Absolutely interferometric calibration of phase liquid crystal spatial light modulators using honeycomb gratings composited with Billet-split Fresnel zone plates.

The traditional interferometric calibration of phase spatial light modulators (SLM) based on interference fringes shift is easily disturbed due to environmental vibration. Here a kind of absolutely interferometric calibration of phase SLM is investigated to eliminate the disturbance using dual honeycomb gratings composited with Billet-split Fresnel zone plates (BsFZP), in which honeycomb gratings split an incident beam into three beams and the first two beams are interfered by BsFZP while the last beam is chosen as the absolute reference point. The experiments on both 532 and 632.8 nm incident wavelengths were separately carried out, and the measuring accuracy was proved by a SID4 wavefront sensor. The proposed high-accuracy calibration provided the basis for SLM application scenarios with high precision.

Neoadjuvant Camrelizumab for Non-Small Cell Lung Cancer: A Retrospective Multicenter, Real-World Study (CTONG2004).

BACKGROUND: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. METHODS: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. RESULTS: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1-6). The median interval from the last dose to surgery was 33 days (range 13-102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5-1200 mL), and the median operative time was 3.0 h (range 1.5-6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4-85.0%), and the disease control rate was 93.8% (95% CI 86.9-97.7%). Twenty-six patients (27.1%, 95% CI 18.5-37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. CONCLUSION: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted.

Tepidiphilus olei sp. nov., isolated from the production water of a water-flooded oil reservoir in PR China.

A novel, moderately thermophilic, Gram-stain-negative bacterium, designated strain J18T, was isolated from a water-flooded oil reservoir. Cells were aerobic, oxidase- and catalase-positive, with a polar flagellum. Growth occurred at 35-60 °C and at pH 6-8.5. The respiratory quinones were ubiquinone 8 and ubiquinone 9. The dominant cellular fatty acids were C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and an unidentified aminophospholipid. The strain showed the highest 16S rRNA gene sequence similarities to Tepidiphilus margaritifer DSM 15129T (98.6 %), Tepidiphilus succinatimandens DSM 15512T (98.4 %) and Tepidiphilus thermophilus DSM 27220T (98.1 %), respectively, and the similarity to other species was lower than 93 %. In the phylogenetic trees, it constituted a unique sub-cluster within the genus Tepidiphilus. The DNA G+C content of strain J18T was 64.44 mol%. As compared with the type strains, the genome-to-genome distances of strain J18T were 34.7-40 %. These results confirmed the separate species status of J18T with its close relatives. On the basis of physiological, chemotaxonomic and phylogenetic analyses along with the low levels of identity at the whole-genome level, it can be concluded that strain J18T represents a new species of the genus Tepidiphilus, for which the name Tepidiphilus olei sp. nov. is proposed. The type strain of T. olei is J18T (=CGMCC 1.16800T=LMG 31400T).

Oleiliquidispirillum nitrogeniifigens gen. nov., sp. nov., a new member of the family Rhodospirillaceae isolated from oil reservoir water.

A novel Gram-staining-negative, spiral-shaped bacterium, designated strain 64-1T, was isolated from oil reservoir water collected from Liaohe oilfield, north-eastern China. Growth occurred at 15-55 °C and pH 6.0-10.0. The sole respiratory quinone was Q-10. The predominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c /C18 : 1 ω6c), C16 : 0 and C19 : 0 cyclo ω8c. The polar lipids consisted of phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), an unidentified aminophospholipid (UAPL), an unidentified aminolipid (UAL) and two unidentified polar lipids (UPL). The genomic DNA G+C content of strain 64-1T was 64.5 mol%. Strain 64-1T shared the highest 16S rRNA gene sequence similarities with Phaeospirillum chandramohanii JA145T (92.0 %) and Telmatospirillum siberiense 26-4b1T (91.8 %). In the phylogenetic trees, the strain constituted a sub-cluster within the family Rhodospirillaceae. Based on the results of morphological, physiological, biochemical and phylogenetic analysis, strain 64-1T represents a new species of a novel genus within the family Rhodospirillaceae, for which the name Oleiliquidispirillum nitrogeniifigens gen. nov., sp. nov. is proposed. The type strain is 64-1T (=CGMCC 1.16798T=LMG 31399T).

Clinical and radiological subsequent fractures after vertebral augmentation for treating osteoporotic vertebral compression fractures: a meta-analysis.

