Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.

Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of G-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778.

Molecular basis for the activation of PAF receptor by PAF.

Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.

Structural basis for activation of somatostatin receptor 5 by cyclic neuropeptide agonists.

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-G complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.

Clinical Evaluation of Polymerase Chain Reaction Coupled with Quantum Dot Fluorescence Analysis for Diagnosis of Infection in Vulvovaginal Candidiasis Practice.

Purpose: Time-consuming culture methods and wet-mount microscopy (WMM) with low sensitivity have difficulties in diagnosing Vulvovaginal candidiasis (VVC). Rapid and highly sensitive polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) for the diagnosis of VVC has not been reported to date. This study was the first to evaluate the performance of PCR-QDFA for diagnosis of strains in the leukorrhea samples from patients with suspected VVC.

Genome-Wide Identification and Evolutionary Analysis of YTH Domain-Containing RNA-Binding Protein Family and the Role of GhYTH8 in Response to Drought Stress.

YTH domain-containing proteins are one kind of RNA-binding protein involved in post-transcriptional regulation and play multiple roles in regulating the growth, development, and abiotic stress responses of plants. However, the YTH domain-containing RNA-binding protein family has not been previously studied in cotton. In this study, a total of 10, 11, 22, and 21 genes were identified in , , , and , respectively.

Clinical evaluation of polymerase chain reaction coupled with quantum dot fluorescence analysis in the identification of bacteria and yeasts in patients with suspected bloodstream infections.

Bloodstream infections are serious and complex infectious diseases that often require a rapid diagnosis. Polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) is a novel diagnostic technique. This study aimed to evaluate the diagnostic performance of PCR-QDFA for pathogen detection in patients with suspected bloodstream infections (BSIs).

RNA Editing and Its Roles in Plant Organelles.

RNA editing, a vital supplement to the central dogma, yields genetic information on RNA products that are different from their DNA templates. The conversion of C-to-U in mitochondria and plastids is the main kind of RNA editing in plants. Various factors have been demonstrated to be involved in RNA editing.

Corrigendum: Complete Genome Sequences of Two Novel KPC-2-Producing IncU Multidrug-Resistant Plasmids From International High-Risk Clones of in China.

[This corrects the article DOI: 10.3389/fmicb.2021.

Complete Genome Sequences of Two Novel KPC-2-Producing IncU Multidrug-Resistant Plasmids From International High-Risk Clones of in China.

The rapidly increasing prevalence of carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the gene have not been fully characterized.

Application of core-satellite polydopamine-coated FeO nanoparticles-hollow porous molecularly imprinted polymer combined with HPLC-MS/MS for the quantification of macrolide antibiotics.

Core-satellite-structured magnetic nanosorbents (MNs) used for the selective extraction of macrolide antibiotics (MACs) were prepared in this study. The MNs (core-satellite polydopamine-coated FeO nanoparticles-hollow porous molecularly imprinted polymer) consisted of polydopamine-coated FeO nanoparticles (FeO@PDA) "core" linked to numerous hollow porous molecularly imprinted polymer (HPMIP) "satellites" with bridging amine functional groups. It is worth mentioning that HPMIPs act as "anchors" for selectively capturing target molecules.

Design of green coating material of combining rigid and flexible properties for the extraction of aminoglycosides residues.

Bio-based and low-cost hybrid polyvinyl alcohol (PVA) and gelatin (Gel) hydrophilic macromolecular complex coated microspheres were prepared based on one-pot process, characterized, and applied as novel sorbent materials for the purification of trace aminoglycosides from complex matrices. PVA acts as a "rigid" component in the hybrid complex to enhance its mechanical properties, while Gel's "flexible" role is to improve the swelling properties of the hybrid complex in water. It is shown that hybrid PVA/Gel-functionalized sorbents are more efficient than the respective PVA or Gel sorbents since the presence of Gel increases the material selectivity for aminoglycosides, which is due to the specific interactions occurring between the targets and amino acid residues in the hybrid materials.

Estimating Radium Activity in Shale Gas Produced Brine.

Shale gas reservoir-produced brines may contain elevated levels of naturally occurring radioactive material, including Ra-226 and Ra-228, which come from the decay of U-238 and Th-232 in shale. While the total Ra activity in shale gas wastewaters can vary by over 3 orders of magnitude, the parent radionuclides tend to only vary by 1 order of magnitude. The extent of Ra mobilization from the shale into produced brines is thought to be largely controlled by adsorption/desorption from the shale, which is influenced by shale cation exchange capacity (CEC) and reservoir brine salinity, often reported as the total dissolved solids (TDS).

Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions.

Coordination-Driven Self-Assembly of Carbazole-Based Metallodendrimers with Generation-Dependent Aggregation-Induced Emission Behavior.

A new family of 120° carbazole-based dendritic donors D1-D3 have been successfully designed and synthesized, from which a series of novel supramolecular carbazole-based metallodendrimers with well-defined shapes and sizes were successfully prepared by [2+2] and [3+3] coordination-driven self-assembly. The structures of newly designed rhomboidal and hexagonal metallodendrimers were characterized by multinuclear NMR ((1) H and (31) P) spectroscopy, ESI-TOF mass spectrometry, FTIR spectroscopy, and the PM6 semiempirical molecular orbital method. The fluorescence emission behavior of ligands D1-D3, rhomboidal metallodendrimers R1-R3, and hexagonal metallodendrimers H1-H3 in mixtures of dichloromethane and n-hexane with different n-hexane fractions were investigated.

