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Detailed characterization of microvascular alterations requires high-resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade-offs between the achievable field of view and spatial resolution with the intense light scattering in biological tissues further limiting the achievable penetration depth. Herein, a new approach for volumetric deep-tissue microangiography based on stereovision combined with super-resolution localization imaging is introduced that overcomes the spatial resolution limits imposed by light diffusion and optical diffraction in wide-field imaging configurations. The method capitalizes on localization and tracking of flowing fluorescent particles in the second near-infrared window (NIR-II, ≈1000-1700 nm), with the third (depth) dimension added by triangulation and stereo-matching of images acquired with two short-wave infrared cameras operating in a dual-view mode. The 3D imaging capability enabled with the proposed method facilitates a detailed visualization of microvascular networks and an accurate blood flow quantification. Experiments performed in tissue-mimicking phantoms demonstrate that high resolution is preserved up to a depth of 4 mm in a turbid medium. Transcranial microangiography of the entire murine cortex and penetrating vessels is further demonstrated at capillary level resolution.

As a background sampling site in western Japan, the Kanazawa University Wajima Air Monitoring Station (KUWAMS) continuously observes the air pollutants, including PM1, PM2.5, organic carbon (OC) and element carbon (EC). Data for September 2019 to April 2020 were compared with data for September 2018 to April 2019. The mean concentrations of both PM1 and PM2.5 were 4.10 µg/m3 (47%) and 5.82 µg/m3 (33%) lower, respectively in the Coronavirus Disease 2019 (COVID-19) period (January to April) than in the same period in 2019. Notably, the average concentrations of both classes of particulate matter (PM) in the COVID-19 period were the lowest for that period in all years since 2016. OC and EC also considerably lower (by 69 and 63%, respectively) during the COVID-19 period than during the same period in 2019. All pollutants were then started to increase after the resumption of the work in 2020. The pollutant variations correspond to the measure implemented during the COVID-19 period, including the nationwide lockdown and work resumption. Furthermore, the reductions in the ratios PM1/PM2.5 and OC/EC during COVID-19 period indicate lighter pollution and fewer emission sources. This analysis of the changes in the pollutant concentrations during the epidemic and non-epidemic periods illustrates the significance of the dominant pollution emissions at KUWAMS and the impact of pollution from China that undergoes long-range transport to KUWAMS.

Modern optical neuroimaging approaches are expanding our ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single-modality functional neuroimaging tools. We devised a hybrid fluorescence optoacoustic tomography (FLOT) platform combined with a custom data processing pipeline based on statistical parametric mapping, accomplishing the first simultaneous noninvasive observation of both direct and indirect brain-wide activation patterns with optical contrast. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation and rapid GCaMP6f fluorescence signals were observed in response to peripheral sensory stimulation. While the concurrent epifluorescence served to corroborate and complement the functional optoacoustic observations, the latter further aided in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases.

Particulate polycyclic aromatic hydrocarbons (PAHs) were continuously observed at Kanazawa University Wajima Air Monitoring Station (KUWAMS), a background site located in western Japan and downwind of mainland China that is constantly under the influence of polluted air masses originating from China The observations showed that the concentration of particulate PAHs at KUWAMS sharply dropped to the lowest level (62 pg m–3) of the cold season in the last 5 years after the implementation of COVID-19 control measures in China Despite the occasional dilution with clean air, the decrease in PAHs at KUWAMS reflected the reduction in emission intensity in China Moreover, the PAH concentrations at KUWAMS in February, March, and April of 2020 compared with the same period in the previous year decreased by 52 6%, 36 6%, and 36 7%, respectively These changes were consistent with the decline in SO2 and NO2 in northern China, which intensified during the control of COVID-19 and was slightly moderated after the resumption of work In addition, there was little change in the composition of PAHs at KUWAMS before and during the COVID-19 outbreak and compared with previous years, which suggests a stable source composition These findings emphasize the importance of decreased emission intensity in China for reducing long-range transport of PAHs and pollution levels in downwind areas © The Author(s)

