YAP1-LATS2 feedback loop dictates senescent or malignant cell fate to maintain tissue homeostasis

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 in hOSEs prevents these cells from natural replicative and YAP1-induced senescence. Most importantly, loss of LATS2 switches ovarian cells from YAP-induced senescence to malignant transformation. Our results demonstrate that LATS2 and YAP1, two major components of the Hippo/YAP signaling pathway, form a negative feedback loop to control YAP1 activity and prevent ovarian cells from malignant transformation. Human cancer genomic data extracted from TCGA datasets further confirm the clinical relevance of our finding

Constitutive behavior and novel characterization of hot deformation of Al-Zn-Mg-Cu aluminum alloy for lightweight traffic

Isothermal compression tests of 7A21 aluminum alloy were carried out on a Gleeble-3500 thermal simulator, and the stress-strain curves were obtained at temperatures ranging from 350 to 500 °C and strain rates ranging from 0.01 to 10 s ^−1 . The Arrhenius-type constitutive models with/without strain compensation were established to predict hot deformation mechanical behavior of the alloy based on friction and temperature corrected stress-strain curves, respectively. The model with strain compensation shows a higher prediction accuracy by calculating the average absolute relative error and correlation coefficient. The hot processing maps at different strains were constructed based on the dynamic material model (DMM). The safety strain rates map, a new form of processing map which reflects the variation of critical safety strain rates with the deformation temperatures and true strains, was generated to simplify the acquisition of safety zones throughout the whole deformation process

Microstructure evolution and properties comparation of industrial grade-maintained 7050-T7451 plate recycled from machining chips

There are 45%–71% machining chips generated during the manufacturing process of aviation components. Most of these MCs are down-grade recycled as cast alloy, causing resource waste. In this work, aviation MCs were added into the melt for grade-maintaining recycling. A systematic evaluation was conducted on the melt quality, microstructure evolution, and properties of industrial recycled 7050-T7451 plates with a capacity of 60t/furnace, as well as a comparison with the primary plates. The composition of the recycled 7050 melt is qualified, and the hydrogen content is below 0.075 mL/100gAl. The results of PoDFA and LiMCA show that the inclusions in the recycled 7050 melt are mainly below 40 μm in diameter, and the number of inclusions is 3 times that of the primary melt. TEM shows that the dispersed phase particles of the recycled plate are more uniform and finer. EBSD shows that the recrystallization ratio of recycled 7050-T7451 plate is 8.3%, much lower than the 23.9% of the primary plate. The mechanical and corrosion properties of the recycled 7050-T7451 all meet the AMS 4050 standard. The cost of grade-maintaining recycling can be saved by 6,130,000 USD per year for a production line with an annual output of 20,000 tons of plates. This work clarified the process, cost, microstructure, and properties of recycled 7050-T7451 plate, laying a foundation for the application of grade-maintaining recycled aviation aluminum alloys

Sustainable recycling of aerospace-grade ultra-clean 7050 aluminum alloy melts through argon refining without secondary aluminum dross generation

The refining of aluminum scraps commonly employs nitrogen-fluxes to eliminate impurities. However, the aluminum nitride (AlN) generated by the reaction between nitrogen and the aluminum melt, along with residual fluxes, contribute to low cleanliness of the recycled aluminum melt and pose difficulties for the disposal of secondary aluminum dross (SAD). Our innovative research has resulted in the recycling of aerospace-grade clean aluminum alloy melts. The results indicate that the argon bubble floating process adsorbs inclusions and hydrogen, achieving an aerospace-grade ultra-clean melt. The solid-liquid interface between the tube wall and the melt provides a diffusion channel for hydrogen atoms, and the bubbles rising up along the wall lead to a higher hydrogen content in the melt. The argon refining dross is primarily composed of Al and Al2O3, which can be recycled as a raw material for aluminum electrolysis. Argon refining can decrease the hydrogen content and the number of inclusions with particle size ≥40 μm in the recycled aluminum melt to the level of aerospace aluminum alloy melt. Nonetheless, the particle size ≥20 μm remains 1.5–2.5 times that of primary aluminum

A Recombinant Thermophilic and Glucose-Tolerant GH1 β-Glucosidase Derived from Hehua Hot Spring

As a crucial enzyme for cellulose degradation, β-glucosidase finds extensive applications in food, feed, and bioethanol production; however, its potential is often limited by inadequate thermal stability and glucose tolerance. In this study, a functional gene (lq-bg5) for a GH1 family β-glucosidase was obtained from the metagenomic DNA of a hot spring sediment sample and heterologously expressed in E. coli and the recombinant enzyme was purified and characterized. The optimal temperature and pH of LQ-BG5 were 55 °C and 4.6, respectively. The relative residual activity of LQ-BG5 exceeded 90% at 55 °C for 9 h and 60 °C for 6 h and remained above 100% after incubation at pH 5.0–10.0 for 12 h. More importantly, LQ-BG5 demonstrated exceptional glucose tolerance with more than 40% activity remaining even at high glucose concentrations of 3000 mM. Thus, LQ-BG5 represents a thermophilic β-glucosidase exhibiting excellent thermal stability and remarkable glucose tolerance, making it highly promising for lignocellulose development and utilization

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms of Cervical Carcinogenesis

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to promote the initiation and progression of cervical cancer. Our mechanistic studies indicated that hyperactivation of YAP1 in cervical epithelial cells facilitated HPV infection by increasing the putative HPV receptor molecules and disrupting host cell innate immunity. Our finding reveals an unconventional mechanism for cervical carcinogenesis

Sb₂O₃ Nanoparticles Anchored on Graphene Sheets via Alcohol Dissolution–Reprecipitation Method for Excellent Lithium-Storage Properties

Sb₂O₃ nanoparticles are uniformly anchored on reduced graphene oxide (rGO) sheets via a facile and ecofriendly route based on the alcohol dissolution–reprecipitation method. Such obtained Sb₂O₃/rGO composite demonstrates a highly reversible specific capacity (1355 mA h g^–1 at 100 mA g^–1), good rate capability, and superior life cycle (525 mA h g^–1 after 700 cycles at 600 mA g^–1) when used an anode electrode for lithium-ion batteries (LIBs). The outstanding electrochemical properties of Sb₂O₃/rGO composite could be attributed to its unique structure in which the strong electronic coupling effect between Sb₂O₃ and rGO leads to an enhanced electronic conductivity, structure stability, and electrochemical activity during reversible conversion-alloying reactions. Also, these findings are helpful in both developing novel high-performance electrodes for LIBs and synthesizing functional materials in an ecofriendly and economical way

YAP1-LATS2 feedback loop dictates senescent or malignant cell fate to maintain tissue homeostasis

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 in hOSEs prevents these cells from natural replicative and YAP1-induced senescence. Most importantly, loss of LATS2 switches ovarian cells from YAP-induced senescence to malignant transformation. Our results demonstrate that LATS2 and YAP1, two major components of the Hippo/YAP signaling pathway, form a negative feedback loop to control YAP1 activity and prevent ovarian cells from malignant transformation. Human cancer genomic data extracted from TCGA datasets further confirm the clinical relevance of our finding