ß-Ga2O3 Air-Channel Field-Emission Nanodiode with Ultrahigh Current Density and Low Turn-On Voltage.

Field-emission nanodiodes with air-gap channels based on single ß-Ga2O3 nanowires have been investigated in this work. With a gap of ∼50 nm and an asymmetric device structure, the proposed nanodiode achieves good diode characteristics through field emission in air at room temperature. Measurement results show that the nanodiode exhibits an ultrahigh emission current density, a high enhancement factor of >2300, and a low turn-on voltage of 0.46 V. More impressively, the emission current almost keeps constant over a wide range (8 orders of magnitude) of air pressures below 1 atm. Meanwhile, the fluctuation in field-emission current is below 8.7% during long-time monitoring, which is better than the best reported field-emission device based on ß-Ga2O3 nanostructures. All of these results indicate that ß-Ga2O3 air-gapped nanodiodes are promising candidates for vacuum electronics that can also operate in air.

Long-term survival analysis of robotic esophagectomy for esophageal cancer.

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer.

Mortality and Risk Factors in Very Elderly Patients Who Start Hemodialysis: Korean Renal Data System, 2016-2020.

INTRODUCTION: The number of elderly patients with end-stage renal disease (ESRD) is increasing worldwide. However, decision-making about elderly patients with ESRD remains complex because of the lack of studies, especially in very elderly patients (≥75 years). We examined the characteristics of very elderly patients starting hemodialysis (HD) and the associated mortality and prognostic factors. METHODS: Data were analyzed retrospectively using a nationwide cohort registry, the Korean Renal Data System. Patients who started HD between January 2016 and December 2020 were included and divided into three groups according to age at HD initiation (<65, 65-74, and ≥75 years). The primary outcome was all-cause mortality during the study period. Risk factors for mortality were analyzed using Cox proportional hazard models. RESULTS: In total, 22,024 incident patients were included with 10,006, 5,668, and 6,350 in each group (<65, 65-74, and ≥75 years, respectively). Among the very elderly group, women had a higher cumulative survival rate than men. The survival rate was lower in patients with vascular access via a catheter than in those with an arteriovenous fistula or graft. Very elderly patients with more comorbid diseases had a significantly lower survival rate than those with fewer comorbidities. In the multivariate Cox models, old age, cancer presence, catheter use, low body mass index, low Kt/V, low albumin concentration, and capable status of partial self-care were associated with high risk of mortality. CONCLUSION: Preparation of an arteriovenous fistula or graft when starting HD should be considered in very elderly patients with fewer comorbid diseases.

Comparison of perioperative outcomes between bipolar sealing, ultrasonic shears and a hybrid device during laparoscopic gastrectomy for early gastric cancer: a prospective, multicenter, randomized study.

BACKGROUND: Although EBDs are essential for minimally invasive surgery, well-established prospective randomized studies comparing EBDs are scarce. This study aimed to compare the intraoperative inflammatory response and short-term surgical outcomes among different energy-based devices (EBDs) in laparoscopic distal gastrectomy (LDG). METHODS: Patients with clinical stage I gastric cancer scheduled for LDG at two different medical centers were prospectively randomized into three groups: ultrasonic shears (US), advanced bipolar (BP) and ultrasonic-bipolar hybrid (HB). The C-reactive protein (CRP) level, operation time, intraoperative blood loss (IBL), laboratory tests, cytokines (interleukin (IL)-6 and IL-10), hospital stay, and complication rate were analyzed. A novel semiquantitative measurement method using indocyanine green (ICG) and a near-infrared camera measured the amount of lymphatic leakage. RESULTS: The primary endpoint, the CRP level, was significantly lower in the BP (n = 60) group than in the US (n = 57) or HB (n = 57) group [9.03 ± 5.55 vs. 11.12 ± 5.02 vs. 12.67 ± 6.14, p = 0.001, on postoperative day (POD) 2 and 7.48 vs. 9.62 vs. 9.48, p = 0.026, on POD 4]. IBL was significantly lower in BP than in US or HB (26.3 ± 25.3 vs. 43.7 ± 42.0 vs. 34.9 ± 37.0, p = 0.032). Jackson-Pratt drainage triglycerides were significantly lower in BP than in US (53.6 ± 33.7 vs. 84.2 ± 59.0, p = 0.11; HB: 71.3 ± 51.4). ICG fluorescence intensity, operation time, laboratory results, cytokines, hospital stay, and complication rate were not significantly different among the 3 groups. CONCLUSION: BP showed a lower postoperative CRP level and less IBL than US and HB, suggesting less collateral thermal damage and better sealing function. Surgeons may consider this when selecting EBDs for laparoscopic surgery.

