Switching from eltrombopag to hetrombopag in patients with primary immune thrombocytopenia: a post-hoc analysis of a multicenter, randomized phase III trial.

While studies have explored the feasibility of switching between various thrombopoietin receptor agonists in treating immune thrombocytopenia (ITP), data on the switching from eltrombopag to hetrombopag remains scarce. This post-hoc analysis of a phase III hetrombopag trial aimed to assess the outcomes of ITP patients who switched from eltrombopag to hetrombopag. In the original phase III trial, patients initially randomized to the placebo group were switched to eltrombopag. Those who completed this 14-week eltrombopag were eligible to switch to a 24-week hetrombopag. Treatment response, defined as a platelet count of ≥ 50 × 109/L, and safety were evaluated before and after the switch. Sixty-three patients who completed the 14-week eltrombopag and switched to hetrombopag were included in this post-hoc analysis. Response rates before and after the switch were 66.7% and 88.9%, respectively. Among those with pre-switching platelet counts below 30 × 109/L, eight out of 12 patients (66.7%) responded, while eight out of nine patients (88.9%) with pre-switching platelet counts between 30 × 109/L and 50 × 109/L responded post-switching. Treatment-related adverse events were observed in 50.8% of patients during eltrombopag treatment and 38.1% during hetrombopag treatment. No severe adverse events were noted during hetrombopag treatment. Switching from eltrombopag to hetrombopag in ITP management appears to be effective and well-tolerated. Notably, hetrombopag yielded high response rates, even among patients who had previously shown limited response to eltrombopag. However, these observations need to be confirmed in future trials.

High-temperature PTT/CDT coordination nanoplatform realizing exacerbated hypoxia for enhancing hypoxia-activated chemotherapy to overcome tumor drug resistance.

BACKGROUND: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. RESULTS: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn2+-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. CONCLUSIONS: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.

Mortality among solid organ transplant recipients with a pretransplant cancer diagnosis.

Little is known about the outcomes among solid organ transplant recipients with a pretransplant cancer diagnosis. We used linked data from the Scientific Registry of Transplant Recipients with 33 US cancer registries. Cox proportional hazards models assessed associations of pretransplant cancer with overall mortality, cancer-specific mortality, and development of a new posttransplant cancer. Among 311 677 recipients, the presence of a single pretransplant cancer was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.23) and cancer-specific mortality (aHR, 1.93; 95% CI, 1.76-2.12); results for 2+ pretransplant cancers were similar. Cancer-specific mortality was not significantly increased for uterine, prostate, or thyroid cancers (aHRs were 0.83, 1.22, and 1.54, respectively) but strongly elevated for lung cancer and myeloma (aHRs were 3.72 and 4.42, respectively). A pretransplant cancer diagnosis was also associated with increased risk of developing posttransplant cancer (aHR, 1.32; 95% CI, 1.23-1.40). Among 306 recipients whose cancer death was confirmed by cancer registry data, 158 deaths (51.6%) were from a de novo posttransplant cancer and 105 (34.3%) from the pretransplant cancer. Pretransplant cancer diagnoses are associated with increased mortality after transplantation, but some deaths are related to posttransplant cancers and other causes. Improved candidate selection and cancer screening and prevention may reduce mortality in this population.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Analysis of N-nitrosodimethylamine in metformin hydrochloride products by high-resolution accurate mass gas chromatography mass spectrometry.

