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Abstract Neutrophils perform essential functions in antimicrobial defense and tissue maintenance at mucosal barriers. However, a dysregulated neutrophil response and, in particular, the excessive release of neutrophil extracellular traps (NETs) are implicated in the pathology of various diseases. In this review, we provide an overview of the basic concepts related to neutrophil functions, including NET formation, and discuss the mechanisms associated with NET activation and function in the context of the prevalent oral disease periodontitis.

“Organoids”, three-dimensional self-organized organ-like miniature tissues, are proposed as intermediary models that bridge the gap between animal and human studies in drug development. Despite recent advancements in organoid model development, studies on toxicity using these models are limited. Therefore, in this study, we aimed to analyze the functionality and gene expression of pre- and post-differentiated human hepatic organoids derived from induced pluripotent stem cells and utilize them for toxicity assessment. First, we confirmed the functional similarity of this hepatic organoid model to the human liver through various functional assessments, such as glycogen storage, albumin and bile acid secretion, and cytochrome P450 (CYP) activity. Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids.

The implementation of deep convolutional neural networks (CNN) in single image super-resolution (SISR) has been successful at improving restoration quality. However, due to analysis made in previous works, it is observed that missing details in low-resolution (LR) images mostly exist in high-frequency regions. Since CNN operates all regions of the low-resolution (LR) image equally, the computation redundancy is observed in the low-frequency area. We generate a gradient-based binary mask (decision mask) to discriminate the high-frequency areas from the low-frequency areas and apply two kinds of convolution to them separately. We propose an Area-Specific CNN (ASCNN) for super-resolution. It consists of high parameter convolutions and low parameter convolutions to process the high-frequency areas and low-frequency areas separately, which efficiently reduces the FLOPs (floating-point operation) while maintaining restoration quality. The settings for reduction are configurable and experimental results show that ASCNN achieves state-of-the-art performance with FLOPs reduction up to 40.1% / 37.0% / 34.0% for $\times 2/\times 3/\times 4$ scale factors.

Although the typical CT findings of Pneumocystis jiroveci pneumonia (PJP) include diffuse or multifocal areas of ground-glass opacities in both lungs, it can also rarely manifest as multiple pulmonary nodules. We report a rare case of atypical PJP in an immunocompromised patient with multiple myeloma, presenting as widespread ground-glass opacities and multiple necrotic subpleural nodules in both lungs on CT, which proved to be granulomatous PJP on percutaneous transthoracic needle biopsy.

Background Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) contribute to an impaired functionality of natural killer (NK) cells that have emerged as a promising therapeutic modality. The interaction between CAFs and NK cells within the TME exerts major inhibitory effects on immune responses, indicating CAF-targeted therapies as potential targets for effective NK-mediated cancer killing.Methods To overcome CAF-induced NK dysfunction, we selected an antifibrotic drug, nintedanib, for synergistic therapeutic combination. To evaluate synergistic therapeutic efficacy, we established an in vitro 3D Capan2/patient-derived CAF spheroid model or in vivo mixed Capan2/CAF tumor xenograft model. The molecular mechanism of NK-mediated synergistic therapeutic combination with nintedanib was revealed through in vitro experiments. In vivo therapeutic combination efficacy was subsequently evaluated. Additionally, the expression score of target proteins was measured in patient-derived tumor sections by the immunohistochemical method.Results Nintedanib blocked the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway and diminished the activation and growth of CAFs, markedly reducing CAF-secreted IL-6. Moreover, coadministration of nintedanib improved the mesothelin (MSLN) targeting chimeric antigen receptor-NK-mediated tumor killing abilities in CAF/tumor spheroids or a xenograft model. The synergistic combination resulted in intense NK infiltration in vivo. Nintedanib alone exerted no effects, whereas blockade of IL-6 trans-signaling ameliorated the function of NK cells. The combination of the expression of MSLN and the PDGFRβ+-CAF population area, a potential prognostic/therapeutic marker, was associated with inferior clinical outcomes.Conclusion Our strategy against PDGFRβ+-CAF-containing pancreatic cancer allows improvements in the therapy of pancreatic ductal adenocarcinoma.

