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We report unique two-step strain glass transition toward different local strain states in NiTi, i.e. R and B19′ strain glasses. This unique transition is evidenced by dynamic mechanical analysis and in-situ HR-TEM. A comprehensive phase diagram is established to illustrate diverse transition pathways and corresponding tunable superelastic properties. This pathway exploits the integrated transition of different phases, lowering the transition energy barrier, yielding superelasticity with large recoverable strain (6%), ultralow modulus (24 GPa) and robust cyclic and wide-temperature stability. Our investigation provides fresh insights into continuous transition pathways among different strain glass states to achieve exceptional properties in shape memory alloys.

Abstract Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive samples by mass spectrometry-based label-free quantification were applied to explore the potential resistant and sensitive mechanisms, and identify predictive markers of ESCC immunotherapy. Comparative analysis found the pathways related to immune and mitochondrial functions were associated with ESCC immunotherapy sensitivity; while platelet activation bioprocess showed negative correlation with CD8+ T cells and related to ESCC immunotherapy non-sensitivity. Finally, we identified 10 ESCC immunotherapy predictive biomarkers with high accuracy (≥ 0.90) to predict the immunotherapeutic response, which was validated in the independent cohort.

Abstract Cetuximab therapy is the major treatment for colorectal cancer (CRC), but drug resistance limits its effectiveness. Here, we perform longitudinal and deep proteomic profiling of 641 plasma samples originated from 147 CRC patients (CRCs) undergoing cetuximab therapy with multi-course treatment, and 90 healthy controls (HCs). COL12A1, THBS2, S100A8, and S100A9 are screened as potential proteins to distinguish CRCs from HCs both in plasma and tissue validation cohorts. We identify the potential biomarkers (RRAS2, MMP8, FBLN1, RPTOR, and IMPDH2) for the initial response prediction. In a longitudinal setting, we identify two clusters with distinct fluctuations and construct the model with high accuracy to predict the longitudinal response, further validated in the independent cohort. This study reveals the heterogeneity of different biomarkers for tumor diagnosis, the initial and longitudinal response prediction respectively in the first course and multi-course cetuximab treatment, may ultimately be useful in monitoring and intervention strategies for CRC.

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Abstract The progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). DNA damage is a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Glucolipid metabolism increase and lower immune cell infiltration are associated with PUC compared to CIS. Proteomic analysis distinguishes the origins of invasive tumors (PUC-derived and CIS-derived), related to distinct clinical prognosis and molecular features. Additionally, loss of RBPMS, associated with CIS-derived tumors, is validated to increase the activity of AP-1 and promote metastasis. This study reveals the characteristics of two distinct branches (PUC and CIS) of UC progression and may eventually benefit clinical practice.

Abstract Background Quantitative proteomics is an indispensable tool in life science research. However, there is a lack of reference materials for evaluating the reproducibility of label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based measurements among different instruments and laboratories. Results Here, we develop the Quartet standard as a proteome reference material with built-in truths, and distribute the same aliquots to 15 laboratories with nine conventional LC–MS/MS platforms across six cities in China. Relative abundance of over 12,000 proteins on 816 mass spectrometry files are obtained and compared for reproducibility among the instruments and laboratories to ultimately generate proteomics benchmark datasets. There is a wide dynamic range of proteomes spanning about 7 orders of magnitude, and the injection order has marked effects on quantitative instead of qualitative characteristics. Conclusion Overall, the Quartet offers valuable standard materials and data resources for improving the quality control of proteomic analyses as well as the reproducibility and reliability of research findings.

