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In the past 10 years since its introduction, phenome-wide association studies (PheWAS) have uncovered novel genotype–phenotype relationships. Along the way, PheWAS have evolved in many aspects as a study design with the expanded availability of large data repositories with genome-wide data linked to detailed phenotypic data. Advancement in methods, including algorithms, software, and publicly available integrated resources, makes it feasible to more fully realize the potential of PheWAS, overcoming the previous computational and analytical limitations. We review here the most recent improvements and notable applications of PheWAS since the second half of the decade from its inception. We also note the challenges that remain embedded along the entire PheWAS analytical pipeline that necessitate further development of tools and resources to further advance the understanding of the complex genetic architecture underlying human diseases and traits. Pleiotropy, the concept that a gene or genetic variant affects more than one phenotype or trait, is at least a century old. By contrast, phenome-wide association studies (PheWAS), an approach used to identify cross-phenotype associations, were introduced only in the past decade. Still relatively young, PheWAS has rapidly matured into a widely used study design and analytical approach that can still benefit from improvements in its pipeline as genome-wide datasets expand in their breadth and depth, challenging the computational and statistical limits of today's PheWAS. [ABSTRACT FROM AUTHOR]

Bilayer is an effective structure to enhance magnetic properties of films. This study employs high magnetic field (HMF) and amorphous Fe–Sm under-layer to tune the magnetic properties of evaporated Co–Sm/Fe–Sm bilayer films. Various analysis methods are used to explore the relation of microstructure evolution under above conditions with magnetic performance. The results show that both the amorphous Fe–Sm under-layer and the HMF can decrease surface roughness. Further, the HMF exhibits other effects that reduces column size, increases interplanar spacing and affects interface at atomic scale. The structural variation has effect on magnetic properties of bilayer films. The amorphous Fe–Sm under-layer increases magnetization, coercivity and squareness through changing the amount of non-magnetic structure at atomic scale. Meanwhile, the HMF decreases coercivity by changing pinning via the interface variation. Both the HMF and amorphous under-layer have no influence on the anisotropy of bilayer films. These results present an effective method to tune the magnetic properties of films through amorphous under-layer and HMF. • Amorphous FeSm under-layer has effect on microstructure and magnetic performance. • High magnetic field improves magnetization by affecting non-magnetic structure. • High magnetic field decreases coercivity by changing interface pinning. • Effect of high magnetic field on squareness is smaller than that of amorphous layer. [ABSTRACT FROM AUTHOR]

Improving the thermoelectric (TE) properties of typical p-type Bi 0.5 Sb 1.5 Te 3 film is crucial for power generation in film-based thermoelectric devices. The shape of the hexagonal structure in the Bi 0.5 Sb 1.5 Te 3 film can be controlled by adjusting the magnetron sputtering parameters. The results indicate that a high nucleation rate under high sputtering power promotes island growth with a preferred orientation of (015). Thermal energy influences the growth in the in-plane direction along the (00 l) orientation and induces the c-axis orientation in the out-of-plane direction. Consequently, a dense layered hexagonal structure with a high grain boundary density is formed, leading to increased defect density, carrier concentration, and phonon scattering. In this case, the power factor reaches 3149.01 μW·m-1·K-2 at 480 K and the ZT value is 1.14 at 480 K. These results indicate that the film with a dense layered hexagonal structure enhances the TE properties. [ABSTRACT FROM AUTHOR]