Activation of microglia, which is the primary immune cell of the central nervous system, plays an important role in neuroinflammation associated with several neuronal diseases. Aminoacyl tRNA synthetase (ARS) complex-interacting multifunctional protein 1 (AIMP1), a structural component of the multienzyme ARS complex, is secreted to trigger a pro-inflammatory function and has been associated with several inflammatory diseases. However, the effect of AIMP1 on microglial activation remains unknown. AIMP1 elevated the expression levels of activation-related cell surface markers and pro-inflammatory cytokines in primary and BV-2 microglial cells. In addition to the AIMP1-mediated increase in the expression levels of M1 markers [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β], the expression levels of CD68, an M1 cell surface molecule, were also increased in AIMP-1-treated microglial cells, while those of CD206, an M2 cell surface molecule, were not, indicating that AIMP1 triggers the polarization of microglial cells into the M1 state but not the M2 state. AIMP1 treatment induced the phosphorylation of mitogen-activated protein kinases (MAPKs), while MAPK inhibitors suppressed the AIMP1-induced microglial cell activation. AIMP1 also induced the phosphorylation of the nuclear factor-kappa B (NF-κB) components and nuclear translocation of the NF-κB p65 subunit in microglial cells. Furthermore, c-Jun N-terminal kinase (JNK) and p38 inhibitors markedly suppressed the AIMP1-induced phosphorylation of NF-κB components as well as the nuclear translocation of NF-κB p65 subunit, suggesting the involvement of JNK and p38 as upstream regulators of NF-κB in AIMP1-induced microglial cell activation. The NF-κB inhibitor suppressed the AIMP1-induced M1 polarization of the microglial cells. Taken together, AIMP1 effectively induces M1 microglial activation via the JNK and p38/NF-κB-dependent pathways. These results suggest that AIMP1 released under stress conditions may be a pathological factor that induces neuroinflammation.

IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.

Threonyl-tRNA synthetase (TRS) is an aminoacyl-tRNA synthetase that catalyzes the aminoacylation of tRNA by transferring threonine. In addition to an essential role in translation, TRS was extracellularly detected in autoimmune diseases and also exhibited pro-angiogenetic activity. TRS is reported to be secreted into the extracellular space when vascular endothelial cells encounter tumor necrosis factor-α. As T helper (Th) type 1 response and IFN-γ levels are associated with autoimmunity and angiogenesis, in this study, we investigated the effects of TRS on dendritic cell (DC) activation and CD4 T cell polarization. TRS-treated DCs exhibited up-regulated expression of activation-related cell-surface molecules, including CD40, CD80, CD86, and MHC class II. Treatment of DCs with TRS resulted in a significant increase of IL-12 production. TRS triggered nuclear translocation of the NF-κB p65 subunit along with the degradation of IκB proteins and the phosphorylation of MAPKs in DCs. Additionally, MAPK inhibitors markedly recovered the degradation of IκB proteins and the increased IL-12 production in TRS-treated DCs, suggesting the involvement of MAPKs as the upstream regulators of NF-κB in TRS-induced DC maturation and activation. Importantly, TRS-stimulated DCs significantly increased the populations of IFN-γ+CD4 T cells, and the levels of IFN-γ when co-cultured with CD4+ T cells. The addition of a neutralizing anti-IL-12 mAb to the cell cultures of TRS-treated DCs and CD4+ T cells resulted in decreased IFN-γ production, indicating that TRS-stimulated DCs may enhance the Th1 response through DC-derived IL-12. Injection of OT-II mice with OVA-pulsed, TRS-treated DCs also enhanced Ag-specific Th1 responses in vivo. Importantly, injection with TRS-treated DC exhibited increased populations of IFN-γ+-CD4+ and -CD8+ T cells as well as secretion level of IFN-γ, resulting in viral clearance and increased survival periods in mice infected with influenza A virus (IAV), as the Th1 response is associated with the enhanced cellular immunity, including anti-viral activity. Taken together, these results indicate that TRS promotes the maturation and activation of DCs, DC-mediated Th1 responses, and anti-viral effect on IAV infection.

