Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still ...remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5Tyr(Me)^2,Dab^5$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5D-Tyr^2,Thr^4OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.
Deuterium has been recognized as an irreplaceable element in industrial and scientific research. However, hydrogen isotope separation still remains a huge challenge due to the identical ...physicochemical properties of the isotopes. In this paper, a partially fluorinated metal-organic framework (MOF) with copper, a so-called FMOFCu, was investigated to determine the separation efficiency and capacity of the framework for deuterium extraction from a hydrogen isotope mixture. The unique structure of this porous material consists of a trimodal pore system with large tubular cavities connected through a smaller cavity with bottleneck apertures with a size of 3.6 Å plus a third hidden cavity connected by an even smaller aperture of 2.5 Å. Depending on the temperature, these two apertures show a gate-opening effect and the cavities get successively accessible for hydrogen with increasing temperature. Thermal desorption spectroscopy (TDS) measurements indicate that the locally flexible MOF can separate D
from anisotope mixture efficiently, with a selectivity of 14 at 25 K and 4 at 77 K.
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•MOF-303, with 1-D ultra-narrow pores, was investigated for D2/H2 separation.•Synergy of binding affinity and KQS significantly increased the D2 uptake.•A high D2/H2 separation ...selectivity of 21.6 was observed at 25 K, 1,000 mbar.•The D2/H2 separation selectivity is ten times higher than the industrial cryogenic method.
The commercial demand for D2 is poised to increase significantly; however, the low natural abundance and the energy- and capital-intensive industrial separation (i.e., 24 K cryogenic distillation) will hamper future scientific and industrial growth in isotopologue separation. Alternatively, kinetic quantum sieving (KQS)-based adsorptive D2 separation has been proposed recently, but the separation performance is reported mostly at near zero pressure or in the sub-few ten mbar range. Herein, an Al-based Metal-Organic Framework, MOF-303, with 1-D narrow-micro pores is studied for D2/H2 adsorptive separation at ambient pressure. Cryogenic thermal desorption spectroscopic analysis of MOF-303 confirmed that the synergetic effect of binding affinity & enhanced KQS (owing to molecular rearrangement of D2 adsorbed phase at high pressure induced by strong D2 confinement), along with D2 partial condensation, leads to a significant increase in the D2 uptake with increasing exposure pressure up to 1,000 mbar. Consequently, a remarkable selectivity of 21.6 at 25 K has been achieved even at an operating pressure of 1000 mbar, which is an industry-friendly condition. The observed D2/H2 separation selectivity is about ten times higher than that of the industrial cryogenic method (best selectivity of below 2.5 at 24 K), and comparable to the performance of the adsorbent materials already reported with low operating pressure, making adsorptive D2/H2 separation through MOF-303 an alternative for cryogenic industrial isotopologue separation.
This study examines the effect of the loss leader strategy on profitable products in a multi-sided platform. We assess different effects of loss leaders according to their substitute versus ...complementary associations with profitable products. We collect a unique dataset containing individual-level transactions and product characteristics and conduct a difference-in-differences analysis along with propensity score matching at the sub-market level. The results suggest that the introduction of a substitute loss leader is negatively associated with the sales of profitable products, while complementary loss leaders have no significant effect on them. We also find that the impact of loss leaders can vary according to the price of related core projects. Our study contributes to the literature on multi-sided platforms by augmenting the current knowledge on product-level association.
Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging ...probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results.
We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol.
Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5
at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration.
A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM.
Oviductosomes (OVS) are nano-sized extracellular vesicles secreted in the oviductal luminal fluid by oviductal epithelial cells and known to be involved in sperm capacitation and fertility. Although ...they have been shown to transfer encapsulated proteins to sperm, cargo constituents other than proteins have not been identified. Using next-generation sequencing, we demonstrate that OVS are carriers of microRNAs (miRNAs), with 272 detected throughout the estrous cycle. Of the 50 most abundant, 6 (12%) and 2 (4%) were expressed at significantly higher levels (P < 0.05) at metestrus/diestrus and proestrus/estrus. RT-qPCR showed that selected miRNAs are present in oviductal epithelial cells in significantly (P < 0.05) lower abundance than in OVS, indicating selective miRNA packaging. The majority (64%) of the top 25 OVS miRNAs are present in sperm. These miRNAs' potential target list is enriched with transcription factors, transcription regulators, and protein kinases and there are several embryonic developmentally-related genes. Importantly, OVS can deliver to sperm miRNAs, including miR-34c-5p which is essential for the first cleavage and is solely sperm-derived in the zygote. Z-stack of confocal images of sperm co-incubated with OVS loaded with labeled miRNAs showed the intracellular location of the delivered miRNAs. Interestingly, individual miRNAs were predominantly localized in specific head compartments, with miR-34c-5p being highly concentrated at the centrosome where it is known to function. These results, for the first time, demonstrate OVS' ability to contribute to the sperm's miRNA repertoire (an important role for solely sperm-derived zygotic miRNAs) and the physiological relevance of an OVS-borne miRNA that is delivered to sperm.