Feasibility and safety of inserting transient biodegradable stents in the pylorus during pylorus-preserving gastrectomy for gastric cancer: a preliminary study in a porcine for proof of concept.

BACKGROUND: To evaluate whether insertion of self-biodegradable stent into the pylorus to prevent delayed-gastric emptying after pylorus-preserving gastrectomy is feasible and safe through porcine experiment. METHODS: Self-biodegradable dumbbell-shaped pyloric stents were designed from absorbable suture materials: poly(glycolide-co-caprolactone) (PGCL) or poly-p-dioxanone (PPDO). After gastrotomy on ten pigs, each stent was inserted: two shams, four PGCL stents, and four PPDO stents. Body weight (Bwt), body temperature (BT), complete blood cell (CBC) count, and plain X-ray were evaluated. On postoperative day (POD) 13, euthanasia was performed for histologic evaluation. RESULTS: Operation was successfully performed in all ten pigs. Without tagging suture, both stents migrated before POD 3. The migration was delayed up to POD 13, when the tagging sutures (-t) were applied between stent and stomach wall. Self-degradation of PGCL started from POD 3, and stents were completely excreted from the abdomen by POD 8. Although PPDO were also weakened as self-degradation progressed, its shape was maintained in gastrointestinal tract for 13 days. Unexpected sudden death occurred in the pig with PPDO-t2 on POD 10, which is more likely due to acute volvulus rather than stent-related complication. There was no significant difference between three groups in terms of Bwt, BT, CBC, and histology (sham vs. PGCL vs. PPDO, all p > 0.05). CONCLUSION: The concept of biodegradable stents made of absorbent suture material seems feasible in porcine experiment. Among them, PGCL which has shown rapid absorption, appears to be a more suitable material for transient pyloric absorbable stent when considering safety aspect.

Developmentally Supportive Care Among Neonatal Intensive Care Unit Nurses in South Korea: Knowledge, Perceived Importance, Perception, and Perceived Competence.

BACKGROUND: The concept of developmentally supportive care in preterm infants is of considerable significance in the neonatal intensive care unit (NICU) setting with regard to preventing complications from preterm birth and promoting optimal growth and development. To provide high-quality developmentally supportive care, NICU nurses must possess high levels of knowledge, importance, perception, and competence. PURPOSE: The purpose of this study was to investigate South Korean NICU nursing staff's level of knowledge concerning developmentally supportive care, as well as the perceived importance, perception, and perceived competence regarding this concept. METHODS: This study employed a cross-sectional descriptive design. Between June 1 and 19, 2020, 160 nurses completed a self-report questionnaire pertaining to developmentally supportive care, which covered the aspects of knowledge, perceived importance, perception (including attitudes, perceived behavioral control, subjective norms, and intentions), and perceived competence. RESULTS: The levels of knowledge, attitude, and intention as a subfactor of perception, and perceived competence pertaining to developmentally supportive care were not high. There was no significant difference in the knowledge and perceived competence of skilled nurses compared with novice nurses. However, skilled nurses recognized that they could provide better developmentally supportive care than novice nurses. Perceived competence was positively correlated with perceived importance and perception. IMPLICATIONS FOR PRACTICE AND RESEARCH: Systematic educational programs that can enhance developmentally supportive care competence should be provided to NICU staff nurses. These must clarify the importance of developmentally supportive care and improve NICU nurses' knowledge, attitudes, self-efficacy, and intentions.

Comparison of East-Asia and West-Europe cohorts explains disparities in survival outcomes and highlights predictive biomarkers of early gastric cancer aggressiveness.

