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C2+ hydrocarbons, especially C2+ olefins, as important basic chemical raw materials, mainly come from petroleum cracking. With the increasing scarcity of petroleum resources, the search for new olefins production routes has become the focus of research, and the production of olefins by the oxidative coupling of methane (OCM) process has attracted extensive attention. The OCM route is an important alternative to the production of olefins from petroleum resources and is also an important direction for the development of efficient and clean utilization of natural gas. In this paper, the mechanism, catalysts, and other key factors for the production of olefins by methane oxidative coupling are reviewed. The mechanism of OCM, including the reaction pathway and the formation of intermediate products, is introduced. Then, commonly used catalysts, such as alkali metal/alkaline earth metal oxides, rare earth metal oxides, composite metal oxides with special structures, and classical catalysts Mn/Na2WO4/SiO2, and their mechanisms of action in the reaction are discussed. In addition, the application of chemical looping oxidative coupling of methane (CLOCM) in olefin production is also investigated, which is a promising alternative way due to the high selectivity of olefins and the low cost of catalysts owing to the excellent performance of the catalyst recycling. These studies will help to further understand the mechanism of OCM for olefin production and provide guidance and support for applications in related fields. [ABSTRACT FROM AUTHOR]

The core-shell nanoparticles of Au@TiO2 were synthesised via a simple and flexible hydrothermal route. The structure and properties were characterised by X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy, ultraviolet/visible diffuse reflectance spectra, photoluminescence spectra and Raman spectra. The photocatalytic activity and the photoelectrochemical behaviours were investigated. Compared to TiO2, Au@TiO2 exhibits superior photocatalytic activity and photoelectrochemical property. The enhanced properties of Au@TiO2 attributed to the Au core as electron trap to promote the separation of photogenerated charge carriers in the photocatalytic process, which was also confirmed by the results of electrochemical impedance spectra and photoluminescence. [ABSTRACT FROM AUTHOR]

In this work, g-C3N4/melem nanorods hybrids were synthesized via a rapid cooling process with H2SO4-assisted treatments of bulk g-C3N4. The results show that post treatment of pristine g-C3N4 using concentrated H2SO4 can produce a hybrid crystal structure containing both melem and g-C3N4. The melem nanorods were formed based on H2SO4 exfoliation, regrowth process and nanoplates roll-up mechanism through a rapid cooling process. The g-C3N4/melem nanorods hybrids exhibited efficient degradation of methyl orange and the efficiency was nearly 100% in 80 min, which presented much better than bulk g-C3N4 (giving a degradation efficiency of 67% in 80 min). The enhanced photocatalytic performance of g-C3N4/melem nanorods hybrids mainly originates from the synergistic effect of g-C3N4 and melem, which the g-C3N4/melem hybrids can improving the efficiency of photogenerated charge separation of g-C3N4. This study contributes towards an effective strategy for optimizing the crystalline structure and nanostructure of g-C3N4/melem hybrids to enhanced g-C3N4 photodegradation activity. [ABSTRACT FROM AUTHOR]

The pathogenesis of LPS-induced acute kidney injury (AKI) requires signaling through tumor necrosis factor-[alpha] (TNF) receptor 1 (TNFR 1), which within the kidney is primarily located in the endothelium. We showed previously that caspase inhibition protected mice against LPS-induced AKI and in parallel significantly inhibited LPS-induced renal inflammation. Therefore we hypothesized that caspase activation amplifies TNF-induced inflammation in renal endothelial cells (ECs). In cultured renal ECs, TNF induced apoptosis through a caspase-8-dependent pathway. TNF caused translocation of the p65 subunit of NF-KB to the nucleus, resulting in upregulation of inflammatory markers such as adhesion molecules ICAM-1 and VCAM-1. However, the broadspectrum caspase inhibitor Boc-D-fmk reduced NF-[kappa]B activation as assessed by gel shift assay, reduced phosphorylation of subunit I[kappa]B[alpha], and significantly inhibited TNF-induced expression of ICAM-1 and VCAM-1 as assessed by both real-time PCR and flow cytometry. Broad-spectrum caspase inhibition markedly inhibited neutrophil adherence to the TNF-activated endothelial monolayer, supporting the functional significance of this effect. Specific inhibitors of caspases-8 and -3, but not of caspase-1, reduced TNF-induced NF-[kappa]B activation. Caspase inhibition also reduced TNF-induced myosin light chain (MLC)-2 phosphorylation, and activation of upstream regulator RhoA. Consistent with this, MLC kinase (MLCK) inhibitor ML-7 reduced TNF-induced NF-[kappa]B activation. Thus caspase activation influences NF-[kappa]B signaling via its affect on cytoskeletal changes occurring through RhoA and MLCK pathways. These cell culture experiments support a role for caspase activation in TNF-induced inflammation in the renal endothelium, a key event in LPS-induced AKI. adhesion molecules; cytokines; sepsis; acute kidney injury; neutrophil

