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Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post-myocardial infarction (MI), causing regional hypoinnervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypoinnervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca 2+ -sensitive dyes. SNS was performed with electrical stimulation of the spinal cord, and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct region of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct versus remote region. Action potential duration (APD) dispersion and tendency for induction of ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI but not sham hearts. SNS decreased APD at 80% repolarization (APD 80 ) in MI but not sham hearts, whereas isoproterenol decreased APD 80 in both groups. Isoproterenol also shortened Ca 2+ transient duration at 80% repolarization in both groups but to a greater extent in MI hearts. Our data suggest that sympathetic remodeling post-MI is similar between rodents and rabbits, with CSPGs associated with sympathetic hypoinnervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underlie increased APD dispersion and tendency for VT/VF. NEW & NOTEWORTHY Here, we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypoinnervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between rodents and rabbits, with hypoinnervation likely associated with enhanced β-adrenergic sensitivity.

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post myocardial infarction (MI), causing regional hypo-innervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypo-innervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca 2+ -sensitive dyes. SNS was performed with electrical stimulation of the spinal cord and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct and border zone of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct vs. remote region. Action potential duration (APD) dispersion and susceptibility to ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI hearts but not in sham. SNS decreased APD 80 in MI but not sham hearts, while isoproterenol decreased APD 80 in both groups. Isoproterenol also shortened Ca 2+ transient duration (CaTD 80 ) in both groups but to a greater extent in MI hearts. Our data suggest sympathetic remodeling post-MI is similar between species, with CSPGs associated with sympathetic hypo-innervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underly increased APD dispersion and susceptibility for VT/VF., New & Noteworthy: Here we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypo-innervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between species, with hypo-innervation likely associated with enhanced β-adrenergic sensitivity.

Rabbits are especially susceptible to adverse effects related to surgery, which can lead to inappetence and gastrointestinal (GI) stasis. However, these adverse effects may be related to discomfort from the procedure, anesthesia, the analgesics used, and the stress of restraint for analgesic administration. Opioid and NSAID analgesics which are frequently used in rabbits, can contribute to these adverse effects. This study compared the clinical GI side effects of buprenorphine and carprofen to saline controls in New Zealand White rabbits after a nonsurgical anesthetic event. Nine rabbits (3 females and 6 males, aged 8 to 20 mo) were randomly rotated through 5 treatment groups with a 7-d washout period between treatments: anesthesia control (no treatment), buprenorphine (0.05 mg/kg SC every 12 h for 72 h), carprofen (5 mg/kg SC every 24 h for 72 h), twice daily saline control (equivalent volume to buprenorphine SC every 12 h for 72 h), and once daily saline control (equivalent volume to carprofen SC every 24 h for 72 h). All rabbits were anesthetized 5 times and received initial treatments on the day of anesthesia. Generalized linear mixed models were used to assess food intake, water intake, and fecal output score for 7 days after anesthesia. Analysis showed that buprenorphine-treated rabbits had a significant 4-d decrease in food intake and a 3-d decrease in fecal output score compared with baseline. None of the other treatment groups showed any changes in food intake or fecal output score compared with baseline. These findings demonstrate that in the absence of pain, buprenorphine significantly depresses food intake in rabbits and that restraint and injections have minimal effect on food intake despite the possibility of increased stress.

A combination product of human mesenchymal stem/stromal cells (MSCs) embedded in an extracellular matrix scaffold and preconditioned with hypoxia and the beta-adrenergic receptor antagonist, timolol, combined with sustained timolol application post implantation, has shown promising results for improving wound healing in a diabetic mouse model. In the present study, we extend those findings to the more translatable large animal porcine wound model and show that the combined treatment promotes wound reepithelialization in these excisional wounds by 40.2% and increases the CD31 immunostaining marker of angiogenesis compared with the matrix control, while maintaining an accumulated timolol plasma concentration below the clinically safe level of 0.3 ng/mL after the 15-day course of topical application. Human GAPDH was not elevated in the day 15 wounds treated with MSC-containing device relative to wounds treated with matrix alone, indicating that the xenografted human MSCs in the treatment do not persist in these immune-competent animals after 15 days. The work demonstrates the efficacy and safety of the combined treatment for improving healing in the clinically relevant porcine wound model., (© 2022 Wiley Periodicals LLC.)

