Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Metabolic disorder and functional disturbance in the central executive network in minimal hepatic encephalopathy.

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.

Oxygen Vacancy Mediation in SnO2 Electron Transport Layers Enables Efficient, Stable, and Scalable Perovskite Solar Cells.

Previous findings have suggested a close association between oxygen vacancies in SnO2 and charge carrier recombination as well as perovskite decomposition at the perovskite/SnO2 interface. Underlying the fundamental mechanism holds great significance in achieving a more favorable balance between the efficiency and stability. In this study, we prepared three SnO2 samples with different oxygen vacancy concentrations and observed that a low oxygen vacancy concentration is conducive to long-term device stability. Iodide ions were observed to easily diffuse into regions with high oxygen vacancies, thereby speeding up the deprotonation of FAI, as made evident by the detection of the decomposition product formamide. In contrast, a high oxygen vacancy concentration in SnO2 could prevent hole injection, leading to a decrease in interfacial recombination losses. To suppress this decomposition reaction and address the trade-off, we designed a bilayer SnO2 structure to ensure highly efficient carrier transport still while maintaining a chemically inert surface. As a result, an enhanced efficiency of 25.06% (certified at 24.55% with an active area of 0.09 cm2 under fast scan) was achieved, and the extended operational stability maintained 90% of their original efficiency (24.52%) after continuous operation for nearly 2000 h. Additionally, perovskite submodules with an active area of 14 cm2 were successfully assembled with a PCE of up to 22.96% (20.09% with an aperture area).

Chemical Reaction of FA Cations Enables Efficient and Stable Perovskite Solar Cells.

Organometal halide perovskite solar cells (PSCs) have received great attention owing to a rapid increase in power conversion efficiency (PCE) over the last decade. However, the deficit of long-term stability is a major obstacle to the implementation of PSCs in commercialization. The defects in perovskite films are considered as one of the primary causes. To address this issue, isocyanic acid (HNCO) is introduced as an additive into the perovskite film, in which the added molecules form covalent bonds with FA cations via a chemical reaction. This chemical reaction gives rise to an efficient passivation on the perovskite film, resulting in an improved film quality, a suppressed non-radiation recombination, a facilitated carrier transport, and optimization of energy band levels. As a result, the HNCO-based PSCs achieve a high PCE of 24.41% with excellent storage stability both in an inert atmosphere and in air. Different from conventional passivation methods based on coordination effects, this work presents an alternative chemical reaction for defect passivation, which opens an avenue toward defect-mitigated PSCs showing enhanced performance and stability.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

Ascorbic acid releases dormancy and promotes germination by an integrated regulation of abscisic acid and gibberellin in Pyrus betulifolia seeds.

Seed dormancy is an important life history state in which intact viable seeds delay or prevent germination under suitable conditions. Ascorbic acid (AsA) acts as a small molecule antioxidant, and breaking seed dormancy and promoting subsequent growth are among its numerous functions. In this study, a germination test using Pyrus betulifolia seeds treated with exogenous AsA or AsA synthesis inhibitor lycorine (Lyc) and water absorption was conducted. The results indicated that AsA released dormancy and increased germination and 20 mmol L-1 AsA promoted cell division, whereas Lyc reduced germination. Seed germination showed typical three phases of water absorption; and seeds at five key time points were sampled for transcriptome analysis. It revealed that multiple pathways were involved in breaking dormancy and promoting germination through transcriptome data, and 12 differentially expressed genes (DEGs) related to the metabolism and signal transduction of abscisic acid (ABA) and gibberellins (GA) were verified by subsequent RT-qPCR. For metabolites, exogenous AsA increased endogenous AsA and GA3 but reduced ABA and the ABA/GA3 ratio. In addition, three genes regulating ABA synthesis were downregulated by AsA, while five genes mediating ABA degradation were upregulated. Taken together, AsA regulates the pathways associated with ABA and GA synthesis, catalysis, and signal transduction, with subsequent reduction in ABA and increase in GA and further the balance of ABA/GA, ultimately releasing dormancy and promoting germination.

Stable Electron-Transport-Layer-Free Perovskite Solar Cells with over 22% Power Conversion Efficiency.