Abstract Background Vesicle trafficking is a highly important process in numerous human diseases, especially in the central nervous system dysfunctions. However, as a key component of vesicle trafficking‐related genes (VRGs), Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) has not been systematically elucidated in glioma so far. Methods Differentially expressed VRGs were selected using molecular signatures database (MSigDB), The Cancer Genome Atlas (TCGA), and Genotype‐Tissue Expression (GTEx) mRNA expression profiles. Further exploration of CNIH4 was determined using LASSO‐Cox regression algorithms. Then Kaplan–Meier (K‐M) plotter, receiver operating characteristic (ROC) curves, and multivariate Cox regression analyses were utilized to assess the independent significance of CNIH4 in the CGGA validation cohort. Functional exploration was performed with Gene Set Enrichment Analysis (GSEA) and then verified using a series of functional experiments in glioma cells. Finally, the consensus clustering algorithm was applied to identify clusters in glioma samples. After that, differences in prognosis, the tumor immune microenvironment (TIME), and therapy response were evaluated between clusters. Results CNIH4 was shown to be overexpressed in malignant glioma variants and was frequently observed in GCSs and TMZ‐resistant cell lines. Higher CNIH4 levels were significantly related to poor outcomes and positively correlated with adverse clinicopathological characteristics. Survival analyses revealed CNIH4 as an independent risk factor that outperformed traditional measures. Enrichment analysis indicated that overactive CNIH4 significantly gathered in stem cell processes. Furthermore, functional assays of silencing CNIH4 expression suppressed stem cell‐like properties in vitro and inhibited tumorigenicity in vivo. Finally, the CNIH4‐enriched subgroup negatively modulated immunotherapeutic response and reflected lower chemotherapy sensitivity for glioma patients. Conclusion Our study identified CNIH4 as a potential VRG that regulates tumor stemness, microenvironment immunity, and chemotherapy sensitivity. It may serve as a novel prognostic factor and a promising target against glioma therapy.

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

The proteogenomic landscape of diffuse gliomas remains to be explored. Here, the authors perform proteogenomic characterisation of diffuse gliomas, investigate the functional role of genomic alterations and suggest three proteomic subgroups.

To improve the handling comfort of Helicopter Flight Control System (HFCS), an adaptive particle swarm optimization optimized variable universe fuzzy proportional-integral-derivative (APSO-VUFPID) strategy for damping force control is proposed. First of all, by the results of the controllable semi-rotary fluid viscous damper (CSFVD) mechanical tests, a hyperbolic tangent model is developed. Afterwards, an equivalent model of HFCS is established. In the next part, aiming at improving the vibration suppression performance of the joystick system, an APSO-VUFPID is proposed to generate the desired damping force in real-time. Finally, numerical simulation and experimental tests are carried out to verify the vibration reduction effect of the proposed APSO-VUFPID method with respect to passive, proportional-integral-derivative (PID), adaptive particle swarm optimization optimized proportional-integral-derivative (APSO-PID) and adaptive particle swarm optimization optimized fuzzy proportional-integral-derivative (APSO-FPID) methods. The results show that the hyperbolic tangent model can accurately describe the nonlinear mechanical characteristics of the CSFVD. Moreover, under the proposed APSO-VUFPID control method, the amplitude of acceleration and velocity of the joystick system are smaller than those obtained from passive, PID, APSO-PID and APSO-FPID methods. Therefore, the proposed APSO-VUFPID controller has better handling comfort compared to passive, PID, APSO-PID and APSO-FPID controllers and can be employed in real applications.

Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. Methods We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression. Results A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway. Conclusions This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.

The mechanisms of resistance to therapy in gastric cancer remain to be explored. Here, proteomic profiling of 206 tumour tissues from patients treated with chemotherapy and anti-HER2-based therapy results in the identification of four molecular subtypes and the development of prognostic models.

Abstract Precise construction of isolated reactive centers on semiconductors with well‐controlled configurations affords a great opportunity to investigate the reaction mechanisms in the photocatalytic process and realize the targeted conversion of solar energy to steer the charge kinetics for hydrogen evolution. In the current research, we decorated isolated Ni atoms on the surface of CdS nanowires for efficient photocatalytic hydrogen production. X‐ray absorption fine structure investigations clearly demonstrate the atomical dispersion of Ni sites on the surface of CdS nanowires. Experimental investigations reveal that the isolated Ni atoms not only perform well as the real reactive centers but also greatly accelerate the electron transfer via direct Ni–S coordination. Theoretical simulation further documents that the hydrogen adsorption process has also been enhanced over the semi‐coordinated Ni centers through electronic coupling at the atomic scale.