PM2.1 was collected at urban and suburban elementary schools in Shanghai during two sampling periods in cold and warm seasons in 2007. Nine polycyclic aromatic hydrocarbons (PAHs) and ten nitro-polycyclic aromatic hydrocarbons (NPAHs) in PM2.1 were determined. During both seasons, the concentrations of PAHs and NPAHs at urban and suburban schools were not significantly different (p>0.05) and were higher in the cold period than in the warm period. According to the diagnostic ratios, PAHs and NPAHs at both schools were subject to the mixed effects of vehicle emission and coal combustion during both periods. Moreover, the results of the backward trajectory showed that PAHs and NPAHs were more susceptible to external polluted air masses in the cold period. At both urban and suburban schools, the inhalation cancer risk of PAHs and NPAHs in PM2.1 for children during elementary period was dozens of times of the acceptable risk level regulated by the U.S.EPA, highlighting the adverse impact of exposure to PAHs and NPAHs on the healthy development of children.

Low back pain (LBP) is a commonly experienced symptom posing a tremendous healthcare burden to individuals and society at large. The LBP pathology is strongly linked to degeneration of the intervertebral disc (IVD), calling for development of early-stage diagnostic tools for visualizing biomolecular changes in IVD. Multimodal measurements of fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) were performed on IVD whole organ culture model using an in-house built FMT system and a high-field MRI scanner. The resulted multimodal images were systematically validated through epifluorescence imaging of the IVD sections at a microscopic level. Multiple image contrasts were exploited, including fluorescence distribution, anatomical map associated with T1-weighted MRI contrast, and water content related with T2 relaxation time. The developed multimodality imaging approach may thus serve as a new assessment tool for early diagnosis of IVD degeneration and longitudinal monitoring of IVD organ culture status using fluorescence markers.

Optoacoustic microscopy (OAM) retrieves anatomical and functional contrast in vivo at depths not resolvable with optical microscopy. Recent progress on reconstruction algorithms have further advanced its imaging performance to provide high lateral resolution ultimately limited by acoustic diffraction. In this work, we suggest a new broadband model-based OAM (MB-OAM) framework efficiently exploiting scanning symmetries for an enhanced performance. By capitalizing on the large detection bandwidth of a spherical polyvinylidene difluoride (PVDF) film while accurately accounting for its spatial impulse response, the new approach significantly outperforms standard OAM implementations in terms of contrast and resolution, as validated by functional in vivo experiments in mice and human volunteers. Furthermore, L1-norm regularization enabled resolving structures separated by less than the theoretical diffraction-limited resolution. This unique label-free angiographic performance demonstrates the general applicability of MB-OAM as a super-resolution deep-tissue imaging method capable of breaking through the limits imposed by acoustic diffraction.

Acoustic-resolution optoacoustic microscopy (AR-OAM) visualizes internal tissue structures at millimeter to centimeter scale depths with high spatial resolution. The imaging performance mainly depends on the geometry and detection characteristics of the ultrasound transducer. Reconstruction methods incorporating transducer effects are essential to optimize achievable resolution, contrast and overall image quality. Model-based (MB) reconstruction has been shown to provide excellent imaging performance in several optoacoustic embodiments, due to its capacity to accurately model the transducer. However, the applicability of MB reconstruction methods in AR-OAM has been hampered by the high computational cost. Here, we propose an efficient MB reconstruction framework for largescale AR-OAM by considering scanning symmetries, which enabled capitalizing the computational power of a graphics processing unit. The suggested MB reconstruction method is shown to significantly improve the imaging performance of AR-OAM compared to synthetic aperture focusing technique, as validated in in vivo mouse skin experiment.

