Postdeposition Halide Exchange for Achieving Deep-Blue Perovskite Light-Emitting Diodes: The Role of the Organic Cations in the Chloride Source.

Postdeposition halide exchange has been a popular strategy for tuning the emission wavelength of metal halide perovskites and is particularly attractive in achieving deep-blue perovskite light-emitting diodes (PeLEDs), where the quality of the emissive layer is largely limited by the low solubility of chlorides in perovskite precursor solution. In this work, the halide exchange strategy is examined for deep-blue PeLEDs, with a focus on understanding the role of the organic cations of the halide salt (i.e., the chloride source for ion exchange) in modifying the properties of the perovskite films and consequently the PeLED performances. By comparatively investigating the treatment effects of two model systems, namely phenethylammonium chloride and 2,2-diphenylethylammonium chloride (DPEACl), it is found that although the two chlorides produce highly similar photoluminescence properties of the perovskite films, they create different landscapes for current flow in the PeLEDs. In particular, the bulky branch-structured DPEA cations exhibit minimal disturbance to the perovskite grains while providing highly effective inter-grain void filling and thus leakage current blocking, leading to 3D perovskite-based PeLEDs with a record high peak external quantum efficiency of 6.4% at 462 nm. The study highlights the importance of organic cation selection in the halide exchange processes for PeLEDs.

Erratum: Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal-ileal bypass with sleeve gastrectomy.

[This corrects the article DOI: 10.3389/fendo.2022.1013959.].

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal-ileal bypass with sleeve gastrectomy.

Background: Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known. Objective: To explore the effects of SADI-S on metabolites in the stool of rats with T2DM. Methods: Twenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry. Results: At 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups. Among them, 16 metabolites such as branched-chain amino acids (valine), aromatic amino acid (phenylalanine), bile acid (cholic acid, lithocholic acid, and ß-muricholic acid), short-chain fatty acid (isobutyric acid), and phospholipid [lysoPE(17:0), lysoPE(20:3) and lysoPS(16:0)] were associated to the T2DM remission after SADI-S. Conclusion: SADI-S improves T2DM in rats by regulating phenylalanine biosynthesis, valine, phenylalanine, alanine, glutamate, proline, bile acid, and phospholipid metabolism pathways.

Diammonium-Mediated Perovskite Film Formation for High-Luminescence Red Perovskite Light-Emitting Diodes.

3D mixed-halide perovskite-based red emitters combine excellent charge-transport characteristics with simple solution processing and good film formation; however, light-emitting diodes (LEDs) based on these emitters cannot yet outperform their nanocrystal counterparts. Here the use of diammonium halides in regulating the formation of mixed bromide-iodide perovskite films is explored. It is found that the diammonium cations preferentially bond to Pb-Br, rather than Pb-I, octahedra, promoting the formation of quasi-2D phases. It is proposed that the perovskite formation is initially dominated by the crystallization of the thermodynamically more favorable 3D phase, but, as the solution gets depleted from the regular A cations, thin shells of amorphous quasi-2D perovskites form. This leads to crystalline perovskite grains with efficiently passivated surfaces and reduced lattice strain. As a result, the diammonium-treated perovskite LEDs demonstrate a record luminance (10745 cd m-2 ) and half-lifetime among 3D perovskite-based red LEDs.

Ion Migration in Perovskite Light-Emitting Diodes: Mechanism, Characterizations, and Material and Device Engineering.

In recent years, perovskite light-emitting diodes (PeLEDs) have emerged as a promising new lighting technology with high external quantum efficiency, color purity, and wavelength tunability, as well as, low-temperature processability. However, the operational stability of PeLEDs is still insufficient for their commercialization. The generation and migration of ionic species in metal halide perovskites has been widely acknowledged as the primary factor causing the performance degradation of PeLEDs. Herein, this topic is systematically discussed by considering the fundamental and engineering aspects of ion-related issues in PeLEDs, including the material and processing origins of ion generation, the mechanisms driving ion migration, characterization approaches for probing ion distributions, the effects of ion migration on device performance and stability, and strategies for ion management in PeLEDs. Finally, perspectives on remaining challenges and future opportunities are highlighted.

Excess Ion-Induced Efficiency Roll-Off in High-Efficiency Perovskite Light-Emitting Diodes.

