Mechanical, Thermal Properties, and Extreme Phase Stability of High-Entropy Diborides (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2.

High-entropy diborides (HEDBs) have gained significant attention in industrial applications due to their vast composition space and tunable properties. We propose a solid solution reaction at high temperatures and pressures that successfully synthesized and sintered a novel, dense, and phase-pure HEDB (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2. A high asymptotic Vickers hardness of 26.3 ± 0.6 GPa and a bulk modulus of 320.5 ± 10.6 GPa were obtained. Additionally, we investigated the thermal oxidation process using TG-DSC from room temperature to 1500 °C and explored the phase stability of HEDBs under high-pressure conditions through in situ high-pressure synchrotron radiation X-ray diffraction. We analyzed the formation of lattice distortion, chemical bonding, and band structure in (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2 using first-principles calculations. Surprisingly, we found that the predominant distortion in diborides occurs in the boron layer, supported by ELF. This may be due to uneven electron transfer rather than a straightforward correlation with the atomic radius. These results provide a novel synthesis process and additional experimental data on the mechanical and thermal properties and high-pressure phase stability of HEDBs. Our study offers further insights into the microscopic structure of lattice distortion in HEDBs, which could prove crucial for the selection and design of engineering advanced HEDBs.

Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice.

Ischemia-reperfusion (I/R) injury, a multifaceted pathological process, occurs when the prolongation of reperfusion duration triggers ferroptosis-mediated myocardial damage. Isoliquiritigenin (ISL), a single flavonoid from licorice, exhibits a wide range of pharmacological impacts, but its function in ferroptosis caused by myocardial I/R injury remains unclear. This study delved into the protective effect of ISL on myocardial I/R injury-induced ferroptosis and its mechanism. Neonatal mouse cardiomyocytes (NMCM) underwent hypoxia/reoxygenation (H/R) to simulate the pathological process of myocardial I/R. ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage. CCK8 experiment revealed that the ferroptosis inhibitor Ferrostatin-1 significantly improved myocardial cell viability after 24 h of reoxygenation, and ISL treatment showed a similar effect. ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis. The Nrf2-specific inhibitor ML385 counteracted ISL's defensive role against H/R-triggered oxidative stress damage and ferroptosis. In vivo experiments further confirmed that by regulating the translocation of Nrf2 into the nucleus, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4, Drp1 to exert the antioxidant role, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R. ML385 nearly abolished ISL's protective impact on the I/R model by inhibiting Nrf2 function. In summary, ISL is capable of mitigating oxidative stress, mitochondrial damage, and cardiomyocyte ferroptosis caused by I/R, thereby reducing myocardial injury. A key mechanism includes triggering the Nrf2/HO-1/SLC7A11/GPX4 pathway to prevent oxidative stress damage and cardiomyocyte ferroptosis caused by I/R.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

BACKGROUND: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-ß (transforming growth factor-ß) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-ß family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-ßR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-ß-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH. METHODS: Bioinformatic analyses were used to explore the mechanism by which BRCC3 deubiquitinates ALK2. Cultured pulmonary artery smooth muscle cells (PASMCs), mouse models, and specimens from patients with idiopathic PAH were used to investigate the rebalance between BMP and TGF-ß signaling in regulating ALK2 phosphorylation and ubiquitination in the context of pulmonary hypertension. RESULTS: BRCC3 was significantly downregulated in PASMCs from patients with PAH and animals with experimental pulmonary hypertension. BRCC3, by de-ubiquitinating ALK2 at Lys-472 and Lys-475, activated receptor-regulated Smad1/5/9, which resulted in transcriptional activation of BMP-regulated PPARγ, p53, and Id1. Overexpression of BRCC3 also attenuated TGF-ß signaling by downregulating TGF-ß expression and inhibiting phosphorylation of Smad3. Experiments in vitro indicated that overexpression of BRCC3 or the de-ubiquitin-mimetic ALK2-K472/475R attenuated PASMC proliferation and migration and enhanced PASMC apoptosis. In SM22α-BRCC3-Tg mice, pulmonary hypertension was ameliorated because of activation of the ALK2-Smad1/5-PPARγ axis in PASMCs. In contrast, Brcc3-/- mice showed increased susceptibility of experimental pulmonary hypertension because of inhibition of the ALK2-Smad1/5 signaling. CONCLUSIONS: These results suggest a pivotal role of BRCC3 in sustaining pulmonary vascular homeostasis by maintaining the integrity of the BMP signaling (ie, the ALK2-Smad1/5-PPARγ axis) while suppressing TGF-ß signaling in PASMCs. Such rebalance of BMP/TGF-ß pathways is translationally important for PAH alleviation.

