A conductive polymer thin film having choline phosphate as the side group was prepared. Quartz crystal microbalance (QCM) was employed to evaluate the adsorption of the model protein, bovine serum ...albumin (BSA), on the films deposited on indium tin oxide (ITO) electrodes. Cell adsorption on the film was evaluated by a fibroblast NIH3T3.
Ability of IL‐17‐producing CD8+ T cells (Tc17) to transform into cytotoxic anti‐tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors ...regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17‐based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL‐4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN‐γ‐producing IECs, an effect dependent on Eomes expression. IL‐4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN‐γ‐producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL‐4/AKT signalling drove the upregulation of the T‐cell receptor‐associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL‐4‐induced T‐cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL‐4 in Tc17 reprogramming. Collectively, these results document a novel IL‐4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL‐4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti‐tumour responses.
IL4 mediated Trat1 expression enhances Tc17 anti‐tumour phenotype. The IL‐4/AKT/Eomes/Trat1 axis is a novel signalling loop that promotes expansion and reprogramming of Tc17 cells into cytotoxic effectors with a therapeutic potential for adoptive cell transfer immunotherapy.
The uniform and smaller-sized (~3 μm) LiNi0.8Co0.1Mn0.1O2 (SNCM) particles are prepared via a fast nucleation process of oxalate co-precipitation, followed by a two-step calcination procedure. It is ...found that the fast nucleation by vigorous agitation enables us to produce oxalate nuclei having a uniform size which then grow into micron-particles in less than a few minutes. The impacts of solution pH, precipitation time, calcination temperature, and surface modification with ZrO2 on the structural, morphological, and electrochemical properties of SNCM are systematically examined to identify the optimal synthetic conditions. A novel bimodal cathode design has been highlighted by using the combination of the SNCM particles and the conventional large (~10 μm) LiNi0.83Co0.12Mn0.05O2 (LNCM) particles to achieve the high volumetric energy density of cathode. The volumetric discharge capacity is found to be 526.6 mAh/cm3 for the bimodal cathode L80% + S20%, whereas the volumetric discharge capacity is found to be only 480.3 and 360.6 mAh/cm3 for L100% and S100% unimodal, respectively. Moreover, the optimal bi-modal cathode delivered higher specific energy (622.4 Wh/kg) and volumetric energy density (1622.6 Wh/L) than the L100% unimodal (596.1 Wh/kg and 1402.1 Wh/L) cathode after the 100th cycle. This study points to the promising utility of the SNCM material in Li-ion battery applications.
(PO) is a commonly known medicinal crop that is an important ingredient for traditional Chinese medicine (TCM) due to its use as a vegetable in the diet. PO has been recorded to be frequently ...adulterated by other related species in the market of herbal plants, distorting the PO plant identity. Thus, identification of the botanical origin of PO is a crucial step before pharmaceutical or functional food application. In this research, a quick assay named "loop-mediated isothermal amplification (LAMP)" was built for the specific and sensitive authentication of PO DNA. On the basis of the divergences in the internal transcribed spacer 2 (ITS2) sequence between PO and its adulterant species, the LAMP primers were designed and verified their specificity, sensitivity, and application for the PO DNA authentication. The detection limit of the LAMP assay for PO DNA identification specifically was 100 fg under isothermal conditions at 63 °C for 30 min. In addition, different heat-processed PO samples can be applied for use in PO authentication in the LAMP assay. These samples of PO were more susceptible to the effect of steaming in authentication by PCR than boiling and drying treatment. Furthermore, commercial PO samples pursued from herbal markets were used to display their applicability of the developed LAMP analysis for PO postharvest authentication, and the investigation found that approximately 68.4% of PO specimens in the marketplace of herbal remedies were adulterated. In summary, the specific, sensitive, and rapid LAMP assay for PO authentication was first successfully developed herein, and its practical application for the inspection of adulteration in PO samples from the herbal market was shown. This LAMP assay created in this study will be useful to authenticate the botanical origin of PO and its commercial products.
Abstract
Background
Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. ...The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort.
Methods
Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score.
Results
A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0–3 low risk, 4–7 moderate risk, and 8–13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001).
Conclusions
The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.
Treated hepatitis B patients remain at risk for liver cancer. The REAL-B score comprising sex, age, alcohol, diabetes, cirrhosis, platelet, and AFP (derived and validated in 8048 Asians, 25 centers) accurately predicts liver cancer risk for patients on oral antivirals.
Studies on temporal changes in noninvasive fibrosis indices and liver stiffness measurement (LSM) in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral agents (DAAs) are ...limited.
We retrospectively enrolled consecutive patients with CHC who had received DAAs.