Pyroptosis is a newly discovered type of programmed cell death associated with inflammatory and fibrotic diseases. Macrophages play an important role in inducing early immune inflammation in systemic sclerosis (SSc). To investigate the effect of macrophages pyroptosis on fibrosis of SSc. Pyroptosis/inflammatory markers in serum and skin of SSc patients were detected. Bleomycin (BLM) was subcutaneously injected to establish SSc mouse model. The levels of pyroptosis markers, dermal thickness and collagen deposition in skin were assessed before and after the administration of pyroptosis inhibitors, including MCC950, Disulfiram and necrosulfonamide (NSA). Human-derived monocyte-macrophage cell line (THP-1) or mouse bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and stimulated by silicon dioxide (SiO 2) to induce cell pyroptosis. Fibroblasts from patients with SSc were co-cultured with pyroptotic THP-1 cells, and the collagen production was assessed. Pyroptotic/inflammatory proteins, including NLRP3, cleaved-Caspase (CASP)1, GSDMD-N terminal and IL-18 were increased in the serum, and ASC aggregation and GSDMD were elevated in macrophages in the skin of SSc patients. SSc mice showed increased pyroptosis markers, dermal thickness and collagen deposition in skins, which were alleviated by MCC950, Disulfiram and NSA. Pyroptosis of THP-1 cells and BMDMs was induced by LPS/SiO 2 , and it was reduced by the inhibitors of Cathepsin B, NLRP3, CASP1 and GSDMD. Co-culture with pyroptotic THP-1 cells increased the fibrotic proteins in fibroblasts, which were alleviated by pyroptosis inhibitors. SSc patients and BLM-induced mouse model presented increased pyroptosis. LPS/SiO 2 -induced macrophage pyroptosis promoted fibrosis of SSc through Cathepsin B/NLRP3/GSDMD pathway. • Macrophage pyroptosis was increased in SSc patients and BLM-induced SSc mouse model. • Inhibition of pyroptosis reduced inflammation and fibrosis of SSc mouse model. • Inhibiting NLRP3/GSDMD-mediated macrophage pyroptosis inactivates fibroblasts. [ABSTRACT FROM AUTHOR]

Bi 2 Te 3 is a successful and commercial thermoelectric material. However, Bi 2 Te 3 is easily generates point defects, which limits its thermoelectric (TE) properties. This study presents a novel method to tune point defects by using short-range atomic diffusion via pulsed electric field (PEF) treatment in C-doped Bi 2 Te 3 films. The C atoms migrate from the interstitial position in the Bi layer (C i) and the Van der Waals gap (C vdw) to the Bi vacancy after the PEF treatment. For this case, it increases the content of the Te–C bonds for the PEF films, resulting in increased electron concentration. And the PEF can eliminate amorphous regions of the C-doped Bi 2 Te 3 films. In addition, the shorter bond length of the Te–C improves the compressive stress of the film and increases the effective mass of carriers. Thus, the conductivity and the Seebeck coefficient are improved simultaneously. In this study, the power factor was 2450.32 μW m−1·K−2 at 513 K after the PEF treatment. Therefore, the PEF is an effective method to improve TE properties by short-range atomic diffusion. [ABSTRACT FROM AUTHOR]

In this work, the competitive relationship between the double amorphous phases is systematically investigated to increase the high-temperature wear resistance of the self-lubricating TiAlSiCN coating. These double amorphous phases combine the SiN x phase with high-temperature resistance and the C-related phase with a low friction coefficient. An increase in the Si content facilitates the change in the phase composition. The resultant coating exhibits an adhesion strength of 153 N, a friction coefficient of 0.24 and a hardness of 25.24 GPa upon generation of the TiAlN(C), the SiN x and the C-related phase. In this case, the TiAlSiCN coating achieves long-term self-lubrication at high temperatures with the titanium alloy friction pair. This mechanism stems from the SiN x phase replacing the portion of the easily oxidized amorphous C-related phase, which yields an enhanced high-temperature wear resistance. The cutting distance of this TiAlSiCN is 120% higher than that of the TiAlCN during the high-speed cutting of the titanium alloy. This outcome provides an effective solution for high-temperature applications of self-lubricating coatings. • Long-term self-lubricating is remained in TiAlSiCN coating by optimal Si content. • Synergistic effect of amorphous SiN x and C-related phase is solved in TiAlSiCN. • Tool life of TiAlSiCN improved 225% by comparing with that of TiAlN. [ABSTRACT FROM AUTHOR]

