Structural basis for lysophosphatidylserine recognition by GPR34.

GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-Gi complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.

Involvement of Embryo-Derived and Monocyte-Derived Intestinal Macrophages in the Pathogenesis of Inflammatory Bowel Disease and Their Prospects as Therapeutic Targets.

Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew. Stimulated by the intestinal inflammatory microenvironment, monocyte-derived IMs can interact with intestinal epithelial cells, intestinal fibroblasts, and intestinal flora, resulting in the increased differentiation of proinflammatory phenotypes and the decreased differentiation of anti-inflammatory phenotypes, releasing a large number of proinflammatory factors and aggravating intestinal inflammation. Based on this mechanism, inhibiting the secretion of IMs' proinflammatory factors and enhancing the differentiation of anti-inflammatory phenotypes can help alleviate intestinal inflammation and promote tissue repair. At present, the clinical medication of IBD mainly includes 5-aminosalicylic acids (5-ASAs), glucocorticoid, immunosuppressants, and TNF-α inhibitors. The general principle of treatment is to control acute attacks, alleviate the condition, reduce recurrence, and prevent complications. Most classical IBD therapies affecting IMs function in a variety of ways, such as inhibiting the inflammatory signaling pathways and inducing IM2-type macrophage differentiation. This review explores the current understanding of the involvement of IMs in the pathogenesis of IBD and their prospects as therapeutic targets.

Electrothermal Phase Change Composite with Flexibility over a Wide Temperature Range for Wearable Thermotherapy.

Flexible electrothermal composite phase change materials (PCMs) are promising candidates for portable thermotherapy. However, a great challenge remains to achieve high PCM loading while maintaining reasonable flexibility. Herein, the polypyrrole-decorated melamine foam (PPy@MF) was fabricated and thereafter applied to confine binary PCM mixtures composed of a high-enthalpy long-chain polyethylene glycol (PEG4000) and its short-chain homologue (PEG200) to make the novel PPy@MF-PEG4000+200 composite PCM. At a high loading of up to 74.1% PEG4000 and a high latent heat energy storage density of 150.1 J/g, the composite PCM remained flexible at temperature (-20 °C) far below its phase transition point thanks to the plasticine effect of PEG200. The composite also demonstrated good Joule heating performance, providing fast heating from 28 to 70 °C at low applied voltages (4.5-6.0 V). The energy could be stored efficiently and released to maintain the composites at the proper temperature. The electrothermal performance of the composite remained undisturbed during curved or repeated bending, showing good potential to be used for personal thermal management and thermotherapy.

Impact of nanoplastics on the biodegradation, ecotoxicity, and key genes involved in imidacloprid metabolic pathways in papyrus (Cyperus papyrus L.).

Both nanoplastics (NPs) and imidacloprid (IMI) are widely distributed in the environment and have attracted significant attention due to their adverse effects on ecosystems. Constructed wetlands have the potential to remove IMI, but there is still limited understanding of how wetland plants interact with IMI, especially when influenced by different charged NPs. This study assessed their ecotoxicological effects, as well as the fate and transformation of IMI in papyrus (Cyperus papyrus L.) under the influence of different charged NPs and identified key driving genes in the plant. Results show that simultaneous exposure to positively charged PS-NH2 and IMI inhibited plant growth. The combined action of NPs and IMI intensified their toxicity, enhancing lipid peroxidation and altering antioxidant enzyme activities. The IMI removal efficiency, which was primarily driven by biodegradation, was 80.61%, 88.91%, and 74.71% in the IMI-alone, co-IMI/PS_COOH, and co-IMI/PS_NH2 systems, respectively. PS-NH2 restricted the roots-to-shoots translocation ability of IMI. PS-COOH enhanced IMI oxidation and nitro reduction, while PS-NH2 inhibited 2-OH-IMI dehydrogenation to IMI-olefin in papyrus. Transcriptomics and gene network analysis identified the genes encoding CYP450 enzymes, reductases, hydrolases, dehydrogenases, and peroxidases as those influencing IMI biodegradation. These enzymes play a crucial role in the hydroxylation, dehydrogenation, reduction, and oxidation processes during biodegradation of IMI in the presence of NPs. This study expands the understanding of the impact of differently charged NPs on the IMI remediation efficacy of papyrus, thus providing new insights into the phytoremediation of organic contaminants in constructed wetlands.