Applying extensively excess ammonium halides in forming perovskites is a widely used approach to achieve high-performance perovskite light-emitting diodes (PeLEDs). However, most of these PeLEDs suffer from severe external quantum efficiency (EQE) roll-off at high current densities, thereby restricting the realization of high-brightness PeLEDs and laser diodes. In this work, we explore the underlying mechanism of the EQE roll-off in high-efficiency formamidinium lead iodide (FAPbI3)-based PeLEDs. By combining voltage-dependent electrical stress measurements and ex situ ion distribution analysis of PeLEDs, we found that the electric field-driven migration and local segregation of excess iodide ions, originated from nonstoichiometric precursors, trigger the EQE roll-off via promoting imbalanced charge injection. Based on this discovery, we introduced a simple wash-off treatment with chloroform to remove the excess iodides from the perovskite surface and demonstrated that the treatment is highly effective in suppressing the roll-off behavior. By combining the treatment and the use of an ultrathin poly(methyl methacrylate) (PMMA) interlayer, we achieved a high-brightness PeLED with an EQEmax of 19.6%, a critical current density of 1550 mA cm-2, and a radiancemax of 875 W sr-1 m-2. The study reveals the double-edge sword effect of precursor nonstoichiometry and highlights the importance of managing excess ions in perovskite films.

Long-Term Impact of Thyroid Biopsy Specialists on Efficiency and Quality of Thyroid Biopsy.

OBJECTIVE: To assess consistency and long-term progress in thyroid biopsy performed by trained sonographers under supervision of a radiologist. METHODS: Trained sonographers started performing thyroid biopsy at our institute in August 2011. The data for this study were extracted from a prospectively maintained database for ultrasound guided thyroid biopsy and included the number of thyroid fine needle aspiration biopsy procedures performed between August 2011 and 2016 and the final cytopathology report as per the Bethesda Classification. For the analysis, the study was divided into two time periods: initial postimplementation period (August 2011 to 2013) and late postimplementation period (2014-2016). RESULTS: In all, 5,538 thyroid biopsies were performed by trained sonographers in the period, 2,561 in the initial implementation period and 2,977 between 2014 and 2016. The unsatisfactory rates dropped from 21% to 10% in the two periods (P < .001), and the proportion of malignant nodules on cytopathology increased from 6% to 7% in the two periods (P = .010). Wait times for thyroid biopsies remained low during the period. CONCLUSION: Sonographers trained to perform ultrasound guided thyroid biopsies provide persistent improved patient care over a long-term period. This reinforces the role of physician extenders in targeted scopes of practice.

Stabilizing Perovskite Light-Emitting Diodes by Incorporation of Binary Alkali Cations.

The poor stability of perovskite light-emitting diodes (PeLEDs) is a key bottleneck that hinders commercialization of this technology. Here, the degradation process of formamidinium lead iodide (FAPbI3 )-based PeLEDs is carefully investigated and the device stability is improved through binary-alkalication incorporation. Using time-of-flight secondary-ion mass spectrometry, it is found that the degradation of FAPbI3 -based PeLEDs during operation is directly associated with ion migration, and incorporation of binary alkali cations, i.e., Cs+ and Rb+ , in FAPbI3 can suppress ion migration and significantly enhance the lifetime of PeLEDs. Combining experimental and theoretical approaches, it is further revealed that Cs+ and Rb+ ions stabilize the perovskite films by locating at different lattice positions, with Cs+ ions present relatively uniformly throughout the bulk perovskite, while Rb+ ions are found preferentially on the surface and grain boundaries. Further chemical bonding analysis shows that both Cs+ and Rb+ ions raise the net atomic charge of the surrounding I anions, leading to stronger Coulomb interactions between the cations and the inorganic framework. As a result, the Cs+ -Rb+ -incorporated PeLEDs exhibit an external quantum efficiency of 15.84%, the highest among alkali cation-incorporated FAPbI3 devices. More importantly, the PeLEDs show significantly enhanced operation stability, achieving a half-lifetime over 3600 min.

Thyroid Biopsy Specialists: A Quality Initiative to Reduce Wait Times and Improve Adequacy Rates.

