Synthetic routes and clinical application of Small-Molecule HER2 inhibitors for cancer therapy.

This comprehensive review undertakes a meticulous scrutiny of the synthesis and clinical applications pertaining to small-molecule tyrosine kinase inhibitors (TKIs) directed towards the human epidermal growth factor receptor 2 (HER2), a pivotal protagonist in the pathogenesis of cancer. Focused on compounds like lapatinib, neratinib, and tucatinib, the review delves into the intricate synthesis strategies, emphasizing the challenges associated with their structural complexity. The clinical utilization of HER2 TKIs underscores noteworthy strides in the therapeutic landscape for HER2-positive breast and gastric malignancies. Lapatinib, a dual HER2/ epidermal growth factor receptor (EGFR) inhibitor, has demonstrated efficacy in combination therapies, addressing the need for overcoming resistance mechanisms. Neratinib, an irreversible HER2 inhibitor, presents a promising avenue for patients with refractory tumors. Tucatinib, strategically engineered to traverse the blood-brain barrier, epitomizes a groundbreaking advancement in the management of metastatic HER2-positive breast cancer manifesting cerebral involvement. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation HER2 TKIs. This comprehensive review serves as a valuable resource for pharmaceutical scientists, offering insights into the synthetic intricacies and clinical impact of small-molecule TKIs targeting HER2.

Evolution of the point defects involved under the action of mechanical forces on mechanically machined fused silica surfaces.

Point defects with different species are concentrated on most mechanically machined fused silica optical surfaces with surface defects, which would sharply decrease the laser damage resistance under intense laser irradiation. Various point defects have distinct roles in affecting the laser damage resistance. Especially, the proportions of various point defects have not been identified, posing the challenge in relating the intrinsic quantitative relationship among various point defects. To fully reveal the comprehensive effect of various point defects, it is necessary to systematically explore the origins, evolution laws and especially the quantitative relationship among point defects. Herein, seven types of point defects are determined. The unbonded electrons in point defects are found to tend to be ionized to induce laser damage and there is a definite quantitative relationship between the proportions of oxygen-deficient point defects and that of peroxide point defects. The conclusions are further verified based on the photoluminescence (PL) emission spectra and the properties (e.g., reaction rule and structural feature) of the point defects. On basis of the fitted Gaussian components and electronic-transition theory, the quantitative relationship between PL and the proportions of various point defects is constructed for the first time. E'-Center accounts for the highest proportion among them. This work is beneficial for fully revealing the comprehensive action mechanisms of various point defects and providing new insights in elucidating the defect-induced laser damage mechanisms of optical components under intense laser irradiation from the atomic scale.

Pathogenic Tconvs promote inflammatory macrophage polarization through GM-CSF and exacerbate abdominal aortic aneurysm formation.

Abdominal aortic aneurysms (AAAs) elicit massive inflammatory leukocyte recruitment to the aorta. CD4+ T cells, which include regulatory T cells (Tregs) and conventional T cells (Tconvs), are involved in the progression of AAA. Tregs have been reported to limit AAA formation. However, the function and phenotype of the Tconvs found in AAAs remain poorly understood. We characterized aortic Tconvs by bulk RNA sequencing and discovered that Tconvs in aortic aneurysm highly expressed Cxcr6 and Csf2. Herein, we determined that the CXCR6/CXCL16 signaling axis controlled the recruitment of Tconvs to aortic aneurysms. Deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF), encoded by Csf2, markedly inhibited AAA formation and led to a decrease of inflammatory monocytes, due to a reduction of CCL2 expression. Conversely, the exogenous administration of GM-CSF exacerbated inflammatory monocyte infiltration by upregulating CCL2 expression, resulting in worsened AAA formation. Mechanistically, GM-CSF upregulated the expression of interferon regulatory factor 5 to promote M1-like macrophage differentiation in aortic aneurysms. Importantly, we also demonstrated that the GM-CSF produced by Tconvs enhanced the polarization of M1-like macrophages and exacerbated AAA formation. Our findings revealed that GM-CSF, which was predominantly derived from Tconvs in aortic aneurysms, played a pathogenic role in the progression of AAAs and may represent a potential target for AAA treatment.

