Assessment of skin sensitization potential of zinc oxide, aluminum oxide, manganese oxide, and copper oxide nanoparticles through the local lymph node assay: 5-bromo-deoxyuridine flow cytometry method.

The advent of nanotechnology has significantly spurred the utilization of nanoparticles (NPs) across diverse sectors encompassing industry, agriculture, engineering, cosmetics, and medicine. Metallic oxides including zinc oxide (ZnO), copper oxide (CuO), manganese oxide (Mn2O3), and aluminum oxide (Al2O3), in their NP forms, have become prevalent in cosmetics and various dermal products. Despite the expanding consideration of these compounds for dermal applications, their potential for initiating skin sensitization (SS) has not been comprehensively examined. An in vivo assay, local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) recognized as an alternative testing method for screening SS potential was used to address these issues. Following the OECD TG 442B guidelines, NPs suspensions smaller than 50 nm size were prepared for ZnO and Al2O3 at concentrations of 10, 25, and 50%, and Mn2O3 and CuO at concentrations of 5, 10, and 25%, and applied to the dorsum of each ear of female BALB/c mice on a daily basis for 3 consecutive days. Regarding the prediction of test substance to skin sensitizer if sensitization index (SI)≥2.7, all 4 NPs were classified as non-sensitizing. The SI values were below 2.06, 1.33, 1.42, and 0.99 for ZnO, Al2O3, Mn2O3, and CuO, respectively, at all test concentrations. Although data presented were negative with respect to adverse SS potential for these 4 NPs, further confirmatory tests addressing other key events associated with SS adverse outcome pathway need to be carried out to arrive at an acceptable conclusion on the skin safety for both cosmetic and dermal applications.

GNUV201, a novel human/mouse cross-reactive and low pH-selective anti-PD-1 monoclonal antibody for cancer immunotherapy.

BACKGROUND: Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. RESULTS: To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™). GNUV201 equally binds to human PD-1 and mouse PD-1, equally inhibits the binding of human PD-1/PD-L1 and mouse PD-1/PD-L1, and effectively suppresses tumor growth in syngeneic mouse models. The epitope of GNUV201 mapped to the "FG loop" of hPD-1, distinct from those of Keytruda® ("C'D loop") and Opdivo® (N-term). Notably, the structural feature where the protruding epitope loop fits into GNUV201's binding pocket supports the enhanced binding affinity due to slower dissociation (8.7 times slower than Keytruda®). Furthermore, GNUV201 shows a stronger binding affinity at pH 6.0 (5.6 times strong than at pH 7.4), which mimics the hypoxic and acidic tumor microenvironment (TME). This phenomenon is not observed with marketed antibodies (Keytruda®, Opdivo®), implying that GNUV201 achieves more selective binding to and better occupancy on PD-1 in the TME. CONCLUSIONS: In summary, GNUV201 exhibited enhanced affinity for PD-1 with slow dissociation and preferential binding in TME-mimicking low pH. Human/monkey/mouse inter-species cross-reactivity of GNUV201 could enable more predictable and translatable efficacy and toxicity preclinical studies. These results suggest that GNUV201 could be an ideal antibody candidate for anti-cancer drug development.

Evaluation of Artemisia dubia folium extract-mediated immune efficacy through developing a murine model for acute and chronic stages of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). RESULTS: The paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage. CONCLUSIONS: Our results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

Oral subacute polypropylene microplastics administration effect on potential immunotoxicity in ICR mice.

Exposure to microplastics may be associated with damage of immune system. Polypropylene microplastics (PP-MPs) with a wide range of beneficial applications have not been extensively studied with respect to the immune system. The aim of this investigation is to examine the influence of two different sizes of PP-MPs (5.2 and 23.9 µm diameter) on immune system components in ICR mice. PP-MPs were administered orally to female and male mice at 0 (corn oil vehicle), 500, 1000, or 2000 mg/kg/d for single and daily for 4-week repeated toxicity test, respectively. No significant differences were observed in number of thymic CD4+, CD8+, CD4+CD8+ T lymphocytes, splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-γ to interleukin-4 in culture supernatants from activated splenocytes ex vivo (48 hr) was lower in females which were repeatedly administered with PP-MPs compared to vehicle irrespective of PP-MPs size and dose. In contrast, the opposite trend was observed in males. Production of tumor necrosis factor-α was upregulated in females that were repeatedly exposed to PP-MPs. The serum IgG2a/IgG1 ratio was lowered in female receiving large-size PP-MPs. Data suggest that immune disturbances resulting in predominant type-2 helper T cell reactivity may occur in mice, especially in females, when repeatedly exposed to PP-MPs. Further investigations with longer exposure periods are necessary to determine the immunotoxicities attributed to PP-MPs.

