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Abstract Elderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.

Background: This work aimed to explore anxiety-associated risk factors in patients diagnosed with ulcerative colitis (UC). Methods: Clinical data from patients diagnosed with UC and hospitalized at the First Affiliated Hospital of Xi’an Jiaotong University between May 2019 and June 2022 were retrospectively analyzed. A total of 260 patients were included and divided into UC with anxiety (n = 86) and UC without anxiety (n = 174) groups according to the Self-Rating Anxiety Scale score. The quality of life and disease activity in patients with UC were assessed using the Inflammatory Bowel Disease Questionnaire and Mayo Score, respectively. Clinical data, disease characteristics, quality of life, disease activity, and noise exposure were compared between the groups, and factors contributing to anxiety in patients with UC were explored through multivariate logistic regression analysis. Results: No significant difference was found between the groups in terms of disease duration (P = 0.73), distribution of disease (P = 0.86), or medication use (P = 0.86). However, compared to UC patients without anxiety, those with anxiety were older (P < 0.05), predominantly female (P < 0.05), had lower quality of life (P < 0.05), experienced higher disease activity (P < 0.05), and had greater noise exposure (P < 0.05). The quality of life [odds ratio (OR) = 0.558, 95% confidence interval (CI) = 0.348–0.895, P = 0.02] was a protective factor for anxiety in patients with UC. Disease activity (OR = 1.680, 95% CI = 1.103–2.561, P = 0.02) and noise exposure (OR = 2.148, 95% CI = 1.084–4.106, P = 0.01) were significant risk factors for anxiety in patients with UC. Conclusion: Noise exposure and disease activity were associated with an increased risk of anxiety in patients with UC, whereas higher quality of life was protective against anxiety in UC patients.

Highlights A new type of metallacage was successfully fabricated and used as containers for hypocrellin-type photosensitizers, which prevented the self-aggregation of photosensitizers in aqueous solution. The metallacage was also employed as an energy donor to promote the singlet oxygen generation ability via fluorescence resonance energy transfer, thereby achieving highly efficient photodynamic therapy.

Abstract Background Several plants are facing drought stress due to climate change in recent years. In this study, we aimed to explore the effect of varying watering frequency on the growth and photosynthetic characteristics of Hosta ‘Guacamole’. Moreover, we investigated the effect of high-nitrogen and -potassium fertilizers on alleviating the impacts of drought stress on the morphology, photosynthetic characteristics, chlorophyll fluorescence, fast chlorophyll a fluorescence transient, JIP-test parameters, and enzymatic and non-enzymatic scavenging system for reactive oxygen species (ROS) in this species. Results Leaf senescence, decreased chlorophyll contents, limited leaf area, and reduced photosynthetic characteristics and oxygen-evolving complex (OEC) activity were observed in Hosta ‘Guacamole’ under drought stress. However, high-nitrogen fertilizer (30-10-10) could efficiently alleviate and prevent the adverse effects of drought stress. High-nitrogen fertilizer significantly increased chlorophyll contents, which was higher by 106% than drought stress. Additionally, high-nitrogen fertilizer significantly improved net photosynthetic rate and water use efficiency, which were higher by 467% and 2900% than those under drought stress. It attributes that high-nitrogen fertilizer could reduce transpiration rate of leaf cells and stomatal opening size in drought stress. On the other hand, high-nitrogen fertilizer enhanced actual photochemical efficiency of PS II and photochemical quenching coefficient, and actual photochemical efficiency of PS II significantly higher by 177% than that under drought stress. Furthermore, high-nitrogen fertilizer significantly activated OEC and ascorbate peroxidase activities, and enhanced the performance of photosystem II and photosynthetic capacity compared with high-potassium fertilizers (15-10-30). Conclusions High-nitrogen fertilizer (30-10-10) could efficiently alleviate the adverse effects of drought stress in Hosta ‘Guacamole’ via enhancing OEC activity and photosynthetic performance and stimulating enzymatic ROS scavenging system.

A 30-year-old man presented to otolaryngology department complaining of nasal congestion and runny nose for six months, with repeated fever, and shortness of breath.The weight loss in the past 20 days was about 5 kg. At first, he was diagnosed with respiratory infection and was treated with antibiotics, but it didn't work. Nasopharynx CT scan showed soft tissue thickening without bone destruction, with obvious inhomogeneous enhancement. Chest CT scan revealed multiple patchy clouding nodules and ground-glass opacity with poorly-defined border. Urine test showed urine microalbumin ≥ 150 mg per liter (reference range, 0–20), white-cell count of 11.0 cells per microliter (reference range, 0–5). Histology of nasopharynx biopsy showed small-medium-vessel necrotizing vasulitis.Although nasopharyngeal histopathology didn’t reveal peri- and extravascular granulomatosis and antineutrophilic cytoplasmic antibodies (ANCA) was negtive, he had ENT signs, lung nodules, and kidney involvement and condition developed fast and biopsy showed small- and- medium-vessel vasculitis. Therefore, the patient met the classification criteria for GPA and his symptoms were disappeared 1 week after starting GPA treatment, the chest CT showed ground-glass opacity decreased and CRP、ESR became normal. He was treated with rituximab combined with glucocorticoids for 4 weeks, after which he was discharged.

Unmanned aerial vehicles (UAVs) and reconfigurable intelligent surfaces (RISs) are increasingly employed in mobile edge computing (MEC) systems to flexibly modify the signal transmission environment. This is achieved through the active manipulation of the wireless channel facilitated by the mobile deployment of UAVs and the intelligent reflection of signals by RISs. However, these technologies are subject to inherent limitations such as the restricted range of UAVs and limited RIS coverage, which hinder their broader application. The integration of UAVs and RISs into UAV–RIS schemes presents a promising approach to surmounting these limitations by leveraging the strengths of both technologies. Motivated by the above observations, we contemplate a novel UAV–RIS-aided MEC system, wherein UAV–RIS plays a pivotal role in facilitating communication between terrestrial vehicle users and MEC servers. To address this challenging non-convex problem, we propose an energy-constrained approach to maximize the system’s energy efficiency based on a double-deep Q-network (DDQN), which is employed to realize joint control of the UAVs, passive beamforming, and resource allocation for MEC. Numerical results demonstrate that the proposed optimization scheme significantly enhances the system efficiency of the UAV–RIS-aided time division multiple access (TDMA) network.

