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Programmed death-ligand 1 (PD-L1) acts as an immune checkpoint inhibitor in various cancers. PD-L1 is known to be more frequently expressed in EBV (+) gastric cancer (GC). However, the mechanisms underlying the regulation of PD-L1 expression in EBV (+) GC remain unclear. We investigated the basal and inducible PD-L1 expressions in GC cells. PD-L1 expression was upregulated upon treatment with IFNγ in both EBV (−) and EBV (+) GC cells. Upon stimulation with the same concentration of IFNγ for 24 h, EBV (+) SNU-719 cells showed dramatically higher PD-L1 expression levels by activating JAK2/STAT1/IRF-1 signaling than those of EBV (−) AGS cells. PD-L1 promoter assays, chromatin immunoprecipitation, and electrophoretic mobility shift assays revealed that IFNγ-inducible PD-L1 overexpression is primarily mediated by the putative IRF-1α site of the PD-L1 promoter in EBV (+) SNU-719 cells. Moreover, EBNA1 knockdown reduced both constitutive and IFNγ-inducible PD-L1 promoter activity by decreasing the transcript and protein levels of JAK2 and subsequently STAT1/IRF-1/PD-L1 signaling. EBNA1 is suggested to be moderately enhance both constitutive and IFNγ-inducible PD-L1 expression in EBV (+) GC cells. Thus, the signaling proteins and EBNA1 that regulate PD-L1 expression are potential therapeutic targets in EBV (+) GC.

Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT. A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4- and 8-weeks post-instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing. At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time. The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected. Our study revealed that PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according to PHMG exposure under the guidance of CT.

The precise clinicopathologic significance of myeloid differentiation primary response gene ( MYD88) L265P mutation in diffuse large B-cell lymphomas (DLBCLs) remains elusive. To investigate the frequency and clinicopathologic significance of the MYD88 L265P mutation in DLBCLs, we conducted a meta-analysis of 40 published studies on 2736 DLBCL patients. We collected relevant published research findings identified using the PubMed and Embase databases. The effect sizes of outcome parameters were calculated using a random-effects model. In this meta-analysis, the MYD88 L265P mutation in DLBCL showed a significant difference according to tumor sites. The overall incidence of the MYD88 L265P mutation in DLBCLs, excluding the central nervous system and testicular DLBCLs, was 16.5%. Notably, the MYD88 L265P mutation rates of CNS and testicular DLBCL patients were 60% and 77%, respectively. Interestingly, the MYD88 L265P mutation was more frequently detected in activated B-cell-like (ABC) or non-germinal center B-cell-like (GCB) than GCB subtype (OR = 3.414, p < 0.001). The MYD88 L265P mutation was significantly associated with old age and poor overall survival, but not with sex and clinical stage. This pooled analysis demonstrates that the MYD88 L265P mutation is significantly associated with the tumor sites and molecular subtypes in DLBCL patients.

To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD). Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed. Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, < 0.001), hyperenhancement (95.1% vs. 70.2%, = 0.005), centripetal enhancement (70.7% vs. 45.6%, = 0.023), penetrating vessels (65.9% vs. 22.8%, < 0.001), and perfusion defects (31.7% vs. 3.5%, < 0.001) on CEUS ( ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively ( = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, < 0.001). US vascular parameters associated with malignancy showed higher MVD ( ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD ( < 0.05). US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.

There have been no studies on the effects of polyhexamethylene guanidine phosphate (PHMG) after a long period of exposure in the rodent model. We aimed to evaluate long-term lung damage after PHMG exposure using conventional chest computed tomography (CT) and histopathologic analysis in a rat model. A PHMG solution was intratracheally administrated to 24 male rats. At 8, 26, and 52 weeks after PHMG instillation, conventional chest CT was performed in all rats and both lungs were extracted for histopathologic evaluation. At 52 weeks after PHMG instillation, four carcinomas had developed in three of the eight rats (37.5%). Bronchiolo-alveolar hyperplasia and adenoma were found in rats at 8, 26, and 52 weeks post-instillation. The number of bronchiolo-alveolar hyperplasia significantly increased over time (P-value for trend< 0.001). The severity of lung fibrosis and fibrosis scores significantly increased over time (P-values for trend = 0.002 and 0.023, respectively). Conventional chest CT analysis showed that bronchiectasis and linear density scores suggestive of fibrosis significantly increased over time (P-value for trend < 0.001). Our study revealed that one instillation of PHMG in a rat model resulted in lung carcinomas and progressive and irreversible fibrosis one year later based on conventional chest CT and histopathologic analysis. PHMG may be a lung carcinogen in the rat model.