Triglyceride glucose index predicts all-cause mortality in oldest-old patients with acute coronary syndrome and diabetes mellitus.

BACKGROUND: Acute coronary syndrome (ACS) and diabetes mellitus (DM) are the leading health risks for the elderly. Triglyceride-glucose (TyG) index is a novel and reliable indicator of insulin resistance (IR). This study aims to explore the relationship between the TyG index and all-cause mortality in oldest-old patients with ACS and DM. METHODS: Seven hundred twenty hospitalized patients with ACS aged ≥ 80 years were enrolled, and 699 patients signed informed consent for the study. During the follow-up period, 37 were lost to follow-up, and the follow-up rate was 94.7%. 231 ACS patients with DM were selected for the study's analyses. Kaplan-Meier curve, Cox regression model and receiver operating characteristic (ROC) curve were used to analyze the association between the TyG index and all-cause mortality. RESULTS: The mean age of participants was 81.58 ± 1.93 years, and 32.47% were women. Compared to TyG tertile 1, the Hazard Ratio (HR) [95% confidence interval (CI)] of all-cause mortality was 2.04 (1.09, 3.81) for TyG tertile 3 in the fully adjusted model. For the TyG index per standard deviation (SD) increment, the HR (95% CI) of all-cause mortality was 1.44 (1.13, 1.83). Further, the association between the TyG index and all-cause mortality was dose-response (P for trend = 0.026). ROC curve analyses indicated that the TyG index outperformed FBG and TG in the prediction of mortality risk and improved the prognostic value of the Gensini score combined with LVEF. CONCLUSION: The TyG index predicts the risk of all-cause mortality in the oldest-old ACS patients with DM.

Evaluation of antioxidation, regulation of glycolipid metabolism and potential as food additives of exopolysaccharide from Sporidiobolus pararoseus PFY-Z1.

At present, there are relatively few studies on the production of exopolysaccharide (EPS) by yeasts. Therefore, exploring the properties of EPS produced by yeast can not only enrich the source of EPS, but also play an important role in its future application in the food field. The aim of this study was to explore the biological activities of EPS (named SPZ) from Sporidiobolus pararoseus PFY-Z1, as well as the dynamic changes in physical and chemical properties that occur during simulated gastrointestinal digestion, and the effects of SPZ on microbial metabolites during fecal fermentation in vitro. The results revealed that SPZ had good water solubility index, water-holding capacity, emulsifying ability, coagulated skim milk, antioxidant properties, hypoglycemic activities, and bile acid-binding abilities. Furthermore, the content of reducing sugars increased from 1.20 ± 0.03 to 3.34 ± 0.11 mg/mL after gastrointestinal digestion, and had little effect on antioxidant activities. Moreover, SPZ could promote the production of short-chain fatty acids during fermentation for 48 h, in particular, propionic acid and n-butyric acid increased to 1.89 ± 0.08 and 0.82 ± 0.04 mmol/L, respectively. Besides this, SPZ could inhibit LPS production. In general, this study can help us to better understand the potential bioactivities, and the changes in bio-activities of compounds after digestion of SPZ.

Raman spectroscopy of graphene-based materials and its applications in related devices.