The order-disorder transition (ODT) of RE zirconate (RE 2 Zr 2 O 7) has received much attention due to its potential applications in the design of thermal barrier coatings (TBCs). A series of high entropy RE zirconates (RE = La, Sm, Gd, Er and Lu) were designed and synthesized in order to regulate the fluorite-pyrochlore phases, and to investigate the effect of phase composition on the microstructures and performances. The results showed that the sintering temperature, as well as equivalent ion radius, played an important role in regulating the phase transformation of fluorite-pyrochlore. The coexistence of pyrochlore-fluorite phases not only can result in the decrease in grain size but also increased the lattice strain of each phase, thereby enhancing the phonon scattering and contributing to the reduction in the thermal conductivity. The CMAS corrosion resistance was mainly related to phase compositions, and the thicknesses of reaction layer decreased gradually with the increasing fluorite phase content. The results will provide theoretical guidance for the microstructural design of high entropy RE zirconates as next generation TBC materials in future. [ABSTRACT FROM AUTHOR]

• Angle of grain boundaries converts to low from high by electrostatic force. • Low energy of low-angle grain boundary scatters carrier but not phonon. • Pulse current treatment provides a method to get high power factor and power density. Current applications of thermoelectric (TE) materials are limited by their low conversion efficiency. Interfacial engineering is a common way to improve TE properties. This study employed a pulsed electric field to tune the grain interfacial structure of Bi 2 Te 3 films and thereby improve their power factor. The high-angle grain boundaries of the as-deposited films were transformed into low-angle grain boundaries (LAGBs) by the electrostatic force of a high pulse current density. The low interfacial energy of LAGBs maintains high carrier mobility while their reduced defects result in a low carrier concentration. These effects improve the Seebeck coefficient and conductivity simultaneously, with the power factor reaching 5394.77 μW·m−1·K−2 at 513 K. In addition, the compression stress generated by LAGBs enhances phonon scattering, creating a film with the highest power density yet reported (1.31 W·m−2). This provides a method for using PEF to improve the performance of TE materials. [ABSTRACT FROM AUTHOR]

Zn 4 Sb 3 has brought into sharp focus by its low cost and excellent thermoelectric (TE) properties in the medium temperature range. Zn atoms can diffuse in the Zn 4 Sb 3 matrix under the treatment of temperature or current. This provides a way to control its TE performance. In this study, the TE properties of the Zn 4 Sb 3 films were improved by the Zn atomic diffusion under the treatment of periodic pulsed electric field. The Zn atomic diffusion is caused by the electrostatic interaction of the pulsed electric field and the diffusion mode is related to the pulse period. When the pulse period is smaller than 10 s, the interstitial Zn atom diffuses first. The Zn vacancy increases, leading to the increase of the carrier concentration and the decrease of the resistivity. When the pulse period increases to 100 s, more Zn(1) atoms diffuse through the interstitial position, resulting in a small amount of ZnSb phase. Thereby in the Zn 4 Sb 3 films, the carrier concentration decreases and the Seebeck coefficient increases. This kind of the synergistic effect decreases the resistivity and increases the Seebeck coefficient. The power factor of the Zn 4 Sb 3 films treated with a pulse period of 100 s is more than 4500 μW m−1 K−2 in the range of 373 K–573 K. This study presents a new method to control atomic diffusion by periodic pulsed electric field, and the TE properties of the Zn 4 Sb 3 films are improved. • Pulsed electric field can control the diffusion of Zn atoms in Zn–Sb films. • The diffusion of interstitial Zn i atoms increased the carrier concentration in films. • The diffusion of Zn(1) atoms increased with the increase of pulse period. • The diffusion of Zn(1) atoms caused a small amount of the ZnSb phase. • The power factor of the film treated with the pulse period is 4901.31 μW m−1 K−2. [ABSTRACT FROM AUTHOR]

