Effect of Preadministration of Nalmefene on Sufentanil-Induced Cough During Induction of General Anesthesia in Patients Undergoing Breast Surgery: A Double-Blind Randomized Controlled Trial.

Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial.

BACKGROUND: Our previous studies showed that curcumin prevented hepatic steatosis in animal models. OBJECTIVES: This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). METHODS: In a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. RESULTS: Curcumin consumption significantly reduced CAP value compared with placebo (-17.5 dB/m; 95% confidence interval [CI]: -27.1, -7.8 dB/m; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95% CI: -4.4, -0.8 kg; P < 0.001) and BMI (-1.0 kg/m2; 95% CI: -2.0, -0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95% CI: -0.20, -0.04 mmol/L; P = 0.004), triglycerides (-0.29 mmol/L; 95% CI: -0.41, -0.14 mmol/L; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95% CI: -0.12, -0.01 mmol/L; P = 0.038), hemoglobin A1c (-0.06%; 95% CI: -0.33, -0.01%; P = 0.019), and insulin (-4.94 µU/L; 95% CI: -9.73, -0.15 µU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). CONCLUSIONS: Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn as ChiCTR2200058052.

No causal association between the volume of strenuous exercise and coronary atherosclerosis: a two-sample Mendelian randomization study.

Objective: Several observational studies have shown that high-volume and high-intensity exercise training increases the prevalence and severity of coronary atherosclerosis, but the causal effect still remains uncertain. This study aims to explore the causal relationship between the volume of strenuous exercise (SE) and coronary atherosclerosis (CA) using the Mendelian randomization (MR) method. Method: The exposure factors were two basic parameters of the volume of strenuous exercise (duration and frequency of strenuous exercise), the outcome factor was coronary atherosclerosis, and the relevant genetic loci were extracted from the summary data of the genome-wide association study (GWAS) as the instrumental variables, and MR analyses were performed using the inverse variance weighting (IVW) method, the weighted median method, and the MR-egger method. Sensitivity analyses were performed using heterogeneity analysis, pleiotropy analysis, and the "leave-one-out" method. The original results were tested using other coronary atherosclerosis data sets. Result: IVW results showed no causal association between duration of strenuous exercise (DOSE) [OR = 0.9937, 95% CI (0.9847, 1.0028), P = 0.1757] and frequency of strenuous exercise (FOSE) in the last 4 weeks [OR = 0.9930, 95% CI (0.9808, 1.0054), P = 0.2660] and coronary atherosclerosis. All of the above results were validated with other coronary atherosclerosis data sets. Conclusion: The present study supports that the causal association of duration and frequency of SE with CA was not found, and provides valuable insights into the choice of scientific and correct volume of SE to cardiac rehabilitation (CR).

Correction: Antimicrobial peptide-modified silver nanoparticles for enhancing the antibacterial efficacy.

[This corrects the article DOI: 10.1039/D0RA05640E.].

Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia.

Peripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long-term controlled release of water-soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel-matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS-ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self-healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS-ROP/dexmedetomidine (DEX), with long-term retention and drug release in vivo is prepared by combining HMS-ROP and Gel/DEX. The drug loading of HMS-ROP reached 41.1%, with a drug release time of over 160 h in vitro, and sensory and motor blockade times in vivo of 48 and 36 h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core-shell microspheres, DEX, and an injectable gel, providing a promising strategy for long-acting postoperative pain management.

Association between the Reduced Expression of RECK and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a recently discovered inhibitor of matrix metalloproteinase (MMP). There is a large number of chronic obstructive pulmonary disease (COPD) patients worldwide; however, the role of RECK on COPD has not been studied. This study explored the expression of RECK in COPD patients and its effect on neutrophil function to provide a new scientific basis for the prevention and treatment of COPD. METHOD: Fifty patients with acute exacerbation of COPD and fifty healthy controls were enrolled in the study. RECK was detected in lung tissue, sputum, and plasma of subjects as well as in BEAS-2B cells stimulated with cigarette smoke extract (CSE) by immunohistochemistry, ELISA, and qRT-PCR. Meanwhile, lung function (FEV1%pred) and inflammatory cytokines (IL-6 and IL-8) were examined, and correlation analysis was performed with RECK expression. The effect of RECK on proliferation, apoptosis, migration, and inflammatory cytokines and its potential mechanism was further quantified by neutrophil stimulated with recombinant human RECK protein (rhRECK) combined with CSE using CCK8, flow cytometry, Transwell assay, qRT-PCR, ELISA, and Western analysis. RESULTS: RECK was mainly expressed on airway epithelial cells in normal lung tissue and was significantly diminished in COPD patients. The levels of RECK in sputum and plasma were also significantly decreased in COPD patients. Pearson correlation analysis showed that RECK level in plasma was positively correlated with FEV1%pred (r = 0.458, p < 0.001) and negatively correlated with IL-6 and IL-8 (r = -0.386, -0.437; p = 0.006, 0.002) in COPD patients. The expression of RECK was decreased in BEAS-2B stimulated with CSE. The migration, inflammation, and MMP-9 expression of neutrophils were promoted by CSE, while inhibited by rhRECK. CONCLUSION: RECK is low expressed in COPD patients and negatively correlated with inflammation. It may inhibit the inflammation and migration of neutrophils by downregulating MMP-9.

