Gastric cancer is the fifth most common disease in the world and the fourth most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy; however, there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patients\' plasma. We attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patients\' plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2% and we found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5\'end-motif analysis.

UNASSIGNED: The efficacy of fractionation is significantly impacted by the colloidal particles\' spontaneous absorption of laser beam radiation. The classification of silver nanoparticles during fragmentation processing is regulated through the collection of a combination of laser pulses with wavelengths of 1064 nm and 532 nm.
UNASSIGNED: This study presents an investigation of the efficacy of a plant extract in conjunction with the incorporation of supplementary silver nanoparticles, as well as the generation of smaller-sized silver nanoparticles using laser fragmentation.and then measure thier toxity on the blood.
UNASSIGNED: Ag nanoparticles were synthesized using pulsed laser fragmentation on green tea AgNPs. The synthesis process involved the utilization of a Q-switch Nd:YAG laser with wavelengths of 1064 nm and 532 nm, with energy ranging from 200 to 1000 mJ. Initially, a silver nano colloid was synthesized through the process of fragmented of the Ag target using the second harmonic generation of 532 nm at various energy levels. The optimal energy within the selected wavelengths was determined in order to facilitate the ultimate comparison. Transmission electron microscopy (TEM) was used to determine surface morphology and average particle size, while a spectrophotometer was used to analyses UV light\'s spectrum characteristics. The measurements focused on the surface plasmon resonance (SPR) phenomenon. The absorption spectra of silver nanoparticles exhibit distinct and prominent peaks at wavelengths of 405 nm and 415 nm. The mean diameter of the silver nanoparticles was found to be 16 nm and 20 nm, corresponding to wavelengths of 1064 nm and 532 nm, respectively.
UNASSIGNED: As a consequence, there is a decrease in the range of particle sizes and a decrease in the mean size to lower magnitudes, resulting in a very stable colloid. This particular methodology has demonstrated considerable efficacy in the production of colloidal suspensions with the intended particle dimensions. Moreover, by the analysis of nanoparticles in human blood, no discernible alterations in the blood constituents were seen, indicating their non-toxic nature.

Microplastics (MPs) are concerning emerging pollutants. Here, MPs in four edible aquatic species of different trophic levels (between ∼2 and 4), including fish species Esox lucius (Esocidae: Esocinae); Cyprinus carpio (Cyprinidae: Cyprininae); and Luciobarbus caspius (Cyprinidae: Barbinae); and the swan mussel Anodonta cygnea (Unionidae), were assessed in the Anzali freshwater ecosystem. It is a listed wetland in the Montreux record. MPs were extracted from gastrointestinal tracts (GI), gills, muscles, and skin. All the studied fish and mussels (n = 33) had MPs. MP fibres, fragments and sheets were detected in every GI examined, however, fibres were the only type of MPs in skins, muscles and gills and were the most abundant MP. The MPs found in the fish and mussels were mainly made of nylon (35% of the total MPs), polypropylene-low density polyethylene (30%), and polycarbonate (25%). The average numbers of MPs found in every fish specimen, expressed per wet body mass, had a moderate negative correlation with the condition factor (K) (MP/g - K: Pearson correlation r = -0.413, p = 0.049), and there was no significant relation with the growth factor (b) (r = -0.376; p = 0.068). Importantly, Luciobarbus caspius (with trophic level 2.7-2.8) bioaccumulated MPs and presented a strong correlation between their MP contamination and age (r = 0.916 p < 0.05). Greater gill mass (or related factors) played an important role in the accumulation of MPs, and there was a strong correlation between these factors for Esox lucius and Cyprinus carpio (r = 0.876; r = 0.846; p < 0.05 respectively). The highest MP/g gills (1.91 ± 2.65) were in the filter feeder Anodonta cygnea inhabiting the benthic zone. Esox lucius (piscivorous, trophic level 4.1) was the most contaminated species overall (a total of 83 MPs in 8 individuals, with 0.92 MP/g fish), and their gills where MPs mainly accumulated. Cyprinus carpio was the most contaminated specimen (MPs in specimens), while the number of MPs per mass unit increased with the trophic level. Their feeding and ecological behavior in the aquatic habitat affected the level of accumulation. This work includes evidence of translocation of MPs within the aquatic organisms.

A composite structure containing a metallic skeleton and polyurea elastomer interpenetrating phase was fabricated, and its anti-penetration performance for low-velocity large mass fragments was experimentally studied. The protection capacity of three polyurea was compared based on the penetration resistance force measurement. Results show that the polyurea coating layer at the backside improves the performance of the polyurea-filled spherical cell porous aluminum (SCPA) plate due to its backside support effect and phase transition effect, which are accompanied by a large amount of energy absorption. The frontal-side-coated polyurea layer failed to shear and provided a very limited strengthening effect on the penetration resistance of the interpenetrating phase composite panel. The filling polyurea in SCPA increased the damage area and formed a compression cone for the backside coating layer, leading to a significant stress diffusion effect. The anti-penetration performance was synergistically improved by the plug block effect of the interpenetrating phase composite and the backside support effect of the PU coating layer. Compared with SCPA, the initial impact failure strength and the average resistance force of the composite plate were improved by 120-200% and 108-274%, respectively.

