Kirschner Wire Prying and Leverage Technique: a new closed reduction method in treatment of pediatric "Irreducible Supracondylar Humerus Fractures".

BACKGROUND: This study employs an innovative closed reduction approach to treat pediatric "Irreducible Supracondylar Humerus Fractures" with the goal of demonstrating its practical application compared to conventional methods. METHODS: This study sampled 146 surgically treated cases of "Irreducible Supracondylar Humerus Fractures" in our department. After applying inclusion and exclusion criteria, 120 children were selected and divided into two groups based on treatment methods. Group 1 underwent Closed Reduction and Percutaneous Pinning (CRPP), while Group 2 received treatment using the Kirschner Wire Prying and Leverage Technique alongside CRPP. The relevant data to the study were collected and assessed during the follow-up period. RESULTS: Results indicate that Group 2 demonstrated significantly shorter operative times and fewer instances of intraoperative fluoroscopy compared to Group 1. Furthermore, the percentage of cases requiring open reduction was notably higher in Group 1 than in Group 2. The analysis also identified age, BMI, time from injury to surgery, and the initial deviation of the distal fragment as independent risk factors associated with the failure of closed reduction. The integration of CRPP with the Kirschner Wire Prying and Leverage Technique emerges as a safe and effective strategy for managing "Irreducible Supracondylar Humerus Fractures." This innovative approach not only reduces operative time and intraoperative fluoroscopy needs but also diminishes the reliance on open reduction without compromising safety.

Open Arthrolysis for Chronic Elbow Dislocation with Extremely Severe Stiffness in Children.

OBJECTIVE: Studies on extremely severe elbow stiffness after chronic dislocation in children are scarce. This study aims to investigate the choice of surgical treatment modalities and to analyze their treatment efficacy in children with chronic elbow dislocation with extremely severe periarticular stiffness. METHODS: Data of 21 children with chronic elbow dislocation with extremely severe periarticular stiffness diagnosed and treated in our department between February 2015 and February 2021 were retrospectively analyzed. Twenty boys and one girl were included in the study, their mean age was 11 ± 2.5 years, and they had concomitant distal humerus fractures. For the treatment protocol, all children with extremely severe elbow stiffness were treated with open arthrolysis, and elbow joint stability was intraoperatively assessed. All children performed passive functional exercises the day after surgery. The elbow flexion and extension angles, range of motion (ROM), and Mayo score were evaluated preoperatively and at the final follow-up. RESULTS: Of the 21 children, only one had recurrent severe stiffness of the elbow joint after surgery; nevertheless, the function was still improved compared with that before surgery. Preoperatively, the mean elbow extension and flexion angles were 72.2° ± 12.7° and 93.6° ± 11.1°, respectively, and the range of motion (ROM) of the elbow joint was 17.8° ± 8.3°. At the final follow-up, the mean elbow extension and flexion angles were 22.7° ± 18.6° and 118.8° ± 15.4°, respectively, and the elbow joint ROM was 96.1° ± 17.4°. The differences in the preoperative and postoperative ROMs, flexion angles, and extension angles of the elbow joint were significant (p < 0.01). The MEPS at the final follow-up was 78.57 ± 14.24, which was significantly higher than preoperative (29.76 ± 10.89), and the excellent rate was 81%. CONCLUSION: Open arthrolysis and open reduction and internal fixation of the elbow joint are effective in treating chronic elbow dislocation with extremely severe stiffness in children.

Non-linear shrinkage of Batson's #17 resin during vascular corrosion casting.

Many studies of cardiovascular function require a realistic representation of vascular geometry. Corrosion casting has been used to acquire such geometries for many decades. However, the fidelity with which this method reproduces vascular anatomy has not been completely determined. Here we report on the non-linear shrinkage characteristics and exothermic properties of Batson's #17, a widely used casting resin, in model systems and in aortas of rats and rabbits. The setting process was captured using high-resolution photography. Shrinkage ranged from 3.4 ± 1.5% of the diameter in 1 ml plastic syringes (inner diameter 4.8 mm) to 19.6 ± 5.6% in the aorta of rats (diameter 1.5-2.6 mm). In addition, aortic curvature and branching angles changed during setting. These effects should be determined and corrected in studies of vascular geometry where high accuracy is required.