Abstract Background Downy mildew of foxtail millet, which is caused by the biotrophic oomycete Sclerospora graminicola (Sacc.) Schroeter, is one of the most disruptive diseases. The foxtail millet-S. graminicola interaction is largely unexplored. Transcriptome sequencing technology can help to reveal the interaction mechanism between foxtail millet and its pathogens. Results Transmission electron microscopy observations of leaves infected with S. graminicola showed that the structures of organelles in the host cells gradually became deformed and damaged, or even disappeared from the 3- to 7-leaf stages. However, organelles in the leaves of resistant variety were rarely damaged. Moreover, the activities of seven cell wall degrading enzymes in resistant and susceptible varieties were also quite different after pathogen induction and most of enzymes activities were significantly higher in the susceptible variety JG21 than in the resistant variety G1 at all stages. Subsequently, we compared the transcriptional profiles between the G1 and JG21 in response to S. graminicola infection at 3-, 5-, and 7-leaf stages using RNA-Seq technology. A total of 473 and 1433 differentially expressed genes (DEGs) were identified in the resistant and susceptible varieties, respectively. The pathway analysis of the DEGs showed that the highly enriched categories were related to glutathione metabolism, plant hormone signalling, phenylalanine metabolism, and cutin, suberin and wax biosynthesis. Some defence-related genes were also revealed in the DEGs, including leucine-rich protein kinase, Ser/Thr protein kinase, peroxidase, cell wall degrading enzymes, laccases and auxin response genes. Our results also confirmed the linkage of transcriptomic data with qRT-PCR data. In particular, LRR protein kinase encoded by Seita.8G131800, Ser/Thr protein kinase encoded by Seita.2G024900 and Seita. 2G024800, which have played an essential resistant role during the infection by S. graminicola. Conclusions Transcriptome sequencing revealed that host resistance to S. graminicola was likely due to the activation of defence-related genes, such as leucine-rich protein kinase and Ser/Thr protein kinase. Our study identified pathways and genes that contribute to the understanding of the interaction between foxtail millet and S. graminicola at the transcriptomic level. The results will help us better understand the resistance mechanism of foxtail millet against S. graminicola.

IntroductionThis study aimed to identify preoperative blood biomarkers related to development of delayed neurocognitive recovery (dNCR) following surgery.MethodsA total of 67 patients (≥65 years old) who underwent head and neck tumor resection under general anesthesia were assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Preoperative serum metabolomics were determined using widely targeted metabolomics technology.ResultsOf the 67 patients, 25 developed dNCR and were matched to 25 randomly selected patients from the remaining 42 without dNCR. Differential metabolites were selected using the criteria of variable importance in projection > 1.0 in orthogonal partial least squares discrimination analysis, false discovery rate 1.2 or

Glioblastoma is a malignant tumor with the highest morbidity and mortality in the central nervous system. Conventional surgical resection combined with radiotherapy or chemotherapy has a high recurrence rate and poor prognosis. The 5-year survival rate of patients is less than 10%. In tumor immunotherapy, CAR-T cell therapy represented by chimeric antigen receptor-modified T cells has achieved great success in hematological tumors. However, the application of CAR-T cells in solid tumors such as glioblastoma still faces many challenges. CAR-NK cells are another potential adoptive cell therapy strategy after CAR-T cells. Compared with CAR-T cell therapy, CAR-NK cells have similar anti-tumor effects. CAR-NK cells can also avoid some deficiencies in CAR-T cell therapy, a research hotspot in tumor immunity. This article summarizes the preclinical research status of CAR-NK cells in glioblastoma and the problems and challenges faced by CAR-NK in glioblastoma.

Objectives To study the factors that influence the 6-minute walking distance (6MWD) among older patients with chronic heart failure. Methods This was a single-center, retrospective, observational study. A total of 123 patients from the First Affiliated Hospital of Nanjing Medical University was selected. The factors associated with the 6MWD were analyzed using Pearson correlation analysis and multivariate linear regression. Results The 6MWD of older patients was negatively correlated with age, fall risk, nutritional score, frailty, and depression but was positively correlated with educational level, fall efficacy, self-care ability, and plasma albumin. The results of independent variable multiple linear regression analysis showed that age (β = −0.098), fall risk (β = −0.262), fall efficacy (β = 0.011), self-care ability (β = −0.021), nutrition (β = −0.405), frailty (β = −0.653), and plasma albumin (β = 0.127) influenced the 6MWD. Conclusions The 6MWD of older patients with chronic heart failure was related to age, self-care ability, fall risk, nutrition, frailty, and depression.

ObjectiveTo compare the differential metabolites in the brain tissue of aged marmosets after long-term anesthesia (≥ 6 h) and the serum of elderly patients by metabolomics methods.MethodsSix aged marmosets (≥ 8 years old) were divided into two groups: anesthesia and control. The aged monkeys in the anesthesia group were induced with 6–8% sevoflurane and 100% oxygen (2 l/min) for 1–2 min and maintained with 1.5–2.5% sevoflurane and 100% oxygen (2 l/min) for 6 h. In the control group (n = 3), anesthesia was only induced under the same conditions for 1–2 min. The prefrontal cortex tissues of the two groups of aged marmosets were collected for metabolomics detection. Twenty-nine elderly patients (≥ 65 years old) who had undergone surgical anesthesia for more than 6 h were enrolled. Serum samples were collected before and on the first day after surgery for metabolomics analysis. Differential metabolites were compared between human serum and marmoset brain tissue.ResultsThe changes in lactate and xanthurenic acid in the serum of elderly patients were consistent with those in the brain tissue of aged marmoset monkeys, that is, lactate was up-regulated and xanthurenic acid was down-regulated. However, serum levels of 5-methylterahydrofolic acid and leucine were down-regulated in elderly patients after anesthesia. In contrast, 5-methylterahydrofolic acid and leucine levels were up-regulated in the prefrontal cortex of aged marmosets compared with control marmosets. Furthermore, glycolysis/gluconeogenesis and pentose phosphate pathway were both significantly enriched in the prefrontal cortex of aged marmosets and serum of elderly patients after surgery.ConclusionThe changes of serum metabolites in elderly patients are not exactly the same as the metabolic changes of brain tissues in aged marmosets. The metabolic changes in serum lactate and xanthurenic acid levels can reflect brain tissue metabolism. The enrichment pathways of differential metabolites in the serum of elderly patients and the brain tissue of aged marmosets were partially the same.

