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Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin−) cells. PBMCs and Lin− cells were cocultured with induced pluripotent stem cell‐derived MSCs (iPSC‐MSCs) under the stimulation of epithelial cytokines IL‐25 and IL‐33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS‐ICOSL pathway. iPSC‐MSCs successfully decreased the high levels of IL‐13, IL‐9, and IL‐5 in PBMCs in response to IL‐25, IL‐33, and the high percentages of IL‐13+ILC2s and IL‐9+ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC‐MSCs. However, iPSC‐MSCs were found directly to enhance ILC2 levels and functions via ICOS‐ICOSL interaction in Lin− cells and pure ILC2s. iPSC‐MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS‐ICOSL interaction. The MSC‐induced Treg cells then suppressed ILC2s by secreting IL‐10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS‐ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders., Human mesenchymal stem cells (MSCs) either directly promote group 2 innate lymphoid cell (ILC2) activation through upregulated ICOS‐ICOSL interaction. MSCs exert inhibitory effects on ILC2s via activating regulatory T (Treg) cells through ICOS‐ICOSL interaction. Treg cells prevent the promotion of MSCs on ILC2s via decreased ICOS‐ICOSL interaction between MSCs and ILC2s. IL‐10 is required for the MSC‐induced Treg cells in suppressing ILC2s alongside ICOS‐ICOSL interaction.

Commercially pure titanium (CP-Ti) has seen major applications in biomedical equipment. The use of selective laser melting (SLM) has become more common concerning the fabrication of CP-Ti components with a complicated shape in biomedical implants, where high strength and ductility are required. However, SLM manufactured CP-Ti often exhibits high strength and low ductility, as well as mechanical anisotropy because SLM process typically results in the formation of long columnar grains comprising of fine acicular α′ martensite. Heat treatment must be preceded to transform the acicular α′ to equiaxed α grain. This study demonstrated that annealing at 650 °C of SLM CP-Ti can create an equiaxed structure, resulting in a weakened texture. The formation of equiaxed grains occurred at two types of microstructural features, acicular α′ and irregular massive (α′m) martensite, which exhibited different sizes, morphologies, and contained different types of substructures under SLM as-fabricated condition. The formation mechanism of equiaxed grains in the α′ region is dominated by the coalescence of acicular α′ of the same variant and the dissolution of α′ into the matrix, whereas the formation mechanism in the α′m region is primarily dominated by the growth of the preexisting subgrains. A small number of equiaxed grains with new orientations were formed in the α′m region. The majority of equiaxed grains were formed in the acicular α′ region and inherited the grain orientations of the preexisting α′ or matrix. Therefore, a similar but weakened texture was inherited from the microstructure of the SLM CP-Ti after annealing.

Aluminum matrix composites (AMCs) reinforced with graphene nanoplatelets (GNPs) were fabricated by using an accumulative roll-compositing (ARC) process. Microstructure, mechanical and electrical properties of the nanostructured AMCs were characterized. The results showed that small addition (0.2 vol% and 0.5 vol%) of GNPs can lead to a simultaneous increase in the tensile strength and ductility of the GNPs/Al nanocomposites, as compared with the same processed pure Al. With increasing GNPs content, the tensile strength of the GNPs/Al nanocomposites can be enhanced to 387 MPa with retained elongation of 15%. Meanwhile, the GNPs/Al nanocomposites exhibited a good electrical conductivity of 77.8%–86.1% that of annealed pure Al. The excellent properties (high strength, high ductility and high conductivity) of the GNPs/Al are associated with the particular ARC process, which facilitates the uniform dispersion of GNPs in the matrix and formation of ultrafine-grained Al matrix. The strengthening and toughening of the GNPs/Al nanocomposites were discussed considering different mechanisms and the unique effect of GNPs.

The present work investigates the thermal stability and mechanical properties of a Co–20Cr–15W–10Ni (wt%) alloy with a bimodal grain (BG) structure. The BG structure consisting of fine grains (FGs) and coarse grains (CGs) is thermally stable under high-temperature exposure treatments of 760 °C for 100 h and 870 °C for 100–1000 h. The size of both FGs and CGs remains no significant changes after thermal exposure treatments. The microstructural stability is associated with the slow kinetics of grain growth and the pinning of carbides. The thermal stability enables to maintain the BG structures, leading to the same mechanical properties as the sample without thermal exposure treatment. In particular, the BG alloy samples after thermal exposure treatment exhibit superior mechanical properties of both high strength and high ductility compared to the unimodal grain (UG) structured ones. The BG structure of the alloy samples after thermal exposure is capable of avoiding severe loss of ductility and retaining high strength. More specifically, the ductility of the BG alloy samples after thermal exposure treatments of 870 °C for 500–1000 h is ten times higher (44.6% vs. 3.5% and 52.6% vs. 5.0%) than that of the UG ones. The finding in the present work may give new insights into high-temperature applications of the Co–20Cr–15W–10Ni alloy and other metallic materials with a BG structure.

