Airborne Nanoparticle Concentrations Are Associated with Increased Mortality Risk in Canada's Two Largest Cities.

RATIONALE: Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated. OBJECTIVES: Estimate the associations between long-term exposure to outdoor ultrafine particles and mortality. METHODS: Outdoor air pollution levels were linked to the residential addresses of a large, population-based cohort from 2001 - 2016. Associations between long-term exposure to outdoor ultrafine particles and nonaccidental and cause-specific mortality were estimated using Cox proportional hazards models. MEASUREMENTS: An increase in long-term exposure to outdoor ultrafine particles was associated with an increased risk of nonaccidental mortality (Hazard Ratio = 1. 073, 95% Confidence Interval = 1. 061, 1. 085) and cause-specific mortality, the strongest of which was respiratory mortality (Hazard Ratio = 1.174, 95% Confidence Interval = 1.130, 1.220). MAIN RESULTS: Long-term exposure to outdoor ultrafine particles was associated with increased risk of mortality. We estimated the mortality burden for outdoor ultrafine particles in Montreal and Toronto, Canada to be approximately 1100 additional nonaccidental deaths every year. Furthermore, we observed possible confounding by particle size which suggests that previous studies may have underestimated or missed important health risks associated with ultrafine particles. CONCLUSIONS: As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.

Flex Meta-Storms elucidates the microbiome local beta-diversity under specific phenotypes.

MOTIVATION: Beta-diversity quantitatively measures the difference among microbial communities thus enlightening the association between microbiome composition and environment properties or host phenotypes. The beta-diversity analysis mainly relies on distances among microbiomes that are calculated by all microbial features. However, in some cases, only a small fraction of members in a community plays crucial roles. Such a tiny proportion is insufficient to alter the overall distance, which is always missed by end-to-end comparison. On the other hand, beta-diversity pattern can also be interfered due to the data sparsity when only focusing on nonabundant microbes. RESULTS: Here, we develop Flex Meta-Storms (FMS) distance algorithm that implements the "local alignment" of microbiomes for the first time. Using a flexible extraction that considers the weighted phylogenetic and functional relations of microbes, FMS produces a normalized phylogenetic distance among members of interest for microbiome pairs. We demonstrated the advantage of FMS in detecting the subtle variations of microbiomes among different states using artificial and real datasets, which were neglected by regular distance metrics. Therefore, FMS effectively discriminates microbiomes with higher sensitivity and flexibility, thus contributing to in-depth comprehension of microbe-host interactions, as well as promoting the utilization of microbiome data such as disease screening and prediction. AVAILABILITY AND IMPLEMENTATION: FMS is implemented in C++, and the source code is released at https://github.com/qdu-bioinfo/flex-meta-storms.

Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway.

CONTEXT: Daphnetin is a natural product with anti-inflammatory, antioxidant, and neuroprotective properties. Reports have found that it has a strong analgesic effect; however, its analgesic mechanism is unknown. OBJECTIVE: We explored the effect and mechanism of daphnetin on neuropathic pain (NP). MATERIALS AND METHODS: The rat model of NP was established by ligation of the sciatic nerve. Male Sprague-Dawley rats were divided into six groups: Control, Model, Sham, morphine (0.375 mg/kg), and daphnetin (0.0625 and 0.025 mg/kg). Rats were intrathecally injected with drugs or normal saline once daily for three days. Hyperalgesia was evaluated by mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). Protein levels were detected using ELISA, immunofluorescence, and western blotting. RESULTS: Compared to the Model group, daphnetin improved TWT (46.70 °C vs. 42.20 °C) and MWT (45.60 g vs. 23.60 g), reduced the expression of interleukin-1ß (0.99 ng/g vs. 1.42 ng/g), interleukin-6 (0.90 ng/g vs. 1.52 ng/g), and tumor necrosis factor-α (0.93 ng/g vs. 1.52 ng/g) in the sciatic nerve. Daphnetin decreased the expression of toll-like receptor 4 (TLR4) (0.47-fold), phosphorylated inhibitor of NF-κB (p-IKBα) (0.29-fold), nuclear factor kappaB (NF-κB) (0.48-fold), glial fibrillary acidic protein (GFAP) (0.42-fold), CXC chemokine ligand type 1 (CXCL1) (0.84-fold), CXC chemokine receptor type 2 (CXCR2) (0.78-fold) in the spinal cord. DISCUSSION AND CONCLUSIONS: Daphnetin alleviates NP by inhibiting inflammation and astrocyte activation in the spinal cord, providing theoretical support for the extensive clinical treatment of NP.