Abstract Age-related hearing loss (ARHL) represents the frequently occurring disability that affects the elderly worldwide. The recent evidence has calculated ARHL to be most potential risk factor to predict dementia. β-amyloid plaques and tau accumulation in brain are hallmarks pathologic feature of Alzheimer’s disease (AD), which is a leading cause resulting in dementia. However, the potential mechanistic associations between ARHL and dementia remains unknown. We performed the present cross-sectional cohort study by enrolling 72 patients from research on hearing as well as the pathologic hallmarks of AD in brain. The exposure of hearing was measured by either word recognition score or mean pure-tone of the superior ear. The brain β-amyloid and tau standardized uptake value ratio (SUVR) were measured by positron emission tomography (PET). The covariates included gender, age, cardiovascular disease, education and hearing aid use. To analyze the association between hearing and β-amyloid/tau, linear regression was used and adjusted for potentially confounding covariates. Our data showed that the mean age was 67.1 ± 2.9 years. After adjusted for all the covariates, SUVR of β-amyloid showed an increase of 0.028 [95% confidence interval (CI) 0.004–0.061; P = 0.026], while that of tau exhibited an increase of 0.026 (95% CI 0.003–0.056; P = 0.033) per mean pure-tone increase by 10 dB (worsening). Likewise, per mean word-recognition score increase by 10%, the SUVR of β-amyloid showed an increase of 0.060 (95% CI 0.008–0.113; P = 0.023), while that of tau exhibited an increase of 0.059 (95% CI 0.009–0.111; P = 0.031). Taken together, our data demonstrates that hearing worsening was related to the increased burdens of β-amyloid as well as tau detected by PET, which were the AD pathological markers.

Abstract Background Urothelial carcinoma (UC) is the most common pathological type of bladder cancer, a malignant tumor. However, an integrated multi-omics analysis of the Chinese UC patient cohort is lacking. Methods We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 116 Chinese UC patients, comprising 45 non-muscle-invasive bladder cancer patients (NMIBCs) and 71 muscle-invasive bladder cancer patients (MIBCs). Result Proteogenomic integration analysis indicated that SND1 and CDK5 amplifications on chromosome 7q were associated with the activation of STAT3, which was relevant to tumor proliferation. Chromosome 5p gain in NMIBC patients was a high-risk factor, through modulating actin cytoskeleton implicating in tumor cells invasion. Phosphoproteomic analysis of tumors and morphologically normal human urothelium produced UC-associated activated kinases, including CDK1 and PRKDC. Proteomic analysis identified three groups, U-I, U-II, and U-III, reflecting distinct clinical prognosis and molecular signatures. Immune subtypes of UC tumors revealed a complex immune landscape and suggested the amplification of TRAF2 related to the increased expression of PD-L1. Additionally, increased GARS, related to subtype U-II, was validated to promote pentose phosphate pathway by inhibiting activities of PGK1 and PKM2. Conclusions This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in urothelial carcinoma of the bladder.

Summary: The eye is a complex organ consisting of multiple compartments with unique and specialized properties, and small disturbances in one eye region can result in impaired vision and blindness. Although there have been advancements in ocular research, the hierarchical molecular network in region-wide resolution, indicating the division of labor and crosstalk among different eye regions, is not yet comprehensively illuminated. Here, we present an atlas of region-resolved proteome and lipidome of mouse eye. Multiphoton microscopy-guided laser microdissection combined with in-depth label-free proteomics identifies 13,536 proteins across various mouse eye regions. Further integrative analysis of spectral imaging, label-free proteome, and imaging mass spectrometry of the lipidome and phosphoproteome reveals distinctive molecular features, including proteins and lipids of various anatomical mouse eye regions. These deposited datasets and our open proteome server integrating all information provide a valuable resource for future functional and mechanistic studies of mouse eye and ocular disease.