A stable polarization mode operation of long-wavelength tunable vertical-cavity surface-emitting lasers is demonstrated.

Objectives. Untreated acromegaly is a nature model for unveiling the diabetogenic effects of GH. CGMS can uncover more glucose profile of acromegaly. This study aimed to evaluate the insulin resistance (IR), β-cell function, and glycemic spectrum of patients with newly diagnosed acromegaly with normal glucose tolerance (NGT). Methods. This study was conducted in Huashan Hospital from January 2015 to February 2019. Eight newly diagnosed acromegalic patients without history of diabetes and eight age- and gender-matched healthy subjects were enrolled. All participants underwent oral glucose tolerance test (OGTT) and 72 h continuous glucose monitoring (CGM). Parameters on β-cell function and IR were calculated. Mean blood glucose (MBG) in 24 hours was adopted for the evaluation of the glycemic level, and standard deviation of blood glucose (SDBG) and mean amplitude of glycemic excursion (MAGE) were used for glucose fluctuation. Results. HbA1c in the acromegaly group was significantly higher than in the control. During OGTT, glucose peaked at 60 min in acromegaly and at 30 min in controls. After glucose load, the acromegaly group had significantly higher insulin levels than controls, especially in 120 min and 180 min. Both insulin sensitivity index and disposal index after glucose load of acromegaly were significantly lower than those of controls. Moreover, acromegalic subjects had significantly higher MBG than controls. Conclusions. The newly diagnosed acromegalic patients with NGT were characterized by IR and impaired β-cell function after glucose load. CGM showed that MBG of NGT acromegaly patients was higher than that of normal people. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI. [ABSTRACT FROM AUTHOR]

Aims. To investigate the association between mean plasma glucose and inhospital death proportion. Methods. We retrospectively collected 162,169 inpatient data in Huashan Hospital from January 2012 to December 2015. Mean plasma glucose was calculated and considered as the average glycemia control during hospitalization. Patients were stratified into six groups according to mean plasma glucose. Nonlinear regression was performed to determine the associations between mean plasma glucose and inhospital death proportion, medical cost, and length of stay. Multivariate logistic regressions were performed to evaluate the relationship of mean plasma glucose and outcomes controlling for confounders including age, gender, and others. Subgroup analyses were performed on basis of whether they were surgical patients, ICU patients, patients with diabetes, or others. Results. Of the 162,169 hospitalized participants, 53.32% were male and 989 died during hospitalization. Nonlinear regression showed there were positive and significant associations between mean plasma glucose and death proportion, medical cost, and length of stay (P < 0.001 for all). Multivariate logistic regressions showed that, compared with group B, a statistically significant association between mean plasma glucose and predicted outcome was apparent, with the odds ratios (95% confidence interval) of 5.79 (3.51–9.55), 2.85 (2.40–3.38), 6.29 (5.24–7.54), 9.34 (7.51–11.62), and 23.52 (16.64–33.26), for group A, group C, group D, group E, and group F, respectively. There was a U-shaped association between mean plasma glucose and death proportion. Subgroup analyses showed similar associations between mean plasma glucose and death proportion, medical cost, and length of stay as in the whole sample. Conclusions. There was a U-curve association between mean plasma glucose with inhospital death proportion. Mean plasma glucose was associated positively with medical cost and length of stay. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs).Methods: We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery.Results: A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05).Conclusion: Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. [ABSTRACT FROM AUTHOR]

