Preemptive QP001, a fast-acting meloxicam formulation, provides analgesia and reduces opioid consumption following abdominal surgery: a randomized controlled trial.

BACKGROUND: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery. METHOD: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration. RESULTS: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05). CONCLUSION: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile.

Effects of an Informational Video About Anesthesia on Pre- and Post-Elective Cesarean Section Anxiety and Recovery: A Randomized Controlled Trial.

BACKGROUND Showing an informational anesthesia video can reduce the preoperative anxiety of parturients undergoing elective cesarean section (CS). However, the best method for presenting such videos remains unclear, and whether such videos can reduce the anxiety level of women during the entire perioperative period for CS (including preoperative and postoperative) has not been studied yet. MATERIAL AND METHODS This study was a single-center prospective randomized trial. We randomly divided 121 pregnant women who were scheduled to undergo elective cesarean section (CS) into 2 groups: one group was shown an informational video (video group) and another group was not (control group). Spielberger's state-trait anxiety inventory was used to evaluate the perioperative anxiety level of parturient women at 3 time points: 1 day before CS, after video education, and 2 days after CS. Salivary cortisol level was evaluated to assess the patients' anxiety level at these 3 time points. Finally, the maternal satisfaction scale for CS and an obstetric quality-of-recovery score (OBsQoR-11) were used to evaluate the satisfaction and recovery of the parturient women 2 days after CS. RESULTS Watching a video about anesthesia significantly reduced the anxiety level of the parturient women during the perioperative period (1 day before CS: p=1.00, p=0.96; after video education: p<0.01, p=0.004; 2 days after CS: p=0.01, p=0.01). The postoperative satisfaction scores were significantly improved in the video group (p=0.007). OBsQoR-11 scores in the video group and control group were not significantly different (p=0.48). Maternal anxiety level was moderately positively correlated with cortisol hormone level. CONCLUSIONS Showing an informational video about anesthesia (video+education) can significantly reduce perioperative anxiety and improve satisfaction after CS. Although it did not improve the postoperative recovery, it was still significant for anesthesia.

Genetic Parts and Enabling Tools for Biocircuit Design.

Synthetic biology aims to engineer biological systems for customized tasks through the bottom-up assembly of fundamental building blocks, which requires high-quality libraries of reliable, modular, and standardized genetic parts. To establish sets of parts that work well together, synthetic biologists created standardized part libraries in which every component is analyzed in the same metrics and context. Here we present a state-of-the-art review of the currently available part libraries for designing biocircuits and their gene expression regulation paradigms at transcriptional, translational, and post-translational levels in Escherichia coli. We discuss the necessary facets to integrate these parts into complex devices and systems along with the current efforts to catalogue and standardize measurement data. To better display the range of available parts and to facilitate part selection in synthetic biology workflows, we established biopartsDB, a curated database of well-characterized and useful genetic part and device libraries with detailed quantitative data validated by the published literature.

CRISPR-powered RNA sensing in vivo.

RNA sensing in vivo evaluates past or ongoing endogenous RNA disturbances, which is crucial for identifying cell types and states and diagnosing diseases. Recently, the CRISPR-driven genetic circuits have offered promising solutions to burgeoning challenges in RNA sensing. This review delves into the cutting-edge developments of CRISPR-powered RNA sensors in vivo, reclassifying these RNA sensors into four categories based on their working mechanisms, including programmable reassembly of split single-guide RNA (sgRNA), RNA-triggered RNA processing and protein cleavage, miRNA-triggered RNA interference (RNAi), and strand displacement reactions. Then, we discuss the advantages and challenges of existing methodologies in diverse application scenarios and anticipate and analyze obstacles and opportunities in forthcoming practical implementations.

ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4+ Th1 responses.

Parasite-specific CD4+ Th1 cell responses are the predominant immune effector for controlling malaria infection; however, the underlying regulatory mechanisms remain largely unknown. This study demonstrated that ATG5 deficiency in myeloid cells can significantly inhibit the growth of rodent blood-stage malarial parasites by selectively enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency suppressed FAS-mediated apoptosis of LY6G- ITGAM/CD11b+ ADGRE1/F4/80- cells and subsequently increased CCL2/MCP-1 production in parasite-infected mice. LY6G- ITGAM+ ADGRE1- cell-derived CCL2 selectively interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2-STAT4 pathway. The administration of recombinant CCL2 significantly promoted parasite-specific CD4+ Th1 responses and suppressed malaria infection. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cells apoptosis and sequentially affecting CCL2 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of immune interventions and effective anti-malarial vaccines.Abbreviations: ATG5: autophagy related 5; CBA: cytometric bead array; CCL2/MCP-1: C-C motif chemokine ligand 2; IgG: immunoglobulin G; IL6: interleukin 6; IL10: interleukin 10; IL12: interleukin 12; MFI: mean fluorescence intensity; JAK2: Janus kinase 2; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; pRBCs: parasitized red blood cells; RUBCN: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; STAT4: signal transducer and activator of transcription 4; Th1: T helper 1 cell; Tfh: follicular helper cell; ULK1: unc-51 like kinase 1.