PURPOSE To investigate dynamic pupil changes after orbital blowout fracture repair. To compare postoperative changes in under photopic and mesopic pupil size and center position after orbital blowout fracture repair surgery. METHODS The study evaluated 19 eyes. Pupils were imaged for pupil size and center position before and 3 months after orbital blowout fracture repair surgery. Pupil size changes were measured, and the correlation between preoperative and postoperative pupil centroid shift was evaluated. RESULTS After repair, operative eyes exhibited a growth of 9.3% ± 8.6% in pupil size, and contralateral eyes showed a growth of 8.6% ± 8.2% (P = 0.011, P = 0.007). Similar findings were noted in mesopic conditions. Under mesopic conditions, the pupil of operative eyes in medial orbital wall fracture deviated 0.030 ± 0.019 mm towards the nasal side along the X-axis (P = 0.031). The postoperative orbital floor fracture group demonstrated statistical significance at a spatial frequency of 5 (P = 0.041). CONCLUSIONS Orbital blowout fracture repair surgery affects pupil size and center position.

The influence of pre-strain on the formation of bimodal grain structures and tensile properties of a Co–20Cr–15W–10Ni alloy was investigated. The bimodal grain structures consist of fine grains (FGs; 2–3 μm in diameter) and coarse grains (CGs; 8–16 μm in diameter), which can be manipulated by changing the pre-strain (ɛ = 0.3–0.7) and annealing temperatures (1000–1100 °C). High pre-strain applied in the samples can intensify the plasticity heterogeneity through increasing the total dislocation density and the local volumes of high-density dislocations. This can essentially result in finer FGs, a higher FG volume fraction, and overall grain refinement in the samples after annealing. High-temperature essentially increases both the size and volume fraction of CGs, leading to an increase in the average grain size. The tensile test suggests that the bimodal grain structured samples exhibited both high strength and ductility, yield strengths of 621–877 MPa and ultimate tensile strengths of 1187–1367 MPa with uniform elongations of 55.0%–71.4%. The superior strength-ductility combination of the samples arises from the specific deformation mechanisms of the bimodal grain structures. The tensile properties strongly depend on the size ratio and volume fraction of FGs/CGs in addition to the average grain size in the bimodal grain structures. The grain structures can be modified via changing the pre-strain and annealing temperature.

BACKGROUND Surgical resection is regarded as the only potentially curative treatment option for patients with metastatic colorectal cancer (CRC). The National Comprehensive Cancer Network clinical practice guidelines do not recommend palliative surgery unless there is a risk of severe symptoms. However, accumulating evidence has shown that palliative surgery is associated with more favorable outcomes for patients with metastatic CRC. AIM To investigate the separate role of palliative primary tumor resection for patients with stage IVA (M1a diseases) and stage IVB (M1b diseases) colorectal adenocarcinoma (CRA). METHODS CRA patients diagnosed from 2010 to 2015 with definite M1a and M1b categories according to the 8th edition of American Joint Committee on Cancer staging system were selected from the Surveillance Epidemiology and End Results (SEER) database. To minimize potential selection bias, the data were adjusted by propensity score matching (PSM). Baseline characteristics, including gender, year of diagnosis, age, marital status, primary site, surgical information, race, grade, chemotherapy, and radiotherapy, were recorded and analyzed. Univariate and multivariate analyses were performed to explore the separate role of palliative surgery for patients with M1a and M1b diseases. RESULTS A total of 19680 patients with metastatic CRA were collected from the SEER database, including 10399 cases of M1a diseases and 9281 cases of M1b diseases. Common independent prognostic factors for both M1a and M1b patients included year of diagnosis, age, race, marital status, primary site, grade, surgery, and chemotherapy. After PSM adjustment, 3732 and 3568 matched patients in the M1a and M1b groups were included, respectively. Patients receiving palliative primary tumor resection had longer survival time than those without surgery (P < 0.001). For patients with M1a diseases, palliative resection could increase the median survival time by 9 mo; for patients with M1b diseases, palliative resection could prolong the median survival time by 7 mo. For M1a diseases, patients with lung metastasis had more clinical benefit from palliative resection than those with liver metastasis (15 mo for lung metastasis vs 8 mo for liver metastasis, P < 0.001). CONCLUSION CRA patients with M1a diseases gain more clinical benefits from palliative primary tumor resection than those with M1b diseases. Those patients with M1a (lung metastasis) have superior long-term outcomes after palliative primary tumor resection.

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)−1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)−1 by chiral HPLC successfully afforded individual enantiomers (+)−1 and (−)−1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)−1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1–7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 μg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

AIM: To investigate the effect of inclination and eccentricity of intraocular lens(IOL),on optical imaging quality via wavefront aberration optical path system.METHODS: The spherical IOL Sensar AR40e, the aspherical monofocal IOL Tecnis ZA9003, and the aspheric multifocal IOL Tecnis ZM900 were measured at the center of the center using a laboratory-built Hartmann-Shack IOL wavefront aberration path system at 5.0mm simulated pupil diameter. 0, 0.2, 0.4, 0.6, 0.8mm, the effect on the optical imaging quality when tilting 5°, 10°, 15°, 20°, 25° to the nasal side and the temporal side, and quantitative imaging quality by high-order aberration and modulation transfer function.RESULTS: The Temnis ZA9003 MTF value was higher than AR40e and Tecnis ZM900 when inclinationed within 5°, while the three IOL MTF values were significantly different when inclinationed 5°, 10°, 15°, and 20°. Tecnis ZA9003 The IOL inclination angle was significantly positively correlated with the coma(r=0.842, Pr=0.229, P=0.241). The three IOL MTF values were obtained when the eccentricity was 0.6 and 0.8 mm. Significant differences(both PCONCLUSION: When the inclination of aspheric IOL(-0.27μm spherical aberration)is less than 5°and the eccentricity is less than 0.4mm, aspherical IOL has a better imaging quality than that of spherical IOL. Tecnis ZM900 IOL has a lower optical imaging quality than that of spherical and aspheric IOL when the eccentricity of IOL is more than 0.4mm.