Background: Unwanted pregnancies cause some type of stress in women, which negatively impacts their way of life. It is important to recognize this type of stress and consider potential interventions. We aimed to comprehend the factors influencing married and parous women’s fertility decisions facing pregnant unintentionally, to provide a reference point for health care, and policy development. Methods: 44 married and parous women with unintended pregnancies who visited a tertiary hospital in Suzhou from May 2021 to July 2021 were chosen using a combination of purposive and theoretical sampling techniques for semi-structured, open-ended interviews. The Lazarus stress-coping model was used to construct the central theme of the analysis, which was “stress-coping style for fertility decision-making among married and parous women with unwanted pregnancy”. The model is divided into three stages: identifying re-fertility stressors, assessing re-fertility coping skills, and making decisions. Results: It takes the combined efforts of society, healthcare, families, and couples to ensure that married and parous women feel secure about having another child. Social support, medical care, and family sharing are all significant factors in the decision to have a child with an unwanted pregnancy. Conclusions: To increase people’s internal motivation to have more children and to support balanced population development, we must first create a healthy and favorable environment for fertility in society.

Abstract Odorant-binding proteins (OBPs), as they occur in insects, form a distinct class of proteins that apparently has no closely related representatives in other animals. However, ticks, mites, spiders and millipedes contain genes encoding proteins with sequence similarity to insect OBPs. In this work, we have explored the structure and function of such non-insect OBPs in the mite Varroa destructor, a major pest of honey bee. Varroa OBPs present six cysteines paired into three disulphide bridges, but with positions in the sequence and connections different from those of their insect counterparts. VdesOBP1 structure was determined in two closely related crystal forms and appears to be a monomer. Its structure assembles five α-helices linked by three disulphide bridges, one of them exhibiting a different connection as compared to their insect counterparts. Comparison with classical OBPs reveals that the second of the six α-helices is lacking in VdesOBP1. Ligand-binding experiments revealed molecules able to bind only specific OBPs with a moderate affinity, suggesting that either optimal ligands have still to be identified, or post-translational modifications present in the native proteins may be essential for modulating binding activity, or else these OBPs might represent a failed attempt in evolution and are not used by the mites.

ObjectiveIn the lipid-rich brain, lipids performed signaling processes associated with the control system of the cell cycle, stress, and inflammatory reactions, as well as maintained brain and cellular homeostasis. The effects of general anesthesia on brain impairment in the elderly were controversial and complex. The study sought to evaluate the effect of lipid metabolism in the brain of aged marmosets and mice under long-term exposure to sevoflurane.MethodsA total of 6 marmosets over 8-year-old and 10 mice aged 18 months were divided into the sevoflurane anesthesia and control groups, respectively. Marmosets in the sevoflurane anesthesia group were exposed to 1.5–2.5% sevoflurane and 100% O2 for 6 h. Mice anesthetized with sevoflurane were exposed to 3% sevoflurane and 60% O2 for 6 h. All prefrontal cortex tissues of marmosets and mice were harvested for the analysis of lipidomics.ResultsCompared to the control group, we found that phosphatidylethanolamine (PE) (18:0/22:5), PE (16:0/22:5), PE (18:2/22:5), PE (14:0/22:5), and PE (18:1/22:5) increased in the prefrontal cortex of marmosets in the sevoflurane group, while triglyceride (TAG)56:5-fatty acid (FA) 20:4, TAG58:10-FA22:6, and TAG60:10-FA22:6 decreased. For aged mice, we indicated that lipid components phosphatidic acid (PA) (18:1/20:2) and TAG52:5-FA20:4 in the sevoflurane group increased, but PE (14:0/22:4), diglyceride (DAG) (16:1/18:2), and lysophosphatidylcholine (LPC) (16:1) + AcO decreased. More deeply, sevoflurane anesthesia resulted in the presence of 70 specific lipids in mice and marmosets. The enriched lipid subclasses were mainly monoacylglycerophosphoethanolamines and five other subclasses.ConclusionSevoflurane caused slight changes in lipid metabolism both in the aged brain of marmosets and mice. However, the pathways of lipid metabolism were not affected. The effects of sevoflurane on lipid metabolism in aged brains may differ among species.

The finite-element (FE) method for three-dimensional (3D) airborne electromagnetic (AEM) modeling can flexibly simulate complex geological structures at high accuracy. However, it has low efficiency and high computational requirements. To solve these problems, one needs to generate meshes more reasonably. In view of this, we develop an adaptive octree meshing scheme for frequency-domain AEM modeling. The octree meshes have the characteristics of regularity and flexibility, while the adaptive algorithm can effectively refine the mesh locally. In our adaptive mesh generation, the posterior errors and weighted coefficients are used to construct the final weighted posterior errors. We verify the accuracy of our method by comparing its results with semi-analytical solutions for a half-space model. Furthermore, we use the spectral-element (SE) method and our method to calculate EM responses for an abnormal block model and compare their computational costs. The results show that our adaptive scheme has obviously technical advantages over SE method for AEM modeling with multiple frequencies and multiple survey stations. Finally, we calculate a model with complex geological structures to verify the feasibility of our algorithm in complex geological circumstances.

Summary: Background: Little is known about the association between sarcopenia and cardiovascular disease (CVD) among middle-aged and older adults. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted cross-sectional and longitudinal analyses to investigate the association between sarcopenia status and CVD in middle-aged and older Chinese population. Methods: The sample comprised 15,137 participants aged at least 45 years from the CHARLS 2015. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 11,863 participants without CVD were recruited from the CHARLS 2015 and were followed up in 2018. Cox proportional hazards regression models were conducted to examine the effect of sarcopenia on CVD. Findings: The pre valence of CVD in total populations, no-sarcopenia, possible sarcopenia and sarcopenia individuals were 12.6% (1905/15,137), 10.0% (1026/10,280), 18.1% (668/3685), 18.0% (211/1172), respectively. Both possible sarcopenia [OR (95% CI): 1.29 (1.13–1.48)] and sarcopenia [1.72 (1.40–2.10)] were associated with CVD in total populations. During the 3.6 years of follow-up, 1,273 cases (10.7%) with incident CVD were identified. In the longitudinal analysis, individuals with the diagnosis of possible sarcopenia (HR:1.22, 95% CI: 1.05–1.43) and sarcopenia participants (HR:1.33, 95% CI: 1.04–1.71) were more likely to have new onset CVD than no-sarcopenia peers. Interpretation: Both possible sarcopenia and sarcopenia, assessed using the AWGS 2019 criteria, were associated with higher CVD risk among middle-aged and older Chinese adults. Funding: None.