Imprinting is a biological process where a young animal acquires several of its behavioural characteristics from its parent and then follows them around and is called filial imprinting. However, imprinting can implicitly be inside the materials that possess a suitable affinity to integrate themselves with the surrounding liquid environment. In this research, an example of imprinting in molybdenum disulfide (MoS2) nanosheets was demonstrated. The as-prepared MoS2 containing a polar edge and low-polar plane faces on its flower-like morphology give it an imprinting ability to adhere to water or n-hexane. Therefore, imprinted MoS2 tends to retain the phase of the imprinting solvent, which is called solvent identification. More interestingly, imprinted MoS2 can in addition fulfill a highly efficient heterophasic extraction of rhodamine B (RhB) from water to n-hexane or lauric acid from n-hexane to water in seconds. At the same time, imprinted MoS2 solvent identification exhibits rapid self-separation after shaking, which avoids tedious centrifugation and filtration in a separation-purification process and makes it more convenient. [ABSTRACT FROM AUTHOR]

We have characterized a novel 21 amino acid-peptide derived from Antrum Mucosal Protein (AMP)-18 that mediates growth promotion of cultured normal epithelial cells and mitigates radiation-induced oral mucositis in animal models, while suppressing in vitro function of cancer cells. The objective of this study was to evaluate these dual potential therapeutic effects of AMP peptide in a clinically relevant animal model of head and neck cancer (HNC) by simultaneously assessing its effect on tumor growth and radiation-induced oral mucositis in an orthotopic model of HNC. Bioluminescent SCC-25 HNC cells were injected into the anterior tongue and tumors that formed were then subjected to focal radiation treatment. Tumor size was assessed using an in vivo imaging system, and the extent of oral mucositis was compared between animals treated with AMP peptide or vehicle (controls). Synergism between AMP peptide and radiation therapy was suggested by the finding that tumors in the AMP peptide/radiation therapy cohort demonstrated inhibited growth vs. radiation therapy-only treated tumors, while AMP peptide-treatment delayed the onset and reduced the severity of radiation therapy-induced oral mucositis. A differential effect on apoptosis appears to be one mechanism by which AMP-18 can stimulate growth and repair of injured mucosal epithelial cells while inhibiting proliferation of HNC cells. RNA microarray analysis identified pathways that are differentially targeted by AMP-18 in HNC vs. nontransformed cells. These observations confirm the notion that normal cells and tumor cells may respond differently to common biological stimuli, and that leveraging this finding in the case of AMP-18 may provide a clinically relevant opportunity. [ABSTRACT FROM AUTHOR]

Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD. [ABSTRACT FROM AUTHOR]

In pH 1.0 acidic medium, 12-Tungstophosphoric acid (TP) reacted with meclofenoxate (MFX) to form an ion-associate complex, which resulted in a significant enhancement of the resonance Rayleigh scattering (RRS) intensity. The RRS intensity at the maximum scattering peak of 374 nm was linear to the concentration of MFX in the range of 0.2-12.0 μg mL-1. Therefore, a novel method for the determination of MFX by RRS method coupled with flow injection analysis (FIA) technique was developed. The method has highly sensitivity and the detection limit (3σ) was 5.6 ng mL-1. The present method was applied to the determination of MFX in pharmaceutical preparations and the results agreed well with those provided by the pharmacopeia. The average recovery of standard addition in capsules was 97.0-103.1%. The proposed method exhibited the satisfactory reproducibility with a relative standard derivation (R.S.D.) of 3.7% for 9 successive determinations of 4.0 μg mL-1 MFX. The maximal sample throughput in the optimized system was 48 h-1. In addition, the optimum experiment condition, the effect of coexisting substance, and influence of FIA variables were investigated in the paper. [ABSTRACT FROM AUTHOR]

