Generation of induced pluripotent stem cells from an HLA-B27 positive ankylosing spondylitis patient with syndesmophyte formation.

Human leukocyte antigen (HLA)-B27 is the genetic marker for ankylosing spondylitis (AS). Here, we generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a male AS patient carrying HLA-B27 with syndesmophyte formation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, expressed pluripotent markers, and could differentiate into three germ layers. This cellular model will provide a platform for studying pathological mechanisms of new bone formation in HLA-B27 positive AS patients.

Environmental quality mediates the ecological dominance of cooperatively breeding birds.

Although social species as diverse as humans and ants are among the most abundant organisms on Earth, animals cooperate and form groups for many reasons. How these different reasons for grouping affect a species' ecological dominance remains unknown. Here we use a theoretical model to demonstrate that the different fitness benefits that animals receive by forming groups depend on the quality of their environment, which in turn impacts their ecological dominance and resilience to global change. We then test the model's key predictions using phylogenetic comparative analysis of >6500 bird species. As predicted, we find that cooperative breeders occurring in harsh and fluctuating environments have larger ranges and greater abundances than non-cooperative breeders, but cooperative breeders occurring in benign and stable environments do not. Using our model, we further show that social species living in harsh and fluctuating environments will be less vulnerable to climate change than non-social species.

A magnified compact galaxy at redshift 9.51 with strong nebular emission lines.

Ultraviolet light from early galaxies is thought to have ionized gas in the intergalactic medium. However, there are few observational constraints on this epoch because of the faintness of those galaxies and the redshift of their optical light into the infrared. We report the observation, in JWST imaging, of a distant galaxy that is magnified by gravitational lensing. JWST spectroscopy of the galaxy, at rest-frame optical wavelengths, detects strong nebular emission lines that are attributable to oxygen and hydrogen. The measured redshift is z = 9.51 ± 0.01, corresponding to 510 million years after the Big Bang. The galaxy has a radius of [Formula: see text] parsecs, which is substantially more compact than galaxies with equivalent luminosity at z ~ 6 to 8, leading to a high star formation rate surface density.

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mouse Corneal Epithelial Cells.

Purpose: Corneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis. Methods: Single cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat. Results: We characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type-specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes. Conclusions: Our study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.

The Function of the Mutant p53-R175H in Cancer.

Wild-type p53 is known as "the guardian of the genome" because of its function of inducing DNA repair, cell-cycle arrest, and apoptosis, preventing the accumulation of gene mutations. TP53 is highly mutated in cancer cells and most TP53 hotspot mutations are missense mutations. Mutant p53 proteins, encoded by these hotspot mutations, lose canonical wild-type p53 functions and gain functions that promote cancer development, including promoting cancer cell proliferation, migration, invasion, initiation, metabolic reprogramming, angiogenesis, and conferring drug resistance to cancer cells. Among these hotspot mutations, p53-R175H has the highest occurrence. Although losing the transactivating function of the wild-type p53 and prone to aggregation, p53-R175H gains oncogenic functions by interacting with many proteins. In this review, we summarize the gain of functions of p53-R175H in different cancer types, the interacting proteins of p53-R175H, and the downstream signaling pathways affected by p53-R175H to depict a comprehensive role of p53-R175H in cancer development. We also summarize treatments that target p53-R175H, including reactivating p53-R175H with small molecules that can bind to p53-R175H and alter it into a wild-type-like structure, promoting the degradation of p53-R175H by targeting heat-shock proteins that maintain the stability of p53-R175H, and developing immunotherapies that target the p53-R175H-HLA complex presented by tumor cells.

Toxic mechanisms of Roth801, Canals, microparticles and nanoparticles of ZnO on MG-63 osteoblasts.