RATIONALE: The high resolving power of the Orbitrap mass spectrometer in a high-resolution accurate mass gas chromatography (HRAM-GC-MS) system provides greater selectivity and sensitivity for the identification and quantification of volatile analytes at low parts per billion (ppb) levels. Hence, it can be applied for the analysis of pharmaceutical impurities like N-nitrosodimethylamine (NDMA) in metformin hydrochloride products (METs). METHODS: Different METs extracted by a dichloromethane/aqueous system were analyzed by HRAM-GC-MS under softer electron ionization (EI) at 30 eV. The accurate masses of NDMA and its internal standard NDMA-d6 were analyzed by full scan and targeted selected ion monitoring modes under 60 000 and 30 000 full width at half maximum at m/z 200, respectively. Data acquisition and processing were managed by Xcalibur and Trace Finder software, respectively. RESULTS: Limits of detection (LOD) and quantification (LOQ) at 10 and 20 ng/g were achieved, which is below the allowed daily intake of 32 ng/g. The mass errors measured from experimental data were within ±2 ppm of the theoretical values over a period of a week. Sample analysis showed that 180 out of 212 samples (85%) were below LOD and 15 out of 212 samples (7 %) were within LOD and LOQ. Only 17 samples (8%) were found to be above LOQ, comprising one active pharmaceutical ingredient (API), five immediate-release METs and 11 extended-released METs. Amongst these, seven extended-release METs and one API exceeded the daily allowed intake, 32 ng/g. CONCLUSIONS: The validated method has been successfully applied for NDMA analysis in various forms of METs. The method is rather straightforward without an additional clean-up step. The scope can also be extended to other volatile impurities in finished pharmaceutical products.

Electrons and phonons of the discharge products in the lithium-oxygen and lithium-sulfur batteries from first-principles calculations.

Batteries have become a ubiquitous daily necessity, which are popularly applied to mobile phones and electric vehicles according to their size. Improving the battery cycle life and storage is important, but unexpected discharge products still restrict the upper limit of batter performance such as Li2O2, LiO2, and Li2S. In this study, we calculated electrons and phonons presenting the basic energy states in crystal using the first-principles calculations. The Li2O2 and Li2S are almost insulating due to the wide bandgap from their electronic structure, and doped-active p-orbital may be one of the pathways to improve crystal conduction due to the tendency of the density of states. The LiO2 is metallic, and the electronic structure and phonons show that the discharge products have an ionic feature. In addition, the ionic crystal can produce a larger DC permittivity because it possesses macroscopic polarisation. For Li2O2 and Li2S, the Raman peak of the O-O bonding is strong, while the Raman peak of the S-ion is very weak. The enhanced Raman peak of the S-ion presents a possibility to prevent the shuttle effect in Li-S batteries.

Three-dimensional relationship between the degree of bilateral impacted mandibular third molars angulation and the mandibular dental arch parameters: a cross-sectional comparative study.

OBJECTIVE: The purpose of this study was to three-dimensionally evaluate the relationship between the degree of bilateral impacted mandibular third molar (IM3M) angulation and the mandibular dental arch parameters in normal skeletal and dental malocclusion patients. MATERIALS AND METHODS: In this retrospective cross-sectional comparative study, 120 adult subjects' cone-beam computed tomography (CBCT) images were three-dimensionally analyzed. The sample included 120 adults aged 20-30 years, with a gender distribution of 51 male and 69 female participants. The sample was divided into 100 adults with bilateral IM3M (study group) and 20 adults with normal bilateral erupted M3M (control group). The study group was sub-divided into three groups according to the degree of IM3M buccolingual angulation (BL°): group A, < 12° on the center of the ridge (N = 30), group B, 12-24° off-center of the ridge (N = 40), group C, > 24° off-center of the ridge (N = 30). The study group was also sub-divided into two groups according to IM3M mesiodistal angulation (MD°): group 1 from 10 to 45° (N = 36), group 2 > 45° (N = 64). Comparison within and between groups was performed using one-way ANOVA followed by Tukey's post hoc test. The correlation between IM3M, BL, and MD angulation and the mandibular arch parameter was calculated using Pearson's correlation coefficient. RESULTS: Statistically significant differences (P < 0.001) were found between the IM3M BL° and anterior teeth inclination, arch length (AL), and inter-second molar width (inter 2nd MW) as well as between the IM3M MD° with anterior crowding and the arch length (P < 0.001). A significant positive correlation was found between IM3M BL° and anterior teeth inclination and between IM3M MD° and anterior teeth crowding and inter 2nd MW. A significant negative correlation was observed between IM3M BL° and inter 1st MW and 2nd MW. CONCLUSION: The degree of buccolingual and mesiodistal angulation of the impacted mandibular third molars was related with mandibular dentoalveolar changes. Increased buccolingual angulation is generally associated with increased anterior teeth inclination and decreased 1st and 2nd inter-molar width. The increase in mesiodistal angulations was generally related with increased anterior teeth crowding and 2nd inter-molar width. CLINICAL RELEVANCE: Assessment of the relationship between the impacted mandibular third molars and the degree of arch discrepancy, and the position of mandibular incisors in the three planes of space might help in the decision-making process for the extraction of the impacted third molars in adult patients.