Background
Currently, there are no high‐resolution impedance manometry (HRIM)‐based diagnostic criteria for non‐obstructive dysphagia (NOD). New impedance parameters, such as the esophageal impedance ...integral (EII) and volume of inverted impedance (VII) ratios, have shown strong correlations with bolus transit. This study compared the EII and VII ratios as diagnostic tools for NOD.
Methods
We analyzed 36 participants (12 patients with achalasia, 12 patients with NOD 7 with normal motility and 5 with ineffective esophageal motility, and 12 asymptomatic controls) who underwent HRIM with a maximum of 5 swallows per participant. The EII and VII ratios were calculated as Z2 (post‐swallow)/Z1 (pre‐swallow). Bolus transit was retrospectively evaluated using transluminal impedance analysis.
Key Results
Both EII and VII ratios could effectively distinguish the achalasia group from the non‐achalasia groups (area under the receiver operating characteristic curve AUROC: 0.83 for VII vs. 0.80 for EII; p = 0.73). However, the VII ratio was significantly better in discriminating asymptomatic controls from patients with dysphagia (NOD + achalasia) (AUROC: 0.81 vs. 0.68; p = 0.01). Moreover, the VII ratio was better in discriminating asymptomatic controls from patients with NOD (AUROC: 0.68 vs. 0.51; p = 0.06). In repeated swallows, the VII ratio was consistently the lowest in controls and the highest in patients with achalasia, whereas the EII ratio did not show a consistent pattern.
Conclusions & Inferences
The VII ratio was more reliable than the EII ratio for describing bolus transit and distinguishing patients with NOD from asymptomatic controls, even during repeated measures of subsequent swallows.
Compared with the EII ratio, the VII ratio is superior for evaluating remnant bolus in dysphagia patients by having a higher sensitivity to saline than air and high consistency across repeated swallows. Unlike the EII ratio, the VII ratio shows a consistent decreasing trend from asymptomatic to NOD and achalasia.
Metal organic polyhedra (MOPs) have potential as supramolecular building blocks, but utilizing MOPs for postsynthetic polymerization has not been explored. Although MOPs with flexible organic ...moieties have been recently reported to target enhanced processability, permanent porosity has not been demonstrated. Here, a novel synthetic strategy involving the cross-linking of MOPs
via
a covalent bond is demonstrated by exploiting a condensation reaction between the MOP and flexible organic linkers. An amine-functionalized Zr-based MOP is cross-linked with acyl chloride linkers in the crystalline state to form cross-linked MOPs. The condensation reaction results in a cross-linked system without significant changes to the structure of the Zr-based MOP. Such cross-linked MOPs provide a microporous tetrahedral cage based on gas sorption analysis. This cross-linking strategy highlights the potential of MOPs as building blocks and provides access to a new class of porous material.
Zr-based MOP cages are cross-linked with flexible organic molecules through a condensation reaction, resulting in a highly crystalline framework.
Zr-based MOP cages are cross-linked with flexible organic molecules through a condensation reaction, resulting in a highly crystalline framework.
Metal organic polyhedra (MOPs) have potential as ...supramolecular building blocks, but utilizing MOPs for postsynthetic polymerization has not been explored. Although MOPs with flexible organic moieties have been recently reported to target enhanced processability, permanent porosity has not been demonstrated. Here, a novel synthetic strategy involving the cross-linking of MOPs
via
a covalent bond is demonstrated by exploiting a condensation reaction between the MOP and flexible organic linkers. An amine-functionalized Zr-based MOP is cross-linked with acyl chloride linkers in the crystalline state to form cross-linked MOPs. The condensation reaction results in a cross-linked system without significant changes to the structure of the Zr-based MOP. Such cross-linked MOPs provide a microporous tetrahedral cage based on gas sorption analysis. This cross-linking strategy highlights the potential of MOPs as building blocks and provides access to a new class of porous material.
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