Competing Mechanisms Determine Oxygen Redox in Doped Ni-Mn Based Layered Oxides for Na-Ion Batteries.

Cation doping is an effective strategy for improving the cyclability of layered oxide cathode materials through suppression of phase transitions in the high voltage region. In this study, Mg and Sc are chosen as dopants in P2-Na0.67Ni0.33Mn0.67O2, and both have found to positively impact the cycling stability, but influence the high voltage regime in different ways. Through a combination of synchrotron-based methods and theoretical calculations it is shown that it is more than just suppression of the P2 to O2 phase transition that is critical for promoting the favorable properties, and that the interplay between Ni and O activity is also a critical aspect that dictates the performance. With Mg doping, the Ni activity can be enhanced while simultaneously suppressing the O activity. This is surprising because it is in contrast to what has been reported in other Mn-based layered oxides where Mg is known to trigger oxygen redox. This contradiction is addressed by proposing a competing mechanism between Ni and Mg that impacts differences in O activity in Na0.67MgxNi0.33- xMn0.67O2 (x < 0 < 0.33). These findings provide a new direction in understanding the effects of cation doping on the electrochemical behavior of layered oxides.

A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Selenophene Substitution Enabled High-Performance n-Type Polymeric Mixed Ionic-Electronic Conductors for Organic Electrochemical Transistors and Glucose Sensors.

High-performance n-type polymeric mixed ionic-electronic conductors (PMIECs) are essential for realizing organic electrochemical transistors (OECTs)-based low-power complementary circuits and biosensors, but their development still remains a great challenge. Herein, by devising two novel n-type polymers (f-BTI2g-SVSCN and f-BSeI2g-SVSCN) containing varying selenophene contents together with their thiophene-based counterpart as the control, it is demonstrated that gradually increasing selenophene loading in polymer backbones can simultaneously yield lowered lowest unoccupied molecular orbital levels, boosted charge-transport properties, and improved ion-uptake capabilities. Therefore, a remarkable volumetric capacitance (C*) of 387.2 F cm-3 and a state-of-the-art OECT electron mobility (µe,OECT ) of 0.48 cm2 V-1 s-1 are synchronously achieved for f-BSeI2g-SVSCN having the highest selenophene content, yielding an unprecedented geometry-normalized transconductance (gm,norm ) of 71.4 S cm-1 and record figure of merit (µC*) value of 191.2 F cm-1 V-1 s-1 for n-type OECTs. Thanks to such excellent performance of f-BSeI2g-SVSCN-based OECTs, a glucose sensor with a remarkably low detection limit of 10 nMm and decent selectivity is further implemented, demonstrating the power of selenophene substitution strategy in enabling high-performance n-type PMIECs for biosensing applications.

Multi-Selenophene Incorporated Thiazole Imide-Based n-Type Polymers for High-Performance Organic Thermoelectrics.

Developing polymers with high electrical conductivity (σ) after n-doping is a great challenge for the advance of the field of organic thermoelectrics (OTEs). Herein, we report a series of thiazole imide-based n-type polymers by gradually increasing selenophene content in polymeric backbone. Thanks to the strong intramolecular noncovalent N⋅⋅⋅S interaction and enhanced intermolecular Se⋅⋅⋅Se interaction, with the increase of selenophene content, the polymers show gradually lowered LUMOs, more planar backbone, and improved film crystallinity versus the selenophene-free analogue. Consequently, polymer PDTzSI-Se with the highest selenophene content achieves a champion σ of 164.0 S cm-1 and a power factor of 49.0 µW m-1 K-2 in the series when applied in OTEs after n-doping. The σ value is the highest one for n-type donor-acceptor OTE materials reported to date. Our work indicates that selenophene substitution is a powerful strategy for developing high-performance n-type OTE materials and selenophene incorporated thiazole imides offer an excellent platform in enabling n-type polymers with high backbone coplanarity, deep-lying LUMO and enhanced mobility/conductivity.

Microbial Necromass, Lignin, and Glycoproteins for Determining and Optimizing Blue Carbon Formation.