Cu 2 Se is one kind of popular thermoelectric materials due to its performance of the phonon glass-electron crystal. However, the poor thermal stability limits its application. Regulating the distribution of the Cu+ by elemental dopant is a general method to solve the stability and to improve the thermoelectric performance. In this study, the Ag-doped β-Cu 2−x Se films were prepared by vacuum thermal evaporation method. The Cu+ distribution on the octahedral 32(f) sites in the Cu 2 Se crystal is tuned by the Ag content. It found that when the Ag content is 1.0%, the Cu+ and Ag+ contents in the 32(f) sites reach the maximum. In this case, the power factor of the film is 1750 μW·m−1·K−2 at 530 K. As the Ag content rises, the second phase of CuAgSe appears. This results in the decrease of the power factor. It shows that controlling the distribution of the Cu+ by the Ag dopant is conducive to improve the thermoelectric properties of the β-Cu 2−x Se films. • Occupancy increase of Cu+ and Ag+ in 32(f) sites decreases resistivity. • CuAgSe second phase increases carrier concentration and effective mass. • Power factor of Ag-1.0% film is maximum and 300% higher than that of Ag-0.0% film. [ABSTRACT FROM AUTHOR]

Psoriasis is characterized by hyperproliferative keratinocytes, dilated capillaries and leukocyte infiltration. 2-Methoxyestradiol (2-ME) has shown significant inhibition on proliferation, angiogenesis and inflammation. To evaluate the anti-psoriatic potential of 2-ME, psoriasis-like dermatitis was induced by topical application of imiquimod (IMQ) on the dorsal skin of C57BL/6 mice for seven consecutive days, followed by treatment of vehicle or 2-ME ointment from Day 4 on. The psoriasis area and severity index (PASI) was assessed daily. On Day 8, skin histology and spleen index were assessed. The effects of 2-ME on the proliferation, apoptosis, cell cycle, vascular endothelial growth factor A (VEGFA), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways of HaCaT cells stimulated by interleukin-17 (IL-17A) were detected, together with its effect on the proliferation, tube formation and VEGF receptor expression of human umbilical vein endothelial cells (HUVECs). We found that topical 2-ME treatment significantly improved IMQ-induced psoriasis-like dermatitis and decreased the PASI scores, the activation of STAT3 in the skin (P < 0.05), and the spleen index in mice (P < 0.01). In vitro, 2-ME inhibited the proliferation of HaCaT cells by inducing apoptosis and G2/M phase arrest (P < 0.01). Moreover, 2-ME suppressed IL-17A-induced VEGFA (2.5 μM: P < 0.05; 5 μM: P < 0.01) and phosphorylation of STAT3 by blocking p-JAK1 in HaCaT cells and prevented tube formation (P < 0.01) and proliferation by targeting VEGF receptors 1 (VEGFR1) and 2 (VEGFR2) in HUVECs. We conclude that 2-ME alleviated psoriasis in vivo and in vitro by inhibiting JAK1/STAT3 pathway and was a promising therapeutic agent for psoriasis. • 2-Methoxyestradiol improves psoriasis-like dermatitis and systemic immune activation in imiquimod-induced mice. • 2-Methoxyestradiol inhibits proliferation and induces apoptosis of HaCaT cells. • 2-Methoxyestradiol suppresses IL-17A-induced JAK1/STAT3 signaling pathway in HaCaT cells. • 2-Methoxyestradiol inhibits the proliferation, tube formation and VEGF receptor expression in HUVECs. [ABSTRACT FROM AUTHOR]