PURPOSE: This study aimed to identify all relevant randomized controlled trials (RCT) and prospective non-RCTs to further investigate whether percutaneous vertebral augmentation (PVA) was associated with clinical and radiological subsequent fractures on unoperated levels. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to January 2020. All eligible studies comparing subsequent fractures after PVA with those after conservative treatment (CT) were incorporated. The pooled risk ratio (RR) with its 95% confidence intervals (95% CIs) was used. Heterogeneity, sensitivity, and publication bias analyses were performed. RESULTS: In all, 32 studies were included in the study: 82/512 patients (16.02%) and 58/433 patients (13.39%) had clinical subsequent fractures in the PVA group and CT group, respectively. No significant differences were observed between the two groups [RR = 1.22, 95% CI 0.70-2.12, P = 0.49]. Further, 175/837 patients (20.91%) in the PVA group and 160/828 patients (19.32%) in the CT group had radiological subsequent fractures. No significant difference was observed between groups [RR = 0.91, 95% CI 0.71-2.12, P = 1.16]. Further, no statistical difference was observed on subgroup analysis between RCTs and non-RCTs or PVP and PKP. CONCLUSION: Our systematic review revealed that subsequent fractures on unoperated levels were not associated with PVA, regardless of whether they were clinical or radiological subsequent fractures.

[Research progress on genetic and molecular mechanisms of hybrid segregation distortion].

Segregation distortion (SD) is defined as abnormal segregation ratio of hybrid offsprings at some genetic loci deviating from the Mendelian ratio. SD results from the incompatibility among genes from different parents, which could be due to loss-of-function or gain-of-function gene interactions. The mechanism for loss-of-function SD is relatively simple: defective gene combination leads to loss of the original function and eventual cell death. The gain-of-function hybrid SD system is a multi-gene genetic system, comprising two basic components: the killer and the protector. Additional modifiers, such as enhancers and repressors, are also involved. There is a general genetic model for gain-of-function hybrid SD: haplotypes with transmission advantage possess high-activity killer⁺ and protector⁺; those with transmission disadvantage possess low-activity killer- and protector-; neutral haplotypes (wide compatibility types) possess killer- and protector⁺. Depending upon close linkage between the killer and the protector and the accumulation of modifiers, the SD system survived through natural selection. Although the genetic mechanisms are highly similar, different gain-of-function hybrid SD systems have distinctive molecular mechanisms. In this review, we summarize the genetic and molecular mechanisms of hybrid SD, and the relationship between hybrid SD and hybrid sterility.

Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia.

RATIONALE: Atrial fibrillation (AF) is the most common cardiac arrhythmia, however the mechanism(s) causing AF remain poorly understood and therapy is suboptimal. The ryanodine receptor (RyR2) is the major calcium (Ca2+) release channel on the sarcoplasmic reticulum (SR) required for excitation-contraction coupling in cardiac muscle. OBJECTIVE: In the present study, we sought to determine whether intracellular diastolic SR Ca2+ leak via RyR2 plays a role in triggering AF and whether inhibiting this leak can prevent AF. METHODS AND RESULTS: We generated 3 knock-in mice with mutations introduced into RyR2 that result in leaky channels and cause exercise induced polymorphic ventricular tachycardia in humans [catecholaminergic polymorphic ventricular tachycardia (CPVT)]. We examined AF susceptibility in these three CPVT mouse models harboring RyR2 mutations to explore the role of diastolic SR Ca2+ leak in AF. AF was stimulated with an intra-esophageal burst pacing protocol in the 3 CPVT mouse models (RyR2-R2474S+/-, 70%; RyR2-N2386I+/-, 60%; RyR2-L433P+/-, 35.71%) but not in wild-type (WT) mice (P<0.05). Consistent with these in vivo results, there was a significant diastolic SR Ca2+ leak in atrial myocytes isolated from the CPVT mouse models. Calstabin2 (FKBP12.6) is an RyR2 subunit that stabilizes the closed state of RyR2 and prevents a Ca2+ leak through the channel. Atrial RyR2 from RyR2-R2474S+/- mice were oxidized, and the RyR2 macromolecular complex was depleted of calstabin2. The Rycal drug S107 stabilizes the closed state of RyR2 by inhibiting the oxidation/phosphorylation induced dissociation of calstabin2 from the channel. S107 reduced the diastolic SR Ca2+ leak in atrial myocytes and decreased burst pacing-induced AF in vivo. S107 did not reduce the increased prevalence of burst pacing-induced AF in calstabin2-deficient mice, confirming that calstabin2 is required for the mechanism of action of the drug. CONCLUSIONS: The present study demonstrates that RyR2-mediated diastolic SR Ca2+ leak in atrial myocytes is associated with AF in CPVT mice. Moreover, the Rycal S107 inhibited diastolic SR Ca2+ leak through RyR2 and pacing-induced AF associated with CPVT mutations.

Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion.

Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca(2+) and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca(2+) homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca(2+) leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca(2+) channel stabilizer S107 ("rycal") inhibited the SR Ca(2+) leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca(2+) leak trough normalization of RyR2 function is cardioprotective.

Research on Detection Efficiency of Imaging Plates for Alpha Particles Using Two Types of Imaging Plate.

ABSTRACT: Imaging plates can measure isotopes with alpha decay (such as radon and its progeny, americium, and so on). However, the detection efficiency of imaging plates is affected by alpha particle energy, types of imaging plates, and the overlapping effect. In this study, simulations were performed to analyze the relationship between detection efficiency and these three influence factors. The research findings suggest that BAS-TR and BAS-MS are well-suited for the detection of alpha particles with energy levels below 6.83 MeV and above, respectively. The track overlap effect correction method proposed in this study is applicable to both BAS-TR and BAS-MS image plates. The measurement results of radon progeny demonstrate that the correction method enhances the detection efficiency from 0.203 to 0.288. This study presents a valuable approach for selecting the appropriate image plate and correcting the track overlap effect in the measurement of alpha radioactive material concentration and other related information.

Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure.

The force frequency relationship (FFR), first described by Bowditch 139 years ago as the observation that myocardial contractility increases proportionally with increasing heart rate, is an important mediator of enhanced cardiac output during exercise. Individuals with heart failure have defective positive FFR that impairs their cardiac function in response to stress, and the degree of positive FFR deficiency correlates with heart failure progression. We have identified a mechanism for FFR involving heart rate dependent phosphorylation of the major cardiac sarcoplasmic reticulum calcium release channel/ryanodine receptor (RyR2), at Ser2814, by calcium/calmodulin-dependent serine/threonine kinase-delta (CaMKIIdelta). Mice engineered with an RyR2-S2814A mutation have RyR2 channels that cannot be phosphorylated by CaMKIIdelta, and exhibit a blunted positive FFR. Ex vivo hearts from RyR2-S2814A mice also have blunted positive FFR, and cardiomyocytes isolated from the RyR2-S2814A mice exhibit impaired rate-dependent enhancement of cytosolic calcium levels and fractional shortening. The cardiac RyR2 macromolecular complexes isolated from murine and human failing hearts have reduced CaMKIIdelta levels. These data indicate that CaMKIIdelta phosphorylation of RyR2 plays an important role in mediating positive FFR in the heart, and that defective regulation of RyR2 by CaMKIIdelta-mediated phosphorylation is associated with the loss of positive FFR in failing hearts.

Research on Three-level Enrichment Method Based on 222Rn.

ABSTRACT: Various low-concentration inert gases, including 222Rn, 133Xe, and 85Kr, pollute the atmosphere near nuclear facilities (e.g., nuclear power plants or reprocessing plants). Owing to the detection limits of instruments, it has become urgent to determine the concentration of these gases efficiently and perform their online monitoring. However, current technologies are limited by low enrichment efficiencies. In this study, a high-pressure, low-flow, large-volume, and high-efficiency adsorption method has been proposed along with a high-temperature, low-pressure, high-flow, and small-volume rapid desorption and collection method, which are based on the gas enrichment principle of activated carbon. The results demonstrated that when dynamic adsorption was implemented using a two-level enrichment method, the final desorbed gas concentration was proportional to the volume ratio of both the large and small activated carbon beds. At a volume ratio of 15:1, 222Rn concentration increased from 110 to 21,016 Bq m-3 after the two-level enrichment; meanwhile, 222Rn concentration increased from 110 to 42,012 Bq m-3 after three-level enrichment. The three-level enrichment technology provides technical support for the enrichment of low-concentration inert gases in the environment, while offering an important technical foundation for improving the monitoring of low-concentration inert gases in specific environments as well as the atmospheric environment.

High Prevalence of Carbapenem-Resistant Enterobacterales Colonization Among Intensive Care Unit Patients in a Tertiary Hospital, China.