Cancer therapy by antibody-targeted Cerenkov light and metabolism-selective photosensitization.

Photodynamic therapy (PDT) is an effective cancer treatment option, but it suffers from penetration limit of light, making it available only for superficial and endoscopically accessible cancers. Recently, there have been reports that Cerenkov luminescence originated from radioisotopes can be utilized as an excitation source for PDT without external light illumination. Here, cancer-selective agents, i.e., (1) clinically available 5-aminolevulinic acid (5-ALA), which promotes cancer metabolism-specific accumulation of protoporphyrin IX (PpIX), and (2) 64Cu-DOTA-trastuzumab, which has HER2-expressing cancer selective uptake, are separately applied as a photosensitizer and an in situ radiator, respectively, to potentiate tumor-specific Cerenkov luminescence energy transfer (CLET) from 64Cu to PpIX for high-precision PDT of cancer. It is shown that the combinational administration and tumor colocalization of 5-ALA and 64Cu-DOTA-trastuzumab exert significant in vitro cytotoxicity (cell viability <9%) as well as in vivo antitumor effects (tumor volume ratio of 0.50 on 14 days post-injection) on HER2-expressing breast and gastric cancer models. This study proves that high-precision treatment regimen using dual-targeted CLET-based PDT is feasible for HER2-expressing cancers. Furthermore, the results offer great potential for clinical translation to the dual-targeted CLET-based PDT because the treatment regimen uses components, 5-ALA and 64Cu-DOTA-trastuzumab, which are already in clinical uses.

Novel Chelating Agents for Zirconium-89-Positron Emission Tomography (PET) Imaging: Synthesis, DFT Calculation, Radiolabeling, and In Vitro and In Vivo Complex Stability.

We report the synthesis and evaluation of novel chelating agents for zirconium-89 (89Zr) with positron emission tomography (PET) imaging applications. New chelating agents NODHA, NOTHA, and NODHA-PY were constructed on 1,4,7-triazacyclononane (TACN) and possess hydroxamic acid or a pyridine ring as an acyclic binding moiety. The new chelating agents were theoretically studied for complexation with Zr(IV). Structures of Zr(IV)-NODHA, Zr(IV)-NOTHA, and Zr(IV)-NODHA-PY were predicted using density functional methods. NODHA was found to form stronger bonds with Zr(IV) when compared to NOTHA and NODHA-PY. The new chelating agents were evaluated for radiolabeling efficiency in binding 89Zr. The corresponding [89Zr]Zr-labeled chelators were evaluated for complex stability in human serum. All new chelating agents rapidly bound to 89Zr in excellent radiolabeling efficiency at room temperature. Among the new [89Zr]Zr-labeled chelators evaluated, [89Zr]Zr-NODHA showed the highest stability in human serum without losing 89Zr, and [89Zr]Zr-NODHA-PY released a considerable amount of 89Zr in human serum. [89Zr]Zr-NODHA, [89Zr]Zr-NODHA-PY, and [89Zr]Zr-DFO were comparatively evaluated for in vivo complex stability by performing biodistribution studies using normal mice. [89Zr]Zr-DFO had the lowest bone uptake at all time points, while [89Zr]Zr-NODHA-PY showed poor stability in mice as evidenced by high bone accumulation at the 24 h time point. [89Zr]Zr-NODHA exhibited better renal clearance but higher bone uptake than [89Zr]Zr-DFO.

The affective, behavioural, and cognitive reactions to a diagnosis of Primary Progressive Aphasia: A qualitative descriptive study.