Due to their low cost and simplified production process, electron-transport-layer-free (ETL-free) perovskite solar cells (PSCs) have attracted great attention recently. However, the performance of ETL-free PSCs is still at a disadvantage compared to cells with a conventional n-i-p structure due to the severe recombination of charge carriers at the perovskite/anode interface. Here, we report a strategy to fabricate stable ETL-free FAPbI3 PSCs by in situ formation of a low dimensional perovskite layer between the FTO and the perovskite. This interlayer gives rise to the energy band bending and reduced defect density in the perovskite film and indirect contact and improved energy level alignment between the anode and perovskite, which facilitates charge carrier transport and collection and suppresses charge carrier recombination. As a result, ETL-free PSCs with a power conversion efficiency (PCE) exceeding 22% are achieved under ambient conditions.

Intravenous lidocaine improves postoperative cognition in patients undergoing laparoscopic colorectal surgery: a randomized, double-blind, controlled study.

BACKGROUND: The risk of postoperative cognitive dysfunction(POCD) in laparoscopic surgery should not be overlooked. Intravenous lidocaine can reduce perioperative inflammatory response in patients undergoing laparoscopic surgery, while the effect of intraoperative intravenous lidocaine on postoperative cognitive function in patients undergoing laparoscopic colorectal cancer surgery has not been well studied. We investigated whether intraoperative lidocaine improves postoperative cognitive function after laparoscopic radical resection for colorectal cancer. METHODS: We conducted a prospective, randomized double blinded controlled trial to investigate the effect of intravenous lidocaine on rapid postoperative recovery in patients undergoing laparoscopic radical resection of colorectal cancer. The patients were randomly assigned to receive either intravenous lidocaine or saline. The primary outcome was cognitive dysfunction defined by a decrease from pre- to postoperative ≥ 2 of the Mini-Mental State Examination (MMSE) score, at the 3rd and the 7th postoperative days. Secondary outcomes were the MMSE raw score and parameters of the patients' postoperative recovery such as agitation and length of stay in the post-anaesthesia care unit (PACU), length of hospital stay, markers of inflammation (white blood cell count and CRP), and incidence of complications. RESULTS: Seventy-three patients in the lidocaine group and 77 patients in the control group completed the trial. The rate of cognitive dysfunction was lower in the lidocaine group than that in the control group, both at the 3rd (18.57% vs. 63.64% for each group respectively; RR = 0.26, 95%CI = 0.19-0.32; p < 0.0001) and at the 7th postoperative day (12.33% vs. 53.25% for each group respectively; RR = 0.28, 95%CI = 0.22-0.35; P < 0.001). The postoperative MMSE scores were also higher in the lidocaine group than in the control group both at the 3rd (median 25 vs. 24 respectively) and at the 7th postoperative day (26 vs. 24 respectively). Also, patients in the lidocaine group displayed a lower white blood cell count than the control group at the 1st postoperative day (8.5 ± 2.7 vs. 10.4 ± 3.3; p < 0. 001). No differences were evidenced for the other secondary outcomes. CONCLUSIONS: Intraoperative intravenous lidocaine can significantly improve postoperative cognitive function in patients undergoing laparoscopic radical resection of colorectal cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (16/1/2022, registration number: ChiCTR2200055683).

Treatment of Hepatitis E.

Hepatitis E virus (HEV) infections are the most common cause of acute hepatitis, but they can also take a chronic course. There is no specific therapy for acute hepatitis, and current treatment is supportive. Choosing ribavirin as the first-line therapy for chronic HEV is advisable, especially immunosuppressed individuals. Moreover, ribavirin therapy in the acute phase of infection provides major benefits for those at high risk of acute liver failure (ALF)/acute-on-chronic liver failure (ACLF). Pegylated interferon α has been used successfully for treatment of hepatitis E but is associated with major side effects. Cholestasis is one of the most common, but devastating, manifestations in hepatitis E. Current therapy for HEV aims to treat symptoms. Therapy generally involves several measures, such as vitamins, albumin, and plasma for supporting treatment, symptomatic treatment for cutaneous pruritus, ursodeoxycholic acid, Obeticholic acid, S-adenosylmethionine, etc. for removing jaundice. HEV infection during pregnancy and patients with underlying liver disease may develop liver failure. For these patients, active monitoring, standard care, and supportive treatment are the foundations. Ribavirin has successfully been used to prevent liver transplantation (LT). Prevention and treatment of complications are important for treatment of liver failure. Liver support devices are intended to support liver function until such time as native liver function recovers, or until LT. LT is widely considered as irreplaceable and definitive treatment for liver failure, particularly for patients who do not improve with supportive measures to sustain life.