Prediction of Short-Term Ultrafine Particle Exposures Using Real-Time Street-Level Images Paired with Air Quality Measurements.

Within-city ultrafine particle (UFP) concentrations vary sharply since they are influenced by various factors. We developed prediction models for short-term UFP exposures using street-level images collected by a camera installed on a vehicle rooftop, paired with air quality measurements conducted during a large-scale mobile monitoring campaign in Toronto, Canada. Convolutional neural network models were trained to extract traffic and built environment features from images. These features, along with regional air quality and meteorology data were used to predict short-term UFP concentration as a continuous and categorical variable. A gradient boost model for UFP as a continuous variable achieved R2 = 0.66 and RMSE = 9391.8#/cm3 (mean values for 10-fold cross-validation). The model predicting categorical UFP achieved accuracies for "Low" and "High" UFP of 77 and 70%, respectively. The presence of trucks and other traffic parameters were associated with higher UFPs, and the spatial distribution of elevated short-term UFP followed the distribution of single-unit trucks. This study demonstrates that pictures captured on urban streets, associated with regional air quality and meteorology, can adequately predict short-term UFP exposure. Capturing the spatial distribution of high-frequency short-term UFP spikes in urban areas provides crucial information for the management of near-road air pollution hot spots.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Near-field nonlinear imaging of an anapole mode beyond diffraction limit.

Nonlinear nanophotonics, as an emerging field in nanophotonics, eagerly calls for experimental techniques for probing and analyzing near-field nonlinear optical signals with subwavelength resolution. Here, we report an aperture-type scanning near-field optical microscopic method for probing near-field nonlinear optical processes. As a demonstration, near-field third-harmonic generation from an anapole dark-mode state generated by a silicon nanodisk is probed and imaged. The measured results agree well with the simulations, with a spatial resolution down to $0.14{\lambda _0}$ and a sensitivity of 0.1 nW. This method provides a powerful tool for characterizing nonlinear light-matter interactions at the nanoscale, which can help, for example, to unveil crystal properties involving subwavelength defects or dislocations.

Link between characteristics of Fe(III) oxides and critical role in enhancing anaerobic methanogenic degradation of complex organic compounds.

Fe(III) oxides have been investigated to accelerate anaerobic methanogenic degradation of complex organic compounds. However, the critical role linked to the characteristics of different types of Fe(III) oxides is still unclear. Study presented here performed a side-by-side comparison of four types of Fe(III) oxides including Fe(III)-citrate, ferrihydrite, hematite and magnetite to evaluate their effectiveness in methanogenic degradation of phenol. Results showed that, amorphous Fe(III)-citrate group showed the fastest phenol degradation and Fe2+ release among all the groups, followed by poorly crystalline ferrihydrite. Although Fe(III)-citrate group also showed the fastest methane production rate, the efficiency of electron recovery in methane production was only 58-78%, which was evidently lower than that in both crystalline hematite (86-89%) and magnetite (93-97%) groups. Methane production rate with non-conductive ferrihydrite was nearly same as that with conductive magnetite, both of which were significantly higher than that with semi-conductive hematite. X-ray Diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis showed that sludge collected from hematite and magnetite group still respectively presented a relatively intact characteristic spectra involved in hematite and magnetite. Differently, the characteristic spectra involved in ferrihydrite was not evident in sludge collected from ferrihydrite group, whereas the characteristic spectra involved in magnetite was detected. Microbial community analysis showed that, both Fe(III)-citrate and ferrihydrite specially enriched Fe(III)-reducing bacteria capable of degrading phenol into fatty acids (Trichococcus and Caloramator) via dissimilatory Fe(III) reduction. Fe(III)-citrate also stimulated the growth of Syntrophus capable of degrading phenol/benzoate into acetate and proceeding direct interspecies electron transfer (DIET). In magnetite and hematite group, the abundance of Enterococcus species evidently increased, and they might proceed DIET with Methanothrix species in syntrophic conversion of fatty acids into methane.