Kirishima is a typical Japanese commercial city, famous for frequent volcanic activity. This is the first study to determine the characteristics of PM2.5-bound polycyclic and nitro-polycyclic aromatic hydrocarbons (PAHs and NPAHs) and water-soluble inorganic ions (WSIIs) in this city. In this study, the non-volcanic eruption period was taken as the target and daily PM2.5 samples were collected from 24 November to 21 December 2016. The daily concentrations in PM2.5 of ƩPAHs, ƩNPAHs, and ƩWSIIs ranged from 0.36 to 2.90 ng/m3, 2.12 to 22.3 pg/m3, and 1.96 to 11.4 &mu, g/m3, respectively. Through the results of the diagnostic ratio analyses of the PAHs, NPAHs, and WSIIs and the backward trajectory analysis of the air masses arriving in Kirishima, the emission sources of PAHs, NPAHs, and WSIIs in PM2.5 in Kirishima were influenced by the coal burning that came from the East Asian continent, although there was no influence from volcanic emission sources during the sampling period. The total benzo[a]pyrene (BaP)-equivalent concentration was lower than many other cities but the health risks in Kirishima were nonetheless notable. These findings are very important for future research on PM samples during the inactive Asian monsoon and volcanic eruption periods, to further understand the characteristics of air pollutants in Kirishima, and to contribute to the improvement in health of residents and a reduction in the atmospheric circulation of air pollutants in East Asia.

Xianglian pill (XLP) is a typical traditional Chinese herbal medicine prescription composed of Coptidis Rhizoma and Aucklandiae Radix. It has been used to treat gastrointestinal disease for centuries. In the present study, the potential mechanisms of XLP in the treatment of ulcerative colitis (UC) were predicted by integrative pharmacology-based approach. Then, the main compounds of XLP were detected by liquid chromatography-mass spectrometry (LC-MS/MS). Finally, we verified the mechanism of XLP in the treatment of UC in a dextran sulfate sodium (DSS) model. C57BL/6 mice were randomly divided into the control group, DSS group, 5-aminosalicylic acid (5-ASA) group which was used as the positive drug control, XLP low, medium, and high dose group, with 10 mice per group. Except for the control group, acute colitis model was induced in the other mice by administering 3% DSS for consecutive 7 days. Mice in 5-ASA and XLP groups were administered with 5-ASA (50 mg/kg) or XLP (0.8, 1.6, 3.2 g/kg) via oral gavage once per day respectively. Body wight and disease activity index were assay during drug intervention. On day 8, all animals in this experiment were sacrificed and colon tissues were collected for analysis after measurement of the length. The results showed that XLP alleviate DSS -induced acute colitis in mice, including inhibition the secretion of pro-inflammatory cytokines, repairing the dysfunction of intestinal epithelial barrier, enhanced autophagy, and blocked the activation of PI3K/Akt/mTOR pathway. Furthermore, inhibiting autophagy by 3-methyladenine attenuated the protective effects of XLP on colitis. The underlying mechanism may be that Xianglian pill promote autophagy by blocking the activation of PI3K/Akt/mTOR signaling pathway.

Background Tau abnormal aggregates have been visualized in‐vivo using intravital microscopy techniques with high resolution, but are limited to a small field‐of‐view and depth. Here, we report a new method for the transcranial detection of tau deposits accross the brain with 6 μm resolution. Method In vitro Thioflavin T fluorescence assay was performed to screen fluorescence imaging probes that bind to tau fibrils. P301L (Thy1.2) mouse models of frontal temporal lobe dementia with four repeat tau and non‐transgenic littermates were imaged in vivo using a novel large‐field multifocal illumination (LMI) fluorescence microscopy technique using luminescent conjugated oligothiophenes h‐FTAA. Immunohistochemical staining were performed on P301L mouse brain tissue sections using anti‐phosphorylated tau antibodies AT8 and AT100. Result In vitro Thioflavin T fluorescence assay and LMI imaging shows that h‐FTAA bind to recombinant full‐length tau fibrils. In vivo LMI imaging using h‐FTAA showed higher retention in the cortex of P301L mice at 10 month‐of‐age compared to age‐matched non‐transgenic littermates. Immunohistochemical staining on P301L mouse brain tissue sections showed co‐localization of h‐FTAA with anti‐phosphorylated tau antibodies AT8 and AT100, thus verifying the specificity of the probe to tauopathy in P301L mice. Conclusion We demonstrate a new in vivo high‐resolution imaging platform for detection of tauopathy in murine models of frontal temporal lobe tauopathy.