Drosophila melanogaster as potential alternative animal model for evaluating acute inhalation toxicity.

Drosophila melanogaster (D. melanogaster) is a promising model biological system. It has a short life cycle and can provide a substantial number of specimens suitable for comprehensive genetic and molecular analyses in a short time. In this study, we investigated the acute inhalation toxicity of methylisothiazolinone (MIT) and chloromethylisothiazolinone (CMIT) in a D. melanogaster model. During exposure, environmental conditions, mass median aerodynamic and geometric standard diameters were measured. After inhalation exposure, the survival rate, climbing ability, and bang sensitivity were measured on days 1, 2, and 7. Notably, the survival rate of flies decreased in an exposure concentration-dependent manner. Climbing ability and bang sensitivity were also altered in the MIT/CMIT group, compared with the negative control group. Overall, these results provide a reliable D. melanogaster model system for inhalation toxicity study.

Association of immunotoxicological indices with lung cancer biomarkers in poultry, grape, and rose farming workers.

Exposure to occupational hazards like dust, pesticides, diesel emission particles, or physical hazards in the agricultural sector is known to cause adverse health effects on farm workers. Our study aimed at addressing the association of immunomodulatory status with plasma levels of lung cancer biomarkers in farming population, attempting to recognition of vulnerable farming group. Blood samples from apparently healthy 51 chicken husbandry, 19 grape orchard, and 21 rose greenhouse workers were subjected to evaluate plasma levels of two representative lung cancer biomarkers, pro-gastrin releasing peptide (Pro-GRP) and cytokeratin fragment 19 (CYFRA 21-1). Peripheral blood mononuclear cells obtained from farmers were used for natural killer (NK) cell phenotyping and cytokines (interferon-gamma, IFN-γ and interleukin-13, IL-13) profiling in the culture supernatant. Compared to the rose greenhouse farmers, the grape orchard and chicken husbandry workers revealed a significantly upregulated plasma Pro-GRP and CYFRA 21-1 level. A low proportion of NK cells was observed among the female grape orchard workers and a lowered IFN- γ:IL-13 ratio was seen in the grape and chicken husbandry workers than the rose workers. Our findings imply that grape orchard and chicken husbandry workers have more disturbed immune homeostasis implicated with augmentation in the levels of lung cancer biomarkers than the rose greenhouse workers.

GammaGAN: Gamma-Scaled Class Embeddings for Conditional Video Generation.

In this paper, we propose a new model for conditional video generation (GammaGAN). Generally, it is challenging to generate a plausible video from a single image with a class label as a condition. Traditional methods based on conditional generative adversarial networks (cGANs) often encounter difficulties in effectively utilizing a class label, typically by concatenating a class label to the input or hidden layer. In contrast, the proposed GammaGAN adopts the projection method to effectively utilize a class label and proposes scaling class embeddings and normalizing outputs. Concretely, our proposed architecture consists of two streams: a class embedding stream and a data stream. In the class embedding stream, class embeddings are scaled to effectively emphasize class-specific differences. Meanwhile, the outputs in the data stream are normalized. Our normalization technique balances the outputs of both streams, ensuring a balance between the importance of feature vectors and class embeddings during training. This results in enhanced video quality. We evaluated the proposed method using the MUG facial expression dataset, which consists of six facial expressions. Compared with the prior conditional video generation model, ImaGINator, our model yielded relative improvements of 1.61%, 1.66%, and 0.36% in terms of PSNR, SSIM, and LPIPS, respectively. These results suggest potential for further advancements in conditional video generation.

Immunodysregulatory potentials of polyethylene or polytetrafluorethylene microplastics to mice subacutely exposed via intragastric intubation.

