Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition.

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.

Carbohydrate antigen 19-9 plus carcinoembryonic antigen for prognosis in colorectal cancer: An observational study.

AIM: Carcinoembryonic antigen (CEA) is a primary prognostic marker and can detect colorectal cancer (CRC) recurrence; however, it has low sensitivity. Carbohydrate antigen 19-9 (CA 19-9) can be used as a supplemental tumour marker along with CEA. The purpose of this study was to determine whether preoperative CA 19-9 added to CEA helped predict long-term prognosis and whether follow-up CA 19-9 added to CEA had additional benefits in diagnosing the recurrence of CRC. METHOD: We retrospectively assessed patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital. Data on demographics, preoperative and follow-up CEA and CA 19-9 levels, recurrence and survival were obtained and analysed with respect to tumour marker levels to ascertain their prognostic and diagnostic values. RESULTS: A total of 4972 and 1530 patients were included to analyse preoperative and follow-up tumour marker levels, respectively. The 5-year relapse-free survival rates were 72.2% ± 0.8%, 52.5% ± 2.2%, 55.5% ± 3.2% and 32.1% ± 2.3% in the normal CEA and CA 19-9, high CEA, high CA 19-9, and high CEA and high CA 19-9 groups, respectively (all P < 0.001). Patients whose elevated CEA or CA 19-9 levels reduced to normal levels had better survival outcomes than those with postoperatively elevated levels. Elevated follow-up CA 19-9 and CEA levels were related to higher incidences of distant metastasis (CA 19-9, 14.0% vs. 23.1%, P = 0.004; CEA, 12.6% vs. 30.1%, P < 0.001) but not to local recurrence. Combined follow-up CEA and CA 19-9 increased the sensitivity for recurrence to 31.4%, with a 5% difference from the sensitivity of CEA alone. In the subgroup with high preoperative CA 19-9 levels, sensitivity increased by 18.2% overall. CONCLUSION: CA 19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA 19-9.

Association between environmental chemical exposure and albumin-to-creatinine ratio is modified by hypertension status in women of reproductive age.

Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.

Plasma Circulating Tumor Necrosis Factor Receptors at Multiple Time Points Can Predict the Outcome of Severe Acute Kidney Injury.

INTRODUCTION: This prospective cohort study investigated the clinical role of circulating tumor necrosis factor receptor (cTNFR) levels as prognostic biomarkers in severe acute kidney injury (AKI) patients requiring continuous renal replacement therapy (CRRT). METHODS: We enrolled 136 patients from 7 hospitals participating in the VENUS (VolumE maNagement Under body composition monitoring in critically ill patientS on CRRT) trial from July 2017 to October 2019. The levels of cTNFR1 and cTNFR2 were measured using plasma samples collected on days 0 (D0), 2 (D2), and 7 (D7). Patients were divided into high- and low-cTNFR groups based on their receptor concentrations. RESULTS: D0 concentrations of cTNFR1 and cTNFR2 were positively correlated with one another (R2 = 0.37, p < 0.001). The high-cTNFR1 group displayed a higher in-hospital mortality rate than the low-TNFR1 group (p = 0.002). Moreover, the mortality rate was significantly higher in the high-TNFR1 group than in the low-TNFR1 group after adjusting for age, sex, and acute physiology, and chronic health evaluation II scores (hazard ratio 1.82, 95% confidence interval 1.09-3.03, p = 0.025). D2 and D7 cTNFR1 levels were also associated with in-hospital mortality; contrastingly, cTNFR2 levels were not associated with this outcome. Additionally, patients were divided into three groups according to the change in cTNFR levels from D0 to D2 (ΔcTNFR). Those in the highest ΔcTNFR tertile had a higher mortality rate than the remaining patients (p = 0.033 for ΔcTNFR1; p = 0.025 for ΔcTNFR2). Patients who underwent AKI-to-chronic kidney disease transition had higher concentrations of cTNFR1 (p = 0.014). DISCUSSION/CONCLUSION: Plasma cTNFR1 concentrations at CRRT initiation and changes in cTNFR1 and 2 levels immediately following CRRT initiation are significant biomarkers for predicting the outcomes of patients with severe AKI.

The effect of biomechanical features on classification of dual-task gait.