Coastal wetlands contribute to the mitigation of climate change through the sequestration of "blue carbon". Microbial necromass, lignin, and glycoproteins (i.e., glomalin-related soil proteins (GRSP)), as important components of soil organic carbon (SOC), are sensitive to environmental change. However, their contributions to blue carbon formation and the underlying factors remain largely unresolved. To address this paucity of knowledge, we investigated their contributions to blue carbon formation along a salinity gradient in coastal marshes. Our results revealed decreasing contributions of microbial necromass and lignin to blue carbon as the salinity increased, while GRSP showed an opposite trend. Using random forest models, we showed that their contributions to SOC were dependent on microbial biomass and resource stoichiometry. In N-limited saline soils, contributions of microbial necromass to SOC decreased due to increased N-acquisition enzyme activity. Decreases in lignin contributions were linked to reduced mineral protection offered by short-range-ordered Fe (FeSRO). Partial least-squares path modeling (PLS-PM) further indicated that GRSP could increase microbial necromass and lignin formation by enhancing mineral protection. Our findings have implications for improving the accumulation of refractory and mineral-bound organic matter in coastal wetlands, considering the current scenario of heightened nutrient discharge and sea-level rise.

Deciphering Biotic and Abiotic Mechanisms Underlying Straw Decomposition and Soil Organic Carbon Priming in Agriculture Soils Receiving Long-Term Fertilizers.

Straw-related carbon (C) dynamics are central for C accrual in agro-ecosystems and should be assessed by investigating their decomposition and soil organic carbon (SOC) priming effects. Our understanding of biotic and abiotic mechanisms underpinning these two C processes, however, is still not sufficiently profound. Soils that had received organic and mineral fertilizers for 26 years were sampled for a 28 day incubation experiment to assess 13C-labeled straw decomposition and SOC priming effects. On the basis of analyzing physicochemical properties, fungal taxonomic (MiSeq sequencing) and functional (metagenomics) guilds, we quantified the contributions of biotic and abiotic attributes to straw decomposition and SOC priming. Here, we propose two distinct mechanisms underlying straw decomposition and SOC priming in agriculture soils: (i) accelerated straw mineralization in manure-treated soils was mainly driven by biotic forces, while (ii) larger SOC priming in NPK-amended soils was through abiotic regulation.

Rhizosphere effects of moso bamboo and dominant tree species of secondary broadleaved forest on soil organic carbon mineralization.

The rhizosphere effect of plants affects soil organic carbon (SOC) mineralization. It is still unclear for the mechanism by which the rhizosphere effect of dominant plants in secondary broadleaved forest habitats invaded by moso bamboo affects SOC mineralization. Taking broadleaved tree species (Quercus glauca and Cunninghamia lanceolata) and moso bamboo, dominating respectively in uninvaded secondary broadleaved forest and bamboo forest formed after the invasion as test materials, we investigated rhizosphere effect of plants on the SOC mineralization in laboratory incubation experiments. The results showed that carbon mineralization rates of Phyllostachys edulis (PE), Quercus glauca (QG) and Cunninghamia lanceolata (CL) rhizosphere soils were 20%, 26%, and 21% higher than bulk soils, respectively. Carbon mineralization of bulk soils of QG and CL was 22% and 26% higher, while that of rhizosphere soils was 14% and 11% higher than PE, respectively. The contents of water-soluble organic carbon and organic carbon in rhizosphere soils of the three species were significantly higher than those of bulk soil, and the abundance of rhizosphere soil bacteria was higher than that of non-rhizosphere. The contents of microbial biomass carbon, water-soluble organic carbon, and total nitrogen were important factors influencing carbon mineralization in rhizosphere, while water-soluble organic carbon and microbial metabolic quotient were important factors influencing carbon mineralization in non-rhizosphere. On the whole, the rhizosphere effect increased total SOC mineralization, driving by changes in microbial biomass carbon, water-soluble organic carbon, and total nitrogen content. The results could provide a theoretical basis for plant-soil interaction on soil carbon cycling in bamboo invasion habitats.

[Progress in Image-planned and Real-time Image-guided Lung Cancer Biopsy 
in the Detection of Biomarkers].

With the progress of targeted therapy and immunotherapy for lung cancer, the clinical demand for lung biopsy is increasing. An ideal biopsy specimen can be used not only for histopathological diagnosis, but also for biomarker detection. The ideal biopsy specimen should meet two requirements, including more than 60 mm2 of tumor tissue and containing more than 20% of tumor cells. In order to obtain ideal lung cancer biopsy specimens, advanced imaging techniques are needed to help. In this article, we reviewed the requirements for biopsy specimens based on biomarker detection, as well as the current status and research progress of using imaging techniques for preoperative planning and intraoperative real time guidance of lung cancer biopsy.
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Soil selenium enrichment in the Loess Plateau of China: Geogenic evidence, spatial distribution, and it's influence factors.