A novel bacterium, designated NAS39 T , was isolated from the interfacial sediment of Taihu Lake in PR China and its taxonomic position was investigated by using a polyphasic approach. Cells of the isolate were Gram-stain-negative, aerobic, non-motile, catalase-positive, yellow and rod-shaped. Phylogenetic analyses based on 16S rRNA gene sequences supported that strain NAS39 T formed a cluster within the genus Flavobacterium , and was most closely related to Flavobacterium laiguense LB2P30 T (98.4 %), followed by Flavobacterium tiangeerense 0563 T (97.4 %). The average nucleotide identity values between strain NAS39 T and F. laiguense LB2P30 T and F. tiangeerense 0563 T were 82.5 and 75.3 %, respectively. The digital DNA-DNA hybridization values between strain NAS39 T and F. laiguense LB2P30 T and F. tiangeerense 0563 T were 40.9 and 18.6 %, respectively. The genomic DNA G+C content was 34.1 mol%. The major respiratory quinone was menaquinone-6. The dominant cellular fatty acids were iso-C 15 : 0 and summed feature 3 comprising C 16 : 1  ω7 c /C 16 : 1  ω6 c . The polar lipids comprised phosphatidyl ethanolamine, two amino lipids, three amino phospholipids and two unidentified lipids. Based on the phenotypic, chemotaxonomic, genotypic and phylogenetic characteristics, strain NAS39 T (=MCCC 1K06094 T =KACC 22328 T ) represents a novel species of the genus Flavobacterium , for which the name Flavobacterium taihuense sp. nov. is proposed.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg -1  · d -1 ) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg -1  · d -1 ) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Objective: To compare the accuracy of photogrammetry and conventional impression techniques for complete-arch implant rehabilitation. Methods: An edentulous maxillary stone cast containing 8 screw-retained implant abutment replicas was derived from a 74-year-old male patient who visited the Department of Dental Implant Center, Capital Medical University School of Stomatology in September 2019. The stone cast was copied through the open-tray splinted impression, and the copied cast was used as the master cast for this study. The abutment-level impressions of master cast were made by photogrammetry (PG) and the conventional impression technique (CNV) by one attending doctor. Group PG: after which scan bodies were connected to each implant replica, a photogrammetry system was used to obtain digital impressions of the master cast ( n =10); Group CNV: conventional open-tray splinted impression technique was performed to fabricate conventional definitive casts ( n =10). After connecting the scan bodies onto each implant replicas, the master cast and the 10 definitive casts from group CNV were digitized with a laboratory reference scanner. All data of group PG, group CNV and mater cast were saved as ".stl" files. For all test scans and reference scan, the three-dimensional information of scan bodies were converted to implant abutment replicas using a computer aided design software (Exocad). The data of the group PG and the group CNV were respectively registered with the reference data (trueness analysis) and pairwise within group (precision analysis) for accuracy evaluation in a three-dimensional analysis software (Geomagic Control X). Results: The trueness and precision of group PG [(17.33±0.34) and (2.50±0.79) μm ] were significantly statistically better than those of group CNV [(24.30±4.16) and (26.12±4.54) μm] respectively ( t =-5.29 and -34.35, P <0.001). Conclusions: For complete-arch implant abutment-level impression, photogrammetry produces significantly better accuracy than conventional impression technique.

Domestic swine have become important large animal models for dermatologic and wound studies owing to the similarity of their skin architecture to that of human skin. To improve on current porcine wound protocols and accomplish postoperational daily wound care or treatment in a welfare-centered, low-stress setting, we developed a unique sling-training program using a commercially available Panepinto-like sling in combination with positive reinforcement of desired behaviors. Training using these methods is initiated during the acclimation period of 7-10 days before the initial surgical manipulation and continued throughout project-specific treatments for the duration of the study. Using this protocol, daily treatments can be administered without additional anesthesia while the animals rest in the sling with the administration of simultaneous nutritional enrichment. This low-stress handling program successfully facilitates the postoperational treatments and wound care without the use of potentially confounding anesthesia or sedation. It has a wide range of potential applications in translational medicine and in data acquisition from a resting state where baseline readouts of unstressed animals can be achieved., (© 2021 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.)