Background The abnormal deposition of beta‐amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently available intravital microscopy techniques for high‐resolution plaque visualization commonly involve highly invasive procedures and are limited to small field‐of‐views within the rodent brain. Method We devised a large‐field multi‐focal illumination (LMI) fluorescence microscopy method that provides a 20 × 20 mm field‐of‐view and an axial resolution of ∼15 mm. In vivo and ex vivo transcranial LMI fluorescence microscopy and wide‐field fluorescence microscopy for amyloid deposits were performed in APP/PS1 and arcAb mouse models of Alzheimer’s disease amyloidosis using luminescent conjugated oligothiophene probe HS‐169. Immunohistochemical staining with HS‐169, anti‐Ab antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections Result LMI fluorescence microscopy detected amyloid‐beta deposits at a single plaque level in APP/PS1 and arcAb mice with high sensitivity and specificity. The contrast‐to‐noise ratio was approximately 24 times higher in LMI fluorescence microscopy of amyloid deposits compared to wide‐field fluorescence microscopy. Immunohistochemical staining showed HS‐169 co‐localized with 6E10 and OC stained compact parenchymal and vessel‐associated amyloid deposits. Conclusion The novel LMI in vivo amyloid imaging platform offers new prospects for studies into Alzheimer’s disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.

Daily PM2.5 (particulate matter with aerodynamic diameter &le, 2.5 &mu, m) samples were simultaneously collected at two background sites (Wajima Air Monitoring Station (WAMS) and Fukue-Jima Atmosphere and Aerosol Monitoring Station (FAMS)) in Japan in the East Asian winter and summer monsoon periods of 2017 and 2019, to compare the characteristics of air pollutants among different regions and to determine the possible variation during the long-range transport process. Polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), and water-soluble inorganic ions (WSIIs) were analyzed. Despite the PM2.5 concentrations at FAMS (8.90 &ndash, 78.5 &micro, g/m3) being higher than those at WAMS (2.33 &ndash, 21.2 &micro, g/m3) in the winter monsoon period, the average concentrations of &sum, PAHs, &sum, NPAHs, and &sum, WSIIs were similar between the two sites. Diagnostic ratios indicated PAHs mainly originated from traffic emissions and mostly aged, whereas NPAHs were mostly secondarily formed during long-range transport. WSIIs at WAMS were mainly formed via the combustion process and secondary reactions, whereas those at FAMS mainly originated from sea salt and dust. Backward trajectories revealed the air masses could not only come from Asian continental coastal regions but also distant landlocked areas in the winter monsoon period, whereas most came from the ocean in the summer monsoon period. These findings can provide basic data for the establishment of prediction models of transboundary air pollutants in East Asia.

Imaging of cerebral vasculature is impeded with the existing fluorescence microscopy methods due to intense light scattering in living tissues and the need for highly invasive craniotomy procedures to resolve structures on a capillary scale. We propose a widefield fluorescence localization microscopy technique for high-resolution transcranial imaging and quantitative assessment of cortical perfusion in mice. The method is based on tracking single fluorescent microparticles sparsely distributed in the blood stream using a simple CMOS camera and a continuous-wave laser source. We demonstrate quantitative transcranial in vivo mapping of the blood flow velocity and direction at capillary level resolution (5 µm) across the entire cortex. The new technique opens a new high-resolution transcranial window into the brain function in health and disease.

Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.

Background To investigate the early prediction value of procalcitonin (PCT) in pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Method Retrospective analysis of clinical data of 67 patients undergoing pancreaticoduodenectomy (PD) and 19 patients undergoing distalpancreatectomy (DP) were performed in the Department of Hepatobiliary Surgery, Leshan People’s Hospital from January 2017 to December 2018. All patients were divided into POPF group and non-POPF group depending on the presence of pancreatic fistula. And fistulas were classified according to the ISGPF classification scheme. Plasma PCT levels, serum CRP concentration, and WBC counts were assessed preoperatively and on postoperative days (PODs) 1, 3, and 5. Statistical analyses were performed with statistical software. The ROC curve was used to analyze the efficacy of PCT and CRP in POPF prediction after surgery and determine their Cut-off value. Result There were no statistically significant differences identified in age, gender, BMI, diabetes, abdominal surgery history, preoperative laboratory data, operation time, intraoperative bleeding volume, tumor nature and medical expenses of PD patients between the two groups (P > 0.05). While the incidence of postoperative hyperglycemia, postoperative ICU rate and postoperative hospital stay were statistically significant (P Conclusion The PCT is valuable for early prediction of pancreatic fistula after Pancreaticoduodenectomy.

