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In agricultural production, weed removal is an important part of crop cultivation, but inevitably, other plants compete with crops for nutrients. Only by identifying and removing weeds can the quality of the harvest be guaranteed. Therefore, the distinction between weeds and crops is particularly important. Recently, deep learning technology has also been applied to the field of botany, and achieved good results. Convolutional neural networks are widely used in deep learning because of their excellent classification effects. The purpose of this article is to find a new method of plant seedling classification. This method includes two stages: image segmentation and image classification. The first stage is to use the improved U-Net to segment the dataset, and the second stage is to use six classification networks to classify the seedlings of the segmented dataset. The dataset used for the experiment contained 12 different types of plants, namely, 3 crops and 9 weeds. The model was evaluated by the multi-class statistical analysis of accuracy, recall, precision, and F1-score. The results show that the two-stage classification method combining the improved U-Net segmentation network and the classification network was more conducive to the classification of plant seedlings, and the classification accuracy reaches 97.7%.

Background Cutaneous mold infections commonly result from an array of traumatic injuries that involve direct inoculation of contaminated soil into wounds. Here, we explored the use of antimicrobial blue light (aBL; 405 nm wavelength) and the combination of aBL with quinine hydrochloride (aBL + Q-HCL) for the treatment of cutaneous mold infections. Methods Efficacy of aBL and aBL + Q-HCL in killing clinically important pathogenic molds (Aspergillus fumigatus, Aspergillus flavus, and Fusarium oxyprorum) was investigated. Ultraperformance liquid chromatography identified and quantified endogenous porphyrins in the mold conidia. Finally, a mouse model of dermabrasion wound infected with a bioluminescent variant of A. fumigatus was developed to investigate the efficacy of aBL in treating cutaneous mold infections. Results We demonstrated that mold conidia are tolerant to aBL, but Q-HCL enhances efficacy. Transmission electron microscopy revealed intracellular damage by aBL. aBL + Q-HCL resulted in intracellular and cell wall damage. Porphyrins were observed in all mold strains, with A. fumigatus having the highest concentration. aBL and aBL + Q-HCL effectively reduced the burden of A. fumigatus within an established dermabrasion infection and limited recurrence posttreatment. Conclusions aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.

Pedestrian detection methods have been significantly improved with the development of deep convolutional neural networks. Nevertheless, detecting ismall-scaled pedestrians and occluded pedestrians remains a challenging problem. In this paper, we propose a pedestrian detection method with a couple-network to simultaneously address these two issues. One of the sub-networks, the gated multi-layer feature extraction sub-network, aims to adaptively generate discriminative features for pedestrian candidates in order to robustly detect pedestrians with large variations on scale. The second sub-network targets on handling the occlusion problem of pedestrian detection by using deformable regional region of interest (RoI)-pooling. We investigate two different gate units for the gated sub-network, namely, the channel-wise gate unit and the spatio-wise gate unit, which can enhance the representation ability of the regional convolutional features among the channel dimensions or across the spatial domain, repetitively. Ablation studies have validated the effectiveness of both the proposed gated multi-layer feature extraction sub-network and the deformable occlusion handling sub-network. With the coupled framework, our proposed pedestrian detector achieves promising results on both two pedestrian datasets, especially on detecting small or occluded pedestrians. On the CityPersons dataset, the proposed detector achieves the lowest missing rates (i.e. 40.78% and 34.60%) on detecting small and occluded pedestrians, surpassing the second best comparison method by 6.0% and 5.87%, respectively.

Stomata are the main medium of water exchange in plants, regulating gas exchange and responsible for the processes of photosynthesis and transpiration. Stomata are surrounded by guard cells and the transpiration rate is controlled by opening and closing stomata. Stomatal state (open and close) plays an important role in describing the health of plants. In addition, counting the number of stomata is of great significance for scientists to study the number of opening and closeing stomata and to measure their density and distribution on the leaf surface through different sampling techniques. Although some techniques for calculating the number of stomata have been proposed, these methods are used to produce samples in isolation and then to identify and classify the states in the sample leaves. We improved YOLO-X and then implemented a transfer learning method to count the number of stomata and identify the stomatal opening and closing status of live black poplar leaves. In the end, the average accuracy and recall of the method were 98.3% and 95.9%, which helped researchers to obtain accurate information on leaf stomatal opening and closing status in an efficient and simple way.

Blue light (BL) has shown bactericidal effectiveness against methicillin-resistant Staphylococcus aureus (MRSA), one of the major clinical pathogens with antibiotic resistance. Bacteria likely respond to the oxidative stress induced by BL; however, the defensive response is still unclear. This study aimed to reveal the phenotypic change in MRSA after being exposed to 15 cycles of sub-lethal BL illumination. The comparative transcriptomic results showed that the expression of peptidoglycan (PG) synthesis gene glmS was significantly upregulated in the cells after the multiple cycle light treatment, and the biochemical analysis determined that the content of PG synthesized was increased by 25.86% when compared with that in control cells. Furthermore, significant thickening of the cell wall was observed under a transmission electron microscope (P < .05). The light sensitivity of the tested MRSA strain was reduced after the multiple cycle light treatment, indicating the possibility of MRSA being more adaptive to the BL stress. The present study suggested that multiple cycles of sub-lethal BL could change the light susceptibility of MRSA through thickening the cell wall.

