Spectroscopic Visualization of Flat Bands in Magic-Angle Twisted Monolayer-Bilayer Graphene: Coexistence of Localization and Delocalization.

Recent transport studies have demonstrated the great potential of twisted monolayer-bilayer graphene (TMBG) as a new platform to host moiré flat bands with a higher tunability than twisted bilayer graphene (TBG). However, a direct visualization of the flat bands in TMBG and its comparison with the ones in TBG remain unexplored. Here, via fabricating on a single sample with exactly the same twist angle of ∼1.13°, we present a direct comparative study between TMBG and TBG using scanning tunneling microscopy and spectroscopy. We observe a sharp density of states peak near the Fermi energy in tunneling spectroscopy, confirming unambiguously the existence of flat electronic bands in TMBG. The bandwidth of this flat-band peak is found to be slightly narrower than that of the TBG, validating previous theoretical predictions. Remarkably, by measuring spatially resolved spectroscopy, combined with continuum model calculation, we show that the flat-band states in TMBG exhibit a unique layer-resolved localization-delocalization coexisting feature, which offers an unprecedented possibility to utilize their cooperation on exploring novel correlation phenomena. Our work provides important microscopic insight of flat-band states for better understanding the emergent physics in graphene moiré systems.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman's R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.

Blood and Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumonia.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has made a revolution in the mode of pathogen identification. We decided to explore the diagnostic value of blood and bronchoalveolar lavage fluid (BALF) as mNGS samples in pneumonia. METHODS: We retrospectively reviewed 467 mNGS results and assessed the diagnostic performance of paired blood and BALF mNGS in 39 patients with pneumonia. RESULTS: For bacteria and fungi, 16 patients had culture-confirmed pathogen diagnosis, while 13 patients were culture-negative. BALF mNGS was more sensitive than blood mNGS (81.3% vs. 25.0%, p=0.003), and the specificity in BALF and blood mNGS was not statistically significant different (76.9% vs. 84.6%, p=0.317). For 10 patients without culture test, treatments were changed in 2 patients. For viruses, Epstein-Barr virus was positive in blood mNGS in 9 patients. Human adenovirus was detected in both BALF and blood mNGS in 3 patients. CONCLUSION: Our study suggests that BALF mNGS is more sensitive than blood mNGS in detecting bacteria and fungi, but blood also has advantages to identify the pathogens of pneumonia, especially for some viruses.

IgG4-related diseases with autoimmune hemolytic anemia: A case report. / IgG4ç›¸å ³ç–¾ç— åˆå¹¶è‡ªèº«å ç–«æ€§æº¶è¡€æ€§è´«è¡€1例.

IgG4-related disease (IgG4-RD) is a rare autoimmune fibrosis disease characterized by elevated serum IgG4 and tissues as well as organs infiltrated with IgG4-positive cells, resulting in swelling and damage.It is currently treated as first-line treatment with glucocorticoids. Autoimmune hemolytic anemia (AIHA) is also a relatively rare disease that caused by autoreactive erythrocyte antibodies. Although both are autoimmune-related diseases, they rarely overlap. The relationship between them is not clear. A case of IgG4-RD combined with AIHA is reported. The patient has shortness of breath, cough, and sputum after physical activity. Physical examination showed appearance of anemia, yellow staining of skin and sclera, palpable neck and multiple swollen lymph nodes. Laboratory examination, bone marrow biopsy, and lymph node biopsy confirmed the diagnosis. Therefore, clinicians should develop ideas and raise awareness of such diseases.

Pre-grafted Group on PE Surface by DBD Plasma and Its Influence on the Oxygen Permeation with Coated SiOx.

In this paper, we report on polyethylene (PE) film modified by atmospheric dielectric barrier discharge (DBD) plasma prior to the deposition of SiOx coating to improve its barrier properties. Three kinds of monomers: allylamine, acrylic acid, and ethanol, are used to modify the PE surface. For comparison, Ar and O2 plasma pre-treatments are also performed. It is found that with the addition of a monomer in the Ar DBD plasma, the grafted active groups on PE surfaces lead to dense, pinhole-free growth of the SiOx film. The oxygen transmission rate (OTR) decreases from 700 cc/m²·day·atm. for the pristine to ca. 70 cc/m²·day·atm. for the pretreatment-coated PE, which is more than a 10-fold reduction. The relationship between the grafted monomer and the great decrease of OTR is then explored via chemical composition by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and via morphology observation by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results show that the grafted functional groups of -NH2, -COOH and -OH increase the surface energy and promote the nucleation of Si⁻O radicals on polymeric surfaces, and the formation of network and cage structures in SiOx film contributes to the significant improvement of OTR.