Colorimetric discriminatory array for detection and discrimination of antioxidants based on HAuCl4/3,3',5,5'-tetramethylbenzidine.

Here, we report a simple but effective nose/tongue-mimic sensor array based on HAuCl4/3,3',5,5'-tetramethylbenzidine (TMB) for colorimetric discrimination and determination of antioxidants. Two concentrations of HAuCl4 were employed as receptor units to construct the colorimetric sensor array. The sensing strategy is based on the fact that HAuCl4 with different concentrations (0.08 and 0.03 mM) could oxidize TMB to oxidized TMB (oxTMB), resulting in a blue and green color solution, respectively, corresponding to an absorption peak centered at 440 nm and 657 nm. However, the presence of different antioxidants could cause the reduction in HAuCl4, leading to the fading of the blue and green color and the decrease in the absorbance at 440 nm and 657 nm to varying degrees. Based on the above phenomena, by taking advantage of linear discriminant analysis (LDA), five antioxidants (i.e. ascorbic acid (AA), melatonin (MT), uric acid (UA), tannic acid (TCA), and glycine (Gly)) at five concentrations (200, 120, 60, 20, and 1 nM) were successfully discriminated both in buffer and serum. More importantly, this approach is simple, fast, and without the use of any nanomaterials.

Coherent fiber-optics-array collimator based on a single unitary collimating lens: proposal design and experimental verification.

In this paper, we propose a design of coherent fiber-optics-array collimator (CFAC) that is mainly composed of a single unitary collimating lens and a prism. The CFAC system is presented conceptually, and corresponding parameters are theoretically analyzed using a geometrical optics method. Then, we set up a proof-of-concept experiment to verify the validity of the CFAC system with three coherent fiber lasers distributed along the symmetry axis through the center of the single unitary lens. After that, we realize the synchronous aberrationless collimating of the three beams with only one collimating lens system and their parallel propagation by utilizing a specific prism array. Finally, we successfully achieve a coherent beam combination of the laterally distributed three beams using a single-frequency dithering algorithm. Through an active piston phase control, the residual phase errors among the laser beams are suppressed below λ/26. By comparing the experimental results with the simulation results, we can see that the distribution of the closed-loop far-field intensity pattern detected by the charge-coupled infrared camera basically matches the ideal intensity distribution.

SOX30 specially prevents Wnt-signaling to suppress metastasis and improve prognosis of lung adenocarcinoma patients.

BACKGROUND: Different histological subtypes of non-small cell lung cancer (NSCLC) show different molecular characteristics and responses to therapeutic strategy. Identification of specific gene, clarification of its special roles and molecular mechanisms are crucial for developing new therapeutic approach for particular subtype patients. METHODS: Surgical specimens of 540 NSCLC patients were recruited. Immunohistochemistry was used to detect SOX30 expression, and correlations with clinical parameters were analyzed. Functional experiments and gene ontology analysis were performed to investigate roles of SOX30. Network analysis, TOP/FOP-Flash assays, luciferase reporter assays and ChIP-PCR assays were performed to determine the mechanism. Survival analyses were calculated by Kaplan-Meier and Cox regression. Recovery experiment was investigated the importance of the target of SOX30. RESULTS: SOX30 expression is closely associated with histological types of NSCLC, and metastasis of adenocarcinoma (ADC) patients but not of squamous cell carcinoma (SCC) patients. SOX30 strongly inhibits cancer cell migration and invasion in ADC cell lines, whrereas not affects cell migration and invasion in SCC cell lines. The genes associated with SOX30 preferentially enrich in metastasis process and Wnt-signaling in only ADC patients. Consistently, SOX30 is negatively associated with the expression of Wnt-signaling and metastasis-related gene CTNNB1 (ß-catenin) in ADC, but not in SCC. At the molecular level, SOX30 represses Wnt-signaling by directly transcriptional inhibition of CTNNB1 in ADC, and also not in SCC. In the clinical, SOX30 is a favorable and independent prognostic factor in ADC patients, whereas is an unfavorable and independent prognostic factor in SCC patients. Moreover, SOX30 expression is a double face early-stage prognostic biomarker in ADC and SCC patients. In addition, forcible restoration of CTNNB1 indeed can inhibit the anti-metastatic role of SOX30 in ADC patients. CONCLUSIONS: In early-stage ADC patients, elevated SOX30 expression inhibits tumor-metastasis by directly binding to CTNNB1 promoter resulting in a favorable prognosis of these patients. However, in early-stage SCC patients, SOX30 has no inhibitory role on tumor-metastasis due to not binding to CTNNB1 promoter leading to an unfavorable prognosis of the patients. This study highlights a special role and prognostic value of SOX30 in ADC, providing a novel therapeutic target for particular subtype NSCLC patients.