We used selective laser melting (SLM) to produce a three-dimensional specimen of pure Ti and found that an equiaxed grain structure and weak crystallographic texture could be achieved simultaneously via subsequent heat treatment. These traits have never been attained simultaneously in pure Ti prepared by traditional methods such as casting and rolling. This remarkable achievement was possible because recrystallization occurred during heat treatment without plastic deformation; such deformation introduces stored energy that drives recrystallization but inevitably causes a strong texture to develop. The occurrence of recrystallization was attributed to unique features of the SLM process including a very high cooling rate and repetitive layer stacking. These features generated considerable stored energy by affecting solidification and the β → α phase transformation. Steep in-grain orientation gradients and a fine lath structure also contributed to the activation of recrystallization by facilitating recrystallization nucleation. The heat-treated specimen showed tensile properties with significantly reduced anisotropy. This finding will provide new strategies for developing isotropic metallic materials and may introduce new applications of SLM.

AIM:To determine the pathological changes in ocular surfaces dry eye excessive evaporation non-obese diabetic(NOD)mice model and to preliminarily explore the feasibility of diabetic dry eye model.METHODS: In this study, 40 females NOD mice were selected. The experimental group consisted of NOD mice that were diagnosed with diabetes while the normal control group consisted of those NOD mice without spontaneous diabetes. Hypodermic injection of Scopolamine hydrobromide(0.5mg/0.2mL)was administered under 40% humidity to the experimental group and placed in a controlled drying box for 12h a day. This was to achieve a dry eye model. Testing indicators on the 1, 7, 10 and 14d after modeling, phenol red thread test was used to measure tear secretion and the eye sections were stained with periodic acid-Schiff(PAS)to examine the morphology and number of conjunctival goblet cells. On the 10d after modeling, the changes in the corneal epithelium were visualized after staining with hematoxylin. RESULTS:For the NOD mice of the experimental group, the tear secretion was gradually decreased with timing, while there were no obvious changes in the normal control group. The volume of the conjunctival goblet cells of the experimental group became larger, and on the 1d after the molding, the experimental group had decreased density of the goblet cells when compared with the normal control group(P=0.008). From the 7d after the molding, as the time was prolonged, the density of the goblet cells was gradually decreased and the differences between the two group at same time point were significant(all PCONCLUSION: Dry eye model of NOD mice was preliminary established, and the changes of ocular surface were similar to those of dry eye in the clinic.

A nearly fully dense β stabilized γ-TiAl alloy was additively manufactured by electron beam melting. The as-fabricated specimen exhibited a fine structure consisting of α2/γ colonies ( 50%) in the sample at 800 °C. Annealing and subsequent stabilization treatments resulted in α2/γ colonies (

Ti-2Al-9.2Mo-2Fe is a low-cost β titanium alloy with well-balanced strength and ductility, but hot working of this alloy is complex and unfamiliar. Understanding the nonlinear relationships among the strain, strain rate, temperature, and flow stress of this alloy is essential to optimize the hot working process. In this study, a deep neural network (DNN) model was developed to correlate flow stress with a wide range of strains (0.025–0.6), strain rates (0.01–10 s−1) and temperatures (750–1000 °C). The model, which was tested with 96 unseen datasets, showed better performance than existing models, with a correlation coefficient of 0.999. The processing map constructed using the DNN model was effective in predicting the microstructural evolution of the alloy. Moreover, it led to the optimization of hot-working conditions to avoid the formation of brittle precipitates (temperatures of 820–1000 °C and strain rates of 0.01–0.1 s−1).

Bimodal grain structures are often produced in a metal by employing severe plastic deformation followed by low-homologous-temperature annealing (≤0.4Tm, where Tm is melting temperature). Here, a bimodal grain structure was achieved in a Co–20Cr–15W–10Ni–C superalloy via moderate cold rolling (strain ≈0.3) and ultrahigh-homologous-temperature annealing (≥0.8Tm). During annealing, carbide-assisted heterogeneous static-recrystallization played a key role in forming the bimodal grain structure. A 40% increase in combined strength and ductility was observed.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulated epigenome has been linked to increased susceptibility to age-related disorders. We aim to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. In this study, we focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed redistribution of of both histone marks, but the changes are more significant for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed “aging-associated repressive domains” (AARDs). These AARDs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Interestingly, maintenance of high H3K9me2 levels in these regions have been shown to correlate with longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear elements (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals, it is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.Author summaryHeterochromatin refers to the portion of the genome that is tightly packed where genes stay silent. Heterochromatin is typically decorated by particular chemical groups called histone modifications, such as trimethylation of lysine 9 or lysine 27 on histone 3 (H3K9me3 or H3K27me3). To understand how the heterochromatin landscape may change from a “youthful” to an “aged” state, we monitored the genome-wide patterns of H3K9me3 and H3K27me3 during aging using the genetic model soil worm C. elegans. We found that while H3K27me3 remained relatively stable with age, H3K9me3 showed profound genome-wide redistribution in aged worms. We observed that new H3K9me3-marked heterochromatin preferentially formed in specific gene-rich regions in aged worms. Interestingly, these particular regions were marked by high levels of three other histone modifications when worms were young. This result suggested that H3K9me3 gain during aging is influenced by the gene-specific landscape of histone modifications established at young age rather than occurs in a stochastic manner. In summary, our study discovered reproducible and gene-specific changes in histone modifications that likely contribute to the aging phenotypes.