Abstract: Mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play an important role in a myriad of cellular processes, including cell proliferation, differentiation, and apoptosis. Abnormal activation of MAP kinases has been shown to participate in a variety of human diseases which include cancer, septic shock, rheumatoid arthritis, diabetes, and cardiovascular diseases. Active MAP kinase enzymes are not only valuable for basic biomedical research but are also critical for the development of pharmacological inhibitors as therapeutic drugs in the treatment of relevant human diseases. MAP kinases produced in a bacterial system are poorly active due to a lack of proper phosphorylation at their characteristic threonine and tyrosine residues. To overcome these limitations, we have developed a mammalian expression system for high level expression and one-step purification of enzymatically MAP kinases. We cloned JNK1, p38, and p38-regulated MAP kinase-activated protein kinase-2 into the mammalian expression vector pEBG, and expressed these protein kinases as glutathione S-transferase fusion proteins in human embryonic kidney 293T cells through transient transfection. The protein kinases were activated in vivo through treating the transfected cells with sodium arsenite and affinity-purified using glutathione–Sepharose beads. The enzymatic activities of these protein kinases were demonstrated by Western blot analysis and in vitro kinase assays. Our results indicate that this system is an extremely powerful tool for generating valuable reagents, and could be very valuable for proteomic studies. [Copyright &y& Elsevier]

Mutations in the FLT3 gene are the most common genetic alteration found in AML patients. FLT3 internal tandem duplication (ITD) mutations result in constitutive activation of FLT3 tyrosine kinase activity. The consequences of this activation are an increase in total phosphotyrosine content, persistent downstream signaling, and ultimately transformation of hematopoietic cells to factor-independent growth. The Src homology (SH)2 domain-containing protein-tyrosine phosphatase (SHP)-1 is involved in the down-regulation of a broad range of growth factor and cytokine-driven signaling cascades. Loss-of-function or deficiency of SHP-1 activity results in a hyperproliferative response of myelomonocytic cell populations to growth factor stimulation. In this study, we examined the possible role of SHP-1 in regulating FLT3 signaling. We found that transformation of TF-1 cells with FLT3/ITD mutations suppressed the activity of SHP-1 by ∼3-fold. Suppression was caused by decreased SHP-1 protein expression, as analyzed at both the protein and RNA levels. In contrast, protein levels of SHP-2, a phosphatase that plays a stimulatory role in signaling through a variety of receptors, did not change significantly in FLT3 mutant cells. Suppressed SHP-1 protein levels in TF-1/ITD cells were partially overcome after cells were exposed to CEP-701, a selective FLT3 inhibitor. SHP-1 protein levels also increased in naturally occurring FLT3/ITD expressing AML cell lines and in primary FLT3/ITD AML samples after CEP-701 treatment. Furthermore, a small but reproducible growth/survival advantage was observed in both TF-1 and TF-1/ITD cells when SHP-1 expression was knocked down by RNAi. Taken together, these data provide the first evidence that suppression of SHP-1 by FLT3/ITD signaling may be another mechanism contributing to the transformation by FLT3/ITD mutations. [ABSTRACT FROM AUTHOR]

Expression of enzymatically active mammalian proteins in Escherichia coli can proven to be a challenging task due to poor solubility, improper folding, and lack of adequate posttranslational modification. Expression of mammalian proteins using baculovirus or yeast systems is time-consuming and may also be subject to inadequate modification. In order to overcome these technical difficulties, we have developed a mammalian expression system for the convenient subcloning of cDNA fragments, high-level expression, and one-step purification of enzymatically active proteins. The mammalian expression vector pEBG that expresses glutathione S-transferase fusion proteins was modified to create an SrfI restriction site in the multiple cloning site. The protein coding sequences of MAP kinase phosphatase-1 (MKP-1), MAP kinase phosphatase-2 (MKP-2), and the tumor suppressor PTEN were PCR-amplified using Pfu DNA polymerase and cloned into the SrfI site through SrfI digestion-coupled ligation. The resulting plasmids were transiently transfected into 293T cells using FuGENE 6 transfection reagent. Forty eight hours after transfection, cells were harvested and bioactive recombinant proteins were purified by glutathione-Sepharose beads. Protein yield, which ranged from 200 to 700 μg, was more than adequate for biochemical studies. The usefulness of this versatile system for studying protein function and its potential application for proteomics research are discussed. [Copyright &y& Elsevier]