The selenium (Se)-deficient soil belt in China has gained widespread attention. During large-scale soil surveys in China, Se-rich soils within low-Se belts have been identified. However, the sources of Se in those soils and the controlling factors for their enrichment remain unclear. Here we summarize Se concentrations and spatial distributions in the Yuanzhou district of the Loess Plateau. We evaluated Se variations in soil profiles, Se migration into water bodies, and considered soil indicators, topographic characteristics and the influence of land-use types on soil Se concentrations. The average Se concentration in the topsoil of the Yuanzhou district was 0.164 µg/g. High-Se soils (>0.222 µg/g) were found in the western valley plain and the southern red bed hilly area, as well as sporadically in higher elevation forestland and grassland areas in the east. Enrichment of Se in the topsoil in the eastern and southern areas was primarily due to Se adsorption and accumulation by soil organic matter as well as enrichment in gypsum, berlinite, and clay minerals during soil formation. Widespread enrichment in the southern area was linked to high Se concentrations in red Tertiary sedimentary rocks. In the western area, enrichment of Se in topsoil was found on both sides of the Qingshui River at low elevations with gentle slopes, with river water being the primary carrier of Se enrichment. These findings provide valuable insights into the epigenetic geochemical behavior of soil Se in China's low-Se belt that accounts for development of Se-rich soils in the region.

Questionnaire-based analysis of autism spectrum disorders and gastrointestinal symptoms in children and adolescents: a systematic review and meta-analysis.

Background: Gastrointestinal (GI) symptoms are frequently experienced by children with autism spectrum disorder (ASD), and these symptoms cause difficulties for these children and their families. However, studies of GI symptom prevalence differ significantly. This meta-analysis aimed to analyze the prevalence of GI symptoms in children with ASD. Methods and findings: PubMed, Scopus, Web of Science, EMBASE were electronically searched to collect all literature on gastrointestinal symptoms of children with ASD collected through questionnaires or scales from January 2012 to May 2021. Four researchers independently scanned the literature and extracted information on general characteristics. First author name, year of publication, geographical location, type of study, sample sizes of ASD and control (if any) children, sex and average age, number of GI cases, number of GI symptoms, GI assessment tools (gastrointestinal symptoms scale), autism diagnosis methods, and other necessary data were collected and analyzed using Stata V16. The questionnaires included the Rome, 6-GSI, GIQ, GSRS, GSIQ, ADI-R, PedsQL-GI, parent-report, GI-related, and self-administered questionnaires. Compared with typically developing (TD) children, the odds ratio for In children with ASD with at least one GI symptom was 3.64, and the total prevalence was 55%. The cumulative prevalence rates of various symptoms were summarized, showing that 37% of children with ASD had constipation, 21% had abdominal pain, 19% had diarrhea, 8% had vomiting, and 23% had abdominal distension. Conclusions: The results of this meta-analysis on GI symptoms in ASD show that patients with ASD are more likely to develop symptoms than TD children. The prevalence of GI symptoms in In children with ASD was 55%. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO, identifier, #CRD42017080579.

Pharmacological interventions for preventing opioid-induced hyperalgesia in adults after opioid-based anesthesia: a systematic review and network meta-analysis.

Background: Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Methods: Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. Results: In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Conclusion: Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. Clinical Trial Registration: https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.

Multi-scale analysis provides insights into the roles of ureide permeases in wheat nitrogen use efficiency.

The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.

Seasonal linkages between soil nitrogen mineralization and the microbial community in broadleaf forests with Moso bamboo (Phyllostachys edulis) invasion.

Plant invasions significantly alter the microbiome of the soil in terms of fungal and bacterial communities, which in turn regulates ecosystem processes and nutrient dynamics. However, it is unclear how soil microbial communities, nitrogen (N) mineralization, and their linkages respond to plant invasions over the growing season in forest ecosystems. The present study investigated the seasonal associations between the microbial composition/function and net N mineralization in evergreen broadleaf, mixed bamboo-broadleaf, and Moso bamboo (Phyllostachys edulis) forests, depicting uninvaded, moderately invaded, and heavily invaded forests, respectively. The ammonification and nitrification rates in the bamboo forest were significantly higher than those in the broadleaf and mixed bamboo-broadleaf forests during the spring season only. The forest type and seasonal variation significantly influenced the net rates of ammonification and nitrification and the abundances of bacterial apr and AOB amoA, fungal cbhI and lcc genes, as well as the microbial composition. Moreover, the partial least squares path model revealed that bamboo invasion enhanced net ammonification through increasing total N and fungal-to-bacterial ratio, and enhanced net nitrification through modifying the bacterial composition and increasing the fungal-to-bacterial ratio during spring. However, microbial parameters had no significant effect on net ammonification and nitrification during autumn. We conclude that shifts in the microbial abundance and composition following bamboo invasion facilitated soil N mineralization during spring, contributing to the rapid growth of Moso bamboo at the beginning of the growth season and its invasion into adjacent subtropical forests.