Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Evolution of laparoscopic liver resection in the last two decades: lessons from 2000 cases at a referral Korean center.

BACKGROUND AND AIMS: Laparoscopic liver resection (LLR) has evolved to become the standard surgical approach in many referral centers worldwide. The aim of this study was to analyze how LLR evolved at a single high-volume referral center since its introduction, more than two decades ago. METHODS: Data from all consecutive LLR between January 2003 and September 2022 at the Seoul National University Bundang Hospital were analyzed. Perioperative outcomes were compared between three time periods, with major technological innovations considered as landmarks: before introduction of laparoscopic-US and CUSA (2003-2006), before (2006-2015) and after (2015-2022) introduction of high-definition scope. RESULTS: During the analyzed time periods the number of technically challenging procedures increased from 39.2 to 61.1% (p < 0.001). The most recent period showed shorter median operation time (from 267.5' to 175', p < 0.001), lower median estimated blood loss (EBL) (from 500 to 300 ml, p < 0.001), lower intraoperative transfusions (from 33.8 to 9.3%, p < 0.001), shorter median postoperative hospital stay (from 12 to 6 days, p < 0.001). The time period, a technical major resection and an underlying liver cirrhosis were found to be the associated with longer operation time (p < 0.001) in the multivariable linear regression analysis, while tumor size, technically major surgeries and liver cirrhosis were associated with higher EBL (p < 0.001). CONCLUSION: During the last two decades, the indications for patients undergoing LLR have expanded significantly, including more and more challenging procedures and frail patients. Despite such challenges, perioperative outcomes improved, although technically major procedures, cirrhotic patients and huge tumors have still to be considered challenging situations.

A Prospective Analysis of the Effects of a Powder-Type Hemostatic Agent on the Short-Term Outcomes after Liver Resection.

Background and Objectives: Postoperative bleeding is a significant cause of morbidity and mortality following liver resection. Therefore, it is crucial to minimize bleeding during liver resection and effectively manage it when it occurs. Arista® AH (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) is a microporous polysaccharide hemosphere (MPH), a new plant-derived polysaccharide powder hemostat that can be applied to the entire surgical field. This study prospectively assessed the effectiveness of Arista for bleeding control when applied intraoperatively to the liver resection surface. Materials and Methods: Data were collected at Seoul National University Bundang Hospital for patients who underwent liver resection owing to malignant hepatocellular carcinoma or benign liver diseases. We compared the outcomes between 45 patients managed with Arista® AH (data were prospectively collected between September 2022 and May 2023) and 156 patients managed without the use of Arista® AH (data were retrospectively collected between January 2021 and December 2021). Results: There were no significant differences in patient characteristics between the two groups. The estimated blood loss (EBL) was significantly lower in the Arista® AH group compared with the control group (495.56 ± 672.7 mL vs. 691.9 ± 777.5 mL, p = 0.049). The mean postoperative hospital stay was significantly shorter in the Arista® AH group (5.93 ± 1.88 days vs. 6.94 ± 4.17 days, p = 0.024). The time to Jackson-Pratt drain removal was also significantly shorter in the Arista® AH group (4.64 ± 1.31 days vs. 5.30 ± 2.87 days, p = 0.030). The patient subgroup was divided into four categories based on the type of resection and the presence or absence of cirrhosis. Within the subgroup of major resections in non-cirrhotic patients, the Arista® AH group demonstrated significantly better outcomes compared to the control group, showed lower EBL, reduced need for blood transfusions, decreased volume of drain fluid collected within 48 h, earlier removal of drains, and shorter hospital stays. In contrast, for the other subgroups such as minor resection (both non-cirrhotic and cirrhotic) and major resection with cirrhosis, the differences between the Arista® AH and control groups in various parameters like EBL, blood transfusion rates, drain fluid volume, time to drain removal, and duration of hospital stay were not statistically significant. Conclusions: Arista® AH significantly improved intraoperative blood management and postoperative recovery in patients undergoing liver resection, particularly in non-cirrhotic patients who underwent major resection.

Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery.

BACKGROUND: The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS: A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS: Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION: Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.

Impact of Drain Position on Drain Fluid Amylase, Fluid Collection and Postoperative Pancreatic Fistula after Distal Pancreatectomy.

