In quantum field theory, Lorentz invariance leads to three types of fermion-Dirac, Weyl and Majorana. Although the existence of Weyl and Majorana fermions as elementary particles in high-energy ...physics is debated, all three types of fermion have been proposed to exist as low-energy, long-wavelength quasiparticle excitations in condensed-matter systems. The existence of Dirac and Weyl fermions in condensed-matter systems has been confirmed experimentally, and that of Majorana fermions is supported by various experiments. However, in condensed-matter systems, fermions in crystals are constrained by the symmetries of the 230 crystal space groups rather than by Lorentz invariance, giving rise to the possibility of finding other types of fermionic excitation that have no counterparts in high-energy physics. Here we use angle-resolved photoemission spectroscopy to demonstrate the existence of a triply degenerate point in the electronic structure of crystalline molybdenum phosphide. Quasiparticle excitations near a triply degenerate point are three-component fermions, beyond the conventional Dirac-Weyl-Majorana classification, which attributes Dirac and Weyl fermions to four- and two-fold degenerate points, respectively. We also observe pairs of Weyl points in the bulk electronic structure of the crystal that coexist with the three-component fermions. This material thus represents a platform for studying the interplay between different types of fermions. Our experimental discovery opens up a way of exploring the new physics of unconventional fermions in condensed-matter systems.
Background
This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF‐α inhibitor, adalimumab, for Chinese patients with moderate‐to‐severe plaque ...psoriasis.
Methods
In the 12‐week, double‐blind, placebo‐controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every‐other‐week (following a single 80 mg dose), or placebo every‐other‐week. In the subsequent 12‐week, open‐label, Period B, all patients received adalimumab 40 mg every‐other‐week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug.
Results
For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All‐adalimumab Population), treatment‐emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All‐adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis 2 (0.5%) patients each. There was one death (chronic heart failure).
Conclusion
In these Chinese patients with moderate‐to‐severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the main source of extracellular pyrophosphate. Along with tissue-nonspecific alkaline phosphatase (TNAP), ENPP1 plays an important role ...in balancing bone mineralisation. Although well established in pre-osteoblasts, the regulating mechanisms of ENPP1 in osteoblasts and osteocytes remain largely unknown. Using bioinformatic methods, osterix (Osx), an essential transcription factor in osteoblast differentiation and osteocyte function, was found to have five predicted binding sites on the ENPP1 promoter. ENPP1 and Osx showed a similar expression profile both in vitro and in vivo. Over-expression of Osx in MC3T3-E1 and MLO-Y4 cells significantly up-regulated the expression of ENPP1 (p < 0.05). The consensus Sp1 sequences, located in the proximal ENPP1 promoter, were identified as Osx-regulating sites using promoter truncation experiments and chromatin immunoprecipitation (ChIP) assays. The p38-mitogen-activated protein kinase (MAPK) signalling pathway was demonstrated to be responsible for ENPP1 promoter activation by Osx. Runt-related transcription factor 2 (Runx2) was confirmed to have synergistic effects with Osx in activating ENPP1 promoter. Taken together, these results provided evidence of the regulating mechanisms of ENPP1 transcription in osteoblasts and osteocytes.
Atomic structure, diffusivity and viscosity of Al1-xMgx (x=0, 0.0039, 0.1172, 0.9180, 0.9961, 1)melts at 875, 1000, 1125, and 1250K were investigated by the ab initio molecular dynamics (AIMD) ...simulations. The simulated results are compared with available experimental and calculated data in the literature with reasonable agreements. Considering the results of pair correlation function g(r), it can be observed that Mg atoms in Al0.8828Mg0.1172 melt aggregate more obviously at 1000 and 1250K. For Al0.0820Mg0.9180, Al atom segregation is more obvious at 875 and 1000K. The tracer diffusion coefficients of Al or Mg in Al1-xMgx (x=0.1172, 0.9180) melts, and interdiffusion coefficients of Al0.8828Mg0.1172 and Al0.0820Mg0.9180 melts are all close to the self-diffusion coefficients of Al or Mg. With the increasing temperature, the diffusivity increases linearly. In dilute melts, the tracer diffusion coefficients of solute atom and the interdiffusion coefficients increase nonlinearly with the increasing temperature. For Al0.8828Mg0.1172 and Al0.0820Mg0.9180 melts, the viscosities ? are comparatively higher than pure melts. The viscosities of all melts decrease with the increasing temperature, then increase at 1250K. The results obtained in the present work provide an insight into the design of Al and Mg alloys.