Optical magnetism and optical activity in nonchiral planar plasmonic metamaterials.

We investigate optical magnetism and optical activity in a simple planar metamolecule composed of double U-shaped metal split ring resonators (SRRs) twisted by 90° with respect to one another. Compared to a single SRR, the resonant energy levels are split and strong magnetic response can be observed due to inductive and conductive coupling. More interestingly, the nonchiral structures exhibit strong optical gyrotropy (1100°/λ) under oblique incidence, benefiting from the strong electromagnetic coupling. A chiral molecule model is proposed to shed light on the physical origin of optical activity. These artificial chiral metamaterials could be utilized to control the polarization of light and promise applications in enantiomer sensing-based medicine, biology, and drug development.

Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177.

Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling.

Clinical values of serum C5a in Alzheimer's disease patients with different dementia stages.

Alzheimer's disease (AD) is characterized by abnormal inflammatory responses, and complement C5a (C5a) is known to initiate inflammation. This study aimed to investigate the associations between serum C5a, inflammatory responses, and cognitive function in AD patients. A total of 242 AD patients and 132 age-matched controls were included. Enzyme-linked immunosorbent assay revealed increased levels of C5a, interleukin (IL)-4, IL-6, IL-10, IL-1ß, and tumor necrosis factor (TNF)-α with advancing stages of AD. Pearson correlation coefficient and receiver operating characteristic curve revealed positive correlations between serum C5a levels, inflammatory cytokine levels, Neuropsychiatric Inventory (NPI) and Activities of Daily Living (ADL) scores, and negative correlations with Mini-mental State Examination (MMSE) and Montreal cognitive assessment (MoCA) scores. Serum C5a above 68.68 pg/mL could aid in the diagnosis of AD. Multivariable logistic analysis revealed that serum C5a was an independent risk factor for IL-1ß/IL-6/IL-10/TNF-α and an independent protective factor for IL-4. Higher serum C5a levels were associated with lower MMSE and MoCA scores. In conclusion, elevated serum C5a levels were beneficial for AD diagnosis and predictive of inflammation and cognitive dysfunction.

Development and validation of a nomogram model for mortality prediction in stable chronic obstructive pulmonary disease patients: A prospective observational study in the RealDTC cohort.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. There is no nomogram model available for mortality prediction of stable COPD. We intended to develop and validate a nomogram model to predict mortality risk in stable COPD patients for personalised prognostic assessment. Methods: A prospective observational study was made of COPD outpatients registered in the RealDTC study between December 2016 and December 2019. Patients were randomly assigned to the training cohort and validation cohort in a ratio of 7:3. We used Lasso regression to screen predicted variables. Further, we evaluated the prognostic performance using the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curve. We used the AUC, concordance index, and decision curve analysis to evaluate the net benefits and utility of the nomogram compared with three earlier prediction models. Results: Of 2499 patients, the median follow-up was 38 months. The characteristics of the patients between the training cohort (n = 1743) and the validation cohort (n = 756) were similar. ABEODS nomogram model, combining age, body mass index, educational level, airflow obstruction, dyspnoea, and severe exacerbation in the first year, was constructed to predict mortality in stable COPD patients. In the integrative analysis of training and validation cohorts of the nomogram model, the three-year mortality prediction achieved AUC = 0.84; 95% confidence interval (CI) = 0.81, 0.88 and AUC = 0.80; 95% CI = 0.74, 0.86, respectively. The ABEODS nomogram model preserved excellent calibration in both the training cohort and validation cohort. The time-dependent AUC, concordance index, and net benefit of the nomogram model were higher than those of BODEx, updated ADO, and DOSE, respectively. Conclusions: We developed and validated a prognostic nomogram model that accurately predicts mortality across the COPD severity spectrum. The proposed ABEODS nomogram model performed better than earlier models, including BODEx, updated ADO, and DOSE in Chinese patients with COPD. Registration: ChiCTR-POC-17010431.

Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats.