Biophotonics is defined as the combination of biology and photonics (the physical science of the light). It is a general term for all techniques that deal with the interaction between biological tissues/cells and photons (light). Biophotonics offers a great variety of techniques that can facilitate the early detection of diseases and promote innovative theragnostic approaches. As the COVID-19 infection can be transmitted due to the face-to-face communication, droplets and aerosol inhalation and the exposure to saliva, blood, and other body fluids, as well as the handling of sharp instruments, dental practices are at increased risk of infection. In this paper, a literature review was performed to explore the application of Biophotonics approaches in Dentistry focusing on the COVID-19 pandemic and how they can contribute to avoid or minimize the risks of infection in a dental setting. For this, search-related papers were retrieved from PubMED, Scielo, Google Schoolar, and American Dental Association and Centers for Disease Control and Prevention databases. The body of evidence currently available showed that Biophotonics approaches can reduce microorganism load, decontaminate surfaces, air, tissues, and minimize the generation of aerosol and virus spreading by minimally invasive, time-saving, and alternative techniques in general. However, each clinical situation must be individually evaluated regarding the benefits and drawbacks of these approaches, but always pursuing less-invasive and less aerosol-generating procedures, especially during the COVID-19 pandemic., Graphical abstract Image, graphical abstract

Blue light (BL) exerts an antimicrobial effect on pathogenic bacteria. It has been hypothesized that its bactericidal activity depends upon the generation of reactive oxygen species (such as anion superoxides) and the resultant cellular damage. However, some aspects of this hypothesis needed to be tested and investigated. Thus, the work conducted herein examined the molecular impact of BL treatment on Cronobacter sakazakii, an emerging foodborne pathogen. The results showed that BL exhibited an efficient bactericidal effect against C. sakazakii. Under a sublethal BL dose, both intracellular anion superoxides and malondialdehyde (a marker of oxidative stress) contents were increased gradually. Moreover, permeability of the outer membrane was increased by approximately 50%, indicating membrane damage. Further investigation revealed alterations to cellular fatty acid profiles, with a decrease and disappearance of unsaturated fatty acids, including C18:2, C16:1, and C18:1. These data indicate that bacterial lipids, especially unsaturated fatty acids, are important molecular targets of BL photo-oxidation. The transcriptional response of bacteria to BL was also studied, and it was found that three genes were upregulated, including genes encoding antioxidants. The current study contributes towards an improved understanding of the bactericidal mechanisms of BL and highlights the importance of lipid and membrane damage.

BACKGROUND AND OBJECTIVE Candida albicans is an opportunistic fungal pathogen of clinical importance and is the primary cause of fungal-associated wound infections, sepsis, or pneumonia in immunocompromised individuals. With the rise in antimicrobial resistance, it is becoming increasingly difficult to successfully treat fungal infections using traditional antifungals, signifying that alternative non-traditional approaches must be explored for their efficacy. STUDY DESIGN/MATERIALS AND METHODS We investigated the combination of antimicrobial blue light (aBL) and quinine hydrochloride (Q-HCL) for improved inactivation of C. albicans, in vitro and in vivo, relative to either monotherapy. In addition, we evaluated the safety of this combination therapy in vivo using the TUNEL assay. RESULTS The combination of aBL (108 J/cm2 ) with Q-HCL (1 mg/mL) resulted in a significant improvement in the inactivation of C. albicans planktonic cells in vitro, where a 7.04 log10 colony forming units (CFU) reduction was achieved, compared with aBL alone that only inactivated 3.06 log10 CFU (P

Hindsight experience replay (HER) is a goal relabelling technique typically used with off-policy deep reinforcement learning algorithms to solve goal-oriented tasks; it is well suited to robotic manipulation tasks that deliver only sparse rewards. In HER, both trajectories and transitions are sampled uniformly for training. However, not all of the agent's experiences contribute equally to training, and so naive uniform sampling may lead to inefficient learning. In this paper, we propose diversity-based trajectory and goal selection with HER (DTGSH). Firstly, trajectories are sampled according to the diversity of the goal states as modelled by determinantal point processes (DPPs). Secondly, transitions with diverse goal states are selected from the trajectories by using k-DPPs. We evaluate DTGSH on five challenging robotic manipulation tasks in simulated robot environments, where we show that our method can learn more quickly and reach higher performance than other state-of-the-art approaches on all tasks., Pacific Rim International Conference on Artificial Intelligence, 2021

Increasing resistance to existing antibiotics by microbes is currently the biggest dilemma. Antimicrobial photodynamic therapy is a promising alternative for the treatment of multidrug-resistant infections. The aim of the current study was to fabricate graphene quantum dots loaded with curcumin as photosensitizer for improved antimicrobial photodynamic therapy. The study involved fabrication of blank and curcumin-loaded graphene quantum dots, their characterizations (TEM, UV-visible and fluorescence emission spectra), cytotoxicity assay, ROS assay and investigation of enhanced antimicrobial photodynamic effect against resistant microbes. The fabrication of blank and loaded graphene quantum dots was confirmed by the observation of peak shift and changes in peak intensity of blank graphene quantum dots, curcumin alone compared with curcumin-loaded graphene quantum dots in UV-visible and fluoresce emission spectra. Cytotoxicity assay showed that 100 µm concentration was not toxic to NIH/3t3 fibroblasts. In ROS assay, the curcumin-loaded formulation showed three-fold increase in ROS production. Blue-light (405 nm) irradiance of 30 J cm-2 and photosensitizer concentration of 100 µm showed ˜3.5 log10 enhanced CUF reduction against Pseudomonas aeruginosa, MRSA, Escherichia coli and Candida albicans. In conclusion, curcumin-loaded graphene quantum dots shoed enhanced antimicrobial photodynamic effects and can be used as an alternative effective treatment for resistant infections.