Abstract Background Posttranslational modification of proteins by small ubiquitin like modifier (SUMO) proteins play an important role during the developmental process and in response to abiotic stresses in plants. However, little is known about SUMOylation in peanut (Arachis hypogaea L.), one of the world’s major food legume crops. In this study, we characterized the SUMOylation system from the diploid progenitor genomes of peanut, Arachis duranensis (AA) and Arachis ipaensis (BB). Results Genome-wide analysis revealed the presence of 40 SUMO system genes in A. duranensis and A. ipaensis. Our results showed that peanut also encodes a novel class II isotype of the SCE1, which was previously reported to be uniquely present in cereals. RNA-seq data showed that the core components of the SUMOylation cascade SUMO1/2 and SCE1 genes exhibited pod-specific expression patterns, implying coordinated regulation during pod development. Furthermore, both transcripts and conjugate profiles revealed that SUMOylation has significant roles during the pod development. Moreover, dynamic changes in the SUMO conjugates were observed in response to abiotic stresses. Conclusions The identification and organization of peanut SUMO system revealed SUMOylation has important roles during stress defense and pod development. The present study will serve as a resource for providing new strategies to enhance agronomic yield and reveal the mechanism of peanut pod development.

Background: Little is known about whether sarcopenia predicts incident depressive symptoms in older adults. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted cross-sectional and longitudinal analyses to estimate the association between sarcopenia and depressive symptoms among older adults.Methods: The sample comprised 7,706 participants aged at least 60 years (50.6% women; mean age 68.0 ± 6.5) from the CHARLS 2015. Based on the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria, sarcopenia status was classified into three types: no-sarcopenia, possible sarcopenia, and sarcopenia. Depressive symptoms were assessed using the validated 10-items of the Center for Epidemiologic Studies Depression Scale. A cross-sectional analysis was used to examine the relationship between sarcopenia status and depressive symptoms. A total of 4,652 participants without depressive symptoms were recruited from the same cohort in 2015 and were followed up in 2018. Cox proportional hazards regression models were conducted to examine the effect of sarcopenia status on subsequent depressive symptoms with the report of hazard ratio (HR).Results: The prevalence of depressive symptoms in total populations, no-sarcopenia, possible sarcopenia, and sarcopenia individuals were 27.1% (2085/7706), 21.5% (927/4310), 33.6% (882/2627), and 35.9% (276/769), respectively. Both possible sarcopenia (OR: 1.75, 95% CI: 1.46–2.10) and sarcopenia (OR: 1.64, 95% CI: 1.23–2.19) were positively associated with higher odds of depressive symptoms (all p < 0.01). During the 3.7 years of follow-up, 956 cases (20.6%) with incident depressive symptoms were identified. In the longitudinal analysis, individuals with the diagnosed possible sarcopenia (HR: 1.27, 95% CI: 1.01–1.58) and sarcopenia participants (HR: 1.49, 95% CI: 1.06–2.09) were more likely to have new onset depressive symptoms than no-sarcopenia peers.Conclusions: Both possible sarcopenia and sarcopenia, assessed using the AWGS 2019 criteria, were independent predictors for the occurrence of depressive symptoms among Chinese older adults. Our findings provided new evidence supporting the longitudinal connection between sarcopenia and mental health problems, it also provides further justification for timely identification and management of both possible sarcopenia and sarcopenia as part of comprehensive strategies to fight against depressive symptoms.

BackgroundMicrotubule-associated proteins (MAPs) have been considered to play significant roles in the tumor evolution of non-small cell lung cancer (NSCLC). Nevertheless, mRNA transcription levels and prognostic value of distinct MAPs in patients with NSCLC remain to be clarified.MethodsIn this study, the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA) database, and Human Protein Atlas were utilized to analyze the relationship between mRNA/protein expression of different MAPs and clinical characteristics in NSCLC patients, including tumor type and pathological stage. The correlation between the transcription level of MAPs and overall survival (OS) of NSCLC patients was analyzed by Kaplan–Meier plotter. Besides, 50 frequently altered neighbor genes of the MAPs were screened out, and a network has been constructed via the cBioPortal and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) dataset. Meanwhile, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the expression data of MAPs and their 50 frequently altered neighbor genes in NSCLC tissues. Furthermore, The Cancer Immunome Atlas (TCIA) was utilized to analyze the relationship between MAP expression and the response to immunotherapy. Finally, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to verify the expression of MAPs in 20 patients with NSCLC.ResultsThe present study discovered that the mRNA transcription levels of MAP7/7D2 were enriched in NSCLC tissues, while those of the MAP2/4/6/7D3 were lower in NSCLC specimens than those in control specimens. The mRNA transcription level of MAP6 was significantly associated with the advanced stage of NSCLC. Besides, survival analysis indicated that higher mRNA expressions of MAP2/4/6/7/7D3 were correlated considerably with favorable OS of NSCLC patients, whereas increased mRNA expression levels of MAP1A/1S were associated with poor OS. Moreover, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was significantly correlated with immunophenoscore (IPS) in NSCLC patients.ConclusionsOur analysis indicated that MAP1A/1S could serve as potential personalized therapeutic targets for patients with NSCLC, and the enriched MAP2/4/6/7/7D3 expression could serve as a biomarker for favorable prognosis in NSCLC. Besides, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was closely related to the response to immunotherapy. Taken together, MAP expression has potential application value in the clinical treatment and prognosis assessment of NSCLC patients, and further verifiable experiments can be conducted to verify our results.