Microplastics (MPs) have been recently recognized as posing a risk to human health. The adverse health effects of MP exposure have been recently reported, especially via the oral exposure route. The present study investigated whether subacute (4 week) exposure to polyethylene (PE) or polytetrafluorethylene (PTFE) MPs via gastric intubation caused immunotoxicity. Two different sizes of PE MPs (6.2 or 27.2 µm) and PTFE MPs (6.0 or 30.5 µm) were administered to 6-week-old mice of both sexes at 0 (corn oil vehicle control), 500, 1000, or 2000 mg/kg/day (n = 4/group). No significant differences were observed between groups in the major thymic or splenic immune cell populations, including thymic CD4+, CD8+, CD4+/CD8+ T lymphocytes, and splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-gamma (IFNγ) to interleukin-4 (IL-4) in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo (48 h) was dose-dependently decreased in female mice that received small- and large-size PTFE MPs. The IFNγ/IL-4 ratio was also decreased in the female mice dosed with large-size PE MPs. The serum IgG2a/IgG1 ratio was dose-dependently increased in male and female animals dosed with small-size PE MPs, in female animals dosed with large-size PTFE MPs, and in male animals dosed with small-size PTFE MPs. The present study implies that immune functions could be affected in animals exposed to MPs via gastric intubation. These effects are dependent on MP size, MP dose, MP polymer type, and mouse sex. Further investigations with longer exposure periods could be necessary to more clearly define the immunotoxic effects of MPs. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00172-6.

Polytetrafluorethylene microplastic particles mediated oxidative stress, inflammation, and intracellular signaling pathway alteration in human derived cell lines.

Microplastics (MPs) are now widely distributed across the aerial, terrestrial, and aquatic environments. Thus, exposure to MPs via the oral, inhalation, or dermal routes is inevitable. Polytetrafluoroethylene (PTFE)-MPs is mainly used for manufacturing nonstick cookware, semiconductors, and medical devices; however, their toxicity has been rarely studied. In the present study, six different human cell lines, which are representative of tissues and cells that directly or indirectly come into contact with MPs, were exposed to two different sizes of irregular shape PTFE-MPs (with an average diameter of 6.0 or 31.7 µm). PTFE-MPs-mediated cytotoxicity, oxidative stress, and changes in proinflammatory cytokine production were then evaluated. We found that the PTFE-MPs did not induce cytotoxicity under any of the experimental conditions. However, PTFE-MPs (especially average diameter of 6.0 µm) induced nitric oxide and reactive oxygen species production in all the cell lines tested. Moreover, both sizes of PTFE-MPs increased the secretion of tumor necrosis factor alpha and interleukin-6 from the U937 macrophage cell line and the A549 lung epithelial cell line, respectively. In addition, PTFE-MPs activated the MAPK signaling pathways, especially the ERK pathway, in A549 and U937 cells, and in the THP-1 dendritic cell line. We also found that the expression of the NLRP3 inflammasome was reduced in the U937 and THP-1 cell lines following treatment with the PTFE-MPs sized 31.7 µm average diameter. Furthermore, expression of the apoptosis regulator, BCL2, was markedly increased in the A549 and U937 cell lines. Thus, although PTFE-MPs exert different effects on different cell types, our findings suggest that PTFE-MPs-associated toxicity may be specifically linked to the activation of the ERK pathway, which ultimately induces oxidative stress and inflammation.

Image Recommendation System Based on Environmental and Human Face Information.