The formation and decomposition of gas hydrates in nanoscale sediments can simulate the accumulation and mining process of hydrates. This paper investigates the Raman spectra of water confined inside the nanoscale pores of silica gel, the decomposition characterizations of methane hydrate that formed from the pore water, and the intrinsic relationship between them. The results show that pore water has stronger hydrogen bonds between the pore water molecules at both 293 K and 223 K. The structure of pore water is conducive to the nucleation of gas hydrate. Below 273.15 K, the decomposition of methane hydrate formed from pore water was investigated at atmospheric pressure and at a constant volume vessel. We show that the decomposition of methane hydrate is accompanied by a reformation of the hydrate phase: The lower the decomposition temperature, the more times the reformation behavior occurs. The higher pre-decomposition pressure that the silica gel is under before decomposition is more favorable to reformation. Thus, reformation is the main factor in methane hydrate decomposition in nanoscale pores below 273.15 K and is attributed to the structure of pore water. Our results provide experimental data for exploring the control mechanism of hydrate accumulation and mining. [ABSTRACT FROM AUTHOR]

Abstract Objective Sulfur dioxide (SO 2) plays an important role in maintaining homeostasis of cardiovascular system. This study was aimed to investigate cardioprotective effects of SO 2 on in the rat and the underlying mechanism. Methods and results Sepsis model induced by cecal ligation and puncture (CLP) in rats were used. SO 2 donor (NaHSO 3 /Na 2 SO 3 , 1:3 M/M) was administered intraperitoneally at a dose of 85 mg/kg. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were stimulated with LPS (1 mg/mL) in presence or absence of different concentrations of SO 2 (10, 50 and 100 μmol/L). SO 2 donor could restore the decreased levels of SO 2 in plasma and heart of septic rats. SO 2 exhibited dramatic improvement in cardiac functions. At 24 h after CLP, SO 2 treatments decreased the number of TUNEL-positive cells, Bax/Bcl-2 ratio and activity of caspase-3. Moreover CLP-induced inflammatory response was also relieved by SO 2. In NRCMs, SO 2 could suppress the LPS-induced myocardial injury, leading to an increase in cell viability, a decrease in LDH and apoptotic rate. Western blot showed that the expression of TLR4, NLRP3, and Caspase-1 were obviously increased in myocardial tissue of CLP group or in NRCMs of LPS group, while SO 2 significantly inhibited the CLP-induced or LPS-induced TLR4, NLRP3, and Caspase-1 expression. Conclusion SO 2 attenuated sepsis-induced cardiac dysfunction likely in association with the inhibiting inflammation via TLR4/NLRP3 signaling pathway. Highlights • Myocardial SO 2 levels decreased in sepsis. • SO 2 ameliorates sepsis-induced myocardial damage. • SO 2 inhibits the increased protein levels of TLR4 in sepsis. • SO 2 attenuates the activation of NLRP3 inflammasome in sepsis. [ABSTRACT FROM AUTHOR]

Herein, the catalysts of ruthenium and molybdenum oxide nanoparticles supported on activated carbon (AC) were synthesized by precursor stepwise impregnation and employed for the hydrodeoxygenation (HDO) of lignin oil. The XRD, TEM, XPS and NH 3 -TPD-MS result of RuMoO x /AC catalysts confirm that the method of loading molybdenum precursor before ruthenium precursor is advantageous for the MoO x and Ru nanoparticles high dispersion and the reduction of MoO x species enhance the amount of acidity of catalyst. Meanwhile, the reduction temperature of RuMoO x /AC-1-T catalysts could effectively regulate the MoO x species that determine the activity and product distribution of HDO. The conversion of aromatic monomers/dimers were up to 96% with high selectivity of hydrocarbon over RuMoO x /AC-1-350 catalyst at 160 °C and 30 bar H 2. Which is attributed to the MoO 3 and Ru species possess the excellent activity of benzene ring deep hydrogenation, ether bond breaking and acid dehydration. The RuMoO x /AC-1-350 catalyst effectively converted lignin oil (from the depolymerization of cornstalk hydrolysis residue) into hydrocarbons (56.9 wt%) and cyclohexanol/ethers (18.7 wt%) under 280 °C and 3 bar H 2. The durability of the RuMoO x /AC-1-350 catalyst for HDO of lignin oil was also investigated and showed that the RuMoO x /AC-1-350 catalyst had good stability, regenerability and repeatability. [ABSTRACT FROM AUTHOR]