Background: This study evaluated the feasibility, safety and effectiveness in patients treated with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) for the treatment of liver malignant tumors with insufficient future liver remnant (FIR). Method: We performed a computer search on the PubMed databases to retrieve the RCT or clinical trials comparing ALPPS and PVE published from January 2010 to January 2020. The quality of the included trials was assessed according to the inclusion and exclusion criteria by two researchers independently. The RevMan 5.3 and STATA 12.0 software were used to extract and analyze the data. Result: A total of 11 retroprospective clinical trial articles comprising 867 patients were included in the study. The number of patients who underwent ALPPS were 247 and 620 for PVE. There were significant differences (P

This study encompassed the regular observation of nine polycyclic aromatic hydrocarbons (PAHs) and three nitro-PAHs (NPAHs) in particulate matter (PM) in Shanghai in summer and winter from 2010 to 2018. The results showed that the mean concentrations of ƩPAHs in summer decreased by 24.7% in 2013 and 18.1% in 2017 but increased by 10.2% in 2015 compared to the data in 2010. However, the mean concentrations of ƩPAHs in winter decreased by 39.7% from 2010 (12.8 ± 4.55 ng/m3) to 2018 (7.72 ± 3.33 ng/m3), and the mean concentrations of 1-nitropyrene in winter decreased by 79.0% from 2010 (42.3 ± 16.1 pg/m3) to 2018 (8.90 ± 2.09 pg/m3). Correlation analysis with meteorological conditions revealed that the PAH and NPAH concentrations were both influenced by ambient temperature. The diagnostic ratios of PAHs and factor analysis showed that they were mainly affected by traffic emissions with some coal and/or biomass combustion. The ratio of 2-nitrofluoranthene to 2-nitropyrene was near 10, which indicated that the OH radical-initiated reaction was the main pathway leading to their secondary formation. Moreover, backward trajectories revealed different air mass routes in each sampling period, indicating a high possibility of source effects from the northern area in winter in addition to local and surrounding influences. Meanwhile, the mean total benzo[a]pyrene-equivalent concentrations in Shanghai in winter decreased by 50.8% from 2010 (1860 ± 645 pg/m3) to 2018 (916 ± 363 pg/m3). These results indicated the positive effects of the various policies and regulations issued by Chinese authorities.

Melanoma, developing from melanocytes, is the deadliest type of malignant skin tumors in the world. Due to high light absorption of melanin, rare circulating melanoma cells, as an endogenous marker for metastasis at the early stage, can be quantitatively detected in small superficial vessels of mouse ears by in vivo photoacoustic flow cytometry (PAFC). Before clinical application, the capability of promising PAFC platform should be verified and optimized by mouse vessels, which are similar in size and depth to human vessels. In the current study, compared with optical resolution PAFC (OR-PAFC), we build acoustic resolution PAFC (AR-PAFC) using focused ultrasonic transducer and 1064 nm laser with lower pulse rate, leading to higher detection depth and lower laser power density in mouse models. Besides, based on laser frequency doubling and high absorption coefficient of hemoglobin at 532nm wavelength, the blood vessels can be positioned by lowcost navigation system rather than the expensive system of two coupled lasers or charged coupled device with depth limitation. We confirm that AR-PAFC can be applied to noninvasive label-free counting of circulating melanoma cells in mouse tail veins, and validated by in vitro assays using phantom models, which simulates the scattering and absorption coefficients of living tissue. These results show that AR-PAFC platform has great potential for preoperative diagnosis and postoperative evaluation of melanoma patients.