The identification of an effective inhibitor is an important starting step in drug development. Unfortunately, many issues such as the characterization of protein binding sites, the screening library, materials for assays, etc., make drug screening a difficult proposition. As the size of screening libraries increases, more resources will be inefficiently consumed. Thus, new strategies are needed to preprocess and focus a screening library towards a targeted protein. Herein, we report an ensemble machine learning (ML) model to generate a CDK8-focused screening library. The ensemble model consists of six different algorithms optimized for CDK8 inhibitor classification. The models were trained using a CDK8-specific fragment library along with molecules containing CDK8 activity. The optimized ensemble model processed a commercial library containing 1.6 million molecules. This resulted in a CDK8-focused screening library containing 1,672 molecules, a reduction of more than 99.90%. The CDK8-focused library was then subjected to molecular docking, and 25 candidate compounds were selected. Enzymatic assays confirmed six CDK8 inhibitors, with one compound producing an IC50 value of ≤100 nM. Analysis of the ensemble ML model reveals the role of the CDK8 fragment library during training. Structural analysis of molecules reveals the hit compounds to be structurally novel CDK8 inhibitors. Together, the results highlight a pipeline for curating a focused library for a specific protein target, such as CDK8.

Dental trauma is one of the most prevalent problems encountered in clinical practice. Traumatic injuries involving fractures of the anterior tooth are one of the most common problems among children and adolescents. There is a physical and social impact on patients\' quality of life due to traumatic dental injuries (TDIs). Children and adolescents frequently present with a crown fracture that necessitates immediate intervention. Clinicians need to be aware of various treatment modalities for TDIs and have to address these injuries immediately. Due to advances in adhesive technologies, fragment reattachment is the treatment of choice when the fragment is available and well stored. The purpose of this article is to cover various techniques for reattaching fractured fragments and the most current developments in adhesive systems for this purpose.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.

Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have 19F-pKi values of 5.3 and 5.4 respectively.

The widespread use of plastic has resulted in the accumulation of plastic waste across a range of sizes, notably including microplastics (MPs). The introduction of MPs into aquatic ecosystems can lead to the contamination of organisms, mainly fish. This study reports for the first time a quantitative and qualitative analysis conducted on the abundance of MPs encountered in water and sediment of milkfish aquaculture ponds in Gresik, East Java, Indonesia. Water and sediment samples were collected at three stations between February to April 2021. The abundance of MPs was analyzed through the application of one-way ANOVA tests and Pearson\'s correlation analysis. The results identified four types of MPs: fragments, fibers, films, and pellets. The highest abundance of MPs in both water (10.40 particle/L) and sediment samples (1.15 particle/g) was observed in March. The predominant MPs size in the water samples is 100-500 μm, while it is below 100 μm in the sediment. The color of the MPs varied across eight colors: black, purple, red, blue, yellow, pink, green, and transparent. The identification of MPs polymers was found to be polypropylene (PP), Polyurethane (PU), Polycarbonate (PC), Polyethylene terephthalate (PETE), High-density polyethylene (HDPE), and low-density polyethylene (LDPE). The presence of MPs in the water column and sediments was correlated with human activities around the ponds. Hence, the abundance of MPs is a source of pollution that has the potential to damage the nutritional quality of farmed milkfish. This study provides important information for the local governments to develop waste management policies for a cleaner environment and improved human health.

Polypropylene (PP), polystyrene (PS), and polyethylene (PE) plastics are commonly used in household items such as electronic housings, food packaging, bottles, bags, toys, and roofing membranes. The presence of inhalable microplastics in indoor air has become a topic of concern as many people spent extended periods of time indoors during the COVID-19 pandemic lockdown restrictions, however, the toxic effects on the respiratory system are not properly understood. We examined the toxicity of PP, PS, and PE microplastic fragments in the pulmonary system of C57BL/6 mice. For 14 days, mice were intratracheally instilled 5 mg/kg PP, PS, and PE daily. The number of inflammatory cells such as macrophages, neutrophils, and eosinophils in the bronchoalveolar lavage fluid (BALF) of PS-instilled mice was significantly higher than that in the vehicle control (VC). The levels of inflammatory cytokines and chemokines in BALF of PS-instilled mice increased compared to the VC. However, the inflammatory responses in PP- and PE-stimulated mice were not significantly different from those in the VC group. We observed elevated protein levels of toll-like receptor (TLR) 2 in the lung tissue of PP-instilled mice and TLR4 in the lung tissue of PS-instilled mice compared with those to the VC, while TLR1, TLR5, and TLR6 protein levels remained unchanged. Phosphorylation of nuclear factor kappa B (NF-κB) and IĸB-α increased significantly in PS-instilled mice compared with that in VC. Furthermore, Nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome components including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 in the lung tissue of PS-instilled mice increased compared with that in the VC, but not in PP- and PE-instilled mice. These results suggest that PS microplastic fragment stimulation induces pulmonary inflammation due to NF-ĸB and NLRP3 inflammasome activation by the TLR4 pathway.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43188-023-00224-x.