Elevated CO2 facilitates C and N accumulation in a rice paddy ecosystem.

Elevated CO2 can stimulate wetland carbon (C) and nitrogen (N) exports through gaseous and dissolved pathways, however, the consequent influences on the C and N pools are still not fully known. Therefore, we set up a free-air CO2 enrichment experiment in a paddy field in Eastern China. After five year fumigation, we studied C and N in the plant-water-soil system. The results showed: (1) elevated CO2 stimulated rice aboveground biomass and N accumulations by 19.1% and 12.5%, respectively. (2) Elevated CO2 significantly increased paddy soil TOC and TN contents by 12.5% and 15.5%, respectively in the 0-15 cm layer, and 22.7% and 26.0% in the 15-30 cm soil layer. (3) Averaged across the rice growing period, elevated CO2 greatly increased TOC and TN contents in the surface water by 7.6% and 11.4%, respectively. (4) The TOC/TN ratio and natural δ15N value in the surface soil showed a decreasing trend under elevated CO2. The above results indicate that elevated CO2 can benefit C and N accumulation in paddy fields. Given the similarity between the paddies and natural wetlands, our results also suggest a great potential for long-term C and N accumulation in natural wetlands under future climate patterns.

M-shaped grating by nanoimprinting: a replicable, large-area, highly active plasmonic surface-enhanced Raman scattering substrate with nanogaps.

Plasmonic nanostructures separated by nanogaps enable strong electromagnetic-field confinement on the nanoscale for enhancing light-matter interactions, which are in great demand in many applications such as surface-enhanced Raman scattering (SERS). A simple M-shaped nanograting with narrow V-shaped grooves is proposed. Both theoretical and experimental studies reveal that the electromagnetic field on the surface of the M grating can be pronouncedly enhanced over that of a grating without such grooves, due to field localization in the nanogaps formed by the narrow V grooves. A technique based on room-temperature nanoimprinting lithography and anisotropic reactive-ion etching is developed to fabricate this device, which is cost-effective, reliable, and suitable for fabricating large-area nanostructures. As a demonstration of the potential application of this device, the M grating is used as a SERS substrate for probing Rhodamine 6G molecules. Experimentally, an average SERS enhancement factor as high as 5×108 has been achieved, which verifies the greatly enhanced light-matter interaction on the surface of the M grating over that of traditional SERS surfaces.

Predicting within-city spatiotemporal variations in daily median outdoor ultrafine particle number concentrations and size in Montreal and Toronto, Canada.

Background: Epidemiological evidence suggests that long-term exposure to outdoor ultrafine particles (UFPs, <0.1 µm) may have important human health impacts. However, less is known about the acute health impacts of these pollutants as few models are available to estimate daily within-city spatiotemporal variations in outdoor UFPs. Methods: Several machine learning approaches (i.e., generalized additive models, random forest models, and extreme gradient boosting) were used to predict daily spatiotemporal variations in outdoor UFPs (number concentration and size) across Montreal and Toronto, Canada using a large database of mobile monitoring measurements. Separate models were developed for each city and all models were evaluated using a 10-fold cross-validation procedure. Results: In total, our models were based on measurements from 12,705 road segments in Montreal and 10,929 road segments in Toronto. Daily median outdoor UFP number concentrations varied substantially across both cities with 1st-99th percentiles ranging from 1389 to 181,672 in Montreal and 2472 to 118,544 in Toronto. Outdoor UFP size tended to be smaller in Montreal (mean [SD]: 34 nm [15]) than in Toronto (mean [SD]: 44 nm [25]). Extreme gradient boosting models performed best and explained the majority of spatiotemporal variations in outdoor UFP number concentrations (Montreal, R 2: 0.727; Toronto, R 2: 0.723) and UFP size (Montreal, R 2: 0.823; Toronto, R 2: 0.898) with slopes close to one and intercepts close to zero for relationships between measured and predicted values. Conclusion: These new models will be applied in future epidemiological studies examining the acute health impacts of outdoor UFPs in Canada's two largest cities.