OBJECTIVES: Receiving a diagnosis of neurodegenerative disorder is life changing. Primary progressive aphasia is one such disease. Understanding how receiving this diagnosis impacts on individuals may help plan support services. However, limited qualitative research from the perspectives of people with Primary Progressive Aphasia are available for suitable care planning. Current literature primarily focuses on experiences of family members. The present study aims to fill this gap by examining the affective, behavioural, and cognitive experiences of people with Primary Progressive Aphasia. METHODS: Semi-structured interviews were conducted with six participants with PPA. A qualitative descriptive approach was used to describe responses from participants on: (i) what they experienced prior to receiving their diagnosis; (ii) their experience of receiving the diagnosis; and (iii) how they were living with their PPA. Verbatim transcripts were analysed using thematic analysis to identify main themes. RESULTS: Analysis revealed a superordinate theme of Multifaceted Grief with subthemes described in sequence of research questions posed, representing the three phases of Pre-Diagnosis, Time of Diagnosis, and Post-Diagnosis. Themes collectively revealed participants' ongoing experience of loss in dealing with the evolving challenges of Primary Progressive Aphasia. Experiences of loss emerged with descriptions of feelings, thoughts, and limitations in relation to changes imposed by the illness, impacting daily activities and life roles central to participants' pre-diagnosis sense of self. CONCLUSION: Participants' affective, behavioural and cognitive reactions to their Primary Progressive Aphasia diagnosis marks the onset of Multifaceted Grief borne of loss of communication and cognition. Participants expressed a need for information regarding a possible Primary Progressive Aphasia trajectory and support to enable a successful transition as their disease progressed. Collaborative engagement between speech pathologists and people with Primary Progressive Aphasia incorporates addressing all levels of the International Classification of Functioning and Health by considering neurological, psychological, and psychosocial experiences of the person with the diagnosis.

High-Resolution Colloidal Quantum Dot Film Photolithography via Atomic Layer Deposition of ZnO.

High-resolution patterning of quantum dot (QD) films is one of the preconditions for the practical use of QD-based emissive display platforms. Recently, inkjet printing and transfer printing have been actively developed; however, high-resolution patterning is still limited owing to nozzle-clogging issues and coffee ring effects during the inkjet printing and kinetic parameters such as pickup and peeling speed during the transfer process. Consequently, employing direct optical lithography would be highly beneficial owing to its well-established process in the semiconductor industry; however, exposing the photoresist (PR) on top of the QD film deteriorates the QD film underneath. This is because a majority of the solvents for PR easily dissolve the pre-existing QD films. In this study, we present a conventional optical lithography process to obtain solvent resistance by reacting the QD film surface with diethylzinc (DEZ) precursors using atomic layer deposition. It was confirmed that, by reacting the QD surface with DEZ and coating PR directly on top of the QD film, a typical photolithography process can be performed to generate a red/green/blue pixel of 3000 ppi or more. QD electroluminescence devices were fabricated with all primary colors of QDs; moreover, compared to reference QD-LED devices, the patterned QD-LED devices exhibited enhanced brightness and efficiency.

Downregulation of NKG2DLs by TGF-ß in human lung cancer cells.

BACKGROUND: Transforming growth factor beta (TGF-ß) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-ß and a TGF-ß inhibitor, Galunisertib (LY2157299). RESULTS: TGF-ß reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-ß on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-ß, it was thought that TGF-ß induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-ß or Galunisertib. CONCLUSIONS: Therefore, inhibition of TGF-ß might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Differential Effects of Histone Deacetylases on the Expression of NKG2D Ligands and NK Cell-Mediated Anticancer Immunity in Lung Cancer Cells.

Histone acetylation is an epigenetic mechanism that regulates the expression of various genes, such as natural killer group 2, member D (NKG2D) ligands. These NKG2D ligands are the key molecules that activate immune cells expressing the NKG2D receptor. It has been observed that cancer cells overexpress histone deacetylases (HDACs) and show reduced acetylation of nuclear histones. Furthermore, HDAC inhibitors are known to upregulate the expression of NKG2D ligands. Humans have 18 known HDAC enzymes that are divided into four classes. At present, it is not clear which types of HDAC are involved in the expression of NKG2D ligands. We hypothesized that specific types of HDAC genes might be responsible for altering the expression of NKG2D ligands. In this study, we monitored the expression of NKG2D ligands and major histocompatibility complex (MHC) class I molecules in lung cancer cells which were treated with six selective HDAC inhibitors and specific small interfering RNAs (siRNAs). We observed that treatment with FK228, which is a selective HDAC1/2 inhibitor, also known as Romidepsin, induced NKG2D ligand expression at the transcriptional and proteomic levels in two different lung cancer cell lines. It also caused an increase in the susceptibility of NCI-H23 cells to NK cells. Silencing HDAC1 or HDAC2 using specific siRNAs increased NKG2D ligand expression. In conclusion, it appears that HDAC1 and HDAC2 might be the key molecules regulating the expression of NKG2D ligands. These results imply that specifically inhibiting HDAC1 and HDAC2 could induce the expression of NKG2D ligands and improve the NK cell-mediated anti-cancer immunity.