The abnormal deposition of beta-amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently available intravital microscopy techniques for high-resolution plaque visualization commonly involve highly invasive procedures and are limited to a small field-of-view within the rodent brain. Here, we report the transcranial detection of amyloid-beta deposits at the whole brain scale with 20 μm resolution in APP/PS1 and arcAβ mouse models of Alzheimer’s disease amyloidosis using a large-field multifocal (LMI) fluorescence microscopy technique. Highly sensitive and specific detection of amyloid-beta deposits at a single plaque level in APP/PS1 and arcAβ mice was facilitated using luminescent conjugated oligothiophene HS-169. Immunohistochemical staining with HS-169, anti-Aβ antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections further showed that HS-169 resolved compact parenchymal and vessel-associated amyloid deposits. The novel imaging platform offers new prospects for in vivo studies into Alzheimer’s disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.

Polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) in PM2.5 samples were collected at a roadside monitoring station in Kanazawa, Japan, in every season from 2017 to 2018. Nine PAHs and five NPAHs were determined using high-performance liquid chromatography with fluorescence detection and chemiluminescence detection, respectively. The mean concentrations of PAHs and NPAHs were highest in winter and lowest in summer. Fluoranthene and pyrene were the dominant PAHs and 1-nitropyrene was the dominant NPAH in all seasons, and these compounds were mainly emitted by diesel vehicles. The concentration ratio of benzo(a)pyrene (BaP) to benzo(ghi)perylene (BgPe) ((BaP)/(BgPe)) and of indeno(1,2,3-cd)pyrene (IDP) to the sum of IDP and benzo(ghi)perylene (BgPe) ((IDP)/((IDP)+(BgPe0) might still be useful indicators for identifying traffic emission sources today. Moreover, our results showed that the carcinogenic risk in all seasons was below the acceptable limit set by the WHO.

Scanning optical microscopy techniques are commonly restricted to a sub‐millimeter field‐of‐view (FOV) or otherwise employ slow mechanical translation, limiting their applicability for imaging fast biological dynamics occurring over large areas. A rapid scanning large‐field multifocal illumination (LMI) fluorescence microscopy technique is devised based on a beam‐splitting grating and an acousto‐optic deflector synchronized with a high‐speed camera to attain real‐time fluorescence microscopy over a centimeter‐scale FOV. Owing to its large depth of focus, the approach allows noninvasive visualization of perfusion across the entire mouse cerebral cortex, not achievable with conventional wide‐field fluorescence microscopy methods. The new concept can readily be incorporated into conventional wide‐field microscopes to mitigate image blur due to tissue scattering and attain optimal trade‐off between spatial resolution and FOV. It further establishes a bridge between conventional wide‐field macroscopy and laser scanning confocal microscopy, thus it is anticipated to find broad applicability in functional neuroimaging, in vivo cell tracking, and other applications looking at large‐scale fluorescent‐based biodynamics., Laser & Photonics Reviews, 14 (2), ISSN:1863-8880, ISSN:1863-8899

Melanoma is a malignant tumor whose circulating tumor cell (CTC) count has been shown as a prognostic marker for metastasis development. Therefore detection of circulating melanoma cells plays an important role in monitoring tumor metastasis and prevention after diagnosis. In Vivo Photoacoustic Flow Cytometry (PAFC) is established here to achieve in vivo melanoma inspection, meanwhile guarantees non-invasive and real-time detection.Accurate tumor cell detection is of great significance to achieve highly specific diagnosis and avoid unnecessary medical tests.However, the amount of data detected by PAFC is large and original photoacoustic signal is mixed with various noises.The traditional triple mean square deviation method has lower accuracy and consumes a lot of time in data processing. Here, a classification approach in photoacoustic is proposed, which could discriminate signals and noises based on features extracted from photoacoustic waves compared to normal cells using Support Vector Machines algorithm. Due to similar shape and structure of cells, the photoacoustic signals usually have similar vibration mode. By analyzing the correlations and the signal features in time domain and frequency domain, we finally choose the continuity, amplitude, and photoacoustic waveform pulse width as the features to characterize the signal.More than 600,000 samples were selected as the training set (normalized in advance), and a classifier with a precision of 85% accuracy to filter out the photoacoustic signals rapidly was trained by the support vector machine method.The classifier introduced here has proved to optimize the signal acquisition and reduce signal processing time, realizing real-time detection and real-time analysis in PAFC.