Background Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. Methods We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. Results Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. Conclusions PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

Abstract High-Efficiency Video Coding (HEVC) is the latest video coding standard, in which the compression performance is double that of its predecessor, the H.264/AVC standard, while the video quality remains unchanged. In HEVC, the test zone (TZ) search algorithm is widely used for integer motion estimation because it effectively searches the good-quality motion vector with a relatively small amount of computation. However, the complex computation structure of the TZ search algorithm makes it difficult to implement it in the hardware. This paper proposes a new integer motion estimation algorithm which is designed for hardware execution by modifying the conventional TZ search to allow parallel motion estimations of all prediction unit (PU) partitions. The algorithm consists of the three phases of zonal, raster, and refinement searches. At the beginning of each phase, the algorithm obtains the search points required by the original TZ search for all PU partitions in a coding unit (CU). Then, all redundant search points are removed prior to the estimation of the motion costs, and the best search points are then selected for all PUs. Compared to the conventional TZ search algorithm, experimental results show that the proposed algorithm significantly decreases the Bjøntegaard Delta bitrate (BD-BR) by 0.84%, and it also reduces the computational complexity by 54.54%.

Abstract The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster–Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.

Mst1 is a multifunctional serine/threonine kinase that is highly expressed in several immune organs. The role of Mst1 in the activation of dendritic cells (DCs), a key player of adaptive immunity, is poorly understood. In this study, we investigated the role of Mst1 in GM-CSF-induced bone marrow-derived DCs and the underlying mechanisms. Mst1−/− DCs in response to GM-CSF expressed higher levels of activation/maturation-related cell surface molecules, such as B7 and MHC class II than Mst1+/+ DCs. Furthermore, the expression of proinflammatory cytokines, such as IL-23, TNF-α, and IL-12p40, was increased in Mst1−/− DCs, indicating that Mst1-deficiency may induce the hyperactivation of DCs. Additionally, Mst1−/− DCs exhibited a stronger capacity to activate allogeneic T cells than Mst1+/+ DCs. Silencing of Mst1 in DCs promoted their hyperactivation, similar to the phenotypes of Mst1−/− DCs. Mst1−/− DCs exhibited an increase in Akt1 phosphorylation and c-myc protein levels. In addition, treatment with an Akt1 inhibitor downregulated the protein level of c-myc increased in Mst1-deficient DCs, indicating that Akt1 acts as an upstream inducer of the de novo synthesis of c-myc. Finally, Akt1 and c-myc inhibitors downregulated the increased expression of IL-23p19 observed in Mst1-knockdown DCs. Taken together, these data demonstrate that Mst1 negatively regulates the hyperactivation of DCs through downregulation of the Akt1/c-myc axis in response to GM-CSF, and suggest that Mst1 is one of the endogenous factors that determine the activation status of GM-CSF-stimulated inflammatory DCs.

Asthma is a common chronic inflammatory disease, which is characterized by airway hyperresponsiveness (AHR), high serum levels of immunoglobulin (Ig)E, and recruitment of various inflammatory cells such as eosinophils and lymphocytes. Korean traditional fermented foods have been reported to exert beneficial effects against allergic diseases such as asthma and atopic dermatitis. In this study, we investigated whether Staphylococcus succinus strain 14BME20 (14BME20) isolated from doenjang, a traditional high-salt-fermented soybean food of Korea, exerts suppressive effects on allergic airway inflammation in a murine model. Mice were orally administered with 14BME20, then sensitized and challenged with ovalbumin as an allergen. Administration of the 14BME20 significantly suppressed AHR and influx of inflammatory cells into the lungs and reduced serum IgE levels. Moreover, the proportion of T helper type 2 (Th2) cells and the production of Th2 cytokines were decreased in 14BME20-treated mice, whereas dendritic cells (DCs) with tolerogenic characteristics were increased. In contrast, oral administration of 14BME20 increased the proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells and the level of interleukin (IL)-10 in 14BME20-treated mice. Furthermore, 14BME20 induced maturation of tolerogenic DCs, and 14BME20-treated DCs increased Treg cell population in a co-culture system of DCs and CD4+ T cells. The addition of a neutralizing anti-IL-10 mAb to the culture of cells that had been treated with 14BME20 decreased the enhanced Treg cell population, thereby indicating that 14BME20-treated DCs increase Treg cell population via DC-derived IL-10. These results demonstrate that oral administration of 14BME20 suppresses airway inflammation by enhancing Treg responses and suggest that the 14BME20 isolated from doenjang may be a therapeutic agent for allergic asthma.