Graphene-based materials exhibit remarkable electronic, optical, and mechanical properties, which has resulted in both high scientific interest and huge potential for a variety of applications. Furthermore, the family of graphene-based materials is growing because of developments in preparation methods. Raman spectroscopy is a versatile tool to identify and characterize the chemical and physical properties of these materials, both at the laboratory and mass-production scale. This technique is so important that most of the papers published concerning these materials contain at least one Raman spectrum. Thus, here, we systematically review the developments in Raman spectroscopy of graphene-based materials from both fundamental research and practical (i.e., device applications) perspectives. We describe the essential Raman scattering processes of the entire first- and second-order modes in intrinsic graphene. Furthermore, the shear, layer-breathing, G and 2D modes of multilayer graphene with different stacking orders are discussed. Techniques to determine the number of graphene layers, to probe resonance Raman spectra of monolayer and multilayer graphenes and to obtain Raman images of graphene-based materials are also presented. The extensive capabilities of Raman spectroscopy for the investigation of the fundamental properties of graphene under external perturbations are described, which have also been extended to other graphene-based materials, such as graphene quantum dots, carbon dots, graphene oxide, nanoribbons, chemical vapor deposition-grown and SiC epitaxially grown graphene flakes, composites, and graphene-based van der Waals heterostructures. These fundamental properties have been used to probe the states, effects, and mechanisms of graphene materials present in the related heterostructures and devices. We hope that this review will be beneficial in all the aspects of graphene investigations, from basic research to material synthesis and device applications.

Serum microRNA-211 as a biomarker for diabetic retinopathy via modulating Sirtuin 1.

Diabetic retinopathy (DR) is a progressive microvascular complication associated with diabetes, and remains the leading cause of preventable blindness worldwide. Recent studies have revealed that microRNAs (miRNAs) were involving in the physiological and pathophysiological processes of diabetes and its microvascular and macrovascular complications. The purpose of the current investigation is to identify the candidate miR-211 as a novel biomarker for occurrence and progression of DR in clinical study and experimental research. Firstly, miR-211 was considered as a candidate miRNA identifying by miRNA microarray analysis, Venn diagram analysis, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and receiver operating characteristic curve in clinical study. Then, the predicted Sirtuin 1 (SIRT1) may be the target gene of miR-211 searching by TargetScan 7.2. Moreover, miR-211 was significantly up-regulated, while SIRT1 mRNA significantly down-regulated measuring by qRT-PCR, meanwhile, SIRT1 protein was significantly down-regulated in coincidence with SIRT1 mRNA detecting by western blot, and even aggravated associated with diabetes duration in diabetic retinal tissues of vivo experiment. Additionally, miR-211 was directly targeted SIRT1 confirming by dual-luciferase reporter assay. Furthermore, with transfection of antagomiR-211, the apoptosis of HUVECs was significantly suppressed employing by flow cytometry analysis, nevertheless the viability of HUVECs was significantly promoted exploiting by Cell Counting Kit-8 assay. Finally, SIRT1 mRNA and SIRT1 protein were significantly up-regulated testing by qRT-PCR and western blot respectively in hyperglycemic HUVECs transfected with antagomiR-211 of vitro experiment. Consequently, the current clinical study and experimental research imply that serum miR-211 as a novel biomarker with high sensitivity and specificity could be associated with occurrence and progression of DR via targeting SIRT1.

Modulating the Surface State of SiC to Control Carrier Transport in Graphene/SiC.

Silicon carbide (SiC) with epitaxial graphene (EG/SiC) shows a great potential in the applications of electronic and photoelectric devices. The performance of devices is primarily dependent on the interfacial heterojunction between graphene and SiC. Here, the band structure of the EG/SiC heterojunction is experimentally investigated by Kelvin probe force microscopy. The dependence of the barrier height at the EG/SiC heterojunction to the initial surface state of SiC is revealed. Both the barrier height and band bending tendency of the heterojunction can be modulated by controlling the surface state of SiC, leading to the tuned carrier transport behavior at the EG/SiC interface. The barrier height at the EG/SiC(000-1) interface is almost ten times that of the EG/SiC(0001) interface. As a result, the amount of carrier transport at the EG/SiC(000-1) interface is about ten times that of the EG/SiC(0001) interface. These results offer insights into the carrier transport behavior at the EG/SiC heterojunction by controlling the initial surface state of SiC, and this strategy can be extended in all devices with graphene as the top layer.

Model of the material removal function and an experimental study on a magnetorheological finishing process using a small ball-end permanent-magnet polishing head.