Objectives: The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer., Methods: The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS., Results: There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P < 0.001) in patients with gastric cancer and 0.872 (P < 0.001) in those with colorectal cancer., Conclusion: HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia., Methods: We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups., Results: In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups., Conclusion: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia.

Flavonoids are important secondary metabolites that exist in many medicinal plants. Flavonoid glycosyltransferases can transfer sugar moieties to their parent rings, producing various flavonoid glycosides with significant pharmacological activities. Here, we report the molecular cloning of the O-glycosyltransferase TwUGT2 from Tripterygium wilfordii and its catalytic activity was explored by heterologous expression in E. coli . The results showed that TwUGT2 has specific glycosyltransferase activity towards C-3 and 7 hydroxyl groups of flavonoids, thereby converting quercetin and pinocembrin into isoquercitrin and pinocembrin 7-O-beta-D-glucoside, respectively. The identification of TwUGT2 will provide a useful molecular tool for synthetic biology and contribute to drug discovery.[Formula: see text].

Objective: Although there is international consensus regarding the importance of cachexia, no tools exist, to our knowledge, for cachexia screening among patients with cancer. The aim of this study was to evaluate whether patients with cancer and cachexia could be identified using the four most commonly used nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS)-2002, the Malnutrition Screening Tool (MST), and the Short Nutritional Assessment Questionnaire (SNAQ)., Methods: Clinical data were prospectively collected for patients who underwent elective radical gastrectomy for gastric cancer in two large centers between August 2014 and February 2018. Patients were also screened using the MUST, NRS-2002, MST, and SNAQ tools. The screening results were subsequently compared with the international consensus diagnostic criteria for cancer cachexia., Results: A total of 1001 patients were evaluated, including 363 patients (36.3%) with cancer cachexia. Among the patients "at nutritional risk" based on each tool, the proportions of cachexia were 87.3% for the MUST tool, 84.3% for the MST tool, 76.6% for the NRS-2002 tool, and 54.3% for the SNAQ tool. The MST tool provided the largest area under the curve for identifying cancer cachexia (0.914; P < 0.001)., Conclusion: Among the tools examined, the MST had the greatest ability to detect cancer cachexia among patients with gastric cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microplastics have garnered much attention worldwide as a new emerging pollutant. As they are gradually detected in freshwaters, understanding how microplastics will behave during current drinking water treatment processes is urgently needed. In recent years, the shortened process with an ultrafiltration (UF) membrane has shown excellent performance because of its low land use and high water purification efficiency. In this work, the membrane performance induced by microplastics was investigated with a shortened UF membrane process. The results showed that membrane fouling was always induced by the cake layer before and after coagulating with microplastics. Owing to the small UF membrane pore size ( d <0.1 μm), slight membrane fouling was caused by microplastics ( d <5 mm) alone. However, although the loose cake layer was formed because of the existence of flocs, the cyberspace formed by flocs was easily entered by small microplastics with increasing coagulant dosage. As a result, server membrane fouling was induced because of the formation of a dense cake layer. It was shown that the specific membrane flux induced by flocs alone was 0.82 and 0.76 in the presence of 0.1 mmol·L -1 and 0.9 mmol·L -1 FeCl 3 ·6H 2 O, respectively. However, after coagulation the specific membrane fouling induced by the 0.1 g small microplastics ( d <0.5 mm) was 0.76 and 0.62 with 0.1 mmol·L -1 and 0.9 mmol·L -1 FeCl 3 ·6H 2 O, respectively. In addition, microplastics were always negatively charged in water. In comparison with alkaline conditions, Fe-based flocs were positively charged under acidic conditions, which were also much smaller. Therefore, microplastics were more easily adsorbed by Fe-based flocs under acidic conditions, leading to severe membrane fouling because of the dense cake layer formed. After coagulating with 0.3 mmol·L -1 FeCl 3 ·6H 2 O, the specific membrane flux induced by 0.1 g small microplastics ( d <0.5 mm) was 0.55 and 0.79 at pH 6.0 and 8.0, respectively.