Oxytocin increases itch sensitivity of mice in late pregnancy and its peripheral receptor mechanism of itch-promoting effect.

Oxytocin (OXT) is secreted in a large amount during the middle and late pregnancy. Except for the regulation of functions related to childbirth, OXT is involved in the regulation of cognition, social behavior, addiction, pain and so on. Our aim is to confirm the increase of OXT content in mice in late pregnancy is the main cause of itch during pregnancy and observe whether exogenously administered OXT can induce or increase itch sensitivity. The research shows that itch sensitivity of mice increased significantly in late pregnancy and basically returned to normal one day after delivery. The number of OXT-positive neurons in paraventricular nucleus (PVN) and the content of OXT in serum of the late pregnant mice increased significantly, and decreased sharply after delivery. Intradermal injection of low concentration of OXT (0.2 nmol/L) could not induce scratching behavior in mice, but high concentration of OXT (5 nmol/L, 10 nmol/L) could do this in a dose-dependent manner. Low concentration of OXT significantly increased the itch sensitivity to histamine. Intradermal injection of oxytocin receptor (OXTR) or arginine vasopressin-1a receptor (AVPR1A) antagonist did not affect histamine-induced scratching behavior, but both reversed the increase of itch sensitivity in late pregnant mice or the facilitated itch sensitivity by OXT. Study suggests that both endogenous and exogenous increases in OXT can increase the body's sensitivity to itch, and even induce itch directly. Pruritus during pregnancy is closely related to the increase of OXT content in vivo. In the periphery, the itch-promoting effect of OXT is mediated by OXTR and AVPR1A.

In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.

Glycyrrhiza uralensis Fisch. ex DC, one of the 3 pharmacopeial species of licorice and widely used in dietary supplements, can inhibit certain cytochrome P450 (CYP) enzymes. Thereby, G. uralensis preparations have the potential to cause pharmacokinetic drug interactions when consumed along with prescription medicines. One compound (1.34 mg dry weight) responsible for inhibiting CYP2B6, CYP2C8, and CYP2C9 was isolated using bioactivity-guided fractionation from 250 g dried roots, stolons, and rhizomes. The enzyme kinetics and mechanisms of inhibition were determined using human liver microsomes, recombinant enzymes, and UHPLC-MS/MS-based assays. Identified as licoisoflavone B, this compound displayed reversible inhibition of CYP2C8 with an IC50 value of 7.4 ± 1.1 µM and reversible inhibition of CYP2C9 with an IC50 value of 4.9 ± 0.4 µM. The enzyme kinetics indicated that the mechanism of inhibition was competitive for recombinant CYP2C8, with a Ki value of 7.0 ± 0.7 µM, and mixed-type inhibition for recombinant CYP2C9, with a Ki value of 1.2 ± 0.2 µM. Licoisoflavone B moderately inhibited CYP2B6 through a combination of irreversible and reversible mechanisms with an IC50 value of 16.0 ± 3.9 µM.

Isosteric Replacement of Ester Linkage of Lysophospholipids with Heteroaromatic Rings Retains Potency and Subtype Selectivity.

Our group has reported various derivatives of lysophosphatidylserine (LysoPS) as potent and subtype-selective agonists for G-protein-coupled receptors (GPCRs). However, the ester linkage between the glycerol moiety and fatty acid or fatty acid surrogate is present in all of them. In order to develop these LysoPS analogs as drug candidates, appropriate pharmacokinetic consideration is essential. Here, we found that the ester bond of LysoPS is highly susceptible to metabolic degradation in mouse blood. Accordingly, we examined isosteric replacement of the ester linkage with heteroaromatic rings. The resulting compounds showed excellent retention of potency and receptor subtype selectivity, as well as increased metabolic stability in vitro.

CdS Nanoparticles Supported by Cobalt@Carbon-Derived MOFs for the Improved Adsorption and Photodegradation of Ciprofloxacin.