A Method Probing High-Temperature Oxidation Behavior of Crystalline Materials.

To date, the oxidation behavior of crystal materials is not fully understood; additional research is needed to understand the oxidation of materials. Herein, density functional theory (DFT) calculations and a 3D kinetic Monte Carlo (KMC) model are used to investigate the infiltration and diffusion behaviors of oxygen atoms within the crystal. Oxygen molecules readily adsorbes on crystal surfaces of the material and rapidly dissociates, verified by both first-principles calculations and energy-dispersive spectrometer (EDS) results. The infiltration ability of oxygen atoms into the inner crystal layers is affected by the surrounding oxygen atom, lattice compactness, and other factors. Energy-barrier calculations show that crystal thin/dense layers have significant effects on the crystal oxidation process, so high-pressure technology is used to investigate this correlation experimentally. KMC calculations and thermogravimetric analyses (TGA) show the infiltration behavior of oxygen atoms in the main crystal plane (211) toward the inner layers has the highest proportion to the actual high-temperature oxidation behavior of the title material. The results of both the KMC calculations and thermal experiments show the material peeled off upon further oxidation, which accelerates oxidation. At the same time, high-pressure treatment increases the oxidation resistance of materials at lower temperatures (<600 °C).

Kinetin inhibits hepatic stellate cell activation and induces apoptosis via interactions with the TGF-ß1/Smad signaling pathway.

Hepatic fibrosis is the pathological repair response of the liver to chronic injury; hepatic stellate cell (HSC) activation is the central link in the pathogenesis of hepatic fibrosis. Previously, we showed that kinetin, a plant cytokinin hormone, has a protective effect on CCl4-induced liver injury in mice. However, the role of kinetin in liver fibrosis remains unclear. We aimed to study these protective effects and to determine the mechanisms by which kinetin mediates HSC activation and apoptosis. For this purpose, the human HSC line LX-2 was treated with 10 ng/ml transforming growth factor-ß1 (TGF-ß1) for 24 h to stimulate activation. We found that treatment with kinetin at the sub-cytotoxic dose of 40 µg/ml for 48 h reduced the expression of the HSC activation marker α-SMA and inhibited the secretion of extracellular matrix proteins. In addition, kinetin was found to inhibit the proliferation and migration of LX-2 cells. We found that kinetin induced apoptosis in LX-2 cells by increasing the level of cleaved-caspase 3 and the Bax-to-Bcl-2 ratio. Interestingly, these effect were not observed in quiescent HSCs, suggesting that they are activation-dependent. Further study showed that kinetin attenuates activation and promotes apoptosis of LX-2 cells in vitro in part by suppressing the TGF-ß1/Smad signaling pathway.

Addition of cellulose degrading bacterial agents promoting keystone fungal-mediated cellulose degradation during aerobic composting: Construction the complex co-degradation system.

To excavate a complex co-degradation system for decomposing cellulose more efficiently, cellulose-degrading bacteria, including Bacillus subtilis WF-8, Bacillus licheniformis WF-11, Bacillus Cereus WS-1 and Streptomyces Nogalater WF-10 were added during maize straw and cattle manure aerobic composting. Bacillus and Streptomyces successfully colonized, which improve cellulose degrading ability. Continuous colonization of cellulose-degrading bacteria can promote the fungi to produce more precursors for humus and promote the negative correlation with Ascomycota. In the current study, the addition of cellulose-degrading bacteria has resulted in the rapid development of Mycothermus and Remersonia in the phylum Ascomycota as keystone fungal genera which constitute the foundation of the co-degradation system. Network analysis reveals the complex co-degradation system of efficient cellulose bacteria and mature fungi to treat cellulose in the process of straw aerobic composting mainly related to the influence of total carbon (TC) /total nitrogen (TN) and humic acid (HA)/fulvic acid (FA). This research offers a complex co-degradation system more efficiently to decompose cellulose aiming to maintain the long-term sustainability of agriculture.