Reactive oxygen species (ROS) contributes to endothelial dysfunction that is involved in the pathogeneses of hypertension. Vascular peroxidase 1 (VPO1) can utilize ROS to catalyze peroxidative reactions, possibly enhancing endothelial dysfunction. This study is to identify VPO1's involvement in endothelial dysfunction and hypertension. Sixty-four spontaneously hypertensive rats (SHRs) and 64 age-matched, bodyweight controlled normotensive Wistar-Kyoto rats (WKYs) were randomly grouped and studied at the age of 5, 8, 13 and 20 weeks (16 animals, each). Blood pressure and vasodilator responses to acetylcholine in aortic rings were observed. The expressions of VPO1 and endothelial NO synthase (eNOS) in aortas were assessed by quantitative reverse transcription-PCR and western blotting analysis. Plasma concentrations of hydrogen peroxide (H2O2) and NO, NOX activity, hypochlorous acid (HOCl) production, and 3-nitrotyrosine content in aortic homogenates were also determined in this study. Along with the development of hypertension in SHR rats, VPO1 expression was up-regulated together with a significant increase in NOX activity, HOCl production, 3-nitrotyrosine content, and plasma H2O2 level compared with WKYs at 8, 13 and 20 weeks of age. In contrast, blood NO levels were decreased and aortic relaxation to acetylcholine was deteriorated in SHRs. The over-expression of VPO1 during the development of hypertension, accompanied by the endothelial dysfunction, the decreased NO levels, the elevated NOX and ROS activities, indicates a clear connection between VPO1 gene and hypertension. VPO1 may pathogenetically contribute to hypertension via signal pathways involving NOX-H2O2-VPO1-HOCl or JNK/p38 MAPK although further studies are needed to determine the precise mechanisms.

Prediction of Hospitalization and Mortality in Patients with Chronic Obstructive Pulmonary Disease with the New Global Initiative for Chronic Obstructive Lung Disease 2023 Group Classification: A Prospective Cohort and a Retrospective Analysis.

Background: The revised Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 group ABE classification has undergone major modifications, which can simplify clinical assessment and optimize treatment recommendations for Chronic Obstructive Pulmonary Disease (COPD). However, the predictive value of the new grouping classification for prognosis is worth further exploration. We aimed to compare the prediction of hospitalization and mortality between this new GOLD group 2023 ABE classification and the earlier 2017 ABCD classification in a Chinese COPD cohort. Methods: Data from 2,499 outpatients with COPD, who first registered in the RealDTC study of Second Xiangya Hospital from December 2016 to December 2019, were collected prospectively and assessed retrospectively. Patients were followed up on all-cause mortality until October 2022 or death. Results: Of the 2,499 patients with COPD, the risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The mortality was higher in group E than in groups A and B, and group B was higher than group A. No differences were seen in the area under the curve (AUC) of 2017 vs 2023 GOLD grouping to predict hospitalization. The time-dependent AUC and concordance index for predicting mortality is slightly higher in the GOLD 2017 ABCD than in the 2023 ABE groups. The new GOLD 12-subgroup (1A-4E) classification combining the GOLD 1-4 staging and grouping performed similarly discriminate predictive power for mortality to the GOLD 2017 16-subgroup (A1-4D) classification. Conclusion: The risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The all-cause mortality increased gradually from GOLD group A to E. The GOLD 2023 classification based on ABE groups did not predict mortality better than the earlier 2017 ABCD classifications.

[Determination of electron density in atmospheric pressure radio frequency dielectric barrier discharges by Stark broadening].

The use of high frequency power to generate plasma at atmospheric pressure is a relatively new development. An apparatus of atmospheric pressure radio frequency dielectric barrier discharge was constructed. Plasma emission based measurement of electron density in discharge columns from Stark broadening Ar is discribed. The spacial profile of electron density was studied. In the middle of the discharge column, as the input power increases from 138 to 248 W, the electron density rises from 4.038 x 10(21) m(-3) to 4.75 x 10(21) m(-3).

Intervention strategies for epidemic spreading on bipartite metapopulation networks.

Intervention strategies are of great significance for controlling large-scale outbreaks of epidemics. Since the spread of epidemic depends largely on the movement of individuals and the heterogeneity of the network structure, understanding potential factors that affect the epidemic is fundamental for the design of reasonable intervention strategies to suppress the epidemic. So far, most of previous studies mainly consider intervention strategies on the network composed of a single type of locations, while ignoring the movement behavior of individuals to and from locations that are composed of different types, i.e., residences and public places, which often presents heterogeneous structure. In addition, the transmission rate in public places with different population flows is heterogeneous. Inspired by the above observation, we build a bipartite metapopulation network model and propose intervention strategies based on the importance of public places. With the Markovian Chain approach, we derive the epidemic threshold under intervention strategies. Experimental results show that, compared with the uniform intervention to residences or public places, nonuniform intervention to public places is more effective for suppressing the epidemic with an increased epidemic threshold. Specifically, interventions to public places with large degree can further suppress the epidemic. Our study opens a new path for understanding the spatial epidemic spread and provides guidance for the design of intervention strategies for epidemics in the future.