Customizing cellular signal processing by synthetic multi-level regulatory circuits.

As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. Towards this mission, novel regulatory mechanisms and genetic circuits with unprecedented complexity have been implemented over the past decade. These regulatory mechanisms, such as transcription and translation control, could be integrated into hybrid circuits termed "multi-level circuits". The multi-level circuit design will tremendously benefit the current genetic circuit design paradigm, from modifying basic circuit dynamics to facilitating real-world applications, unleashing our capabilities to customize cellular signal processing and address global challenges through synthetic biology.

Identification of Dioscorea opposite Thunb. CDPK gene family reveals that DoCDPK20 is related to heat resistance.

Temperature affects the growth and yield of yam (Dioscorea opposite Thunb.), and calcium-dependent protein kinases (CDPKs) play an important role in the plant stress response. However, there has been a lack of system analyses of yam's CDPK gene family. In this study, 29 CDPK transcriptome sequences with complete open reading frames (ORFs) were identified from yam RNA sequencing data. The sequences were classified into four groups (I-VI) using phylogenetic analysis. Two DoCDPK genes were randomly selected from each group and the gene patterns of yam leaves were determined using quantitative real-time PCR (qRT-PCR) under high and low temperature stress in order to show their unique functions in mediating specific responses. Among them, DoCDPK20 was significantly induced in high temperatures. The pPZP221-DoCDPK20 was transformed into tobacco leaves using an agrobacterium-mediated method. Under high temperature stress, DoCDPK20 overexpression reduced photosynthesis and improved heat tolerance in transgenic tobacco. Our research offers meaningful perspectives into CDPK genes and new avenues for the genetic engineering and molecular breeding of yam.

Multiple headspace solid-phase microextraction using a new fiber for avoiding matrix interferences in the quantitative determination of ethyl carbamate in pickles.

Multiple headspace solid-phase microextraction (HS-SPME) using a novel fiber coated with anilino-methyl triethoxy silicane-methacrylic acid/terminated silicone oil has been introduced as a useful pretreatment technique coupled to gas chromatography-flame ionization detector for the detection of ethyl carbamate in pickles. Anilino-methyl triethoxy silicane and methacrylic acid are put into use simultaneously with the aim to increase the hydrogen interaction strength between ethyl carbamate and the coating. In addition, the new fiber exhibits high thermal stability, good reproducibility, and long lifetime. Extraction temperature, extraction time, amount of desiccant, and amount of sample were well optimized to guarantee the suitability of multiple HS-SPME. Significant matrix interference was observed among various types of pickles and the multiple HS-SPME procedure was proved to be effective in avoiding the matrix effect by a complete recovery of the analyte. The method showed satisfactory linearity (0.1-100 mg kg(-1)), precision (4.25%, n = 5), and detection limit (0.038 mg kg(-1)). The accuracy of the method was evaluated by comparison with standard addition method and the results were statistically equivalent. The study indicates that the multiple HS-SPME procedure is simple, convenient, accurate, and low-cost, and most of all, can be used for quantitative analysis in complex matrix without matrix effect.

The Dynamic Change of Immune Responses Between Acute and Recurrence Stages of Rodent Malaria Infection.

Malaria infections are persistent as frequent recrudescence of the disease may occur following the acute infection stage, but the different immune responses that control the acute and recrudescence stages are still largely unknown. Using single-cell RNA sequencing (scRNA-seq), we showed that the number of Th1 and plasma cells in the spleen was significantly reduced during the recurrence stage compared to the acute stage of Plasmodium chabaudi chabaudi AS (P. chabaudi) infection. Additionally, the ability of both CD4+ T cell responses and B cells to control P. chabaudi recurrence was significantly reduced compared to their roles in the control of acute infection. In contrast, the number of innate immune cells, including red pulp macrophages (RPMs), gamma delta (γδ) T cells, and Dendritic cells (DCs) were significantly increased during the recurrence stage and showed to be critical for P. chabaudi infection recurrence control. Thus, our data strongly suggest the complementary role of innate immune responses in controlling malaria recrudescence when adaptive immune responses are suppressed. These findings shed new light on the development of immune interventions against malaria.

Lipopolysaccharide enhances asymmetrical production of cytokines and nitric oxide by left and right cerebral cortical microglial cells in BALB/C mice.

Lipopolysaccharide (LPS)-induced inflammatory factors production by the cerebral cortical glial cells in two sides of the murine brain are different. To determine if microglial cells, a subset of glial cells, are involved in asymmetric production, interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and nitric oxide (NO) responses to LPS by microglial cells in the right and left cerebral cortices were examined. Primary microglial cells were isolated from BALB/C neonatal mice, treated with LPS (10 µg ml(-1) ) for 24 h and examined for IL-6, IL-1ß and NO production. At untreated state, the levels of IL-6, IL-1ß and NO showed no statistical difference between left and right. However, after LPS treatment, the levels of IL-6, IL-1ß and NO for the right microglial cells was statistically significant higher than the left (P < 0·05). Our results denote that enhanced production of IL-6, IL-1ß and NO after LPS treatment in microglia is directly proportional to their basal-state levels, and right cortical microglia produce higher levels of IL-6, IL-1ß and NO than left cortical microglia.

