A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor ß diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

hsa-miR-CHA2, a novel microRNA, exhibits anticancer effects by suppressing cyclin E1 in human non-small cell lung cancer cells.

Despite considerable therapeutic advancements, the global survival rate for lung cancer patients remains poor, posing challenges in developing an effective treatment strategy. In many cases, microRNAs (miRNAs) exhibit abnormal expression levels in cancers, including lung cancer. Dysregulated miRNAs often play a crucial role in the development and progression of cancer. Therefore, understanding the mechanisms underlying aberrant miRNA expression during carcinogenesis may provide crucial clues to develop novel therapeutics. In this study, we identified and cloned a novel miRNA, hsa-miR-CHA2, which is abnormally downregulated in non-small cell lung cancer (NSCLC)-derived cell lines and tissues of patients with NSCLC. Furthermore, we found that hsa-miR-CHA2 regulates the post-transcriptional levels of Cyclin E1 (CCNE1) by binding to the 3'-UTR of CCNE1 mRNA. CCNE1, a cell cycle regulator involved in the G1/S transition, is often amplified in various cancers. Notably, hsa-miR-CHA2 overexpression led to the alteration of the Rb-E2F pathway, a significant signaling pathway in the cell cycle, by targeting CCNE1 in A549 and SK-LU-1 cells. Subsequently, we confirmed that hsa-miR-CHA2 induced G1-phase arrest and exhibited an anti-proliferative effect by targeting CCNE1. Moreover, in subcutaneous xenograft mouse models, intra-tumoral injection of polyplexed hsa-miR-CHA2 mimic suppressed tumor growth and development. In conclusion, hsa-miR-CHA2 exhibited an anticancer effect by targeting CCNE1 both in vitro and in vivo. These findings suggest the potential role of hsa-miR-CHA2 as an important regulator of cell proliferation in molecular-targeted therapy for NSCLC.

NiAlFe LTH /MoS2 p-n junction heterostructure composite as an effective visible-light-driven photocatalyst for enhanced degradation of organic dye under high alkaline conditions.

Designing of an effectual heterostructure photocatalyst for catalytic organic pollutant exclusion has been the subject of rigorous research intended to resolve the related environmental aggravation. Fabricating p-n junctions is an effective strategy to promote electron-hole separation of semiconductor photocatalysts as well as enhance the organic toxin degradation performance. In this study, a series of n-type NiAlFe-layered triple hydroxide (LTH) loaded with various ratios of p-type MoS2 was synthesized for forming a heterostructure LTH/MoS2 (LMs) by an in situ hydrothermal strategy. The photocatalysts were characterized by XRD, SEM&EDX, TEM, FT-IR, XPS, as well as UV-vis DRS. The photoactivity of photocatalysts was tested by the degradation of Indigo Carmine (IC) dye. The optimized catalyst (LM1) degrades 100% of indigo dye in high alkaline pH under UV light for 100 min. Besides, the degradation rate of LM1 is 15 times higher than that of pristine NiAlFe-LTH. The enhanced photoactivity is attributed to the synergistic effect between NiAlFe-LTH and MoS2 as well as the p-n junction formation.

Non-destructive monitoring and prediction of fouling by organic matters and residual anionic coagulant during membrane process.

Physical fouling characteristics on silicon carbide (SiC) membranes induced by various organic matter compounds vary depending on the presence of calcium ions (Ca2+). Both destructive techniques (morphological surface analysis) and non-destructive techniques (fouling properties monitoring) were used to determine the fouling mechanisms and behavior during the membrane filtration systems. Destructive analysis and a modified Hermia model were employed to assess the fouling mechanisms. Fouling behavior was also analyzed through non-destructive monitoring techniques including optical coherence tomography (OCT) and three-dimensional laser scanning confocal microscopy (3D-LSM). At concentrations of 10, 30, and 100 mg/L without Ca2+, the flux decreased by 57-95% for humic acid (HA) and anionic polyacrylamide (APAM). APAM exhibited a notable removal rate of up to 56% without Ca2+. At concentration of 10, 30, and 100 mg/L in the absence of Ca2+, the flux decreased by 6-8% for sodium alginate (SA). However, the addition of Ca2+ led to a reduction in the flux for SA by up to 91% and resulted in a removal rate of 40%. Furthermore, addition of Ca2+ led to an alteration of the fouling characteristics of HA and SA. In the case of HA, higher concentrations resulted in elevated thickness and roughness with correlation coefficients of 0.991 and 0.992, respectively. For SA, increased SA concentration led to a thicker (correlation coefficient of 0.999) but smoother surfaces (correlation coefficients of 0.502). Monitoring of these physical characteristics of the fouling layer through non-destructive analysis is crucial for effective fouling management, optimization of the system performance and extending the lifespan of the membrane. By continuously assessing the fouling layer thickness and surface roughness, we expect to be able to provide insights on the fouling behavior, identify trends, that can help scientists and engineers to make informed decisions regarding fouling control strategies in future.