Early detection of Alzheimer's Disease and Related Disorders (ADRD) has been a focus of research with the hope that early intervention may improve clinical outcomes. The manifestation of motor impairment in early stages of ADRD has led to the inclusion of gait assessments including spatiotemporal parameters in clinical evaluations. This study aims to determine the effect of adding kinetic and kinematic gait features to classification of different levels of cognitive load in healthy individuals. A dual-task paradigm was used to simulate cognitive impairment in 40 healthy adults, with single-task walking trials representing normal, healthy gait. The Paced Auditory Serial Addition Task was administered at two different inter-stimulus intervals representing two levels of cognitive load in dual-task gait. We predicted that a richer dataset would improve classification accuracy relative to spatiotemporal parameters. Repeated Measures ANOVA showed significant changes in 15 different gait features across all three levels of cognitive load. We used three supervised machine learning algorithms to classify data points using a series of different gait feature sets with performance based on the area under the curve (AUC). Classification yielded 0.778 AUC across all three conditions (0.889 AUC Single vs. Dual) using kinematic and spatiotemporal features compared to 0.724 AUC using spatiotemporal features only (0.792 AUC Single vs. Dual). These data suggest that additional kinematic parameters improve classification performance. However, the benefit of measuring a wider set of parameters compared to their cost needs consideration. Further work will lead to a clinically viable ADRD detection classifier.

Trajectory of AKI and hospital mortality among patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. Characterization of AKI by timing and trajectory and early prediction of AKI progression is required for better preventive management and the prediction of patient outcomes. METHODS: A total of 858 patients who were hospitalized due to coronavirus disease 2019 (COVID-19) were retrospectively enrolled from December 2020 to August 2021. The occurrence of AKI was evaluated throughout hospitalization. The hazard ratios (HRs) of mortality outcomes according to the trajectory of AKI were measured using Cox regression models after adjustment for multiple variables. RESULTS: Among 858 patients, 226 (26.3%) presented AKI at admission, and 44 (5.1%) developed AKI during hospitalization. Patients with AKI at admission or hospital-acquired AKI had a higher risk of mortality than those without AKI, with HRs of 9.87 (2.81-34.67) and 13.74 (3.57-52.84), respectively. Of 226 patients with AKI at admission, 104 (46.0%) recovered within 48 hr, 83 (36.7%) had AKI beyond 48 hr and recovered in 7 days, and 39 (17.3%) showed no recovery from AKI on Day 7. Delayed recovery and persistent AKI were significantly associated with an increased risk of mortality, with HRs of 4.39 (1.06-18.24) and 24.33 (7.10-83.36), respectively. CONCLUSIONS: The onset and progression of AKI was significantly associated with in-hospital mortality in patients with COVID-19. A thorough observation of the recovery trajectory of early AKI after infection is necessary.

Triptycene-Fused Sterically Shielded Multi-Resonance TADF Emitter Enables High-Efficiency Deep Blue OLEDs with Reduced Dexter Energy Transfer.

Designing multi-resonance (MR) emitters that can simultaneously achieve narrowband emission and suppressed intermolecular interactions is challenging for realizing high color purity and stable blue organic light-emitting diodes (OLEDs). Herein, a sterically shielded yet extremely rigid emitter based on a triptycene-fused B,N core (Tp-DABNA) is proposed to address the issue. Tp-DABNA exhibits intense deep blue emissions with a narrow full width at half maximum (FWHM) and a high horizontal transition dipole ratio, superior to the well-known bulky emitter, t-DABNA. The rigid MR skeleton of Tp-DABNA suppresses structural relaxation in the excited state, with reduced contributions from the medium- and high-frequency vibrational modes to spectral broadening. The hyperfluorescence (HF) film composed of a sensitizer and Tp-DABNA shows reduced Dexter energy transfer compared to those of t-DABNA and DABNA-1. Notably, deep blue TADF-OLEDs with the Tp-DABNA emitter display higher external quantum efficiencies (EQEmax =24.8 %) and narrower FWHMs (≤26 nm) than t-DABNA-based OLEDs (EQEmax =19.8 %). The HF-OLEDs based on the Tp-DABNA emitter further demonstrate improved performance with an EQEmax of 28.7 % and mitigated efficiency roll-offs.

Boron-Based Multi-Resonance TADF Emitter with Suppressed Intermolecular Interaction and Isomer Formation for Efficient Pure Blue OLEDs.

