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BACKGROUND Soybean residue (okara) is an agricultural by‐product, which is rich in protein and fiber. This study evaluated a novel sequential process which combined fungal pretreatment (F) and twin screw extruder (E), to hydrolyze okara. The sequence of the pretreatment steps, and extruder at screw speeds 200 rpm (200) or 600 rpm (600), were tested. Next, soluble nutrients were extracted to create Fokara, EFokara200, EFokara600, FEokara200 and FEokara600 okara media. RESULTS: All the prepared okara media could support the growth and carotenoid production by the yeast Rhodosporidium toruloides. This suggested that okara proteins and polysaccharides were successfully hydrolyzed by extrusion and fungal pretreatment, into soluble nutrients. Rhodosporidium toruloides accumulated the highest biomass of 23.7 mg mL−1 dry cell weight (DCW), when grown on FEokara600 media. This was higher as compared to commercial YPG (yeast extract–peptone–glycerol) media (18.7 mg mL−1 DCW). However, R. toruloides accumulated the highest carotenoid production of 13.2 µg mL−1 when grown on EFokara200 media as the nutrient source. This was comparable to carotenoid production of 13.1 µg mL−1 when R. toruloides was grown on YPG media. CONCLUSION: Extrusion in combination with fungal pretreatment, is a low cost process, to hydrolyze and re‐use okara, for carotenoid production. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about the prevalence of food allergy (FA) in China. The aim of this study was to investigate the disparity of FA between urban and rural areas in southern China. Methods: EuroPrevall questionnaire responses were obtained from 5542 school‐age children in urban Guangzhou and 5319 in rural Shaoguan. A case‐control study enrolled 190 children with adverse reactions (ARs) after food intake as cases and 212 controls in Guangzhou, whereas 116 cases and 233 controls in Shaoguan. These subjects underwent skin prick test (SPT) and serum IgE measurements to food and inhalant allergens. Allergen extracts from shrimp, house dust mite (HDM), and cockroach were prepared for IgE cross‐reactivity testing in 23 Guangzhou and 20 Shaoguan shrimp‐sensitized subjects. Results: The prevalence of ARs to shrimp was higher in Guangzhou than in Shaoguan children (3.5% vs 1.4%, P < .001). However, sensitization rate to shrimp (SPT: 3.7% vs 11.2%, P = .015; IgE: 12.6% vs 36.2%, P < .001) and cockroach (SPT: 5.3% vs 33.5%; IgE: 2.6% vs 27.6%, P < .001) was lower in Guangzhou. A significant correlation between shrimp and HDM/cockroach IgE was found in Shaoguan children. The proportions of positive IgE to tropomyosin (Pen a 1, Der p 10) were lower than 7.4% in both areas. Cockroach allergen has a significantly higher inhibition rate of binding to IgE to house dust mite allergens in Shaoguan sera. Conclusion: Shrimp is a common allergic food in southern China. Higher proportion of shrimp sensitization in rural subjects could be explained by cross‐reactivity to cockroach. Tropomyosin was not a major allergen responding to the cross‐reactivity. [ABSTRACT FROM AUTHOR]

ABSTRACT A large number of etiological factors and the complexity of breast cancers present challenges for prevention and treatment. Recently, the emergence of microRNAs ( miRNAs) as cancer biomarkers has added an extra dimension to the 'molecular signatures' of breast cancer. Bioinformatic analyses indicate that each miRNA can regulate hundreds of target genes and could serve functionally as 'oncogenes' or 'tumour suppressor' genes, and co-ordinate multiple cellular processes relevant to cancer progression. A number of studies have shown that miRNAs play important roles in breast tumorigenesis, metastasis, proliferation and differentiation of breast cancer cells. This review provides a comprehensive overview of miRNAs with established functional relevance in breast cancer, their established target genes and resulting cellular phenotype. The role and application of circulating miRNAs in breast cancer is also discussed. Furthermore, we summarize the role of miRNAs in the hallmarks of breast cancer, as well as the possibility of using miRNAs as potential biomarkers for detection of breast cancer. [ABSTRACT FROM AUTHOR]