This article presents a wide-locking range divide-by-2 quadrature injection-locked frequency divider (QILFD) with capacitive cross-coupled oscillator. The ILFD consists of a quadrature voltage-controlled oscillator (QVCO) and two NMOS switches, which are in parallel with the QVCO resonators for signal injection. The proposed CMOS QILFD has been implemented with the tsmc 0.18-µm CMOS technology and the core power consumption is 20.4mW at the supply voltage of 1V. At the input power of 0dBm, the divide-by-2 locking range is 90.322% from 3.4 GHz to 9.0 GHz. The phase noise of the locked output spectrum is lower than that of free running QILFD in the ÷2 mode for RFI reduction

Background To explore the dynamic distribution of pupil size and center,the eccentricity distribution of angle kappa, and its correlation with other biomechanics about suitable for excimer laser refractive surgery. Methods Randomly selected 225 patients (407 eyes) who underwent femtosecond laser combined with excimer laser in situkeratomileusis,preoperative use of Wavelight Allegro Topolyzer Corneal Topography ( Wavelight Laser Technologies AG, Erlangen, Germany ) to measure the pupil size and center position, the German Wavelight EX500 excimer Laser (500Hz) records the deviation between the pupil center and the coaxially sighted corneal light reflex when the patient is supine. Results The average displacement distribution of P-Dist (the eccentricity between the pupil center and the coaxially sighted corneal light reflex point) is 0.225 ± 0.102 mm, and 80% of the eyes are ≤ 0.30 mm.The coaxially sighted corneal light reflex point is mainly deviated to the superior temporal side of the corneal center (34%).Under the dark light condition, the x-axis of the left eye was: -0.046 ± 0.091 mm, the x-axis of the right eye was: -0.152 ± 0.084 mm, with statistical difference ( P = 0.015) (the right eye shifted to the temporal side), the y-axis direction had no statistical change ( P = 0.062). The WTW was positively correlated with changes of pupil diameter (dark pupil diameter-bright pupil diameter) ( r = 0.270, P

The isothermal compression tests were carried out to study the hot deformation behavior and microstructure evolution of Ti–19Al–22Mo alloy. The samples were deformed in the temperature range from 1100 to 1250 °C with an interval of 50 °C, strain rate ranging from 0.01 to 1 s−1 and the height reduction of 50% using Gleeble-3800 thermal–mechanical simulator. By using this experimental data an artificial neural network (ANN) model was developed and evaluated with unseen data. Further, the developed ANN model was used to predict flow stress correction from adiabatic heating at finer intervals of strain rates and temperatures. The predicted isothermal flow stress values were utilized to construct processing maps for Ti–19Al–22Mo alloy at true strain of 0.4 and 0.6. The maximum efficiency was noticed at 1100 °C with the strain rate of 0.01 s−1 associated with dynamic recrystallization and dynamic recovery. The deformation conditions of the instability domains in processing map showed wedge cracking and flow localization. Using the processing maps safe working parameters for hot deformation of Ti–19Al–22Mo alloy was identified.

Half-metallic materials have gained a lot of attention because of their unique properties and applications in spintronic devices. Despite the fact that these materials have been studied by several research groups there are very limited studies on their heterostructure (HS) systems. In the current study we have investigated the electronic and magnetic properties of (LaAlO3)6.5/(SrTiO3)2.5(111) HS using density functional theory (DFT) calculations. We demonstrate that the system exhibits a 100% spin-polarized two-dimensional electron gas (2DEG) which is extremely confined to the Ti 3d orbitals of the SrTiO3 layers. In particular, this system can keep its half-metallic properties under different in-plane strains from −3 to 2%. This property proves that this material has relatively stable half-metallic properties. In addition, the conducting and magnetic ground states of the system can also be tailored by changing in-plane strain and interfacial cation intermixing of La and Sr (Sr ⇔ La intermixing). By increasing the in-plane lattice parameters, this system has the ability to evolve from a nonmagnetic to a ferromagnetic metal and then to a half-metal and by further increasing the in-plane lattice parameter it becomes a ferromagnetic insulator. Sr ⇔ La intermixing can destroy the original half-metallic properties and the system exhibits an AFM Mott-type insulator phase. Our results demonstrate that the system has high potential for application in the field of spintronics, and opens the prospect of using LaAlO3/SrTiO3(111) HSs to explore quantum phase transitions.

Background Several studies probed into the connection between esophageal cancer (EC) risk and PRKAA1 rs13361707 C/T polymorphism, but obtained insignificant findings. Methods In this study, 814 EC cases and 961 controls from Eastern China were recruited to validate the relationship between this polymorphism and EC susceptibility. Results Data suggested rs13361707 C/T polymorphism in PRKAA1 gene was significantly related with a lower risk for EC. Such significant connection was also uncovered in subgroups of males, smokers, drinkers and individuals with age ≥ 60 years. In addition, this polymorphism was linked with the pathological grading, distant metastasis, and histology of EC. Conclusion In summary, PRKAA1 rs13361707 C/T polymorphism is related to the risk and clinical properties of EC patients in East China.

