pollutants, during winter in a case analysis of Wuhan. Measurements of hourly trace gases and segmental meteorological factors were applied as proxies for complex chemical reactions and dense industrial activities. The results of this study offer reasonable estimations of particle impacts and provide references for emissions control strategies in industrial cities of developing countries.

Spatial and temporal characteristics of insulator contaminations revealed by daily observations of equivalent salt deposit density.

The accurate estimation of deposits adhering on insulators is of great significance to prevent pollution flashovers which cause huge costs worldwide. Researchers have developed sensors using different technologies to monitor insulator contamination on a fine time scale. However, there is lack of analysis of these data to reveal spatial and temporal characteristics of insulator contamination, and as a result the scheduling of periodical maintenance of power facilities is highly dependent on personal experience. Owing to the deployment of novel sensors, daily Equivalent Salt Deposit Density (ESDD) observations of over two years were collected and analyzed for the first time. Results from 16 sites distributed in four regions of Hubei demonstrated that spatial heterogeneity can be seen at both the fine and coarse geographical scales, suggesting that current polluted area maps are necessary but are not sufficient conditions to guide the maintenance of power facilities. Both the local emission and the regional air pollution condition exert evident influences on deposit accumulation. A relationship between ESDD and PM10 was revealed by using regression analysis, proving that air pollution exerts influence on pollution accumulations on insulators. Moreover, the seasonality of ESDD was discovered for the first time by means of time series analysis, which could help engineers select appropriate times to clean the contamination. Besides, the trend component shows that the ESDD increases in a negative exponential fashion with the accumulation date (ESDD = a - b × exp(-time)) at a long time scale in real environments.

Analysis of photosynthetically active radiation in Northwest China from observation and estimation.

Photosynthetically active radiation (PAR) observed at Fukang, China from 2005 to 2012 was used to investigate PAR variability and its relationship with global solar radiation (G) under various sky conditions in Northwest China. Clearness index (K t) was used for characterizing the sky conditions and model development; it was discovered that daily PAR/G (F p) generally increased from 1.79 ± 0.016 mol MJ(-1) in November to 1.95 ± 0.004 mol MJ(-1) in July with annual average being about 1.89 mol MJ(-1); F p generally decreased with sky conditions changing from overcast skies to clear skies in each month. Meanwhile, an efficient all-sky PAR model under any sky conditions has been proposed by investigating the dependence of hourly PAR on K t and cosine of solar zenith angle µ. The model was assessed through the statistical indices: mean bias error (MBE), mean absolute error (MAE), and root-mean-square error (RMSE) whose values were only -0.34% (-1.75%), 3.62% (3.47%), and 5.52% (4.79 %), respectively, at hourly (daily) basis. The model has also been tested at three other four sites with distinctly different climates in China. Finally, PAR values during 1961-2012 in Northwest China were reconstructed and annual mean daily PAR was 29.25 mol m(-2) d(-1). PAR decreased at 0.18 mol m(-2) d(-1) per decade during 1961-2012, and the decreases were sharpest in spring (0.63 mol m(-2) d(-1) per decade). The possible reasons for the long-term variability have also been analyzed, which will lay foundations for cloud effect study in the near future.

[Study progress on triterpenoids from Ganoderma lucidum].

In this review, recent progress in the extraction and purification, and the chemical composition analysis of triterpenoids from Ganoderma lucidum was summarized. Triterpenoids are an important class of active components in G. lucidum. Because of its low content, complex procedures of extraction and purification, the preparation of high purity triterpenoids from G. lucidum is currently limited at the laboratory scale. This review discussed the industrial preparation of triterpenoids, aiming to promote the industrial development of G. lucidum, and to provide scientific basis for its study, production, and application in health food and medicine.

Simple multiscale algorithm for layer detection with lidar.

Lidar is a powerful active remote sensing device used in the detection of the optical properties of aerosols and clouds. However, there are difficulties in layer detection and classification. Many previous methods are too complex for large dataset analysis or limited to data with too high a signal-to-noise ratio (SNR). In this study, a mechanism of multiscale detection and overdetection rejection is proposed based on a trend index function that we define. Finally, we classify layers based on connected layers employing a quantity known as the threshold of the peak-to-base ratio. We find good consistency between retrieved results employing our method and visual analysis. The testing of synthetic signals shows that our algorithm performs well with SNRs higher than 4. The results demonstrate that our algorithm is simple, practical, and suited to large dataset applications.

Study of the determination and pharmacokinetics of Compound Danshen Dripping Pills in human serum by column switching liquid chromatography electrospray ion trap mass spectrometry.

Compound Danshen Dripping Pill (CDDP) is an important drug widely used for the treatment of cardiovascular diseases. An active component Danshensu (DS) of CDDP was separated by reversed-phase high performance liquid chromatography using column-switching system and analyzed by electrospray mass spectrometry. With this validated assay the pharmacokinetics of CDDP was studied in 10 healthy volunteers after a single oral administration of 250 mg. After trichloroacetic acid precipitation of serum proteins, the analytes were preconcentrated and black-flushed on a reversed-phase column for separation using a switching valve. The analytes were ionized using negative electrospray ionization (ESI) mode. The precursor ion of m/z 196.6 was used to quantify DS in serum. The linear calibration curve ranged from 1.25 to 175 microg/mL. The limit of quantification (LOQ) for DS was 0.15 microg/mL. The intra-day and inter-day precision (R.S.D.) was less than 7.4 and 7.9%, respectively.