A New Method for Erosion Prediction of 90° Elbow Based on Non-Axisymmetric Ultrasonic-Guided Wave and the PSO-LSSVM Algorithm.

The non-axisymmetric exciting guided wave can detect the thinning section of the elbow, and the time domain energy value of the signal collected at the outer arch position of the receiving end displays a downward trend as the remaining thickness of the erosion area decreases. To address the difficulty in detecting the erosion degree of the elbow with high accuracy, this paper uses the linear frequency modulation (LFM) signal to excite a non-axisymmetric guided wave that propagates in the 90° elbow and collects signals through four PZT receivers. To predict the erosion degree, the corresponding relationship between the energy value of the four signals after fractional Fourier filtering and the degree of elbow erosion is established through the particle swarm optimization (PSO)-least squares support vector machine (LSSVM) algorithm. The results show that the method proposed has an average accuracy rate of 98.1864%, 94.7167%, 99.119%, and 99.9593% for predicting the erosion degree of four elbow samples, and 94.0039%. and 81.2976% for two new erosion degrees, which are higher than the nonlinear regression model, LSSVM algorithm, and BP neural network algorithm. This study has guiding significance for real-time monitoring of elbow erosion.

The Nasal Bacteria Microbiome Comparison Among Fungal Ball Sinusitis, Chronic Sinusitis with Polyps.

To evaluate the composition of the microbial community of the middle nasal in paranasal sinus fungus ball (FB), chronic sinusitis with nasal polyps (CRSwNP) and healthy controls, providing new insights into the pathogenesis of FB and CRSwNP. Through 16 s rRNA gene high-throughput sequencing to determine the microbial characterization from patients with FB (n = 29) and CRSwNP (n = 10), and healthy controls (n = 4). The FB group had significantly lower αdiversity and significantly different ß diversity compared to the other groups. All three groups mainly consisted of four bacterial phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria). In the FB group, the highest relative abundance was found in Proteobacteria (47.04%). However, pairwise comparisons resulted in statistically significant differences only for Firmicutes (CRSwNP, p = 0.003, Control, p = 0.008). The CRSwNP group was statistically different from the control group in TM7(p = 0.010), Chloroflexi(p = 0.018) and Bacteroidete(p = 0.027). At the genus level, the FB group had the highest relative abundance of Haemophilus (11.53%), followed by Neisseria (7.39%), and Neisseria abundance (p < 0.001) was significantly different from the remaining two groups. Ruminococcacea abundance (p < 0.001) and Comamonadaceae abundance (p < 0.001) were increased in the CRSwNP group. The relative abundance of Lactobacillus (p < 0.001), Bacteroides S24_7 (p < 0.001), and Desulfovibrio (p < 0.001) was significantly decreased in the FB and CRSwNP groups compared to the control group. The imbalance of the microbial community is related to the pathogenesis of sinusitis.

Precisely controlled polydopamine-mediated antibacterial system: mathematical model of polymerization, prediction of antibacterial capacity, and promotion of wound healing.