In total, we recruited 395 consecutive patients, of which 388 (98.2%) achieved a sustained virologic response (SVR) at 12 weeks after therapy. In patients who received DAA therapy and achieved SVR 12 weeks after therapy (n = 388), the median aspartate aminotransferase/platelet ratio index (APRI) value decreased from 1.19 (0.62-2.44) at baseline to 0.50 (0.32-0.95), 0.51 (0.31-0.92), 0.48 (0.31-0.88), and 0.52 (0.33-0.92) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median FIB-4 value decreased from 2.88 (1.56-5.60) at baseline to 2.10 (1.30-3.65), 2.15 (1.30-3.65), 2.11 (1.37-3.76), and 2.22 (1.45-3.82) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median alanine aminotransferase level significantly decreased from week 2 until PW12 (all P < 0.001). The platelet count significantly increased from 2 weeks after DAA therapy initiation until PW12 (all P < 0.001); however, the magnitude of changes in the platelet count was low. In patients with paired LSMs obtained using acoustic radiation force impulse elastography at baseline and PW12 (n = 199), the median LSM decreased from 1.78 (1.25-2.30) m/s at baseline to 1.38 (1.14-1.88) m/s at PW12 (P < 0.001).
Noninvasive fibrosis indices, namely APRI and FIB-4, exhibited a rapid and sustained decline from week 2 until PW12 in patients with CHC who achieved SVR to DAA therapy. The rapid decline in APRI and FIB-4 values might mainly result from improvement in necroinflammation.
We compared rates of hepatitis B surface antigen (HBsAg) loss and hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients without cirrhosis who continued or ...discontinued entecavir.
Patients who discontinued entecavir treatment for at least 12 months (discontinued group; n = 234) and patients who continued entecavir treatment for at least 4 years (continued group; n = 226) were recruited.
In the discontinued group, the 5-year cumulative incidences of virological relapse (VR), clinical relapse (CR), and HBsAg loss were 71.9%, 58.9%, and 13%, respectively. Patients with sustained response, VR but no CR, and CR without retreatment were 49-, 13-, and 18-fold more likely to develop HBsAg loss than those with retreatment. Patients who discontinued entecavir therapy had a higher rate of HBsAg loss than those who continued entecavir therapy, in all and 360 propensity score (PS)-matched patients. Cox regression analysis revealed that the discontinued group was an independent predictor for HBsAg loss. There was no significant difference in HCC development between the 2 groups in all and PS-matched patients.
HBeAg-negative patients without cirrhosis who discontinued entecavir treatment exhibited a higher HBsAg loss rate without an increased risk of HCC compared to those who continued entecavir treatment.
Background: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been ...observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2–12 years.Methods and Results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio OR 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval CI 2.33–321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10–129.81) were independent risk factors for AR progression after closure.Conclusions: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.
Regulation of cellular actin dynamics is pivotal in driving cell motility. During cancer development, cells migrate to invade and spread; therefore, dysregulation of actin regulators is often ...associated with cancer progression. Here we report the role of ABRACL, a human homolog of the
actin regulator Costars, in migration and tumorigenic growth of cancer cells. We found a correlation between ABRACL expression and the migratory ability of cancer cells. Cell staining revealed the colocalization of ABRACL and F-actin signals at the leading edge of migrating cells. Analysis of the relative F-/G-actin contents in cells lacking or overexpressing ABRACL suggested that ABRACL promotes cellular actin distribution to the polymerized fraction. Physical interaction between ABRACL and cofilin was supported by immunofluorescence staining and proximity ligation. Additionally, ABRACL hindered cofilin-simulated pyrene F-actin fluorescence decay in vitro, indicating a functional interplay. Lastly, analysis on a colorectal cancer cohort demonstrated that high ABRACL expression was associated with distant metastasis, and further exploration showed that depletion of ABRACL expression in colon cancer cells resulted in reduced cell proliferation and tumorigenic growth. Together, results suggest that ABRACL modulates actin dynamics through its interaction with cofilin and thereby regulates cancer cell migration and participates in cancer pathogenesis.
We developed an optimal noninvasive index comprising routine laboratory parameters for predicting cirrhosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. This study included ...992 CHB patients and 1,284 CHC patients who received liver biopsy. We developed the new index, named modified Fibrosis-4 (mFIB-4) according to four independent variables of the model: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The formula of the mFIB-4 index is 10 × Age(years) × AST(U/L)/Platelet count(10
/L) × AST(U/L). For predicting cirrhosis, the bootstrap areas under the receiver operating characteristic curve for platelet count, AST/ALT ratio (AAR), AAR/platelet ratio index (AARPRI), AST/platelet ratio index (APRI), FIB-4, Pohl score, age-platelet (AP) index, Lok index, fibrosis quotient (FibroQ), and mFIB-4 were 0.7680, 0.7400, 0.8070, 0.6090, 0.7690, 0.6990, 0.7850, 0.7960, 0.8110, and 0.8070 in CHB patients, and 0.8170, 0.7210, 0.8400, 0.7310, 0.8310, 0.6730, 0.8220, 0.8440, 0.8570, and 0.8480 in CHC patients, respectively. FibroQ and mFIB-4 exhibited the highest diagnostic performance levels for liver cirrhosis in CHB and CHC despite the inclusion of the international normalised ratio in the formulation of FibroQ. Thus, mFIB-4 is a simple, inexpensive, and readily available method for assessing the liver fibrosis stage of Asian patients with CHB or CHC.
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