We have investigated {332} twinning and detwinning mechanisms in β-Ti alloys. Microstructure-twinning relations were evaluated in a β-Ti-15Mo (wt.%) alloy by statistical analysis of the evolving twin structure upon deformation by in-situ SEM testing and electron backscattering diffraction (EBSD). We find that most of the primary twins (~80%) correspond to the higher stressed variant and follow Schmid’s law with respect to the macroscopic stress. Detwinning mechanism was evaluated in a multilayered β-Ti-10Mo-xFe (x: 1-3 wt.%) by EBSD. We find that the detwinning process consists of two independent events that occur at two different microstructural regions, i.e. twin tips located at grain interiors and grain boundaries. Both detwinning modes can be explained from a thermodynamic standpoint where the boundary dissociation processes minimize the boundary free energy.

Background Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. Methods The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. Results The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. Conclusion The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

A bimodal grain structure consisting of fine grains (d ~ 1–2 µm) and coarse grains (d ~ 10–20 µm) was achieved in the biomedical Co–20Cr–15W–10Ni alloy via medium cold rolling (area reduction of 50%) followed by short-term annealing (15 min) at relatively low temperatures (950–1100 °C). The medium cold rolling induced a heterogeneous microstructure featuring the coexistence of severely deformed regions and weakly deformed domains. With short-term annealing at low temperatures, fine and coarse grains were preferentially recrystallized in severely deformed regions and weakly deformed domains, respectively, resulting a bimodal grain size distribution. During tension, dislocations were more rapidly generated in the fine grains, thus increasing the strain hardening, while they glided longer on the {111} planes in the coarse grains, contributing a high ductility. The combination of these two factors provided well-balanced strength–ductility behavior with an ultimate tensile strength of 1278 MPa, a yield strength of 787 MPa, and an elongation to fracture of 53%, making the alloy suitable for surgical implant and stent applications where the strength and ductility are both important to ensure mechanical reliability in a human body.

We have performed quantitative analysis of {332}〈113〉 twinning in a β-Ti-15Mo (wt.%) alloy by in situ scanning electron microscopy and electron backscattering diffraction (EBSD). Microstructure-twinning relations were evaluated by statistical analysis of the evolving twin structure upon deformation at room temperature. Our analysis reveals that at the early stages of deformation (ε < 1.5 to 2.0%), primary twinning is mainly determined by the applied macroscopic stress resolved on the twin system. Most of the primary twins (~70–80% of the analyzed twins) follow Schmid’s law with respect to the macroscopic stress, and most of the growth twins (~ 85% of the analyzed twins) correspond to the higher stressed variant. In the grain size range studied here (40–120 μm), we find that several twin parameters such as number of twins per grain and number of twins per grain boundary area exhibit grain size dependence. We ascribe these effects to the grain size dependence of twin nucleation stress and apparent critical resolved shear stress for twinning, respectively.

Background Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2)-dominant eosinophilic allergic airway inflammation. However, the role of iPSC-MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC-MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. Methods A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. Results We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORγt were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. Conclusions iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation. Electronic supplementary material The online version of this article (10.1186/s13287-018-0897-y) contains supplementary material, which is available to authorized users.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed “aging-specific repressive regions” (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology., Author summary Heterochromatin refers to the portion of the genome that is tightly packed where genes stay silent. Heterochromatin is typically decorated by particular chemical groups called histone modifications, such as trimethylation of lysine 9 or lysine 27 on histone 3 (H3K9me3 or H3K27me3). To understand how the heterochromatin landscape may change from a "youthful" to an "aged" state, we monitored the genome-wide patterns of H3K9me3 and H3K27me3 during aging using the genetic model soil worm C. elegans. We found that while H3K27me3 remained relatively stable with age, H3K9me3 showed substantial gain and loss at specific loci in aged worms. We observed that new H3K9me3-marked heterochromatin preferentially formed in specific gene-rich regions in aged worms. Interestingly, these particular regions were marked by high levels of three other histone modifications when worms were young. This result suggested that H3K9me3 gain during aging is influenced by the gene-specific landscape of histone modifications established at young age rather than that it occurs in a stochastic manner. In summary, our study discovered reproducible and gene-specific changes in histone modifications that likely contribute to the aging phenotypes.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of long non-coding RNA (lncRNA) in mouse fibroblasts L929 cell line. Methods L929 cells were cultured in vitro and randomly divided into simulated microgravity (SMG) group and normal gravity (NG) group. Each group had three samples, the rotator axis of SMG group was paralleled to the ground rotation, while the rotator axis of NG group was vertical to the ground rotation, and the speed of rotation was consistent for the two groups. The samples of two groups were collected on 7th day of culture and the total RNAs were extracted, labeled and hybridized in sequence. The lncRNA and mRNA were detected by Agilent Mouse lncRNA Chips respectively. Differentially expressed lncRNA were identified and then validated by RT-qPCR. GO and Pathway analysis were applied to determine the functional distribution of these target genes. The integration predictions of the lncRNA and mRNA co-expression had been proposed to refine the functional lncRNA-mRNA relationships. Results There were 238 differentially ex-pressed lncRNAs including 134 lncRNAs up-regulated and 104 lncRNAs down-regulated, and 237 differentially expressed mRNAs including 53 mRNAs up-regulated and 184 mRNAs down-regulated significantly in mouse fibroblasts L929 cell line under simulated microgravity by RCCS. The RT-qPCR showed a high concordance with chip microarray results in 4 differentially expressed lncRNA. GO analysis showed that the differentially expressed lncRNAs were related to the biological processes such as negative regulation of megakaryocyte differentiation and negative regulation of wound healing. Pathway analysis showed that these target genes were related to the signal pathways of systemic lupus erythematosus and TGF-β. The lncRNA-mRNA co-expression networks were also established. Conclusion The simulated microgravity by RCCS could significantly affect the expression profiles of lncRNA and mRNA in mouse fibroblasts L929. The lncRNA target genes prediction and functional enrichment analysis based on gene chip technology may provide the theoretical basis for illustrating the mechanism and management of weightlessness stress injury. DOI: 10.11855/j.issn.0577-7402.2017.10.07