PM

Particulate matter (PM) was collected in three different areas, SY-1, SY-2, and SY-3, in Shenyang, China, during the warm and cold seasons from 2012 to 2014. SY-1 was located beside a thermal power plant, far from the central area. SY-2 was near a coal heating boiler on the main road, close to the central area. SY-3 was on the main road, without fixed emission sources. Nine PM-bound polycyclic aromatic hydrocarbons (PAHs) were analyzed. The results showed that the mean concentration of total PAHs was higher in the cold season (92.6&ndash, 316 ng m&minus, 3) than in the warm season (18.4&ndash, 32.2 ng m&minus, 3). Five- and six-ring PAHs occupied a large percentage at all sites in the warm season, and four-ring PAHs were the dominant components in the cold season. Several diagnostic PAH ratios indicated that the main sources of PAHs in Shenyang in the warm and cold seasons were not only coal burning but also vehicle emission. In this study, we suggest that a benzo[a]pyrene/benzo[ghi]perylene ratio ([BaP]/[BgPe]) of 0.6 was a useful indicator to speculate the relative significance of coal burning and vehicle exhaust. Although the Shenyang government has undertaken actions to address air pollution, the PM and PAH concentrations did not decrease significantly compared to those in our previous studies. The cancer risk calculated from the BaP equivalent total concentration at all three sites in the warm and cold seasons exceeded the acceptable limit established by the US EPA.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the atmosphere and they mostly stem from the imperfect combustion of fossil fuels and biofuels. PAHs are inherently associated with homogenous fine particles or distributed to different-sized particles during the aging of air masses. PAHs carried by fine particles undergo a long-range transport to remote areas while those adsorbed on coarse particles have a shorter lifetime in ambient air. More importantly, PAHs with higher molecular weights tend to be bound with finer particles and can deeply enter the lungs, posing severe health risks to humans. Thus, the environmental fate and health effects of particulate PAHs are strongly size-dependent. This review summarizes the size distributions of particulate PAHs freshly emitted from combustion sources as well as the distribution patterns of PAHs in ambient particles. It was found that PAHs from stationary sources are primarily bound to fine particles, which are slightly larger than particles to which PAHs from mobile sources are bound. In ambient air, particulate PAHs are distributed in larger size modes than those in the combustion fume, and the particle size decreases with PAH molecular weight increasing. The relevant mechanisms and influencing factors of particle size distribution changes are illustrated in this article, which are essentially attributed to combustion and ambient temperature as well as the physical and chemical properties of PAHs. Overall, the study on the particle size distribution of PAHs will contribute for a full understanding of the origin, atmospheric behaviors and health effects of particulate PAHs.

Malignant melanoma, developing from melanocytes, is a kind of high metastatic tumor. Circulating melanoma cells, as a marker for metastasis development, are found in blood or lymphatic system at the early stage. Thus, quantitative detection of circulating melanoma cells has great significance to diagnose carcinoma and monitor tumor metastasis. In contrast to in vitro detection methods and in vivo fluorescence-based flow cytometry (IVFC), the in vivo photoacoustic flow cytometry (PAFC) utilizes melanoma cells’ predominant optical absorption in the near-infrared range over other absorbers to receive the photoacoustic (PA) signals without fluorescent dye labeling in a non-invasive way. The sensitivity of the PAFC system was verified by in vitro and in vivo experiments. Besides, we solves the technical problem that blood vessels cannot be positioned in the process of in vivo detection by designing the laser signal positioning navigation system using frequency doubling technique. PAFC provides a new tool for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs) and has strong practicality and favorable clinical prospects.

Fluorescence microscopy is a powerful enabling tool for biological discovery, albeit its effective penetration depth and resolving capacity are limited due to intense light scattering in living tissues. The recently introduced short-wave infrared cameras and contrast agents featuring fluorescence emission in the second near-infrared (NIR-II) window have extended the achievable penetration to about 2 mm. However, the effective spatial resolution progressively deteriorates with depth due to photon diffusion. Here we introduce diffuse optical localization imaging (DOLI) to enable super-resolution deep-tissue fluorescence microscopy beyond the limits imposed by light diffusion. The method is based on localization of flowing microdroplets encapsulating lead sulfide (PbS)-based quantum dots in a sequence of epi-fluorescence images acquired in the NIR-II spectral window. Experiments performed in tissue mimicking phantoms indicate that high-resolution detection of fluorescent particles can be preserved over 4 mm depth range, while in vivo microangiography of murine cerebral vasculature can be accomplished through intact scalp and skull. The method further enables retrieving depth information from planar fluorescence image recordings by exploiting the localized spot size. DOLI operates in a resolution-depth regime previously inaccessible with optical methods, thus massively enhancing the applicability of fluorescence-based imaging techniques.