Antisense long non-coding RNAs (AS lncRNAs) play important roles in refined regulation of animal gene expression. However, their functions and molecular mechanisms for domestic animal adipogenesis are largely unknown. Here, we found a novel AS lncRNA transcribed from the porcine PU.1 gene (also known as SPI1) by strand-specific RT-PCR. Results showed that PU.1 AS lncRNA was expressed and generally lower than the level of PU.1 mRNA in porcine subcutaneous adipose, heart, liver, spleen, lympha, skeletal muscle and kidney tissues. We further found that the levels of PU.1 mRNA and PU.1 protein were significantly lower in subcutaneous and intermuscular adipose than in mesenteric and greater omentum adipose, whereas the levels of PU.1 AS lncRNA showed no difference in porcine adipose tissues from four different parts of the body. During porcine adipogenesis, levels of PU.1 mRNA increased at day 2 and then gradually decreased. Meanwhile, PU.1 AS lncRNA exhibited an expression trend similar to PU.1 mRNA but sharply decreased after day 2. Interestingly, PU.1 protein level rose during differentiation. In addition, at day 6 after differentiation, knockdown of endogenous PU.1 promoted adipogenesis, whereas knockdown of endogenous PU.1 AS lncRNA had the opposite effect. Moreover, peroxisome proliferator-activated receptor gamma (PPARG) and fatty acid synthase (FASN) were significantly upregulated in the PU.1 shRNA treatment group (P < 0.05), whereas they were downregulated in the PU.1 AS shRNA treatment group (P < 0.05). Adipose triglyceride lipase [ATGL; also known as patatin-like phospholipase domain containing 2 (PNPLA2)] and hormone-sensitive lipase [HSL; also known as lipase, hormone-sensitive (LIPE)] contrasted with PPARG and FASN. Finally, the PU.1 mRNA/PU.1 AS lncRNA duplex was detected by an endogenous ribonuclease protection assay combined with RT-PCR. Based on the above results, we suggest that PU.1 AS lncRNA (vs. its mRNA translation) promotes adipogenesis through the formation of a sense-antisense RNA duplex with PU.1 mRNA. [ABSTRACT FROM AUTHOR]

The oxidation behavior of AlON translucent ceramic was investigated both in non-isothermal (from room temperature to 1573 K) and isothermal (at 1373 and 1473 K) conditions. The mass gains, phase compositions and micromorphology of oxidized samples were examined by thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM), respectively. The results suggest that in non-isothermal environment the oxidation reaction starts at about 1173 K for both AlON bulk sample and powder. In isothermal condition, the mass gain indicates the two-stage reaction mechanism which starts with chemical reaction, followed by diffusion controlled stage. XRD patterns suggest that AlON is thermodynamically unstable and it partly decomposes into corundum phase Al2O3 and AlN during the oxidation process. SEM results indicate that different micromorphology is obtained at different temperatures in the oxidation process. The estimated apparent activation energy for the diffusion rate controlled stage from isothermal experiment is about 245.2 kJ/mol. [ABSTRACT FROM AUTHOR]

Background and Objective Follicular dendritic cell secreted protein ( FDC- SP), has been identified in human periodontal ligament ( PDL) in a recent study. It is suggested that the expression of FDC- SP might be associated with the osteogenic differentiation and mineralization of human periodontal ligament cells (h PDLCs). However, the intrinsic mechanism regarding this is still unclear. The aim of this study was to establish h PDLCs with safe and efficient overexpression of FDC- SP and to elucidate the influence of FDC- SP transfection on h PDLC osteogenesis in periodontal regeneration. Material and Methods We first applied a recombinant lentiviral vector containing FDC- SP to transfect h PDLCs via different multiplicity of infection ( MOI) levels (1, 10, 20, 50 and 100). Western blot was performed to confirm the expression of FDC- SP. MTT assay was employed to evaluate the proliferation status of transfected cells. Then, the extent of osteogenic differentiation was investigated by simultaneous monitoring of alkaline phosphatase ( ALP) activity assessment, immunofluorescent staining, the expression patterns of osteoblastic markers and mineralization staining. Results We found that h PDLCs transfected via MOI 20, 50 and 100 exhibited expression of FDC- SP protein compared with MOI 1 and 10. There was no significant effect of FDC- SP transfection (at different MOI levels of 1, 10 and 20) on the proliferation of h PDLCs, whereas higher MOI levels (50 and 100) inhibited cell proliferation ability. In addition, ALP activity decreased significantly in FDC- SP-transfected h PDLCs at day 7. When stained with alizarin red, cells overexpressing FDC- SP formed less mineralized nodules at 21 d post-induction of differentiation, compared with the control cultures. Osteogenic inhibition was also confirmed by ALP immunostaining. Moreover, m RNA expression levels of osteoblastic markers decreased after FDC- SP transfection, which were in accordance with western blot results. Conclusion Our data suggest that MOI 20 is optimal to transfect h PDLCs, which achieves safe and efficient overexpression of FDC- SP in transfected cells. Moreover, FDC- SP overexpression inhibits osteogenic differentiation of h PDLCs. The present study contributes to a better understanding of the biological functions governing FDC- SP-induced h PDLC differentiation. [ABSTRACT FROM AUTHOR]