Detection of aberrant DNA methylation patterns in sperm of male recurrent spontaneous abortion patients.

Aberrant DNA methylation patterns in sperm are a cause of embryonic failure and infertility, and could be a critical factor contributing to male recurrent spontaneous abortion (RSA). The purpose of this study was to reveal the potential effects of sperm DNA methylation levels in patients with male RSA. We compared sperm samples collected from fertile men and oligoasthenospermia patients. Differentially methylated sequences were identified by reduced representation bisulfite sequencing (RRBS) methods. The DNA methylation levels of the two groups were compared and qRT-PCR was used to validate the expression of genes showing differential methylation. The results indicated that no difference in base distribution was observed between the normal group and the patient group. However, the chromosome methylation in these two groups was markedly different. One site was located on chromosome 8 and measured 150 bp, while the other sites were on chromosomes 9, 10, and X and measured 135 bp, 68 bp, and 136 bp, respectively. In particular, two genes were found to be hypermethylated in these patients, one gene was DYDC2 (placed in the differential methylation region of chromosome 10), and the other gene was NXF3 (located on chromosome X). Expression levels of DYDC2 and NXF3 in the RSA group were significantly lower than those in the normal group (P < 0.05). Collectively, these results demonstrated that changes in DNA methylation might be related to male RSA. Our findings provide important information regarding the potential role of sperm DNA methylation in human development.

Intraflagellar transport 20 cilia-dependent and cilia-independent signaling pathways in cell development and tissue homeostasis.

Intraflagellar transport (IFT) is an essential condition for ciliogenesis. The primary cilia protrude like antennae and act as chemical or mechanical sensory organelles that coordinate specific receptor localization and signal transduction. IFT20 is the smallest molecule in IFT complex B, which is located in both the cilia and the Golgi complex. Recent studies have shown that IFT20 is a key molecule in multiple signaling pathways. Importantly, in the function of IFT20, signal transduction is not restricted to cilia, but is also involved in non-ciliary functions. Here we summarize current knowledge regarding IFT20-mediated signaling pathways and their relationship with cell development and tissue homeostasis, and analyse the cilia-dependent and cilia-independent mechanisms of IFT20 coordinated signaling pathways and potential crosstalk between the mechanisms. This review provides a comprehensive perspective on IFT20 coordinates signaling mechanisms in cell development and tissue homeostasis.

Does Technostress Increase R&D Employees' Knowledge Hiding in the Digital Era?

Technostress as an antecedent factor exploring knowledge hiding continues to be seldomly discussed in the digital era. Based on the job demand-resource theory, this article introduces work exhaustion as a mediator variable and constructs a model that the five sub-dimensions of technostress (i.e., overload, invasion, complexity, insecurity, and uncertainty) affect knowledge hiding for R&D employees. Similarly, this study analyzes the moderation of workplace friendship as the resource buffering effect. Based on data from the 254 questionnaires of the two-stage survey, empirical results show that: (1) Techno-invasion, techno-insecurity, and techno-complexity have significant positive effects on work exhaustion, and techno-invasion has the greatest effect. However, techno-overload and techno-uncertainty have no significant relationship with work exhaustion. (2) Work exhaustion plays a mediating role in the relationships between the three aspects of technostress (techno-invasion, techno-insecurity, techno-complexity) and knowledge hiding; However, its mediating effects are insignificant in the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and knowledge hiding. (3) Workplace friendship negatively moderates the relationships between the two aspects of technostress (techno-invasion and techno-insecurity) and work exhaustion, leading to less knowledge hiding. Nonetheless, its negative moderation for the relationships between the two aspects of technostress (techno-overload and techno-uncertainty) and work exhaustion are insignificant. Empirical results further show that workplace friendship positively moderates the relationship between techno-complexity and work exhaustion.

Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice.

Background: Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model. Methods: Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery. Results: Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI. Conclusion: The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.

Pressure-Induced Phase Transition and Compression Properties of HfO2 Nanocrystals.

