As a new class of materials, implantable flexible electrical conductors have recently been developed and applied to bioelectronics. An ideal electrical conductor requires high conductivity, ...tissue‐like mechanical properties, low toxicity, reliable adhesion to biological tissues, and the ability to maintain its shape in wet physiological environments. Despite significant advances, electrical conductors that satisfy all these requirements are insufficient. Herein, a facile method for manufacturing a new conductive hydrogels through the simultaneous exfoliation of graphite and polymerization of zwitterionic monomers triggered by microwave irradiation is introduced. The mechanical properties of the obtained conductive hydrogel are similar to those of living tissue, which is ideal as a bionic adhesive for minimizing contact damage due to mechanical mismatches between hard electronics and soft tissues. Furthermore, it exhibits excellent adhesion performance, electrical conductivity, non‐swelling, and high conformability in water. Excellent biocompatibility of the hydrogel is confirmed through a cytotoxicity test using C2C12 cells, a biocompatibility test on rat tissues, and their histological analysis. The hydrogel is then implanted into the sciatic nerve of a rat and neuromodulation is demonstrated through low‐current electrical stimulation. This hydrogel demonstrates a tissue‐like extraneuronal electrode, which possesses high conformability to improve the tissue–electronics interfaces, promising next‐generation bioelectronics applications.
A new conductive hydrogel is developed through the simultaneous exfoliation of graphite and polymerization of zwitterionic monomers triggered by microwave irradiation. This hydrogel demonstrates tissue‐like extraneuronal electrodes satisfying requirements of bioelectronics such as low storage modulus, high viscoelasticity, low toxicity, reliable adhesion, and conformability to biological tissues, and maintenance of conductivity and hydrogel volume in wet environments.
Mo-doped TiNb2O7 (TNO) anode material has shown excellent electrochemical performance, especially at high C-rates. Doping TNO with Mo(6+) resulted in charge redistribution, leading to the enhancement ...of electronic conductivity (caused by bandgap narrowing) and Li(+) diffusivity in the lattice.
We investigated the optical and electrical properties of red AlGaInP light-emitting diodes (LEDs) as functions of chip size, p-cladding layer thickness, and the number of multi-quantum wells (MQWs). ...External quantum efficiency (EQE) decreased with decreasing chip size. The ideality factor gradually increased from 1.47 to 1.95 as the chip size decreased from 350 μm to 15 μm. This indicates that the smaller LEDs experienced larger carrier loss due to Shockley-Read-Hall nonradiative recombination at sidewall defects. S parameter, defined as ∂lnL/∂lnI, increased with decreasing chip size. Simulations and experimental results showed that smaller LEDs with 5 pairs of MQWs had over 30% higher IQE at 5 A/cm
than the LED with 20 pairs of MQWs. These results show that the optimization of the number of QWs is needed to obtain maximum EQE of micro-LEDs.
Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been found to have therapeutic potential for treating cancers associated with impaired DNA repair capabilities, particularly those with ...deficiencies in the homologous recombination repair (HRR) pathway. Histone deacetylases (HDACs) are important for enabling functional HRR of DNA by regulating the expression of HRR-related genes and promoting the accurate assembly of HRR-directed sub-nuclear foci. Thus, HDAC inhibitors have recently emerged as a therapeutic agent for treating cancer by inhibiting DNA repair. Based on this, HDAC inhibition could be predicted to enhance the anti-tumor effect of PARP inhibitors in cancer cells by blocking the HRR pathway.
We determined whether suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, could enhance the anti-tumor effects of olaparib on breast cancer cell lines using a cytotoxic assay, cell cycle analysis, and Western blotting. We evaluated how exposure to SAHA affects the expression of HRR-associated genes. The accumulation of DNA double strand breaks (DSBs) induced by combination treatment was assessed. Induction of autophagy was monitored by imaging green fluorescent protein-tagged microtubule-associated protein 1A/1B-light chain 3 (LC3) expression following co-treatment with olaparib and SAHA. These in vitro data were validated in vivo using a human breast cancer xenograft model.
Triple-negative breast cancer cell (TNBC) lines showed heterogeneous responses to the PARP and HDAC inhibitors. Co-administration of olaparib and SAHA synergistically inhibited the growth of TNBC cells that expressed functional Phosphatase and tensin homolog (PTEN). This effect was associated with down-regulation of the proliferative signaling pathway, increased apoptotic and autophagic cell death, and accumulation of DNA damage. The combined anti-tumor effect of olaparib and SAHA was also observed in a xenograft model. These data suggest that PTEN expression in TNBC cells can sensitize the cell response to simultaneous inhibition of PARP and HDAC both in vitro and in vivo.
Our findings suggest that expression of functional PTEN may serve as a biomarker for selecting TNBC patients that would favorably respond to a combination of olaparib with SAHA. This provides a strong rationale for treating TNBC patients with PTEN expression with a combination therapy consisting of olaparib and SAHA.