In order to achieve the deterministic finishing of optical components with concave surfaces of a curvature radius less than 10 mm, a novel magnetorheological finishing (MRF) process using a small ball-end permanent-magnet polishing head with a diameter of 4 mm is introduced. The characteristics of material removal in the proposed MRF process are studied. The model of the material removal function for the proposed MRF process is established based on the three-dimensional hydrodynamics analysis and Preston's equation. The shear stress on the workpiece surface is calculated by means of resolving the presented mathematical model using a numerical solution method. The analysis result reveals that the material removal in the proposed MRF process shows a positive dependence on shear stress. Experimental research is conducted to investigate the effect of processing parameters on the material removal rate and improve the surface accuracy of a typical rotational symmetrical optical component. The experimental results show that the surface accuracy of the finished component of K9 glass material has been improved to 0.14 µm (PV) from the initial 0.8 µm (PV), and the finished surface roughness Ra is 0.0024 µm. It indicates that the proposed MRF process can be used to achieve the deterministic removal of surface material and perform the nanofinishing of small curvature radius concave surfaces.

Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis, oxidative stress and pro-inflammatory cytokine expression in vivo.

BACKGROUND: Complications of diabetes mellitus (DM) are related not only to elevated plasma glucose, but also plasma glucose fluctuations. However, the specific mechanism underlying the role of plasma glucose fluctuation in the pathogenesis of DM complications remains poorly understood. In the present study, the influence of acute fluctuant hyperglycemia and persistent hyperglycemia on vascular endothelial cell apoptosis, function, oxidative stress and inflammation was examined in vivo. METHODS: Rats were assigned to three different groups (n = 10/group) that received 48-h infusions of saline (SAL group), continuous 50 % glucose (constant high glucose group [CHG]), or intermittent 50 % glucose (acute blood glucose fluctuation group [AFG]). Plasma 8-isoprostaglandin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were quantified by using enzyme-linked immunosorbent assay (ELISA) commercial kits. Plasma insulin levels were measured by radioimmunoassays (RIAs) using kits. The aortic segment was collected. The levels of malondialdehyde (MDA) and activity of glutathione peroxidase (GSH-PX) were measured in endothelial homogenates prepared from endothelial cells harvested from the aorta using colorimetric kits. Apoptosis of vascular endothelial cells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Endothelial dysfunction was assessed by isometric tension recording to evaluate the endothelial function. The expression of B cell lymphoma-2 (Bcl-2), Bcl-2 Associated X protein (Bax), pro caspase-3, caspase-3 p17, 3-nitrotyrosine (3-NT) and p47phox protein in rat aortic endothelial cells were tested with Western blot analysis. Endothelial cells reactive oxygen species (ROS) formation was determined using dihydroethidium-dependent fluorescence microtopography in aortic cryo-sections. Expression of IL-6, TNF-α and ICAM-1 mRNAs in vascular endothelial cells were determined by real-time quantitative PCR. RESULTS: Endothelial cells apoptosis and dysfunction were observed significantly in the aortas of the AFG group (P < 0.05). The AFG had reduced Bcl-2 and pro caspase-3 levels and enhanced Bax mitochondrial translocation and caspase-3 p17 protein levels in comparison with the CHG group (P < 0.05). Both AFG and CHG induced ß-cell dysfunction and insulin resistance (P < 0.05). AFG increased MDA and 8-isoprostaglandin levels in plasma, oxidative stress in vascular endothelial cells, and inflammatory cytokines in plasma and vascular endothelial cells (P < 0.05). CONCLUSION: Acute glucose fluctuation may cause significant oxidative stress and inflammation in endothelial cells, increase the adhesion of monocytes to endothelial cells, and elevate endothelial cell apoptosis, resulting in severe cardiovascular injury.

Quantum Oscillations in a Two-Dimensional Electron Gas at the Rocksalt/Zincblende Interface of PbTe/CdTe (111) Heterostructures.