Asymmetrical release of interleukin-6 by cultured cerebral cortical astrocytes treated with lipopolysaccharide.

BACKGROUND & OBJECTIVES: The distribution of brain interleukin-6 (IL-6) may be asymmetrical both in cortex and hippocampus. While the brain asymmetry has been extensively investigated, the cellular origin of asymmetrical cytokine induction in the cortex has not been addressed. It was hypothesized that the immune function of glia cell to the inflammatory insults is asymmetrically distributed in the two brain hemispheres. To test this hypothesis, we examined the IL-6 secreting ability of the astrocytes in both the left and right neocortex treated with lipopolysaccharide(LPS) cultured in vitro. METHODS: Two groups of astrocytes cultured in vitro from the two cerebral cortices of the neonatal BALB/ c mice were selected and experimental group was treated with LPS (10 mug/ml) for 24 h. IL-6 levels were measured in both LPS-treated and untreated astrocytes. To confirm the gene array data on the secretion of IL-6 by cortical astrocytes in the left and right hemispheres, semi-quantitative reverse transcriptionpolymerase chain reaction (RT-PCR) was conducted. RESULTS: A statistically significant difference between the levels of IL-6 in cortical astrocytes in the left and right hemispheres of culture supernatants was observed (P<0.05). Cortical astrocytes in the left hemisphere had significantly increased IL-6 mRNA levels compared with cortical astrocytes in right hemisphere (P<0.05). INTERPRETATION & CONCLUSION: The results showed asymmetrical release of brain IL-6 by cerebral cortical astrocytes to the inflammatory insults both in protein and mRNA levels.

Apoptosis and proinflammatory cytokine responses of primary mouse microglia and astrocytes induced by human H1N1 and avian H5N1 influenza viruses.

Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid (SA)-alpha2,3-Galactose (Gal) and SA-alpha2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1beta, IL-6 and TNF-alpha mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1beta, IL-6 and TNF-alpha at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis.

Sol-gel molecularly imprinted polymer for selective solid phase microextraction of organophosphorous pesticides.

A sol-gel technique was applied for the preparation of water-compatible molecularly imprinted polymer (MIP) for solid phase microextraction (SPME) using diazinon as template and polyethylene glycol as functional monomer. The MIP-coated fiber demonstrated much better selectivity to diazinon and its structural analogs in aqueous cucumber sample than in distilled water, indicating its potential in real samples. Thanks to its specific adsorption as well as rough and porous surface, the coating revealed rather larger extraction capability than the non-imprinted polymer and commercial fibers. In addition, the fiber exhibited excellent thermal (about 350°C) and chemical stability (organic and inorganic). After optimization of several parameters affecting extraction efficiency, a method based on MIP-SPME combined with gas chromatography was developed for the determination of organophosphorus pesticides (OPPs) in vegetable samples. The limits of detection for the tested OPPs were in the range of 0.017-0.77 µg kg(-1). The proposed method was applied to evaluate OPPs in spiked cucumber, green pepper, Chinese cabbage, eggplant and lettuce samples, and recoveries of 81.2-113.5% were obtained by the standard addition method with three spiking levels in each kind of vegetable.

Multiple headspace solid-phase microextraction after matrix modification for avoiding matrix effect in the determination of ethyl carbamate in bread.

This study presents the potential of multiple headspace solid-phase microextraction (multiple HS-SPME) for the quantification of analytes in solid samples. Multiple HS-SPME shares the same advantages as SPME. It also enables a complete recovery of the target compound and therefore the matrix effect, which commonly appears in SPME-based analysis, is avoided. A method based on multiple HS-SPME for the determination of the toxic contaminant ethyl carbamate (EC) in bread samples has been developed and validated, using gas chromatography with flame ionization detector. A novel polyethylene glycol/hydroxy-terminated silicone oil fiber was prepared for the first time and subsequently used instead of commercial ones because of its high extraction ability and good operational stability. An important problem still remained in multiple HS-SPME of EC in fresh bread samples. The adsorption of EC by water in the samples caused low transport of analyte to the headspace, which made multiple HS-SPME invalidated. Mixing with anhydrous sodium sulphate, the sensitivity of the method was improved and the problem was solved. The proposed method showed satisfactory linearity (0.15-1500 µg g(-1)), precision (1.6%, n=5) and limit of detection (0.041 µg g(-1)). Good recoveries, from 92.5 to 103.4%, were observed at three spiking levels. The method was applied to 14 bread samples. The multiple HS-SPME technique offers several advantages including reducing the manipulation time and cost, and avoiding analyte losses, especially in the analysis of a large number of samples in different matrices.