Refereed/Peer-reviewed As antimicrobial resistance continues to compromise the therapeutic efficacy of countless antibiotics, the significant risk this poses to the global population is without question and should be considered emergent. Antimicrobial resistance can be deadly, specifically in terms of case numbers and disease prognosis. The United States Centers for Disease Control and Prevention released a report stating that in the U.S., two million people suffer from severe infections that are highly resistant to conventional treatment regimens.

Objective: The incidence of severe infectious complications after burn injury increases mortality by 40%. However, traditional approaches for managing burn infections are not always effective. High-voltage, pulsed electric field (PEF) treatment shortly after a burn injury has demonstrated an antimicrobial effect in vivo; however, the working parameters and long-term effects of PEF treatment have not yet been investigated. Approach: Nine sets of PEF parameters were investigated to optimize the applied voltage, pulse duration, and frequency or pulse repetition for disinfection of Pseudomonas aeruginosa infection in a stable mouse burn wound model. The bacterial load after PEF administration was monitored for 3 days through bioluminescence imaging. Histological assessments and inflammation response analyses were performed at 1 and 24 h after the therapy. Results: Among all tested PEF parameters, the best disinfection efficacy of P. aeruginosa infection was achieved with a combination of 500 V, 100 μs, and 200 pulses delivered at 3 Hz through two plate electrodes positioned 1 mm apart for up to 3 days after the injury. Histological examinations revealed fewer inflammatory signs in PEF-treated wounds compared with untreated infected burns. Moreover, the expression levels of multiple inflammatory-related cytokines (interleukin [IL]-1α/β, IL-6, IL-10, leukemia inhibitory factor [LIF], and tumor necrosis factor-alpha [TNF-α]), chemokines (macrophage inflammatory protein [MIP]-1α/β and monocyte chemoattractant protein-1 [MCP-1]), and inflammation-related factors (vascular endothelial growth factor [VEGF], macrophage colony-stimulating factor [M-CSF], and granulocyte–macrophage colony-stimulating factor [G-CSF]) were significantly decreased in the infected burn wound after PEF treatment. Innovation: We showed that PEF treatment on infected wounds reduces the P. aeruginosa load and modulates inflammatory responses. Conclusion: The data presented in this study suggest that PEF treatment is a potent candidate for antimicrobial therapy for P. aeruginosa burn infections.

BACKGROUND The purpose of this study was to compare the efficacy of blue light therapy (BLT) and 5% topical benzoyl peroxide (BPO) gel in combination with standard chlorhexidine (CHX) preparation in eradicating Cutibacterium acnes at the deltopectoral interval measured by positive, quantitative culture findings. METHODS Adult male volunteers were randomized to 1 of 3 treatment groups: BPO, BLT, and BPO followed by BLT. Contralateral shoulders served as matched controls. Volunteers randomized to BPO applied the gel for a total of 5 treatments. In the BLT group, a single 23-minute treatment was administered at an estimated irradiance of 40 mW/cm2 (radiant exposure, 55.2 J/cm2). In the BPO-BLT group, volunteers received both treatments as described earlier. After treatment with either BPO, BLT, or both, a single swab culture was taken from the treatment shoulder. Next, control and treatment shoulders were prepared with CHX, and cultures were taken from each shoulder. Cultures were sent for anaerobic quantitative growth analysis with both polymerase chain reaction and Sanger sequencing confirmation of presumptive C acnes colonies. RESULTS This study enrolled 60 male volunteers, 20 per group, with no loss to follow-up. After treatment but prior to CHX administration, all culture samples in the BPO group and BLT group grew C acnes. Prior to CHX, 16 samples (80%) in the BPO-BLT group grew C acnes. On quantitative analysis, the BPO group and BPO-BLT group had significantly less growth of C acnes compared with the BLT group after treatment but prior to CHX (P < .05 for each). Following CHX administration, the BPO and BPO-BLT groups had significantly fewer positive culture findings (odds ratios of 0.03 and 0.29, respectively) and less quantity of growth compared with their control arms (P < .05). This was not seen in the BLT group. For quantitative between-group analysis, no significant synergistic effects were seen with BPO-BLT compared with BPO alone (P = .688). There was no difference in side effects between groups. CONCLUSION The combination of topical BPO and CHX was effective at eliminating C acnes in most cases. BLT alone did not demonstrate effective antimicrobial properties against C acnes at the radiant exposure administered in this study. Combining BPO and BLT did not lead to significant synergistic antimicrobial effects. Both BPO and BLT are safe with few, transient side effects reported. More work is needed to determine whether BLT at higher radiant exposures or serial treatment results in bactericidal effects against C acnes in vivo.

Background Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. Methods In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. Results Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. Conclusions In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.