Abstract Even though the fundamental rules governing dislocation activities have been well established in the past century, we report a phenomenon, dislocation transformation, governed by the generalized-stacking-fault energy surface mismatch (GSF mismatch for short) between two co-existing phases. By carrying out ab-initio-informed microscopic phase-field simulations, we demonstrate that the GSF mismatch between a high symmetry matrix phase and a low symmetry precipitate phase can transform an array of identical full dislocations in the matrix into an array of two different types of full dislocations when they shear through the precipitates. The precipitates serve as a passive Shockley partial source, creating new Shockley partial dislocations that are neither the ones from the dissociation of the full dislocation. This phenomenon enriches our fundamental understanding of partial dislocation nucleation and dislocation-precipitate interactions, offering additional opportunities to tailor work-hardening and twinning processes in alloys strengthened by low-symmetry precipitate phases.

Large super-elasticity approaching its theoretically expected value was achieved in Ti-13.3Nb-4.6Mo alloy having an ultrafine-grained β-phase. In-situ synchrotron radiation X-ray diffraction analysis revealed that the dominant yielding mechanism changed from dislocation slip to martensitic transformation by decreasing the β-grain size down to sub-micrometer. Different grain size dependence of the critical stress to initiate dislocation slip and martensitic transformation, which was reflected by the transition of yielding behavior, was considered to be the main reason for the large super-elasticity in the ultrafine-grained specimen.

Abstract The coronary slow flow phenomenon (CSFP) is common in coronary angiography, however its impact on left atrial (LA) function is still controversial. This study aims to evaluate the LA structure and function of patients with CSFP using two-dimensional speckle tracking echocardiography (2D-STE). Consecutive patients scheduled for coronary angiography from January 2016 to September 2017 were enrolled in this study. Patients’ demographic data, clinical histories, laboratory and angiographic findings were collected and recorded. Diagnostic criteria for CSFP is based on Beltrame et al. proposed in 2012. Meanwhile 139 patients who have no significant stenosis (≤ 40%) and normal blood flow were selected as control. All patients received an echocardiographic examination 24 h before coronary angiography. LA structure and function were measured with echocardiography and 2D-STE. Our results showed that among the 1,954 patients who had received coronary angiography, 512 patients were included in the analysis after the exclusion criteria was implemented. Of those, 101 patients met the CSFP criteria (5.5%). CSFP is mainly seen in LAD (~ 70%). There was no statistical difference in baseline characteristics between the CSFP group and control group, except for a higher proportion of smokers in the CSFP group (P = 0.001). The percentage of monocytes is an independent risk factor for the occurrence of CSFP (P = 0.036) after binary logistic regression analysis. The LA global longitudinal strain (LA-GLS, represents reservoir functions) decreased and LA strain rate at late diastole (LA-SRa, represents booster function) increased in patients with CSFP compared to the control group (P

The stress-dependent core structures of dislocations for basal slip in magnesium are calculated using ab initio generalized stacking fault energy surface and microscopic phase-field method. The dissociation of dislocation cores exhibits the dependence on the non-shear component in the stress tensor; the Peierls stress is found to either become virtually zero or increase by an order of magnitude, depending on the applied shear stress magnitude and direction. The results, in contrast to the classical Schmid's law for crystal plasticity, are explained using the Escaig stress concept and the resulting implication on plastic deformation is discussed.

Solar magnetic fields play an important role in many solar activities, such as the solar wind, coronal mass ejections, and coronal oscillation. Coronal loops are curvilinear structures in the solar atmosphere and are closely related to coronal magnetic fields, so the study of their structure is very important. However, it is difficult to identify coronal loops accurately because of the complexity of their features. Therefore, we propose a two-stage detection method, using multiscale convolutional neural networks, to identify coronal loops. The regions including initial coronal loops are first marked by a improved Res-UNet model. The loop structures in the region are then detected using a improved dense extreme inception network for edge detection model. We selected the coronal images observed by the Transition and Coronal Explorer and the Atmospheric Imaging Assembly of the Solar Dynamics Observatory in the 171 Å channel to illustrate the detection processing. Meanwhile, we also compared the accuracy of our method to others. The results demonstrate that our proposed method has a high recognition rate and good robustness over previous identification methods and can be used to study the physical characteristics of coronal loops.