•The TiO2 nanotube powders are prepared by rapid breakdown anodization process.•The effects of anion additives for nonmetal-doped TiO2 are investigated.•A nitrate acts as a catalyst that accelerates ...the mass production of powders.•P- and S-doped TiO2 nanotube powders are obtained without altering the morphology.•The band-gap energy significantly reduced for S-doped TiO2 nanotube powders.
Nonmetal-doped TiO2 powders consisting of one-dimensional nanotube bundles are prepared using electrolytes containing different kinds of anion additives via a one-step rapid breakdown anodization (RBA) process in a short time. The results show that although no nitrogen species are observed when nitrate is used as an additive, it acts as a catalyst to increase current density during the RBA process. However, substitutional P- or S-doped TiO2 nanotube powders with reduced band gap energy are obtained when electrolytes containing phosphate or sulfate are used. Compared with that of undoped-TiO2 nanotube powders, S-doped TiO2 nanotube powders exhibit significantly reduced band gap energy, from 3.36 eV to 2.93 eV as the concentration of sulfate ions increases.
When timely access to deceased‐donor livers is not feasible, living‐donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary ...objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single‐center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non‐HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post‐LT renal recovery. The HRS group had a higher death rate than the non‐HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post‐LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non‐recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post‐LT sepsis (p < 0.001) and non‐recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre‐LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post‐LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post‐LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post‐LT renal recovery.
When timely access to deceased‐donor livers is not available for candidates with hepatorenal syndrome, expeditious living‐donor liver transplantation can reduce the risk of death or permanent renal failure. Selzner and Wong comment on page 2291
Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas (redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic blocks and dasatinib ...(DAS, an oncogenic tyrosine kinases inhibitor) conjugated hydrophobic blocks, were designed as dual-functional carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles facilitated efficient cleavage of DAS from prodrug micelles in tumor cells/tissues, leading to a higher level of anti-tumor activity in vitro and in vivo. In addition, DOX-loaded POEG-b-PSSDas micelles exhibited triggered DOX release under a redox environment (10mM glutathione, GSH), and demonstrated enhanced cytotoxicity against 4T1.2 and PC3 cell lines compared to DOX and DOX-loaded POEG-b-PCCDas micelles. More importantly, DOX-loaded POEG-b-PSSDas micelles were more effective in inhibiting the tumor growth and prolonging the survival rate in an aggressive murine breast cancer model (4T1.2) compared to DOX-loaded POEG-b-PCCDas micelles and a micellar formulation co-loaded with DOX and DAS. This redox-responsive prodrug micellar system provides an attractive strategy for effective combination of tumor targeted therapy and traditional chemotherapy, which warrants further investigation.
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Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end‐stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric ...LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single‐center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n = 81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n = 113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n = 93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center‐oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero‐mortality rate in pediatric LDLT.
Salvage liver transplantation is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. ADV score is calculated by multiplying α-fetoprotein and des-γ-carboxyprothrombin ...concentrations and tumor volume. Prognostic accuracy of ADV score was assessed in patients undergoing salvage living donor liver transplantation (LDLT) and their outcomes were compared with patients undergoing primary LDLT.
This study was a retrospective, single-center, case-controlled study. Outcomes were compared in 125 patients undergoing salvage LDLT from 2007 to 2018 and in 500 propensity score-matched patients undergoing primary LDLT.
In patients undergoing salvage LDLT, median intervals between hepatectomy and tumor recurrence, between first HCC diagnosis and salvage LDLT, and between hepatectomy and salvage LDLT were 12.0, 37.2, and 29.3 months, respectively. Disease-free survival (DFS, P = .98) and overall survival (OS, P = .44) rates did not differ significantly in patients undergoing salvage and primary LDLT. Pretransplant and explant ADV scores were significantly predictive of DFS and OS in patients undergoing salvage and primary LDLT (P < .001). DFS after prior hepatectomy (P = .52) and interval between hepatectomy and LDLT (P = .82) did not affect DFS after salvage LDLT. Milan criteria and ADV score were independently prognostic of DFS and OS following salvage LDLT, and prognosis of patients within and beyond Milan criteria could be further stratified by ADV score.
Risk factors and posttransplant outcomes were similar in patients undergoing salvage and primary LDLT. ADV score is surrogate biomarker for posttransplant prognosis in salvage and primary LDLT recipients. Prognostic model incorporating ADV scores can help determine whether to perform salvage LDLT.
The contributors to this book explore the current situation of North Korea in various aspects and provide policy suggestions for North Korea to become part of the international community and achieve ...sustainable development.
Focusing on three key areas of economic development, namely, international sectors, agriculture and urban development, and energy and environment, this book lays out recommendations and prospects for North Korea. Authors assess the current situation of North Korea, explore preconditions for becoming a member of the international community, and suggest policies necessary for the sustainable development of North Korea. They cover a wide range of areas including reforestation, WTO accession, and the potential for economic integration with South Korea. These evaluations draw on both what is understood about the current situation in North Korea and comparisons with other countries and territories.
This book will be a valuable resource for scholars and policy planners who focus on North Korea.
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