The anatomical organization of distinct regions in the insect brain often reflects their functions. In the present study, the brain structure of Apolygus lucorum was examined by using immunolabeling and three-dimensional reconstruction. The results revealed the location and volume of prominent neuropils, such as the antennal lobes (AL), optic lobes (OL), anterior optic tubercles (AOTU), central body (CB), lateral accessory lobes (LAL), mushroom lobes, and distinct tritocerebral neuropils. As expected, this brain is similar to that of other insects. One exception, however, is that the antennal lobes were found to be the most prominent neuropils. Their size relative to the entire brain is the largest among all insect species studied so far. In contrast, the calyx, a region getting direct input from the antennal lobe, has a smaller size relative to the brain than that of other species. These findings may suggest that olfaction plays an essential role for A. lucorum .

Background: The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer., Materials and Methods: We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications., Results: The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309-4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274-5.944; P = 0.010) were independent risk factors for short-term postoperative complications., Conclusion: Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: The aim of this study was to investigate the prevalence of sarcopenia in patients without nutritional risk and the association between sarcopenia and postoperative outcomes after radical gastrectomy in these patients., Method: We conducted a study of non-nutritional risk patients with gastric cancer who underwent gastrectomy from August 2014 to December 2017 in two centers. Nutritional Risk Screening 2002 (NRS 2002) was used to evaluate the nutritional risk. Patients who with NRS 2002 score <3 were classified as having no nutritional risk and were included in the study. Demographic and perioperative data were gathered. Sarcopenia was diagnosed based on the European Working Group on Sarcopenia in Older People criteria. Univariate and multivariate analysis were performed to determine the association between preoperative risk factors and postoperative complications., Results: In all, 545 patients were included, in which the prevalence of sarcopenia and postoperative complications was 7.3% and 21.1%, respectively. Sarcopenia was significantly associated with higher age, lower body mass index, lower handgrip strength, lower usual walking speed, longer postoperative hospital length of stay, and higher costs. Multivariate analysis of prognostic factors revealed that sarcopenia was an independent predictor (odds ratio, 2.330; 95% confidence interval, 1.132-4.796; P = 0.022] for postoperative complications. Male sex, diabetes, and preoperative anemia also were risk factors for postoperative complications., Conclusion: Sarcopenia was a significant independent risk factor for postoperative complications after gastrectomy in patients without nutritional risk. Preoperative assessment and management of sarcopenia should be helpful for improving clinical outcomes for patients without nutritional risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process., Methods: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology., Results: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle., Conclusion: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Owing to the small land use and high pollutant removal efficiency, the integrated ultrafiltration (UF) membrane process has been gradually applied in water treatment. However, not only would the membrane surface be damaged by the commonly used granular adsorbents over time, but these types of adsorbents are expensive, such as nano zerovalent iron, carbon nanotubes, etc. To overcome these disadvantages, the loose Al-based flocs were directly injected into the membrane tank in the presence of humic acid and Miyun reservoir water. Results showed that severe membrane fouling was induced by HA alone, and the transmembrane pressure (TMP) significantly increased to 76.4 kPa after 12 d of operation. However, it dramatically decreased to 10.1 kPa after washing with tap water on day 13, indicating that the cake layer was the main fouling mechanism. The average HA removal efficiency was only 23.3% during filtration. In addition, the performance of the integrated flocs-membrane process could be influenced by floc dosage, injection frequency, and solution pH. The integrated membrane performed well with flocs (43.2 mmol·L -1 ) continuously injected at pH 6.0 (aeration rate at 0.3 L·min -1 ). The corresponding TMP only increased to 19.5 kPa after running for 12 d, which decreased to 5.6 kPa after washing with tap water on day 13. The average HA removal efficiency increased to 61.2%. Additionally, serious membrane fouling was also induced by Miyun reservoir alone. The TMP increased to 38.0 kPa on day 12, while it decreased to 3.8 kPa after washing with tap water on day 13. The cake layer was also the main fouling mechanism, and the average pollutant removal efficiency was only 7.5%. With floc continuously injected, however, the TMP only increased to 6.1 kPa on day 12. After washing with tap water, the TMP decreased to 2.3 kPa on day 13, and the average pollutant removal efficiency was as high as 58.6%. Based on the excellent membrane performance, the integrated membrane process exhibited potential application in drinking water treatment.