This work provides a phase-field simulation framework that bridges the structure of defects (e.g., dislocations and grain boundaries (GBs)) to their characteristic properties, such as stresses and energies. The validity of the current methodology is examined first by predicting the stress field of a single infinitely long screw dislocation using both the analytical solutions based on anisotropic elasticity and the current phase-field framework. The well-known stress singularity associated with the dislocation core in the former method has been effectively avoided in the latter. The framework is then applied to predicting the dislocation network of {0 0 0 1} twisted GB in Mg, which is found to consist of triangular-shaped regions of stacking faults and perfect crystals separated by partial dislocations. This prediction is consistent with some existing atomistic simulations and the underlying formation mechanism is analyzed rigorously using the displacement field predicted by our model, revealing the energy minimization process via the dissociation of a 〈112¯0〉/3 screw dislocation into a pair of 〈1100〉/3 screw dislocations. Based on the structure prediction, the associated stress field is further simulated, which provides critical information in evaluating the interaction of GBs and other crystalline defects such as impurities and dislocations.

Abstract DNA modifications, represented by 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC), and 5‐carboxylcytosine (5caC), play important roles in epigenetic regulation of biological processes. The specific recognition of DNA modifications by the transcriptional protein machinery is thought to be a potential mechanism for epigenetic‐driven gene regulation, and many modified DNA‐specific binding proteins have been uncovered. However, the panoramic view of the roles of DNA modification readers at the proteome level remains largely unclear. Here, a recently developed concatenated tandem array of consensus transcription factor (TF) response elements (catTFREs) approach is employed to profile the binding activity of TFs at DNA modifications. Modified DNA‐binding activity is quantified for 1039 TFs, representing 70% of the TFs in the human genome. Additionally, the modified DNA‐binding activity of 600 TFs is monitored during the mouse brain development from the embryo to the adult stages. Readers of these DNA modifications are predicted, and the hierarchical networks between the transcriptional protein machinery and modified DNA are described. It is further demonstrated that ZNF24 and ZSCAN21 are potential readers of 5fC‐modified DNA. This study provides a landscape of TF–DNA modification interactions that can be used to elucidate the epigenetic‐related transcriptional regulation mechanisms under physiological conditions.

Stacking fault energy (SFE) plays an important role in deformation mechanisms and mechanical properties of face-centered cubic (fcc) metals and alloys. In many concentrated fcc alloys, the SFEs determined from density functional theory (DFT) calculations and experimental methods are found having opposite signs. Here, we show that the negative SFE by DFT reflects the thermodynamic instability of the fcc phase relative to the hexagonal close-packed one; while the experimentally determined SFEs are restricted to be positive by the models behind the indirect measurements. We argue that the common models underlying the experimental measurements of SFE fail in metastable alloys. In various concentrated solid solutions, we demonstrate that the SFEs obtained by DFT calculations correlate well with the primary deformation mechanisms observed experimentally, showing a better resolution than the experimentally measured SFEs. Furthermore, we believe that the negative SFE is important for understanding the abnormal behaviors of partial dislocations in metastable alloys under deformation. The present work advances the fundamental understanding of SFE and its relation to plastic deformations, and sheds light on future alloy design by physical metallurgy.

The generation and motion of crystalline defects during plastic deformation are critical processes that determine the mechanical properties of a crystal. The types of defect generated are not only related to the symmetry of a crystal but also associated with the symmetry-breaking process during deformation. Proposed here is a new mathematical framework to capture the intrinsic coupling between crystal symmetry and deformation-induced symmetry breaking. Using a combination of group theory and graph theory, a general approach is demonstrated for the systematic determination of the types of crystalline defect induced by plastic deformation, through the construction of a crystal deformation group and a deformation pathway graph. The types of defect generated in the deformation of a face-centered cubic crystal are analyzed through the deformation pathway graph and compared with experimental observations.