Intestinal colonization with carbapenem-resistant Enterobacterales (CRE) has been shown as a significant risk factor for subsequent CRE infections, especially in intensive care units (ICUs). The aim of this study was to determine the prevalence of intestinal CRE colonization among ICU patients in a Chinese tertiary hospital. Fecal sample screenings for CRE were performed on ICU patients weekly. Antibiotic-susceptibility profile of CRE strains was determined using the Vitek-2 analysis system and broth microdilution method. The carbapenemases of all isolates were determined by phenotypes and genotypes. Clonal relatedness was analyzed by pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was used to identify the multilocus sequence type (ST), plasmid replicons, and insertion sequences (ISs) of isolates. The overall colonization rate of CRE was 40.4% (82/203). A total of 84 CRE strains were detected, mostly with Klebsiella pneumoniae (92.9%). Antibiotic susceptibility testing profile revealed that 84 CRE strains were resistant to most antibiotics except for tigecycline and colistin. The carbapenemase-encoding genes including blaKPC-2, blaNDM-1, and blaIMP-4 were detected, and blaKPC-2 was the predominant genotype (90.8%). A total of 9 STs were identified among 84 CRE strains, and ST11 was the most common type (83.3%). A variety of mobile genetic elements, including plasmids and ISs, were detected via online tool prediction. PFGE analysis of the 78 K. pneumoniae strains showed 8 different pulsotypes, and pulsotype A was highly prevalent. This study found that the prevalence of CRE colonization was alarmingly high in the ICU, and that effective infection control measures are urgently needed to prevent the dissemination of CRE.

Mitogen-activated protein kinase inhibitors improve heart function and prevent fibrosis in cardiomyopathy caused by mutation in lamin A/C gene.

BACKGROUND: Mutations in the lamin A/C gene, LMNA, can cause dilated cardiomyopathy. We have shown abnormal activation of the extracellular signal-regulated kinase (ERK) and the c-jun N-terminal kinase (JNK) branches of the mitogen-activated protein kinase signaling cascade in hearts from Lmna(H222P/H222P) mice that develop dilated cardiomyopathy. We recently showed that partial inhibition of ERK and JNK signaling before the onset of cardiomyopathy in Lmna(H222P/H222P) mice prevented the development of left ventricle dilatation and decreased cardiac ejection fraction at a time when they occurred in untreated mice. METHODS AND RESULTS: To determine whether pharmacological inhibitors of ERK and JNK signaling could be clinically useful to treat cardiomyopathy caused by LMNA mutation, we administered them to Lmna(H222P/H222P) mice after they developed left ventricular dilatation and decreased ejection fraction. Lmna(H222P/H222P) mice were treated with ERK and JNK signaling inhibitors from 16 to 20 or, in pilot experiments, 19 to 24 weeks of age. The inhibitors blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere architecture that occurred in placebo-treated mice. Echocardiography and histological analysis demonstrated that treatment prevented left ventricular end-systolic dilatation, increased ejection fraction, and decreased myocardial fibrosis. CONCLUSION: Inhibitors of ERK and JNK signaling could potentially be used to treat humans with cardiomyopathy caused by LMNA mutations.

Imbalance of regulatory T cells to Th17 cells in IgA nephropathy.

BACKGROUND: Dysregulation of CD4 (+) T cell subsets participates in the pathogenesis of IgA nephropathy (IgAN). FoxP3 (+) regulatory T cells (Treg) and Th17 cells are two novel subsets of CD4 (+) T cells. This study aims to investigate Treg/Th17 balance in IgAN patients. METHODS: Peripheral frequencies of Th17 and Treg functional subsets - CD45RA (+) FoxP3(low) resting Treg (rTreg) and CD45RA(-)FoxP3(high) activated Treg (aTreg) were assessed in 63 adult IgAN patients. Expression of transcription factors (FoxP3 and RORγt) and related cytokines of Treg and Th17 were analysed. Renal expression of FoxP3 and IL-17A were detected by immunohistochemistry. RESULTS: Compared with normal controls, IgAN patients had decreased frequency of CD45RA(-)FoxP3(high) aTreg subset (p < 0.05), increased frequency of Th17 (p < 0.05) and decreased ratio of Treg/Th17 (p < 0.05). Frequency of aTreg subset correlated with SBP(r = - 0.57, p < 0.05), DBP (r = - 0.50, p < 0.05), eGFR (r = 0.68, p < 0.05) and 24 h proteinuria (r = - 0.58, p < 0.05). RORγtmRNA/FoxP3mRNA ratio increased in IgAN (p < 0.05). Serum IL-17A, IL-21, IL-23, IL-1ß and IL-6 elevated while IL-10 decreased in IgAN (p < 0.05), and serum IL-17A correlated with 24 h proteinuria (r = 0.35, p < 0.05). Serum TGF-ß1 wasn't different between the two groups. Renal interstitial infiltration of FoxP3 (+) mononuclear cells were observed in IgAN patients, particularly prominent in those with > 25% tubular atrophy/interstitial fibrosis. Tubular IL-17A expression was found in 34 out of 63 IgAN patients. Compared with 29 patients without IL-17A expression, these patients had lower renal function, greater proteinuria, and more severe tubulointerstitial damage. CONCLUSIONS: Imbalance of Treg/Th17 found in IgAN may play a role in disease pathogenesis and progression.