Grass carp ( Ctenopharyngodon idellus) are important Chinese freshwater fish, and in China, the faba bean has been used as the sole food source for grass carp to transform them into crisp grass carp. Because of this, crisp grass carp has become an economically important fish because of its increased muscle hardness. To study the nutritional regulation of type I collagen in faba bean-fed grass carp, we isolated type I collagen alpha 2 ( COL1A2) on the basis of our isolation of COL1A1. The COL1A2 cDNA was found to be 4899 bp in length and included a 4059-bp coding sequence ( CDS) and encoded a polypeptide of 1352 AA. The protein peptide molecular weight was 127.39 kD, and the theoretical isoelectric point was 9.37. The COL1A2 protein possessed five α-helixes, eight β-sheets, 16 regions of triple helical repeats, 21 low-complexity regions, 10 function domains and two zinc-binding sites; however, no calcium-binding sites were observed. The mRNA expression of COL1A1 and COL1A2 was assessed in eight tissues (muscle, hepatopancreas, intestine, gills, skin, fin, kidney and spleen) from grass carp and crisp grass carp by semi-quantitative RT-PCR. Expression of COL1A1 in the muscle, intestines and skin of crisp grass carp was higher than that in grass carp, and expression of COL1A2 in the muscle, gills, fin and skin of crisp grass carp was higher than that in grass carp. In the muscle of crisp grass carp, expression of COL1A1 and COL1A2 was higher than that in grass carp, which was further confirmed by real-time PCR, and collagen content also was enhanced. These results demonstrated that type I collagen was closely related to the increased muscle hardness of faba bean-fed grass carp. [ABSTRACT FROM AUTHOR]

Background There has been growing interest in the use of faecal microbiota transplantation ( FMT) for the treatment of gastrointestinal and nongastrointestinal diseases. Aim To review systematically the reported efficacy and safety of FMT in the management of gastrointestinal and nongastrointestinal disorders in adults and children. Methods The systematic review followed Cochrane and PRISMA recommendations. Available articles were identified using three electronic databases in addition to hand searching and contacting experts. Inclusion criteria were any reports of FMT therapy written in English. Results A total of 844 patients who had undergone FMT were identified from 67 published studies. The most common indications were refractory/relapsing Clostridium difficile infection ( CDI) (76.3%) and inflammatory bowel disease ( IBD) (13.2%). There has been only one placebo-controlled trial, a successful trial in 43 patients with recurrent CDI. Seven publications report FMT in paediatric patients with a total of 11 treated, 3 with chronic constipation and the remainder with recurrent CDI or ulcerative colitis ( UC). 90.7% of patients with refractory/relapsing CDI were cured and 78.4% of patients with IBD were in remission after FMT. FMT therapy could also be effective in treatment of some nongastrointestinal disorders such as chronic fatigue syndrome. The only reported serious adverse event attributed to the therapy was a case of suspected peritonitis. Conclusions Although more controlled trials are needed, faecal microbiota transplantation therapy shows promise in both adults and children with gastrointestinal diseases such as CDI and IBD. [ABSTRACT FROM AUTHOR]

Aim To examine the association of in-hospital diabetes regimen intensification with subsequent 30-day risk for unplanned readmission/emergency department admission. Methods We retrospectively studied 1949 adults with Type 2 diabetes receiving primary care within an academic health network admitted to the hospital between January 2007 and December 2009. Glucose therapy intensification was defined as new start of insulin or oral hypoglycaemic agents, or addition of prandial insulin or insulin mixtures. The association of glucose therapy intensification with subsequent 30-day risk for unplanned readmission/emergency department admission was examined, with focus on medicine service patients with poorly controlled glycaemia (baseline HbA1c ≥ 64 mmol/mol). Results One in six patients (324/1949, 17%) had early readmission/emergency department admission. Compared with patients without early readmission, readmitted patients were more often male (58 vs. 52%, P = 0.03), had higher Charlson co-morbidity score [mean ( sd) 3.0 (2.0) vs. 2.8 (1.8), P = 0.02], longer length of stay [5 (4.4) vs. 3.9 (3.3) days, P < 0.01] and were more often discharged home with nursing services (38 vs. 32%, P = 0.03). Overall, glucose therapy intensification was not associated with early hospital readmission/emergency department admission (odds ratio 0.94, 95% CI 0.64-1.37, P = 0.74). However, among medicine service patients with baseline HbA1c ≥ 64 mmol/mol (8%), glucose therapy intensification was associated with a significantly decreased early readmission risk (adjusted odds ratio 0.33, 95% CI 0.12-0.88, P = 0.03) and lower post-discharge HbA1c {mean decrease ( sd): 20 (26) mmol/mol [1.8 (2.4)%] vs. 7 (15) mmol/mol [0.6 (1.4)%], P < 0.01}. Conclusions Diabetes medical regimen intensification during hospitalization was not associated with early readmission. Among patients with elevated HbA1c, glucose therapy intensification was associated with a decreased 30-day readmission/emergency department admission risk and lower outpatient HbA1c levels. Our findings support the safety and durable impact of diabetes regimen optimization during hospital admission. [ABSTRACT FROM AUTHOR]

