Chromodomain Y-like (CDYL) inhibition ameliorates acute kidney injury in mice by regulating tubular pyroptosis.

Acute kidney injury (AKI) is a common disease, but lacking effective drug treatments. Chromodomain Y-like (CDYL) is a kind of chromodomain protein that has been implicated in transcription regulation of autosomal dominant polycystic kidney disease. Benzo[d]oxazol-2(3H)-one derivative (compound D03) is the first potent and selective small-molecule inhibitor of CDYL (KD = 0.5 µM). In this study, we investigated the expression of CDYL in three different models of cisplatin (Cis)-, lipopolysaccharide (LPS)- and ischemia/reperfusion injury (IRI)-induced AKI mice. By conducting RNA sequencing and difference analysis of kidney samples, we found that tubular CDYL was abnormally and highly expressed in injured kidneys of AKI patients and mice. Overexpression of CDYL in cisplatin-induced AKI mice aggravated tubular injury and pyroptosis via regulating fatty acid binding protein 4 (FABP4)-mediated reactive oxygen species production. Treatment of cisplatin-induced AKI mice with compound D03 (2.5 mg·kg-1·d-1, i.p.) effectively attenuated the kidney dysfunction, pathological damages and tubular pyroptosis without side effects on liver or kidney function and other tissue injuries. Collectively, this study has, for the first time, explored a novel aspect of CDYL for tubular epithelial cell pyroptosis in kidney injury, and confirmed that inhibition of CDYL might be a promising therapeutic strategy against AKI.

Monochorionic-triamniotic triplet pregnancy following artificial reproductive technology: Report of a rare case in Taiwan.

OBJECTIVE: Monochorionic-triamniotic (MCTA) triplet pregnancies following artificial reproductive technologies are uncommon. We report a case in which one of two transferred embryos differentiated into an MCTA triplet. This study aimed to investigate the potential factors contributing to MCTA triplet pregnancy. CASE REPORT: A 39-year-old woman underwent her second frozen embryo transfer with hatching blastocysts, which resulted in the detection of an MCTA triplet on ultrasonography. She delivered by cesarean section at 32 weeks of gestation, resulting in the birth of three live male infants. Her medical history and in vitro fertilization treatment were reviewed to identify potential causes. CONCLUSION: The etiology of MCTA triplet pregnancy remains multifactorial. In the presented case, prolonged in vitro culture to the blastocyst stage and inner cell mass splitting were potential contributing factors. Further research is needed to fully understand the complexity of MCTA triplet pregnancy.

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Trichothecenes with cytotoxic activity and benzene derivatives with hypolipidemic activity from trichothecium sp.

Five trichothecenes including a new one, together with two previously undescribed benzene derivatives were isolated from the solid culture of Trichothecium sp. Their structures were established by 1D and 2D NMR data in conjunction with HR-ESI-MS analysis. Compounds 1-5 exhibited cytotoxicity against MCF-7 cell lines at various levels ranging from IC50 of 7.23 to 16.95 µM. Compound 6 decreased the concentration of blood lipids in zebra fish at the concentration of 20 µM.

Is use of a long-term proton pump inhibitor or histamine-2 receptor antagonist a risk factor for iron-deficiency anaemia in Taiwan? A neglected clinical drug-drug interaction.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

Self-Enhancement of Water Electrolysis by Electrolyte-Poled Ferroelectric Catalyst.

Efficient and durable electrocatalysts with superior activity are needed for the production of green hydrogen with a high yield and low energy consumption. Electrocatalysts based on transition metal oxides hold dominance due to their abundant natural resources, regulable physical properties, and good adaptation to a solution. In numerous oxide catalyst materials, ferroelectrics, possessing semiconducting characteristics and switchable spontaneous polarization, have been considered promising photoelectrodes for solar water splitting. However, few investigations noted their potential as electrocatalysts. In this study, we report an efficient electrocatalytic electrode made of a BiFeO3/nickel foam heterostructure, which displays a smaller overpotential and higher current density than the blank nickel foam electrode. Moreover, when in contact with an alkaline solution, the bond between hydroxyls and the BiFeO3 surface induces a large area of upward self-polarization, lowering the adsorption energy of subsequent adsorbates and facilitating oxygen and hydrogen evolution reaction. Our work demonstrates an infrequent pathway of using functional semiconducting materials for exploiting highly efficient electrocatalytic electrodes.

Photothermal nanozymes to self-augment combination cancer therapy by dual-glutathione depletion and hyperthermia/acidity-activated hydroxyl radical generation.