Single-cell immunoblotting resolves estrogen receptor-α isoforms in breast cancer.

An array of isoforms of the nuclear estrogen receptor alpha (ER-α) protein contribute to heterogeneous response in breast cancer (BCa); yet, a single-cell analysis tool that distinguishes the full-length ER-α66 protein from the activation function-1 deficient ER-α46 isoform has not been reported. Specific detection of protein isoforms is a gap in single-cell analysis tools, as the de facto standard immunoassay requires isoform-specific antibody probes. Consequently, to scrutinize hormone response heterogeneity among BCa tumor cells, we develop a precision tool to specifically measure ER-α66, ER- α46, and eight ER-signaling proteins with single-cell resolution in the highly hetero-clonal MCF-7 BCa cell line. With a literature-validated pan-ER immunoprobe, we distinguish ER-α66 from ER-α46 in each individual cell. We identify ER-α46 in 5.5% of hormone-sensitive (MCF-7) and 4.2% of hormone-insensitive (MDA-MB-231) BCa cell lines. To examine whether the single-cell immunoblotting can capture cellular responses to hormones, we treat cells with tamoxifen and identify different sub-populations of ER-α46: (i) ER-α46 induces phospho-AKT at Ser473, (ii) S6-ribosomal protein, an upstream ER target, activates both ER-α66 and ER-α46 in MCF-7 cells, and (iii) ER-α46 partitions MDA-MB-231 subpopulations, which are responsive to tamoxifen. Unlike other single-cell immunoassays, multiplexed single-cell immunoblotting reports-in the same cell-tamoxifen effects on ER signaling proteins and on distinct isoforms of the ER-α protein.

Pyridine-containing octadentate ligand NE3TA-PY for formation of neutral complex with 177Lu(III) and 90Y(III) for radiopharmaceutical applications: Synthesis, DFT calculation, radiolabeling, and in vitro complex stability.

Targeted radionuclide therapy is a developing therapeutic modality for cancer and employs a cytotoxic radionuclide bound to a chelating agent and a bioactive molecule with high binding affinity for a specific biomarker in tumors. An optimal chelator is one of the critical components to control therapeutic efficacy and toxicity of targeted radionuclide therapy. We designed a new octadentate ligand NE3TA-PY (7-[2-[(carboxymethyl)(2-pyridylmethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) for ß-particle-emitting 177Lu and 90Y with targeted radionuclide therapy applications. The pyridine-containing polyaminocarboxylate ligand was proposed to form a neutral complex with Lu(III) and Y(III). The new chelator NE3TA-PY was synthesized and experimentally and theorectically studied for complexation with 177Lu(III) and 90Y(III). DFT-optimized structures of Y(III)-NE3TA-PY and Lu(III)-NE3TA-PY complexes were predicted. NE3TA-PY displayed excellent radiolabeling efficiency with both 177Lu and 90Y. The new chelator (NE3TA-PY) bound to 177Lu was more stable in human serum and better tolerated when challenged by EDTA than 90Y-labeled NE3TA-PY. Our findings suggest that the new chelator (NE3TA-PY) produced excellent Lu-177 radiolabeling and in vitro complex stability profiles.

An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells.

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.

Antibacterial and Antibiofilm Activities of Novel Antimicrobial Peptides against Multidrug-Resistant Enterotoxigenic Escherichia Coli.

Post-weaning diarrhea due to enterotoxigenic Escherichia coli (ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of conventional antibiotics has caused serious problems because of the growing emergence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 µg/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 µg/mL) and the highest minimal hemolysis concentration (MHC, 256 µg/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time-kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 µg/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 µg/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC.

Analog Memristive Characteristics of Square Shaped Lanthanum Oxide Nanoplates Layered Device.