Economic development is accompanied by the production of pollutants. Coordinating the relationship between economic development and haze pollution is of great significance to future development in China. Based on the original decoupling index (Tapio decoupling index), this study developed a new decoupling index that overcomes some of the original defects and highlights the trends to a better extent. It also analyzes the transformation relationship among the new decoupling index, the original decoupling index and the EKC curve. Firstly, we compared the changing trends of the two decoupling indexes and then derived the factors that influence the new and original decoupling indexes based on C-D-Kaya equation. Finally, we compared the factors influencing the two decoupling indexes from the perspective of decomposition analysis and measurement. The conclusions are as follows: (1) Based on the limit theory, the boundary point for relative decoupling and absolute decoupling derived from the original decoupling index can be used to determine the inflection point of the EKC curve. The new decoupling index can also reflect this property. At the inflection point of the EKC curve, the ratio of the new decoupling index of two adjacent periods satisfies equation (12), which is only related to GDP. (2) In 2003, the new decoupling index showed a downward trend, and the fluctuation was smaller than that of the original decoupling index. The original decoupling index is more sensitive to short-term policies than the new decoupling index, but the new decoupling index is more conducive to the comprehensive analysis of China’s decoupling trend. (3) After decomposing the new decoupling index and the original decoupling index, per capita GDP and the emission coefficient are the largest positive and negative driving forces, respectively. However, the trend of the contribution made by each factor was more obvious when the new decoupling index was used. The emission coefficient for Shandong made the largest negative contribution, and the per capita GDP for Shanxi made the greatest positive contribution. (4) The geographically and temporally weighted regression (GTWR) analysis showed that the fitting degree of the new decoupling index is much higher than that of the original decoupling index. The analysis of the influencing factors affecting the new decoupling index showed that there was temporal and spatial heterogeneity among the factors in east, middle, and west China, and there were significant differences in the impacts due to energy structure, energy intensity, technological progress, and urban population factors, respectively. These findings will significantly improve the formulation of efficient and pertinent policies for energy conservation and haze reduction.

The dried stigmas of Crocus sativus, commonly known as saffron, are consumed largely worldwide because it is highly valuable in foods and has biological activities beneficial for health. Saffron has important economic and medicinal value, and thus, its planting area and global production are increasing. Petals, which are a by-product of the stigmas, have not been fully utilized at present. We compared the metabolites between the stigmas and petals of C. sativus using a non-targeted metabolomics method. In total, over 800 metabolites were detected and categorized into 35 classes, including alkaloids, flavonoids, amino acids and derivatives, phenols and phenol esters, phenylpropanoids, fatty acyls, steroids and steroid derivatives, vitamins, and other metabolites. The metabolite composition in the petals and stigmas was basically similar. The results of the study showed that the petals contained flavonoids, alkaloids, coumarins, and other medicinal components, as well as amino acids, carbohydrates, vitamins, and other nutritional components. A principal components analysis (PCA) and an orthogonal partial least-squares discriminant analysis (OPLS-DA) were performed to screen the different metabolic components. A total of 339 differential metabolites were identified, with 55 metabolites up-regulated and 284 down-regulated. The up-regulated metabolites, including rutin, delphinidin-3-O-glucoside, isoquercitrin, syringaresinol-di-O-glucoside, dihydrorobinetin, quercetin, and gallocatechin, were detected in the petals. The down-regulated metabolites were mainly glucofrangulin B, acetovanillone, daidzein, guaiazulene, hypaphorine, indolin-2-one, and pseudouridine. KEGG annotation and enrichment analyses of the differential metabolites revealed that flavonoid biosynthesis, amino acids biosynthesis, and arginine and proline metabolism were the main differentially regulated pathways. In conclusion, the petals of C. sativus are valuable for medicine and foods and have potential utility in multiple areas such as the natural spice, cosmetic, health drink, and natural health product industries.

Norepinephrine (NE) is often administered during the perioperative period of liver transplantation to address hemodynamic instability and to improve organ perfusion and oxygen supply. However, its role and safety profile have yet to be evaluated in pediatric living donor liver transplantation (LDLT). We hypothesized that intraoperative NE infusion might affect pediatric LDLT outcomes. A retrospective study of 430 pediatric patients (median [interquartile range] age, 7 [6.10] months; 189 [43.9%] female) receiving LDLT between 2014 and 2016 at Renji Hospital was conducted. We evaluated patient survival among recipients who received intraoperative NE infusion (NE group, 85 recipients) and those that did not (non-NE group, 345 recipients). The number of children aged over 24 months and weighing more than 10 kg in NE group was more than that in non-NE group. And children in NE group had longer operative time, longer anhepatic phase time and more fluid infusion. After multivariate regression analysis and propensity score regression adjusting for confounding factors to determine the influence of intraoperative NE infusion on patient survival, the NE group had a 169% more probability of dying. Although there was no difference in mean arterial pressure changes relative to the baseline between the two groups, we did observe increased heart rates in NE group compared with those of the non-NE group at anhepatic phase (P=0.025), neohepatic phase (P=0.012) and operation end phase (P=0.017) of the operation. In conclusion, intraoperative NE infusion was associated with a poorer prognosis for pediatric LDLT recipients. Therefore, we recommend the application of NE during pediatric LDLT should be carefully re-considered.

Polyploidy plays an important role in crop improvement. Polyploid plants, particularly those produced through unreduced gametes (2n gametes), show increased organ size, improved buffering capacity for deleterious mutations, and enhanced heterozygosity and heterosis. Induced polyploidy has been widely used for improving floriculture crops, however, there are few reported sexual polyploid plants in the floriculture industry. This study evaluated nine cultivars of Cymbidium Swartz and discovered that 2n male gametes occurred in this important orchid. Depending on cultivars, 2n male gamete formation frequencies varied from 0.15 to 4.03%. Interspecific hybrids generally produced more 2n male gametes than traditional cultivars. To generate sexual polyploid plants, seven pairs of crosses were made, which produced five triploid and two tetraploid hybrids. Two triploid hybrids were evaluated for in vitro regeneration and growth characteristics. Compared to the diploid parents, the triploids were more easily regenerated through rhizomes or protocorms, and regenerated plants had improved survival rates after transplanting to the greenhouse. Furthermore, the sexual polyploid plants had more compact growth style, produced fragrant flowers, and demonstrated heterosis in plant growth. Through this study, a reliable protocol for selection of appropriate parents for 2n gamete production, ploidy level evaluation, in vitro culture of polyploid progenies, and development of new polyploid cultivars was established. Our study with Cymbidium suggests that the use of 2n gametes is a viable approach for improving floriculture crops.

We present a wavelet finite-element method (WFEM) based on B-spline wavelets on the interval (BSWI) for three-dimensional (3D) frequency-domain airborne EM modeling using a secondary coupled-potential formulation. The BSWI, which is constructed on the interval (0, 1) by joining piecewise B-spline polynomials between nodes together, has proved to have excellent numerical properties of multiresolution and sparsity and thus is utilized as the basis function in our WFEM. Compared to conventional basis functions, the BSWI is able to provide higher interpolating accuracy and boundary stability. Furthermore, due to the sparsity of the wavelet, the coefficient matrix obtained by BSWI-based WFEM is sparser than that formed by general FEM, which can lead to shorter solution time for the linear equations system. To verify the accuracy and efficiency of our proposed method, we ran numerical experiments on a half-space model and a layered model and compared the results with one-dimensional (1D) semi-analytic solutions and those obtained from conventional FEM. We then studied a synthetic 3D model using different meshes and BSWI basis at different scales. The results show that our method depends less on the mesh, and the accuracy can be improved by both mesh refinement and scale enhancement.