A superoxide dismutase (SOD) with the molecular weight of 31,079 has been purified as a homodimer from Panax ginseng by employing neutral pH buffer extraction, ammonium sulfate precipitation, isoelectric point precipitation and ion exchange methods. The enzyme's specific activity determined by an improved Marklund method was 9480.43 U/mg. Metal analysis showed that the SOD contained iron with the stoichiometry of 0.9 ± 0.3 Fe/subunit and exhibited high thermal stability (70°C) over the pH range from 4.0 to 9.0. Its maximum absorption wavelength was 278 nm and it was sensitive to hydrogen peroxide, trichloromethane-ethanol and urea. These results indicate that the enzyme is an iron SOD. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy., Materials and Methods: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery., Results: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%)., Conclusions: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy., Trial Registration: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: We aimed to investigate the association of the left ventricular ejection fraction (LVEF) spectrum with 1-year clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA)., Methods: In a prospective registry for the Third China National Stroke Registry (CNSR-III), AIS or TIA patients with echocardiography records during hospitalization were recruited. All LVEFs were categorized into intervals of 5% in width. The lowest and highest intervals are ≤40% and >70%, respectively. The primary outcome was all-cause death at 1 year. Cox proportional hazards regression analysis was performed to investigate the association between baseline LVEF and clinical outcomes., Results: This analysis included a total of 14,053 patients. In total, 418 patients died during 1-year follow-up. Overall, LVEF ≤60% was associated with a higher risk of all-cause death compared to LVEF >60%, independent of demographic and clinical characteristics (aHR 1.29 [95% CI 1.06-1.58]; p = 0.01). The cumulative incidence of all-cause death was significantly different among the eight LVEF groups that survival declined successively with the decrease of LVEF (log-rank p ≤ 0.0001)., Conclusions: Patients with AIS or TIA with decreased LVEF (≤60%) had a lower 1-year survival rate after onset. LVEF 50%-60% even within the normal range, may still contribute to poor outcomes in AIS or TIA. Comprehensive evaluation of cardiac function after acute ischemic cerebrovascular disease should be strengthened., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized., Methods: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Aβ), and some new targeted therapeutic drugs., Results: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%)., Conclusion: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Stem cells offer a promising therapeutic strategy for patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI), but the optimal transplantation sites and cells are not clear. Although the paraventricular thalamus (PVT) and claustrum (CLA) are associated with consciousness and are candidate transplantation targets, few studies have been designed to investigate this possibility., Methods: Controlled cortical injury (CCI) was performed to establish a mouse model of DOC. CCI-DOC paradigm was established to investigate the role of excitatory neurons of PVT and CLA in disorders of consciousness. The role of excitatory neuron transplantation in promoting arousal and recovery of consciousness was determined by optogenetics, chemogenetics, electrophysiology, Western blot, RT-PCR, double immunofluorescence labeling, and neurobehavioral experiments., Results: After CCI-DOC, neuronal apoptosis was found to be concentrated in the PVT and CLA. Prolonged awaking latency and cognitive decline were also seen after destruction of the PVT and CLA, suggesting that the PVT and CLA may be key nuclei in DOC. Awaking latency and cognitive performance could be altered by inhibiting or activating excitatory neurons, implying that excitatory neurons may play an important role in DOC. Furthermore, we found that the PVT and CLA function differently, with the PVT mainly involved in arousal maintenance while the CLA plays a role mainly in the generation of conscious content. Finally, we found that by transplanting excitatory neuron precursor cells in the PVT and CLA, respectively, we could facilitate awakening with recovery of consciousness, which was mainly manifested by shortened awaking latency, reduced duration of loss of consciousness (LOC), enhanced cognitive ability, enhanced memory, and improved limb sensation., Conclusion: In this study, we found that the deterioration in the level and content of consciousness after TBI was associated with a large reduction in glutamatergic neurons within the PVT and CLA. Transplantation of glutamatergic neuronal precursor cells could play a beneficial role in promoting arousal and recovery of consciousness. Thus, these findings have the potential to provide a favorable basis for promoting awakening and recovery in patients with DOC., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: The definitive treatment for pyrrolizidine alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS) is not available. The effectiveness of anticoagulation therapy remains controversial. The efficacy of low molecular weight heparin (LMWH) should be investigated in patients and animal models, and the underlying mechanism should be explored., Methods: The prognosis of patients with PAs-HSOS who received anticoagulation therapy was retrospectively analysed. The effect of enoxaparin on the liver injury was determined in animal models of monocrotaline (MCT)-induced HSOS was determined, and the underlying mechanism was investigated using a murine model., Results: The cumulative survival rate of patients with PAs-induced HSOS was 60.00% and 90.90% in the non-anticoagulation group and anticoagulation group. Enoxaparin attenuated liver injury effectively in a rat model of MCT-induced HSOS. Additionally, the improvement of severe liver injury was observed in MCT-treated mice after the administration of enoxaparin (40 mg/kg). The alleviation of liver injury was observed in mice with hepatocyte-specific deletion of oncostatin M (Osm △Hep ). In MCT-treated mice administrated with enoxaparin, no significant differences in liver injury were observed between Osm △Hep mice and Osm flox/flox mice. Additionally, adenovirus-mediated overexpression of Osm resulted in severe liver injury in MCT-induced mice after the administration of enoxaparin., Conclusions: LMWH attenuated severe liver injury in patients with PAs-Induced HSOS and animal models of MCT-induced HSOS, which provides a rationale for the application of anticoagulation therapy., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To investigate relationships between hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor -α (TNF-α), interleukin-17A (IL-17A), and interferon -γ (IFN-γ), with left ventricular geometry (LVG) and function in patients with primary hypertension (PHT)., Methods: A total of 396 PHT patients were assigned into four groups: Normal Geometry (NG), Concentric Remodeling (CR), Eccentric Hypertrophy (EH), and Concentric Hypertrophy (CH). The correlation between hs-CRP, TNF-α, IL-17A, IFN-γ, and clinical, biochemical parameters were analyzed by Pearson correlation analysis and Logistic regression. Receiver Operating Characteristic (ROC) curve was used to analyze the clinical values of hs-CRP, TNF-α, IL-17A, and IFN-γ for abnormal LVG prediction., Results: NG, CR, EH, and CH group all presented increasingly higher levels of Hs-CRP, TNF-α, IL-17A, and IFN-γ, and the increase was the most prominent in the CH group. Pearson correlation analysis showed that hs-CRP, IL-17A, and IFN-γ were all positively correlated with LASct. Hs-CRP, TNF-α, and IL-17A were all negatively correlated with GLS, LASr, and LAScd. However, IFN-γ was only negatively correlated with GLS and LAScd. Logistic regression analysis showed that hs-CRP and IL-17A were independently correlated with CR; hs-CRP, TNF-α, IFN-γ, and IL-17A were independently correlated with EH and CH. ROC curve analysis showed that the area under the curve (AUC) of hs-CRP was 0.816. When the optimal diagnostic threshold of hs-CRP was 3.04 mg/L, the sensitivity and specificity of the abnormal LVG were 72.1% and 81.5%, respectively., Conclusion: In PHT patients, hs-CRP, TNF-α, IL-17A, and IFN-γ were correlated with abnormal LVG and left ventricular function, suggesting that inflammatory cytokines may be involved in the process of PHT-induced abnormal left ventricular structure and function. In addition, hs-CRP can be used as a health screening index for patients at high risk of abnormal LVG., (© 2022 Wiley Periodicals LLC.)