Chemodynamic therapy (CDT) has emerged as a promising strategy for tumor treatment. Nevertheless, the low Fenton catalytic efficiency and the high concentration of glutathione (GSH) in cancer cells largely decline antitumor efficacy of CDT. To self-augment antitumor effect of the CDT by combining with photothermal therapy (PTT), the unique photothermal nanozymes that doubly depleted GSH, and generated massive hydroxyl radicals (·OH) in the hyperthermia/acidity-activated manner were developed. Through the coordination of Fe3+ ions with PEGylated chitosan (PEG-CS)-modified polydopamine (PDA) nanoparticles, the attained Fe3+@PEG-CS/PDA nanozymes showed outstanding colloidal stability, photothermal conversion efficiency and acidity-triggered Fe3+ release. By GSH-mediated valence states transition of Fe3+ ions and Michael reaction between GSH and quinone-rich PDA, the nanozymes sufficiently executed dual depletion of GSH with the elevated temperature.Under mimic tumor acidity and near-infrared (NIR) irradiation condition, the endocytosed nanozymes effectively converted intracellular H2O2 into toxic ·OH upon amplified Fenton reaction, thereby potently killing 4T1 cancer cells and RAW 264.7 cells. Importantly, the nanozymes prominently suppressed 4T1 tumor growth in vivo and metastasis of cancer cells by CDT/PTT combination therapy without significant systemic toxicity. Our study provides novel visions in design of therapeutic nanozymes with great clinical translational prospect for tumor treatment.

Applying expanded metal mesh for outdoor shades in outdoor thermal environments.

This study investigated the applicability of expanded metal meshes (EMMs) in horizontal shading devices. We performed simulations and experiments with EMMs with different opening ratios and directions. We established various experimental and control groups to measure air temperature, surface temperature, and black globe temperature. After the comparison of simulation and experimental data, we used Grasshopper to simulate long-term climate situations. The research results can serve as reference for users in Tainan and provide customized suggestions. The findings can serve as a paradigm for parametric design to analyze EMMs. In design projects involving outdoor horizontal shading devices, these results can be used in the design phase for evaluation. Full-day measurements revealed that EMMs with small openings exhibited favorable shading effects. In the Tainan area, we suggest using north-facing EMMs; in our simulations result, 70% of sunshine did not pass through the mesh in a day. For shading equipment in the morning, west-facing EMMs should be used because they blocked 50-90% of sunshine. For recreational areas in the afternoon and evening, east-facing EMMs can block 50-90% of sunshine after noon. In Taiwan, south-facing EMMs are not advised because their shading performance is suboptimal in the morning and afternoon.

Comparing the Variants of Iron Oxide Nanoparticle-Mediated Delivery of miRNA34a for Efficiency in Silencing of PD-L1 Genes in Cancer Cells.

The blocking of programmed death-ligand 1 (PD-L1) in tumor cells represents a powerful strategy in cancer immunotherapy. Using viral vectors to deliver the cargo for inactivating the PD-L1 gene could be associated with host cell genotoxicity and concomitant immune attack. To develop an alternative safe gene delivery method, we designed a unique combination for miRNA34a delivery using a transgene carrier in the form of iron oxide magnetic nanoparticles (IONPs) via magnetofection to downregulate PD-L1 expression in cancer cells. We synthesized IONPs of multiple shapes (IONRs (iron oxide nanorods), IONSs (iron oxide nanospheres), and ITOHs (iron oxide truncated octahedrons)), surface-functionalized with polyethyleneimine (PEI) using the ligand exchange method, as gene delivery systems. Under the guidance of an external magnetic field, PEI@IONPs loaded with plasmid DNA (DNA/PEI@IONPs) encoding GFP showed high transfection efficiency at different weight ratios and time points in A549 and MDA-MB-231 cells. Additionally, the DNA/PEI@IONPs with miRNA34a inserts under a static magnetic field resulted in significant knockdown of the PD-L1 gene, as demonstrated via immunoblotting of the PD-L1 protein. Among the three shapes of IONPs, IONRs showed the highest PD-L1 knockdown efficiency. The genetic expression of miRNA34a was also studied using qPCR and it showed high expression of miRNA in cells treated with PEI@IONRs. Flow cytometry and a live/dead assay confirmed apoptosis after transfection with miRNA34a. To conclude, in this paper, a promising transgene carrier with low cost, negligible cytotoxicity, and high transfection efficiency has been successfully established for miRNA gene delivery in the context of cancer immunotherapy.