Peptide materials have recently been considered for use in various industrial fields. Because of their efficacy, safety, and low cost, therapeutic peptides are studied for various diseases, including atopic dermatitis (AD). AD is a common inflammatory skin disease impairing the patient’s quality of life. Various therapies, such as treatments with corticosteroids, calcineurin inhibitors, and antibody drugs, have been applied, but numerous side effects have been reported, including skin atrophy, burning, and infection. In the case of antibody drugs, immunogenicity against the drugs can be a problem. To overcome these side effects, small peptides are considered therapeutic agents. We previously identified the small wound healing peptide AES16-2M with a sequence of REGRT, and examined its effects on AD in this study. Interestingly, the administration of AES16-2M downregulated the AD disease score, ear thickness, serum IgE, and thymic stromal lymphopoietin (TSLP) in AD mice. The thickness of the epidermal layer was also improved by AES16-2M treatment. In addition, quantities of IL-4-, IL-13-, and IL-17-producing CD4 T cells from peripheral lymph nodes and spleens were reduced by injection of AES16-2M. Furthermore, the expression of TSLP was significantly reduced in AES16-2M-treated human keratinocytes. Therefore, these results suggest that AES16-2M can be a novel candidate for AD treatment.

Pulmonary arteriovenous fistula (PAVF) is abnormally dilated vessels that provide a right-to-left shunt between pulmonary artery and pulmonary vein and is clinically divided into simple and complex type. Here, we report four cases of surgically resected sporadic PAVFs presenting various clinical and histologic spectrums. Cases 1 (a 57-old-female) and 2 (a 54-old-female) presented as incidentally identified single aneurysmal fistulas and the lesions were surgically removed without complication. On the other hand, case 3 (an 11-old-male) showed diffuse dilated vascular sacs involving both lungs and caused severe hemodynamic and pulmonary dysfunction. Embolization and surgical resection of the main lesion failed to relieve the symptoms. Case 4 (a 36-old-male) had a localized multiloculated cyst clinically mimicking congenital cystic adenomatoid malformation. Microscopically, the lesion consisted of dilated thick vessels, consistent with the diagnosis of fistulous arteriovenous malformation/hemangioma.

T helper type 17 (Th17) cells are a subset of pro-inflammatory T helper cells that mediate host defense and pathological inflammation. We have previously reported that host dendritic cells (DCs) infected with Vibrio vulnificus induce Th17 responses through the production of several pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. V. vulnificus produces RTX toxin (RtxA), an important virulence factor that determines successful pathophysiology. In this study, we investigated the involvement of RtxA from V. vulnificus in Th17 cell induction through the activation and maturation of DCs. The increased expression of the DC surface marker CD40 caused by V. vulnificus wild-type infection was reduced by rtxA gene mutation in V. vulnificus. The mRNA and protein levels of Th17 polarization-related cytokines also decreased in V. vulnificus rtxA mutant-infected DCs. In addition, the co-culture of Th cells and DCs infected with rtxA mutant V. vulnificus resulted in reduction in DC-mediated Th17 responses. Th17 cell responses in the small intestinal lamina propria decreased in mice inoculated with V. vulnificus rtxA mutant as compared to those inoculated with the wild-type strain. These decreases in DC maturation, Th17-polarizing cytokine secretion, and Th17 responses attributed to rtxA mutation were restored following infection with the rtxA revertant strain. Furthermore, the mutation in the hlyU gene encoding the activator of rtxA1 gene reproduced the results observed with rtxA mutation. Taken together, V. vulnificus, by means of RtxA, induces inflammatory Th17 responses, which may be associated with adaptive responses of the host against V. vulnificus infection.

Fiber reinforced thermoplastics (FRTP) attracts attention as a lightweight material for mass-produced automobiles due to advantages such as excellent formability and recyclability in addition to high specific strength and specific rigidity. Many factors influence the improvement of the mechanical properties of FRTP. We have revealed that the tensile strength of injection-molded glass fiber/polyamide66 (GF/PA) improves as the reinforcement fiber diameter decreases in the wide strain rate range in previous researches. In addition, it was suggested that by using a strength prediction model of discontinuous fiber reinforcement, if the strength can be obtained for one diameter, the strength can be predicted for other diameters. In this study, we investigated the mechanism of the strength enhancement of the GF/PA associated with thinning of the reinforcement fibers and increase of the strain rate. To ascertain the interface properties, single-fiber pull-out tests were conducted on the GF/PA and it was confirmed that the interfacial shear strength (IFSS) of the GF/PA had strain rate dependency. The strength prediction of the GF/PA with the strain rate dependency of IFSS taken into account showed values closer to the experimental values than the values obtained from the prediction with an assumption that IFSS is constant regardless of the strain rate. Furthermore, investigating the factor of the increase in strength due to the thinning of the fibers suggested that the increase of the fiber strength is the dominant factor.

