Despite the utmost importance and decades of experimental studies on fatigue in metallic glasses (MGs), there has been so far little or no atomic-level understanding of the mechanisms involved. Here ...we perform molecular dynamics simulations of tension–compression fatigue in Cu50Zr50 MGs under strain-controlled cyclic loading. It is shown that the shear band (SB) initiation under cyclic loading is distinctly different from that under monotonic loading. Under cyclic loading, SB initiation takes place when aggregates of shear transformation zones (STZs) accumulating at the MG surface reach a critical size comparable to the SB width, and the accumulation of STZs follows a power law with rate depending on the applied strain. It is further shown that almost the entire fatigue life of nanoscale MGs under low cycle fatigue is spent in the SB-initiation stage, similar to that of crystalline materials. Furthermore, a qualitative investigation of the effect of cycling frequency on the fatigue behavior of MGs suggests that higher cycling frequency leads to more cycles to failure. The present study sheds light on the fundamental fatigue mechanisms of MGs that could be useful in developing strategies for their engineering applications.
Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various ...cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC‐derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium‐dependent phospholipid‐binding protein, was expressed in a PC cell line (CFPAC‐1)‐derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC‐derived exosomes and its involvement in PC biology.
Background and Aim
Carbapenem resistance has become a major obstacle in combating Acinetobacter baumannii infections. Although enzymatic degradation by β‐lactamases is the pivotal mechanism of ...carbapenem resistance, porin deficiency has also been implicated in the mechanism. In this study, outer membrane proteins (OMPs) pattern of a clinical multidrug‐resistant A. baumannii isolate were analysed in order to attain a deeper understanding of carbapenem‐resistance strategies.
Methods
OMPs extracts, respectively, separated from carbapenem‐resistant and ‐susceptible clinical A. baumannii isolates were compared using two‐dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF).
Results
Twenty‐three differently expressed proteins were identified between the resistant and susceptible isolates. Among them, six were annotated convincingly as OMPs in UniProt database. CarO was found absent from the resistant isolate and the expression levels of Omp33‐36 and Omp25 were significantly lower than that in the susceptible counterpart. Strikingly, a LysM domain/BON superfamily protein, which has been linked to carbapenem resistance in Klebsiella pneumoniae, was found underexpressed by tenfold in the resistant isolate.
Conclusion
Our study verified some porins which have been proven to play an important role in bacterial resistance against carbapenems. Underexpression of the LysM domain/BON superfamily protein may indicate its possible engagement in bacterial drug resistance, but its actual role requires more investigation.
Significance and Impact of the Study: This study identified some porins including CarO, Omp33‐36 and OmpA that are differentially expressed in carbapenem‐resistant Acinetobacter baumannii by comparing outer membrane proteomes of a clinical carbapenem‐resistant isolate vs a susceptible one through 2‐DE. More strikingly, this study discovered an association between carbapenem resistance and the LysM domain/BON superfamily protein in A. baumannii.
Yak milk is an essential and predominant food resource for Tibetan people for subsistence purposes and to combat altitude-induced challenges. Due to its unique qualities, yak milk has recently been ...gaining broader attention from consumers across China as well in other parts of the world. One of the key characteristics of yak milk is the protein content, which is about 40 to 60% higher than that of native bovine milk. In this work, a sensitive and reproducible high-throughput analytical method was developed employing both ultra high-performance liquid chromatography Orbitrap (Thermo Fisher Scientific) high-resolution accurate mass spectroscopy (UHPLC-HRAM-MS) and UHPLC coupled with triple quadrupole tandem MS (UHPLC-QqQ-MS) to simultaneously analyze 8 milk proteins. A total of 15 Maiwa yak milk samples and 15 bovine milk samples were qualitatively and quantitatively analyzed using targeted proteomics and compared for α-lactalbumin, β-lactoglobulin, αS1-casein, αS2-casein, β-casein, κ-casein, lactoferrin, and osteopontin. Peptides of β-lactoglobulin were used to specifically distinguish yak and bovine milk. The results showed that this novel detection method could quantitatively detect these major and minor milk proteins with >0.99 linear correlation coefficient and a recovery rate between 90 and 120%, with relative standard deviations typically less than 10%. The data revealed that yak milk not only had higher overall milk protein content than bovine milk but higher lactoferrin and osteopontin contents as well. The lactoferrin content of yak milk was about 30% higher than that of bovine milk, and the osteopontin content of yak milk was nearly twice that of bovine milk. The application of this method demonstrates that UHPLC-HRAM-MS and UHPLC-QqQ-MS are suitable for high-throughput qualitative and quantitative analysis of major and minor proteins of yak and bovine milk.