Nanoparticles exhibit unique properties due to their surface effects and small size, and their behavior at high pressures has attracted widespread attention in recent years. Herein, a series of in situ high-pressure X-ray diffraction measurements with a synchrotron radiation source and Raman scattering have been performed on HfO2 nanocrystals (NC-HfO2) with different grain sizes using a symmetric diamond anvil cell at ambient temperature. The experimental data reveal that the structural stability, phase transition behavior, and equation of state for HfO2 have an interesting size effect under high pressure. NC-HfO2 quenched to normal pressure is characterized by transmission electron microscopy to determine the changing behavior of grain size during phase transition. We found that the rotation of the nanocrystalline HfO2 grains causes a large strain, resulting in the retention of part of an orthorhombic I (OI) phase in the sample quenched to atmospheric pressure. Furthermore, the physical mechanism of the phase transition of NC-HfO2 under high pressure can be well explained by the first-principles calculations. The calculations demonstrate that NC-HfO2 has a strong surface effect, that is, the surface energy and surface stress can stabilize the structures. These studies may offer new insights into the understanding of the physical behavior of nanocrystal materials under high pressure and provide practical guidance for their realization in industrial applications.

Hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video).

BACKGROUND AND AIMS: We previously reported a new and combined EUS-guided intervention in a patient with portal hypertension, consisting of obliteration of varices and partial splenic embolization (PSE). Performing PSE is known to diminish the increase in portal venous pressure after endoscopic intervention for varices. The aim of this study was to use multidetector CT portal venography to evaluate the anatomy of esophagogastric varices (EGV) and the impact on hemodynamics of portosystemic collaterals shortly after the concomitant procedures. METHODS: From October 2019 to December 2020, 5 patients with cirrhosis and with clinically significant portal hypertension who had variceal bleeding history and hypersplenism were treated with combined endoscopic obliteration for varices and EUS-guided PSE. Multidetector CT portal venography was applied to assess the anatomic drainage patterns of the EGV, diameters of feeders and drainage vessels, and splenic embolization rate. RESULTS: Within 5 days after concomitant endoscopic interventions, we observed decreased mean diameters of the left gastric vein, short gastric vein, and azygos vein as .3 mm, 1.0 mm, and 5.2 mm compared with 3.11 mm, 7.1 mm, and 5.4 mm before the procedures, respectively. Patients showed increased white blood cells (mean count of 2.7 × 109/L before vs 5.8 × 109/L after) and platelets (mean count of 52.8 × 109/L before vs 95.8 × 109/L after). The mean splenic embolization rate was 64.5% (range, 28.8%-84.6%). CONCLUSIONS: Our experience may illustrate an alternative technique of combining EUS-guided PSE with endoscopic therapy of varices to treat patients with portal hypertension.

Warming effects on the flux of CH4 from peatland mesocosms are regulated by plant species composition: Richness and functional types.

Peatlands in northeast China are experiencing severe climate warming. Most studies on peatlands focus on the responses of CH4 dynamics to temperature. However, they rarely consider the synchronous changes in the composition of plant communities caused by the expansion of vascular plants. In this study, an experiment combined warming with the manipulation of plants to examine the concentrations of CH4 porewater and its fluxes in the mesocosm. We found that warming increased the concentration of CH4 and its fluxes relative to the control treatments, and it was strongly modulated by plant richness and functional types. The average CH4 fluxes in the warming and non-warming mesocosms varied from 72.10 to 119.44 and 97.95 to 194.43 mg m-2 h-1, respectively. Plant species richness significantly increased CH4 flux at the warming level of 3.2 °C (P < 0.01). The presence of vascular plants, such as Carex globularis and Vaccinium uliginosum, significantly increased the CH4 fluxes after warming had occurred. Our results suggest that the distinct response of CH4 to richness and species primarily stemmed from the direct or indirect effects of plant biomass and functional characteristics. Therefore, more consideration should be given to the diversity changes caused by vascular plant expansion when estimating CH4 flux in boreal peatland, especially in the context of future climate warming.

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

BACKGROUND: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB). AIM: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy. METHODS: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio. RESULTS: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017). CONCLUSIONS: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.

Insights into the Bond Behavior and Mechanical Properties of Hafnium Carbide under High Pressure and High Temperature.