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.

In this study, we aimed to investigate the molecular biomarkers that are pivotal for the development and progression of gastric cancer (GC). We analyzed clinical specimens using RNA sequencing to identify the target genes. We found that the expression of HOXC6 mRNA was upregulated with the progression of cancer, which was validated by quantitative real time PCR and RNA in-situ hybridization. To compare the protein expression of HOXC6, we evaluated GC and normal gastric tissue samples using western blot analysis and immunohistochemistry. We detected significantly higher levels of HOXC6 in the GC tissues than in the normal controls at both mRNA and protein levels. The expression levels of HOXC6 mRNA in patients with advanced gastric cancer (AGC) were significantly higher than those in patients with early gastric cancer (EGC). Kaplan-Meier curves showed that high expression of HOXC6 mRNA is significantly associated with poor clinical prognosis. Our findings suggest that HOXC6 mRNA may be a novel biomarker and can be potentially valuable in predicting the prognosis of GC patients. Especially, HOXC6 mRNA in-situ hybridization may be a diagnostic tool for predicting prognosis of individual GC patients.

An experimental investigation into the nonlinear optical properties of rhenium diselenide (ReSe 2 ) was conducted at a wavelength of 1.9 μm using the open-aperture and closed-aperture Z-scan techniques for the nonlinear optical coefficient (β) and nonlinear refractive index ( n 2 ) of ReSe 2 , respectively. β and n 2 measured at 1.9 μm were ~ − 11.3 × 10 3  cm/GW and ~ − 6.2 × 10 –2 cm 2 /GW, respectively, which to the best of our knowledge, are the first reported measurements for ReSe 2 in the 1.9-μm spectral region. The electronic band structures of both ReSe 2 and its defective structures were also calculated via the Perdew–Becke–Erzenhof functional to better understand their absorption properties. A saturable absorber (SA) was subsequently fabricated to demonstrate the usefulness of ReSe 2 for implementing a practical nonlinear optical device at 1.9 μm. The 1.9-μm SA exhibited a modulation depth of ~ 8% and saturation intensity of ~ 11.4 MW/cm 2 . The successful use of the ReSe 2 -based SA for mode-locking of a thulium–holmium (Tm–Ho) co-doped fiber ring cavity was achieved with output pulses of ~ 840 fs at 1927 nm. We believe that the mode-locking was achieved through a hybrid mechanism of saturable absorption and nonlinear polarization rotation.

Metallic 2D materials can be promising saturable absorbers for ultrashort pulsed laser production in the long wavelength regime. However, preparing and manipulating their 2D structures without layer stacking have been nontrivial. Using a combined experimental and theoretical approach, we demonstrate here that a metallic titanium carbide (Ti ), the most popular MXene 2D material, can have excellent nonlinear saturable absorption properties even in a highly stacked state due to its intrinsically existing surface termination, and thus can produce mode-locked femtosecond pulsed lasers in the 1.9-μm infrared range. Density functional theory calculations reveal that the electronic and optical properties of Ti MXene can be well preserved against significant layer stacking. Indeed, it is experimentally shown that 1.914-μm femtosecond pulsed lasers with a duration of 897 fs are readily generated within a fiber cavity using hundreds-of-layer stacked Ti MXene saturable absorbers, not only being much easier to manufacture than mono- or few-layered ones, but also offering character-conserved tightly-assembled 2D materials for advanced performance. This work strongly suggests that as-obtained highly stacked Ti MXenes can serve as superb material platforms for versatile nanophotonic applications, paving the way toward cost-effective, high-performance photonic devices based on MXenes.

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar–alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar–alveolar hyperplasia progression, although bronchiolar–alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.