BACKGROUND: The current definition for postoperative pancreatic fistula (POPF) is based on the drain fluid amylase (DFA), and drains must be positioned adequately. We investigated the impact of DFA level, drain position and fluid collection after distal pancreatectomy (DP). METHODS: We performed a retrospective study of 516 patients who underwent DP between June 2004 and December 2018. Patients were excluded if DP was not main procedure, DFA was not measured, postoperative computed tomography (CT) was not performed, or drains were removed before CT. Demographic and perioperative data were analyzed in 422 eligible patients. RESULTS: Of 422 patients, 49(11.6%) had clinically relevant (CR)-POPF and 102(24.2%) had a malpositioned drain. There was no difference in CR-POPF rate between the high and low DFA groups (12.6% vs 10.7%, P = 0.649). Drain malposition was more frequently associated with symptomatic fluid collection and CR-POPF than well-positioned drains. Male sex, high body mass index, transfusion, and drain malposition were CR-POPF risk factors. In subgroup analysis, drain malposition was also an independent risk factor for CR-POPF in the low DFA group. CONCLUSIONS: After DP, the incidence of CR-POPF in the high and low DFA groups was similar and drain malposition increased the risk of CR-POPF. Thus, the ISGPS definition of POPF based on DFA levels is limited in DP, and DFA levels should be interpreted together with the drain position.

Comparison of Open versus Laparoscopic Approaches in Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation.

Background and Objectives: Although radiofrequency ablation (RFA) is widely used as an effective local treatment for hepatocellular carcinoma (HCC), evidence on salvage hepatectomy for local recurrence after RFA is limited. This study aims to compare open and laparoscopic approaches in salvage hepatectomy for recurrent HCC after RFA. Materials and Methods: Among patients who underwent hepatectomy between January 2004 and August 2022 at a single tertiary referral center, 55 patients who underwent salvage hepatectomy for marginal recurrence after RFA were selected. An open approach was used in 23 (41.8%) patients, while 32 (58.2%) patients underwent laparoscopic surgery. Short-term and long-term outcomes were compared between the two groups. Results: Major hepatectomy was more often performed in the open group (9 [39.1%] vs. 4 [12.5%], p = 0.022). Intraoperative blood loss was also greater in the open group (450 (325-750) vs. 300 (200-600), p = 0.034). Operation time (p = 0.144) and postoperative morbidity rates (p = 0.639) were similar, and there was no postoperative mortality in either group. Postoperative hospital stay was significantly longer in the open group compared to the laparoscopy group (8 (6-11) days vs. 5 (4-7) days, p = 0.028). The 1-, 3-, and 5-year disease-free survival rates showed no difference between the two groups (44.6% vs. 62.5%, 16.5% vs. 13.5%, and 8.3% vs. 13.5%, respectively; p = 0.154). The 1-, 3-, and 5-year overall survival rates between the two groups were also similar (85.7% vs. 96.8%, 79.6% vs. 86.0%, and 79.6% vs. 79.4%, respectively; p = 0.480). Conclusions: Laparoscopic salvage hepatectomy shows oncologic outcomes comparable to the open approach with faster postoperative recovery rates. Considering that recurrence rates are high after RFA, the laparoscopic approach should be considered as a first-line option in selected patients.

Comparative Study of Long-Term Outcomes of Laparoscopic Liver Resection versus Radiofrequency Ablation for Single Small Hepatocellular Carcinoma Located in Left Lateral Segments of the Liver.

Background and Objectives: Laparoscopic liver resection (LLR) is now widely recognized as the primary surgical option for hepatocellular carcinomas (HCC) smaller than 3 cm located in the left lateral segment of the liver. Nevertheless, there is a scarcity of studies comparing laparoscopic liver resection with radiofrequency ablation (RFA) in these cases. Materials and Methods: We retrospectively compared the short- and long-term outcomes of Child-Pugh class A patients who underwent LLR (n = 36) or RFA (n = 40) for a newly diagnosed single small (≤3 cm) HCC located in the left lateral segment of the liver. Results: Overall survival (OS) was not significantly different between the LLR and RFA groups (94.4% vs. 80.0%, p = 0.075). However, disease-free survival (DFS) was better in the LLR group than in the RFA group (p < 0.001), with 1-, 3-, and 5-year DFS rates of 100%, 84.5%, and 74.4%, respectively, in the LLR group vs. 86.9%, 40.2%, and 33.4%, respectively, in the RFA group. The hospital stay was significantly shorter in the RFA group than in the LLR (2.4 vs. 4.9 days, p < 0.001). The overall complication rate was higher in the RFA group than in the LLR group (15% vs. 5.6%). In patients with an α-fetoprotein level of ≥20 ng/mL, the 5-year OS (93.8% vs. 50.0%, p = 0.031) and DFS (68.8% vs. 20.0%, p = 0.002) rates were greater in the LLR group. Conclusions: LLR showed superior OS and DFS compared to RFA in patients with a single small HCC situated in the left lateral segment of the liver. LLR can be considered for patients with an α-fetoprotein level of ≥20 ng/mL.

Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis.

BACKGROUND: Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. METHODS: A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4). RESULTS: In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

A scoring system to predict the risk of major complications after laparoscopic liver resection in elderly patients with hepatocellular carcinoma.

BACKGROUND: The safety of laparoscopic liver resection (LLR) in elderly patients is a matter of concern because the reduced physiologic reserve increases the risk of postoperative complications. However, there are few score systems for predicting complications after LLR in elderly patients. The aim of this study is to propose a new simplified scoring system based on the Geriatric Nutritional Risk Index (GNRI) to predict major complications after LLR in elderly patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 257 consecutive patients aged ≥ 65 years who underwent LLR for HCC between 2004 and 2019. The GNRI formula was 1.489 × serum albumin (g/L) + 41.7 × present weight/ideal weight (kg). A scoring system to predict the risk of major complications was developed by assigning points to each risk factor equal to its regression coefficient determined in the multivariable analysis. Major complications were defined as complications of Clavien-Dindo grade III or higher. RESULTS: Of the 257 patients, 219 patients were finally included in this study. Major complications occurred after LLR in 24 patients (10.9%). Multivariable analysis showed that the GNRI (hazard ratio [HR] 3.396, 95% confidence interval [CI] 1.242-9.288, P = 0.017), Child-Turcotte-Pugh score (HR 2.191, 95% CI 1.400-8.999, P = 0.036), major liver resection (HR 2.683, 95% CI 1.082-7.328, P = 0.050), and intraoperative transfusion (HR 1.802, 95% CI 1.428-7.591, P = 0.022) were independent predictors of major postoperative complications. These variables were assigned points based on their HRs, and the resulting 10-point model showed good discrimination (area under the curve 0.756, 95% CI 0.649-0.836, P = 0.001). CONCLUSION: The scoring system outperformed the GNRI for predicting major complications after LLR in elderly patients with HCC.

A Case-Matched Analysis of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver According to Adaption of Developed Techniques.

Background and Objectives: Laparoscopic liver resection (LLR) for the hepatocellular carcinoma (HCC) located in posterosuperior (PS) segment is technically demanding, but has been overcome by accumulated experiences and technological improvements. We analyzed peri-and post-operative results before and after the adaptation of the enhanced techniques. Materials and Methods: We retrospectively reviewed 246 patients who underwent LLR for HCC in PS segments from September 2003 to December 2019. According to the introduction of advanced techniques including intercostal trocars, Pringle maneuver, and semi-lateral French position, the patients were divided into Group 1 (n = 43), who underwent LLR from September 2003 to December 2011, and Group 2 (n = 203), who underwent LLR from January 2012 to December 2019. Among these cases, 136 patients (Group 1 = 34, Group 2 = 102) were selected by case-matched analysis using perioperative variables. Results: Mean operation time (362 min vs. 291 min) and hospital stay (11 days vs. 8 days, p = 0.023) were significantly longer in Group 1 than Group 2. Otherwise, disease-free survival (DFS) rate was shorter and resection margin (1.3 mm vs. 0.7 mm, p = 0.034) were smaller in Group 2 than Group 1. However, there was no difference in type of complication (p = 0.084), severity of complication graded by the Clavien-Dindo grade system (p = 0.394), and 5-year overall survival (OS) rates (p = 0.986). In case-matched analysis, operation time (359 min vs. 266 min p = 0.002) and hospital stay (11.5 days vs. 8.0 days, p = 0.032) were significantly different, but there was no significant difference in resection margin, DFS, and OS. Conclusions: The adaptation of improved techniques has reduced the complexity of LLR in PS segments.

Long-Term Outcomes of Laparoscopic Liver Resection for Centrally Located Hepatocellular Carcinoma.