Hafnium carbide (HfC) is a potential candidate of ultrahigh-temperature ceramics (UHTCs) and has attracted significantly widespread interest in recent years. Here, we have synthesized high-purity HfC samples with NaCl-type structure by using a high-pressure solid-solid reaction. The structural stability, equation of state, plastic deformation, yield strength, and bonding properties under high pressure are investigated by a series of in situ high-pressure synchrotron-radiation angle-dispersive X-ray diffraction experiments combined with first-principles calculations. The yield strength of HfC (∼18 GPa) is obtained from analyzing the plastic deformation behavior under high pressure. In addition, we have successfully prepared bulk HfC ceramics with high density using a high-pressure and high-temperature method. The synthesized sample possesses a desirable Vickers hardness of 24.2 GPa and an excellent fracture toughness of 5.0 MPa·m1/2. The present results offer insights into the achievable application of HfC ceramics under extreme conditions and provide a powerful guide for the further design and synthesis of other high-performance UHTCs.

Early identification of carotid vulnerable plaque in asymptomatic patients.

BACKGROUND: This study was to explore the influencing factors of atherosclerotic plaque formation and stability in patients with asymptomatic carotid atherosclerotic plaques, so as to identify the vulnerable plaques at early stage, and then find high-risk group of cardio-cerebrovascular events for early clinical intervention to reduce related mortality and disability. METHODS: A total of 302 enrolled patients with asymptomatic carotid atherosclerotic plaques were divided into 3 groups based on the results of carotid artery color Doppler ultrasound: atherosclerotic unstable plaque (UP) group, atherosclerotic stable plaque (SP) group, and control group without plaques. Serum markers were measured by ELISA. χ2 test, t test, Pearson correlation analysis, and Logistic multivariate regression analysis were used in the analysis, and P < 0.05 was considered statistically significant. RESULTS: It revealed that high MMP-9, LOX-1and YKL-40 were independent risk factors for unstable plaque formation. The area under the curve (AUC) of serum markers combined with MMP-9, LOX-1 and YKL-40 was 0.850, with sensitivity 87.67%, specificity 81.13%, and diagnostic accuracy 84.92%, which was significantly better than the individual diagnostic efficacy of other three factors. The accuracy rate of Crouse Plaque Score (CPS) in the diagnosis of vulnerable plaques was 61.90%, the 10-year ICVD diagnosis accuracy rate was 56.75%, and the diagnostic accuracy of serum markers was significantly better than CPS and 10-year ICVD. CONCLUSION: Noninvasive cervical color Doppler ultrasound combined with serum markers MMP-9, LOX-1 and YKL-40 have significant early recognition effect on asymptomatic carotid vulnerable plaque patients.

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. METHODS: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). RESULTS: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. CONCLUSIONS: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. LAY SUMMARY: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.

Mechanical properties of tantalum carbide from high-pressure/high-temperature synthesis and first-principles calculations.

As a member of the refractory metal carbide family of materials, TaC is a promising candidate for ultra-high temperature ceramics (UHTC) with desirable mechanical strength. TaC sample quality and therefore mechanical properties are strongly dependent on synthesis method, and atomistic origins of mechanical failure are difficult to assign. Here, we have successfully synthesized high quality densified TaC samples at 5.5 GPa and 1400 °C using the high pressure and high temperature (HPHT) sintering method, with Vickers hardness determined to be 20.9 GPa. First-principles calculations based on the recently developed strain-stress method show that the ideal indentation strength of TaC is about 23.3 GPa in the (11[combining macron]0)[001] direction, in excellent agreement with experimental results. The detailed indentation shear deformation analysis and structural snapshots from the calculations indicate that the slip dislocations of TaC layers are the main structural deformation mode during the Vickers indentation process, and that the strong directional Ta-C bonds are responsible for the high mechanical strength of TaC. HPHT synthesis is shown to produce TaC samples with superior strength, and together with accurate first-principles calculations offers crucial insights for rational design and synthesis of novel and advanced UHTC materials.

Intraflagellar transport 20: New target for the treatment of ciliopathies.

Cilia are ubiquitous in mammalian cells. The formation and assembly of cilia depend on the normal functioning of the ciliary transport system. In recent years, various proteins involved in the intracellular transport of the cilium have attracted attention, as many diseases are caused by disorders in cilia formation. Intraflagellar transport 20 (IFT20) is a subunit of IFT complex B, which contains approximately 20 protein particles. Studies have shown that defects in IFT20 are associated with numerous system -related diseases, such as those of the urinary system, cardiovascular system, skeletal system, nervous system, immune system, reproductive system, and respiratory system. This review summarizes current research on IFT20.We describe studies related to the role of IFT20 in cilia formation and discuss new targets for treating diseases associated with ciliary dysplasia.