Many physiologically based pharmacokinetic (PBPK) models for environmental chemicals, drugs, and nanomaterials have been developed to aid risk and safety assessments using acslX. However, acslX has ...been rendered sunset since November 2015. Alternative modeling tools and tutorials are needed for future PBPK applications. This forum article aimed to: (1) demonstrate the performance of 4 PBPK modeling software packages (acslX, Berkeley Madonna, MATLAB, and R language) tested using 2 existing models (oxytetracycline and gold nanoparticles); (2) provide a tutorial of PBPK model code conversion from acslX to Berkeley Madonna, MATLAB, and R language; (3) discuss the advantages and disadvantages of each software package in the implementation of PBPK models in toxicology, and (4) share our perspective about future direction in this field. Simulation results of plasma/tissue concentrations/amounts of oxytetracycline and gold from different models were compared visually and statistically with linear regression analyses. Simulation results from the original models were correlated well with results from the recoded models, with time-concentration/amount curves nearly superimposable and determination coefficients of 0.86-1.00. Step-by-step explanations of the recoding of the models in different software programs are provided in the Supplementary Data. In summary, this article presents a tutorial of PBPK model code conversion for a small molecule and a nanoparticle among 4 software packages, and a performance comparison of these software packages in PBPK model implementation. This tutorial helps beginners learn PBPK modeling, provides suggestions for selecting a suitable tool for future projects, and may lead to the transition from acslX to alternative modeling tools.
A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol ...morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe.
Research on symptom clusters is a newly emerging field in oncology; however, little evidence regarding symptom clusters in head and neck cancer (HNC) is currently available. To clarify this ...under-researched area, we investigated symptom clusters among patients with HNC treated with surgery and postoperative radiotherapy. We also examined the pattern of symptom clusters throughout the treatment course.
A convenience sample of 100 patients with HNC was recruited in the Ear, Nose, and Throat unit of a medical center in Taiwan. Before undergoing postoperative radiotherapy, patients were asked to complete the MD Anderson Symptom Inventory and a demographic sheet. Patients completed the same inventory questionnaire at week 1, 2, 3, 4, 5, and 6 of radiotherapy.
Two symptom clusters were observed, and they were stable throughout the course of radiotherapy. Cluster 1, the HNC-specific cluster, comprised the symptoms of pain, dry mouth, lack of appetite, sleep disturbance, fatigue, drowsiness, distress, and sadness. Cluster 2, the gastrointestinal cluster, included nausea, vomiting, numbness, shortness of breath, and difficulty remembering.
This study advanced our knowledge of symptom clusters in patients with HNC. The results are expected to contribute to the development of appropriate assessment and nursing interventions targeting multiple symptoms that may coexist in postoperative radiotherapy.
•There are two symptom clusters in patients with head and neck cancer.•These symptom clusters are relatively stable throughout postoperative radiotherapy.•Information of symptom clusters should be taken into account to devise care plan.
The present study aimed to investigate how bats protect their brain in a hypothermic situation. Formosan leaf-nosed bats (Hipposideros terasensis) were used in this study and treated under three ...conditions: room temperature (25±1°C), low temperature (4±1°C), and hibernation. The reactive oxygen species (ROS) levels in the blood and apoptosis-related proteins in the brain tissue were assessed and then compared among those bats under three conditions. Our results showed that the blood ROS levels of bats treated under conditions of low temperature and hibernation were significantly reduced compared with bats treated under the condition of room temperature. Both immunohistochemistry and immunoblotting expressions of hypoxia, inflammation, and apoptosis-related proteins in the brain tissue of bats treated under the condition of hibernation were significantly reduced compared with those bats treated under conditions of room temperature and low temperature. Thus, we suggested that bats can protect the brain in cold environment by reducing blood ROS levels and decreasing expressions of hypoxia, inflammation, and apoptosis-related proteins in the brain. Possible protection mechanisms involved in hypothermic adaptations need to be further clarified.
Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. ...α-Tubulin image of rCCN2 treatment (upper panel in CL1-5) only showed eight lanes, when there should be nine.
Membranous nephropathy is an autoimmune-mediated glomerulonephritis and a major cause of nephrotic syndrome. We studied the kinetics of adaptive immunity in the pathogenesis of membranous nephropathy ...in T1/T2 double transgenic mice (T1/T2 TG mice) that express human Thy1 protein under the control of interferon-γ (INF-γ) and mouse Thy1.1 protein under the control of interleukin (IL)-4. Nephropathy was induced by cationic bovine serum albumin. We found that splenocytes expressed a progressive Th2 response and a subsequent compensatory T-helper 1 (Th1) response, with a gradual augmentation of IL-4-producing Th2 cells and INF-γ-producing Th1 cells. Increased Th2 marker expression was seen in peripheral blood and kidney cells, with the immunoglobulin G1 (IgG1) antibody isotype predominant in the serum and kidneys. We found that CD8+ T cells contribute more to the augmented INF-γ production than CD4+ T cells. Moreover, CD19+ B cells demonstrated a greater production of IL-4 than the CD4+ T cells. Cytokine-related gene expression in kidneys and splenocytes showed an upregulation of proinflammatory Th1 and Th2 cytokines. Th2 cells but not Th1 cells were significantly correlated with serum cholesterol and proteinuria. Our study shows that both peripheral and renal immune reactions are strongly polarized toward Th2-type immune responses during the course of membranous nephropathy. The T1/T2 mouse model may help decipher the kinetic changes of adaptive immunity in glomerulonephritis.
Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been ...well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intra-articular formulations.
The 380-nm InGaN/AlGaN light-emitting diodes (LEDs) were fabricated on a conventional and patterned sapphire substrates (PSSs) by metalorganic vapor phase epitaxy (MOVPE). Micro-photoluminescence ...(PL) measurements showed superior near-band-edge luminescence intensity from the overhang area as compared to the layer directly on the flat sapphire region. This was accompanied by a small redshift of the PL peak wavelength that could be attributed to a relief of compressive stress in the epitaxial lateral overgrowth region. From the temperature-dependent PL measurements, we obtain an integrated PL intensity ratio at 300–10
K of ∼13.7% and thermal activation energy of 94
meV from the InGaN/AlGaN MQW PSS LED sample. Under a 20-mA current injection, the output power increased from 3.75 to 5.06
mW, corresponding to about 35% increase in external quantum efficiency. It is evident that the increase in output power depends on both the defect reduction of epitaxial lateral overgrowth of GaN and the scattering of emitted light at the GaN/sapphire interface.
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