With the advancement of computer hardware and communication technologies, deep learning technology has made significant progress, enabling the development of systems that can accurately estimate human emotions. Factors such as facial expressions, gender, age, and the environment influence human emotions, making it crucial to understand and capture these intricate factors. Our system aims to recommend personalized images by accurately estimating human emotions, age, and gender in real time. The primary objective of our system is to enhance user experiences by recommending images that align with their current emotional state and characteristics. To achieve this, our system collects environmental information, including weather conditions and user-specific environment data through APIs and smartphone sensors. Additionally, we employ deep learning algorithms for real-time classification of eight types of facial expressions, age, and gender. By combining this facial information with the environmental data, we categorize the user's current situation into positive, neutral, and negative stages. Based on this categorization, our system recommends natural landscape images that are colorized using Generative Adversarial Networks (GANs). These recommendations are personalized to match the user's current emotional state and preferences, providing a more engaging and tailored experience. Through rigorous testing and user evaluations, we assessed the effectiveness and user-friendliness of our system. Users expressed satisfaction with the system's ability to generate appropriate images based on the surrounding environment, emotional state, and demographic factors such as age and gender. The visual output of our system significantly impacted users' emotional responses, resulting in a positive mood change for most users. Moreover, the system's scalability was positively received, with users acknowledging its potential benefits when installed outdoors and expressing a willingness to continue using it. Compared to other recommender systems, our integration of age, gender, and weather information provides personalized recommendations, contextual relevance, increased engagement, and a deeper understanding of user preferences, thereby enhancing the overall user experience. The system's ability to comprehend and capture intricate factors that influence human emotions holds promise in various domains, including human-computer interaction, psychology, and social sciences.

Synthetic RNA Therapeutics in Cancer.

Recent advances in the RNA delivery system have facilitated the development of a separate field of RNA therapeutics, with modalities including mRNA, microRNA (miRNA), antisense oligonucleotide (ASO), small interfering RNA, and circular (circRNA) that have been incorporated into oncology research. The main advantages of the RNA-based modalities are high flexibility in designing RNA and rapid production for clinical screening. It is challenging to eliminate tumors by tackling a single target in cancer. In the era of precision medicine, RNA-based therapeutic approaches potentially constitute suitable platforms for targeting heterogeneous tumors that possess multiple sub-clonal cancer cell populations. In this review, we discussed how synthetic coding and non-coding RNAs, such as mRNA, miRNA, ASO, and circRNA, can be applied in the development of therapeutics. SIGNIFICANCE STATEMENT: With development of vaccines against coronavirus, RNA-based therapeutics have received attention. Here, the authors discuss different types of RNA-based therapeutics potentially effective against tumor that are highly heterogeneous giving rise to resistance and relapses to the conventional therapeutics. Moreover, this study summarized recent findings suggesting combination approaches of RNA therapeutics and cancer immunotherapy.

Development of a transcriptome-based determination of innate immune suppressor (TDIS) assay as an in vitro test for immunotoxicity.

Immunotoxicity has been an important topic in toxicology since inadvertent exposures to xenobiotics were found to alter immune functions in humans. While rodent toxicity tests can reveal some levels of immunotoxicity, alternative methods must be developed to identify the detailed mechanisms. In this study, a method of in vitro prediction of innate immune suppression by substances was developed using a genomics approach. The primary selection of immune suppressors was based on their ability to downregulate MCP-1, CCL3, TNF, IL-8, and IL-12p40 expression levels in lipopolysaccharide (LPS)-stimulated THP-1 cells. Among 11 substances classified as potent immune suppressors, six including dexamethasone, tacrolimus, tofacitinib, prednisolone, sodium lauryl sulfate, and benzoic acid were used to create a dataset by transcriptomics of chemical-treated THP-1 cells using bulk RNA sequencing. We selected genes that were significantly upregulated by suppressor treatment while filtering out genes also upregulated in LPS-treated THP-1 cells. We identified a 226-gene immunosuppressive gene set (ISG). Innate immune suppressor signature scores were calculated as the median expression of the ISG. In a validation dataset, the signature score predicted acyclovir, cyclosporine, and mercuric chloride as immune suppressors, while selecting genistein as a non-immune suppressor. Although more dataset integration is needed in the future, our results demonstrated the possibility and utility of a novel genomics-based approach, the transcriptome-based determination of innate immune suppressor (TDIS) assay, to evaluate innate immune suppression by different substances. This provides insight into the development of future alternative testing methods because it reflects a comprehensive genetic signature derived from multiple substances rather than one cytokine.

Teratogenicity of D-allulose.