The investigation of composition and thermal behavior of two types of backfilling gutta-percha.

Background/purpose: In the warm gutta-percha technique, soft-type and regular-type gutta-percha are using for backfilling thermoplasticized injection system. However, there are limited reports about the properties of these backfilling gutta-percha. This study aimed to analyze and compare the composition, thermal behavior and compact force of two types of backfilling gutta-percha. Materials and methods: Soft-type and regular-type backfilling gutta-percha (B&L BioTech, Fairfax, VA, USA) were investigated. The inorganic and organic fractions of these gutta-perchas were separated by quantitative chemical analysis (n = 6). Their composition was analyzed using energy dispersive spectroscopy. Thermal behavior in response to temperature variations was analyzed using differential scanning calorimetry. Additionally, a compaction model was used to investigate the relation between compaction force and temperature (n = 10). Results: The soft-type contained more gutta-percha (3.69-5.85%), carbon ratio (38.96-48.52%) and less inorganic substance (86.51-90.45%), zinc ratio (29.36-35.67%). The composition ratio of two types gutta-percha were statistically significant different (P < 0.05). There were three phase transitions of the soft-type gutta-percha which started at 39.84 °C, 49.32 °C and 54.15 °C while the two phase transitions of the regular-type gutta-percha started at 40.48 °C and 53.45 °C. The glass transition temperature of the regular-type gutta-percha (44.24 °C) was higher than that of the soft-type gutta-percha (40.66 °C). Under various setting temperature, the higher compaction force in the regular-type gutta-percha was required (P < 0.05). Conclusion: The different components in gutta-percha contribute to its differences in thermal behavior. The soft-type had a higher proportion of gutta-percha and lower ZnO which makes the fluidity better than the regular-type.

Hybridization chain reaction-assisted enzyme cascade genosensor for the detection of Listeria monocytogenes.

Foodborne diseases caused by pathogens may threaten public health and the social economy. We demonstrated a method for identifying pathogenic Listeria monocytogenes using DNA logic operations. To achieve accurate species distinguishing, three specific sequences of Listeria monocytogenes genomic DNA were screened out and used as the feature sequences. Three complementary probes with tag modification were designed as sensing elements and exert affinity for magnetic beads, glucose oxidase (GOx), and horseradish peroxidase (HRP). To obtain a digital output (YES/NO answer) for rapid determination, a Boolean logic function was employed. Three sensing probes enabled the recognition of the target sequence (input) and the formation of a target DNA/probe hybrid. Through magnetic separation and affinity binding events, the target DNA/probes hybrid led to the construction of GOx/HRP enzyme cascade, which produced a visualized color signal (output) in the presence of substrates, glucose, and 3, 3', 5, 5'-tetramethylbenzidine (TMB). A hybridization chain reaction (HCR) was coupled with this sensing scaffold to increase the binding of the enzyme cascade and amplify the output signal. The logical functional biosensor showed high selectivity of Listeria monocytogenes over other Listeria species. This sensing platform provides a simple, sensitive, and highly specific method for detecting Listeria monocytogenes.

Evaluation of two gene ablation methods for the analysis of pregnenolone function in zebrafish embryonic development.

Pregnenolone (P5) is a steroid that functions in the brain and in zebrafish embryogenesis. It is synthesized from cholesterol via the enzymatic activity of P450scc, encoded by CYP11A1. P5 exerts its function by activating CLIP1, which in turn promotes microtubule assembly necessary for many biological processes including embryogenesis. To examine the functional relatedness of CYP11A1 and CLIP1, we ablated the embryonic expression of both genes in zebrafish, i.e. cyp11a1 and clip1a. Two cyp11a1 knockout fish lines were generated. Both homozygous cyp11a1 knockout lines appeared normal. But the development of fish embryos was delayed and embryonic cell migration was reduced when cyp11a1 function was depleted of by morpholinos. This discrepancy in phenotypes by two different gene depletion methods was also observed for clip1a. While clip1a morphants are defective in embryogenesis, clip1a knockout fish appeared normal. The phenotypes depend on the methods that create gene depletion. While knockout fish lines do not have expected phenotypic defects, clip1a and cyp11a1 morpholinos both reduce embryonic cell migration. We have evaluated the usefulness of both methods of gene ablation, and conclude that CYP11A1 and CLIP1 function in the same pathway to promote embryogenesis.