Objectives
To study the aggregation of multiple comorbidities in people with gout and explore differences in prognosis of gout flares among different subgroups.
Methods
Hierarchical clustering was ...performed to identify homogeneous subgroups among 2639 people with gout using eight comorbidities. A one-year follow-up of acute gout flares in 463 of these people was conducted; the incidence and the timing of gout flare
s
in each cluster were assessed to explore prognosis of gout flares. Binary logistic regression was applied to assess factors associated with gout flares.
Results
In baseline study, we identified five subgroups (C1–C5). C1 (
n
= 671, 25%) was characterized by isolated gout with few comorbidities. C2 (
n
= 258, 10%) were all obese. Almost all people in C3 (
n
= 335, 13%) had diabetes (99.7%). All people in C4 (
n
= 938, 36%) had dyslipidemia. C5 (
n
= 437, 17%) had the highest proportion of cardiovascular disease (CVD, 53%), chronic kidney disease (CKD, 56%), and cancer (7%). In follow-up study, C5 had the highest incidence (71.9%) and earliest onset (median 3 months) of gout flares. C2 had the lowest incidence (52.1%) and the latest onset (median 10 months) of gout flares. The highest relative risk for gout recurrent was seen for C5 (OR = 2.09). Other factors associated with the risk of gout flares were age at diagnosis of gout, duration of gout, presence of tophi, and smoking ≥ 20 cigarettes/day.
Conclusions
We clustered people with gout into five groups with varying comorbidities. People with CVD, CKD, and cancer had the highest risk of gout flares and should receive comprehensive care.
A triple-shape memory effect represents that polymers can memorize two temporary shapes and show a subsequent recovery from the second temporary shape to the first temporary shape and further to the ...permanent shape with heating, which provides more design freedom for the applications of shape-memory polymers. In this work, we investigate the shapememory performance of three polymers produced by a commercial 3D printer. Two polymers with a pure component exhibit distinct glass transition regions spanning 30°C for each material. The copolymer has a broader glass transition region from -4 to 59 °C. The dual-shape memory tests show that the deformation temperature has a limited influence on the two pure polymers, while a clear temperature memory effect can be observed in the copolymer. For the copolymer, the recovery region has only a small overlap when deformed at 60 and 20 °C, which allows programming two temporary shapes at these two temperatures. Both uniaxial tension tests and three-dimensional demonstration show that the copolymer exhibits a good triple-shape memory effect.
TGF-β has paradoxical effects on cancer cell proliferation, as it suppresses proliferation of normal epithelial and low-invasive cancer cells, but enhances that of high-invasive cancer cells. ...However, how cancer cells acquire the ability to evade the tumor-suppressing effects of TGF-β, yet still take advantage of its tumor-promoting effects, remains elusive. Here, we identified miR-106b as a molecular switch to determine TGF-β effects on cell proliferation. TGF-β1 enhances the transcription of miR-106b via a promoter independent of its host gene MCM7 by activating c-jun. In high-invasive breast cancer cells, miR-106b is upregulated by TGF-β1 at a much higher level than that in normal or low-invasive cancer cells. Accumulation of miR-106b counterbalances TGF-β growth-inhibiting effects by eliminating activated retinoblastoma (RB) and results in enhanced proliferation. Furthermore, miR-106b mediates TGF-β effects on tumor growth and metastasis in breast cancer xenografts. In addition, miR-106b expression is elevated in higher stage tumors and correlated with tumor progression in breast cancer patients. These findings suggest that high level of miR-106b induced by TGF-β determines the tumor-promoting effects of TGF-β in breast cancer.