Exploring the triple burden of social disadvantage, mobility poverty, and exposure to traffic-related air pollution.

Understanding the relationships between ultrafine particle (UFP) exposure, socioeconomic status (SES), and sustainable transportation accessibility in Toronto, Canada is crucial for promoting public health, addressing environmental justice, and ensuring transportation equity. We conducted a large-scale mobile measurement campaign and employed a gradient boost model to generate exposure surfaces using land use, built environment, and meteorological conditions. The Ontario Marginalization Index was used to quantify various indicators of social disadvantage for Toronto's neighborhoods. Our findings reveal that people in socioeconomically disadvantaged areas experience elevated UFP exposures. We highlight significant disparities in accessing sustainable transportation, particularly in areas with higher ethnic concentrations. When factoring in daily mobility, UFP exposure disparities in disadvantaged populations are further exacerbated. Furthermore, individuals who do not generate emissions themselves are consistently exposed to higher UFPs, with active transportation users experiencing the highest UFP exposures both at home and at activity locations. Finally, we proposed a novel index, the Community Prioritization Index (CPI), incorporating three indicators, including air quality, social disadvantage, and sustainable transportation. This index identifies neighborhoods experiencing a triple burden, often situated near major infrastructure hubs with high diesel truck activity and lacking greenspace, marking them as high-priority areas for policy action and targeted interventions.

Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord.

Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1ß, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X4, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.

Tip-enhanced Raman spectroscopy based on plasmonic lens excitation and experimental detection.

A tip-enhanced Raman spectroscopy (TERS) based on plasmonic lens (PL) excitation is proposed in this work. A PL expected to realize a strong longitudinal electric field focus is designed. The focusing performance of the PL is calculated via finite-difference time-domain (FDTD) simulation and experimentally detected by a scattering-type scanning near-field optical microscope. The PL is introduced to a TERS system as a focusing device. Experimental results with carbon nanotube samples indicate that the Raman scatting signal is significantly enhanced. It proves experimentally that the combination of a PL focused excitation field with a metallic tip in a TERS system is a promising method.

Holographic plasmonic lenses for surface plasmons with complex wavefront profile.

We present a direct-method solution toward the general problem of plasmonic wavefront manipulation and shaping to realize pre-designated functionalities based on the surface-wave holography (SWH) method. We demonstrate theoretically and experimentally the design and fabrication of holographic plasmonic lenses over surface plasmons with complex wavefront profiles. We show that visible light at 632.8 nm transmitting through a high-aspect-ratio slit or a micro-rectangle hole in a silver film can be focused to a preset three-dimensional point spot in free space via appropriately manipulating the interaction of excited surface plasmons with the nanoscale groove pattern of the holographic lens. The experiment results of scanning near-field optical microscopy for measuring the three-dimensional optical field distribution agree well both with designs and with numerical simulations, and this strongly supports the effectiveness and efficiency of the SWH method in the design of plasmonic devices that can fulfill manipulation and transformation of complicated-profile surface plasmons.

Comprehensive Assessment of 16S rRNA Gene Amplicon Sequencing for Microbiome Profiling across Multiple Habitats.