A strategy for the microstructural design to achieve a critical upper limit of uniform nano α precipitates by controlling the amount of dislocations in the pre-deformed matrix after short time aging treatment was proposed in Ti–10Mo–8V–1Fe–3.5Al (all in wt.%, TB3 alloy) β alloy. The optimal processes focused on the interaction of defects, mainly point defects and dislocations that are generated during cold rolling (CR). Texture evolution of α and β phases was also specified. Amount of nano-scaled α precipitates was characterized by the number density of precipitates observed by SEM, which is saturated at ∼204.1 μm−2. For the CR 20% sample, a good combination of tensile strength (∼1400 MPa) and elongation (∼12%) was achieved after secondary aging at 550 for 1 h, which provides an enlightenment for the re-engineering of traditional precipitate-hardening alloys. Keywords: β-Ti alloy, Short-time aging saturation, Uniform α precipitates, Mechanical properties

Ultrafine β grain structures with recrystallized morphologies were fabricated by severe plastic deformation and subsequent annealing in Ti-10Mo-8 V-1Fe-3.5Al alloy. The minimum mean β grain size of 480 nm was obtained for the first time as a recrystallized structure in Ti alloys. Precipitation behavior of α in subsequent aging significantly changed with decreasing the recrystallized β grain size. Both tensile strength and total ductility of the aged Ti-alloy were increased by the β grain refinement. Tensile strength of 1.6 GPa and total elongation of 9.1% were achieved in the aged specimen having the prior β grain size of 480 nm, which was attributed to its finer and more homogeneous precipitated microstructure having a mixture of nanoscale thin-plate α and globular α without side α plates along β grain boundaries.

The development of high-temperature heavy-duty turbine disk materials is critical for improving the overall efficiency of combined cycle power plants. An alloy development strategy to this end involves superalloys strengthened by ‘compact’ γ′-γ″ coprecipitates. Compact morphology of coprecipitates consists of a cuboidal γ′ precipitate such that γ″ discs coat its six {001} faces. The present work is an attempt to investigate the microstructure and creep behavior of a fully aged alloy exhibiting compact coprecipitates. We conducted heat treatments, detailed microstructural characterization, and creep testing at 1200 °F (649 °C) on an IN718-variant alloy. Our results indicate that aged IN718-27 samples exhibit a relatively uniform distribution of compact coprecipitates, irrespective of the cooling rate. However, the alloy ruptured at low strains during creep tests at 1200 °F (649 °C). At 100 ksi (689 MPa) load, the alloy fails around 0.1% strain, and 75 ksi (517 MPa) loading causes rupture at 0.3% strain. We also report extensive intergranular failure in all the tested samples, which is attributed to cracking along grain boundary precipitates. The results suggest that while the compact coprecipitates are indeed thermally stable during thermomechanical processing, the microstructure of the alloy needs to be optimized for better creep strength and rupture life.

As a circadian organ, liver functions are regulated by circadian clock. Here, the authors present a comprehensive proteomics landscape of the mouse liver, including transcription factor binding profiles, phosphorylation and ubiquitylation patterns, nuclear and whole proteome, and the transcriptome.

Structural transformation: a less linear approach A method for modeling complex changes in the crystal structures of solids is developed by researchers in the USA. Yunzhi Wang from the Ohio State University and his colleagues’ model provides a more accurate description of crystal structure rearrangement during a phase change known as martensitic transformation. Even though this structural evolution has be modeled successfully using the phase-field microelasticity theory, the existing models do not incorporate some the more complex nonlinear transformation pathways that have been seen when using atomistic simulations. Wang and co-workers now extended phase-field microelasticity theory to include these complex pathways. They show that configuration and activation energies of a critical nucleus of the martensitic phase differ significantly when such nonlinear coupling is considered. This model has applications to understanding structural transformations in metals and ceramics.

As a signature of symmetry-breaking processes, the generation and annihilation of topological defects (domain walls, strings, etc.) are of great interest in condensed matter physics and cosmology. Here we propose a distinctive self-organization process through phase transitions, in which all the generated topological defects are dimensionality reduced and self-annihilated. In crystalline solids, such a unique mechanism allows a perfect single crystal after plastic deformation, which originates from the coupling of different types of broken symmetries.