Purpose
Though type 2 diabetes mellitus (T2DM) is an important and independent risk factor for coronary artery disease (CAD) in the general population, the impact of T2DM on CAD in patients with ...familial hypercholesterolemia (FH) is less understood. Thus, the current study aimed to examine the features of FH patients with T2DM and explore the effects of T2DM on CAD in FH.
Methods
A total of 289 clinical heterozygous FH (HeFH) patients diagnosed with Dutch Lipid Clinic Criteria were consecutively recruited and divided into a T2DM group (
n
= 58) and non-T2DM group (
n
= 231). Clinical characteristics and laboratory findings were compared between the two groups. Target exome sequencing was used for gene mutation analysis.
Results
HeFH patients with T2DM had significantly higher levels of triglycerides, body mass index and free fatty acids than did non-T2DM patients; moreover, patients with T2DM more frequently exhibited hypertension. However, the spectrum of FH-causing mutations was not significantly different (
p
= 0.061). Notably, patients with T2DM had higher prevalence of CAD (
p
= 0.012) and higher Gensini Score (
p
= 0.002). The regression analysis confirmed that HbA1c was an independent risk factor for both the presence and severity of CAD OR 2.321 (1.098–4.904),
p
= 0.027; OR 1.349 (1.032–1.762),
p
= 0.028, respectively in patients with HeFH.
Conclusions
Although there were not many differences in the clinical, lipid and genetic aspects of HeFH patients with and without T2DM, T2DM and HbA1c were associated with worse coronary lesions, suggesting that diabetes and the degree of blood glucose control are also important determinants of cardiovascular disease in these patients.
Summary
Background
The patatin‐like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non‐alcoholic fatty liver disease (NAFLD). However, the associations ...between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied.
Aim
To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis.
Methods
Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes.
Results
Non‐alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high‐density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima‐media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype.
Conclusions
PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic‐related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.
Telemedicine can alleviate the problems faced in rural settings in providing access to specialist stroke care. The evidence of the cost-effectiveness of this model of care outside high-income ...countries is limited. This study aimed to conduct: (a) a systematic review of economic evaluations of telestroke and (b) a cost-utility analysis of telestroke, using China as a case study.
We systematically searched Embase, Medline Complete and Cochrane databases. Inclusion criteria: full economic evaluations of telemedicine/telestroke networks examining the use of thrombolysis in patients with acute ischaemic stroke, published in English. A cost-utility analysis was undertaken using a Markov model incorporating a decision tree to simulate the delivery of telestroke for acute ischaemic stroke in rural China, compared to no telestroke from a societal and healthcare perspective. One-way deterministic sensitivity analyses and probabilistic sensitivity analyses were performed to test the robustness of results.
Of 559 publications found, eight met the eligibility criteria and were included in the systematic review (two cost-effectiveness analyses and six cost-utility analyses, all performed in high-income countries). Telestroke was a cost-saving/cost-effective intervention in five out of the eight studies. In our modelled analysis for rural China, telestroke was the dominant strategy, with estimated cost savings of Chinese yuan 4,328 (US$627) and additional 0.0925 quality-adjusted life years per patient. Sensitivity analyses confirmed the base case results.
Consistent with published economic evaluations of telestroke in other jurisdictions, telestroke represents a cost-effective solution to enhance stroke care in rural China.
The role of lipoprotein (a) Lp(a) in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present ...study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD.