ApUGT, a diterpene glycosyltransferase from Andrographis paniculata, could transfer a glucose to the C-19 hydroxyl moiety of andrograpanin to form neoandrographolide. This glycosyltransferase has a broad substrate scope, and it can glycosylate 26 natural and unnatural compounds of different structural types. This study provides a basis for exploring the glycosylation mechanism of ent-labdane-type diterpenes and plays an important role in diversifying the structures used in drug discovery.

Objective: The aim of this study was to evaluate and compare three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) diagnostic criteria for malnutrition among elderly patients with gastrointestinal cancer., Research Methodsandprocedures: Nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), the Malnutrition Universal Screening Tool (MUST) and the Short Form of Mini Nutritional Assessment (MNA-SF), were applied to 255 patients with gastrointestinal cancer. We compared the diagnostic values of these tools for malnutrition, using the new ESPEN diagnostic criteria for malnutrition as the 'gold standards'., Results: According to the new ESPEN diagnostic criteria for malnutrition, 20% of the patients were diagnosed as malnourished. With the use of NRS 2002, 52.2% of the patients were found to be at high risk of malnutrition; with the use of MUST, 37.6% of the patients were found to be at moderate/high risk of malnutrition; and according to MNA-SF, 47.8% of the patients were found to be at nutritional risk. MUST was best correlated with the ESPEN diagnostic criteria (К=0.530, p<0.001) compared with NRS 2002 (К=0.312, p<0.001) and MNA-SF (К=0.380, p<0.001). The receiver operating characteristic curve of MUST had the highest area under the curve (AUC) compared with NRS 2002 and MNA-SF., Conclusions: Among the tools, MUST was found to perform the best in identifyingmalnourished elderly patients with gastrointestinal cancer distinguished by the new ESPEN diagnostic criteria for malnutrition. Nevertheless, further studies are needed to verify our findings., Trial Registration Number: ChiCTR-RRC-16009831; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In recent years, the integrated ultrafiltration (UF) membrane process has been widely used due to its high removal efficiency, slight membrane fouling, and small land use. However, a number of problems gradually occurred regarding the integrated UF process caused by the granular adsorbents used, such as powdered activated carbon, carbon nano-tube, nanoscale zerovalent iron, etc. Severe membrane surface damage was easily caused by these granular adsorbents after a long running time, and the cost of most adsorbents was very high. In this study, to effectively overcome these problems, cheap and loose aluminum hydrolyzed flocs were directly injected into the membrane tank in the presence of humic acid (HA), with the aim of investigating the removal efficiency of HA and the corresponding membrane behavior. The results showed that the removal efficiency of HA could be influenced by aeration mode, floc injection frequency, and floc dosage. Compared with intermittent aeration and one-time injection, a loose "protection membrane" layer was formed with continuous aeration and batch injections. Therefore, HA molecules were largely removed, leading to the dramatic alleviation of membrane fouling. The transmembrane pressure significantly increased to 74.8 kPa in the absence of flocs after running for 5 days, but that only increased by 6.3 kPa with continuous aeration and an injection frequency of once every 2 d (each addition consisted of 5.4 mmol·L -1 flocs) after running for 8 days. The removal efficiency of HA was 73.3% (8 d), which was much higher than in the absence of flocs (5 d, 32.1%). Additionally, only a few HA molecules were adsorbed onto the membrane pores with the batch injections, and a loose cake layer was the main fouling mechanism. With higher dosages of flocs injected each time, the average membrane pore diameter was larger after washing. Based on this excellent performance, this floc-integrated UF membrane technology indeed shows large application potential in water treatment.

Background: In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting., Methods: We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses., Results: The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023)., Conclusions: Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting., (Copyright © 2018. Published by Elsevier Inc.)