Clinical Evaluation and Exploration of Mechanisms for Modified Xiebai Powder or Modified Xiebai Powder Combined with Western Medicine in the Treatment of Pneumonia.

Objective: To systematically evaluate the clinical efficacy of modified Xiebai Powder or modified Xiebai Powder combined with Western medicine in the treatment of pneumonia and explore its potential mechanism of action. Methods: Meta-analysis was used to screen the eligible literature on randomized controlled trials (RCTs) about Xiebai Powder in the treatment of pneumonia, and Review Manager 5.3 software was used for statistical analysis of the data. Based on the results of the meta-analysis, the active ingredients in Xiebai Powder and their therapeutic targets, disease-related targets, and intersection targets were screened using methods of network pharmacology, and their biological processes and key signaling pathways were analyzed using bioinformatics tools. Molecular docking was carried out to verify and predict the mechanisms for Xiebai Powder combined with Western medicine in the treatment of pneumonia. Results: A total of 16 papers were screened out, with a total of 1,465 patients. The results of the meta-analysis showed that modified Xiebai Powder or modified Xiebai Powder combined with Western medicine were superior to conventional Western medicine in terms of clinical efficacy, shortening the disappearance time of symptoms (body temperature, cough, and pulmonary rales) and reducing the level of C-reactive protein, and the incidence of adverse reactions was significantly reduced. A total of 40 active ingredients in Xiebai Powder and 285 therapeutic targets of Xiebai Powder combined with azithromycin after deduplication were screened out from the database. KEGG enrichment analysis showed that Xiebai Powder combined with azithromycin might play a role in the treatment of pneumonia through the IL-17 signaling pathway, tumor necrosis factor signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. Conclusions: Modified Xiebai Powder or modified Xiebai Powder combined with azithromycin has better effects in treating pneumonia, and modified Xiebai Powder combined with azithromycin may play a role in treating pneumonia through several pathways such as the IL-17 signaling pathway.

Genomic Features of Solid Tumor Patients Harboring ALK/ROS1/NTRK Gene Fusions.

The fusions of receptor tyrosine kinase (RTK) involving anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neurotrophic receptor tyrosine kinase (NTRK) represent the potential targets of therapeutic intervention for various types of solid tumors. Here, the genomic features of 180 Chinese solid tumor patients with ALK, ROS1, and NTRK fusions by next generation sequencing (NGS) were comprehensively characterized, and the data from 121 patients in Memorial Sloan Kettering Cancer Center (MSKCC) database were used to compare. We found that ALK, ROS1, and NTRK fusions were more common in younger female patients (p<0.001) and showed a higher expression of programmed death ligand 1 (PD-L1). The gene-intergenic fusion and the fusion with rare formation directions accounted for a certain proportion in all samples and 62 novel fusions were discovered. Alterations in TP53 and MUC16 were common in patients with RTK fusions. The mutational signatures of patients were mainly distributed in COSMIC signature 1, 2, 3, 15 and 30, while had a higher frequency in copy number variations (CNVs) of individual genes, such as IL-7R. In the MSKCC cohort, patients with fusions and CNVs showed shorter overall survival than those with only fusions. Furthermore, the differentially mutated genes between fusion-positive and -negative patients mainly concentrated on MAPK signaling and FOXO signaling pathways. These results may provide genomic information for the personalized clinical management of solid tumor patients with ALK, ROS1, and NTRK fusions in the era of precision medicine.

Effect of aeration modes on nitrogen removal and N2O emission in the partial nitrification and denitrification process for landfill leachate treatment.

The anoxic/multi-aerobic process is widely applied for treating landfill leachate with low carbon to nitrogen ratio. In this study, the effect of two aeration modes in the aerobic phase, i.e. decreasing dissolved oxygen (DO) and increasing DO, on nitrogen removal and N2O emission in the process were systematically compared. The results demonstrate that the aerobic phase with increasing DO mode has a positive effect on improved total nitrogen removal (78 %) under the COD/N ratio as low as 3.45 and minimized N2O emission. DO concentration higher than 1.5 mg/L in the aerobic phase reduced nitrogen removal and led to a significant high N2O emission in the process. Complete nitrite denitrification in the anoxic phase correlated with minimized N2O emission. Under efficient nitrogen removal stage, N2O emission factor was 2.4 ± 1.0 % of the total incoming nitrogen. Microbial analysis revealed that increasing DO mode increased the abundance of ammonia oxidizing bacteria and denitrifiers.