In this study, the electrical conductivity (EC) and mechanical properties of extruded state Al-1Si-0.6Mg-0.2Fe alloy (ES-Alloy) are enhanced through T6 heat treatment, and the underlying mechanisms are analyzed in conjunction with model calculations. Results demonstrate that the optimal heat treatment process for the ES-Alloy is 550 °C / 2 h + 230 °C / 16 h. Through the heat treatment process, the alloy's EC and ultimate tensile strength are 57.0% IACS and 247.6 MPa, respectively, which are improved by 4.6% and 54.8%, respectively. For ES-Alloy, after heat treatment, owing to reversion and recrystallization, the average grain size of the alloy is 175.9 μm and becomes 6.93 times larger. Combined with theoretical calculation, the contribution of grain boundary strengthening to the alloy's strength is only reduced by 9.1 MPa. However, the reduction of grain boundary area reduces the scattering of free electrons during the transport process, which is beneficial to improving EC. Moreover, by modifying the heat treatment parameters, nanoscale Mg 2 Si and large-size AlFeSi second phases present in the alloy keep a favorable lattice match with the Al matrix, proving that this makes the main contribution to the alloy's strength. The microstructures give consideration for both the high efficiency of electron transport and the enhancement of mechanical properties. So, it is advantageous for the improvement of EC and mechanical properties. • 550 °C/2 h + 230 °C/16 h balances alloy's electrical conductivity and mechanical properties. • Second phase strengthening contributes more to alloy's strength than grain boundary. • High angle grain boundary and β" phase are useful to improve electrical conductivity. [ABSTRACT FROM AUTHOR]

Three kinds of high entropy (Y 0.25 Sc 0.25 Er 0.25 Yb 0.25) 2 Si 2 O 7 , (Y 0.2 Sc 0.2 Er 0.2 Yb 0.2 Lu 0.2) 2 Si 2 O 7 and (Y 0.2 Sc 0.2 Er 0.2 Yb 0.2 Gd 0.2) 2 Si 2 O 7 were designed and synthesized in order to investigate the relation of microstructures and CMAS corrosion resistance. At low temperature of 1300 °C, lattice distortion played a crucial role in resistance to CMAS corrosion, and larger lattice distortion contributed to CMAS corrosion resistance. However, the corrosion behavior at 1500 °C was related to the equivalent ionic radius and RE species. The smaller equivalent ionic radius tended to promote the re-precipitation of high entropy RE disilicate in residual CMAS glass rather than apatite. The results will provide theoretical guidance for the microstructural design of high entropy RE disilicate and selection of RE elements in future. • High entropy ceramics were synthesized by solid state reaction method. • (Y 0.2 Sc 0.2 Er 0.2 Yb 0.2 Gd 0.2) 2 Si 2 O 7 ceramics had a maximum lattice distortion. • (Y 0.2 Sc 0.2 Er 0.2 Yb 0.2 Gd 0.2) 2 Si 2 O 7 presented a best CMAS corrosion resistance. [ABSTRACT FROM AUTHOR]

The self-lubricating TiAlTaCN coating with high-temperature resistance above 800 °C is developed using magnetron sputtering. This mechanism stems from the TaN phase is easily oxidized to form a protective Ta 2 O 5 that compensates for the insufficient antioxidant capacity of Al 2 O 3. Moreover, the TaC phase, being resistant to oxidation, contributes to achieving the self-lubrication effect with amorphous C-related phases. The cutting distance of the TiAlTaCN is 250% greater than that of the TiAlCN during the high-speed cutting of titanium alloy. These results reveal the oxidation mechanism of different carbon nitrides and provide a new solution for the self-lubricating coatings applied at high temperatures. • A new high-temperature resistant (800 °C) self-lubricating (COF=0.27) TiAlTaCN nanocomposite coating was prepared. • The Ta addition inhibits the phase transition and increases the high thermal stability from 600 °C to 1000 °C. • The wear rate of the TiAlTaCN is 38.7% lower than that of the TiAlCN at 600 °C. • The cutting distance of the TiAlTaCN is 250% higher than the TiAlCN during the high-speed cutting of titanium alloy. [ABSTRACT FROM AUTHOR]