Applications of fiber reinforced plastics have been expanding due to improvement of not only fuel efficiency but also the motion performance of some recent vehicles. Especially, the demand for injection-molded fiber reinforced thermoplastics is expected to increase because of their superior moldability, productivity and recyclability. In this study, the influence the fiber diameter has on the impact tensile properties of long glass-fiber reinforced polyamide (GF/PA) is investigated using the split Hopkinson pressure bar method. Prior to the tensile tests, an investigation of the fiber-orientation distribution was conducted in order to cut out specimens with the same fiber orientation angle from the injection molded plate. Two types of specimens, referred to as specimens with high- and low orientation angle, were manufactured using glass fibers with average diameters of 13, 17, 23 μm. In the tensile test, the GF/PA with smallest fiber diameter showed the highest tensile strength and the most significant strain rate dependency on the strength. These effects were more significant for the specimens with high orientation angle. From SEM observations on the fracture surface and an average fiber length measurement, it was observed that the interfacial fracture and the fiber breakage were dominant failure modes under the considered tensile loading conditions. It was suggested that decreasing the stress acting on the fiber/matrix interface by reducing the fiber diameter affected the improvement of the GF/PA strength. Using the modified linear rule of mixtures, the tensile strength was predicted. The predictions showed good agreement with experimental results. Therefore, it is believed that the decrease of critical fiber length is the reason that the impact tensile properties are higher for the samples with smaller fiber diameter.

Application of carbon fiber reinforced plastics (CFRP) pipes to torque transmission shafts makes it possible to improve automotive driving performance as well as fuel efficiency. A modified simultaneous multi ply winding method was developed as a new forming method for CFRP pipes using prepregs. The CFRP pipes formed by the method have fewer initial flaws, such as voids and fiber waviness. It resulted in 20 % increase in the static torsional strength than conventional CFRP pipes formed by a filament winding method. In this study, effects of stacking sequence on the torsional fatigue properties of the CFRP pipes formed by the modified method were investigated. Torsional fatigue tests were conducted under load control. All tests were conducted at the test frequency f=1 Hz, the maximum applied torque Tmax=1.0 kNm and the stress ratio R=0.1. [902/-45/+45]6 and [90/-45/90/+45]6 pipes were formed to investigate effects of lamination angle difference between adjacent plies. Maximum lamination angle difference of the [90/-45/90/+45]6 pipe is smaller than that of the [902/-45/+45]6 pipe. When the CFRP pipes had smaller lamination angle difference, the initiation and growth of the delamination from the prepreg end in the innermost layer were delayed because interlaminar stress was reduced. Moreover, [(90/-45/90/+45)6/90] pipes were formed to investigate effects of an application of a 90° layer on the innermost layer. As the result, the delamination hardly initiated since the shear stress on the prereg end was reduced. Consequently, the fatigue life of the [(90/-45/90/+45)6/90] pipes increased seven-fold than that of the [902/-45/+45]6 pipes due to improvement of delamination resistance under cyclic torsional loading.

This study conducted a composite risk assessment to evaluate the environmental impacts of phenol, a Hazardous and Noxious Substance (HNS) released or leaked from port facilities. The study area was designated as the vicinity of Incheon Port, South Korea, where the volume of petrochemical-related materials is substantial and various industrial facilities are located. For the composite risk assessment, various vulnerability maps were developed, incorporating the dispersion range of phenol calculated through numerical modeling. The vulnerability maps were generated by classifying socio-environment, legally protected areas, habitats, and species, followed by integrating these individual vulnerability maps to construct an integrated vulnerability map. The composite risk assessment was conducted by considering both the integrated vulnerability map and the dispersion range of phenol. The assessment results indicated that the highest risk by depth was observed in the lower layers due to the settling characteristics of phenol. Spatially, areas where islands and coastlines converge exhibited relatively higher risks. This was attributed to the high concentrations of phenol released from industrial facilities, such as crude oil refineries, petrochemical plants, and organic compound manufacturers, in regions characterized by intense human activity, sensitive habitats, and legally protected areas. Continuous monitoring of these high-risk areas is crucial for assessing the environmental impacts of HNS substances like phenol.