The oriental armyworm, Mythimna separata (Walker), is a polyphagous, migratory pest relying on olfactory cues to find mates, locate nectar, and guide long-distance flight behavior. In the present study, a combination of neuroanatomical techniques were utilized on this species, including backfills, confocal microscopy, and three-dimensional reconstructions, to trace the central projections of sensory neurons from the antenna and the labial pit organ, respectively. As previously shown, the axons of the labial sensory neurons project via the ipsilateral labial nerve and terminate in three main areas of the central nervous system: (1) the labial-palp pit organ glomerulus of each antennal lobe, (2) the gnathal ganglion, and (3) the prothoracic ganglion of the ventral nerve cord. Similarly, the antennal sensory axons project to multiple areas of the central nervous system. The ipsilateral antennal nerve targets mainly the antennal lobe, the antennal mechanosensory and motor center, and the prothoracic and mesothoracic ganglia. Specific staining experiments including dye application to each of the three antennal segments indicate that the antennal lobe receives input from flagellar olfactory neurons exclusively, while the antennal mechanosensory and motor center is innervated by mechanosensory neurons from the whole antenna, comprising the flagellum, pedicle, and scape. The terminals in the mechanosensory and motor center are organized in segregated zones relating to the origin of neurons. The flagellar mechanosensory axons target anterior zones, while the pedicular and scapal axons terminate in posterior zones. In the ventral nerve cord, the processes from the antennal sensory neurons terminate in the motor area of the thoracic ganglia, suggesting a close connection with motor neurons. Taken together, the numerous neuropils innervated by axons both from the antenna and labial palp indicate the multiple roles these sensory organs serve in insect behavior.

By using immunostaining and three-dimensional reconstruction, the anatomical organization of the antennal lobe glomeruli of the female cotton bollworm Helicoverpa armigera was investigated. Eighty-one glomeruli were identified, 15 of which were not previously discovered. The general anatomical organization of the AL of female is similar to that of male and all glomeruli were classified into four sub-groups, including the female-specific glomerular complex, posterior complex, labial-palp pit organ glomerulus, and ordinary glomeruli. A global-wide comparison on the complete glomerular map of female and male was performed and for the first time the quantitative difference in volume for each individual homologous glomerulus was analyzed. We found that the sexual dimorphism includes not only the sex-specific glomeruli but also some of the other glomeruli. The findings in the present study may provide a reference to examine the antennal-lobe organization more in detail and to identify new glomeruli in other moth species. In addition, the complete identification and global-wide comparison of the sexes provide an important basis for mapping the function of distinct glomeruli and for understanding neural mechanisms underlying sexually dimorphic olfactory behaviors.

The mirid bug Apolygus lucorum (Meyer-Dür), a polyphagous pest, is dependent on olfactory cues to locate various host plant species and mates. In this study, we traced the projection pathway of the antennal sensory neurons and visualized their projection patterns in the central nervous system of A. lucorum through confocal microscopy and digital reconstructions. We also examined the glomerular organization of the primary olfactory center of the brain, the antennal lobe, and created a three-dimensional model of the glomeruli. We found that the axons of the sensory neurons project into the brain via the ipsilateral antennal nerve, and descend further into the gnathal ganglion, prothoracic ganglion, mesothoracic ganglion, and metathoracic ganglion, and reach as far as to the abdominal ganglion. Such a projection pattern indicates that antennal sensory neurons of A. lucorum may be potentially directly connected to motor neurons. The antennal lobe, however, is the major target area of antennal sensory neurons. The antennal lobe is composed of a large number of glomeruli, i.e. 70-80 glomeruli in one AL of A. lucorum. The results of this study which provide information about the basic anatomical arrangement of the brain olfactory center of A. lucorum, are important for further investigations of chemosensory encoding mechanisms of the mirid bug.

A series of tenofovir analogues with potential antiviral and immunobiologically active compounds were synthesized through an asymmetric transfer hydrogenation reaction from achiral purine derivatives. Up to 97% ee and good to excellent yields were achieved under mild conditions through short reaction steps. The present report suggests an efficient process to acquire tenofovir and its analogues.

The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals.

The title Schiff base compound, C(9)H(12)N(2)O(2), was obtained from a condensation reaction of butan-2-one and furan-2-carbohydrazide. The furan ring and the hydrazide fragment are roughly planar, the largest deviation from the mean plane being 0.069 (2)Å, but the butanyl-idene group is twisted slightly with respect to this plane by a dihedral angle of 5.2 (3)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds link pairs of inversion-related mol-ecules, forming dimers of R(2) (2)(8) graph-set motif.