In this work, the polydopamine (PDA)-mediated antibacterial system is synthesized to carry out antimicrobial activities in vitro and in vivo. First, to precisely control the surface modification of nanodiamonds (NDs), a mathematical kinetics model of PDA deposition is established, and the conditions of synthesis reaction are discussed including influencing factors such as the concentrations of dopamine, reaction time, and the kinetic constant k1, which is a function of several variables associated with the reaction temperature, light irradiance (especially at ultraviolet wavelengths), pH value and concentration of dissolved O2 in the solution. A simulated visualization demonstrates that the deposition thickness of PDA is positively correlated with temperature and light irradiance, and PDA is easier to deposit in an alkaline solution and will be terminated if the dissolved O2 is insufficient. Then, the precisely controlled thickness of PDA can control the growth of AgNPs, rendering the intensity of Raman peaks increased and providing a predictable antibacterial effect against E. coli in vitro. An optimized antibacterial hydrogel containing NDs-PDA/Ag is prepared and characterized by the Fourier transform infrared spectroscopy and field emission scanning electron microscopy. Finally, the antibacterial experiments to promote wound healing in vivo are performed, which are verified by pathological and immunohistochemical-stained sections. This work provides a theoretical basis of predicting the PDA-assisted surface modification of NDs, giving a divinable antibacterial effect, and promoting wounds healing in vivo.

Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer.

BACKGROUND: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. RESULTS: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. CONCLUSIONS: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy.

BACKGROUND: Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. RESULTS: The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen-antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. CONCLUSIONS: aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.

Deoxymikanolide adversely altered physiology and ultrastructure of Ralstonia solanacearum.

Deoxymikanolide (DEO) was isolated from Mikania micrantha Bunge and identified as a novel antibacterial compound previously. However, the mode of antimicrobial mechanism of DEO was not clear but hypothesized to affect the morphology and physiology of Ralstonia solanacearum cells. In this study, we confirmed our hypothesis via transmission electron microscopy (TEM) observation and comprehensive physiological analyses, including electric conductivity, glycan and phosphorus metabolism, activities of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), intrabacterial reactive oxygen species (ROS), and malondialdehyde (MDA) levels. We found that glycan and phosphorus metabolism, electric conductivity, intracellular ROS and MDA levels of R. solanacearum cells were significantly increased, while the activities of three antioxidant enzymes were significantly inhibited by DEO treatment. Moreover, TEM analysis showed that DEO treatment led to an early-stage of cell shrinkage, intermediate-stages of cytoplasmic damage, and a final-stage of cell disruption. Altogether, our data presented here indicate that DEO could adversely affect the physiology and morphology of R. solanacearum cells and be treated as an alternative antibacterial treatment in the future.

[Analysis of result of gene screening of neonatal deafness in Huizhou and surrounding urban areas].

OBJECTIVE: To detect common pathogenic variants associated with congenital deafness among neonates from Huizhou and surrounding areas and discuss its implications. METHODS: Thirteen hot-spot mutations in four most common pathogenic genes were screened among 20 934 neonates from March 2017 to December 2019. RESULTS: In total 760 neonates were found to carry common pathogenic variants (3.63%). Sixty two neonates have carried homozygous/compound heterozygous variants or homoplasmy/heteroplasmy mutations of mtDNA (0.29%). Further analysis of five abnormal cases revealed that 3 of them have carried compound heterozygous mutations of GJB2 gene, and 2 were due to compound heterozygous variants of the CDH23 gene. CONCLUSION: Genetic testing has a great clinical significance for the prevention and reduction of congenital hearing loss, but the scope needs to be updated and redefined by removing mutation sites with a very low rate, adding new significant sites, and improvement of the technical strategies.

Lkb1 is an important regulator of Treg differentiation and proliferation of amniotic mesenchymal stem cells.

