•Plastic yielding is affected by the normal stress acting on the shear plane, which is verified by finite element methods.•The internal friction coefficient is found to decrease with the increase of ...concentration of flow defects.•The effect of structural state modified by annealing or rejuvenation is rationalized by the flow defects concentration.•Under different structural states, the displacement bursts are different, changing from obvious to inapparent serration.•The schematic illustrats the correlation between the displacement burst and the shear band size.
Unraveling the microstructural heterogeneity is an important issue to understand the physical and mechanical properties of metallic glasses. Structural relaxation below the glass transition temperature Tg and cold rolling at ambient temperature are effective ways to tune the state within the potential energy landscape of metallic glasses, modifying the microstructural heterogeneity. With the help of nanoindentation technique, by scrutinizing the local reduced modulus and hardness of a typical Zr50Cu40Al10 metallic glasses in different energy states (from structural relaxed state to rejuvenated state), we demonstrate that the enhancement of microstructural heterogeneity plays an important role in tailoring the mechanical behavior. The internal friction coefficient is obtained by fitting the experimental load-displacement curves with finite element simulation. It is found that internal friction coefficient decreases with the increase of concentration of flow defects. The stress exponent obtained from the creep stage shows a strong dependence on the structural state of metallic glasses. Effects of structural relaxation and rejuvenation on the structural state are rationalized in terms of the relative flow defects concentration. Finally, the statistics of discrete displacement bursts during the deformation process were probed. We find that the displacement bursts behavior is sensitive to the structural energy state (microstructural heterogeneity). The displacement bursts phenomenon changes from obvious (relaxed state) to unapparent behaviors (rejuvenated state). By given a physical schematic, the correlation between the displacement bursts size and the shear band size in the local plastic zones is well established, which will lead to a deeper understanding of the rejuvenation-induced plasticity of metallic glasses.
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AbstractObjectiveTo compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and ...tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options.DesignSystematic review and network meta-analysis.Data sourcesOvid Medline, Embase, and Cochrane Central up to 14 October 2022.Eligibility criteria for selecting studiesEligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach.ResultsThe analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference −8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes).ConclusionsThis network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.Systematic review registrationPROSPERO CRD42022325948.
Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; ...therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies.
From November 2012 to April 2013, a total of 7372 healthy women aged 18–45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay.
The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0–15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18–26 years) and middle-aged women (27–45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18).
This study revealed that the majority of Chinese women aged 18–26 years and 27–45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.
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The interaction between resident cells and electrospun nanofibers is critical in determining resultant osteoblast proliferation and activity in orthopedic tissue scaffolds. The use of ...techniques to evaluate cell–nanofiber interactions is critical in understanding scaffold function, with visualization promising unparalleled access to spatial information on such interactions. 3D tomography exploiting focused ion beam (FIB)–scanning electron microscopy (SEM) was used to examine electrospun nanofiber scaffolds to understand the features responsible for (osteoblast-like MC3T3-E1 and UMR106) cell behavior and resultant scaffold function. 3D imaging of cell–nanofiber interactions within a range of electrospun poly(d,l-lactide-co-glycolide acid) (PLGA) nanofiber scaffold architectures indicated a coherent interface between osteoblasts and nanofiber surfaces, promoting osteoblast filopodia formation for successful cell growth. Coherent cell–nanofiber interfaces were demonstrated throughout a randomly organized and aligned nanofiber network. Gene expression of UMR106 cells grown on PLGA fibers did not deviate significantly from those grown on plastic, suggesting maintenance of phenotype. However, considerably lower expression of Ibsp and Alpl on PLGA fibers might indicate that these cells are still in the proliferative phase compared with a more differentiated cell on plastic. This work demonstrates the synergy between designing electrospun tissue scaffolds and providing comprehensive evaluation through high resolution imaging of resultant 3-dimensional cell growth within the scaffold.