Background and objectives Biofilms cause more than 80% of infections in humans, including more than 90% of all chronic wound infections and are extremely resistant to antimicrobials and the immune system. The situation is exacerbated by the fast spreading of antimicrobial resistance, which has become one of the biggest threats to current public health. There is consequently a critical need for the development of alternative therapeutics. Antimicrobial blue light (aBL) is a light-based approach that exhibits intrinsic antimicrobial effect without the involvement of exogenous photosensitizers. In this study, we investigated the antimicrobial effect of this non-antibiotic approach against biofilms formed by microbial isolates of multidrug-resistant bacteria. Study design/materials and methods Microbial isolates of Acinetobacter baumannii, Candida albicans, Escherichia coli, Enterococcus faecalis, MRSA, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Proteus mirabilis were studied. Biofilms were grown in microtiter plates for 24 or 48 hours or in the CDC biofilm reactor for 48 hours and exposed to aBL at 405 nm (60 mW/cm2 , 60 or 30 minutes). The anti-biofilm activity of aBL was measured by viable counts. Results The biofilms of A. baumannii, N. gonorrhoeae, and P. aeruginosa were the most susceptible to aBL with between 4 and 8 log10 inactivation after 108 J/cm2 (60 mW/cm2 , 30 minutes) or 216 J/cm2 (60 mW/cm2 , 60 minutes) aBL were delivered in the microplates. On the contrary, the biofilms of C. albicans, E. coli, E. faecalis, and P. mirabilis were the least susceptible to aBL inactivation (-0.30, -0.24, -0.84, and -0.68 log10 inactivation, respectively). The same aBL treatment in biofilms developed in the CDC biofilm reactor, caused -1.68 log10 inactivation in A. baumannii and -1.74 and -1.65 log10 inactivation in two different strains of P. aeruginosa. Conclusions aBL exhibits potential against pathogenic microorganisms and could help with the significant need for new antimicrobials in clinical practice to manage multidrug-resistant infections. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Antimicrobial resistance is a concern to public health, with methicillin resistant Staphylococcus aureus (MRSA) being particularly important. Blue light at 405 nm has demonstrated efficacy for the treatment of localized infections. With respect to MRSA, aBL is not effective enough to be developed into a stand-alone therapy. Findings demonstrated the antioxidant properties of the S. aureus pigment, staphyloxanthin (STX). We hypothesized that the efficacy of 405 nm light on MRSA may improve with STX photolysis using 460 nm light. We report an approach that exploits the STX photolysis effect of 460 nm light to sensitize MRSA to 405 nm light.

As antimicrobial resistance continues to threaten the efficacy of conventional antibiotic therapy, it is paramount that we investigate innovative approaches to treat infectious diseases. In this study, we investigated the antimicrobial capabilities of the innovative combination of antimicrobial blue light (aBL; 405 nm wavelength) with the Pseudomonas aeruginosa pigment pyocyanin against methicillin resistant Staphylococcus aureus (MSRA. We explored the effects of different radiant exposures of aBL and increasing concentrations of pyocyanin against planktonic cells and those within biofilms. In addition, we investigated the effect of the aBL/pyocyanin on the endogenous staphyloxanthin pigment, as well as the role of hydrogen peroxide and singlet oxygen scavenging in the efficacy of this combination. Lastly, we investigated the potential for the aBL/pyocyanin to reduce the MRSA burden within a proof-of-principle mouse abrasion infection model. We found pyocyanin to be a powerful potentiator of aBL activity under all in vitro conditions tested. In addition, we serendipitously discovered the capability of the aBL/pyocyanin combination to bleach staphyloxanthin within colonies of MRSA. Furthermore, we established that singlet oxygen is an important mediator during combined aBL/pyocyanin exposure. Moreover, we found that the combination of aBL and pyocyanin could significantly reduce the viability of MRSA within a proof-of-principle early onset MRSA skin abrasion infection. Exposure to the treatment did not have deleterious effects on skin tissue. In conclusion, the combination of aBL and pyocyanin represents a potentially powerful therapeutic modality for the treatment of infections caused by MRSA.

With the effectiveness of antimicrobials declining as antimicrobial resistance continues to threaten public health, we must look to alternative strategies for the treatment of infections. In this study, we investigated an innovative, drug-free, dual-wavelength irradiation approach that combines 2 wavelengths of light, 460 nm and 405 nm, against methicillin-resistant Staphylococcus aureus (MRSA). MRSA was initially irradiated with 460-nm light (90–360 J/cm(2)) and subsequently irradiated with aliquots of 405-nm light (54–324 J/cm(2)). For in vivo studies, mouse skin was abraded and infected with approximately 10(7) CFUs of MRSA and incubated for 3 hours before irradiating with 460 nm (360 J/cm(2)) and 405 nm (342 J/cm(2)). Naive mouse skin was also irradiated to investigate apoptosis. We found that staphyloxanthin, the carotenoid pigment in MRSA cells, promoted resistance to the antimicrobial effects of 405-nm light. In addition, we found that the photolytic effect of 460-nm light on staphyloxanthin attenuated resistance of MRSA to 405-nm light killing. Irradiation of 460 nm alone did not elicit any antimicrobial effect on MRSA. In a proof-of-principle mouse skin abrasion infection model, we observed significant killing of MRSA using the dual-wavelength irradiation approach. However, when either wavelength of light was administered alone, no significant decrease in bacterial viability was observed. Moreover, exposure of the dual-wavelength irradiation to naive mouse skin did not result in any visible apoptosis. In conclusion, a dual-wavelength irradiation strategy may offer an innovative, effective, and safe approach for the treatment of skin infections caused by MRSA.

The global dissemination of the novel coronavirus disease (COVID-19) has accelerated the need for the implementation of effective antimicrobial strategies to target the causative agent SARS-CoV-2. Light-based technologies have a demonstrable broad range of activity over standard chemotherapeutic antimicrobials and conventional disinfectants, negligible emergence of resistance, and the capability to modulate the host immune response. This perspective article identifies the benefits, challenges, and pitfalls of repurposing light-based strategies to combat the emergence of COVID-19 pandemic., Highlights • Light-based technologies currently are cost-effective and widely available in market. • Photons can be used to inactivate SARS-CoV-2 in air, liquids and on surfaces. • Phototherapy can be used as an adjuvant to control virus infection and to modulate host immune system. • Light-based solutions can significantly contribute to mitigate the impacts of COVID-19 pandemic