[Chemical composition analysis and value evaluation of stems and leaves of Astragalus membranaceus var. mongholicus].

This study aimed to provide data support for resource utilization of the stems and leaves of Astragalus membranaceus var. mongholicus(SLAM) by analyzing and evaluating the chemical constituents. The crude protein, crude fiber, and soluble saccharide of SLAM were analyzed by Kjeldahl method, filtration method, and UV-Vis spectrophotometry, respectively. The nucleosides, amino acids, flavonoids, and saponins of SLAM were analyzed by ultraperformance liquid chromatography-triple quadrupole mass spectrometry(UPLC-TQ-MS). Combined with principal component analysis(PCA), the quality difference of resource components of SLAM was comprehensively evaluated. The results showed that the average content of crude protein, crude fiber, total polysaccharide, and redu-cing sugar in SLAM was 5.11%, 30.33%, 11.03 mg·g~(-1), and 31.90 mg·g~(-1), respectively. Six nucleosides, 15 amino acids, 22 flavonoids, and one saponin were detected, with an average content of 1.49 mg·g~(-1), 6.00 mg·g~(-1), 1.86 mg·g~(-1), and 35.67 µg·g~(-1), respectively. The content of various types of chemical components in SLAM differed greatly in different harvesting periods and growing years. The results of PCA showed that the quality of SLAM produced in Ningxia was superior. The results can provide references for the utilization of SLAM.

Reversal of right ventricular pressure loading improves biventricular function independent of fibrosis in a rabbit model of pulmonary artery banding.

Right ventricular (RV) pressure loading leads to RV and left ventricular (LV) dysfunction through RV hypertrophy, dilatation and fibrosis. Relief of RV pressure load improves RV function. However, the impact and mechanisms on biventricular reverse-remodelling and function are only partially characterized. We evaluated the impact of RV pressure overload relief on biventricular remodelling and function in a rabbit model of reversible pulmonary artery banding (PAB). Rabbits were randomized to three groups: (1) Sham-operated controls (n = 7); (2) PAB (NDef, n = 7); (3) PAB followed by band deflation (Def, n = 5). Sham and NDef animals were sacrificed at 6 weeks after PAB surgery. Def animals underwent PAB deflation at 6 weeks and sacrifice at 9 weeks. Biventricular geometry, function, haemodynamics, hypertrophy and fibrosis were compared between groups using echocardiography, magnetic resonance imaging, high-fidelity pressure-tipped catheters and histology. RV pressure loading caused RV dilatation, systolic dysfunction, myocyte hypertrophy and LV compression which improved after PAB deflation. RV end-diastolic pressure (RVEDP) decreased after PAB deflation, although remaining elevated vs. Sham. LV end-diastolic pressure (LVEDP) was unchanged following PAB deflation. RV and LV collagen volumes in the NDef and Def group were increased vs. Sham, whereas RV and LV collagen volumes were similar between NDef and Def groups. RV myocyte hypertrophy (r = 0.75, P < 0.001) but not collagen volume was related to RVEDP. LV myocyte hypertrophy (r = 0.58, P = 0.016) and collagen volume (r = 0.56, P = 0.031) correlated with LVEDP. In conclusion, relief of RV pressure overload improves RV and LV geometry, hypertrophy and function independent of fibrosis. The long-term implications of persistent fibrosis and increased biventricular filling pressures, even after pressure load relief, need further study. KEY POINTS: Right ventricular (RV) pressure loading in a pulmonary artery banding rabbit model is associated with RV dilatation, left ventricular (LV) compression; biventricular myocyte hypertrophy, fibrosis and dysfunction. The mechanisms and impact of RV pressure load relief on biventricular remodelling and function has not been extensively studied. Relief of RV pressure overload improves biventricular geometry in conjunction with improved RV myocyte hypertrophy and function independent of reduced fibrosis. These findings raise questions as to the importance of fibrosis as a therapeutic target.