The 16S rRNA gene works as a rapid and effective marker for the identification of microorganisms in complex communities; hence, a huge number of microbiomes have been surveyed by 16S amplicon-based sequencing. The resolution of the 16S rRNA gene is always considered only at the genus level; however, it has not been verified on a wide range of microbes yet. To fully explore the ability and potential of the 16S rRNA gene in microbial profiling, here, we propose Qscore, a comprehensive method to evaluate the performance of amplicons by integrating the amplification rate, multitier taxonomic annotation, sequence type, and length. Our in silico assessment by a "global view" of 35,889 microbe species across multiple reference databases summarizes the optimal sequencing strategy for 16S short reads. On the other hand, since microbes are unevenly distributed according to their habitats, we also provide the recommended configuration for 16 typical ecosystems based on the Qscores of 157,390 microbiomes in the Microbiome Search Engine (MSE). Detailed data simulation further proves that the 16S amplicons produced with Qscore-suggested parameters exhibit high precision in microbiome profiling, which is close to that of shotgun metagenomes under CAMI metrics. Therefore, by reconsidering the precision of 16S-based microbiome profiling, our work not only enables the high-quality reusability of massive sequence legacy that has already been produced but is also significant for guiding microbiome studies in the future. We have implemented the Qscore as an online service at http://qscore.single-cell.cn to parse the recommended sequencing strategy for specific habitats or expected microbial structures. IMPORTANCE 16S rRNA has long been used as a biomarker to identify distinct microbes from complex communities. However, due to the influence of the amplification region, sequencing type, sequence processing, and reference database, the accuracy of 16S rRNA has not been fully verified on a global range. More importantly, the microbial composition of different habitats varies greatly, and it is necessary to adopt different strategies according to the corresponding target microbes to achieve optimal analytical performance. Here, we developed Qscore, which evaluates the comprehensive performance of 16S amplicons from multiple perspectives, thus providing the best sequencing strategies for common ecological environments by using big data.

The core of maintaining neuropathic pain: Crosstalk between glial cells and neurons (neural cell crosstalk at spinal cord).

BACKGROUND: Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment is relatively scarce. Hyperalgesia mediated by pro-inflammatory factors and chemokines plays an important role in the occurrence and maintenance of NP. DATA TREATMENT: Therefore, we conducted a systematic literature review of experimental NP (PubMed Medline), in order to find the mechanism of inducing central sensitization and explore the intervention methods of hyperalgesia caused by real or simulated injury. RESULT: In this review, we sorted out the activation pathways of microglia, astrocytes and neurons, and the process of crosstalk among them. It was found that in NP, the microglia P2X4 receptor is the key target, which can activate the mitogen-activated protein kinase pathway inward and then activate astrocytes and outwardly activate neuronal tropomyosin receptor kinase B receptor to activate neurons. At the same time, activated neurons continue to maintain the activation of astrocytes and microglia through chemokines on CXCL13/CXCR5 and CX3CL1/CX3CR1. This crosstalk process is the key to maintaining NP. CONCLUSION: We summarize the further research on crosstalk among neurons, microglia, and astrocytes in the central nervous system, elaborate the ways and connections of relevant crosstalk, and find potential crosstalk targets, which provides a reference for drug development and preclinical research.

Predicting spatial variations in annual average outdoor ultrafine particle concentrations in Montreal and Toronto, Canada: Integrating land use regression and deep learning models.

BACKGROUND: Concentrations of outdoor ultrafine particles (UFP; <0.1 µm) and black carbon (BC) can vary greatly within cities and long-term exposures to these pollutants have been associated with a variety of adverse health outcomes. OBJECTIVE: This study integrated multiple approaches to develop new models to estimate within-city spatial variations in annual median (i.e. average) outdoor UFP and BC concentrations as well as mean UFP size in Canada's two largest cities, Montreal and Toronto. METHODS: We conducted year-long mobile monitoring campaigns in each city that included evenings and weekends. We developed generalized additive models trained on land use parameters and deep Convolutional Neural Network (CNN) models trained on satellite-view images. Using predictions from these models, we developed final combined models. RESULTS: In Toronto, the median observed UFP concentration, UFP size, and BC concentration values were 16,172pt/cm3, 33.7 nm, and 1225 ng/m3, respectively. In Montreal, the median observed UFP concentration, UFP size, and BC concentration values were 14,702pt/cm3, 29.7 nm, and 1060 ng/m3, respectively. For all pollutants in both cities, the proportion of spatial variation explained (i.e., R2) was slightly greater (1-2 percentage points) for the combined models than the generalized additive models and a greater (approximately 10 percentage points) than the deep CNN models. The Toronto combined model R2 values in the test set were 0.73, 0.55, and 0.61 for UFP concentrations, UFP size, and BC concentration, respectively. The Montreal combined model R2 values were 0.60, 0.49, and 0.60 for UFP concentration, UFP size, and BC concentration models respectively. For each pollutant, predictions from the combined, deep CNN, and generalized additive models were highly correlated with each other and differences between models were explored in sensitivity analyses. CONCLUSION: Predictions from these models are available to support future epidemiological research examining long-term health impacts of outdoor UFPs and BC.