The design and synthesis of efficient photocatalysts that promote the degradation of organic pollutants in water have attracted extensive attention in recent years. In this work, CdS nanoparticles are grown in situ on Co@C derived from metal-organic frameworks. The resulting hierarchical CdS/Co@C nanostructures are evaluated in terms of their adsorption and photocatalytic ciprofloxacin degradation efficiency under visible-light irradiation. The results show that, apart from offering a large surface area (55.69 m2·g-1), the prepared material can effectively suppress the self-agglomeration of CdS and enhance the absorption of visible light. The CdS/Co@C-7 composite containing 7% wt Co@C has the highest photodegradation rate, and its activity is approximately 4.4 times greater than that of CdS alone. Moreover, this composite exhibits remarkable stability after three successive cycles of photocatalysis. The enhanced photocatalytic performance is largely ascribed to the rapid separation of electron-hole pairs and the effective electron transfer between CdS and Co@C, which is confirmed via electrochemical experiments and photoluminescence spectra. The active substance capture experiment and the electron spin resonance technique show that h+ is the main active entity implicated in the degradation of CIP, and accordingly, a possible mechanism of CIP photocatalytic degradation over CdS/Co@C is proposed. In general, this work presents a new perspective on designing novel photocatalysts that promote the degradation of organic pollutants in water.

The addition of iron-carbon enhances the removal of perfluoroalkyl acids (PFAAs) in constructed wetlands.

Hazardous perfluoroalkyl acids (PFAAs), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have become ubiquitous environmental persistent organic contaminants, posing serious threats to environmental health, which has led to the development of PFAA treatment methods. Wetland construction in combination with iron-carbon (CW-I), a low-maintenance and high-efficiency technology, may be capable of removing PFAAs through physico-biochemical processes. In this study, we aim to investigate the removal efficiency of PFAAs by CW-I as well as the critical functions of all components within the wetlands. Pairwise comparisons of iron-carbon and control groups revealed that iron-carbon significantly enhanced 15.9% for PFOA and 17.9% for PFOS absorption through phytouptake and substrate adsorption, with respective removal efficiencies of 71.8% ± 1.03% and 85.8% ± 1.56%. The generated iron ions stimulated plant growth and further enhanced phytouptake of PFAAs, with PFAAs accumulated primarily in root tissues with limited translocation. Observations of batch adsorption suggest that chemical and electrostatic interactions are involved in the iron-carbon adsorption process, with film and intraparticle diffusions being the rate-limiting events. Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy revealed that PFAA adsorption by substrates occurs at the molecular level, as well as the occurrence of hydrophobic force effects and ligand exchanges during the iron-carbon adsorption process. Additionally, iron-carbon significantly altered the genera, phyla, and community structure of microorganisms, and some microorganisms and their extracellular polymers may possess ability to bind PFAAs. The information provided in this study contributes to our understanding of the PFAA removal processes in CW-I and enriched the classical cases of PFAA removal by CWs.

Exploration of LPS2 agonist binding modes using the combination of a new hydrophobic scaffold and homology modeling.

Lysophosphatidylserine (LysoPS) is an endogenous pan-agonist of three G-protein coupled receptors (GPCRs): LPS1/GPR34, LPS2/P2Y10, and LPS3/GPR174, and we previously reported a series of LysoPS-based agonists of these receptors. Interestingly, we found that LPS1 agonist activity was very sensitive to structural change at the hydrophobic fatty acid moiety, whereas LPS2 agonist activity was not. Here, to probe the molecular basis of LPS2 agonist binding, we developed a new class of hydrophobic fatty acid surrogates having a biphenyl-ether scaffold. The LPS2 agonist activity of these compounds proved sensitive to molecular modification of the hydrophobic skeleton. Thus, we next constructed an LPS2 model by homology modeling and docking/molecular dynamics (MD) simulation, and validated it by means of SAR studies together with point mutations of selected receptor amino-acid residues. The putative ligand-binding site of LPS2 is Γ-shaped, with a hydrophilic site horizontally embedded in the receptor transmembrane helix bundles and a perpendicular hydrophobic groove adjoining transmembrane domains 4 and 5 that is open to the membrane bilayer. The binding poses of LPS2 agonists to this site are consistent with easy incorporation of various kinds of fatty acid surrogates. Structural development based on this model afforded a series of potent and selective LPS2 full agonists, which showed enhanced in vitro actin stress fiber formation effect.

Leucine 434 is essential for docosahexaenoic acid-induced augmentation of L-glutamate transporter current.

Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.

Perioperative transcutaneous electrical acupoint stimulation (pTEAS) in pain management in major spinal surgery patients.