Spider mites are one of the major agricultural pests, feeding on a large variety of plants. As a contribution to understanding chemical communication in these arthropods, we have characterized a recently discovered class of odorant-binding proteins (OBPs) in Tetranychus urticae. As in other species of Chelicerata, the four OBPs of T. urticae contain six conserved cysteines paired in a pattern (C1–C6, C2–C3, C4–C5) differing from that of insect counterparts (C1–C3, C2–C5, C4–C6). Proteomic analysis uncovered a second family of OBPs, including twelve members that are likely to be unique to T. urticae. A three-dimensional model of TurtOBP1, built on the recent X-ray structure of Varroa destructor OBP1, shows protein folding different from that of insect OBPs, although with some common features. Ligand-binding experiments indicated some affinity to coniferyl aldehyde, but specific ligands may still need to be found among very large molecules, as suggested by the size of the binding pocket.

An electronic biosensor for odors was assembled by immobilizing the silk moth Bombyx mori pheromone binding protein (BmorPBP1) on a reduced graphene oxide surface of a field-effect transistor. At physiological pH, the sensor detects the B. mori pheromones, bombykol and bombykal, with good affinity and specificity. Among the other odorants tested, only eugenol elicited a strong signal, while terpenoids and other odorants (linalool, geraniol, isoamyl acetate, and 2-isobutyl-3-methoxypyrazine) produced only very weak responses. Parallel binding assays were performed with the same protein and the same ligands, using the common fluorescence approach adopted for similar proteins. The results are in good agreement with the sensor’s responses: bombykol and bombykal, together with eugenol, proved to be strong ligands, while the other compounds showed only poor affinity. When tested at pH 4, the protein failed to bind bombykol both in solution and when immobilized on the sensor. This result further indicates that the BmorPBP1 retains its full activity when immobilized on a surface, including the conformational change observed in acidic conditions. The good agreement between fluorescence assays and sensor responses suggests that ligand-binding assays in solution can be used to screen mutants of a binding protein when selecting the best form to be immobilized on a biosensor.

Strategies for insect population control are currently targeting chemical communication at the molecular level. The diamondback moth Plutella xylostella represents one of the most serious pests in agriculture, however detailed information on the proteins mediating olfaction in this species is still poor. This species is endowed with a repertoire of a large number of olfactory receptors and odorant binding proteins (OBPs). As a contribution to map the specificities of these chemical sensors in the moth and eventually unravel the complexity of chemodetection, we have measured the affinities of three selected OBPs to a series of potential odorants. Three proteins are highly divergent in their amino acid sequences and show markedly different expression profiles. In fact, PxylOBP3 is exclusively expressed in the antennae of both sexes, PxylOBP9 is male specific and present only in antennae and reproductive organs, while PxylOBP19, an unusual OBP with nine cysteines, is ubiquitously present in all the organs examined. Such expression pattern suggests that the last two proteins may be involved in non-chemosensory functions. Despite such differences, the three OBPs exhibit similar binding spectra, together with high selectivity. Among the 26 natural compounds tested, only two proved to be good ligands, retinol and coniferyl aldehyde. This second compound is particularly interesting being part of the chemical pathway leading to regeneration of lignin, one of the defense strategies of the plant against insect attack, and might find applications as a repellent for P. xylostella and other pests.

Niemann-Pick proteins type C2 (NPC2) are carriers of cholesterol in vertebrates, with a single member in each species. The high sequence conservation between mammals and across vertebrates is related to their common function. In contrast, NPC2 proteins in arthropods have undergone extensive duplication and differentiation, probably under environmental pressure, and are likely to have different functions. Recent studies have suggested that in arthropods these proteins might act as carriers for semiochemicals and other hydrophobic compounds. In this study we focused on the function of a specific NPC2 gene in the moth Helicoverpa armigera (HarmNPC2-1). This protein binds several flavonoids with micromolar dissociation constants. The best ligand was gossypol, present in cotton, one of the main host plants for H. armigera. Western blot revealed the presence of HarmNPC2-1 in different parts of the body, including the antennae, proboscis, and abdomen. In the antennae, in situ hybridization experiments produced strong staining in auxiliary cells at the base of sensilla trichodea, basiconica, coeloconica, and chaetica. Immunocytochemistry confirmed the expression of the protein in sensilla chaetica. Our results support a role of semiochemical carriers for NPC2 proteins in insects and indicate such proteins as new targets for insecticide-free pest population control.

Water deficit is a key factor to induce flowering in many woody plants, but reports on the molecular mechanisms of floral induction and flowering by water deficit are scarce. Here, we analyzed the morphology, cytology, and different hormone levels of lemon buds during floral inductive water deficits. Higher levels of ABA were observed, and the initiation of floral bud differentiation was examined by paraffin sections analysis. A total of 1638 differentially expressed genes (DEGs) were identified by RNA sequencing. DEGs were related to flowering, hormone biosynthesis, or metabolism. The expression of some DEGs was associated with floral induction by real-time PCR analysis. However, some DEGs may not have anything to do with flowering induction/flower development; they may be involved in general stress/drought response. Four genes from the phosphatidylethanolamine-binding protein family were further investigated. Ectopic expression of these genes in Arabidopsis changed the flowering time of transgenic plants. Furthermore, the 5′ flanking region of these genes was also isolated and sequence analysis revealed the presence of several putative cis-regulatory elements, including basic elements and hormone regulation elements. The spatial and temporal expression patterns of these promoters were investigated under water deficit treatment. Based on these findings, we propose a model for citrus flowering under water deficit conditions, which will enable us to further understand the molecular mechanism of water deficit-regulated flowering in citrus.Highlight:Based on gene activity during floral inductive water deficits identified by RNA sequencing and genes associated with lemon floral transition, a model for citrus flowering under water deficit conditions is proposed.