ZnO eugenol-based materials are widely used for restoration of caries cavity, apical retrograde filling and root canal sealer. Their effects on apical bone healing await investigation. The toxic mechanisms of ZnO particles and nanoparticles to MG-63 osteoblastic cells were studied. We found the different morphology and size of various particles as observed by scanning electron microscope. Particles of Canals and Roth801 were larger than ZnO-205532 microparticles and ZnO-677450 nanoparticles. Four ZnO particles showed cytotoxicity (>25 µg/ml) as analyzed by MTT. Transmission electron microscope found intracellular vacuoles with particle content. Exposure to ZnO particles induced ROS production and cell cycle arrest as studied by DCF and propidium iodide flow cytometry. ZnO particles activated ATM, ATR, Chk1, Chk2, γ-H2AX, ERK and p38 phosphorylation as detected by immunofluorescent staining and western blotting. The protein expression of cdc2, cyclin B1 and cdc25C were decreased, whereas GADD45α and hemeoxygenase-1 (HO-1) were stimulated. ZnO particles' cytotoxicity to MG63 cells was prevented by N-acetylcysteine (NAC), but not CGK733, AZD7762, U0126 and SB203580. ZnO showed little effect on IL-8 and sICAM-1 secretion. These results indicated that ZnO particles are toxic to osteoblasts. ZnO particles' toxicity were related to ROS, and DNA damage responses, checkpoint kinases, cell cycle arrest, ERK and p38 signaling, but not IL-8 and ICAM-1. These results were useful for materials' development and promote apical healing. Dentists should avoid of extruding ZnO-based sealers excessively over root apex and prevent residual ZnO-based retrograde filling materials in apical area during endodontic practice.

A chemically triggered transition from conflict to cooperation in burying beetles.

Although interspecific competition has long been recognised as a major driver of trait divergence and adaptive evolution, relatively little effort has focused on how it influences the evolution of intraspecific cooperation. Here we identify the mechanism by which the perceived pressure of interspecific competition influences the transition from intraspecific conflict to cooperation in a facultative cooperatively breeding species, the Asian burying beetle Nicrophorus nepalensis. We not only found that beetles are more cooperative at carcasses when blowfly maggots have begun to digest the tissue, but that this social cooperation appears to be triggered by a single chemical cue - dimethyl disulfide (DMDS) - emitted from carcasses consumed by blowflies, but not from control carcasses lacking blowflies. Our results provide experimental evidence that interspecific competition promotes the transition from intraspecific conflict to cooperation in N. nepalensis via a surprisingly simple social chemical cue that is a reliable indicator of resource competition between species.

A fiber-progressive-engagement model to evaluate the composition, microstructure, and nonlinear pseudoelastic behavior of porcine arteries and decellularized derivatives.

The theoretical fiber-progressive-engagement model was proposed to describe the pseudoelastic behavior of an artery pre- and post-decellularization treatments. Native porcine arteries were harvested and decellularized with 0.05% trypsin for 12 h. The uniaxial tensile test data were fitted to the fiber-progressive-engagement model proposed herein. The effects of decellularization on the morphology, structural characteristics, and composition of vessel walls were studied. The experimental stress-strain curve was fitted to the model in the longitudinal and circumferential direction, which demonstrated the adequacy of the proposed model (R2>0.99). The initial and turning strains were similar in the longitudinal and circumferential directions in the aorta, suggesting the occurrence of collagen conjugation in both directions. Discrepancies in the initial and turning strain and initial and stiff modulus in both directions in the coronary artery revealed the anisotropic features of this vessel. Decellularization induced a decrease in the initial and turning strains, a slight change in the initial modulus, and a substantial decrease in the stiffness modulus. The decrease in the initial and turning strain can be attributed to the loss of waviness of collagen bundles because of the considerable decrease in elastin and glycosaminoglycan contents. This simple non-linear model can be used to determine the fiber modulus and waviness degree of vascular tissue. Based on these results, this mechanical test can be used as a screening tool for the selection of an optimized decellularization protocol for arterial tissues. STATEMENT OF SIGNIFICANCE: Decellularized vascular graft has potential in clinical application, such as coronary artery bypass surgery, peripheral artery bypass surgery or microsurgery. An ideal decellularization protocol requires balance in cell removal efficiency and extracellular matrix preserving. Both biochemical and biomechanical properties are crucial to the success of scaffold in cell seeding and animal study. A comprehensive understanding of the composition, microstructure, and mechanical behavior of the arterial wall is the key to the development of decellularized vascular grafts. For this purpose, we proposed this "Fiber-Progressive-Engagement" model to evaluate the microstructure, composition and mechanical properties of porcine coronary artery. The model provides a new perspective regarding the non-linear behavior of arterial tissue and its decellularized derivatives. It can be widely applied to different types of tissues, as demonstrated in the aorta and coronary artery. This model has several advantages; it provides an improved fit of non-linear curves (R2>0.99), can be used to elucidate the pseudoelastic properties of porcine vascular tissues using the concept of fiber engagement, and can estimate an elastic modulus with greater accuracy (compared to the graphical estimation or calculation by simple linear fittings), as well as to plot typical stress-strain curves.