In this study, we aimed to explore the role of liver kinase b1 (Lkb1) in the biological characteristics and immune regulation of amniotic mesenchymal stem cells (AMSCs). AMSCs were identified via the cell surface markers using flow cytometry. We knocked down the expression of Lkb1 in AMSCs using lentivirus-mediated Lkb1-specific shRNA. The efficiency of the knockdown was detected by flow cytometry, RT-qPCR, and western blot. The AMSC-related phenotype was determined by flow cytometric analysis via staining surface markers. Fibroblast colony-forming cells (CFU-F) assay and Ki-67 intracellular staining assay were used to determine the proliferative capacity. The differentiated and immunosuppressive capabilities were determined by conditional induction of differentiation and co-culture experiments. We observed that AMSCs along with Lkb1 knockdown (AMSCs-Lkb1) displayed similar cellular morphology and surface antigen expression patterns as those observed in AMSCs. However, AMSCs-Lkb1 exhibited an enhanced differentiation capacity towards osteogenesis and chondrogenesis while it showed defective proliferation and increased apoptosis. Furthermore, AMSCs-Lkb1 showed an enhanced immunosuppressive capacity by directly inhibiting conventional T cells and indirectly inducing production of regulatory T cells (Treg). Interestingly, Treg produced by AMSCs-Lkb1 displayed stronger proliferative capacity as compared to those produced by AMSCs. Our results indicate that Lkb1 plays a vital role in maintaining self-renewal of AMSCs and regulating immune equivalence, and may hold potential for the clinical management of diseases such as GVHD.

TRPC1 inhibits the proliferation and migration of estrogen receptor-positive Breast cancer and gives a better prognosis by inhibiting the PI3K/AKT pathway.

PURPOSE: Previous studies have indicated that transient receptor potential (TRP) channels can influence cancer development. The TRPC subfamily consists of seven subtypes, TRPC1 - TRPC7. Interestingly, the expression levels of TRPC1 have been shown to be totally different in different breast cancer cell lines. Nevertheless, the underlying mechanism remains unknown. In this study, we explore the significance of TRPC1 expression in breast cancer. METHODS: Immunohistochemical TRPC1 staining was performed in 278 samples. TRPC1 expression in different breast tissues were examined. Then, the influence of TRPC1 on migration, invasion and proliferation was explored. We analyzed the protein of TRPC1 by Western blot to prove which pathway may be involved in. Finally, we use online database to predict the prognosis of TRPC1 in breast cancer. RESULTS: Through immunohistochemistry and in vitro experiments, we found that the expression level of TRPC1 was higher in breast cancer cells as compared with that in normal breast epithelial cells. Moreover, the expression level of TRPC1 was different between estrogen receptor-positive (ER +) and -negative (ER -) breast cancer. It was shown that TRPC1 inhibited MCF7 cell proliferation, migration, and invasion in vitro. Western blotting revealed that TRPC1 inhibited the PI3K/AKT pathway and epithelium-mesenchymal transformation, leading to subsequent inhibition of cell proliferation and metastasis. In luminal A and luminal B patients, those with high TRPC1 expression had a better prognosis. On the contrary, in basal-like and triple-negative breast cancer (TNBC) subtypes, patients with high-TRPC1 expression had a worse prognosis. CONCLUSIONS: We confirmed that TRPC1 was high expression in breast cancer. Overexpression of TRPC1 inhibits proliferation and migration of ER + breast cancer and gives a better prognosis by inhibiting PI3K/AKT pathway activation. TRPC1 may be an independent prognostic predictor in breast cancer patients.

Activatable Fluorescence Probes for "Turn-On" and Ratiometric Biosensing and Bioimaging: From NIR-I to NIR-II.