Quantum oscillations are observed in the 2DEG system at the interface of novel heterostructures, PbTe/CdTe (111), with nearly identical lattice parameters (a(PbTe) = 0.6462 nm, a(CdTe) = 0.648 nm) but very different lattice structures (PbTe: rock salt, CdTe: zinc blende). The 2DEG formation mechanism, a mismatch in the bonding configurations of the valence electrons at the interface, is uniquely different from the other known 2DEG systems. The aberration-corrected scanning transmission electron microscope (AC-STEM) characterization indicates an abrupt interface without cation interdiffusion due to a large miscibility gap between the two constituent materials. Electronic transport measurements under magnetic field up to 60 T, with the observation of Landau level filling factor ν = 1, unambiguously reveal a π Berry phase, suggesting the Dirac Fermion nature of the 2DEG at the heterostructure interface, and the PbTe/CdTe heterostructure being a new candidate for 2D topological crystalline insulators.

Halobacillus andaensis sp. nov., a moderately halophilic bacterium isolated from saline and alkaline soil.

A Gram-stain-positive, endospore-forming, moderately halophilic bacterial strain, NEAU-ST10-40T, was isolated from a saline and alkaline soil in Anda City, China. It was strictly aerobic, rod-shaped and motile by peritrichous flagella. It formed light yellow colonies and grew at NaCl concentrations of 3-15 % (w/v) (optimum, 8 %, w/v), at pH 7.0-9.0 (optimum, pH 8.0) and at 4-60 °C (optimum, 30 °C). It contained meso-diaminopimelic acid in the cell-wall peptidoglycan. Phylogenetic analysis based on 16S rRNA gene sequences indicated that it belonged to the genus Halobacillus. Levels of 16S rRNA gene sequence similarity between strain NEAU-ST10-40T and the type strains of related species of the genus Halobacillus ranged from 98.8 % (Halobacillus alkaliphilus FP5T) to 97.1 % (Halobacillus kuroshimensis IS-Hb7T). DNA-DNA hybridization relatedness values between strain NEAU-ST10-40T and H. alkaliphilus DSM 18525T, Halobacillus campisalis KCTC 13144T, Halobacillus yeomjeoni DSM 17110T, Halobacillus halophilus DSM 2266T, Halobacillus litoralis DSM 10405T, Halobacillus dabanensis DSM 18199T, Halobacillus salinus DSM 18897T, Halobacillus naozhouensis DSM 21183T, Halobacillus trueperi DSM 10404T and Halobacillus salsuginis DSM 21185T were from 43 ± 1 to 19 ± 1 % (mean ± sd). The DNA G+C content was 39.3 mol%. The major fatty acids (>10 %) were anteiso-C15:0, anteiso-C17:0 and iso-C16:0, the only respiratory quinone detected was MK-7, and polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unknown phospholipids and three unknown lipids. On the basis of the data presented, strain NEAU-ST10-40T is considered to represent a novel species, for which the name Halobacillus andaensis sp. nov. is proposed. The type strain is NEAU-ST10-40T ( = CGMCC 1.12153T = DSM 25866T).

Kocuria dechangensis sp. nov., an actinobacterium isolated from saline and alkaline soils.