BACKGROUND: Lumbar disc herniation is seen in 5-15% of patients with lumbar back pain and is the most common spine disorder demanding surgical correction. Spinal surgery is one of the most effective management for these patients. However, current surgical techniques still present complications such as chronic pain in 10-40% of all patients who underwent lumbar surgery, which has a significant impact on patients' quality of life. Research studies have shown that transcutaneous electrical acupoint stimulation (TEAS) may reduce the cumulative dosage of intraoperative anesthetics as well as postoperative pain medications in these patients. OBJECTIVE: To investigate the effect of pTEAS on pain management and clinical outcome in major spinal surgery patients. METHODS: We conducted a prospective, randomized, double-blind study to verify the effect of pTEAS in improving pain management and clinical outcome after major spinal surgery. Patients (n = 90) who underwent posterior lumbar fusion surgery were randomized into two groups: pTEAS, (n = 45) and Control (n = 45). The pTEAS group received stimulation on acupoints Zusanli (ST.36), Sanyinjiao (SP.6), Taichong (LR.3), and Neiguan (PC.6). The Control group received the same electrode placement but with no electrical output. Postoperative pain scores, intraoperative outcome, perioperative hemodynamics, postoperative nausea and vomiting (PONV), and dizziness were recorded. RESULTS: Intraoperative outcomes of pTEAS group compared with Control: consumption of remifentanil was significantly lower (P < 0.05); heart rate was significantly lower at the end of the operation and after tracheal extubation (P < 0.05); and there was lesser blood loss (P < 0.05). Postoperative outcomes: lower pain visual analogue scale (VAS) score during the first two days after surgery (P < 0.05); and a significantly lower rate of PONV (on postoperative Day-5) and dizziness (on postoperative Day-1 and Day-5) (P < 0.05). CONCLUSION: pTEAS could manage pain effectively and improve clinical outcomes. It could be used as a complementary technique for short-term pain management, especially in patients undergoing major surgeries. TRIAL REGISTRATION: ChiCTR1800014634, retrospectively registered on 25/01/2018. http://medresman.org/uc/projectsh/projectedit.aspx?proj=183.

DNA G-Quadruplex in Human Telomeres and Oncogene Promoters: Structures, Functions, and Small Molecule Targeting.

DNA G-quadruplex secondary structures formed in guanine-rich human telomeres and oncogene promoters are functionally important and have emerged as a promising new class of cancer-specific drug targets. These globular intramolecular structures are stabilized by K+ or Na+ and form readily under physiological solution conditions. Moreover, G-quadruplexes are epigenetic features and can alter chromatin structure and function together with interactive proteins. Here, we discuss our efforts over the last two decades to understand the structures and functions of DNA G-quadruplexes formed in key oncogene promoters and human telomeres and their interactions with small molecules. Using high-field NMR spectroscopy, we determined the high-resolution structures of physiologically relevant telomeric G-quadruplexes in K+ solution with a major form (hybrid-2) and a minor form (hybrid-1), as well as a two-tetrad intermediate. The intrinsic structural polymorphism of telomeric DNA may be important for the biology of human telomeres, and we proposed a model for the interconversion. More recently, we have worked on G-quadruplexes of MYC, BCL2, PDGFR-ß, VEGF, and k-RAS oncogene promoters. We determined the structure of the major G-quadruplex formed in the MYC promoter, a prototype for parallel G-quadruplexes. It is the first example of the parallel-stranded G3NG3 structure motif with a 1-nt loop, which is prevalent in promoter sequences and likely evolutionarily selected to initiate folding. Remarkably, the parallel MYC promoter G-quadruplexes are highly stable. Additionally, we determined the molecular structures of G-quadruplexes formed in human BCL2, VEGF, and PDGFR-ß promoters, each adopting a unique structure. For example, the BCL2 promoter contains distinct interchangeable G-quadruplexes in two adjacent regions, suggesting precise regulation by different proteins. The PDGFR-ß promoter adopts unique "broken-strand" and vacancy G-quadruplexes, which can be recognized by cellular guanine metabolites for a potential regulatory role.Structural information on G-quadruplexes in complex with small-molecules is critical for understanding specific recognition and structure-based rational drug design. Our studies show that many G-quadruplexes contain unique structural features such as capping and loop structures, allowing specific recognition by drugs and protein. This represents a paradigm shift in understanding DNA as a drug target: Rather than a uniform, nonselective binding site in duplex DNA, the G-quadruplex is being pursued as a new class of selectively targetable drug receptors. We focus on targeting the biologically relevant MYC promoter G-quadruplex (MycG4) with small molecules and have determined its first and additional drug complex structures. Very recently, we have discovered clinically tested indenoisoquinolines as strong MycG4 binders and potent MYC inhibitors. We have also discovered drugs targeting the unique dGMP-bound-vG4 formed in the PDGFR-ß promoter. Moreover, we determined the complex structures of the first small molecules that specifically recognize the physiologically relevant human telomeric G-quadruplexes. Unlike the previously recognized dogma that the optimal G-quadruplex ligands are large aromatic or cyclic compounds, our results suggest that smaller asymmetric compounds with appropriate functional groups are better choices to specifically bind G-quadruplexes. This body of work lays a strong foundation for future work aimed at understanding the cellular functions of G-quadruplexes and G-quadruplex-targeted drug design.