The mol-ecule of the title Schiff base compound, C(16)H(15)N(3)O(5), obtained from a condensation reaction of 4-acet-oxy-3-meth-oxy-benzaldehyde and 4-nitro-phenyl-hydrazine, adopts an E geometry with respect to the C=N double bond. The mol-ecule is roughly planar, with the two benzene rings twisted slightly with respect to each other by a dihedral angle of 6.90 (9)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds link centrosymmetrically related pairs of mol-ecules, forming dimers of R(2) (2)(22) graph-set motif. The dimers are further connected through slipped π-π inter-actions between symmetry-related benzene rings [centroid-centroid distance of 3.646 (1) Å, offset angle of 15.4°].

The plant-derived acetylcholinesterase inhibitor physostigmine has previously been shown to act on the nicotinic acetylcholine receptor (nAChR) causing either direct activation or potentiation of currents elicited by low concentrations of nicotinic agonists, or, at higher concentrations, channel block. We examined mouse adult-type muscle nAChR activation by physostigmine and found that channel activation by physostigmine exhibits many characteristics common with channel activity elicited by nicotinic agonists. Single-channel conductance was indistinguishable, and mutants known to slow channel closing in the presence of nicotinic agonists had a similar effect in the presence of physostigmine. However, physostigmine is a very inefficacious agonist. The presence of physostigmine did not alter the effective opening rate for a subsaturating dosage of carbachol, suggesting that physostigmine does not interact with the nicotinic agonist binding site. Mutations to a residue (alphaLys125) previously identified as part of the putative binding site for physostigmine reduced the duration of openings elicited by physostigmine, but the effects were generally small and, in most cases, nonsignificant. At higher concentrations, physostigmine blocked channel activity. Block manifested as a reduction in the mean open time and the emergence of a closed state, with a mean duration of 3 to 7 ms. The properties of block were consistent with two equivalent blocking sites per receptor with microscopic binding and unbinding rate constants for physostigmine of 20 microM(-1) s(-1) and 450 s(-1) (K(D) = 23 microM). These observations indicate that physostigmine is able to activate muscle nAChR by interacting with a site other than the nicotinic ligand binding site.

The Cromer blood group system consists of eight high incidence and three low incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high incidence antigen, named SERF. Sequence analyses of DNA from a Thai female whose serum contained the alloantibody to a high incidence antigen in the Cromer blood group system (anti-SERF) and from her two children were performed. Reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis on cDNA from the proband and PCR-restriction fragment length polymorphism analysis on DNA from Thais were also performed. To map the epitope, DAF deletion mutants were tested by immunoblotting with anti-SERF. Sequence analysis revealed a substitution of 647C>T in exon 5 DAF in the proband. The proband's two children and two of 100 Thais were heterozygotes 647C/T. Analysis using DAF deletion mutants revealed the antigenic determinant to be within short consensus repeat 3 (SCR3), which is encoded by exon 5. This study describes a novel high incidence antigen (SERF) in the Cromer blood group system characterized by the amino acid proline at position 182 in SCR3 of DAF. The SERF-negative proband has a substitution mutation that predicts for leucine at this position. SERF has been provisionally assigned the International Society of Blood Transfusion number 021.012 (CROM 12).

Background: The Cromer blood group system consists of seven high-incidence and three low-incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high-incidence antigen, named GUTI., Study Design and Methods: RT-PCR and sequence analysis were performed on cDNA prepared from a Chilean donor whose serum contained the alloantibody (anti-GUTI). Based on the observed point mutation, a PCR-RFLP assay using MaeII was developed. To map the epitope, DAF-deletion mutants were tested by immunoblotting with anti-GUTI., Results: Sequence analysis revealed a substitution of 719G>A in DAF in the proband. The proband's parents and two daughters were heterozygotes for 719G>A, one sister whose RBCs typed GUTI- was homozygous for 719A, and one sister had the wild-type DAF (719G). Seven additional heterozygote samples were identified among 214 Chileans. No heterozygotes were found in 197 New York donors. Analysis using DAF-deletion mutants showed the antigenic determinant to be within short consensus repeat (SCR) 4., Conclusion: This study describes a novel high- incidence antigen (GUTI) in the Cromer blood group system characterized by the amino acid arginine at position 206 in SCR4 of DAF. The GUTI-negative proband has a substitution mutation that predicts for histidine at this position.