uclear import of HuR, a shuttling RNA-binding protein, is associated with reduced stability of its target mRNAs. Increased function of the AMP-activated protein kinase (AMPK), an enzyme involved in responding to metabolic stress, was recently shown to reduce the cytoplasmic levels of HuR. Here, we provide evidence that importin α1, an adaptor protein involved in nuclear import, contributes to the nuclear import of HuR through two AMPK-modulated mechanisms. First, AMPK triggered the acetylation of importin α1 on Lys22, a process dependent on the acetylase activity of p300. Second, AMPK phosphorylated importin α1 on Ser105. Accordingly, expression of importin α1 proteins bearing K22R or S105A mutations failed to mediate the nuclear import of HuR in intact cells. Our results point to importin α1 as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import. [ABSTRACT FROM AUTHOR]

Examines the effect of human proto-oncogene (HER-2) gene targeting on the growth of HeLa cells. Introduction of HER-2 to HeLa cells by electroporation; Selection of HER-2 allies by G418 and Gancyclovir; Location of HER-2.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by epithelial proliferation and progressive cyst enlargement. Using a non-targeted high-resolution metabolomics approach, we analyzed biofluids from 36 ADPKD and 18 healthy controls with estimated glomerular filtration rate (eGFR) > 60 ml/min to identify features specific to ADPKD or that associate with disease severity [eGFR or height-corrected total kidney volume (htTKV)]. Multiple pathways differed between ADPKD subjects and controls, with the histidine pathway being the most highly represented. Plasma histidine, urinary N-methylhistamine, methylimidazole-acetaldehyde, and imidazole-acetaldehyde, as well as 3-methylhistidine and anserine were increased, while plasma N-acetylhistamine and urinary imidazole-acetic acid were decreased in ADPKD compared to controls. In ADPKD, urinary histidine and a histidine derivative, urocanate (a precursor of glutamate), were significantly associated. HtTKV and eGFR were inversely associated with urinary glutamine and plasma 4-imidazolone-5-propionic acid, respectively. Supernatant from cultured human ADPKD renal cystic epithelia demonstrated increased aspartate and glutamate levels at 8 and 24 hours compared to primary tubular epithelia (p < 0.001). Following exposure over 48 hours to α-fluromethylhistidine, an inhibitor of histamine production, primary human PKD1 cyst epithelia proliferation increased significantly from baseline (p < 0.01) and greater than non-cystic epithelia (p < 0.05). The histidine ammonia lyase inhibitor nitromethane reversed α-fluromethylhistidine-induced cyst epithelia proliferation indicating a role for glutamate in cyst growth. In conclusion, histidine metabolism is altered preferentially leading to glutamate production and epithelial proliferation in ADPKD and associates with disease severity., (© 2024 The American Clinical and Climatological Association.)

Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis., Methods and Design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events., Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis., Clinical Trial Registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Li, Sun, Li, Liu, Wang, Sun, Xu, Qi, Xie, Zhou, Ni, Yao, Chen, Yu, Jiang, Ning, Sheng, Chen, Wang, Tong, Cao, Sun and Mao.)