Removing nutrients from wastewater by constructed wetlands under perfluoroalkyl acids stress.

Constructed wetlands (CWs) are often used to treat wastewater discharged from wastewater treatment plants (WWTPs), while emerging contaminants (such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS)) have been commonly discovered in WWTPs. However, no research has examined whether PFOA/OS (i.e. PFOA and PFOS) affects the performance of CW. Therefore, this study compared the nutrient removal efficiencies of four CWs with varied configurations under PFOA/OS and no PFOA/OS stress conditions. We found that CW containing plants or/and iron-carbon had higher removal efficiency for nutrients (except NH4+-N) than conventional CW in stable operation under wastewater without PFOA/OS. Plants or/and iron increased the nutrient removal efficiency by plant uptake, chemical reaction, and co-precipitation of iron hydroxides. In contrast, the iron-carbon inhibited the nitrification of nitrifying bacteria by consuming dissolved oxygen, converting NO3--N to NH4+-N. Although the removal efficiencies of nutrients by CWs differed after introducing PFOA/OS, the removal order was consistent with those before adding PFOA/OS. Plants or/and iron-carbon effectively increased CWs' resistance to PFOA/OS loading and toxicity, and the function of iron-carbon was superior to the plants. In addition, PFOA/OS reduced the abundances of microbes Hydrogenophaga, Pseudomonas, Sphingomonas, Nitrospira, and Candidatus_Accumulibacter that contributed to nutrient removal.

Integrated Janus cellulosic composite with multiple thermal functions for personalized thermal management.

The effective integration of multiple thermal functions into one material is highly attractive in personal thermal management, taking the complex application environment into consideration. Herein, a multifunctional Janus cellulosic composite encompassing superior electrical heating, energy storage, thermal insulation, and infrared camouflage performance was firstly developed by integrating Janus cellulose nanofibers (CNF) aerogel, polypyrrole (PPy), and polyethylene glycol (PEG). In practice, the active heating-thermal regulation layer (PPy@CNFphilic-PEG) of multifunctional Janus cellulosic composite is faced inward to provide heating on-demand through the joint action of the electrically conductive PPy and thermally regulative PEG. The outward-facing hydrophobic aerogel layer (CNFphobic) serves as the thermal insulator, which simultaneously enables infrared camouflage by reducing heat loss to the environment via infrared radiation. This work presents an effective and facile strategy toward multifunctional Janus materials for efficient personal thermal management, showing great promise for potential applications, such as thermal comfort, infrared camouflage, and security protection.

Building on endogenous lipid mediators to design synthetic receptor ligands.

Large numbers of diverse biologically active molecules are produced from phospholipids, the constituents of biological membranes. Indeed, many lipid-derived ligands, which can undergo inter-transformation between one and another by certain kinases or enzymes, bind to protein receptors such as G-protein-coupled receptors, and serve to regulate multiple biological processes through a variety of signaling pathways. Thus, lipid mediators are likely involved in a synergistic regulatory network, and dysfunction of this network may result in diseases. Here, we reviewed recent progress in the drug development targeting related receptors, focusing on the identification of common structural features which can both come from endogenous ligands or artificial ligands. We also discussed how these features have been utilized in drug design and relevant issues such as potency, selectivity, metabolic stability, and toxicity.

Real-Time Ultrasound-Guided Versus Ultrasound-Assisted Spinal Anesthesia in Elderly Patients With Hip Fractures: A Randomized Controlled Trial.