(E)-3-[2,5-Dioxo-3-(propan-2-yl-idene)pyrrolidin-1-yl]acrylic acid.

The title compound, C(10)H(11)NO(4), was extracted from a culture broth of Penicillium verruculosum YL-52. The mol-ecular structure is essentially planar, with an r.m.s. deviation of 0.01342 (2) Šfor the non-H atoms. In the crystal structure, adjacent mol-ecules are connected into a centrosymmetric dimer through a pair of O-H⋯O hydrogen bonds. The dimers are further extended into a chain by weak C-H⋯O hydrogen bonds.

The effects of nonredox metal ions on the activation of peroxymonosulfate for organic pollutants degradation in aqueous solution with cobalt based catalysts: A new mechanism investigation.

Herein, a new peroxymonosulfate (PMS) activation system was proposed employing nonredox metal ions as Lewis acids (LA), which have been widely recognized to play important roles in many biological and chemical oxidations. With Co2+ ions as model catalysts, it was found that oxidizing power of PMS was enhanced after binding weak LA such as Ca2+ ions, leading to its easier reduction to active radicals and substantial enhancement of dye degradation. The promoting effect of Ca2+ was also observed with other cobalt catalysts including CoFe2O4 and Co3O4. The rate of PMS decomposition in Co2++LA/PMS system was correlated with Lewis acidity; while in the presence of strong LA including La3+ and Y3+, the dye degradation rate declined. The interactions of LA with PMS were characterized and the detailed mechanism was proposed. The present study provides the first example of the promoting effect of weak LA on PMS activation with cobalt based catalysts.

The Genomic Characteristics of ALK Fusion Positive Tumors in Chinese NSCLC Patients.

Anaplastic lymphoma kinase (ALK) fusion events account for ~3-7% genetic alterations in patients with non-small cell lung cancer (NSCLC). In this study, we identified the ALK fusion patterns and a novel ALK fusion partner in 44 ALK positive NSCLC patients using a customized HapOncoCDx panel, and identified ALK fusion partners. The most common partner is EML4, forming the variant 1 (v1, E13:A20, 18/44), variant 2 (v2, E20:A20, 5/44), and variant 3 (v3, E6:A20, 13/44). Moreover, we detected a new ALK fusion partner HMBOX1. At the mutation level, TP53 is the most frequently mutated gene (24%), followed by ALK (12%) and STED2 (12%). The median tumor mutation burden (TMB) of these samples is 2.29 mutations/Mb, ranging from 0.76 mut/Mb to 16.79 muts/Mb. We further elaborately portrayed the TP53 mutation sites on the peptide sequence of the encoded protein by lollipop. The mutational signature and copy number alterations (CNAs) of the samples were also analyzed. The CNA events were found in 13 (13/44) patients, and the most commonly amplified genes were MDM2 (n = 4/13) and TERT (n = 4/13). Together, these results may guide personalized clinical management of patients with ALK fusion in the era of precision medicine.

Research on the Effects of the Chronic Treatment With Different Doses of Urocortin 2 in Heart Failure Rats.

Corticotropin-releasing factor (CRF) receptor type 2 (CRF2) exists in both cardiomyocytes and neurocytes. The purpose of this research was to explore if chronic treatment with urocortin 2 (UCN2), a CRF2 receptor agonist, at different doses can improve prognosis and regulate the expression of CRF2 receptor and calcium handling proteins without any adverse effects on behavior in heart failure. Heart failure was established in Sprague-Dawley rats and was confirmed by echocardiography. Heart failure rats were injected intraperitoneally with UCN2 (5, 10, or 20 µg·kg-1·d-1) for 30 days. Survival rate, cardiac function, expressions of cardiac CRF2 receptor, RyR2, SERCA2, and hypothalamic and hippocampal c-FOS, CRF receptor type 1 (CRF1) and CRF2 receptor were determined. Behavior was evaluated by Morris Water-Maze and Open-Field tests. Results showed that chronic peripheral UCN2 treatment improved survival rate in a dose-response manner and increased cardiac function and expression of CRF2 receptor and SERCA2 in heart failure, especially at the high dosage. Moreover, cellular-fos (c-FOS), CRF1 receptor, and CRF2 receptor expressions of both hypothalamic and hippocampal tissues were significantly increased in high dosage group. Furthermore, the behavior tests suggested that chronic UCN2 treatment did not exacerbate stress/anxiety-like behavior in HF. In conclusion, chronic peripheral treatment with UCN2 increases survival in a dose-response manner in heart failure rats without inducing stress/anxiety-like behavior.