PURPOSE: To develop and implement a program where selected sonographers would be trained to perform thyroid biopsies independently under the supervision of a radiologist, with the goal of improving efficiency and quality. MATERIALS AND METHODS: Institutional research ethics board approval was obtained for this retrospective study, with waiver of informed consent. After approval from the relevant regulatory bodies, four sonographers successfully completed a training program and began to perform all thyroid biopsies (with informed consent) in a room adjacent to the main radiologist-run biopsy room, where the radiologist was available for backup as needed. In the preimplementation period (January 2010 to April 2011), 1321 nodules were biopsied, 29 of which included on-site cytopathology assessment. In the postimplementation period (August 2011 to July 2012), 1347 nodules were biopsied, 103 of which underwent on-site cytopathology assessment. Wait times and adequacy rates were calculated for both periods. RESULTS: Patient wait times decreased from a mean of 80-90 days before implementation of the thyroid biopsy specialist program to 20-30 days afterward. The percentage of adequate samples improved from 74.6% (985 of 1321 nodules) to 78.6% (1059 of 1347 nodules), with a P value of .015 (74.1% [957 of 1292 nodules] to 77.5% [964 of 1244 nodules] when excluding nodules with on-site cytopathology assessment, P = .0497). The percentage of malignant samples showed no significant change in the two time periods, 5.1% (68 of 1321 nodules) before implementation of the program versus 5.4% (73 of 1347 nodules) after implementation, P = .823 (5.1% [66 of 1292 nodules] vs 5.3% [66 of 1244 nodules] in the respective time periods when excluding nodules with on-site cytopathology assessment, P = .888). No major procedural complications occurred. CONCLUSION: Sonographers can be successfully trained to perform ultrasonography-guided thyroid biopsies safely under the supervision of a radiologist, which can improve wait times and adequacy rates.

Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa.

GluR5-containing kainate receptors (KARs) are known to be involved in nociceptive transmission. Our previous work has shown that the activation of presynaptic KARs regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn neurons. However, the role of GluR5-containing KARs in the modulation of inhibitory transmission in the spinal substantia gelatinosa (SG) in slices remains unknown. In the present study, pharmacological, electrophysiological and genetic methods were used to show that presynaptic GluR5 KARs are involved in the modulation of inhibitory transmission in the SG of spinal slices in vitro. The GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in SG neurons. ATPA increased sIPSC frequency in all neurons with different firing patterns as delayed, tonic, initial and single spike patterns. The frequency of either GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could also induce inward currents in all SG neurons recorded. The frequency, but not amplitude, of action potential-independent miniature IPSCs (mIPSCs) was also facilitated by ATPA in a concentration-dependent manner. However, the effect of ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5-/- mice. Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results suggest that GluR5 KARs, which may be located at presynaptic terminals, contribute to the modulation of inhibitory transmission in the SG. GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord.

Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain.

The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in learning and memory. Recent studies show that painful stimuli activate the prefrontal cortex and that brain chemistry is altered in this area in patients with chronic pain. Components of the CNS that are involved in pain transmission and modulation, from the spinal cord to the ACC, are very plastic and undergo rapid and long-term changes after injury. Patients suffering from chronic pain often complain of memory and concentration difficulties, but little is known about the neural circuitry underlying these deficits. To address this question, we analyzed synaptic transmission in the ACC from mice with chronic pain induced by hindpaw injection of complete Freund's adjuvant (CFA). In vitro whole-cell patch-clamp recordings revealed a significant enhancement in neurotransmitter release probability in ACC synapses from mice with chronic pain. Trace fear memory, which requires sustained attention and the activity of the ACC, was impaired in CFA-injected mice. Using knock-out mice, we found that calmodulin-stimulated adenylyl cyclases, AC1 and/or AC8, were crucial in mediating the long-lasting enhanced presynaptic transmitter release in the ACC of mice with chronic pain. Our findings provide strong evidence that presynaptic alterations caused by peripheral inflammation contribute to memory impairments after injury.

Effect of age on progesterone receptor expression, and osteoprogenitor proliferation and differentiation in female rat vertebral cell populations.

In the present investigation, we evaluated whether the capacity for proliferation and differentiation of progesterone (Prog)-dependent osteoprogenitors in the female rat skeleton is related to the level of Prog receptors (PRs) and/or the level of circulating estrogen. We confirmed that in rats, estrogen levels at 18 months of age are higher than those at 3 months, and higher again in rats of 22.5, 25.5, and 26 months of age. Prog levels in rats of ages between 18 and 25.5 months were lower than those at 26 and 3 months of age. PR-A levels were tenfold higher than those of PR-B in cell populations where PR-B was detectable; PR-B receptors were not detectable in all cell populations. In populations derived from 22.5 to 26 months old rats, the basal levels of PR-A were higher than those derived from 3 and 18 months old rats by five- and twofold respectively. Prog treatment enhanced PR-A expression in animals of all ages. Estrogen enhanced the effect of Prog on PR-A expression in cell populations from the 3 and 18 months old rats, but had no effect on PR-A expression in cell populations from 22.5, 25.5, and 26 months old rats. This might be related to the high basal expression of PR in 22.5-26 months old rats (the 'persistent estrous' phase). Our results also confirm our previous observation that in rats, the number of Prog- and dexamethasone (Dex)- dependent osteoprogenitors, and the effect of estrogen on the response to Prog do not decrease with age. In conclusion, we have shown that the basal level of PR-A was increased in old rats, and that this correlated with increased serum estrogen levels, but not with the number of detectable Prog-dependent osteoprogenitors. We also found that Prog upregulates the expression of its own receptors and that estrogen enhances this in young rats but not in rats over 22.5 months of age, in which estrogen levels are elevated.