Background and Objectives: The feasibility of laparoscopic liver resection (LLR) for centrally located hepatocellular carcinoma (cHCC 1 cm of the hilum, major hepatic veins, and inferior vena cava) is still controversial. This study aims to evaluate the feasibility and safety of LLR for cHCC and compare the perioperative outcomes with those of open liver resection (OLR). Materials and Methods: This retrospective study included 110 patients who underwent LLR (n = 59) or open liver resection (OLR) (n = 51) for cHCC between January 2004 and September 2018. LLR group was divided into the following two subgroups according to the date of operation: Group 1 (n = 19) and Group 2 (n = 40), to account for the advancement in the laparoscopic techniques. Results: No mortality within 3 months was observed. There were no significant differences in operation time (285 vs. 280 min; p = 0.938) and postoperative complication rate (22.0% vs. 27.5%; p = 0.510) between both groups. However, intraoperative blood loss (500 vs. 700 mL; p < 0.001), transfusion rate (10.2% vs. 31.4%; p = 0.006), and hospital stay (6 vs. 10 days; p < 0.001) were significantly lower in the LLR group than in the OLR group. In the LLR group, Group 2, showed a shorter hospital stay than Group 1 (6 vs. 8 days; p = 0.006). There were improvements in the operation time (280 vs. 360 min; p = 0.036) and less intraoperative blood loss (455 vs. 500 mL; p = 0.075) in Group 2. Conclusions: We demonstrated that LLR can be safely performed in highly selected patients with cHCC.

Development and Validation of a Difficulty Scoring System for Laparoscopic Liver Resection to Treat Hepatolithiasis.

Background and Objectives: A difficulty scoring system was previously developed to assess the difficulty of laparoscopic liver resection (LLR) for liver tumors; however, we need another system for hepatolithiasis. Therefore, we developed a novel difficulty scoring system (nDSS) and validated its use for predicting postoperative outcomes. Materials and Methods: This was a retrospective study. We used clinical data of 123 patients who underwent LLR for hepatolithiasis between 2003 and 2021. We analyzed the data to determine which indices were associated with operation time or estimated blood loss (EBL) to measure the surgical difficulty. We validated the nDSS in terms of its ability to predict postoperative outcomes, namely red blood cell (RBC) transfusion, postoperative hospital stay (POHS), and major complications defined as grade ≥IIIa according to the Clavien−Dindo classification (CDC). Results: The nDSS included five significant indices (range: 5−17; median: 8). The RBC transfusion rate (p < 0.001), POHS (p = 0.002), and major complication rate (p = 0.002) increased with increasing nDSS score. We compared the two groups of patients divided by the median nDSS (low: 5−7; high: 8−17). The operation time (210.7 vs. 240.7 min; p < 0.001), EBL (281.9 vs. 702.6 mL; p < 0.001), RBC transfusion rate (5.3% vs. 37.9%; p < 0.001), POHS (8.0 vs. 13.3 days; p = 0.001), and major complication rate (8.8% vs. 25.8%; p = 0.014) were greater in the high group. Conclusions: The nDSS can predict the surgical difficulty and outcomes of LLR for hepatolithiasis and may help select candidates for the procedure and surgical approach.

Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure.

BACKGROUND: To investigate whether the administration of nafamostat mesilate (NM) reduces the risk of posthepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the 1114 patients who underwent hepatectomy for HCC between 2004 and 2020. NM was selectively administered to patients undergoing major hepatectomy with an estimated blood loss of >500 mL. NM group was administered via intravenous of 20 mg of NM from immediately after surgery until postoperative day 4. We performed 1:1 propensity score matching and included 56 patients in each group. PHLF was defined according to the International Study Group of Liver Surgery (ISGLS). RESULTS: The incidence of PHLF was lower in the NM group than control group (P = 0.018). The mean peak total bilirubin (P = 0.006), aspartate transaminase (P = 0.018), and alanine aminotransferase (P = 0.018) levels postoperatively were significantly lower in the NM group. The mean hospital stays (P = 0.012) and major complication rate (P = 0.023) were also significantly lower in the NM group. CONCLUSION: Prophylactic administration of NM reduced the risks of complication and decreased the frequency of PHLF after hepatectomy. A further prospective study is needed to verify our findings.

Incidence, risk factors, and outcomes of jejunal varix of the afferent loop after pancreatoduodenectomy.