Effect of Topical Programmed Death-Ligand1 on Corneal Epithelium in Dry Eye Mouse.

Dry eye disease (DED) is a growing health concern that impacts millions of individuals every year, and is associated with corneal injury, excessive oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to achieve a permanent clinical cure due to their temporary nature or adverse side effects. Therefore, here, we investigated the effectiveness of the topical administration of programmed death-ligand 1 (PD-L1) in the mouse model of DED. The model was generated in C57BL/6 mice by excising the extra orbital lacrimal gland and causing desiccation stress with scopolamine injections. Subsequently, either phosphate-buffered saline (3 µL/eye) or PD-L1 (0.5 µg/mL) was topically administered for 10 days. Tear volume was evaluated with phenol red thread, and corneal fluorescein staining was observed to quantify the corneal epithelial defect. Corneas were collected for histological analysis, and the expression levels of inflammatory signaling proteins such as CD4, CD3e, IL-17, IL-1ß, pIkB-α, pNF-kB and pERK1/2 were assessed through immunofluorescence and Western blot techniques. Our results demonstrate that desiccating stress-induced corneal epithelial defect and tear secretion were significantly improved by topical PD-L1 and could reduce corneal CD4+ T cell infiltration, inflammation and apoptosis in a DED mouse model by downregulating IL-17 production and ERK1/2-NFkB pathways.

Machine learning analysis to interpret the effect of the photocatalytic reaction rate constant (k) of semiconductor-based photocatalysts on dye removal.

Photocatalytic reactions with semiconductor-based photocatalysts have been investigated extensively for application to wastewater treatment, especially dye degradation, yet the interactions between different process parameters have rarely been reported due to their complicated reaction mechanisms. Hence, this study aims to discern the impact of each factor, and each interaction between multiple factors on reaction rate constant (k) using a decision tree model. The dyes selected as target pollutants were indigo and malachite green, and 5 different semiconductor-based photocatalysts with 17 different compositions were tested, which generated 34 input features and 1527 data points. The Boruta Shapley Additive exPlanations (SHAP) feature selection for the 34 inputs found that 11 inputs were significantly important. The decision tree model exhibited for 11 input features with an R2 value of 0.94. The SHAP feature importance analysis suggested that photocatalytic experimental conditions, with an importance of 59%, was the most important input category, followed by atomic composition (39%) and physicochemical properties (2%). Additionally, the effects on k of the synergy between the metal cocatalysts and important experimental conditions were confirmed by two feature SHAP dependence plots, regardless of importance order. This work provides insight into the single and multiple factors that affect reaction rate and mechanism.

Assessing the Seafood Trade Diversion Arising from Economic Sanctions: Evidence from Russia and Western Countries.

Since 2014, economic sanctions between Russia and Western nations have significantly altered the global seafood trade. The consequent decline in bilateral trade also had spillover effects on the rest of the world (ROW). According to earlier studies, economic sanctions appear to negatively impact bilateral trade and income. However, few studies examine how Russian sanctions affect the world as a whole and estimate their effects on the fisheries industry. This study seeks to close this gap by quantifying the extent to which Russian sanctions have impacted trade in terms of trade deflection, trade destruction, trade depression, and trade creation. To this end, panel data from 185 countries were created for the years from 2005 to 2020. With trade policy variables that account for changes in trade channels, a structural gravity trade model was specified. Based on calculations using the Poisson pseudo-maximum likelihood (PPML) fixed effect model, economic sanctions led to a 119.28% surge in Russia's seafood imports from the rest of the world (ROW), alongside a 39% decline in imports from Western countries. The extent of trade deflection, which includes the exports of Western nations diverted from Russia to the ROW markets, increased by 5.49%. The results demonstrate that trade between sanctioned states, as well as global trade, is significantly impacted by economic sanctions.

Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Near-surface termination of upward-propagating strike-slip ruptures on the Yangsan Fault, Korea.

We present a new example of the termination of strike-slip paleoearthquake ruptures in near-surface regions on the Yangsan Fault, Korea, based on multi-scale structural observations. Paleoearthquake ruptures occur mostly along the boundary between the inherited fault core and damage zone (N10-20°E/> 75°SE). The ruptures propagated upward to the shallow subsurface along a < 3-cm-wide specific slip zone with dextral-slip sense, along which the deformation mechanism is characterized mainly by granular flow in near-surface region. The ruptures either reach the surface or are terminated in unconsolidated sediment below the surface. In the latter case, the rupture splays show westward bifurcation, and their geometry and kinematics show a change to NNW-strike with low-angle dip and dextral-reverse oblique-slip sense in the strata. We suggest that the upward termination of the contractional strike-slip ruptures is controlled by the inherited fault geometry that is unfavorable with respect to the stress field (ENE-WSW σHmax) at basement depths in terms of movement on the fault, and the lack of extension of the fault into shallow subsurface; a depth-dependent change in stress from σHmax > σv > σHmin to σHmax > σHmin > σv at depth of a ~ 200 m; and the physical properties of unconsolidated sediment, which have low inter-granular cohesion, resulting in distributed deformation.

High-efficient and rapid removal of anionic and cationic dyes using a facile synthesized sole adsorbent NiAlFe-layered triple hydroxide (LTH).

It would be extremely momentous to familiarize a low-cost sole adsorbent NiAlFe-layered triple hydroxides (LTHs) having a strong sorption affinity towards both anionic and cationic dyes. Using the urea hydrolysis hydrothermal method LTHs were fabricated and by altering the ratio of participant metal cations the adsorbent was optimized. BET analysis revealed that the optimized LTHs possess an elevated surface area (160.04 m2/g) while TEM and FESEM analysis portrayed the stacked sheets-like 2D morphology. LTHs were employed for the amputation of anionic congo red (CR) and cationic brilliant green (BG) dye. The adsorption study showed that within 20 and 60 min, respectively, maximum adsorption capacities were achieved at 57.47 mg/g and 192.30 mg/g for CR and BG dye. Adsorption isotherm, kinetics, and thermodynamics study revealed that both chemisorptions with physisorptions were the assertive factor for the dye encapsulation. This enhanced adsorption performance of the optimized LTH for the anionic dye is attributed to its inherent anions exchange properties and new bond formation with the adsorbent skeleton. Whereas for the cationic dye, it was because of the formation of strong hydrogen bonds, and electrostatic interaction. Morphological manipulation of LTHs, formulates the optimized adsorbent LTH111, provokes the adsorbent for this elevated adsorption performance. Overall, this study revealed that LTHs have a high potential for the effectual remediation of dyes from wastewater as a sole adsorbent at a low cost.

Structure of fish TRAF4 and its implication in TRAF4-mediated immune cell and platelet signaling.

Due to an increasing interest in immunity and signal transduction in teleost fish, important key signaling molecules associated with the immune response, including TRAF molecules, have been recently cloned and characterized. To better understand the role of TRAF4 in fish immune signaling and compare it with the human system, our study cloned the TRAF4 gene from the Antarctic yellowbelly rockcod Notothenia coriiceps (ncTRAF4) and purified the protein. Here, we report the first crystal structure of teleost fish TRAF4. Based on biochemical characterization, our findings elucidated the mechanisms through which signaling molecules gain cold adaptivity. Additionally, we identified a platelet receptor GPIbß homolog in N. coriiceps (ncGPIbß) and found that the "RRFERLFKEARRTS" region of this homolog directly binds to ncTRAF4, indicating that ncTRAF4 also recognizes the "RLXA" motif for receptor interactions and further TARF4-mediated cellular signaling. Collectively, our findings provide novel insights into the mechanisms of TRAF4-mediated immune cell and platelet signaling in fish and the structural flexibility-mediated cold adaptiveness of signaling molecules.