Resolution is an active process that protects the host damage from inflammation responses induced by infections. Simultaneously resolving inflammation and eliminating pathogens may be effective to treat infectious diseases, but it is required to deliver therapeutics to infectious sites. Here, we proposed a strategy to incorporate RvD1 and an antibiotic (ceftazidime) in human neutrophil-membrane derived nanovesicles that can specifically target inflamed vasculature for treatment of lung infection caused by P. aeruginosa. Using the nitrogen cavitation method, we generated liposome-like nanovesicles from human neutrophil membrane. The results showed that nanovesicles loaded with RvD1 decreased cytokine levels and neutrophil lung infiltration, thus shortening the resolution intervals of lung inflammation. When RvD1 and ceftazidime were co-loaded in nanovesicles, they alleviated both inflammation and bacterial growth in the mouse lung. The studies reveal a new strategy to treat infectious diseases by designing nanoparticles to simultanesouly target host inflammatory pathways and pathogens., Gao et al. design a lung targeting nanovesicles made from human neutrophils membrane, and co-loaded inflammatory resolving mediator RvD1 and antibiotic CAZ inside the nanovesicles. These nanovesicles could accelerate the inflammation resolution and release the antibiotics to treat bacterial infections in mice. This approach is useful in developing multifunctional nanoparticle-based therapeutics for lung bacterial infections treatment.

Pedestrian detection methods have been significantly improved with the development of deep convolutional neural networks. Nevertheless, robustly detecting pedestrians with a large variant on sizes and with occlusions remains a challenging problem. In this paper, we propose a gated multi-layer convolutional feature extraction method which can adaptively generate discriminative features for candidate pedestrian regions. The proposed gated feature extraction framework consists of squeeze units, gate units and a concatenation layer which perform feature dimension squeezing, feature elements manipulation and convolutional features combination from multiple CNN layers, respectively. We proposed two different gate models which can manipulate the regional feature maps in a channel-wise selection manner and a spatial-wise selection manner, respectively. Experiments on the challenging CityPersons dataset demonstrate the effectiveness of the proposed method, especially on detecting those small-size and occluded pedestrians.

Salient object detection has achieved great improvements by using the Fully Convolutional Networks (FCNs). However, the FCN-based U-shape architecture may cause dilution problems in the high-level semantic information during the up-sample operations in the top-down pathway. Thus, it can weaken the ability of salient object localization and produce degraded boundaries. To this end, in order to overcome this limitation, we propose a novel pyramid self-attention module (PSAM) and the adoption of an independent feature-complementing strategy. In PSAM, self-attention layers are equipped after multi-scale pyramid features to capture richer high-level features and bring larger receptive fields to the model. In addition, a channel-wise attention module is also employed to reduce the redundant features of the FPN and provide refined results. Experimental analysis demonstrates that the proposed PSAM effectively contributes to the whole model so that it outperforms state-of-the-art results over five challenging datasets. Finally, quantitative results show that PSAM generates accurate predictions and integral salient maps, which can provide further help to other computer vision tasks, such as object detection and semantic segmentation.

Moraxella catarrhalis is one of the major otopathogens of otitis media (OM) in childhood. M. catarrhalis tends to form biofilm, which contributes to the chronicity and recurrence of infections, as well as resistance to antibiotic treatment. In this study, we aimed to investigate the effectiveness of antimicrobial blue light (aBL; 405 nm), an innovative nonpharmacological approach, for the inactivation of M. catarrhalis OM. M. catarrhalis either in planktonic suspensions or 24-h old biofilms were exposed to aBL at the irradiance of 60 mW cm(−2). Under an aBL exposure of 216 J cm(−2), a >4-log(10) colony-forming units (CFU) reduction in planktonic suspensions and a >3-log(10) CFU reduction in biofilms were observed. Both transmission electron microscopy and scanning electron microscopy revealed aBL-induced morphological damage in M. catarrhalis. Ultraperformance liquid chromatography results indicated that protoporphyrin IX and coproporphyrin were the two most abundant species of endogenous photosensitizing porphyrins. No statistically significant reduction in the viability of HaCaT cells was observed after an aBL exposure of up to 216 J cm(−2). Collectively, our results suggest that aBL is potentially an effective and safe alternative therapy for OM caused byM. catarrhalis. Further in vivo studies are warranted before this optical approach can be moved to the clinics.

Otopathogens such as Moraxella Catarrhalis and Haemophilus influenzae are the major causes of pediatric chronic and recurrent otitis media (OM). This pilot study showed that both M. catarrhalis and H. influenzae were highly susceptible to antimicrobial blue light (aBL) inactivation at 405 nm, either in suspensions and biofilms. Transmission electron microscopy showed aBL-induced damage of cell membrane in M. catarrhalis cells. Ultra-performance liquid chromatography results revealed that protoporphyrin IX and coproporphyrin are the most abundant species of endogenous porphyrins in M. catarrhalis. Our findings suggest that aBL is potentially an effective alternative antimicrobial therapy for OM.

Over the past decade, antimicrobial blue light (aBL) at 400 - 470 nm wavelength has demonstrated immense promise as an alternative approach for the treatment of multidrug-resistant infections. Since our last review was published in 2017, there have been numerous studies that have investigated aBL in terms of its, efficacy, safety, mechanism, and propensity for resistance development. In addition, researchers have looked at combinatorial approaches that exploit aBL and other traditional and non-traditional therapeutics. To that end, this review aims to update the findings from numerous studies that capitalize on the antimicrobial effects of aBL, with a focus on: efficacy of aBL against different microbes, identifying endogenous chromophores and targets of aBL, Resistance development to aBL, Safety of aBL against host cells, and Synergism of aBL with other agents. We will also discuss our perspective on the future of aBL.