A Gram-stain positive, strictly aerobic, non-motile and coccus-shaped actinobacterium, designated strain NEAU-ST5-33(T), was isolated from saline and alkaline soils in Dechang Township, Zhaodong City, PR China. It formed beige-yellow colonies and grew at NaCl concentrations of 0-5% (w/v) (optimum 0%), at pH 6.0-9.0 (optimum pH 7.0) and over a temperature range of 4-50 °C (optimum 35 °C). Based on 16S rRNA gene sequence analysis, strain NEAU-ST5-33(T) was phylogenetically closely related to the type strains of species of the genus Kocuria, Kocuria polaris CMS 76or(T), Kocuria rosea DSM 20447(T), Kocuria turfanensis HO-9042(T), Kocuria aegyptia YIM 70003(T), Kocuria himachalensis K07-05(T) and Kocuria flava HO-9041(T), with respective sequence similarities of 98.8%, 98.8%, 98.3%, 98.1%, 98.1% and 97.9%. DNA-DNA hybridization relatedness values of strain NEAU-ST5-33(T) with type strains of the closely related species ranged from 54 ± 1% to 34 ± 1%. The DNA G+C content was 61.2 mol%. The major fatty acids (>5%) were C15 : 0 anteiso, C15 : 0 iso and C16 : 1ω7c and/or C16 : 1ω6c. The major menaquinone detected was MK-8 (H2), and the polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unknown aminolipid and one unknown lipid. On the basis of the genotypic, chemotaxonomic and phenotypic data, we propose that strain NEAU-ST5-33(T) represents a novel species of the genus Kocuria, with the name Kocuria dechangensis sp. nov. The type strain is NEAU-ST5-33(T) ( = CGMCC 1.12187(T) = DSM 25872(T)).

Planococcus dechangensis sp. nov., a moderately halophilic bacterium isolated from saline and alkaline soils in Dechang Township, Zhaodong City, China.

Strain NEAU-ST10-9(T) is a moderately halophilic, coccoid and non-motile bacterium isolated from saline and alkaline soils in the Dechang Township, Zhaodong City, China. The bacterium was found to be aerobic and Gram-stain positive. It forms orange colonies and grows at NaCl concentrations of 2-10 % (w/v) (optimum, 4 % w/v), at 4-50 °C (optimum, 30 °C) and at pH 6.0-10.0 (optimum, pH 7.0). Phylogenetic analyses based on 16S rRNA gene sequences indicated that it belongs to the genus Planococcus within the family Planococcaceae. The most closely related species was Planococcus maritimus, whose type strain (TF-9(T)) showed gene sequence similarities of 99.1 % for 16S rRNA, 83.7 % for gyrB and 87.0 % for rpoB with those of strain NEAU-ST10-9(T), respectively. DNA-DNA hybridization relatedness values between strain NEAU-ST10-9(T) and type strains P. maritimus DSM 17275(T) , P. rifietoensis DSM 15069(T) , P. plakortidis DSM 23997(T), P. citreus DSM 20549(T), P. maitriensis DSM 15305(T), P. salinarum KCTC 13584(T) and P. columbae DSM 17517(T) were from 55 ± 1 to 32 ± 2 %. The DNA G+C content was found to be 45.2 mol %. The major fatty acids (>5 %) were determined as C15:0 anteiso, C16:1 ω7c alcohol, C17:1 ω9c and C17:0 anteiso. The major menaquinones of strain NEAU-ST10-9(T) were identified as MK-7 and MK-8. The polar lipids were found to contain of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphocholine and two unknown lipids. The genotypic, chemotaxonomic and phenotypic analysis indicated that strain NEAU-ST10-9(T) represents a novel species of the genus Planococcus, for which we proposed the name Planococcus dechangensis sp. nov. The type strain is NEAU-ST10-9(T) (=CGMCC 1.12151(T)=DSM 25871(T)).

Association of MTHFR C677T with total homocysteine plasma levels and susceptibility to Parkinson's disease: a meta-analysis.

The C677T single-nucleotide polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) may elevate homocysteine (Hcy) levels and increase the risk of Parkinson's disease (PD); however, results are conflicting. Our aim was to resolve contradictions in the literature and to determine whether MTHFR C677T has a significant role in regulating Hcy levels and/or is a significant risk factor for PD. MEDLINE, EMBASE, the Cochrane Library, China Biological Medicine Database and Google Scholar were searched until May 2014. Strict selection and exclusion criteria were determined, and odds ratios (ORs)/weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed using STATA 12.0. Fifteen studies that together assessed 2690 PD cases and 8465 controls were included. Meta-analysis showed that no significant difference in the distribution of MTHFR C677T between PD cases and controls was found. While stratifying for ethnicity, significant association was revealed in Europeans (T vs. C, OR = 1.17, 95 % CIs 1.04-1.31) but not in Asians. Significant association between the T allele and increased Hcy levels was found in PD cases and controls; Hcy levels were higher in PD cases and controls carrying the MTHFR T677 allele than in non-carriers (TT vs. CC, PD WMD = 6.50, 95 % CIs 6.20-6.80; controls WMD = 4.52, 95 % CIs 4.24-4.80). Other within-group comparisons showed similar results. This meta-analysis suggests that MTHFR C667T may confer PD susceptibility in Europeans. The T allele may be an independent risk factor for elevated Hcy levels in PD patients.