Multi-resonance (MR) thermally activated delayed fluorescent (TADF) emitters are highly attractive due to their superior color purity as well as efficient light-harvesting ability from singlets and triplets. However, boron and nitrogen-based MR-TADF emitters suffer from their strong π-π interaction owing to their rigid flat cores. Herein, a boron-based multi-resonance blue TADF emitter with suppressed intermolecular interaction and isomer formation is developed through a simple synthetic process by introducing meta-xylene and meta-phenyphenyl groups to the core. The MR-TADF emitter, mBP-DABNA-Me, shows a narrowband blue emission with a peak at 467 nm, along with full width at half maximum of 28 nm, and photoluminescence quantum yield of 97%. Notably, highly efficient pure blue organic light-emitting diode (OLED) is realized using mBP-DABNA-Me, showing a maximum external quantum efficiency of 24.3% and a stable blue emission with a Commission Internationale de L'Eclairage coordinate of (0.124, 0.140). The color purity of the OLED is maintained at a high doping concentration of over 20%, attributed to the suppressed intermolecular interaction between the MR emitters.

Zebrafish (Danio rerio) as a model organism for screening nephrotoxic chemicals and related mechanisms.

Because of essential role in homeostasis of the body fluid and excretion of wastes, kidney damage can lead to severe impacts on health and survival of humans. For most chemicals, nephrotoxic potentials and associated mechanisms are unclear. Hence, fast and sensitive screening measures for nephrotoxic chemicals are required. In this study, the utility of zebrafish (Danio rerio) was evaluated for the investigation of chemical-induced kidney toxicity and associated modes of toxicity, based on the literature review. Zebrafish has a well-understood biology, and many overlapping physiological characteristics with mammals. One such characteristic is its kidneys, of which histology and functions are similar to those of mammals, although unique differences of zebrafish kidneys, such as kidney marrow, should be noted. Moreover, the zebrafish kidney is simpler in structure and easy to observe. For these advantages, zebrafish has been increasingly used as an experimental model for screening nephrotoxicity of chemicals and for understanding related mechanisms. Multiple endpoints of zebrafish model, from functional level, i.e., glomerular filtration, to transcriptional changes of key genes, have been assessed to identify chemical-induced kidney toxicities, and to elucidate underlying mechanisms. The most frequently studied mechanisms of chemical-induced nephrotoxicity in zebrafish include oxidative stress, inflammation, DNA damage, apoptosis, fibrosis, and cell death. To date, several pharmaceuticals, oxidizing agents, natural products, biocides, alcohols, and consumer chemicals have been demonstrated to exert different types of kidney toxicities in zebrafish. The present review shows that zebrafish model can be efficiently employed for quick and reliable assessment of kidney damage potentials of chemicals, and related toxic mechanisms. The toxicological information obtained from this model can be utilized for identification of nephrotoxic chemicals and hence for protection of public health.

cMet agonistic antibody prevents acute kidney injury to chronic kidney disease transition by suppressing Smurf1 and activating Smad7.

We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-ß1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1ß) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-ß1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-ß1/Smad pathway.

Variability of urinary creatinine, specific gravity, and osmolality over the course of pregnancy: Implications in exposure assessment among pregnant women.

Due to dilution status of the urine, chemical concentrations measured in spot urine are frequently adjusted using correction factors, such as creatinine, specific gravity (SG), or osmolarity of the urine. Urinary correction factors, however, can be influenced dramatically by physiological changes such as pregnancy. Details about the variation of urine dilution over the course of pregnancy are not well characterized. In the present study, we investigated the variation of urine correction factors over time among the pregnant women of Korea (n = 69) and Thailand (n = 102). Creatinine, SG, and osmolality were determined in the urine samples obtained in each trimester of the participating women, and were compared by sampling time and by nationality. Implication of the variation in these correction factors was studied using phthalate metabolites measured in the urine samples as model chemicals. Urinary correction factors significantly varied across the trimesters especially in Korean pregnant women: urinary creatinine and osmolality were significantly lower in the third trimester (T3) urine than the first trimester (T1) urine. Urinary creatinine and SG of the T3 urine of Korean pregnant women were also significantly lower than those reported from the non-pregnant women who participated in Korean National Environmental Health Survey (KoNEHS) 2015-2017. Among Thai women, however, these correction factors were rather stable across the pregnancy. Differences in ethnicity, or in behavior such as water consumption amount may partly explain the differences. Temporal changes in these urine correction factors influenced the urinary phthalate metabolite concentrations adjusted for dilution, in both Korean and Thai pregnant women. The present observations show that the variations of urinary correction factors should be considered in exposure assessment of urinary chemicals for pregnant women, in order to circumvent potential bias due to physiological changes occurring during pregnancy, and to reduce errors in exposure classification and association.

Effects of Depression and Resilience of Public Workers on Work-related Stress and Anxiety in Response to the COVID-19 Pandemic.