BACKGROUND: Traditional landmark-guided spinal anesthesia can be challenging in elderly patients with hip fractures. Ultrasound assistance (USAS) and real-time ultrasound guidance (USRTG) techniques can facilitate lumbar neuraxial blocks. However, it remains undetermined which method is optimal for use in elderly patients. This study aimed to evaluate which technique was associated with a higher success rate of spinal anesthesia in elderly patients with hip fractures: USAS or USRTG technique. METHODS: A total of 114 elderly patients (≥70 years of age) with hip fractures were randomly assigned to receive spinal anesthesia using either the USAS or USRTG technique. The primary outcome was the first-attempt success rate, analyzed using the χ2 test. Secondary outcomes included first-pass success rate, the number of needle attempts and passes, locating time, procedure time, total time, adverse reactions and complications, patient satisfaction, and procedural difficulty score. RESULTS: The first-attempt success rate (80.7% vs 52.6%; 95% confidence interval [CI], for the difference, 11.6-44.6) and first-pass success rate (63.2% vs 31.6%; 95% CI for the difference, 14.2-49) were both significantly higher in the USAS compared with the USRTG group (both P = .001). The number of attempts (1 [1-1] vs 1 [1-3]; P = .001) and median passes (1 vs 3; P < .001) were both significantly lower in the USAS group than in the USRTG group. The USRTG group had a shorter locating time (175 seconds [129-234 seconds] vs 315 seconds [250-390 seconds]; P < .001) but a longer procedure time (488 seconds [260-972 seconds] vs 200 seconds [127-328 seconds]; P < .001) and total time (694 seconds [421-1133 seconds] vs 540 seconds [432-641 seconds]; P = .036). There were no significant differences between the 2 groups with regard to the adverse reactions and complications. More patients in the USAS group had a high satisfaction score of 3 to 5 (P = .008). Overall, anesthesiologists rated the USRTG group procedure as "more difficult" (P = .008). CONCLUSIONS: In elderly patients with hip fractures, spinal anesthesia with the USRTG technique is not superior to the USAS technique since it has a lower success rate, longer procedure time, lower satisfaction score, and is more difficult to perform. So USAS technique may be more suitable for elderly patients.

Identification of source information for sudden hazardous chemical leakage accidents in surface water on the basis of particle swarm optimisation, differential evolution and Metropolis-Hastings sampling.

A quick and accurate identification of source information on sudden hazardous chemical leakage accident is crucial for early accident warning and emergency response. This study firstly regards source identification problem of sudden hazardous chemical leakage accidents as an inverse problem and presents a source identification model based on the Bayesian framework. Secondly, a new identification method is designed on the basis of particle swarm optimisation (PSO), differential evolution (DE) and the Metropolis-Hastings (M-H) sampling method. Lastly, the designed method, i.e. PSO-DE-MH, is verified by an outdoor experiment analyses in a section of the South-North Water Transfer Project. Results show that the number of iterations, the average absolute error, the average relative error and the average standard deviations of the identification results obtained by PSO-DE-MH are less than those of PSO-DE and DE-MH. Moreover, the relative error and the sampling relative error of the identification results under five different measurement errors (MEs) (σ = 0.01, 0.05, 0.1, 0.15, 0.2) are less than 9.5% and 0.2%, respectively. The designed method is effective even when the standard deviation of the ME increases to 0.2. Therefore, the designed method can effectively and accurately obtain the source information of sudden hazardous chemical leakage accidents. This study provides a new idea and method to solve the difficult problems of emergency management.

Switching Lysophosphatidylserine G Protein-Coupled Receptor Agonists to Antagonists by Acylation of the Hydrophilic Serine Amine.

Three human G protein-coupled receptors (GPCRs)-GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3-are activated specifically by lysophosphatidylserine (LysoPS), an endogenous hydrolysis product of a cell membrane component, phosphatidylserine (PS). LysoPS consists of l-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages. We previously generated potent and selective GPCR agonists by modification of the three modules and the ester linkage. Here, we show that a novel modification of the hydrophilic serine moiety, that is, N-acylations of the serine amine, converted a GPR174 agonist to potent GPR174 antagonists. Structural exploration of the amide functionality provided access to a range of activities from agonist to partial agonist to antagonist. The present study would provide a new strategy for the development of lysophospholipid receptor antagonists.