The greatest advantage of activatable fluorescence probes (AFPs) is the inherent responsiveness to manipulate spectroscopic properties by chemical/physical interactions with the biological analytes/microenvironmental factors. As alternatives to "always-on" fluorescence probes, AFPs in the first near-infrared (NIR-I) window expanded dramatically over the past decade and served as powerful tools in fluorescence biosensing and bioimaging. Benefiting from the deep tissue penetration, minimal tissue damage, and negligible background signal within longer wavelength, recent progress of fluorescent materials in the second near-infrared (NIR-II) window has been creating vast new opportunities in developing AFPs. Here, we review the current role of AFPs in biosensing and bioimaging, with emphasis on NIR-II AFPs developed for biomedical applications. The challenges and prospects of AFPs are also discussed by considering the clinical translation from bench to bedside.

Impact of hydrogen dopant incorporation on InGaZnO, ZnO and In2O3 thin film transistors.

In this work, hydrogen (H) plasma treatment is implemented to dope indium gallium zinc oxide (InGaZnO), zinc oxide (ZnO), and indium oxide (In2O3) thin-film transistors (TFTs). We systematically analyze the active defect states inside these n-type metal oxides and reveal how they are impacted by H dopant incorporation, combining the device transfer characteristics (including the threshold voltage, subthreshold slope, and carrier mobility), the X-ray photoelectron spectra, and numerical and theoretical investigations. An increase of the field-effect mobility of these TFTs is mainly attributed to the decreased interface and bulk tail-distributed traps, after an appropriate amount of H dopants is incorporated. In ZnO, hydrogen exclusively acts as a shallow donor during the plasma treatment, while the zinc vacancies Zn(Vac) cannot be passivated by the H dopants as no improvement of the subthreshold slope (SS) is observed in the hydrogenated ZnO TFT. The H interstitials (Hi) incorporated into In2O3 are stable in the + charge state at equilibrium, then change into the - charge state as the Fermi level energy EF gets closer to the bottom of the conduction band. Due to the H insertion into an oxygen vacancy VO, the VOH complex (acting as an acceptor) is formed in InGaZnO with increased H plasma treatment duration, leading to the degraded SS. This paper clarifies the H dopants' role and the different dominant defects inside the three types of TFTs, which may benefit systematic understanding and exploration of H dopant incorporation into InGaZnO, ZnO and In2O3 films for TFT improvement and optimization.

Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways.

Britanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

Long non-coding RNA Arid2-IR affects advanced glycation end products-induced human retinal endothelial cell injury by binding to Smad3.

PURPOSE: Long non-coding RNAs (lncRNAs) have been reported to play significant roles in the pathogenesis of diabetic retinopathy (DR). The aim of the present study was to investigate the role of lncRNA Arid2-IR in advanced glycation end product (AGE)-induced human retinal endothelial cells (HRECs) injury. MATERIALS AND METHODS: Cell viability was determined by Cell Counting Kit-8 assay following induction with AGEs. The expression of Arid2-IR and Smad3 was detected by reverse transcription-quantitative PCR or western blotting. A luciferase reporter assay was conducted to determine the interaction between Arid2-IR and Smad3. The levels of inflammation-related and oxidative stress-related factors were evaluated by respective kits. The expression of extracellular matrix (ECM)-related and apoptosis-related proteins was detected by western blotting. Immunofluorescence assay was used to detect the level of vascular endothelial growth factor, and flow cytometry was applied to measure the levels of apoptosis. RESULTS: The results revealed that AGE treatment decreased HREC proliferation and upregulated the expression of Arid2-IR and Smad3. The luciferase assay indicated that Smad3 was able to bind to the promoter region sequence of Arid2-IR. Moreover, Arid2-IR silencing reduced inflammation, oxidative stress and ECM production induced by AGEs in HRECs, and Smad3 inhibition further reduced the levels of the aforementioned factors, while Smad3 overexpression exerted the opposite effect. Furthermore, apoptosis of HRECs induced by AGEs was decreased following Arid2-IR silencing, which was further reduced following treatment with Smad3 inhibitor, but was reversed after transfection with Smad3 pcDNA3.1. CONCLUSION: The findings demonstrated that Arid2-IR affects AGE-induced HREC injury by binding to Smad3.