Membranes made from electrospun nanofibers are potentially excellent for promoting bone growth for next-generation tissue scaffolds. The effectiveness of an electrospun membrane is shown here using high resolution 3D imaging to visualize the interaction between cells and the nanofibers within the membrane. Nanofibers that are aligned in one direction control cell growth at the surface of the membrane whereas random nanofibers cause cell growth into the membrane. Such observations are important and indicate that lateral cell growth at the membrane surface using aligned nanofibers could be used for rapid tissue repair whereas slower but more extensive tissue production is promoted by membranes containing random nanofibers.
The cross section of the e+e−→Λc+Λ¯c− process is measured with unprecedented precision using data collected with the BESIII detector at /¯s=4574.5, 4580.0, 4590.0 and 4599.5 MeV. The nonzero cross ...section near the Λc+Λ¯c− production threshold is cleared. At center-of-mass energies /¯s=4574.5 and 4599.5 MeV, the higher statistics data enable us to measure the Λc polar angle distributions. From these, the Λc electric over magnetic form-factor ratios (|GE/GM|) are measured for the first time. They are found to be 1.14±0.14±0.07 and 1.23±0.05±0.03, respectively, where the first uncertainties are statistical and the second are systematic.
•An FPLC-RID method was firstly developed.•FPLC-RID was successfully used for preparation and purification of fructooligosaccharides.•Fructooligosaccharides with degree of polymerization 3–9 from ...burdock were purified and identified.
A fast protein liquid chromatography coupled with refractive index detection (FPLC-RID) method was firstly developed for preparation and purification of fructooligosaccharides with different degree of polymerization from burdock, Arctium lappa. After extraction with 60% ethanol and decolorization with MCI gel CHP20P, total fructooligosaccharides were purified on Bio-Gel P-2 column eluted with water at the flow rate of 0.3ml/min, which was the optimized conditions. The obtained fructooligosaccharides with degree of polymerization of 3–9 were identified based on their methylation analysis, MS and NMR data. This method has the advantages of high automation, good recovery and easy performance, which could be used for preparation of FOS from other sources, as well as other targeted compounds without UV absorbance.
•A fast method for analysis of saponins in Panax notoginseng was established on conventional HPLC instrument.•A quantitative estimation of multiple components by one marker without correction factors ...was proposed and applied.•An extract derived mixed saponins standard, as reference standard is low-cost and feasible to access.•A novel strategy suitable for quality control of functional foods was proposed and applied.
Root of Panax notoginseng (Burk.) F.H. Chen (Sanqi in Chinese) is one of traditional Chinese medicines (TCMs) based functional food. Saponins are the major bioactive components. The shortage of reference compounds or chemical standards is one of the main bottlenecks for quality control of TCMs. A novel strategy, i.e. standardized reference extract based qualification and single calibrated components directly quantitative estimation of multiple analytes, was proposed to easily and effectively control the quality of natural functional foods such as Sanqi. The feasibility and credibility of this methodology were also assessed with a developed fast HPLC method. Five saponins, including ginsenoside Rg1, Re, Rb1, Rd and notoginsenoside R1 were rapidly separated using a conventional HPLC in 20min. The quantification method was also compared with individual calibration curve method. The strategy is feasible and credible, which is easily and effectively adapted for improving the quality control of natural functional foods such as Sanqi.
Based on an e+e− collision data sample corresponding to an integrated luminosity of 567 pb−1 taken at the center-of-mass energy of s=4.6 GeV with the BESIII detector, we measure the absolute ...branching fraction of the inclusive decay Λc+→Λ+X to be B(Λc+→Λ+X)=(38.2−2.2+2.8±0.9)% using the double-tag method, where X refers to any possible final state particles. In addition, we search for direct CP violation in the charge asymmetry of this inclusive decay for the first time, and obtain ACP≡B(Λc+→Λ+X)−B(Λ¯c−→Λ¯+X)/B(Λc+→Λ+X)+B(Λ¯c−→Λ¯+X)=(2.1−6.6+7.0±1.6)%, a statistically limited result with no evidence of CP violation.
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