Relationship between childhood sexual abuse and attitudes toward premarital sexual permissiveness among middle school students in Luzhou, China.

BACKGROUND: In recent years, the number of adolescents engaging in premarital sex has increased, and an increasing number of childhood sexual abuse (CSA) cases have been reported in China. Many studies have indicated that CSA has a well-established association with risky sexual activities. However, only a limited number of studies have explored possible reasons for this association among middle school students, a population that may engage in premarital sex, which is critical for the development of interventions to prevent risky sexual behavior. Based on random samples of middle school students from a Chinese city, this article investigated the relationship between CSA and students' premarital sexual permissiveness (PSP). METHODS: In a cross-sectional study conducted between 2016 and 2017 in Luzhou, China, 2292 middle school and high school students aged 12-18 years were recruited by multistage random sampling. All students were administered anonymous questionnaires. Multiple linear regression and binary logistic regression analyses were conducted to analyze the relationship between CSA and PSP. RESULTS: The prevalence of CSA was 15.4% (354/2292; 95% CI: 14-16.9%). A higher percentage of male respondents (18.2%) than female respondents (12.9%) had experienced CSA. A positive association between CSA and PSP was found among students. Respondents who had suffered CSA exhibited greater PSP, and this relationship was observed in the male sample, female sample and the total student sample in Luzhou (ß = - 3.76, P < 0.05; ß = - 2.79, P < 0.05; and ß = - 2.84, P < 0.05, respectively). Respondents who had suffered CSA were also more likely to express a double standard about premarital sex (odds ratio [OR] =1.41, P < 0.05), especially among male students (odds ratio [OR] =1.63, P < 0.05). CONCLUSIONS: Sex differences in CSA and the relationship between CSA and PSP were significant among this large sample of middle school students in Luzhou (China). The findings suggest that experiencing CSA may be closely related to youth attitudes toward premarital sex, especially among males. Therefore, it is important to emphasize the prevention of CSA and provide adolescent reproductive health programs to reduce the impact of CSA on sexual cognition and attitude, prevent premarital sex and promote positive attitudes toward sexual equality for middle school students.

Zinc induces reactive astrogliosis through ERK-dependent activation of Stat3 and promotes synaptic degeneration.

Reactive astrogliosis is an early event in Alzheimer's disease (AD) brain and plays a key role in synaptic degeneration in AD development. Zinc accumulates in extracellular fraction and synaptosomes in AD human brains with its effect on reactive astrocytes remaining unknown. Through Western blotting, Quantitative polymerase chain reaction (qPCR), and immunofluorescence detection on primary astrocytes treated by zinc and/or zinc chelator, we revealed that zinc induced harmful A1-type reactive astrogliosis in cultured primary astrocytes; the latter, promoted synaptic degeneration in primary neurons. The mechanism investigation showed that zinc induced activation of extracellular regulated protein kinase (ERK) and Janus kinase 2 (JAK2), which phosphorylated signal transduction and transcription activator 3 (Stat3) at serine 727 (S727-Stat3) and tyrosine 705 (Y705-Stat3), respectively, resulting in activation of Stat3. Stat3 phosphorylation at S727 by ERK plays a key role in zinc-induced astrogliosis. These data imply a new molecular mechanism of reactive astrogliosis in AD, in which excessive zinc activates Stat3 through up-regulating ERK signaling pathway.

Phase Tailoring of Ruddlesden-Popper Perovskite at Fixed Large Spacer Cation Ratio.