Eleven years (2005–2015) of data from long-term monitoring at a Japanese remote background site in Wajima, were analyzed to investigate temporal trends and sources. Water-soluble inorganic ions (WSIIs) were analyzed for aerosol chemical composition. The total WSIIs concentration was 7.93 ± 3.93 μg/m3, accounting for 42.3% of TSP mass, ranged from 11.4 to 93.9%. SO42− is the most abundant ion, contributing a total WSII mass from 18.0 to 79.8%, and non-sea-salt (nss-) SO42− contributed from 63.6% to 99.6% of total SO42−, which was related to human activities on the Asian continent and the effects of marine precursors in spring and summer, respectively. NO3− and NH4+ contribute 6.3 and 7.4% of the total WSIIs and were affected by long-range transport and local sources as well. The increasing trend of Na+ and Cl− indicates the increased influence of sea salt, which is caused by more frequent strong winds. K+ is mainly produced from biomass burning with a stable seasonal variation, Ca2+ as the characteristic ion of dust has the highest concentration in spring. Mg2+ comes from minerals and marine sources during spring and summer, respectively. This work describes in detail the annual change trend of the WSIIs of atmospheric particles in the Wajima area, seasonal characteristics, and source contributions, provide a comprehensive understanding of long-term variation in atmospheric particulate.

Natural aeolian dust (AD) particles are potential carriers of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere. The heterogeneous interaction between them may lead to worsened air quality and enhanced cytotoxicity and carcinogenicity of ambient particulates in downwind areas, and this topic requires in-depth exploration. In this study, AD samples were collected from four Asian dust sources, and their physical properties and compositions were determined, showing great regional differences. The physical and chemical interactions of different AD particles with naphthalene (Nap; model PAH) were observed in aqueous systems. The results showed that AD particles from the Loess Plateau had weak adsorption to Nap, which was fitted by the Langmuir isotherm. There was no obvious adsorption to Nap found for the other three AD samples. This difference seemed to depend mainly on the specific surface area and/or the total pore volume. In addition, the Nap in the aqueous solution did not undergo chemical reactions under dark conditions and longwave ultraviolet (UV) radiation but degraded under shortwave UV radiation, and 2-formylcinnamaldehyde and 1,4-naphthoquinone were the first-generated products. The degradation of Nap in the aqueous solution was probably initiated by photoionization, and the reaction rate constant (between 1.44 × 10−4 min−1 and 8.55 × 10−4 min−1) was much lower than that of Nap with hydroxyl radicals. Instead of inducing or promoting the chemical change in Nap, the AD particles slowed photodegradation due to the extinction of radiation. Therefore, it is inferred that natural AD particles have no substantial effect on the transportation and transformation of PAHs in the atmosphere.

Objective: Visualizing cell interactions in blood circulation is of great importance in studies of anticancer immunotherapy or drugs. However, the lack of a suitable imaging system hampers progress in this field. Methods: In this work, we built a dual-channel in vivo imaging flow cytometer to visualize the interactions of circulating tumor cells (CTCs) and dendritic cells (DCs) simultaneously in the bloodstream. Two artificial neural networks were trained to identify blood vessels and cells in the acquired images. Results and Conclusion: Using this technique, single CTCs and CTC clusters were readily distinguished by their morphology. Interactions of CTCs and DCs were identified, while their moving velocities were analyzed. The CTC-DC clusters moved at a slower velocity than that of single CTCs or DCs. This may provide new insights into tumor metastasis and blood rheology. Significance: This in vivo imaging flow cytometry system holds great potential for assessing the efficiency of targeting CTCs with anticancer immune cells or drugs.