Square-shaped or rectangular nanoparticles (NPs) of lanthanum oxide (LaOx) were synthesized and layered by convective self-assembly to demonstrate an analog memristive device in this study. Along with non-volatile analog memory effect, selection diode property could be co-existent without any implementation of heterogeneous multiple stacks with ~1 µm thick LaOx NPs layer. Current-voltage (I-V) behavior of the LaOx NPs resistive switching (RS) device has shown an evolved current level with memristive behavior and additional rectification functionality with threshold voltage. The concurrent memristor and diode type selector characteristics were examined with electrical stimuli or spikes for the duration of 10-50 ms pulse biases. The pulsed spike increased current levels at a read voltage of +0.2 V sequentially along with ±7 V biases, which have emulated neuromorphic operation of long-term potentiation (LTP). This study can open a new application of rare-earth LaOx NPs as a component of neuromorphic synaptic device.

New Bifunctional Chelator 3p-C-NEPA for Potential Applications in Lu(III) and Y(III) Radionuclide Therapy and Imaging.

We have developed structurally unique bifunctional chelators in the NETA, NE3TA, and DEPA series for potential radiopharmaceutical applications. As part of our continued research efforts to generate efficient bifunctional chelators for targeted radionuclide therapy and imaging of various diseases, we designed a scorpion-like chelator that is proposed to completely saturate the coordination spheres of Y(III) and Lu(III). We herein report the synthesis and evaluation of a new chelator (3p-C-NEPA) with 10 donor groups for complexation with ß-emitting radionuclides 90Y(III), 86Y(III), and 177Lu(III). The chelator was synthesized and evaluated for radiolabeling kinetics with the readily available radioisotopes 90Y and 177Lu, and the corresponding 90Y or 177Lu-radiolabeled complexes were evaluated for in vitro stability in human serum and in vivo complex stability in mice. The new chelator rapidly bound 90Y or 177Lu and formed a stable complex with the radionuclides. The new chelator 3p-C-NEPA radiolabeled with either 90Y or 177Lu remains stable in human serum without dissociation for 10 days. 177Lu-labeled 3p-C-NEPA produced a favorable in vivo biodistribution profile in normal mice.

Treatment of pediatric lateral condylar humerus fractures with closed reduction and percutaneous pinning.

BACKGROUND: Lateral condylar humerus fractures (LCHFs) are the second most common pediatric distal humerus fractures. Open reduction and internal fixation is recommended for fractures displaced by more than 2 mm. Few studies described using closed reduction and percutaneous pinning (CRPP) for treating fractures with greater displacements. This study aims to explore the feasibility of CRPP in treating displaced LCHFs. METHODS: All patients underwent attempted CRPP first. Once a satisfying reduction was obtained, as determined using fluoroscopy based on the relative anatomical position of the fragments, an intraoperative arthrogram was performed to further confirm the congruence of the articular surface of the distal humerus. Open reduction is necessary to ensure adequate reduction if the fracture gap is more than 2.0 mm on either anteroposterior view or oblique internal rotational view by fluoroscopy after CRPP. All included fractures were treated by a single pediatric surgeon. RESULTS: Forty-six patients were included, 29 boys and 17 girls, with an average age of 5.2 years. Of these, 22/28 (78%) Jakob type II fractures and 14/18 (78%) Jakob type III fractures were treated with CRPP. All cases in Song stages II and III, 19/25 (76%) cases in Song stage IV, and 14/18 (78%) cases of Song stage V were treated with CRPP. The remaining converted to open reduction with internal fixation. Overall, 36 of the 46 patients (78%) were treated with CRPP. The average pre-op displacement was 7.2 mm, and the average post-op displacement was 1.1 mm on the anteroposterior or oblique internal rotational radiograph in cases treated with CRPP. CRPP was performed in an average of 37 min. The average casting period was 4 weeks and the average time of pin removal was 6 weeks postoperatively. The average time of follow-up was 4 months. All patients achieved union, regardless of closed or open reduction. No infection, delayed union, cubitus varus or valgus, osteonecrosis of the trochlea or capitellum, or pain were recorded during follow-up. CONCLUSIONS: Closed reduction and percutaneous pinning effectively treats LCHFs with displacement more than 4 mm. More than 3/4 of Song stage V or Jakob type III patients can avoid an incision.

Diffraction and Polarization Properties of Electrically-Tunable Nematic Liquid Crystal Grating.