Summary
It is unknown whether a relationship exists between bone mineral density (BMD) and atherosclerosis with or without vascular calcification. In our study, a negative correlation between carotid ...atherosclerosis and BMD was found in female T2DM patients with vascular calcification, but not in those without calcification and males.
Introduction
Atherosclerosis is considered associated with low bone mineral density (BMD). However, most previous studies focus on patients with arterial atherosclerosis with vascular calcification. It is still unknown whether a relationship exists between atherosclerosis and BMD in patients without calcification. It is also unknown if sex plays a role in this relationship.
Methods
We performed a retrospective cross-sectional study, which included 1459 type 2 diabetes mellitus (T2DM) patients (648 males ≥ 50 years old, and 811 postmenopausal females). They were assigned to three groups: group 1 (patients without carotid plaques and without carotid calcification), group 2 (patients with carotid plaques but without carotid calcification), and group 3 (patients with carotid plaques and with carotid calcification). Clinical characteristics and BMD were compared. The relationship between atherosclerosis and BMD was determined by binary logistic regression analysis. Statistical analysis was performed using SPSS 25.0.
Results
Significant differences were only observed in women. The percentage of osteoporosis was higher in group 3 (43.64%) than in groups 1 (34.82%) and 2 (32.14%) (
P
= 0.016). Low BMD was found in the lumbar (
P
= 0.032), hip (
P
< 0.001), and femoral neck (
P
< 0.001). The odds ratio for osteoporosis increased significantly in a score-dependent manner in postmenopausal female patients with calcified atherosclerosis, but not in uncalcified patients. In men, no differences or relationships were identified.
Conclusion
A negative correlation between carotid atherosclerosis and BMD was found in female T2DM patients with vascular calcification, but not in those without calcification. A similar relationship was not observed in male patients with or without calcification. Thus, the relationship between atherosclerosis and bone mineral density in patients with type 2 diabetes depends on vascular calcifications and sex.
The electrochemical corrosion and passive behavior of activated combustion high-velocity air fuel FeCrMoMnWBCSi amorphous metallic coatings (AMCs) under different geometries that produced a variable ...tensile residual stresses were investigated in chloride-containing solutions by using electrochemical measurements and X-ray photoelectron spectroscopy. The tensile residual stresses of AMCs were determined by the mechanical method of sharp indentation testing. A systematic detrimental effect of tensile residual stress on passive current density and localized corrosion was found. The detrimental effect of residual stress was aggravated at higher temperatures and acidity. The implication of high donor density on the passive film stability, derived from Mott–Schottky analysis, is also discussed.
•The amorphous metallic coatings (AMCs) with convex arc were prepared by AC-HVAF.•The tensile residual stresses of AMCs were determined by sharp indentation testing.•The high tensile residual stress increased the corrosion susceptibility of AMCs.•The tensile residual stress decreased the uniform corrosion and pitting resistance.
Oxidative stress has an important role in the development of obesity and obesity-associated metabolic disorders. As an endogenous antioxidant enzyme, superoxide dismutase 3 (SOD3) has the potential ...to affect diet-induced obesity and obesity-associated complications. In the current work, we overexpressed SOD3 in C57BL/6 mice fed a high-fat diet (HFD) to study its effect on HFD-induced obesity, fatty liver and insulin resistance. We demonstrated that the Sod3 gene transfer blocked HFD-induced obesity, fatty liver and insulin resistance. Real-time PCR analysis of adipose and liver tissues revealed that overexpression of the Sod3 gene suppressed expression of pro-inflammatory genes in adipose tissue including F4/80, Tnfα, Cd11c, Mcp1 and Il6, and increased expression of anti-inflammatory genes such as adiponectin. In the liver, high levels of SOD3 activity in animals enhanced expression of the genes responsible for energy expenditure including Cpt1α, Cpt1β, Pgc1α, Pgc1β and Ucp2. These results suggest that overexpression of the Sod3 gene through gene transfer is an effective approach in preventing diet-induced obesity and obesity-associated complications.
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