Economic benefits of preventing bird collisions in South Korea: findings from a choice experiment survey.

Bird deaths due to collisions with artificial structures, such as glass windows of buildings and transparent noise barriers, are continuing to occur in South Korea. The government is trying to prevent bird collisions by increasing the attachment of specially designed tapes to help birds avoid windows. This article estimates the economic benefits arising from the prevention of collisions by applying a choice experiment (CE). For this purpose, a CE survey of 1000 South Korean interviewees was conducted. The four attributes to be attached with the tapes for the CE application were a transparent soundproof wall window on an expressway, a transparent soundproof wall window on a general road, a glass window in a public building, and a glass window in a private building. The unit was the percentage of each structure with the tapes attached to the window. The marginal values of a one-unit (1%p) increase in each attribute were computed to be KRW 534 (USD 0.46), KRW 233 (USD 0.20), KRW 1,318 (USD 1.13), and KRW 12,930 (USD 11.05), respectively. This quantitative information will be an important reference for implementing the prevention policy. For example, based on the collision prevention of 1000 birds per structure, the priority for attaching tapes can be placed in the order of expressways, public buildings, private buildings, and general roads.

Combined treatment with medial unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction is effective on long-term follow-up.

PURPOSE: The purpose of the present study was to evaluate the long-term outcome of combined medial unicompartmental knee arthroplasty (UKA) and anterior cruciate ligament reconstruction (ACLR). The authors hypothesized that the combined procedure leads to good long-term outcome in patients with isolated medial knee osteoarthritis (OA) and anterior cruciate ligament (ACL) deficiency. METHODS: Twenty-three patients with ACL deficiency and concomitant medial knee OA were treated from 2008 to 2016 with a combined UKA (Oxford Partial Knee) and ACLR using a hamstring tendon autograft. The follow-up assessment included VAS pain score, Lysholm score, Oxford Knee Score (OKS), American Knee Society scores (AKSS), International Knee Documentation Committee (IKDC 2000), Tegner and UCLA activity scores. Instrumented laxity test was done using the KT-1000 arthrometer. Survivorship analysis was performed using the Kaplan-Meier method. Implant loosening and disease progression was assessed by conventional radiography. RESULTS: Average follow-up duration was 10 years (6-14.5). VAS, Lysholm, Tegner and UCLA scores improved significantly. OKS, AKSS and IKDC 2000 showed excellent results on follow-up. Implant survivorship was 91.4% at 14.5 years. There were 2 revisions with conversion to total knee arthroplasty at 6 and 12 years postoperatively due to trauma and disease progression, respectively. There were no radiological or clinical signs of instability or disease progression in any of the remaining knees. The side-to-side difference using the KT-1000 arthrometer was insignificant. CONCLUSIONS: UKA combined with ACLR is an effective therapeutic option with good outcome and return to sport rate on the long-term. LEVEL OF EVIDENCE: IV.

Current Advances in Regenerative Strategies for Dry Eye Diseases: A Comprehensive Review.

Dry eye disease (DED) is an emerging health issue affecting millions of individuals annually. Ocular surface disorders, such as DED, are characterized by inflammation triggered by various factors. This condition can lead to tear deficiencies, resulting in the desiccation of the ocular surface, corneal ulceration/perforation, increased susceptibility to infections, and a higher risk of severe visual impairment and blindness. Currently, the clinical management of DED primarily relies on supportive and palliative measures, including the frequent and lifelong use of different lubricating agents. While some advancements like punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts have been attempted, they have shown limited effectiveness. Recently, there have been promising developments in the treatment of DED, including biomaterials such as nano-systems, hydrogels, and contact lenses for drug delivery, cell-based therapies, biological approaches, and tissue-based regenerative therapy. This article specifically explores the different strategies reported so far for treating DED. The aim is to discuss their potential as long-term cures for DED while also considering the factors that limit their feasibility and effectiveness. These advancements offer hope for more effective and sustainable treatment options in the future.

Obesity and periodontitis: A systematic review and updated meta-analysis.