Risk factors for pulmonary cement embolism associated with percutaneous vertebral augmentation: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cement embolism (PCE) was a rare but fatal complication for percutaneous vertebral augmentation (PVA). Thus we did a systematic review and meta-analysis of cohort studies to investigate the risk factors for PCE after PVA. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to September 2021. All eligible studies assessing the risk factors for PCE after PVA were incorporated. Dichotomous data was calculated by risk difference (RD) from Mantel-Haenszel method (M - H method); continuous data was analyzed by mean difference (MD) from Inverse-Variance method (I-V method). All variables were taken as measure of effect by fixed effect model. Heterogeneity, sensitivity, and publication bias analyses were also performed. RESULTS: This study totally included 13 studies. According to the Newcastle-Ottawa Scale (NOS), 7 studies were considered as low quality, with NOS< 6. The others were of relatively high quality, with NOS≥6. 144/6251 patients (2.3%) had PCE after PVA. percutaneous vertebroplasty (PVP) (RD = 0.02, 95%CI: [0.01, 0.04], Z = 3.70, P < 0.01), thoracic vertebra (RD = 0.03, 95%CI: [0.01, 0.05], Z = 3.53, P < 0.01), higher cement volume injected per level (MD = 0.23, 95%CI: [0.05, 0.42], Z = 2.44, P = 0.01), more than three vertebrae treated per session (MD = -0.05, 95%CI: [-0.08, -0.02], Z = 3.65, P < 0.01), venous cement leakage (RD = 0.07, 95%CI: [0.03, 0.11], Z = 3.79, P < 0.01) were more likely to cause PCE. CONCLUSION: This study showed that risk factors for PCE included PVP, thoracic vertebra, higher cement volume injected per level, more than three vertebrae treated per session, venous cement leakage. As a serious complication, PCE should be paid attention and avoided.

LaOx modified MnOx loaded biomass activated carbon and its enhanced performance for simultaneous abatement of NO and Hg0.

A battery of agricultural straw derived biomass activated carbons supported LaOx modified MnOx (LaMn/BACs) was prepared by a facile impregnation method and then tested for simultaneous abatement of NO and Hg0. 15%LaMn/BAC manifested excellent removal efficiency of Hg0 (100%) and NO (86.7%) at 180 °C, which also exhibited splendid resistance to SO2 and H2O. The interaction between Hg0 removal and NO removal was explored; thereinto, Hg0 removal had no influence on NO removal, while NO removal preponderated over Hg0 removal. The inhibitory effect of NH3 was greater than the accelerative effect of NO and O2 on Hg0 removal. The physicochemical characterization of related samples was characterized by SEM, XRD, BET, H2-TPR, NH3-TPD, and XPS. After incorporating suitable LaOx into 15%Mn/BAC, the synergistic effect between LaOx and MnOx contributed to the improvement of BET surface area and total pore volume, the promotion of redox ability, surface active oxygen species, and acid sites, inhibiting the crystallization of MnOx. 15%LaMn/BAC has the best catalytic oxidation activity at low temperature. That might be answerable for superior performance and preferable tolerance to SO2 and H2O. The results indicated that 15%LaMn/BAC was a promising catalyst for simultaneous abatement of Hg0 and NO at low temperature.

Pharmacological inhibition of c-Jun N-terminal kinase signaling prevents cardiomyopathy caused by mutation in LMNA gene.