Aims: Proton pump inhibitors (PPIs) are often prescribed to prevent or treat gastrointestinal disease. Whether the combination of systemic anti-tumour therapy and PPIs leads to poor outcomes in patients with advanced non-small cell lung cancer (NSCLC) is unclear. This systematic review explored the relationship between PPIs and survival outcomes of patients with advanced NSCLC who are receiving systemic anti-tumour therapy., Methods: We searched studies reporting the overall survival (OS) and/or progression-free survival (PFS) of advanced NSCLC patients who are receiving systemic anti-tumour therapy with or without PPIs on PubMed, EMBASE and the Cochrane Library for literature published prior to 31 August 2021. The meta-analysis used a random effects model to estimate the hazard ratio (HR) with 95% confidence intervals (CI) and I 2 to assess statistical heterogeneity. Publication bias and sensitivity analysis were performed., Results: Fourteen retrospective studies comprising 13 709 advanced NSCLC patients were identified. Subgroup analyses showed that the use of PPI was correlated with the OS or PFS of patients receiving chemotherapy, targeted therapy, and immunotherapy (PPI users' group vs non-users' group: HR for OS = 1.35, 95% CI = 1.21-1.51, P < .00001; HR for PFS = 1.50, 95% CI = 1.25-1.80, P < .0001). Publication bias and sensitivity analyses confirmed that the results were robust., Conclusion: Meta-analysis demonstrated that PPI use in advanced NSCLC patients who were undergoing systemic anti-tumour therapy was correlated with increased mortality risk. Until results are further confirmed, caution should be applied when administering PPIs and systemic anti-tumour therapy to advanced NSCLC patients., (© 2022 British Pharmacological Society.)