Surgical resection with lymphadenectomy and perioperative chemotherapy is the universal mainstay for curative treatment of gastric cancer (GC) patients with locoregional disease. However, GC survival remains asymmetric in West- and East-world regions. We hypothesize that this asymmetry derives from differential clinical management. Therefore, we collected chemo-naïve GC patients from Portugal and South Korea to explore specific immunophenotypic profiles related to disease aggressiveness and clinicopathological factors potentially explaining associated overall survival (OS) differences. Clinicopathological and survival data were collected from chemo-naïve surgical cohorts from Portugal (West-Europe cohort [WE-C]; n = 170) and South Korea (East-Asia cohort [EA-C]; n = 367) and correlated with immunohistochemical expression profiles of E-cadherin and CD44v6 obtained from consecutive tissue microarrays sections. Survival analysis revealed a subset of 12.4% of WE-C patients, whose tumors concomitantly express E-cadherin_abnormal and CD44v6_very high, displaying extremely poor OS, even at TNM stages I and II. These WE-C stage-I and -II patients tumors were particularly aggressive compared to all others, invading deeper into the gastric wall (P = .032) and more often permeating the vasculature (P = .018) and nerves (P = .009). A similar immunophenotypic profile was found in 11.9% of EA-C patients, but unrelated to survival. Tumours, from stage-I and -II EA-C patients, that display both biomarkers, also permeated more lymphatic vessels (P = .003), promoting lymph node (LN) metastasis (P = .019), being diagnosed on average 8 years earlier and submitted to more extensive LN dissection than WE-C. Concomitant E-cadherin_abnormal/CD44v6_very-high expression predicts aggressiveness and poor survival of stage-I and -II GC submitted to conservative lymphadenectomy.

Glucose metabolic profiles evaluated by PET associated with molecular characteristic landscape of gastric cancer.

BACKGROUND: Although FDG-PET is widely used in cancer, its role in gastric cancer (GC) is still controversial due to variable [18F]fluorodeoxyglucose ([18F]FDG) uptake. Here, we sought to develop a genetic signature to predict high FDG-avid GC to plan individualized PET and investigate the molecular landscape of GC and its association with glucose metabolic profiles noninvasively evaluated by [18F]FDG-PET. METHODS: Based on a genetic signature, PETscore, representing [18F]FDG avidity, was developed by imaging data acquired from thirty patient-derived xenografts (PDX). The PETscore was validated by [18F]FDG-PET data and gene expression data of human GC. The PETscore was associated with genomic and transcriptomic profiles of GC using The Cancer Genome Atlas. RESULTS: Five genes, PLS1, PYY, HBQ1, SLC6A5, and NAT16, were identified for the predictive model for [18F]FDG uptake of GC. The PETscore was validated in independent PET data of human GC with qRT-PCR and RNA-sequencing. By applying PETscore on TCGA, a significant association between glucose uptake and tumor mutational burden as well as genomic alterations were identified. CONCLUSION: Our findings suggest that molecular characteristics are underlying the diverse metabolic profiles of GC. Diverse glucose metabolic profiles may apply to precise diagnostic and therapeutic approaches for GC.

Clinical significance of lipid droplets formed in the peritoneal fluid after laparoscopic surgery for gastric cancer.

BACKGROUND: Several studies have previously reported that laparoscopic surgery using an energy sealing device generates hazardous surgical smoke. However, the droplets appearing on the surface of peritoneal fluid irrigated with saline, after dissection phase of laparoscopic gastrectomy were ignored for a long time. This study aimed to investigate the composition and clinical significance of these droplet particles. METHODS: This study prospectively enrolled 15 patients with early gastric cancer (cT1NanyM0) who were scheduled for laparoscopic gastrectomy. Floating phases of peritoneal irrigation fluid containing droplets in dissected area were retrieved before and after surgical dissection. Using gas chromatography analysis, the areas under the peak were compared between the samples retrieved before and after surgical dissection. We also analyzed if the area value with significant change was related to the inflammatory response. RESULTS: In gas chromatography, the area values after laparoscopic surgical dissection were significantly increased in 10 out of 37 kinds of fatty acids, compared to those before surgical dissection. The significant increase in area value of α-linoleic and eicosadienoic acids were positively correlated with the elevated level of C-reactive protein at postoperative day 2 (Spearman's ρ = 0.843, P < 0.001; Spearman's ρ = 0.785, P = 0.001). CONCLUSIONS: The lipid droplets, generated after laparoscopic lymphadenectomy during gastric cancer surgery, contained various types of fatty acids, and some of them have been found to be associated with inflammatory response.