A total of 2040 consecutive patients with T2DM who received selective coronary angiography (CAG) due to angina-like chest pain were enrolled. The patients were subsequently divided into CAD and non-CAD groups according to the results of CAG. The severity of CAD was evaluated by the Gensini Score (GS), number of stenotic vessels, and history of myocardial infarction (MI). Data showed that Lp(a) levels were higher in the CAD group than in the non-CAD group (median: 15.00 mg/dL vs. 11.88 mg/dL, P = 0.025). The results from CAD subgroup analysis indicated that the patients with MI, multiple-vessel disease and high GS had higher Lp(a) levels compared with those in their matched subgroups (P < 0.05, respectively). After adjustment for confounders, Lp(a) levels were independently related to the presence and severity of CAD (CAD:OR = 1.564; MI:OR = 1.523; high GS:OR = 1.388; multiple-vessel disease:OR = 1.455; P < 0.05, respectively).
Elevated Lp(a) levels were independently associated with the presence and severity of CAD in patients with T2DM. More studies are necessary to confirm our findings.
•Lp(a) levels were significantly increased in T2DM patients with CAD and were gradually increased with the severity of CAD.•Lp(a) levels were independent associated with the presence and severity of angiography-proven CAD in patients with T2DM.•Lp(a) might be useful to evaluate the presence and severity of CAD and Lp(a) screening might be considered in diabetic patients.
Purpose
It has been reported that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can significantly reduce lipoprotein(a) Lp(a), and the mechanism for Lp(a) reduction remains ...unclear. Recently an interesting clinical research with a small sample showed a positive correlation between plasma PCSK9 and Lp(a) levels in diabetes. Here we aimed to use a relatively large sample to investigate whether such an association exists in Han Chinese.
Methods
A total of 783 inpatients were consecutively enrolled and composed of 172 patients with type 2 diabetes mellitus (T2DM) and 611 non-T2DM subjects. Plasma PCSK9 level was measured by ELISA, and its association with Lp(a) was assayed by Spearman’s correlation and multiple regression. Clinical and biochemical parameters were determined in all subjects studied.
Results
No significant differences in PCSK9 and Lp(a) levels were found between T2DM and non-T2DM patients. PCSK9 level was not related to Lp(a) level either in T2DM or non-T2DM group in bivariate correlation and multiple linear regression analysis. Additionally, no association between the levels of PCSK9 and Lp(a) was found in well, poorly controlled T2DM patients or in T2DM patients with or without coronary artery disease (CAD). Besides, no difference was found among the PCSK9 values across tertiles of Lp(a) level.
Conclusion
We found no association of plasma PCSK9 levels with Lp(a) level in Han Chinese with or without T2DM, suggesting that Lp(a) reduction by PCSK9 inhibitors may not be achieved simply through PCSK9 pathway at least in Chinese.
•Studied binary Lanthanide–Cobalt intermetallic alloys by high temperature calorimetry.•Determined the enthalpies of formation of 16 magnetostrictive alloys.•Compared the experimental measurements ...with theoretical predictions by two different models.
The standard enthalpies of formation of intermetallic compounds of some Lanthanide–Cobalt systems have been measured by high temperature direct synthesis calorimetry at 1373±2K. The following results in kJ/mol of atoms are reported: CeCo5(−9.4±3.3); Ce2Co17(−6.8±3.2); PrCo5(−10.5±2.4); Pr2Co17(−6.8±3.6); NdCo5(−12.7±2.6); Nd2Co17(−6.6±2.7); SmCo5(−12.2±1.8); Sm2Co17(−7.2±2.5); GdCo5(−10.0±2.4); Tb2Co17(−7.7±2.9); Dy2Co17(−8.1±2.9); HoCo3(−17.5±2.2); ErCo3(−19.7±3.3); TmCo3(−22.9±3.0); LuCo3(−23.0±2.6). The measurements are compared with values from the literature and with predicted values of the semi empirical model of Miedema and Coworkers. We also compare the measurements with predicted values by ab initio calculations. We will present a systematic picture of how the enthalpies of formation may be related to the atomic number of the Lanthanide element (LA). We will also compare the thermochemical behavior of the Fe, Co and Ni binary alloys with Lanthanide elements.
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