BACKGROUND: Jejunal varix is a concerning late complication after pancreatoduodenectomy (PD) due to the risk of recurrent and intractable bleeding. Our aim was to investigate the incidence, risk factors, and outcomes of jejunal varix after PD. METHODS: A total of 709 patients who underwent PD between 2007 and 2017 were included. Preoperative and postoperative CT images were reviewed to evaluate the development of portal vein (PV) stenosis (≥50%) and jejunal varices. RESULTS: Jejunal varix developed in 83 (11.7%) patients at a median of 12 months after PD. Eighteen (21.7%) patients experienced variceal bleeding. PV stenosis (P < 0.001; odds ratio [OR] 33.2, 95% confidence interval [CI] 15.6-66.7) and PV/superior mesenteric vein resection (P = 0.028; OR 2.3, 95% CI 1.1-4.7) were independent risk factors for jejunal varix. Of the nine patients who underwent stent placement for PV stenosis before the formation of jejunal varices, none experienced variceal bleeding. By contrast, 18 (27.3%) of the 135 patients without PV stent placement experienced at least one episode of variceal bleeding. CONCLUSIONS: The incidence of jejunal varix was substantial after PD. PV stenosis was a strong risk factor for jejunal varix. Early PV stent placement and maintaining stent patency could reduce the risk of variceal bleeding in patients with PV stenosis.

Improved Outcomes of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver.

BACKGROUND: LLR is widely adapted for HCC, while LLR in PS segments is still challenging. With recent improvement of techniques and accumulation of experiences, LLR in PS segments is feasible, but studies investigating the result after the modifications are lacking. METHODS: In this single-center, retrospective study, 149 patients who underwent LLR for HCC located in PS segments from September 2003 to December 2016 were analyzed. The patients were divided into Group 1 (n=43) and Group 2 (n=106) who underwent LLR before and after 2012, respectively, when advanced techniques including use of intercostal trocars, Pringle maneuver, and semi-lateral position of patient were introduced. Also, these patients were compared with those who underwent open liver resection (OLR; n=124) for HCC in PS segments during the same period. RESULTS: Mean operative time (394.7 minutes vs 331.2 minutes; P=0.013), intraoperative blood loss (1545.8 ml vs 1208.2 ml; P=0.020), and hospital stay (11.6 days vs 9.2, P<0.001) were significantly less in Group 2. Postoperative complication rate (18.6% vs 18.9%; P=0.970), open conversion rate (23% vs 17%; P=0.374), 5-year overall (79% vs 89%; P=0.607) and 5-year disease-free (52% vs 53%; P=0.657) survival rates were not significantly different between the groups. Compared to the OLR group, complication rate (40.3% vs 18.8%; P< 0.001) and hospital stay (17.6 days vs 9.7 days; P< 0.001) were significantly lower in the LLR group. CONCLUSION: The complexity of LLR for HCC in PS segments is being gradually overcome by the introduction of advanced techniques.

Proteomic evaluation of kimchi, a traditional Korean fermented vegetable, and comparison of kimchi manufactured in China and Korea.

Kimchi is a traditional Korean fermented vegetable, which is also widely consumed in Japan and China. However, little is known about the kimchi proteome. In this study, Korean and Chinese kimchi proteomes were evaluated by shotgun proteomics. A total of 250 proteins were annotated, and 29 of these were expressed at > 1% of the average relative abundance. Discrimination of the geographical origins of Korean and Chinese kimchi samples was possible using multivariate analysis of the proteomic data, and 23 proteins were expressed differently between the two types (p < 0.001), and represent possible markers to discriminate between Chinese and Korean kimchi. This study provides important insights into the kimchi proteome and illustrates the proteomic differences caused by geographical origin.

Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF.

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase (RPTK), plays an oncogenic role by activating an unidentified TKI-258 (dovitinib)-sensitive RPTK in esophageal squamous cell carcinoma (ESCC) cells. Here, we demonstrate that among TKI-258-sensitive RPTKs, fibroblast growth factor receptor (FGFR) 1 is significantly up-regulated in ESCC tissues and cell lines. We show that PTK7 colocalizes with FGFR1 and binds it via its extracellular domain in human embryonic kidney 293 and ESCC TE-10 cells. PTK7 knockdown not only reduced ligand-free and fibroblast growth factor (FGF)-induced phosphorylation of FGFR1 but also the interaction of signaling adaptor proteins with FGFR1 and activation of downstream signaling proteins in TE-10 cells. In addition, PTK7 knockdown reduced FGF-induced oncogenic phenotypes including proliferation, anchorage-independent colony formation, wound healing, and invasion in ESCC cells. Taken together, our data demonstrate that PTK7 binds and activates FGFR1 independent of FGF and thus increases oncogenicity of PTK7- and FGFR1-positive cancers such as ESCC.-Shin, W.-S., Lee, H. W., Lee, S.-T. Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF.