Prediction Model for Screening Patients at Risk of Malnutrition After Gastric Cancer Surgery.

BACKGROUND: Malnutrition after gastrectomy is associated with a poor prognosis; however, no accurate model for predicting post-gastrectomy malnutrition exists. Hence, we conducted a retrospective study to develop a prediction model identifying gastric cancer patients at high risk of malnutrition after gastrectomy. METHOD: Gastric cancer patients who underwent curative gastrectomy with more than one weight measurement during a 3-year follow-up period were included. Malnutrition was defined as body mass index (BMI) < 18.5 kg/m2 according to the European Society of Clinical Nutrition and Metabolism diagnostic criteria. BMI-loss pattern was analyzed using a group-based trajectory model. A prediction model for malnutrition 6 months after gastrectomy was developed based on significant risk factors, and then validated. RESULTS: Overall, 1421 patients were examined. The BMI-loss trajectory model showed significant BMI loss at 6 months after gastrectomy. Severe BMI loss (mean 21.5%; n = 109) was significantly associated with the elderly, female sex, higher preoperative BMI, advanced cancer stage, open surgery, total gastrectomy, Roux-en-Y reconstruction, chemotherapy, and postoperative complications (all p < 0.05). Malnutrition 6 months after gastrectomy was observed in 152 (11.9%) of 1281 patients. Preoperative BMI, sex, and type of operation were included in the final prediction model as predictive factors (p < 0.05). The C-index of the developmental set and bootstrap validation of the prediction model was 0.91 (95% confidence interval 0.89-0.94) and 0.91, respectively. CONCLUSION: The prediction model for the risk of malnutrition 6 months after gastrectomy was accurately developed, with three independent risk factors: low preoperative BMI, female sex, and total or proximal gastrectomy.

Development of an in vitro coculture device for the investigation of host-microbe interactions via integrative multiomics approaches.

The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.

Preservation of hepatic branch of the vagus nerve reduces the risk of gallstone formation after gastrectomy.

BACKGROUND: Injury to the vagus nerve has been proposed to be associated with occurrence of gallstones after gastrectomy. We investigated the effect of preservation of hepatic branch of the vagus nerve on prevention of gallstones during laparoscopic distal (LDG) and pylorus-preserving gastrectomy (LPPG). METHODS: Preservation of the vagus nerve was reviewed of cT1N0M0 gastric cancer patients underwent LDG (n = 323) and LPPG (n = 144) during 2016-2017. Presence of gallstones was evaluated by ultrasonography (US) and computed tomography (CT). Incidences of gallstones were compared between the nerve preserved (h-DG, h-PPG) group and sacrificed (s-DG, s-PPG) group. Clinicopathological features were also compared. RESULTS: The 3-year cumulative incidence of gallstones was lower in the h-DG (2.7%, n = 85) than the s-DG (14.6%, n = 238) (p = 0.017) and lower in the h-PPG (1.6%, n = 123) than the s-PPG (12.9%, n = 21) (p = 0.004). Overall postoperative complication rate was similar between the h-DG and s-DG (p = 0.861) as well as between the h-PPG and s-PPG (p = 0.768). The number of retrieved lymph nodes station #1 and 3-year recurrence-free survival were not significantly different between the preserved group and sacrificed group. Injury to the vagus nerve (p = 0.001) and high body mass index (BMI) (≥ 27.5 kg/m2) (p = 0.040) were found to be independent risk factors of gallstone formation in multivariate analysis. CONCLUSIONS: Preservation of hepatic branch of the vagus nerve can be recommended for LDG as well as LPPG of early gastric cancer patients to reduce postoperative gallstone formation.

Kushenol C Prevents Tert-Butyl Hydroperoxide and Acetaminophen-Induced Liver Injury.

Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.

Near-infrared fluorescence-guided surgery using indocyanine green facilitates secure infrapyloric lymph node dissection during laparoscopic distal gastrectomy.