Ruddlesden-Popper (RP) metal halide perovskites are considered as promising optoelectronic materials due to their good environmental stability and desirable optoelectronic properties. However, the phase composition and ordering in the deposited film, with a fixed ratio of large organic spacer cation in the precursor solution, are hard to be further tailored for specific optoelectronic applications. Herein, it is shown that even with a fixed spacer cation ratio, the phase composition and ordering can still be largely regulated by utilizing different crystallization kinetics of various cations with the inorganic octahedral lead halide. By using two different short cations to compete with the large spacer cation, the phase composition can be continuously tailored from thin multiple quantum wells (MQWs) dominated to 3D perovskite dominated. The phase ordering can be reversed from small n phases' prior to large n phases' prior near the substrate. Finally, with the same amount of large spacer cation protection, the perovskite can be tailored for both high-performance electroluminescence and photovoltaics with favorable energetic landscape for the corresponding desired first-order excitonic recombination and second-order free electron-hole recombination, respectively. This exploration substantially contributes to the understanding of precise phase engineering in RP perovskite and may provide a new insight into the design of multiple functional devices.

The association of procedural variables and lipid parameters with coronary rotational atherectomy outcomes.

The aim of our study is to evaluate the association of rotational atherectomy (RA) operation procedural indices and baseline lipid parameters with the prognosis of the patients with severe coronary calcification who underwent RA. Our study population consists of 287 patients treated with RA in Fuwai Hospital from January 2013 to December 2019. We analyzed the patients' rotation procedural indices including the number of burrs, the size of burrs, approach site, the size of guiding catheter, along with the baseline level of lipoprotein(a) (Lp(a)), low-density lipoprotein-cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) to examine the association of these measurements with the prognosis of these patients using Cox regression analysis and Kaplan-Meier survival analysis. We find that during the follow-up period of 56.7 months with the median, the use of single burr in the patients who underwent RA was significantly associated with the occurrence of cumulative major adverse cardiac events (MACE) when compared with using non-single burrs [Hazard Ratio (HR) 0.43, 95% confidence interval (95% CI) 0.24-0.77, p = 0.004] from univariate Cox regression analysis; (HR 0.36, 95% CI 0.20-0.66, p = 0.001) from multivariate Cox regression analysis In addition, we find a higher event-free survival rate in the single-burr group after Kaplan-Meier survival analysis (Log rank p = 0.0033). However, there was no significant association of the size of burrs with the occurrence of MACE (HR 0.90, 95% CI 0.47-1.73, p = 0.76). Similarly, we find no significant associations between the approach site and the occurrence of MACE (HR 0.79, 95% CI 0.24-2.53, p = 0.69), the baseline Lp(a) (HR 1.07, 95% CI 0.76-1.49, p = 0.71), the level of LDL-C (HR 0.83, 95% CI 0.55-1.26, p = 0.38) or hs-CRP (HR 0.85, 95% CI 0.45-1.58, p = 0.60). We find that the patients who receive RA with a single burr have better outcomes than those who receive RA with non-single burrs. Moreover,we find that the number of burrs used in RA instead of the size of burrs, approach site, the size of guiding catheter, or baseline levels of Lp(a), LDL-C or hs-CRP had significant association with the prognosis of RA patients.

TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils.

Stringent control of NF-κB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-ß activated kinase-1 (TAK1) is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(ΔM/ΔM)) led to development of splenomegaly and lymphomegaly associated with neutrophilia. Compared with wild-type cells, TAK1-deficient neutrophils enhanced the phosphorylation of the kinases IKK, p38, and JNK and the production of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) after lipopolysaccharide (LPS) stimulation. Map3k7(ΔM/ΔM) mice were significantly more susceptible to LPS-induced septic shock and produced higher amounts of IL-1ß, IL-6, and TNF-α in plasma than do wild-type mice. Specific ablation of p38 rescued the phenotype and functional properties of Map3k7(ΔM/ΔM) mice. Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner.

Relationship between the sodium fluorescein yellow fluorescence boundary and the actual boundary of high-grade gliomas during surgical resection.