Objective: To assess the relationship of interleukin-6 (IL-6) and C-reactive protein (CRP) levels with left ventricular geometry (LVG) and function in patients with obstructive sleep apnea syndrome (OSAS) and pre-hypertension., Methods: A total of 458 patients were assigned into four groups: normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH). Pearson correlation and multivariate logistic regression analyses were used to determine the correlation between IL-6, CRP, and clinical, polysomnographic, and biochemical parameters with LVG and function., Results: IL-6 and CRP levels were higher in the EH and CH groups than those in the NG and CR groups. The results of the Pearson correlation analysis showed that IL-6 level was positively correlated with the E/e' ratio and peak systolic pulmonary venous reverse velocity (PVa) duration time (PVaD), while negatively correlated with the E/A ratio, s', and left ventricular ejection fraction (LVEF). CRP level was positively correlated with A-wave duration time (AD), peak systolic pulmonary venous flow velocity (PVs), PVa and PVaD, while negatively correlated with the E/A ratio. The results of the multivariate logistic regression analysis revealed that IL-6 and CRP levels were correlated with EH (β = 1.213, odds ratio [OR] = 3.363, p < 0.001; β = 1.258, OR = 3.518, p < 0.001) and CH (β = .938, OR = 2.555, p = 0.008; β = 1.239, OR = 3.454, p < 0.001)., Conclusion: IL-6 and CRP levels are associated with LVG and function, suggesting that IL-6 and CRP levels are involved in OSAS and pre-hypertension, leading to abnormal left ventricular structure and function., (© 2022 Wiley Periodicals LLC.)

Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Our results provide evidence for a novel role of tau in the regulation of presynaptic function., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Impairments of dendritic trees and spines have been found in many neurodegenerative diseases, including Alzheimer's disease (AD), in which the deficits of melatonin signal pathway were reported. Melatonin receptor 2 (MT2) is widely expressed in the hippocampus and mediates the biological functions of melatonin. It is known that melatonin application is protective to dendritic abnormalities in AD. However, whether MT2 is involved in the neuroprotection and the underlying mechanisms are not clear. Here, we first found that MT2 is dramatically reduced in the dendritic compartment upon the insult of oligomer Aβ. MT2 activation prevented the Aβ-induced disruption of dendritic complexity and spine. Importantly, activation of MT2 decreased cAMP, which in turn inactivated transcriptional factor CCAAT/enhancer-binding protein α(C/EBPα) to suppress miR-125b expression and elevate the expression of its target, GluN2A. In addition, miR-125b mimics fully blocked the protective effects of MT2 activation on dendritic trees and spines. Finally, injection of a lentivirus containing a miR-125b sponge into the hippocampus of APP/PS1 mice effectively rescued the dendritic abnormalities and learning/memory impairments. Our data demonstrated that the cAMP-C/EBPα/miR-125b/GluN2A signaling pathway is important to the neuroprotective effects of MT2 activation in Aβ-induced dendritic injuries and learning/memory disorders, providing a novel therapeutic target for the treatment of AD synaptopathy., (© 2019 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