Odour perception has been the object of fast growing research interest in the last three decades. Parallel to the study of the corresponding biological systems, attempts are being made to model the olfactory system with electronic devices. Such projects range from the fabrication of individual sensors, tuned to specific chemicals of interest, to the design of multipurpose smell detectors using arrays of sensors assembled in a sort of artificial nose. Recently, proteins have attracted increasing interest as sensing elements. In particular, soluble olfaction proteins, including odorant-binding proteins (OBPs) of vertebrates and insects, chemosensory proteins (CSPs) and Niemann-Pick type C2 (NPC2) proteins possess interesting characteristics for their use in sensing devices for odours. In fact, thanks to their compact structure, their soluble nature and small size, they are extremely stable to high temperature, refractory to proteolysis and resistant to organic solvents. Moreover, thanks to the availability of many structures solved both as apo-proteins and in complexes with some ligands, it is feasible to design mutants by replacing residues in the binding sites with the aim of synthesising proteins with better selectivity and improved physical properties, as demonstrated in a number of cases.

Since the first attempts to mimic the human nose with artificial devices, a variety of sensors have been developed, ranging from simple inorganic and organic gas detectors to biosensing elements incorporating proteins of the biological olfactory system. In order to design a device able to mimic the human nose, two major issues still need to be addressed regarding the complexity of olfactory coding and the extreme sensitivity of the biological system. So far, only 50 of the approximately 300–400 functioning olfactory receptors have been de-orphanized, still a long way from breaking the human olfactory code. On the other hand, the exceptional sensitivity of the human nose is based on amplification mechanisms difficult to reproduce with electronic circuits, and perhaps novel approaches are required to address this issue. Here, we review the recent literature on chemical sensing both in biological systems and artificial devices, and try to establish the state-of-the-art towards the design of an electronic nose.

This paper presents a simplified finite‐control‐set model predictive control (S‐FCS‐MPC) based on fast vector selection method in a three‐level VIENNA rectifier. This method features a high‐power factor, a low input current THD as a well‐controlled DC‐link voltage with fewer redundant vectors and lower computational load. Moreover, the converter with the proposed control technique exhibits a faster dynamic response in terms of input current and DC‐link voltage compared with conventional finite‐control‐set model predictive control (C‐FCS‐MPC). In addition, the average switching frequency can be effectively reduced due to fewer switching times in a subset sector using the proposed method, which means fewer switching losses. Finally, the operation principle of the proposed algorithm has been analysed and an execution time comparison between S‐FCS‐MPC and C‐FCS‐M has been undertaken. The effectiveness of the proposed control technique has been validated using both simulation and experimental results. [ABSTRACT FROM AUTHOR]

Objective: Defects in the human solute carrier family 26 member 4 (SLC26A4) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC26A4 mutations in Chinese patients with CH and analyze the function of the mutations. Methods: Patients with primary CH were screened for 21 CH candidate genes mutations by targeted next-generation sequencing. All the exons and exon-intron boundaries of SLC26A4 were identified and analyzed. The function of six missense mutation in SLC26A4 were further investigated in vitro. Results: Among 273 patients with CH, seven distinct SLC26A4 heterozygous mutations (p.S49R, p.I363L, p.R409H, p.T485M, p.D661E, p.H723R, c.919-2A>G) were identified in 10 patients (3.66%, 10/273). In vitro experiments showed that mutation p.I363L, p.R409H, p.H723R affect the membrane location and ion transport of SLC26A4, while p.S49R did not. Mutation p.T485M and p.D661E only affected ion transport, but had no effect on the membrane location. Conclusion: The prevalence of SLC26A4 mutations was 3.66% in Chinese patients with CH. Five mutations (p.I363L, p.R409H, p.T485M, p.D661E and p.H723R) impaired the membrane location or ion transport function of SLC26A4, suggesting important roles for Ile363, Arg409, Thr485, Asp661, and His723 residues in SLC26A4 function. As all variants identified were heterozygous, the pathogenesis of these patients cannot be explained, and the pathogenesis of these patients needs further study. [ABSTRACT FROM AUTHOR]

A dpppy-protected (dpppy = 2,6-bis(diphenylphosphino)pyridine) d10–d10 heterooctanuclear cluster complex [Ag3Cu5(ebzcz)6(dpppy)3](ClO4)2 (Hebzcz = 1-(3,6-di-tert-butylcarbazol-9-yl)-4-ethynylbenzene) was prepared by self-assembly reaction and characterized by single crystal X-ray diffraction. The diphosphine-supported Ag3Cu5 cluster structure is highly stabilized through substantial Cu–Ag and Cu–Cu intermetallic interactions. Since the Ag3Cu5 cluster is sufficiently shielded by bulky ligands (three ebzcz and three dpppy), thermally non-radiative relaxation is strongly prohibited so as to give brilliant photoluminescence under ambient conditions. As revealed by TD-DFT studies, the luminescence arises from metal cluster-centred 3[d → p/s] and 3[π (ebzcz) → π* (dpppy)] 3LLCT (ligand-to-ligand charge transfer) transitions. Taking advantage of Ag3Cu5 cluster complex as a phosphorescent dopant, a high-efficiency solution-processed organic light-emitting diode is achieved with a peak current efficiency of 38.1 cd A−1, a power efficiency of 29.9 lm W−1 and an external quantum efficiency of 14.7%. [ABSTRACT FROM AUTHOR]

Using relativistic density-functional theory calculations, we investigate magnetocrystalline anisotropy energy (MAE) of the poly(vinylidene fluoride)(PVDF)/Fe/Cu/Ag heterostructure. We find that MAE of this heterostructure can be flexibly manipulated by the ferroelectric polarization of PVDF. In particular, by carefully designing the interface structure, we demonstrate that the ferroelectric polarization reversal can switch the easy axis of the Fe layer from in-plane to out-of-plane, due to the surface/interface magnetoelectric effect. We expect such strategy would be beneficial to electric-field controlled magnetic data storage. [ABSTRACT FROM AUTHOR]