OBJECTIVE: Resection of high-grade glioma with sodium fluorescein can improve the resection rate of the glioma and improve survival. However, it is unclear whether the yellow fluorescence boundary of the high-grade glioma is consistent with the actual boundary of the tumor. This study explores the yellow fluorescence boundary and the actual tumor boundary in high-grade glioma surgery. METHODS: This is a retrospective analysis of 10 patients with high-grade gliomas who underwent tumor visualization with sodium fluorescein. After staining of the tumor, random selections of both developed and non-developed yellow fluorescent border tissue at the fluorescence chromogenic boundary were made, followed by pathological examination. Claudin-5, an important component of the tight connections between vascular endothelial cells, was assessed by immunohistochemistry and qRT-PCR in the tumor and surrounding tissues in order to determine the tumor cell content of the tissue, blood-brain barrier damage, and vascular proliferation. The yellow fluorescence boundary was compared with the actual tumor boundary and the results analyzed. RESULTS: Tumor cells were still detected outside the yellow fluorescence boundary during high-grade glioma surgery (P < 0.05). Claudin-5 expression was higher in high-grade gliomas than in adjacent normal tissues (P < 0.05), while disconnected Claudin-5 expression was associated with intraoperative yellow fluorescence imaging (r = 0.67). CONCLUSIONS: There is a difference between the yellow fluorescence boundary and the actual boundary of the tumor in high-grade glioma, and there are glioma cell infiltrations in the brain tissue of the undeveloped yellow fluorescent border. To ensure patient recovery and function, it is recommended that tumor resection be expanded based on yellow fluorescence visualization. Claudin-5 is overall up-regulated in high-grade gliomas, but some Claudin-5 expression is disconnected. This Claudin-5 expression pattern may be related to the development of yellow fluorescence.

Detoxification of Ochratoxin A by a novel Aspergillus oryzae strain and optimization of its biodegradation.

The mycotoxin Ochratoxin A (OTA) causes serious health risks and is found in food products throughout the world. The most promising method to detoxify this compound is biodegradation. In this study, Aspergillus oryzae strain M30011 was isolated and characterized based on its considerable capacity to degrade OTA. The degradation product (compound I) of A. oryzae-treated OTA was isolated, and its toxicity response was also evaluated. Furthermore, the relationships between three key cultivation condition factors affecting the OTA degradation rate were examined using the response surface methodology (RSM). Compound I was identified as ochratoxin α (C11H9O5Cl), and the toxicity response experiments indicated that A. oryzae detoxified OTA to a great extent. A maximum degradation rate of 94% was observed after 72h. This study demonstrates the potential for using A. oryzae to detoxify OTA and suggests that it could be applied in the food industry to improve food safety and quality.

Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease.

BACKGROUND: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM). METHODS: This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization. RESULTS: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026). CONCLUSIONS: The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial.

INTRODUCTION: A decline in physical function is highly prevalent and a poor prognostic factor in cirrhosis. We assessed the benefits of a home-based physical activity program (HB-PAP) in patients with cirrhosis with a randomized pilot trial. METHODS: All participants received a personal activity tracker to monitor daily activities and were given 12 g/day of an essential amino acid supplement. The HB-PAP intervention consisted of biweekly counseling sessions to increase physical activity for 12 weeks. Six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) assessed changes in aerobic fitness. Different anthropometric measuring tools were used for skeletal muscle and adiposity assessment. RESULTS: Seventeen patients (60% male; 29% nonalcoholic steatohepatitis/cryptogenic, 29% hepatitis C, 24% alcohol, 18% other) were randomized, 9 to HB-PAP group. There were no significant differences in MELD-sodium between HB-PAP and controls at baseline or after the 12-week intervention. By the end of study, there was a significant between-group difference in daily step count favoring the active group (2627 [992-4262], p = 0.001), with less sedentary patients in the active group (33-17% vs. 25-43%, p = 0.003). The 6MWT improved in the HB-PAP group (423 ± 26 m vs. 482 ± 35 m), while the controls had a nonsignificant drop (418 ± 26 m vs. 327 ± 74 m) with a significant between-group difference. CPET did not change. Other than an improvement in psoas muscle index, there were no differences in anthropometry, or in quality of life. CONCLUSIONS: HB-PAP maintained physical performance and improved aerobic fitness according to 6MWT but not CPET, supporting the use of personal activity trackers to monitor/guide home-based prehabilitation programs in cirrhosis.