Evidence for a role of CaMKIV in the development of opioid analgesic tolerance.

cAMP response-element binding protein (CREB), a transcription factor involved in learning, memory and drug addiction, is phosphorylated by calcium-calmodulin-dependent protein kinase IV (CaMKIV). Here, we show that CaMKIV-knockout (KO) mice developed less analgesic tolerance after chronic morphine administration with no alteration in physical dependence or acute morphine-induced analgesia. The increase in phosphorylated CREB expression observed in wild-type mice after chronic morphine was absent in CaMKIV-KO mice, while there was no difference in the expression or phosphorylation of the micro-opioid receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the micro-opioid receptor than did wild-type mice, while uncoupling was similar in control wild-type and KO mice. In addition, morphine reduced inhibitory transmission to a greater degree in CaMKIV-KO mice than in controls after chronic morphine exposure. Our results provide novel evidence for the role of CaMKIV in the development of opioid analgesic tolerance but not physical dependence.

Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory.

Cortical plasticity is thought to be important for the establishment, consolidation, and retrieval of permanent memory. Hippocampal long-term potentiation (LTP), a cellular mechanism of learning and memory, requires the activation of glutamate N-methyl-D-aspartate (NMDA) receptors. In particular, it has been suggested that NR2A-containing NMDA receptors are involved in LTP induction, whereas NR2B-containing receptors are involved in LTD induction in the hippocampus. However, LTP in the prefrontal cortex is less well characterized than in the hippocampus. Here we report that the activation of the NR2B and NR2A subunits of the NMDA receptor is critical for the induction of cingulate LTP, regardless of the induction protocol. Furthermore, pharmacological or genetic blockade of the NR2B subunit in the cingulate cortex impaired the formation of early contextual fear memory. Our results demonstrate that the NR2B subunit of the NMDA receptor in the prefrontal cortex is critically involved in both LTP and contextual memory.

The effect of reloading on bone volume, osteoblast number, and osteoprogenitor characteristics: studies in hind limb unloaded rats.

Skeletal unloading during space flight results in bone loss. In astronauts the extent to which bone is lost varies greatly between different bones of the skeleton as well as between different individuals. Following return to earth, recovery of bone mass during reloading also varies between different bones and different individuals. Due to this variability and the limited number of subjects it is difficult to study the effects of unloading/reloading on bone in humans. A viable alternative is to use the rat model of hind limb unloading developed at NASA. We have previously demonstrated that, in 6-week-old male rats, 14 days of unloading result in a decrease in osteoprogenitor number in cell populations isolated from the proximal femur. The goal of the present study was to determine the number of osteoprogenitor cells present in cell populations derived from the proximal femur of young rats after 14 days of unloading followed by 14 days of reloading and to characterize their proliferative capacity. To do this, we determined the number of alkaline phosphatase-positive colony forming units (CFU-AP) and osteoblast CFU (CFU-O). To establish whether the effects of unloading and reloading were specific for cells of the osteoblast lineage, we also determined the number of fibroblastic CFU (CFU-F). Effects on proliferation were evaluated by measuring the size of CFU-O. Unloading resulted in a 66% reduction in CFU-AP. CFU-O numbers were decreased by 76% and mean colony size was 33% less than controls. The decrease in osteogenic and osteoprogenitor cells in vitro paralleled the decrease in bone volume (- 50%), osteoblast number (- 35%), and bone formation rate (- 46%) observed in the proximal tibial metaphysis of unloaded rats. Unloading had no effect on osteoclast number or surface. Subsequent reloading for 14 days restored CFU-AP. CFU-O numbers were only partially restored at 14 days (83% of controls) but nodule size was 1.2-fold greater than controls. Neither unloading nor reloading had an effect on the total number of progenitors (CFU-F). Reloading restored bone volume back to control values, but osteoblast number and bone formation rate were still lower than those in corresponding controls. Both osteoclast number and surface were lower in reloaded animals than in age-matched controls. Our results indicate that 14 days of unloading result in a decrease in osteoprogenitor number and that reloading for 14 subsequent days completely restores CFU-AP and bone volume to control levels, while the number of CFU-O in vitro and osteoblasts in vivo were partially recovered but still lower than corresponding controls. Strikingly, osteoclastic bone resorption after 14 days of reloading was greatly reduced compared to controls, suggesting a significant contribution of this to the recovery process.