Development of alternatives to antibiotics is one of the top priorities in the battle against multidrug-resistant (MDR) bacterial infections. Here, we report that two naturally occurring nonantibiotic modalities, blue light and phytochemical carvacrol, synergistically kill an array of bacteria including their planktonic forms, mature biofilms, and persisters, irrespective of their antibiotic susceptibility. Combination but not single treatment completely or substantially cured acute and established biofilm-associated Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus infections of full thickness murine third-degree burn wounds and rescued mice from lethal Pseudomonas aeruginosa skin wound infections. The combined therapy diminished bacterial colony-forming units as high as 7.5 log10 within 30 min and introduced few adverse events in the survival of cocultured mammalian cells, wound healing, or host DNA. Mechanistic studies revealed that carvacrol was photocatalytically oxidized into a series of photoreactive substrates that underwent photolysis or additional photosensitization reactions in response to the same blue light, forming two autoxidation cycles that interacted with each other resulting in robust generation of cytotoxic reactive oxygen species. This phototoxic reaction took place exclusively in bacteria, initiated by blue light excitation of endogenous porphyrin-like molecules abundantly produced in bacteria compared with mammalian cells. Moreover, no bacterial resistance developed to the combined treatment after 20 successive passages. This highly selective phototoxic reaction confers a unique strategy to combat the growing threat of MDR bacteria.

UVC radiation is known to be highly germicidal. However, exposure to 254-nm-UVC light causes DNA lesions such as cyclobutane pyrimidine dimers (CPD) in human cells, and can induce skin cancer after long-term repeated exposures. It has been reported that short wavelength UVC is absorbed by proteins in the membrane and cytosol, and fails to reach the nucleus of human cells. Hence, irradiation with 222-nm UVC might be an optimum combination of effective disinfection and biological safety to human cells. In this study, the biological effectiveness of 222-nm UVC was investigated using a mouse model of a skin wound infected with methicillin-resistant Staphylococcus aureus (MRSA). Irradiation with 222-nm UVC significantly reduced bacterial numbers on the skin surface compared with non-irradiated skin. Bacterial counts in wounds evaluated on days 3, 5, 8 and 12 after irradiation demonstrated that the bactericidal effect of 222-nm UVC was equal to or more effective than 254-nm UVC. Histological analysis revealed that migration of keratinocytes which is essential for the wound healing process was impaired in wounds irradiated with 254-nm UVC, but was unaffected in 222-nm UVC irradiated wounds. No CPD-expressing cells were detected in either epidermis or dermis of wounds irradiated with 222-nm UVC, whereas CPD-expressing cells were found in both epidermis and dermis irradiation with 254-nm UVC. These results suggest that 222-nm UVC light may be a safe and effective way to reduce the rate of surgical site and other wound infections.

Recently, there have been increasing numbers of publications illustrating the potential of light-based antimicrobial therapies to combat antimicrobial resistance. Several modalities, in particular, which have proven antimicrobial efficacy against a wide range of pathogenic microbes include: photodynamic therapy (PDT), ultraviolet light (UVA, UVB and UVC), and antimicrobial blue light (aBL). Using these techniques, microbial cells can be inactivated rapidly, either by inducing reactive oxygen species that are deleterious to the microbial cells (PDT, aBL and UVA) or by causing irreversible DNA damage via direct absorption (UVB and UVC). Given the multi-targeted nature of light-based antimicrobial modalities, it has been hypothesised that resistance development to these approaches is highly unlikely. Furthermore, with the exception of a small number of studies, it has been found that resistance to light based anti-infective agents appears unlikely, irrespective of the modality in question. The concurrent literature however stipulates, that further studies should incorporate standardised microbial tolerance assessments for light-based therapies to better assess the reproducibility of these observations.

Made available in DSpace on 2022-04-28T19:41:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 In December 2019, a severe case of pneumonia of unknown etiology appeared in Wuhan, China. Three months later, the highly contagious coronavirus disease, Covid-19, was declared a pandemic. Covid-19 is caused by a novel coronavirus SARS-CoV-2, that in March 2021 has infected more than 120 million people worldwide and killed more than 2.7 million. Covid-19 has been the deadliest pandemic to arise since the 1918 Spanish flu, shutting down economies and societies worldwide. Covid-19 caused patients to neglect routine visitations to their healthcare providers, out of fear of catching the disease. Fortunately, within our arsenal exist great tools to limit transmission of Covid-19, including face masks and persistent decontamination of surfaces. They have allowed the population to safely return to work and feel safer when visiting their healthcare providers. Arguably, dental workers and patients face a great risk. Although dental workers are appropriately masked during procedures, patients cannot be masked. With 50% of Covid-19 patients presenting as asymptomatic, contamination of dental clinics with SARS-CoV-2 is a genuine concern. An unmasked patient undergoing routine dental procedures can easily spread saliva containing SARS-CoV-2 across dental clinics, which may facilitate transmission of Covid-19. Therefore, an effective decontamination method, such as ultraviolet C (UVC) light, capable of inactivating SARS-CoV-2 on different surfaces as well as within aerosols, may warranted lower the risk of transmission within the dental clinic. In this review, we propose to discuss the studies that have investigated the potential for UVC to decontaminate face masks, surfaces, and aerosols, with a focus on how these may be applied to the dental clinic. Wellman Center for Photomedicine Massachusetts General Hospital Harvard Medical School Vaccine and Immunotherapy Center Massachusetts General Hospital Harvard Medical School Department of Internal Medicine Faculty of Veterinary Medicine and Animal Science University of São Paulo - USP Department of Restorative Dentistry School of Dentistry São Paulo State University - UNESP Department of Restorative Dentistry School of Dentistry São Paulo State University - UNESP

Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune response. Broad bacterial susceptibility to antimicrobial peptides offers an additional tool to expand knowledge about the evolution of antimicrobial resistance. Structural and functional limitations, combined with a stricter regulatory environment, have hampered the clinical translation of antimicrobial peptides as potential therapeutic agents. Existing computational and experimental tools attempt to ease the preclinical and clinical development of antimicrobial peptides as novel therapeutics. This Review identifies the benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens, highlights advances in the deployment of novel promising antimicrobial peptides, and underlines the needs and priorities in designing focused development strategies taking into account the most advanced tools available.

