Intratumor subsets with tumor-initiating features in glioblastoma are likely to survive treatment. Our goal is to identify the key factor in the process by which cells develop temozolomide (TMZ) ...resistance.
Resistant cell lines derived from U87MG and A172 were established through long-term co-incubation of TMZ. Primary tumors obtained from patients were maintained as patient-derived xenograft for studies of tumor-initating cell (TIC) features. The cell manifestations were assessed in the gene modulated cells for relevance to drug resistance.
Among the mitochondria-related genes in the gene expression databases, superoxide dismutase 2 (SOD2) was a significant factor in resistance and patient survival. SOD2 in the resistant cells functionally determined the cell fate by limiting TMZ-stimulated superoxide reaction and cleavage of caspase-3. Genetic inhibition of the protein led to retrieval of drug effect in mouse study. SOD2 was also associated with the TIC features, which enriched in the resistant cells. The CD133
specific subsets in the resistant cells exhibited superior superoxide regulation and the SOD2-related caspase-3 reaction. Experiments applying SOD2 modulation showed a positive correlation between the TIC features and the protein expression. Finally, co-treatment with TMZ and the SOD inhibitor sodium diethyldithiocarbamate trihydrate in xenograft mouse models with the TMZ-resistant primary tumor resulted in lower tumor proliferation, longer survival, and less CD133, Bmi-1, and SOD2 expression.
SOD2 plays crucial roles in the tumor-initiating features that are related to TMZ resistance. Inhibition of the protein is a potential therapeutic strategy that can be used to enhance the effects of chemotherapy.
To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without ...hepatic arteriovenous shunt (HAVS).
This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE.
The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups.
For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.
The continuous mutation of SARS-CoV-2 highlights the need for rapid, cost-effective, and high-throughput detection methods. To better analyze the antibody levels against SARS-CoV-2 and its variants ...in vaccinated or infected subjects, we developed a multiplex detection named Barcode Bead Fluorescence (BBF) assay. These barcode beads were magnetic, characterized by 2-dimensional edges, highly multiplexed, and could be decrypted with visible light. We conjugated 12 magnetic barcode beads with corresponding nine spike proteins (wild-type, alpha, beta, gamma, delta, and current omicrons), two nucleocapsid proteins (wild-type and omicron), and one negative control. First, the conjugated beads underwent serial quality controls via fluorescence labeling, e.g., reproducibility (R square = 0.99) and detection limits (119 pg via anti-spike antibody). Next, we investigated serums from vaccinated subjects and COVID-19 patients for clinical applications. A significant reduction of antibody levels against all variant beads was observed in both vaccinated and COVID-19 studies. Subjects with two doses of mRNA-1273 exhibited the highest level of antibodies against all spike variants compared to two doses of AZD1222 and unvaccinated. We also found that COVID-19 patients showed higher antibody levels against spike beads from wild-type, alpha, beta, and delta. Finally, the nucleocapsid beads served as markers to distinguish infections from vaccinated subjects. Overall, this study developed the BBF assay for analyzing humoral immune responses, which has the advantages of robustness, automation, scalability, and cost-effectiveness.
This study highlights the importance of electronic hybridizations in the FeO6 octahedral distortion, structural evolution, magnetization, oxidation state and atomic bonding covalency in multiferroic ...(Bi1−xNdx)FeO3 (x = 0–0.10) ceramics as the system approaches the morphotropic phase boundary (MPB). The Rietveld-refinement analysis reveals reductions of bismuth deficiency, oxygen vacancies, and nonpolar Bi2Fe4O9 phase as Nd increases. The piezoresponse domain switching reveals a coexistence of polar ferroelectric rhombohedral and minor orthorhombic (nonpolar) phases. The piezoresponse ferroelectric polarization hysteresis loops are attributed to the reduced leaky conductivity in the Nd-doped compositions. The Fe K- and L2,3-edges synchrotron X-ray absorptions suggest a mixture of Fe3+ and Fe4+ valence states and reduction of the FeO6 octahedral distortion by the A-site Nd substitution. The oxygen K-edge synchrotron X-ray absorptions reveal that the hybridizations of the O 2p–Fe 3d and the O 2p–Bi 6sp orbitals were decreased with increasing Nd content.