This work demonstrates an electrically-tunable nematic liquid crystal (NLC) diffraction grating with a periodic electrode structure, and discusses the polarization properties of its diffraction. The efficiency of the first-order diffraction can be gradually controlled by applying external electric fields cross the NLC, and the maximum diffraction efficiency of the first-order diffraction that can be obtained is around 12.5% under the applied voltage of 5.0 V. In addition to the applied electric field, the efficiency of the first-order diffraction can also vary by changing the polarized state of the incident beam. Antisymmetric polarization states with symmetrical intensities in the diffractions corresponding to the +1 and -1 order diffraction signals are also demonstrated.

Potentiation of TRAIL­induced cell death by nonsteroidal anti­inflammatory drug in human hepatocellular carcinoma cells through the ER stress­dependent autophagy pathway.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. The limited success with relapse of the disease in HCC therapy is frequently associated with the acquired resistance to anticancer drugs. To develop a strategy and design for overcoming the resistance of HCC cells to TNF­related apoptosis inducing ligand (TRAIL)­induced cell death, we evaluated the efficacy of a non­steroidal anti­inflammatory drug (NSAID) in combination with TRAIL against TRAIL­resistant HCC cells expressing a high level of CD44. We revealed by MTT and western blotting, respectively, that celecoxib (CCB), an NSAID, and 2,5­dimethyl celecoxib (DMC), a non­cyclooxygenase (COX)­2 inhibitor analog of CCB, were able to sensitize TRAIL­resistant HCC cells to TRAIL, implicating a COX­independent mechanism. CCB dose­dependently enhanced LC3­II and reduced p62 levels through AMPK activation and inhibition of the Akt/mTOR pathway and upregulated expression of ATF4/CHOP, leading to activation of endoplasmic reticulum (ER) stress­dependent autophagy. The TRAIL sensitization capacity of CCB in TRAIL­resistant HCC cells was abrogated by an ER stress inhibitor. In addition, we also revealed by flow cytometry and western blotting, respectively, that accelerated downregulation of TRAIL­mediated c­FLIP expression, DR5 activation and CD44 degradation/downregulation by NSAID resulted in activation of caspases and poly(ADP­ribose) polymerase (PARP), leading to the sensitization of TRAIL­resistant HCC cells to TRAIL and thereby reversal of TRAIL resistance. From these results, we propose that NSAID in combination with TRAIL may improve the antitumor activity of TRAIL in TRAIL­resistant HCC, and this approach may serve as a novel strategy that maximizes the therapeutic efficacy of TRAIL for clinical application.

The coexistence of threshold and memory switching characteristics of ALD HfO2 memristor synaptic arrays for energy-efficient neuromorphic computing.

The development of bioinspired electronic devices that can mimic the biological synapses is an essential step towards the development of efficient neuromorphic systems to simulate the functions of the human brain. Among various materials that can be utilized to attain electronic synapses, the existing semiconductor industry-compatible conventional materials are more favorable due to their low cost, easy fabrication and reliable switching properties. In this work, atomic layer deposited HfO2-based memristor synaptic arrays are fabricated. The coexistence of threshold switching (TS) and memory switching (MS) behaviors is obtained by modulating the device current. The TS characteristics are exploited to emulate essential synaptic functions. The Ag diffusive dynamics of our electronic synapses, analogous to the Ca2+ dynamics in biological synapses, is utilized to emulate synaptic functions. Electronic synapses successfully emulate paired-pulse facilitation (PPF), post-tetanic potentiation (PTP), spike-timing-dependent plasticity (STDP), short-term potentiation (STP), long-term potentiation (LTP) and transition from STP to LTP with rehearsals. The psychological memorization model of short-term memory (STM) to long-term memory (LTM) transition is mimicked by image memorization in crossbar array devices. Reliable and repeatable bipolar MS behaviors with a low operating voltage are obtained by a higher compliance current for energy-efficient nonvolatile memory applications.

17ß-Estradiol Inhibits Lysophosphatidylcholine-Induced Apoptosis in Cultured Vascular Smooth Muscle Cells.

OBJECTIVES: Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17ß-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. METHODS: VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. RESULTS: After pre-treatment for 24 hours, 17ß-E2 suppressed lysoPC-induced (15 µM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17ß-E2 (10⁻6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17ß-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF-κB-mediated transcriptional activity were reduced with 17ß-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. CONCLUSIONS: In cultured VSMCs treated with lysoPC, 17ß-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.