Tracking of anatomical structures has multiple applications in the field of biomedical imaging, including screening, diagnosing and monitoring the evolution of pathologies. Semi-automated tracking of elongated structures has been previously formulated as a problem suitable for deep reinforcement learning (DRL), but it remains a challenge. We introduce a maximum entropy continuous-action DRL neural tracker capable of training from scratch in a complex environment in the presence of high noise levels, Gaussian blurring and detractors. The trained model is evaluated on two-photon microscopy images of mouse cortex. At the expense of slightly worse robustness compared to a previously applied DRL tracker, we reach significantly higher accuracy, approaching the performance of the standard hand-engineered algorithm used for neuron tracing. The higher sample efficiency of our maximum entropy DRL tracker indicates its potential of being applied directly to small biomedical datasets.

Blue light (BL) exerts an antimicrobial effect on pathogenic bacteria. It has been hypothesized that its bactericidal activity depends upon the generation of reactive oxygen species (such as anion superoxides) and the resultant cellular damage. However, some aspects of this hypothesis needed to be tested and investigated. Thus, the work conducted herein examined the molecular impact of BL treatment on

Platelet (PLT) storage is currently limited to 5 days in clinics in the United States, in part, due to an increasing risk for microbial contamination over time. In light of well-documented antimicrobial activity of blue light (405–470 nm), we investigated potentials to decontaminate microbes during PLT storage by antimicrobial blue light (aBL). We found that PLTs produced no detectable levels of porphyrins or their derivatives, the chromophores that specifically absorb blue light, in marked contrast to microbes that generated porphyrins abundantly. The difference formed a basis with which aBL selectively inactivated contaminated microbes prior to and during the storage, without incurring any harm to PLTs. In accordance with this, when contamination with representative microbes was simulated in PLT concentrates supplemented with 65% of PLT additive solution in a standard storage bag, all “contaminated” microbes tested were completely inactivated after exposure of the bag to 405 nm aBL at 75 J/cm(2) only once. While killing microbes efficiently, this dose of aBL irradiation exerted no adverse effects on the viability, activation or aggregation of PLTs ex vivo and could be used repeatedly during PLT storage. PLT survival in vivo was also unaltered by aBL irradiation after infusion of aBL-irradiated mouse PLTs into mice. The study provides proof-of-concept evidence for a potential of aBL to decontaminate PLTs during storage.

BACKGROUND AND OBJECTIVES The aim of this study was to investigate the efficacy, safety, and mechanism of action of antimicrobial blue light (aBL) for the inactivation of Neisseria gonorrhoeae, the etiological agent of gonorrhea. STUDY DESIGN/MATERIALS AND METHODS The susceptibilities of N. gonorrhoeae (ATCC 700825) in planktonic suspensions to aBL at 405- and 470-nm wavelengths were compared. The roles of oxygen in the anti-gonococcal activity of aBL were studied by examining the effects of hypoxic condition (blowing N2 ) on the anti-gonococcal efficiency of 405-nm aBL. The presence, identification, and quantification of endogenous photosensitizers in N. gonorrhoeae cells and human vaginal epithelial cells (VK2/E6E7 cells) were determined using fluorescence spectroscopy and ultra-performance liquid chromatography (UPLC). Finally, the selectivity of aBL inactivation of N. gonorrhoeae over the host cells were investigated by irradiating the co-cultures of N. gonorrhoeae and human vaginal epithelial cells using 405-nm aBL. RESULTS About 3.12-log10 reduction of bacterial colony forming units (CFU) was achieved by 27 J/cm 2 exposure at 405 nm, while about 3.70-log10 reduction of bacterial CFU was achieved by 234 J/cm2 exposure at 470 nm. The anti-gonococcal efficacy of 405-nm aBL was significantly suppressed under hypoxic condition. Spectroscopic and UPLC analyses revealed the presence of endogenous porphyrins and flavins in N. gonorrhoeae. The concentrations of endogenous photosensitizers in N. gonorrhoeae (ATCC 700825) cells were more than 10 times higher than those in the VK2/E6E7 cells. In the co-cultures of N. gonorrhoeae and VK2/E6E7 cells, 405-nm aBL at 108 J/cm2 preferentially inactivated N. gonorrhoeae cells while sparing the vaginal epithelial cells. CONCLUSIONS aBL at 405-nm wavelength is more effective than 470-nm wavelength in inactivating N. gonorrhoeae while sparing the vaginal epithelial cells. Reactive oxygen species generated from the photochemical reactions between aBL and endogenous photosensitizers play a vital role in the anti-gonococcal activity of 405-nm aBL. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Confronted with the severe situation that the pace of resistance acquisition is faster than the clinical introduction of new antibiotics, health organizations are calling for effective approaches to combat methicillin‐resistant Staphylococcus aureus (MRSA) infections. Here, an approach to treat MRSA through photolysis of staphyloxanthin, an antioxidant residing in the microdomain of S. aureus membrane, is reported. This photochemistry process is uncovered through transient absorption imaging and quantitated by absorption spectroscopy, Raman spectroscopy, and mass spectrometry. Photolysis of staphyloxanthin transiently elevates the membrane permeability and renders MRSA highly susceptible to hydrogen peroxide attack. Consequently, staphyloxanthin photolysis by low‐level 460 nm light eradicates MRSA synergistically with hydrogen peroxide and other reactive oxygen species. The effectiveness of this synergistic therapy is well validated in MRSA planktonic culture, MRSA‐infected macrophage cells, stationary‐phase MRSA, persisters, S. aureus biofilms, and two mice wound infection models. Collectively, the work demonstrates that staphyloxanthin photolysis is a new therapeutic platform to treat MRSA infections.