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•Reduction of Bi and O vacancies by the A-site rare earth Nd substitution in BiFeO3.•Coexistence of polar ferroelectric rhombohedral and nonpolar orthorhombic phases.•Mixture of Fe3+ and Fe4+ valences and reduction of the FeO6 octahedral distortion.•Important roles of the O 2p–Fe 3d and the O 2p–Bi 6sp orbital hybridizations.
We propose and experimentally demonstrate a 2.333-Tbit/s bi-directional optical mobile network using optical wireless communication (OWC). The proposed network architecture is divided into: fronthaul ...network connecting between the distributed-unit (DU) and the remote-radio-unit (RRU); and midhaul network connecting between the central unit (CU) and the DU. At the midhaul, an aggregated 2.333-Tbit/s transmission is achieved using wavelength division multiplexed (WDM) infrared (IR) based invisible light communication (IVLC). For the link between the RRU and user-equipment (UE), 2.7 Gbit/s white-light visible-light-communication (VLC) transmission is achieved for indoor 1.5 m transmission. It can provide communication and lighting simultaneously. A gateway (GW) is also proposed acting as the interface between the IVLC and VLC transmissions. In the proposed architecture, about 400 VLC end-users can be supported.
•We demonstrated a 2.333-Tbit/s bi-directional optical mobile network.•Optical wireless communication (OWC) was used.•2.7-Gbit/s white-light visible-light-communication (VLC) is achieved.•The VLC can provide communication and lighting simultaneously.
•Blood transfusion requirement and total blood loss were higher in the drained group than in the undrained group of proximal femoral nail antirotation (PFNA) system fixation for intertrochanteric ...fractures (ITFs).•The closed drainage system may have manifested no short-term benefit for wound condition postoperatively.•We suggest that the closed suction system should not be routinely used for treating intertrochanteric fractures with PFNA fixation.
Introduction: The effect of using closed suction drainage system with the proximal femoral nail antirotation (PFNA) system fixation on outcomes in treating intertrochanteric fractures (ITFs) is still unknown. This prospective randomized controlled trial aimed to examine whether routine drainage is useful for PFNA fixation in ITFs.
Methods: A total of 80 patients with acute ITFs were treated with closed or mini-open reduction with PFNA fixation at the National Cheng Kung University Hospital and 60 eligible patients were randomized for whether to receive suction drainage. In clinical outcomes, the visual analog scale (VAS), morphine equivalent dosage, injured thigh width, body temperature, wound condition and wound infection were measured on postoperative day 1, 2, 4, 10, and 90. In laboratory outcomes, we evaluated hemoglobin and hematocrit levels postoperatively at different time points. Blood transfusion and total blood loss (TBL) were measured by Mercuriali's formula in millimeter.
Results: The results revealed that the amount of blood transfusion received by the drained group (543.3 mL) was more than that by the undrained group (367.8 mL; p = 0.0074), and similarly, TBL in the drained group (750.1 mL) was more than that in the undrained group (537.4 mL; p = 0.0067). Regarding clinical and laboratory outcomes, compared with the undrained group, the drained group had a higher VAS score on postoperative day 2 (p = 0.0216). No difference was observed between the 2 groups for morphine equivalent dosage, thigh swelling, wound infection and hematoma, hospitalization period, or total number of complications at every time point after index procedure.
Conclusions: Blood transfusion requirement and TBL were higher in the drained group than in the undrained group of PFNA fixation for ITFs. In addition, the closed drainage system may have manifested no short-term benefit for wound condition postoperatively.