Backgrounds: Neratinib is a potent EGFR/HER2 kinase inhibitor. Gastrointestinal complications (i.e. diarrhea, vomiting and nausea) are the most common adverse events. In this study, we aimed to investigate (1) the overall incidence and relative risk (RR) of diarrhea, vomiting and nausea and (2) whether combination neratinib therapy increased the incidence of gastrointestinal complications versus neratinib alone. Methods: Relevant studies were identified from the PubMed database, from abstracts presented at the American Society of Clinical Oncology annual conference and from the Web of Science database. Incidences, RRs, and 95% confidence intervals (CIs) were calculated. Results: The incidences of all-grade diarrhea, vomiting and nausea in the neratinib groups were 89% (95% CI = 77–95%), 31% (95% CI = 25–37%) and 44% (95% CI = 33–55%), respectively. The neratinib arms significantly increased the risk of diarrhea and vomiting in comparison with the control groups (diarrhea: all-grade, RR = 2.06, 95% CI = 1.38–3.08, P = 0.0004; grade 3/4, RR = 8.77, 95% CI = 2.91–26.40, P = 0.0001; vomiting: all-grade, RR = 2.02, 95% CI = 1.10–3.71, P = 0.02; grade 3/4, RR = 7.10, 95% CI = 3.33–15.15, P Conclusions: Our meta-analysis demonstrates that the neratinib arms are associated with a significantly increased risk of diarrhea and vomiting.

We have studied {332} detwinning mechanism in a bcc-Ti–10Mo–xFe (x = 1–3 wt%) multilayered alloy upon annealing treatment at 900 °C by electron backscatter diffraction and electron channeling contrast imaging. Our analysis reveals that in the present material the detwinning process consists of two independent detwinning events that occur at two different microstructural regions, namely twin tips located at grain interiors and grain boundaries. Boundary dissociation reactions and mobilities were analyzed by tracking the evolution of the twin structure upon thermal annealing. We find that the first detwinning process is characterized by the evolution of incoherent twin boundaries into a Σ3 boundary and its subsequent migration. The second detwinning event is characterized by the detachment of the twin crystal from a grain boundary by the formation and migration of Σ11 {113} incoherent twin boundaries. Both detwinning modes can be explained from a thermodynamic standpoint where the boundary dissociation processes minimize the boundary free energy.

In Caenorhabditis elegans, mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Here, we show that wdr-5 mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. In addition, we find that the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2, and can be recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. Finally, we show that the transgenerational acquisition of longevity in jhdm-1 mutants is associated with accumulating genomic H3K9me2 that is inherited by their long-lived wild-type descendants at a subset of loci. These results suggest that heterochromatin facilitates the transgenerational establishment and inheritance of a complex trait. Based on these results, we propose that transcription-coupled H3K4me via COMPASS limits lifespan by encroaching upon domains of heterochromatin in the genome.

Purpose. To analyze the distribution of the offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist), the effects of 50% and 100% angle kappa adjustments on refractive and visual quality in patients with moderate myopia were investigated. Methods. A randomly selected 254 patients (254 eyes) with moderate myopia who underwent femtosecond laser-combined LASIK were examined. During the operation, the P-Dist of the patients was recorded by the x- and y-axis eyeball-tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system. Preoperatively and 3 months postoperatively, the WaveLight® ALLEGRO Topolyzer was used to measure the pupil size and center position, and the wavefront sensor was used to measure the wavefront aberrations. The visual function tester (OPTEC 6500) measured contrast sensitivity. Results. The average P-Dist was 0.220 ± 0.102 mm. When the P-Dist >0.220 mm, the postoperative residual cylinder was 0.29 ± 0.34 D in the group with the 50% adjustment and 0.40 ± 0.32 D in the 100% group, which was significantly higher than the 50% group P = 0.036 . The coma was 0.21 ± 0.17 μm in the 50% adjusted group and 0.34 ± 0.25 μm in the 100% group, which was significantly higher than that in the 50% group P = 0.021 . At the 1.5 c/d spatial frequency, contrast sensitivity in the adjusted 100% group was significantly lower than that in the 50% group under visual glare conditions P = 0.039 . Conclusion. The postoperative visual acuity and spherical equivalent were not affected in the two groups. However, when P-Dist >0.220 mm, the residual astigmatism and coma were lower in the 50% group. Individualized operations for those with moderate myopia and large-angle kappa in which 100% adjustment is chosen may not result in a better visual quality effect than 50%.