The novel rare earth monosilicates (xRE 1/x) 2 SiO 5 (RE=Yb, Tm, Er, Y, Dy and Tb, x = 2–6) were prepared in order to establish the relationship between configurational entropy and lattice distortion, and the effect of configurational entropy on their properties was investigated. The results showed that the lattice distortion of (xRE 1/x) 2 SiO 5 increased gradually with the increase of configurational entropy, but the multi-principal component solid solution tended to form a highly symmetrical crystal structure when the configurational entropy was large enough, thus inhibiting the lattice distortion. (5RE 1/5) 2 SiO 5 had a maximum lattice distortion, which leaded to a relatively low thermal conductivity and coefficient of thermal expansion, and good CMAS corrosion resistance. • The effect of configurational entropy on microstructure and properties was investigated. • (5RE 0.2) 2 SiO 5 ceramic had a maximum lattice distortion. • (5RE 0.2) 2 SiO 5 ceramic presented the relatively good thermal properties and CMAS corrosion resistance. [ABSTRACT FROM AUTHOR]

• Different dimensions of carbon have different effects on thermoelectric performance. • The lower the dimension of carbon, the higher the carrier concentration of the film. • The CNT composite makes ZnO: Al films have the best performance. The low-dimensional carbon composite is expected to improve electrical conductivity and reduce the thermal conductivity of thermoelectric (TE) materials, which is considered an effective method to improve the TE properties of materials. However, the different dimensions of carbon have various effects on the properties of TE film composite. This study investigated the effects of zero-dimensional fullerene, one-dimensional carbon nanotubes (CNT), and two-dimensional graphene on the TE properties of vacuum evaporated ZnO: Al films. The results demonstrated that these three types of composites influenced the carrier concentration and mobility of the films, which in turn affected the TE properties and output power. The lower the dimension of carbon, the higher the carrier concentration of the film. The CNT composite did not affect the microstructure and preferred orientation. However, it increased the particle size and surface roughness. The interface between CNT and ZnO: Al provided more carriers and improved effective mass, thereby increasing the Seebeck coefficient. In addition, the CNT can be used as a carrier transport channel to improve carrier mobility because of its unique tubular structure. Therefore, the CNT composited ZnO: Al films demonstrated the best TE performance and output power. Its power factor reached 136.5 μWm−1K−2 at room temperature. [ABSTRACT FROM AUTHOR]

[Display omitted] • The TiAlCN coating with high adhesion (156 N) and low friction coefficient (0.231) was deposited. • The TiAlCN coating can form a special structure of nano-crystalline wrapped by C-related amorphous phase by adjusting the C/N ratio. • The TiAlCN coating reduces wear and inhibits the adhesive wear during high-speed cutting titanium alloy. The cutting temperature will be significantly increased while cutting high reactive titanium alloy due to the large friction coefficient of the traditional TiAlN coated tools. The tool could also easily appear adhesive wear and thereby reduce the service life. In this work, TiAlCN coatings with high adhesion and low friction coefficient were deposited by changing the C 2 H 2 and N 2 flow rates and using medium-frequency magnetron sputtering. Compared with the TiAlN coating, the hardness of the TiAlCN coating increases up to the value of 20.36 GPa, the toughness is improved by about 230%, the adhesion reaches the value of 156 N. However, the friction coefficient is only 0.231. This performance improvement is attributed to the special structure of (Ti,Al)(C,N) nano-crystalline wrapped by a C-related amorphous phase that is formed in the coating. The structure can be formed by adjusting the C/N ratio to make the C atom content exceed the solid solubility but the C/N ratio does not reach saturation. This kind of TiAlCN coating reduces the wear and inhibits the adhesive wear during the high-speed cutting process of titanium alloy. The cutting distance is also increased by 50% compared with the TiAlN coating. [ABSTRACT FROM AUTHOR]