Abstract We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+ ·DOTA, through supramolecular assembly of ...molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+ ·DOTA-encapsulated supramolecular nanoparticles (Gd3+ ·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+ ·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+ ·DOTA⊂SNPs with an r1 of 17.3 s−1 mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1 -weighted imaging of Gd3+ ·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+ ·DTPA. A Gd3+ ·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+ ·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1 -weighted imaging after injecting Gd3+ ·DOTA⊂SNPs but not after injecting Gd3+ ·DTPA. The MRI results are supported by ICP-MS analysis ex vivo . These results show that Gd3+ ·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.
Over one-third of energy is generated from coal consumption in Taiwan. In order to estimate the health impact assessment attributable to PM2.5 concentrations emitted from coal consumption in Taiwan. ...We applied a Gaussian trajectory transfer-coefficient model to obtain county-wide PM2.5 exposures from coal consumption, which includes coal-fired power plants and combined heat and power plants. Next, we calculated the mortality burden attributable to PM2.5 emitted by coal consumption using the comparative risk assessment framework developed by the Global Burden of Disease study. Based on county-level data, the average PM2.5 emissions from coal-fired plants in Taiwan was estimated at 2.03 ± 1.29 (range: 0.32–5.64) μg/m3. With PM2.5 increments greater than 0.1 μg/m3, there were as many as 16 counties and 66 air quality monitoring stations affected by coal-fired plants and 6 counties and 18 monitoring stations affected by combined heat and power plants. The maximum distances affected by coal-fired and combined heat and power plants were 272 km and 157 km, respectively. Our findings show that more counties were affected by coal-fired plants than by combined heat and power plants with significant increments of PM2.5 emissions. We estimated that 359.6 (95% CI: 334.8–384.9) annual adult deaths and 124.4 (95% CI: 116.4–132.3) annual premature deaths were attributable to PM2.5 emitted by coal-fired plants in Taiwan. Even in six counties without power plants, there were 75.8 (95% CI: 60.1–91.5) deaths and 25.8 (95%CI: 20.7–30.9) premature deaths annually attributable to PM2.5 emitted from neighboring coal-fired plants. This study presents a precise and effective integrated approach for assessing air pollution and the health impacts of coal-fired and combined heat and power plants.
Cholelithiasis is a disease with increasing prevalence over the decades. Gallbladder drainage (GBD) is an alternative choice in critically ill patients who cannot tolerate early surgery for acute ...cholecystitis. In previous data, early or delayed cholecystectomy (CCY) leads to less recurrent biliary events (RBEs) comparing to using a wait‐and‐see strategy. We wondered if a subsequent CCY strategy after GBD can benefit patients with high surgical risk. This study aimed to explore the clinical outcome after percutaneous transhepatic GBD and risk factors for RBEs. We studied 180 adult acute cholecystitis patients who received percutaneous transhepatic GBD during index admission between July 2017 and December 2018 in Chung Shan Medical University Hospital and Changhua Christian Hospital after exclusion of patients died during the index admission or lost follow‐up within 30 days. We further divided these patients into those who received subsequent CCY within 2 months and those who received no CCY within 2 months. RBEs, mortality, and biliary event‐related mortality were compared. Multivariate analysis was applied to find the most important factors of RBE‐free survival. There were 8 cases (13.6%) in the subsequent CCY group that experienced recurrent biliary events, whereas 39 cases (32.2%) experienced recurrent biliary events in the no CCY within 2 months group. The proportion and average recurrent biliary events per person were all significantly lower in the subsequent CCY group. Although the overall mortality rate was higher in the group that had no CCY within 2 months (16.5% vs 5.1%), the RBE‐related mortality difference was insignificant. The most decisive factor to determine RBE‐free survival is whether there was a subsequent CCY or not (HR: 0.485, 95% CI: 0.250‐0.941, P = .032). We found that subsequent CCY can decrease further RBEs and improve RBE‐free survival in high‐risk patients with acute cholecystitis that accepted percutaneous transhepatic GBD initially.
•N-3 PUFAs are nutraceuticals with high tolerability and safety profiles.•Six months of n-3 PUFAs adjunctive therapy has reduced the recurrence of bipolar depression.•Fish oil or placebo therapy for ...6 months did not induce mania in our subjects.
This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.
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