Pigment epithelium-derived factor (PEDF) is an oncogene found in various types of cancers. However, how PEDF affects the development of human esophageal squamous cell carcinoma (ESCC) is unknown. This study investigates the role of PEDF in ESCC cell proliferation, migration, and cell cycle both in vitro and in vivo. The PEDF expression was examined in patient tumor samples and ESCC cell lines. Short hairpin RNA technology was used to inhibit the PEDF expression in ESCC EC9706 and KYSE150 cells. In vitro cell proliferation and migration assays were performed. The effects of PEDF on tumor growth and progression were examined in vivo in murine subcutaneous xenograft tumor models. It was found that PEDF was overexpressed in esophageal cancer cells and patient tumor tissues compared to normal control samples. PEDF enhanced cell cycle progression and inhibited cell apoptosis. Knock down of PEDF inhibited esophageal cell proliferation and migration in vitro. Moreover, Inhibition of PEDF significantly reduced tumor growth and tumor size in vivo. These results indicate that PEDF induce tumorigenesis in ESCC and can be a potential therapeutic target for cancer treatment.

Half-metallic materials have gained a lot of attention because of their unique properties and applications in spintronic devices. Despite the fact that these materials have been studied by several research groups there are very limited studies on their heterostructure (HS) systems. In the current study we have investigated the electronic and magnetic properties of (LaAlO3)6.5/(SrTiO3)2.5(111) HS using density functional theory (DFT) calculations. We demonstrate that the system exhibits a 100% spin-polarized two-dimensional electron gas (2DEG) which is extremely confined to the Ti 3d orbitals of the SrTiO3 layers. In particular, this system can keep its half-metallic properties under different in-plane strains from -3 to 2%. This property proves that this material has relatively stable half-metallic properties. In addition, the conducting and magnetic ground states of the system can also be tailored by changing in-plane strain and interfacial cation intermixing of La and Sr (Sr ⇔ La intermixing). By increasing the in-plane lattice parameters, this system has the ability to evolve from a nonmagnetic to a ferromagnetic metal and then to a half-metal and by further increasing the in-plane lattice parameter it becomes a ferromagnetic insulator. Sr ⇔ La intermixing can destroy the original half-metallic properties and the system exhibits an AFM Mott-type insulator phase. Our results demonstrate that the system has high potential for application in the field of spintronics, and opens the prospect of using LaAlO3/SrTiO3(111) HSs to explore quantum phase transitions.

Background: To investigate the characteristics and distribution of anterior and posterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods: A total of 121 myopic patients (121 eyes, 14-46 years old) who underwent corneal refractive surgery were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -1.50 to -12.00 D. The corneal anterior and posterior aberrations (higher-order aberration, HOA; spherical aberration, SA; Coma; Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results: The root-mean-square (RMS) of the third to sixth order aberrations of the ocular and corneal wave surface aberrations at a 6.0-mm pupil showed a decreasing trend in patients suitable for the corneal refractive surgery, and the RMS of the third order aberrations accounted for 62.92% of the total HOAs. The coma ratio (coma ratio: coma/total cornea higher-order aberrations) was increased with the increasing diopters, while the spherical aberration ratio (spherical aberration/ total cornea higher-order aberrations) was not changed. In addition, the spherical aberration was 0.203± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19±0.03 (range: -0.58 to 0.31). There were significant differences in the coma aberrations of preoperative corneal anterior surface (3, 1) between the low, middle and high myopia groups (P=0.013). The spherical equivalent was positively correlated with the corneal coma of the preoperative anterior corneal surfaces (R=-0.241, P=0.009), and the Q value was positively correlated with the total higher-order aberrations (R=0.326, P

Background To investigate the characteristics and distribution of anterior and posterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods Sixty myopic patients (120 eyes, 14-46 years old) who underwent corneal refractive surgery were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -1.50 to -12.00 D. The corneal anterior and posterior aberrations (higher-order aberration, HOA; spherical aberration, SA; Coma; Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results The root mean square (RMS) values from 3 to 6 (RMS 3 to 6) of the whole eye higher-order wave surface aberrations at a 6.0 mm pupil diameter showed a decreasing trend in patients with corneal refractive surgery, and an RMS value of 3 accounted for 62.92% of the total HOAs. The coma ratio increased with increasing diopter, while the spherical aberration ratio was not changed. In addition, the spherical aberration was 0.203 ± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19 ± 0.03 (range: -0.58 to 0.31), which showed a normal distribution. There were significant differences in coma aberrations (3, 1) in the low, middle and high myopia groups (P=0.013). The spherical equivalent was positively correlated with corneal coma (R = -0.241, P = 0.009), and the Q value was positively correlated with total higher-order as well as spherical aberrations (R = 0.326, P

In order to develop a new titanium alloy with a good combination of strength–ductility–toughness, a near-beta titanium alloy was designed based on the already widely used Ti-1023 alloy. To avoid beta fleck occurring in the microstructure, the new Ti–Al–Fe–V (Cr, Zr) alloy has been made through decreasing the content of Fe, based on molybdenum equivalency and Bo–Md molecular orbital method (a method for new alloy designing based on the molecular orbital calculating). After primary design computation, Ti–Al–Fe–V (Cr, Zr) alloy was optimized as Ti–3Al–4.5Cr–1Fe–4V–1Zr finally. The microstructure and tensile properties of this alloy subjected to several commonly used heat treatments were investigated. The results show that the tensile strength of the alloy after solution treated below the β-transus temperature comes between 850 and 1100 MPa, with elongation in the range of 12.5 %–17.0 %. In solution-treated and solution-aged samples, a low-temperature aging at 500 °C results in the precipitation of finer α phase. With the increase in aging temperature, the secondary α phase becomes coarser and decreases in amount. Thus, it will lead to the increase in tensile ductility, but reduction in strength. Eventually, after modulated aging treatment, the alloy can obtain high-strength level with acceptable ductility. The tensile strength of the alloy can achieve 1273 MPa, with an elongation of 11.0 %. At the same time, the fracture toughness (K IC) of the alloy achieves 83.8 MPa·m1/2. It is obvious that the newly designed alloy has achieved a good blend of strength–ductility–toughness.