Cloning and identification of Group 1 mrp operon encoding a novel monovalent cation/proton antiporter system from the moderate halophile Halomonas zhaodongensis.

The novel species Halomonas zhaodongensis NEAU-ST10-25(T) recently identified by our group is a moderate halophile which can grow at the range of 0-2.5 M NaCl (optimum 0.5 M) and pH 6-12 (optimum pH 9). To explore its halo-alkaline tolerant mechanism, genomic DNA was screened from NEAU-ST10-25(T) in this study for Na(+)(Li(+))/H(+) antiporter genes by selection in Escherichia coli KNabc lacking three major Na(+)(Li(+))/H(+) antiporters. One mrp operon could confer tolerance of E. coli KNabc to 0.8 M NaCl and 100 mM LiCl, and an alkaline pH. This operon was previously mainly designated mrp (also mnh, pha or sha) due to its multiple resistance and pH-related activity. Here, we will also use mrp to designate the homolog from H. zhaodongensis (Hz_mrp). Sequence analysis and protein alignment showed that Hz_mrp should belong to Group 1 mrp operons. Further phylogenetic analysis reveals that Hz_Mrp system should represent a novel sub-class of Group 1 Mrp systems. This was confirmed by a significant difference in pH-dependent activity profile or the specificity and affinity for the transported monovalent cations between Hz_Mrp system and all the known Mrp systems. Therefore, we propose that Hz_Mrp should be categorized as a novel Group 1 Mrp system.

Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF.

AIMS: This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). METHODS AND RESULTS: We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P < 0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6 months (P < 0.05), and LVEDVI decreased significantly in the S/V group (P = 0.001). In the S/V group, ΔLVEF (t = -2.745, P = 0.006), ΔNT-proBNP (P = 0.009), ΔLVEDVI (t = 4.203, P = 0.001), and ΔLVESVI (t = 3.907, P = 0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r = -0.244, P = 0.004), ΔLVMI (r = -0.190, P = 0.028), ΔLVEDVI (r = -0.173, P = 0.045), and ΔLVESVI (r = -0.261, P = 0.002). In Cox regression model analysis, ΔLVEF {hazard ratio [HR] = 0.87 [95% confidence interval (CI) 0.80-0.95], P = 0.003}, ΔLVEDVI [HR = 1.04 (95% CI 1.01-1.06), P = 0.013], and ΔLVESVI [HR = 1.04 (95% CI 1.01-1.08), P = 0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t = 6.290, P = 0.001), ΔLVEDVI (t = 2.581, P = 0.011), and ΔNT-proBNP (P = 0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t = -3.365, P = 0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t = -3.928, P = 0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P = 0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P = 0.004). CONCLUSIONS: The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Geriatric nutritional risk index predicts all-cause mortality in the oldest-old patients with acute coronary syndrome: A 10-year cohort study.