Using first-principles methods, we investigate the effect of Al on the generalized stacking fault energy of face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy as a function of temperature. Upon Al addition or temperature increase, the intrinsic and extrinsic stacking fault energies increase, whereas the unstable stacking fault and unstable twinning fault energies decrease monotonously. The thermodynamic expression for the intrinsic stacking fault energy in combination with the theoretical Gibbs energy difference between the hexagonal close packed (hcp) and fcc lattices allows one to determine the so-called hcp-fcc interfacial energy. The results show that the interfacial energy is small and only weakly dependent on temperature and Al content. Two parameters are adopted to measure the nano-twinning ability of the present high-entropy alloys (HEAs). Both measures indicate that the twinability decreases with increasing temperature or Al content. The present study provides systematic theoretical plasticity parameters for modeling and designing high entropy alloys with specific mechanical properties.

Purpose. To examine the difference in the vitreal protein profiles of patients with proliferative diabetic retinopathy (PDR) with and without preoperative intravitreal conbercept (IVC) treatment. Methods. Liquid chromatography-tandem mass spectrometry- (LC-MS/MS-) based proteomic methods were used to determine the protein profiles of the vitreous humor in patients with PDR treated with (IVC group; n=9) and without (PDR group; n=8) preoperative IVC. Gene ontology (GO) annotation and REACTOME pathway analysis were obtained to overview differentially expressed proteins between each group. Intravitreal levels of apolipoprotein A-II (APOA2) and ceruloplasmin (CP) were measured using enzyme-linked immunosorbent assays. Results. 307 proteins were expressed differentially between PDR and IVC groups, including 218 proteins downregulated in response to IVC. The most notable GO annotations in level 3 and REACTOME pathways describing the differentially expressed proteins were “innate immune response” and “platelet degranulation.” The intravitreal levels of APOA2 and CP were lower in the IVC group than in the PDR group (p

Retrovirus (RV) is efficient for gene transfer and integration in dividing cells of diverse organisms. RV provides a powerful tool for insertional mutagenesis (IM) to identify and functionally analyze genes essential for normal and pathological processes. Here we report RV-mediated gene transfer and genome-wide IM in fish stem cells from medaka and zebrafish. Three RVs were produced for fish cell transduction: rvLegfp and rvLcherry produce green fluorescent protein (GFP) and mCherry fluorescent protein respectively under control of human cytomegalovirus immediate early promoter upon any chromosomal integration, whereas rvGTgfp contains a splicing acceptor and expresses GFP only upon gene trapping (GT) via intronic in-frame integration and spliced to endogenous active genes. We show that rvLegfp and rvLcherry produce a transduction efficiency of 11~23% in medaka and zebrafish stem cell lines, which is as 30~67% efficient as the positive control in NIH/3T3. Upon co-infection with rvGTgfp and rvLcherry, GFP-positive cells were much fewer than Cherry-positive cells, consistent with rareness of productive gene trapping events versus random integration. Importantly, rvGTgfp infection in the medaka haploid embryonic stem (ES) cell line HX1 generated GTgfp insertion on all 24 chromosomes of the haploid genome. Similar to the mammalian haploid cells, these insertion events were presented predominantly in intergenic regions and introns but rarely in exons. RV-transduced HX1 retained the ES cell properties such as stable growth, embryoid body formation and pluripotency gene expression. Therefore, RV is proficient for gene transfer and IM in fish stem cells. Our results open new avenue for genome-wide IM in medaka haploid ES cells in culture.

In order to remove aquatic organic dye contaminants by utilizing the inexpensive and inexhaustible solar energy, the Keggin-type H3PW12O40 was loaded on the surface of SiO2 with the sol-gel method and sensitized by H2O2 solution. The photocatalytic degradation of rhodamine B (RhB) by H3PW12O40/SiO2(x) under simulated natural light irradiation was investigated. The effects of the initial RhB concentration, the solution pH, and catalyst dosage on the photocatalytic degradation rate of RhB were also studied. The results demonstrated that at optimal condition (initial concentration of methyl orange is 10 mg/L, catalyst dosage is 0.8 g, and the pH is 2.5) the degradation rate of RhB is as high as 97.7% after 2 h under simulated natural light irradiation. The reaction of photocatalysis for RhB can be expressed as a first-order kinetic model.