Transcriptional response and functional analysis of ATP-binding cassette transporters to tannic acid in pea aphid, Acyrthosiphon pisum (Harris).

Although tannins are widely distributed in broad beans and alfalfa, the pea aphid (Acyrthosiphon pisum) can still destroy them. The ATP binding cassette (ABC) transporters participate in the metabolism of plant secondary metabolites and pesticides in insects. However, whether ABC transporter genes play a role in the metabolism of tannins in the pea aphid is unclear. Here, we found that verapamil (an ABC transporter inhibitor) significantly increased the mortality of tannic acid to pea aphid, which indicated that ABC transporter gene was related to the metabolism of tannic acid by pea aphid. Then, we identified 54 putative ABC transporter genes from the genome database of A. pisum. These genes were divided into eight subfamilies, ApABCA to ApABCH, of which subfamily G has the largest number of genes with 19, followed by the subfamily C with 14. RT-qPCR results show that the expression levels of ApABCA2, ApABCC7, ApABCG2, and ApABCG3 were highly expressed in the first instar, while those of ApABCA3, ApABCG6, ApABCG7, ApABCH3, and ApABCH4 were highly expressed in adults. Furthermore, transcription levels of many ABC transporter genes were induced by tannic acid. Especially, ApABCG17 and ApABCH2 were obviously induced after being exposed to tannic acid. Meanwhile, knockdown of ApABCG17 by RNA interference resulted in increased sensitivity of pea aphid to tannic acid. These results suggest that ApABCG17 may be involved in tannic acid metabolism in pea aphid. This study will help us to understand the mechanism of tannic acid metabolism in pea aphid, and provides a basis for further research on the physiological function of ABC transporter genes in pea aphid.

Exercise Normalized the Hippocampal Renin-Angiotensin System and Restored Spatial Memory Function, Neurogenesis, and Blood-Brain Barrier Permeability in the 2K1C-Hypertensive Mouse.

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.

Integration of Deep Learning Network and Robot Arm System for Rim Defect Inspection Application.

Automated inspection has proven to be the most effective approach to maintaining quality in industrial-scale manufacturing. This study employed the eye-in-hand architecture in conjunction with deep learning and convolutional neural networks to automate the detection of defects in forged aluminum rims for electric vehicles. RobotStudio software was used to simulate the environment and path trajectory for a camera installed on an ABB robot arm to capture 3D images of the rims. Four types of surface defects were examined: (1) dirt spots, (2) paint stains, (3) scratches, and (4) dents. Generative adversarial network (GAN) and deep convolutional generative adversarial networks (DCGAN) were used to generate additional images to expand the depth of the training dataset. We also developed a graphical user interface and software system to mark patterns associated with defects in the images. The defect detection algorithm based on YOLO algorithms made it possible to obtain results more quickly and with higher mean average precision (mAP) than that of existing methods. Experiment results demonstrated the accuracy and efficiency of the proposed system. Our developed system has been shown to be a helpful rim defective detection system for industrial applications.

A Deep Learning-Based Chinese Semantic Parser for the Almond Virtual Assistant.

Almond is an extendible open-source virtual assistant designed to help people access Internet services and IoT (Internet of Things) devices. Both are referred to as skills here. Service providers can easily enable their devices for Almond by defining proper APIs (Application Programming Interfaces) for ThingTalk in Thingpedia. ThingTalk is a virtual assistant programming language, and Thingpedia is an application encyclopedia. Almond uses a large neural network to translate user commands in natural language into ThingTalk programs. To obtain enough data for the training of the neural network, Genie was developed to synthesize pairs of user commands and corresponding ThingTalk programs based on a natural language template approach. In this work, we extended Genie to support Chinese. For 107 devices and 261 functions registered in Thingpedia, 649 Chinese primitive templates and 292 Chinese construct templates were analyzed and developed. Two models, seq2seq (sequence-to-sequence) and MQAN (multiple question answer network), were trained to translate user commands in Chinese into ThingTalk programs. Both models were evaluated, and the experiment results showed that MQAN outperformed seq2seq. The exact match, BLEU, and F1 token accuracy of MQAN were 0.7, 0.82, and 0.88, respectively. As a result, users could use Chinese in Almond to access Internet services and IoT devices registered in Thingpedia.

Functional Reuniens and Rhomboid Nuclei Are Required for Proper Acquisition and Expression of Cued and Contextual Fear in Trace Fear Conditioning.