We have investigated the propagation of {332} twins in a multilayered Ti-10Mo-xFe (x = 1–3) alloy fabricated by multi-pass hot rolling. The material contains a macroscopic Fe-graded structure (about 130 μm width) between 1 and 3 wt% Fe in the direction perpendicular to rolling. We observe strong influence of the Fe-graded structure in the twin propagation behavior. The propagation of {332} twins that are nucleated in Fe-lean regions (~1 wt% Fe) is interrupted in the grain interiors at a specific Fe content, namely, about 2 wt% Fe. We ascribe this effect to the role of Fe content in solid solution on the stress for twin propagation. The interruption of twins in the grain interiors results in the development of characteristic dislocation configurations such as highly dense dislocation walls (HDDWs) associated to strain localization phenomena. The nucleation and propagation of these dislocation configurations is ascribed to the underlying plastic accommodation mechanisms of the stress field at the twin tips. We find that the crystallographic alignment of HDDWs is determined by the stress field at the twin tips and the deformation texture. The excellent plastic accommodation at the interrupted twin tips allows attaining the good ductility of the present material (total elongation of 28%).

Objective: To explore the influence of vascular endothelial function and inflammatory cytokines on patients with transumbilical single-port access laparoscopic cholecystectomy (TSPALC). Methods: A total of 86 cases with laparoscopic cholecystectomy, they were divided into single span treatment group (n=46) and normal group (n=40) according to the treatment. Patients in single span treatment group were treated with TSPALC, while patients in normal group were treated with normal LC. Surgery and postoperative recovery, tested and compared vascular endothelial function index: nitric oxide (NO), endothelin (ET) and inflammation factors: interleukin-6 (IL-6) and interleukin-8 (IL-8), high sensitivity C-reactive protein (hs-CRP) before and after surgery at different time points were compared. Results: VAS score at 6 h after surgery was similar between the two groups, while the VAS score at 12 h, 24 h after surgery in two groups were significantly reduce than 6h after surgery, and the VAS score at same point in single span treatment group were significantly lower than normal group, the difference had statistical significance (P0.05). Conclusions: The vascular endothelial function injury and inflammation stress are similar between normal LC and TSPALC, but TSPALC has small trauma. The postoperative pain is light, it’s worth clinical promotion positively.

Titanium and its alloys have been widely used as implants replacing hard human tissues in biomedical fields. To improve the stability of implants in the surrounding bone tissues, the materials with porous structures were fabricated. In this paper powder metallurgy technique was employed to fabricate porous Ti-39Zr-6Nb (wt.%) alloys. The porous structures and mechanical properties of the porous alloys were examined by scanning electron microscopy (SEM) and compressive tests. The results showed that with increasing the sintering temperature the porosity of the alloys decreased and the compressive strength and the elastic modulus increased. The porosity of the alloys was in the range from 20.8% to 23.2%, and the pore sizes mostly centered in 10~30μm. The compressive strength and the elastic modulus were in the range from 110.4 to 292.4MPa and 4.7 to 12.4GPa respectively, which was close to human bone.

The effect of Al addition on ω precipitation and age-hardening behavior of Ti-9.2Mo-2Fe and Ti-2Al-9.2Mo-2Fe alloy during aging treatment was investigated. The results showed that athermal and isothermal ω phase formation in Ti-2Al-9.2Mo-2Fe alloy was suppressed to a certain extent due to Al addition. In addition, a small amount of athermal ω phase was observed in the β matrix with a size of about ~5 nm during water quenching from above the β transus temperature for both alloys. Isothermal ω formation was also found during aging at temperatures ranging from 573 K to 773 K (300 °C to 500 °C) in both alloys, although it had a limited time of stability at 773 K (500 °C). The hardening due to isothermal ω precipitation exhibited no over-aging as long as ω phase existed in both alloys, and ω phase played a more important role in hardening than α phase. And the ω phase in 50 to 100 nm size exhibited the best hardening effect in Ti-9.2Mo-2Fe alloy. Similarly, α phase with 100 to 200 nm in length showed better hardening effects in Ti-2Al-9.2Mo-2Fe alloy. Both the alloys showed stronger age hardening at an intermediate temperature of 673 K (400 °C) and in the first aging stage at a higher temperature of 773 K (500 °C) due to the sufficiently fine size (50 nm), while they exhibited weaker age hardening at a lower temperature of 573 K (300 °C) and long period aging at a higher temperature of 773 K (500 °C) due to incomplete ω formation and/or coarsening of α phase. No over or peak aging stage was found at 573 K and 673 K (300 °C and 400 °C) during the aging for 72 hours, while the peak hardness values of both alloys aged at 773 K (500 °C) were obtained in the first stage of aging. The hardness of the alloys was very sensitive to size and volume fraction of ω phase, which depends on aging temperature, time, and composition of the involved alloys.