The objective of this study was to evaluate whether D-allulose has teratogenic effects on rats. A prenatal developmental toxicity test was conducted in SD rats in compliance with modified OECD guidelines test number 414, prenatal developmental toxicity study. Pregnant female rats received repeated doses of 1250, 2500, or 5000 mg/kg body weight D-allulose, or a vehicle control by gavage on GD 6-15. On GD 20, one day prior to the expected day of delivery, pregnant rats were weighed and anesthetized, and laparotomized to remove the uterine and its content were weighed. Fetuses were examined macroscopically for any soft tissue and skeletal changes. The evaluation indicators included general sign observation, body weight, food consumption, animal death, corpora lutea, numbers of embryonic or fetal deaths, and viable fetuses including live birth rate, fetal resorption rate, and stillbirth rate, as well as sex, body weights, and skeletal and soft tissue alterations of fetuses. No treatment-related abnormalities were observed in prenatal developmental toxicity and fetal malformation parameters, indicating that D-allulose had no teratogenic effects on pregnant rats and fetuses. From the findings of this prenatal developmental toxicity study, the NOAEL of D-allulose was estimated to be 5000 mg/kg/day in pregnant SD rats.

The High-Resolution Structure Reveals Remarkable Similarity in PD-1 Binding of Cemiplimab and Dostarlimab, the FDA-Approved Antibodies for Cancer Immunotherapy.

Multiple tumors have responded well to immunotherapies, which use monoclonal antibodies to block the immune checkpoint proteins and reactivate the T-cell immune response to cancer cells. Significantly, the anti-PD-1 antibodies pembrolizumab and nivolumab, which were approved in 2014, have revolutionized cancer therapy, demonstrating dramatic improvement and longer duration. The US FDA authorized the third anti-PD-1 medication, cemiplimab, in 2018 for use in patients with cutaneous squamous cell carcinoma. To further understand the molecular mechanism of the antibody drug, we now reveal the intricate structure of PD-1 in complex with the cemiplimab Fab at a resolution of 1.98 Å. The cemiplimab-PD-1 interaction preoccupies the space for PD-L1 binding with a greater binding affinity than the PD-1/PD-L1 interaction, which is the basis for the PD-1 blocking mechanism. The structure reveals that cemiplimab and dostarlimab are significantly similar in PD-1 binding, although the precise interactions differ. A comparative investigation of PD-1 interactions with the four FDA-approved antibodies reveals that the BC, C'D, and FG loops of PD-1 adopt distinct conformations for optimal interaction with the antibodies. The structural characteristics in this work could be helpful information for developing more potent anti-PD-1 biologics against cancer.

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs. < 5 min) and increased bioavailability (90%) compared to native glucagon in mice. Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI.

Efficient Multi-Scale Stereo-Matching Network Using Adaptive Cost Volume Filtering.

While recent deep learning-based stereo-matching networks have shown outstanding advances, there are still some unsolved challenges. First, most state-of-the-art stereo models employ 3D convolutions for 4D cost volume aggregation, which limit the deployment of networks for resource-limited mobile environments owing to heavy consumption of computation and memory. Although there are some efficient networks, most of them still require a heavy computational cost to incorporate them to mobile computing devices in real-time. Second, most stereo networks indirectly supervise cost volumes through disparity regression loss by using the softargmax function. This causes problems in ambiguous regions, such as the boundaries of objects, because there are many possibilities for unreasonable cost distributions which result in overfitting problem. A few works deal with this problem by generating artificial cost distribution using only the ground truth disparity value that is insufficient to fully regularize the cost volume. To address these problems, we first propose an efficient multi-scale sequential feature fusion network (MSFFNet). Specifically, we connect multi-scale SFF modules in parallel with a cross-scale fusion function to generate a set of cost volumes with different scales. These cost volumes are then effectively combined using the proposed interlaced concatenation method. Second, we propose an adaptive cost-volume-filtering (ACVF) loss function that directly supervises our estimated cost volume. The proposed ACVF loss directly adds constraints to the cost volume using the probability distribution generated from the ground truth disparity map and that estimated from the teacher network which achieves higher accuracy. Results of several experiments using representative datasets for stereo matching show that our proposed method is more efficient than previous methods. Our network architecture consumes fewer parameters and generates reasonable disparity maps with faster speed compared with the existing state-of-the art stereo models. Concretely, our network achieves 1.01 EPE with runtime of 42 ms, 2.92M parameters, and 97.96G FLOPs on the Scene Flow test set. Compared with PSMNet, our method is 89% faster and 7% more accurate with 45% fewer parameters.