Mutations in LMNA, which encodes A-type nuclear lamins, cause disorders of striated muscle that have as a common feature dilated cardiomyopathy. We have demonstrated an abnormal activation of both the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) branches of the mitogen-activated protein kinase signaling cascade in hearts from Lmna(H222P/H222P) mice that develop dilated cardiomyopathy. We previously showed that pharmacological inhibition of cardiac ERK signaling in these mice delayed the development of left ventricle dilatation and deterioration in ejection fraction. In the present study, we treated Lmna(H222P/H222P) mice with SP600125, an inhibitor of JNK signalling. Systemic treatment with SP600125 inhibited JNK phosphorylation, with no detectable effect on ERK. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in the architecture of the sarcomere that occurred in placebo-treated mice. Furthermore, treatment with SP600125 significantly delayed the development of left ventricular dilatation and prevented decreases in cardiac ejection fraction and fibrosis. These results demonstrate a role for JNK activation in the development of cardiomyopathy caused by LMNA mutations. They further provide proof-of-principle for JNK inhibition as a novel therapeutic option to prevent or delay the cardiomyopathy in humans with mutations in LMNA.

Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.

Autosomal Emery-Dreifuss muscular dystrophy and related disorders with dilated cardiomyopathy and variable skeletal muscle involvement are caused by mutations in LMNA, which encodes A-type nuclear lamins. How alterations in A-type lamins, intermediate filament proteins of the nuclear envelope expressed in most differentiated somatic cells, cause cardiomyopathy is only poorly understood. We demonstrated previously abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P 'knock in' mice, a model of autosomal Emery-Dreifuss muscular dystrophy. We therefore treated Lmna(H222P/H222P) mice that develop cardiomyopathy with PD98059, an inhibitor of ERK activation. Systemic treatment of Lmna(H222P/H222P) mice with PD98059 inhibited ERK phosphorylation and blocked the activation of downstream genes in heart. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere organization that occurred in placebo-treated mice. Histological analysis and echocardiography demonstrated that treatment with PD98059 delayed the development of left ventricular dilatation. PD98059-treated Lmna(H222P/H222P) mice had normal cardiac ejection fractions assessed by echocardiography when placebo-treated mice had a 30% decrease. These results emphasize the role of ERK activation in the development of cardiomyopathy caused by LMNA mutations. They further provide proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA.

Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors.

Despite the use of the sirolimus (rapamycin) drug-eluting coronary stent, diabetics are at increased risk of developing in-stent restenosis for unclear reasons. Hyperleptinemia, which often coexists with diabetes and metabolic syndrome, is an independent risk factor for progression of coronary artery disease. It has not been determined whether elevated circulating leptin decreases the efficacy of the sirolimus drug-eluting stent in inhibiting neointimal hyperplasia, the process underlying restenosis after stenting. Here we show that leptin activates the mammalian target of rapamycin (mTOR) signaling pathway in primary murine vascular smooth muscle cells (VSMC) and stimulates VSMC proliferation in a PI3K-dependent fashion. Exogenous leptin, administered at levels comparable to those found in obese humans, promotes neointimal VSMC hyperplasia in a murine femoral artery wire injury model. Leptin significantly increases the dose of the mTOR inhibitor sirolimus that is required for effective inhibition of neointimal formation. Combination therapy with LY294002, a PI3K inhibitor, and sirolimus effectively inhibits leptin-enhanced neointimal hyperplasia. These data show that, in the setting of hyperleptinemia, higher doses of an mTOR inhibitor, or combination therapy with mTOR and PI3K inhibitors, inhibits neointimal hyperplasia after arterial injury. These studies may explain the higher rates of restenosis observed in diabetics treated with a sirolimus-eluting coronary stent and suggest a potential novel therapeutic approach for inhibiting in-stent restenosis in such patients.

Study on the Performance of an Alpha Energy Spectrum Radon Measuring Instrument Based on CdZnTe Detector.

ABSTRACT: To realize a fast and reliable approach for continuous radon measurements, a CdZnTe (CZT) detector based on the electrostatic collection method was developed. The experimental results show that when the external temperature varies from 5 °C to 30 °C, the maximum drifts of the characteristic peak positions of 218Po and 214Po are only 8 and 6. Furthermore, the measurement error associated with the constant radon concentration is less than 5.5%. As the temperature increases or decreases, the measurement error becomes larger, with the maximum error being 43.1%. The response of the proposed instrument for constant radon concentration is better than that of the RAD7 radon measurement instrument. At 25 °C, the value measured using the NRL-II radon meter with the PIPS detector is in good agreement with the actual value. The new radon measurement instrument exhibits a good compliance from the third measurement cycle (measurement deviation 0.53-3.95%), while RAD7 has good compliance from the fourth measurement cycle (measurement deviation of 1.17-4.88%). The theoretical and practical values of the iterative correction factor (influence of the previous measurement on the current measurement) of the radon measurement instrument are in good agreement. The iterative correction factor can be used for performing continuous radon measurements independently, with the aim of achieving a rapid response to environmental radon concentrations.