The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.

AIM: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. MAIN METHODS: The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. KEY FINDINGS: Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. SIGNIFICANCE: WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.

Attitude determination using a MEMS-based flight information measurement unit.

Obtaining precise attitude information is essential for aircraft navigation and control. This paper presents the results of the attitude determination using an in-house designed low-cost MEMS-based flight information measurement unit. This study proposes a quaternion-based extended Kalman filter to integrate the traditional quaternion and gravitational force decomposition methods for attitude determination algorithm. The proposed extended Kalman filter utilizes the evolution of the four elements in the quaternion method for attitude determination as the dynamic model, with the four elements as the states of the filter. The attitude angles obtained from the gravity computations and from the electronic magnetic sensors are regarded as the measurement of the filter. The immeasurable gravity accelerations are deduced from the outputs of the three axes accelerometers, the relative accelerations, and the accelerations due to body rotation. The constraint of the four elements of the quaternion method is treated as a perfect measurement and is integrated into the filter computation. Approximations of the time-varying noise variances of the measured signals are discussed and presented with details through Taylor series expansions. The algorithm is intuitive, easy to implement, and reliable for long-term high dynamic maneuvers. Moreover, a set of flight test data is utilized to demonstrate the success and practicality of the proposed algorithm and the filter design.

Evaluation of cutting efficiency of ultrasonic tips used in orthograde endodontic treatment.

The purpose of the present study was to evaluate the cutting efficiency of the three different ultrasonic tips for orthograde endodontic treatment: stainless steel, zirconium nitride-coated, and diamond-coated tips. An ultrasonic handpiece was mounted on a custom-made automated balance, and each tip repeatedly penetrated dental stone blocks to a depth of 3 mm for 10 times. The amount of time taken to penetrate 3 mm of stone was measured. The diamond-coated tips showed significantly greater cutting efficiency than either stainless steel tips or zirconium-nitride coated tips. The stainless steel tips showed initial better cutting efficiency, but over time , there is no significant difference between the cutting efficiency of the stainless steel tips and the zirconium nitride coated tips. The diamond coated tips were the only group that showed breakage in this study.

Effectiveness of selected materials against Enterococcus faecalis: part 3. The antibacterial effect of calcium hydroxide and chlorhexidine on Enterococcus faecalis.

It has been found that Enterococcus faecalis is most commonly isolated in failed endodontic treatment. Irrigation with chlorhexidine gluconate has been suggested based on its antimicrobial effect and substantivity. Calcium hydroxide also is an effective antimicrobial agent because of its high alkalinity. The purpose of this study was to test the individual and combined effect of calcium hydroxide and chlorhexidine against E. faecalis. The agar-diffusion test was performed on Mueller-Hinton plates. Paper disks were impregnated with: (a) CaOH powder with sterile water; (b) Pulpdent; (c) 0.12% Peridex; (d) CaOH powder with Peridex; and (e) Pulpdent with Peridex. Ampicillin served as a control. The plates were incubated at 37 degrees C for 72 h. Peridex showed significantly larger zones of inhibition compared with CaOH. No statistically significant difference was found between Peridex and the combination of CaOH and Peridex.