PURPOSE: We aimed to investigate the usefulness of near-infrared indocyanine green (ICG)-enhanced fluorescence guidance for infrapyloric LN dissection in laparoscopic distal gastrectomy. METHODS: This study enrolled patients with early gastric cancer scheduled for laparoscopic distal gastrectomy. After intraoperative submucosal injection of ICG (0.1 mg/mL), LN dissection was conducted under near-infrared ICG fluorescence guidance. The operation time, bleeding events during infrapyloric LN dissection were analyzed. Cases were retrospectively 1:3 propensity-score matched to patients who underwent laparoscopic distal gastrectomy without ICG injection. RESULTS: The mean time from midline omentectomy to exposure of the right gastroepiploic vein was significantly shorter in the ICG group (n = 20) than in the non-ICG group (n = 60) (13.05 ± 5.77 vs 18.68 ± 7.92 min; p = 0.001), and the incidence of bleeding during infrapyloric LN dissection was lower in the ICG group (20% vs 68.3%, p < 0.001). The two groups did not differ significantly regarding the number of LNs retrieved from the infrapyloric area (p = 0.434). CONCLUSIONS: Near-infrared ICG fluorescence guidance facilitates safe and fast infrapyloric LN dissection in laparoscopic distal gastrectomy.

Characterization of Lysine Acetyltransferase Activity of Recombinant Human ARD1/NAA10.

Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration.

Is lower tourniquet pressure during total knee arthroplasty effective? A prospective randomized controlled trial.

BACKGROUND: Higher tourniquet pressures may be associated with an increased risk of complications. We aimed to determine (1) whether a lower tourniquet pressure [systolic blood pressure (SBP) + 120 mmHg] is as effective as conventional tourniquet pressure (SBP + 150 mmHg) in providing a bloodless surgical field and decreasing blood loss, and (2) whether lowering the tourniquet pressure decreases tourniquet-related complications compared to conventional inflation pressure. METHODS: One hundred and sixty knees in 124 patients undergoing total knee arthroplasty (TKA) were randomly allocated to either conventional (n = 80) or lower inflation pressure group (n = 80). The quality of the initial surgical field and occurrence of intraoperative blood oozing, hemoglobin drop, drained volume and calculated blood loss were assessed as efficacy variables. Safety outcome variables included post-operative pain, tourniquet site skin problems (ecchymosis, bullae, skin necrosis), and other tourniquet-related complications such as nerve palsy, venous thromboembolism, and delayed rehabilitation. RESULTS: A comparable bloodless surgical field was successfully provided in both groups (100% vs. 99%, p = 1.000). One case in the conventional pressure group and two cases in the lower pressure group showed intraoperative blood oozing (p = 1.000), which was successfully controlled after an increase of 30 mmHg in the tourniquet inflation pressure. There was no difference in the hemoglobin drop, drained volume, and calculated blood loss. The two groups did not differ in any safety outcomes such as post-operative pain, thigh complications, and other tourniquet related complications. CONCLUSION: This study demonstrates that a tourniquet inflation pressure of 120 mmHg above the SBP is effective method during TKA. TRIAL REGISTRATION: The trial was with ClinicalTrials.gov ( NCT01993758 ) on November 25, 2013.

IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells.

Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ-producing T(H)1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12-producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4-mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/T(H)17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/T(H)17 responses without blocking IL-12/T(H)1, selective IL-4-mediated IL-23/T(H)17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12-dependent T(H)1 responses.

Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu.

Alloyed 2D Metal-Semiconductor Atomic Layer Junctions.

Heterostructures of compositionally and electronically variant two-dimensional (2D) atomic layers are viable building blocks for ultrathin optoelectronic devices. We show that the composition of interfacial transition region between semiconducting WSe2 atomic layer channels and metallic NbSe2 contact layers can be engineered through interfacial doping with Nb atoms. WxNb1-xSe2 interfacial regions considerably lower the potential barrier height of the junction, significantly improving the performance of the corresponding WSe2-based field-effect transistor devices. The creation of such alloyed 2D junctions between dissimilar atomic layer domains could be the most important factor in controlling the electronic properties of 2D junctions and the design and fabrication of 2D atomic layer devices.

Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required.