Comparison of Overall Immunity Levels among Workers at Grape Orchard, Rose Greenhouse, and Open-Field Onion Farm.

Background: Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. Methods: Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. Results: Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8 ± 3.3%) in comparison to the onion farmers (26.4 ± 3.1%) and the rose farmers (26.9 ± 2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3 ± 0.3%) and the onion (1.6 ± 0.8%) farmers compared with the rose farmers (1.0 ± 0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. Conclusion: Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

Evaluation of potential toxicity of polyethylene microplastics on human derived cell lines.

Microplastics bare of major concern for environmental conservation and animal welfare in recent years as its use has increased tremendously. Polyethylene microplastics (PE-MPs) are the most common microplastics and could get exposed to humans via different routes with oral>inhalation>dermal. Internalization of MPs through epithelial tissue could expose MPs to various cells such as dendritic cells, macrophages/monocytes, and/or T cells. In this study, we aimed at identifying the effects of two different sized (30.5 ± 10.5 and 6.2 ± 2.0 µm) PE-MPs on different human cell lines representing different tissues or cells that get exposed to MPs directly or indirectly. Six cell lines were cultured with different concentrations of PE-MPs and cell viability, intracellular reactive oxygen species (ROS), nitric oxide (NO), and cytokines were measured. PE-MPs did not substantially lower the cell viability of cells however highest concentration (1000 µg/mL) of both sized MPs slightly reduced cell viability in intestinal epithelial Caco-2 and lung epithelial A549 cells. Both sized PE-MPs induced higher NO in all the cell lines and upregulation of ROS generation was demonstrated at THP-1, Jurkat, and U937 immune cell lines. A pro-inflammatory cytokine response was seen in HaCaT keratinocyte cells when cultured with PE-MPs whereas the opposite effect was observed in THP-1 and U937 cells except with THP-1 cells cultured with larger-sized MPs. We found that the PE-MPs do not have the same effects on all kinds of cells and tissues exposed and the immune modulation is not necessarily inflammatory. Thus, this study gives insight into why more detailed studies focused on exposure routes and organ-specific effects of different MPs need to be carried out.

Semantic Segmentation Using Pixel-Wise Adaptive Label Smoothing via Self-Knowledge Distillation for Limited Labeling Data.

To achieve high performance, most deep convolutional neural networks (DCNNs) require a significant amount of training data with ground truth labels. However, creating ground-truth labels for semantic segmentation requires more time, human effort, and cost compared with other tasks such as classification and object detection, because the ground-truth label of every pixel in an image is required. Hence, it is practically demanding to train DCNNs using a limited amount of training data for semantic segmentation. Generally, training DCNNs using a limited amount of data is problematic as it easily results in a decrease in the accuracy of the networks because of overfitting to the training data. Here, we propose a new regularization method called pixel-wise adaptive label smoothing (PALS) via self-knowledge distillation to stably train semantic segmentation networks in a practical situation, in which only a limited amount of training data is available. To mitigate the problem caused by limited training data, our method fully utilizes the internal statistics of pixels within an input image. Consequently, the proposed method generates a pixel-wise aggregated probability distribution using a similarity matrix that encodes the affinities between all pairs of pixels. To further increase the accuracy, we add one-hot encoded distributions with ground-truth labels to these aggregated distributions, and obtain our final soft labels. We demonstrate the effectiveness of our method for the Cityscapes dataset and the Pascal VOC2012 dataset using limited amounts of training data, such as 10%, 30%, 50%, and 100%. Based on various quantitative and qualitative comparisons, our method demonstrates more accurate results compared with previous methods. Specifically, for the Cityscapes test set, our method achieved mIoU improvements of 0.076%, 1.848%, 1.137%, and 1.063% for 10%, 30%, 50%, and 100% training data, respectively, compared with the method of the cross-entropy loss using one-hot encoding with ground truth labels.

Recent Advances in Antibody Therapeutics.

Antibody-based therapeutics have achieved unprecedented success in treating various diseases, including cancers, immune disorders, and infectious diseases [...].