Dysfunctions of gene transcription and translation in the nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown or Ago2 overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 component n-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targeting Ubr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: Cephalosporin C acylase (CA) plays a key role in the one‐step enzymatic catalysis of 7‐aminocephalosporanic acid (7‐ACA) from Cephalosporin C (CPC). However, the synthesis of 7‐ACA needs low‐temperature conditions: unless catalyzed at 13 °C, it will produce large amounts of undesired products. Unfortunately, cephalosporin CA catalyzes CPC to 7‐ACA directly at a very low efficiency at 13 °C or below. RESULTS: In this work, multiple techniques including molecular docking, multi‐site random‐directed mutagenesis and high‐throughput screening were adopted and combined into an engineering strategy to improve the cold adaptability of CA. Thus, the best‐hit mutant 9H9 containing mutations of P238G, P449G and P582G was screened revealing a specific activity of 1.94 U mg−1 at 13 °C, which is 1.3‐fold higher than that of the parent. Compared with the parent, the mutant 9H9 shows a slight decline in the Km value and significant improvement in the Vmax value. In addition, the yield of 7‐ACA catalyzed by 9H9 was obviously higher than that of the parent at low temperature. CONCLUSION: A new and viable strategy was established for improving the cold adaptability of CA and investigations were made into enhancing its conformational flexibility. This might lay a solid foundation for future study and industrial application of CAs. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The giant panda Ailuropoda melanoleuca belongs to the family of Ursidae; however, it is not carnivorous, feeding almost exclusively on bamboo. Being equipped with a typical carnivorous digestive apparatus, the giant panda cannot get enough energy for an active life and spends most of its time digesting food or sleeping. Feeding and mating are both regulated by odors and pheromones; therefore, a better knowledge of olfaction at the molecular level can help in designing strategies for the conservation of this species. In this context, we have identified the odorant-binding protein (OBP) repertoire of the giant panda and mapped the protein expression in nasal mucus and saliva through proteomics. Four OBPs have been identified in nasal mucus, while the other two were not detected in the samples examined. In particular, AimelOBP3 is similar to a subset of OBPs reported as pheromone carriers in the urine of rodents, saliva of the boar, and seminal fluid of the rabbit. We expressed this protein, mapped its binding specificity, and determined its crystal structure. Structural data guided the design and preparation of three protein mutants bearing single-amino acid replacements in the ligand-binding pocket, for which the corresponding binding affinity spectra were measured. We also expressed AimelOBP5, which is markedly different from AimelOBP3 and complementary in its binding spectrum. By comparing our binding data with the structures of bamboo volatiles and those of typical mammalian pheromones, we formulate hypotheses on which may be the most relevant semiochemicals for the giant panda. [ABSTRACT FROM AUTHOR]

MicroRNA-181a (miR-181a) is upregulated in osteosarcoma, and its overexpression promotes the proliferation and inhibits the apoptosis of osteosarcoma cells. However, the mechanism of miR-181a as an oncogene remains to be fully elucidated in osteosarcoma. Cleavage factor (CF) Im25 links alternative polyadenylation to glioblastoma tumor suppression, however, its role in osteosarcoma has not been reported. In the present study, it was confirmed that the expression of miR-181a was upregulated in osteosarcoma, and that silencing miR-181a inhibited the proliferation and promoted the apoptosis of osteosarcoma cells. miRNAs are short non-coding RNAs, which regulate target mRNAs by binding predominantly to the 3'untranslated region (3'UTR), inducing either translational repression or degradation of the target. In the present study, target genes of miR-181a were screened using miRanda, which is a commonly used prediction algorithm. It was found that miR-181a targeted the 3'UTR of CFIm25 mRNA. Subsequent experiments confirmed that miR-181a downregulated the expression of CFIm25 in osteosarcoma cells. Finally, it was demonstrated that the CFIm25 protein was also downregulated in osteosarcoma tissues, and inhibited the proliferation and promoted the apoptosis of the cells. Elucidating the roles of miR-181a and CFIm25 in osteosarcoma not only assists in further understanding the pathogenesis and progression of this disease, but also offers novel targets for effective therapies. [ABSTRACT FROM AUTHOR]

DNA 5-hydroxylmethylcytosine (5hmC) catalyzed by ten-eleven translocation methylcytosine dioxygenase (TET) occurs abundantly in neurons of mammals. However, the in vivo causal link between TET dysregulation and nociceptive modulation has not been established. Here, we found that spinal TET1 and TET3 were significantly increased in the model of formalin-induced acute inflammatory pain, which was accompanied with the augment of genome-wide 5hmC content in spinal cord. Knockdown of spinal TET1 or TET3 alleviated the formalin-induced nociceptive behavior and overexpression of spinal TET1 or TET3 in naive mice produced pain-like behavior as evidenced by decreased thermal pain threshold. Furthermore, we found that TET1 or TET3 regulated the nociceptive behavior by targeting microRNA-365-3p (miR-365-3p). Formalin increased 5hmC in the miR-365-3p promoter, which was inhibited by knockdown of TET1 or TET3 and mimicked by overexpression of TET1 or TET3 in naive mice. Nociceptive behavior induced by formalin or overexpression of spinal TET1 or TET3 could be prevented by downregulation of miR-365-3p, and mimicked by overexpression of spinal miR- 365-3p. Finally, we demonstrated that a potassium channel, voltage-gated eag-related subfamily H member 2 (Kcnh2), validated as a target of miR-365-3p, played a critical role in nociceptive modulation by spinal TET or miR-365-3p. Together, we concluded that TET-mediated hydroxymethylation of miR-365-3p regulates nociceptive behavior via Kcnh2. [ABSTRACT FROM AUTHOR]

Most of the ultrasonic gas flow-meters measure the gas flow rate by calculating the ultrasonic transmission time difference between the downstream and upstream. Ultrasonic energy attenuation occurs in the processes of the ultrasonic generation, conversion, transmission, and reception. Additionally, at the same time, the gas flow will also affect the ultrasonic propagation during the measurement, which results in the ultrasonic energy attenuation and the offset of ultrasonic propagation path. Thus, the ultrasonic energy received by the transducer is weaker. When the gas flow rate increases, this effect becomes more apparent. It leads to the measurement accuracy reduced, and the measurement range narrowed. An energy transfer model, where the ultrasonic gas flow-meter under without/with the gas flow, is established by adopting the statistical analysis and curve fitting based on a large amount of experimental data. The static sub model without the gas flow expresses the energy conversion efficiency of ultrasonic gas transducers, and the dynamic sub model with the gas flow reflects the energy attenuation pattern following the flow rate variations. The mathematical model can be used to determine the minimum energy of the excitation signal for meeting the requirement of specific measurement range, and predict the maximum measurable flow rate in the case of fixed energy of excitation signal. Based on the above studies, a method to enhance the excitation signal energy is proposed under the output power of the transmitting circuit being a finite value so as to extend the measurement rage of ultrasonic gas flow-meter. [ABSTRACT FROM AUTHOR]