With the increasing number of pathogenic microbes that are becoming resistant to routinely used antimicrobials, it is important to look to non-traditional approaches for the treatment of infections. Antimicrobial blue light (aBL;405 nm) is a novel strategy for the treatment of infections. Here we report an investigation into the potential for resistance development to aBL in three clinically important Gram-negative bacteria, through sequential exposure in vitro and in vivo. We found that 20 cycles of aBL exposure, in vitro, did not incur resistance development, in any of the species tested (Acinetobacter baumanii, Pseudomonas aeruginosaor Escherichia coli). In addition, sub-curative sequential aBL treatment of a wound infected with a bioluminescent variant of the P. aeruginosa PAO1 strain, did not influence sensitivity to aBL. In conclusion, it is unlikely that sequential treatment of aBL will result in resistance generation, suggesting that multiple treatments of aBL may be administered without resistance development becoming a concern.

Antimicrobial resistance in Neisseria gonorrhoeae is a major issue of public health, and there is a critical need for the development of new anti-gonococcal strategies. In this study, we investigated the effectiveness of antimicrobial blue light (aBL; 405 nm wavelength), an innovative non-pharmacological approach, for the inactivation of N. gonorrhoeae. Our findings indicated that aBL preferentially inactivated N. gonorrhoeae, including antibiotic-resistant strains, over human vaginal epithelial cells in vitro. Furthermore, no genotoxicity of aBL to the vaginal epithelial cells was observed at the radiant exposure for inactivating N. gonorrhoeae. aBL also effectively inactivated N. gonorrhoeae that had attached to and invaded into the vaginal epithelial cells in their co-cultures. No gonococcal resistance to aBL developed after 15 successive cycles of sub-therapeutic aBL inactivation. Taken together, aBL represents a potent potential treatment for antibiotic-resistant gonococcal infection.

Background and Objectives: Antimicrobial resistance is a rapidly evolving and emerging threat to modern medicine. Non-antibiotic approaches can be alternatives to minimize the development of antimicrobial resistance. The present study aims at investigation of synergistic effects of antimicrobial blue light (aBL) at 405 nm with oregano oil on bacterial inactivation, both of which are non-antibiotic approaches and possess different and multiple targets.

With the effectiveness of antimicrobials waning because of antimicrobial resistance, it is imperative that novel strategies are investigated for the treatment of infections. Antimicrobial blue light (aBL) is an innovative strategy that has proven efficacy against an array of pathogens, albeit, with different species having variable susceptibilities to the therapy. Quinine was discovered during the mid-17th century as a plant-derived potent antimalarial. More recently, its bactericidal properties were revealed, illustrating its potential as an antimicrobial adjuvant. Here we report a novel combination therapy, aBL+quinine hydrochloride (Q-HCL) for the treatment of multi-drug resistant infections. QHCL successfully potentiated the antimicrobial effects of aBL in numerous microbial pathogens of different etiologies, in vitro and in vivo. In addition, it synergistically improved the antimicrobial effects of aBL against bacterial biofilms. Raman spectroscopy revealed that concurrent exposure of aBL and Q-HCL improved uptake of Q-HCL into bacterial cells, when compared to the non aBL exposed sample. In addition, ultra-pure liquid chromatography (UPLC) revealed that Q-HCL increased the relative abundance of porphyrins in bacteria, suggesting the mechanism of this synergistic interaction is through increased production of intermediate photosensitizing porphyrins arising through perturbation of the heme biosynthesis pathway by Q-HCL. Genotoxic potential of the combination therapy against mouse skin tissue, was evaluated using the TUNEL assay, where it was revealed that a high dose exposure of aBL+Q-HCL (

Catheter–associated urinary tract infections (CAUTIs) cause millions of infections in the US every year, with direct medical costs exceeding billions of dollars and resulting in > 1 million ER visits and hospitalizations, resulting in thousands of deaths. CAUTI is thought to be a major reservoir both containing and creating highly drug-resistant infections, due to the chronicity of infection, biofilm formation, and the setting of institutionalization with chronic exposure to antibiotics, thus enabling resistance. To reduce antibiotic resistance developing in this setting, we are attempting to apply both antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and combinations of both with minimal use of antibiotics. To this end, we established a rat model of UTI. In this model, we catheterized female rats, infected them with a standard uropathogenic E.Coli (UPEC; UTI89), infused the bladder with methylene blue (MB) and potassium Iodide (KI), and illuminated the bladder once with a diffusing fiber connected to a 1W 660nm laser. Multilog killing was observed, but given the transient nature of ROS generation, regrowth of UPEC was seen 24 hours later. To this end, we are experimenting with the combination of illumination with antibiotics. When tetracyclines are illuminated by aBL, we have found > 6 log(10) steps of microbial killing in vitro, and significant drops in the antibiotic MIC effected by the combination of light and drug. Multiple treatments with aBL and aPDT both with and without limited intravesical application of antimicrobials may light the way to solving this problem.