Background: A previous 2014 meta-analysis reported a positive association between obesity and periodontitis. It was considered necessary to update the recently published papers and to analyse subgroups on important clinical variables that could affect the association between obesity and periodontitis. Therefore, we updated the latest studies and attempted to derive more refined results. Methods: All observational studies were eligible for inclusion. The Newcastle-Ottawa scale was used to qualitatively evaluate the risk of bias. Subgroup analyses were conducted for patients aged 18-34, 35-54, and 55+ years and the countries (European countries, USA, Brazil, Japan, Korea, and other Asian countries). Results: Thirty-seven full-text articles were included. Obesity conferred increased odds of periodontal disease with an odds ratio (1.35, 95% CI: 1.05-1.75). In the subgroup analysis by age, the odds ratio was the highest in the 18-34 years group (2.21, 95% CI: 1.26-3.89). In the subgroup analysis by country, European countries had the highest odds ratio (2.46, 95% CI: 1.11-5.46). Conclusion: Despite the differences in degree, a positive association between obesity and periodontitis was found regardless of country or age. Therefore, medical professionals should try to prevent periodontitis by controlling patient weights, and more studies should be conducted to determine the association between obesity and oral health. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022301343.

Multiplexed Digital Spatial Protein Profiling Reveals Distinct Phenotypes of Mononuclear Phagocytes in Livers with Advanced Fibrosis.

Background and Aims: Intrahepatic mononuclear phagocytes (MPs) are critical for the initiation and progression of liver fibrosis. In this study, using multiplexed digital spatial protein profiling, we aimed to derive a unique protein signature predicting advanced liver fibrosis. Methods: Snap-frozen liver tissues from various chronic liver diseases were subjected to spatially defined protein-based multiplexed profiling (Nanostring GeoMXTM). A single-cell RNA sequencing analysis was performed using Gene Expression Omnibus (GEO) datasets from normal and cirrhotic livers. Results: Sixty-four portal regions of interest (ROIs) were selected for the spatial profiling. Using the results from the CD68+ area, a highly sensitive and specific immune-related protein signature (CD68, HLA-DR, OX40L, phospho-c-RAF, STING, and TIM3) was developed to predict advanced (F3 and F4) fibrosis. A combined analysis of single-cell RNA sequencing data from GEO datasets (GSE136103) and spatially-defined, protein-based multiplexed profiling revealed that most proteins upregulated in F0-F2 livers in portal CD68+ cells were specifically marked in tissue monocytes, whereas proteins upregulated in F3 and F4 livers were marked in scar-associated macrophages (SAMacs) and tissue monocytes. Internal validation using mRNA expression data with the same cohort tissues demonstrated that mRNA levels for TREM2, CD9, and CD68 are significantly higher in livers with advanced fibrosis. Conclusions: In patients with advanced liver fibrosis, portal MPs comprise of heterogeneous populations composed of SAMacs, Kupffer cells, and tissue monocytes. This is the first study that used spatially defined protein-based multiplexed profiling, and we have demonstrated the critical difference in the phenotypes of portal MPs between livers with early- or late-stage fibrosis.

Studies on Preformulation and Formulation of JIN-001 Liquisolid Tablet with Enhanced Solubility.

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in vivo antitumor activity; however, JIN-001 was a crystalline solid with very low solubility in an aqueous solution, and therefore, Capryol 90, which has excellent solubilization ability, was selected as an optimal liquid vehicle based on solubility studies. JIN-001 liquisolid (JLS) powder was successfully prepared by dissolving JIN-001 in Capryol 90 and mixing colloidal silicon dioxide (CSD) used as an oil adsorption agent. The prepared JLS was confirmed to be amorphous. Based on the result of the solubility test of JLS, compared to JIN-001, the solubility of the former was significantly improved in all solvents regardless of pH. JLS tablets were prepared through wet granulation using JIN-001 and stable excipients based on the compatibility test. The developed JLS tablet significantly increased the drug release rate in all tested solutions; however, the liquisolid method had no significant effect on bioavailability in the pharmacokinetics study in beagle dogs. In conclusion, the liquisolid system influenced the solubility and dissolution rate of JIN-001.

Better survival of patients with hepatitis B virus-related hepatocellular carcinoma in South Korea: Changes in 16-years cohorts.

AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) have decreased over time in South Korea, where hepatitis B virus (HBV) in endemic. This study investigated the changes in the characteristics and clinical outcomes of HCC patients in Korea. METHODS: Patients initially diagnosed with HCC and treated at the National Cancer Center, Korea between 2000 and 2015 (n = 4,291) were followed up until February 2017. Differences in patient characteristics and outcomes were compared between chronological cohorts: cohort A (2000-2004, n = 1,157) vs. B (2005-2009, n = 1,678) vs. C (2010-2015, n = 1,456). RESULTS: The median age of the patient cohort was 57 years (range, 13-98 years), and male predominance was noted (81.6%). HBV infection was the most common etiology (74.8%). The proportion of patients diagnosed with good liver function and small tumors (<2 cm) increased significantly over time: 74.6%, 79.9%, and 87.4% for Child-Pugh class A (p<0.001) and 8.0%, 8.5%, and 12.0% for modified UICC stage I (p<0.001) in cohorts A, B, and C, respectively. Median overall survival improved significantly over time: 14.4 months (95% confidence interval [CI], 12.0-16.8 months), 22.9 months (95% CI, 20.3-25.5 months), and 53.6 months (95% CI, 45.7-61.5 months) in cohorts A, B, and C, respectively. HBV-related patients showed significantly improved survival (12.7 vs. 20.4 vs. 64.5 months, p<0.001) associated with the use of antiviral treatments (adjusted hazard ratio, 0.72; 95% CI, 0.64-0.80). CONCLUSIONS: The survival of patients with HCC, especially HBV-related HCC, has improved significantly over time in Korea.

A Unique Immune-Related Gene Signature Represents Advanced Liver Fibrosis and Reveals Potential Therapeutic Targets.

Innate and adaptive immune responses are critically associated with the progression of fibrosis in chronic liver diseases. In this study, we aim to identify a unique immune-related gene signature representing advanced liver fibrosis and to reveal potential therapeutic targets. Seventy-seven snap-frozen liver tissues with various chronic liver diseases at different fibrosis stages (1: n = 12, 2: n = 12, 3: n = 25, 4: n = 28) were subjected to expression analyses. Gene expression analysis was performed using the nCounter PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA). Biological meta-analysis was performed using the CBS Probe PINGSTM (CbsBioscience, Daejeon, Korea). Using non-tumor tissues from surgically resected specimens, we identified the immune-related, five-gene signature (CHIT1_FCER1G_OSM_VEGFA_ZAP70) that reliably differentiated patients with low- (F1 and F2) and high-grade fibrosis (F3 and F4; accuracy = 94.8%, specificity = 91.7%, sensitivity = 96.23%). The signature was independent of all pathological and clinical features and was independently associated with high-grade fibrosis using multivariate analysis. Among these genes, the expression of inflammation-associated FCER1G, OSM, VEGFA, and ZAP70 was lower in high-grade fibrosis than in low-grade fibrosis, whereas CHIT1 expression, which is associated with fibrogenic activity of macrophages, was higher in high-grade fibrosis. Meta-analysis revealed that STAT3, a potential druggable target, highly interacts with the five-gene signature. Overall, we identified an immune gene signature that reliably predicts advanced fibrosis in chronic liver disease. This signature revealed potential immune therapeutic targets to ameliorate liver fibrosis.

Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from Acinetobacter baumannii.

Peptidoglycan digestion by murein-degrading enzymes is a critical process in bacterial cell growth and/or cell division. The membrane-bound lytic murein transglycosylase A (MltA) is a murein-degrading enzyme; it catalyzes the cleavage of the ß-1,4-glycosidic linkage between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans. Although substrate recognition and cleavage by MltA have been examined by previous structural and mutagenesis studies, the overall mechanism of MltA in conjunction with other functionally related molecules on the outer membrane of bacterial cells for peptidoglycan degradation has remained elusive. In this study, the crystal structure of MltA from the virulent human pathogen Acinetobacter baumannii is characterized and presented. The study indicated that MltA from A. baumannii forms homodimers via an extra domain which is specific to this species. Furthermore, the working mechanism of MltA with various functionally related proteins on the bacterial outer membrane was modeled based on the structural and biochemical analysis.