The popular distilled Chinese strong-flavour liquor (CSFL) is produced by solid fermentation in the ground pit. Microbes inhabiting in the pit mud (PM) on the walls of the fermentation pit are responsible for the production of caproic acid (CA) that determines the quality of CSFL to a large degree. However, little is known about the active microbial populations and metabolic potential of the PM microbiome. Here, we investigated the overall metabolic features of the PM microbiome and its active microbial components by combining metagenomics and MiSeq-sequencing analyses of the 16S rRNA genes from DNA and RNA (cDNA). Results showed that prokaryotes were predominant populations in the PM microbiome, accounting for 95.3% of total metagenomic reads, while eukaryotic abundance was only 1.8%. The dominant prokaryotic phyla were Firmicutes, Euryarchaeota, Bacteroidetes, Actinobacteria and Proteobacteria, accounting for 48.0%, 19.0%, 13.5%, 2.5% and 2.1% of total metagenomic reads respectively. Most genes encoding putative metabolic pathways responsible for the putative CA production via chain elongation pathway were detected. This indicated that the PM microbiome owned functional potential for synthesizing CA from ethanol or lactate. Some key genes encoding enzymes involved in hydrogenotrophic and acetoclastic methanogenesis pathways were detected in the PM metagenome, suggesting the possible occurrence of interspecies hydrogen transfer between CA-producing bacteria and methanogens. The 16S rDNA and 16S rRNA profiles showed that the Clostridial cluster IV, Lactobacillus, Caloramator, Clostridium, Sedimentibacter, Bacteroides and Porphyromonas were active populations in situ, in which Clostridial cluster IV and Clostridium were likely involved in the CA production. This study improved our understandings on the active populations and metabolic pathways of the PM microbiome involved in the CA synthesis in the CSFL fermentation., (© 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Prior work has extensively studied neural deficits in children with reading impairment (RI) in their native language but has rarely examined those of RI children in their second language (L2). A recent study revealed that the function of the local brain regions was disrupted in children with RI in L2, but it is not clear whether the disruption also occurs at a large-scale brain network level. Using fMRI and graph theoretical analysis, we explored the topology of the whole-brain functional network during a phonological rhyming task and network reconfigurations across task and short resting phases in Chinese children with English reading impairment versus age-matched typically developing (TD) children. We found that, when completing the phonological task, the RI group exhibited higher local network efficiency and network modularity compared with the TD group. When switching between the phonological task and the short resting phase, the RI group showed difficulty with network reconfiguration, as reflected in fewer changes in the local efficiency and modularity properties and less rearrangement of the modular communities. These findings were reproducible after controlling for the effects of in-scanner accuracy, participant gender, and L1 reading performance. The results from the whole-brain network analyses were largely replicated in the task-activated network. These findings provide preliminary evidence supporting that RI in L2 is associated with not only abnormal functional network organization but also poor flexibility of the neural system in responding to changing cognitive demands., (© 2016 John Wiley & Sons Ltd.)

The two estrogen receptors (ERs), ERα and ERβ, mediate the diverse biological functions of estradiol. Opposite effects of ERα and ERβ have been found in estrogen-induced cancer cell proliferation and differentiation as well as in memory-related tasks. However, whether these opposite effects are implicated in the pathogenesis of Alzheimer's disease (AD) remains unclear. Here, we find that ERα and ERβ play contrasting roles in regulating tau phosphorylation, which is a pathological hallmark of AD. ERα increases the expression of miR-218 to suppress the protein levels of its specific target, protein tyrosine phosphatase α (PTPα). The downregulation of PTPα results in the abnormal tyrosine hyperphosphorylation of glycogen synthase kinase-3β (resulting in activation) and protein phosphatase 2A (resulting in inactivation), the major tau kinase and phosphatase. Suppressing the increased expression of miR-218 inhibits the ERα-induced tau hyperphosphorylation as well as the PTPα decline. In contrast, ERβ inhibits tau phosphorylation by limiting miR-218 levels and restoring the miR-218 levels antagonized the attenuation of tau phosphorylation by ERβ. These data reveal for the first time opposing roles for ERα and ERβ in AD pathogenesis and suggest potential therapeutic targets for AD., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial., (© 2014 Wiley Periodicals, Inc.)

Background: Patients with Diabetes are at greater risk for ischemic stroke and usually suffer more severe ischemic brain damage than nondiabetic patients. However, the underlying mechanism of the exaggerated injury is not well defined., Aims: Macroautophagy (hereafter called autophagy in this report) plays a key role in cellular homeostasis and may contribute to cell death as well. Our aim was to determine whether autophagy was involved in the enhanced susceptibility of diabetic brain cells to ischemic injury and explore it as a possible target for the treatment of stroke in a diabetic condition., Results: A type II diabetic mouse model generated by combined administration of streptozotocin and nicotinamide showed enlarged infarct volume, increased cell death and excessive blood-brain barrier (BBB) disruption compared with nondiabetic stroke mice. After ischemic stroke, both diabetic and nondiabetic mice showed enhanced autophagosome formation and autophagic flux as demonstrated by increased expression of autophagy signals Beclin 1, microtubule-associated protein light-chain II (LC3-II), and decreased autophagy-specific substrate p62. The increased autophagic activity was significantly higher in diabetic stroke mice than that in nondiabetic stroke mice. The autophagy inhibitor 3-methyladenine (3-MA) attenuated the exaggerated brain injury and improved functional recovery., Conclusions: These data suggest that autophagy contributes to exacerbated brain injury in diabetic condition, and autophagy-mediated cell death may be a therapeutic target in diabetic stroke., (© 2013 John Wiley & Sons Ltd.)