Background and objective: Nutritional status assessment in acute coronary syndrome (ACS) patients has been neglected for a long time. The geriatric nutritional risk index (GNRI) is a sensitive indicator for assessing the nutritional status of the elderly. This study aims to explore the association between GNRI and all-cause mortality in the oldest-old patients with ACS. Methods: The patients who met the inclusion criteria were consecutively enrolled from January 2006 to December 2012. Clinical data were collected on admission, and all subjects were followed after being discharged. The nutritional status was evaluated using GNRI. The relationship between GNRI and all-cause mortality was assessed by using different analyses. Results: A total of 662 patients with a mean age of 81.87 ± 2.14 years old were included in our study, and followed (median: 63 months, IQR 51-71). Patients whose GNRI ≤ 98 were reported as at risk of malnutrition (31.11%, n = 206). In multivariable analysis, we found that for each SD increase in GNRI, the risk of all-cause mortality lowered by 23%, and the HR for GNRI ≤ 98 was 1.39 (95% CI 1.04-1.86). After stratifying patients into three groups by tertiles of GNRI, we found that the HRs for tertile 2 and tertile 3 were 1.49 (95% CI 1.02-2.19) and 1.74 (95% CI 1.22-2.50), respectively. The trend test revealed a dose-response relationship between GNRI and all-cause mortality in the oldest-old with ACS. Lastly, in subgroup analyses, we found a reliable association between GNRI and all-cause mortality. Conclusion: Malnutrition is common in the oldest-old patients with ACS, and GNRI could predict their long-term all-cause mortality in a dose-dependent manner. GNRI may be a prospective index for risk-stratification and secondary-prevention in the oldest-old patients with ACS.

Unveiling sub-bandgap energy-level structures on machined optical surfaces based on weak photo-luminescence.

Sub-bandgap defect energy levels (SDELs) introduced by the point defects located in surface defect areas are considered the main factors in decreasing laser-induced damage thresholds (LIDTs). The suppression of SDELs could greatly increase LIDTs. However, no available method could detect SDELs, limiting the characterization and suppression of SDELs. Herein, a self-designed photo-luminescence detection system is developed to explore the weak transient-steady photo-luminescence properties of machined surfaces. Based on the excitation laser wavelength dependence of photo-luminescence properties, a sub-bandgap energy-level structure (SELS) containing SDELs is unveiled for the first time. Based on the developed mathematical model for predicting LIDTs, the feasibility of the detection method was verified. In summary, this work provides a novel approach to characterize SDELs on machined surfaces. This work could construct electronic structures and explore the transition behaviors of electrons, which is vital to laser-induced damage. Besides, this work could predict the LIDTs of the machined surfaces based on their PL properties, which provides convenience for evaluating the LIDTs of various optical elements in industrial production. Moreover, this work provides a convenient method for raising the LIDTs of various optical elements through monitoring and suppressing the SDELs on machined surfaces.

[Biodiversity of culturable halotolerant and halophilic bacteria isolated from saline-alkaline soils in Songnen Plain].

OBJECTIVE: To analyze the biodiversity of halotolerant and halophilic bacteria the bacteria in saline-alkaline soils in Songnen Plain, we isolated and purified bacteria samples in the area. METHODS: Halotolerant and halophilic bacteria were isolated from the enriched cultures of the saline-alkline soil samples through the traditional culture method, and 16S rRNA sequences were amplified and analyzed for the determination of phylogenetic relationships. RESULTS: Forty strains were obtained and classified into 34 species, 16 genera, 8 families, 3 phylum (Firmicutes, gamma-Proteobacteria and Actinobacteria) in the Domain Bacteria. The genus Staphylococcus is the predominant group, followed by Halomonas, Oceanbacillus, Bacillus, Kocuria and Pseudomonas. The 16S rRNA sequences of 9 strains showed 97.2 to 99.0% similarities with their closest type strains, suggesting that they may be the potential novel species. The salt tolerance of the strains is mainly concentrated on the 5% - 10% NaCl while alkaline pH resistance of the strains is between pH 9 and 12. Based on the NaCl dependence, 62.5% of the strains were grouped into the halotolerant bacteria, and the rest into the moderate halophiles. CONCLUSION: The halotolerant and halophilic bacteria are very rich in the saline-alkaline soils in Songnen Plain, and the genera Staphylococcus and Halomonas are the predominant groups. Almost all the bacteria from this area could tolerate not only at the high concentration of NaCl, but also at high alkaline pH. More importantly, a number of novel species may be included in this area.