Design and evaluation of potentiometric principles for bladder volume monitoring: a preliminary study.

Recent advances in microelectronics and wireless transmission technology have led to the development of various implantable sensors for real-time monitoring of bladder conditions. Although various sensing approaches for monitoring bladder conditions were reported, most such sensors have remained at the laboratory stage due to the existence of vital drawbacks. In the present study, we explored a new concept for monitoring the bladder capacity on the basis of potentiometric principles.

Influence of serotonergic mechanisms on the urine flow rate in male rats.

This study extensively examined the role of a 5-HT(1A) receptor in controlling voiding function in anesthetized male rats. A simultaneous recording of the intravesical pressure (IVP), external urethral sphincter (EUS)-electromyography (EMG), and urine flow rate (UFR) during continuous cystometry was used. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT(1A) receptor agonist, significantly improved the voiding efficiency, as detected by increases in the evoked contraction amplitude, EUS burst period, and silent period, and decreases in the volume threshold, pressure threshold, and residual volume.

[Particulate distribution characteristics of Chinese phrase V diesel engine based on butanol-diesel blends].

With a common rail diesel engine without any modification and the engine exhaust particle number and particle size analyzer EEPS, this study used the air-fuel ratio to investigate the particulate number concentration, mass concentration and number distribution characteristics of a diesel engine fueled with butanol-diesel blends (Bu10, Bu15, Bu20, Bu30 and Bu40) and petroleum diesel. The results show: for all test fuels, the particle number distributions turn to be unimodal. With the increasing of butanol, numbers of nucleation mode particles and small accumulation mode particle decrease.

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat.

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry.

Pudendal neuromodulation improves voiding efficiency in diabetic rats.

Aims: Diabetic cystopathy is typically manifested as bladder voiding dysfunction, and numerous patients are refractory to standard therapy. In this study, we determined whether electrical stimulation (ES) of the sensory branch of the pudendal nerve could engage an augmenting reflex and thereby improve bladder emptying in a diabetic animal model with cystopathy.

Methods: The efficiency of bladder emptying with ES of the sensory branch of the pudendal nerve at different stimulation intensities was measured in rats at 8 or 18 weeks after the induction of diabetes with streptozotocin.

Effect of a 5-HT(1A) receptor agonist (8-OH-DPAT) on the external urethral sphincter activity in the rat.

Background/purpose: This study examined the effects of a 5-HT(1A) receptor agonist (8-OH-DPAT) on external urethral sphincter (EUS) activity in urethane-anesthetized rats.

Methods: An EUS electromyogram (EMG) and intravesical pressure (IVP) were simultaneously recorded during continuous cystometrographic monitoring, to provide a quantitative evaluation of EUS activity and urethral urodynamics of voiding.

Results: When examining the EUS burst activity, durations of the active (AP) and silent periods (SP) as a function of the time axis, respectively, exhibited concave- and convex-shaped curves.

Investigation on quantitative structure activity relationships and pharmacophore modeling of a series of mGluR2 antagonists.

MGluR2 is G protein-coupled receptor that is targeted for diseases like anxiety, depression, Parkinson's disease and schizophrenia. Herein, we report the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a series of 1,3-dihydrobenzo[ b][1,4]diazepin-2-one derivatives as mGluR2 antagonists. Two series of models using two different activities of the antagonists against rat mGluR2, which has been shown to be very similar to the human mGluR2, (activity I: inhibition of [(3)H]-LY354740; activity II: mGluR2 (1S,3R)-ACPD inhibition of forskolin stimulated cAMP.

Bilateral pudendal afferent stimulation improves bladder emptying in rats with urinary retention.

Objective: To determine whether bilateral electrical stimulation (BiES) of the transected pudendal sensory nerves could further enhance the voiding efficiency beyond that produced by unilateral electrical stimulation (UniES) of transected pudendal afferents in rats with urinary retention.

Materials And Methods: The efficiency of bladder emptying with either UniES or BiES of pudendal nerve afferents was measured after acute bilateral transection of the sensory branch of the pudendal nerve. The effects of UniES and BiES on voiding in a partially denervated bladder and acute spinal transection, respectively, were determined.

Effect of a 5-HT1A receptor agonist (8-OH-DPAT) on external urethral sphincter activity in a rat model of pudendal nerve injury.

Although serotonergic agents have been used to treat patients with stress urinary incontinence, the characteristics of the external urethral sphincter (EUS) activity activated by 5-HT receptors have not been extensively studied. This study examined the effects of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on the EUS-electromyography and resistance of the urethra in a rat model with bilateral pudendal nerve injury (BPNI). Two measurements were utilized to assess the effects of the drug on bladder and urethral functions: the simultaneous recordings of transvesical pressure under isovolumetric conditions [isovolumetric intravesical pressure (IVP)] and urethral perfusion pressure, and the simultaneous recordings of IVP during continuously isotonic transvesical infusion with an open urethra (isotonic IVP) and EUS-electromyography.