Background: Although needlestick and sharps injuries (NSI) represent a significant occupational hazard for physicians worldwide, their epidemiology has not been previously examined in Mainland China. This study describes the prevalence, distribution, and risk factors for NSI among a cross-section of Chinese physicians., Methods: Data was obtained by an anonymous, self-reporting survey administered to all 361 physicians at a university teaching hospital, during 2004., Results: Seventy-nine percent of the physicians responded. Among them, 64% had experienced an NSI in the previous 12 months, 50.3% of which involved contaminated devices. By device, 22.8% were caused by hollow-bore syringe needles, 19.1% by suture needles, and 12.1% by scalpel blades. Surgical procedures accounted for 27.9% of all injuries. Only 15.3% of physicians had officially reported their NSI to management, of which 10% went unreported because the individual felt they were not unlucky enough to get a disease. A statistically significant correlation was demonstrated between NSI and working in the intensive care unit (adjusted odds ratio: 5.3, 95% CI: 1.7-23.4)., Conclusions: Although this study suggests that NSI are an important workplace hazard for Chinese physicians, future measures should consider the unique cultural beliefs of Chinese people and its effect on preventive behaviors. The concept of "luck," and its relationship with NSI reporting in particular, may also need to be addressed., ((c) 2006 Wiley-Liss, Inc.)

The specific oxygen uptake rate (q(O)2, respiration rate) of Bacillus thuringiensis subsp. kurstaki HD-1 was very high at inoculation and was found to decrease essentially monotonically throughout both vegetative growth phase and transition phase under different batch culture conditions. Average q(O)2 values decreased from 8-10 mmol/g h at 1 h after inoculation to less than 2 mmol/g h by the time growth ended. The results are shown to be consistent with the few previous reports on q(O)2 in B. thuringiensis in the literature but also novel in that this pattern of monotonic decline has not been described previously. Both pH control and EDTA in low concentration shortened the vegetative growth phase and reduced the 10 h biomass concentration. Using plots of q(O)2 versus specific growth rate, mu, biomass yield based on the oxygen used for growth, was calculated for transition phase to be 0.041-0.047 g/mmol, consistent with literature values. The same plot also showed that the presence of EDTA resulted in an atypical q(O)2-mu trajectory and apparently much higher biomass yield from the oxygen consumed.

This article presents the performance test results of the CFVAD3 continuous flow blood pump in an artificial human circulation system. The CFVAD3 utilizes magnetic bearings that support a thin pancake impeller, the shape of which allows for a very compact pump whose total axial length is less than 5 cm with a radial length of about 10 cm. This gives a total volume of about 275 cc. The impeller itself has 4 vanes with a designed operating point of 6 L/min at 100 mm Hg of differential pressure and 2,000 rpm. The advantages of magnetic bearings, such as large clearance spaces and no mechanical wear, are elaborated upon. Furthermore, bearing model parameters such as load capacity and current gains are described. These parameters in conjunction with the operating conditions during testing are then used to estimate the fluid forces, stiffness, and damping properties while pumping. Knowledge of these parameters is desirable because of their effects on pump behavior. In addition, a better plant model will allow more robust control algorithms to be devised that can boost pump performance and reliability.

A new continuous flow ventricular assist device using full magnetic suspension has been designed, constructed, and tested. The magnetic suspension centers the centrifugal pump impeller within the clearance passages in the pump, thus avoiding any form of contact. The noncontact operation is designed to give very high expected mechanical reliability, large clearances, low hemolysis, and a relatively small size compared to current pulsatile devices. A unique configuration of magnetic actuators on the inlet side and exit sides of the impeller provides full 5 axis control and suspension of the impeller. The bearing system is divided into segments which allow for 3 displacement axes and 2 angular control axes. The controller chosen for the first suspension tests consists of a decentralized set of 5 proportional integral derivative (PID) controllers. This document describes both the controller and an overview of some results pertaining to the magnetic bearing performance. The pump has been successfully operated in both water and blood under design conditions suitable for use as a ventricular assist device.

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open-loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional-integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.

Monarticular flares occurring in patients with rheumatoid arthritis (RA) usually signify either a worsening of the underlying condition or a superimposed septic process. This report describes 2 patients with RA who had stress fractures of the fibular head, masquerading as monarticular flares of ankle arthritis.