BACKGROUND: This study explored the clinical variables related to public workers' stress and anxiety regarding the viral epidemic, and the mediating effect of resilience on the relationship between their depression and anxiety in response to coronavirus disease 2019 (COVID-19) pandemic. METHODS: A total of 938 public workers answered anonymous questionnaires in May 2020. The survey included rating scales such as the Stress and Anxiety to Viral Epidemics-9 (SAVE-9), Patients Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Connor-Davidson Resilience Scale 2 items (CD-RISC 2), and subjects also answered whether they were employed in COVID-19 related fields. RESULTS: Married, female, junior, public workers reported a higher level of stress and anxiety in response to the viral epidemic. Furthermore, high levels of stress and anxiety toward the epidemic are defined by high PHQ-9, high GAD-7, and low CD-RISC 2 scores. It could also be seen that resilience mediated the effect of depression in public workers and their stress and anxiety levels toward the epidemic. CONCLUSION: It is important to reduce the psychological burden of public workers and manage their mental health to help them cope with the epidemic wisely and efficiently. Among many mental health factors, psychological resilience represents an essential target for psychological intervention among public workers.

Effect of Noise on Sleep and Autonomic Activity in Children according to Source.

BACKGROUND: Noise has been a major issue in children due to its effect on emotional symptoms and sleep problems. The present study investigated the effect of noise on sleep and autonomic activity in children according to three variables, namely, road traffic noise, aircraft noise, and noise sensitivity (NS). METHODS: The study is epidemiological in nature. A total of 474 subjects of four elementary schools were evaluated in conjunction with the 2014 noise map data gathered from two metropolitan regions, Seoul and Ulsan, in South Korea. Each subject completed the children's sleep habits questionnaire, and heart rate variability (HRV) was recorded. Analysis of covariance was performed using monthly income as a covariate. RESULTS: Aircraft noise was associated with night waking (P = 0.047), whereas no significant association was observed between sleep and road traffic noise. After stratifying by NS, no significant results were obtained for road traffic noise. However, high levels of aircraft noise in the high-NS group were associated with high degrees of bedtime resistance (P = 0.049). In terms of HRV, no significant difference was observed in the results between groups. CONCLUSION: Road traffic noise did not significantly alter sleep or autonomic activity in children, whereas aircraft noise exerted a negative effect on sleep. The findings suggest that the impact of noise on sleep in children varies depending on noise sources.

Urinary cMet as a prognostic marker in immunoglobulin A nephropathy.

The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below-median (Group 2) and above-median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary-cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)-α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria (P < .001). During the follow-up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr < 300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF-α treatment, the proliferation of mesangial cells and increased interleukin-8 and intercellular adhesion molecule-1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.

cMet agonistic antibody attenuates apoptosis in ischaemia-reperfusion-induced kidney injury.

Acute kidney injury (AKI) is a very common complication with high morbidity and mortality rates and no fundamental treatment. In this study, we investigated whether the hepatocyte growth factor (HGF)/cMet pathway is associated with the development of AKI and how the administration of a cMet agonistic antibody (Ab) affects an AKI model. In the analysis using human blood samples, cMet and HGF levels were found to be significantly increased in the AKI group, regardless of underlying renal function. The administration of a cMet agonistic Ab improved the functional and histological changes after bilateral ischaemia-reperfusion injury. TUNEL-positive cells and Bax/Bcl-2 ratio were also reduced by cMet agonistic Ab treatment. In addition, cMet agonistic Ab treatment significantly increased the levels of PI3K, Akt and mTOR. Furthermore, after 24 hours of hypoxia induction in human proximal tubular epithelial cells, treatment with the cMet agonistic Ab also showed dose-dependent antiapoptotic effects similar to those of the recombinant HGF treatment. Even when the HGF axis was blocked with a HGF-blocking Ab, the cMet agonistic Ab showed an independent dose-dependent antiapoptotic effect. In conclusion, cMet expression is associated with the occurrence of AKI. cMet agonistic Ab treatment attenuates the severity of AKI through the PI3K/Akt/mTOR pathway and improves apoptosis. cMet agonistic Ab may have important significance for the treatment of AKI.

Evaluation of Joint Motion Sensing Efficiency According to the Implementation Method of SWCNT-Coated Fabric Motion Sensor.