BACKGROUND: The reuniens (Re) and rhomboid (Rh) nuclei (ReRh) of the midline thalamus interconnect the hippocampus and the medial prefrontal cortex. The hippocampus and medial prefrontal cortex are both involved in the acquisition of trace fear conditioning, in which a conditioned stimulus (tone) and an aversive unconditioned stimulus (footshock) are paired but separated in time with a trace interval. Earlier, we demonstrated that ReRh inactivation during trace conditioning impaired the acquisition of cued fear. In contrast, ReRh inactivation during both conditioning and test resulted in heightened fear to tones during retrieval. Because there was a generalized contextual fear on top of heightened fear to tones in the latter experiment, here we aimed to examine the specific importance of the functional ReRh in cued fear and contextual fear through introducing prolonged contextual exposure. METHODS: The ReRh were pharmacologically inactivated with muscimol (or saline as controls) before each experimental session. RESULTS: We showed that although ReRh inactivation before trace fear conditioning impaired the acquisition of cued fear, the animals still acquired a certain level of fear to the tones. However, without the functional ReRh throughout the entire behavioral sessions, these animals showed heightened contextual fear that did not decline much with the passage of time, which generalized to the other context, and fear to tones reoccurred when the tones were presented. CONCLUSIONS: Our results suggested that functional ReRh are important for proper acquisition and expression of fear to context and tones acquired under trace procedure.

Quality of life after oesophageal stenting in patients with palliative oesophageal cancer.

AIM: Patients with incurable oesophageal cancer have poor outcomes, with disabling symptoms and a poor quality of life (QOL), which may be improved by oesophageal stenting. We aimed to measure change in symptoms related specifically to oesophageal cancer and overall QOL before and 30 days after stent insertion, to measure adverse effects and to define any patient factors that may be significant in predicting patients who may benefit most. METHODS: We prospectively enrolled patients in an observational study at Middlemore Hospital, New Zealand, and administered validated QOL- and symptomatology-based questionnaires before and 30 days after stent insertion. Additional patient-related demographics, procedural characteristics, adverse events and outcomes were collected. RESULTS: Between 31 March 2014 and 3 July 2020, 57 patients were initially recruited. Four patients withdrew from the study, and 13 patients died before 30 days. Forty patients (29 males; mean±SD age, 72±12 years) completed the study. A significant improvement was noted at one-month post stent insertion in the overall global QOL score (mean 35 to 46, p=0.01). The most significant score improvements were seen in dysphagia, trouble eating, trouble swallowing saliva and dry mouth (p<0.001). Physical, emotional, cognitive and social functioning did not change. Post-procedural adverse events occurred in 17 patients (43%). A poorer initial level of functioning was associated with reduced improvement in global QOL (p≤0.04). Patients followed-up died a mean of 2.8 months after insertion. CONCLUSION: In patients surviving longer than 30 days, there is significant improvement of overall QOL and dysphagia one-month post oesophageal stent insertion for malignant, palliative dysphagia. Multiple psychosocial facets were unchanged with this intervention. Stent-related adverse events were common.

Arginine-tocopherol bioconjugated lipid vesicles for selective pTRAIL delivery and subsequent apoptosis induction in glioblastoma cells.

The incorporation of specific therapeutic gene into glioblastoma offers potent therapeutic strategy to treat the disease. Non-viral gene delivery vectors are of particular interest due to their tuneable transfection efficiency and easy scale-up. Herein, we demonstrate successful delivery of plasmid encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (pTRAIL) using arginine-conjugated tocopherol lipid (AT) nanovesicles into glioblastoma cell lines. Another cationic lipid, glycine-conjugated tocopherol lipid (GT) having glycine in the head group region is also synthesized as a control lipid. Both lipid-derived liposomes effectively condensed the pDNA and the corresponding biomacromolecular assemblies (lipoplexes) are efficiently transfected into different cell lines. AT-based liposomes exhibit higher transfection efficacy in various cell lines, particularly selective in glioma cell lines. At an optimized N/P ratio, both the liposomal formulations show low cytotoxicity. AT-based lipoplexes have superior cellular uptake in U87 than the control lipid GT. The expression of TRAIL protein regulated death receptor and apoptosis signaling pathway is assayed by western blot using transfection of AT-based/pTRAIL into U87 cell lines. Induction of apoptosis in U87 cells exposed to AT-based/pTRAIL plasmid is evaluated by MTT assay as well as Annexin V-propidium iodide dual-staining assay. All results indicate that the developed AT-based/pTRAIL system offers a potentially safe and efficient therapeutic strategy for glioblastoma gene therapy.