Estrogen-related receptor γ negatively regulates osteoclastogenesis and protects against inflammatory bone loss.

Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor that plays an important role in various metabolic processes under physiological and pathophysiological conditions. Here, we report that ERRγ functions as a negative regulator in receptor activator of nuclear factor κΒ ligand (RANKL)-induced osteoclast differentiation. We observed that ERRγ was strongly expressed in osteoclast precursors, bone marrow-derived macrophages (BMMs) while its expression was significantly reduced by RANKL during osteoclastogenesis. Overexpression of ERRγ in BMMs suppressed the formation of multinucleated osteoclasts and attenuated the induction of c-Fos and nuclear factor of activated T cells c1, which are critical modulators in osteoclastogenesis. Similarly, the treatment of ERRγ agonists, N-(4-(diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) or GSK4716, also inhibited osteoclast generation and the expression of these key modulators. On the other hand, shRNA-mediated knockdown of ERRγ accelerated the formation of bone-resorbing cells and the expression of osteoclastogenic markers. Forced expression of ERRγ blocked RANKL-stimulated phosphorylation of the nuclear factor κB (NF-κB) inhibitor IκBα and suppressed NF-κB transcriptional activity induced by RANKL or the NF-κB subunit p65. Furthermore, by employing a pharmacological approach, we showed that the ERRγ agonist DY131 protected against inflammatory bone loss induced by lipopolysaccharide in vivo. Together, our findings reveal that ERRγ is a pivotal regulator in RANKL-mediated osteoclastogenesis and suggest that ERRγ may have potential as a therapeutic target for pathological bone loss.

Dietary intake assessment of macro, trace, and toxic elements via consumption of kimchi in South Korea.

BACKGROUND: Kimchi, a Korean food, is now produced and consumed in many other countries. In this study, the macro, trace, and toxic element content in varieties of kimchi from Korea and China was evaluated. A health-risk assessment, involving the calculation of estimated dietary intake values, was undertaken. To discriminate among samples with different origins, linear discriminant analysis (LDA) and principal component analysis (PCA) were applied. RESULTS: The analytical methods used for analyses were successfully validated. In the quantification of elements, no significant differences were detected in the concentrations of the elements that were analyzed. Based on the fresh weight of kimchi, among the macro elements, the concentrations of Na and K were relatively high, with values of 4181.9-9919.8 mg kg-1 and 1661.8-6623.5 mg kg-1 , respectively. Among the trace elements that were analyzed, zinc in Korean samples, and strontium in Chinese samples showed the highest concentrations, at 2.67 and 2.98 mg kg-1 , respectively. Concentration levels of the toxic trace elements were within permissible limits. The amount of daily intake and provisional daily intake of each element calculated based on kimchi intake confirmed its safety for consumption. Linear discriminant analysis and PCA successfully discriminated among the samples of Chinese and Korean origin. CONCLUSION: The provisional daily intake of the toxic elements was within provisional tolerable daily intake values. The normal intake of kimchi could not pose a threat upon consumption. © 2019 Society of Chemical Industry.

G protein-coupled receptor 84 controls osteoclastogenesis through inhibition of NF-κB and MAPK signaling pathways.

GPR84, a member of the G protein-coupled receptor family, is found predominantly in immune cells, such as macrophages, and functions as a pivotal modulator of inflammatory responses. In this study, we investigated the role of GPR84 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. Our microarray data showed that GPR84 was significantly downregulated in osteoclasts compared to in their precursors, macrophages. The overexpression of GPR84 in bone marrow-derived macrophages suppressed the formation of multinucleated osteoclasts without affecting precursor proliferation. In addition, GPR84 overexpression attenuated the induction of c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which are transcription factors that are critical for osteoclastogenesis. Furthermore, knockdown of GPR84 using a small hairpin RNA promoted RANKL-mediated osteoclast differentiation and gene expression of osteoclastogenic markers. Mechanistically, GPR84 overexpression blocked RANKL-stimulated phosphorylation of IκBα and three MAPKs, JNK, ERK, and p38. GPR84 also suppressed NF-κB transcriptional activity mediated by RANKL. Conversely, GPR84 knockdown enhanced RANKL-induced activation of IκBα and the three MAPKs. Collectively, our results revealed that GPR84 functions as a negative regulator of osteoclastogenesis, suggesting that it may be a potential therapeutic target for osteoclast-mediated bone-destructive diseases.