Objective: In intensive care units (ICUs), carbapenem-resistant Enterobacterales (CRE) pose a significant threat. We aimed to examine the distribution, epidemiological characteristics, and risk factors for CRE positivity in ICUs., Materials and Methods: This cross-sectional study was conducted in 96 ICUs of 78 hospitals in Henan Province, China. The clinical and microbiological data were collected. A multivariable logistic regression model was used to analyze the risk factors for CRE positivity., Results: A total of 1,009 patients were enrolled. There was a significant difference in CRE positive rate between pharyngeal and anal swabs (15.16 vs. 19.13%, P < 0.001). A total of 297 carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 22 carbapenem-resistant Escherichia coli (CR-ECO), 6 carbapenem-resistant Enterobacter cloacae (CR-ECL), 19 CR-KPN/CR-ECO, and 2 CR-KPN/CR-ECL were detected. Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and a combination of KPC and NDM were detected in 150, 9, and 11 swab samples, respectively. Multivariable logistic regression analysis determined length of ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotics exposure as independent risk factors for CRE positivity. Age and cardiovascular diseases were independent risk factors for mixed infections of CRE. The occurrence of CRE in secondary and tertiary hospitals was 15.06 and 25.62%, respectively ( P < 0.05). Patients from tertiary hospitals had different clinical features compared with those from secondary hospitals, including longer hospital stays, a higher rate of patients transferred from other hospitals, receiving renal replacement therapy, exposure to immunosuppressive drugs, use of antibiotics, and a higher rate of the previous infection., Conclusion: In ICUs in Henan Province, CRE positive rate was very high, mostly KPC-type CR-KPN. Patients with prolonged ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotic exposure are prone to CRE. Age and cardiovascular diseases are susceptibility factors for mixed infections of CRE. The CRE positive rate in tertiary hospitals was higher than that in secondary hospitals, which may be related to the source of patients, antibiotic exposure, disease severity, and previous infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Guo, Zhang, Shi, Qin, Wang, Chang, Chen, Chen, Guo, Guo, Han, Han, Hu, Jin, Li, Liu, Lou, Lu, Ma, Shan, Sun, Zhang, Zheng and Shao.)

Background: Acute lung injury (ALI) caused by sepsis is the most common disease and the leading cause of death in intensive care units. Recent studies have revealed that long non-coding RNAs (LncRNAs) are abnormally expressed in sepsis. This study aimed to clarify the role and mechanism of Taurine up-regulated gene 1 (TUG1) in ALI caused by sepsis., Methods: Lipopolysaccharide (LPS) was used to simulate sepsis-induced ALI model. RT-PCR, Dual luciferase reporter (DLR) assay and RNA immunoprecipitation (RIP) were used to detect TUG1 and miR-494. The rat model with sepsis-induced ALI was established by intraperitoneal injection of LPS to verify the results of in vitro experiments., Results: The expressions of TUG1 and PDK4 were down-regulated while the expression of miR-494 was up-regulated in lung tissues and human small airway epithelial cells (HSAECs). TUG1 was indirectly mediated. Overexpression of TUG1 or inhibition of miR-494 could significantly improve the survival rate of HSAECs. Transfection of miR-494 mimics achieved the opposite effect. Enzyme-linked immunosorbent assay (ELISA) showed that the expression of arthritis-related factors in rats was increased after up-regulating TUG1., Conclusion: TUG1 is lowly expressed in sepsis. Up-regulating TUG1 can alleviate the inflammatory response in ALI caused by LPS-induced sepsis, which may be a clinical treatment target., Competing Interests: None., (AJTR Copyright © 2021.)

This article presents new spectroscopic results in standoff chemical detection that are enabled by monolithic arrays of Distributed Feedback (DFB) Quantum Cascade Lasers (QCLs), with each array element at a slightly different wavelength than its neighbor. The standoff analysis of analyte/substrate pairs requires a laser source with characteristics offered uniquely by a QCL Array. This is particularly true for time-evolving liquid chemical warfare agent (CWA) analysis. In addition to describing the QCL array source developed for long wave infrared coverage, a description of an integrated prototype standoff detection system is provided. Experimental standoff detection results using the man-portable system for droplet examination from 1.3 meters are presented using the CWAs VX and T-mustard as test cases. Finally, we consider three significant challenges to working with droplets and liquid films in standoff spectroscopy: substrate uptake of the analyte, time-dependent droplet spread of the analyte, and variable substrate contributions to retrieved signals.