The purpose of this study was to investigate the effects of the shape and attachment position of stretchable textile piezoresistive sensors coated with single-walled carbon nanotubes on their performance in measuring the joint movements of children. The requirements for fabric motion sensors suitable for children are also identified. The child subjects were instructed to wear integrated clothing with sensors of different shapes (rectangular and boat-shaped), attachment positions (at the knee and elbow joints or 4 cm below the joints). The change in voltage caused by the elongation and contraction of the fabric sensors was measured for the flexion-extension motions of the arms and legs at 60°/s (three measurements of 10 repetitions each for the 60° and 90° angles, for a total of 60 repetitions). Their reliability was verified by analyzing the agreement between the fabric motion sensors and attached acceleration sensors. The experimental results showed that the fabric motion sensor that can measure children's arm and leg motions most effectively is the rectangular-shaped sensor attached 4 cm below the joint. In this study, we developed a textile piezoresistive sensor suitable for measuring the joint motion of children, and analyzed the shape and attachment position of the sensor on clothing suitable for motion sensing. We showed that it is possible to sense joint motions of the human body by using flexible fabric sensors integrated into clothing.

Expression and In Vitro Function of Anti-Breast Cancer Llama-Based Single Domain Antibody VHH Expressed in Tobacco Plants.

Overexpression of human epidermal growth factor receptor type 2 (HER2) is considered as a prognostic factor of breast cancer, which is positively associated with recurrence when cancer metastasizes to the lymph nodes. Here, we expressed the single variable domain on a heavy chain (VHH) form of anti-HER2 camelid single domain antibody in tobacco plants and compared its in vitro anticancer activities with the anti-HER2 full size antibody. The gene expression cassette containing anti-HER2 camelid single domain antibody VHH fused to human IgG Fc region with KDEL endoplasmic reticulum (ER) (VHH-FcK) was transferred into the tobacco plant via the Agrobacterium-mediated transformation. The transformants were screened with polymerase chain reaction and Western blot analyses. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding of the purified anti-HER2 VHH-FcK to the HER2-positive breast cancer cell line, SK-BR-3. Migration assay results confirmed anticancer activity of the plant-derived anticancer camelid single chain antibody. Taken together, we confirmed the possibility of using anti-HER2 VHH-FcK as a therapeutic anticancer agent, which can be expressed and assembled and purified from a plant expression system as an alternative antibody production system.

Perovskite Light-Emitting Diodes with Improved Outcoupling Using a High-Index Contrast Nanoarray.

Organic-inorganic hybrid perovskite light-emitting diodes (PeLEDs) are promising for next-generation optoelectronic devices due to their potential to achieve high color purity, efficiency, and brightness. Although the external quantum efficiency (EQE) of PeLEDs has recently surpassed 20%, various strategies are being pursued to increase EQE further and reduce the EQE gap compared to other LED technologies. A key point to further boost EQE of PeLEDs is linked to the high refractive index of the perovskite emissive layer, leading to optical losses of more than 70% of emitted photons. Here, it is demonstrated that a randomly distributed nanohole array with high-index contrast can effectively enhance outcoupling efficiency in PeLEDs. Based on a comprehensive optical analysis on the perovskite thin film and outcoupling structure, it is confirmed that the nanohole array effectively distributes light into the substrate for improved outcoupling, allowing for 1.64 times higher light extraction. As a result, highly efficient red/near-infrared PeLEDs with a peak EQE of 14.6% are demonstrated.

Natural History of Gastric Cancer: Observational Study of Gastric Cancer Patients Not Treated During Follow-Up.

BACKGROUND: Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to analyze the natural history of gastric cancer. PATIENTS AND METHODS: We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed. RESULTS: A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for T1 and 6.2 months for T4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV. CONCLUSIONS: The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.

Optimal Nitrogen Incorporation in Nickel Silicide for Thermally Stable Contact Formation.

Nickel silicide (NiSi) is commonly used as a contact material for metal junctions but the poor thermal instability of NiSi above 600 °C has limited the further scaling down of devices and the implementation of novel schemes, such as monolithic 3-dimensional integration. This paper suggests a process to improve the thermal stability of NiSi through nitrogen incorporation during the silicidation process. The optimal level of nitrogen incorporation in NiSi reduced the nickel diffusion rate and enhanced the thermal stability by preventing the formation of a nickel disilicide phase. On the other hand, a higher level of N incorporation led to Ni3N formation, which impeded the complete transformation to NiSi. Therefore, it is essential to incorporate the optimal content of N. In this study, NiSi with 3.9% N incorporation showed superior electrical characteristics, such as the sheet resistance, junction leakage, and stable Schottky barrier height, even after high-temperature post silicidation annealing at 600 °C for 30 min.