KXNet: A Model-Driven Deep Neural Network for Blind Super-Resolution

Although current deep learning-based methods have gained promising performance in the blind single image super-resolution (SISR) task, most of them mainly focus on heuristically constructing diverse network architectures and put less emphasis on the explicit embedding of the physical generation mechanism between blur kernels and high-resolution (HR) images. To alleviate this issue, we propose a model-driven deep neural network, called KXNet, for blind SISR. Specifically, to solve the classical SISR model, we propose a simple-yet-effective iterative algorithm. Then by unfolding the involved iterative steps into the corresponding network module, we naturally construct the KXNet. The main specificity of the proposed KXNet is that the entire learning process is fully and explicitly integrated with the inherent physical mechanism underlying this SISR task. Thus, the learned blur kernel has clear physical patterns and the mutually iterative process between blur kernel and HR image can soundly guide the KXNet to be evolved in the right direction. Extensive experiments on synthetic and real data finely demonstrate the superior accuracy and generality of our method beyond the current representative state-of-the-art blind SISR methods. Code is available at: https://github.com/jiahong-fu/KXNet.Comment: Accepted by ECCV202

Stem cells in a three-dimensional scaffold environment

Abstract Stem cells have emerged as important players in the generation and maintenance of many tissues. However, the accurate in vitro simulation of the native stem cell niche remains difficult due at least in part to the lack of a comprehensive definition of the critical factors of the stem cell niche based on in vivo models. Three-dimensional (3D) cell culture systems have allowed the development of useful models for investigating stem cell physiology particularly with respect to their ability to sense and generate mechanical force in response to their surrounding environment. We review the use of 3D culture systems for stem cell culture and discuss the relationship between stem cells and 3D growth matrices including the roles of the extracellular matrix, scaffolds, soluble factors, cell-cell interactions and shear stress effects within this environment. We also discuss the potential for novel methods that mimic the native stem cell niche in vitro as well as the current associated challenges

MDM2-p53 Pathway in Hepatocellular Carcinoma

Abnormalities in the TP53 gene and overexpression of MDM2, a transcriptional target and negative regulator of p53, are commonly observed in cancers. The MDM2-p53 feedback loop plays an important role in tumor progression and thus, increased understanding of the pathway has the potential to improve clinical outcomes for cancer patients. Hepatocellular carcinoma (HCC) has emerged as one of the most commonly diagnosed forms of human cancer; yet, the current treatment for HCC is less effective than those used against other cancers. We review the current studies of the MDM2-p53 pathway in cancer with a focus on HCC, and specifically discuss the impact of p53 mutations along with other alterations of the MDM2-p53 feedback loop in HCC. We also discuss the potential diagnostic and prognostic applications of p53 and MDM2 in malignant tumors as well as therapeutic avenues that are being developed to target the MDM2-p53 pathway

RPL23 Links Oncogenic RAS Signaling to p53-Mediated Tumor Suppression

The ribosomal protein (RP)-MDM2 interaction is a p53 response pathway critical for preventing oncogenic c-MYC-induced tumorigenesis. To investigate whether the RP-MDM2-p53 pathway is a broad anti-oncogenic mechanism, we crossed mice bearing an MDM2C305F mutation, which disrupts RPL11 binding to MDM2, with mice expressing an oncogenic HrasG12V transgene. Interestingly, the MDM2C305F mutant mice, which are hypersensitive to c-MYC-induced tumorigenesis, are not hypersensitive to oncogenic HrasG12V-induced tumorigenesis. Unlike c-MYC, which induces expression of RPL11, RAS overexpression leads to an increase in RPL23 mRNA and protein while RPL11 expression remains unchanged. The induction of RPL23 involves both MEK and PI3K signaling pathways and requires mTOR function. Increased expression of RPL23, which maintains binding to MDM2C305F mutant, correlates with increased p53 expression in MDM2C305F cells. Furthermore, RAS overexpression can induce p53 in the absence of p19ARF, and the induction can be abolished by down-regulation of RPL23. Thus, while the RPL11-MDM2-p53 pathway coordinates with the p19ARF-MDM2-p53 pathway against oncogenic c-MYC-induced tumorigenesis, the RPL23-MDM2-p53 pathway coordinates with the p19ARF-MDM2-p53 pathway against oncogenic RAS-induced tumorigenesis

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk

Electronic structures and optical properties of monoclinic ZrO2 studied by first-principles local density approximation + U approach

Abstract The electronic structures and optical properties of the monoclinic ZrO2 (m-ZrO2) are investigated by means of first-principles local density approximation (LDA) + U approach. Without on-site Coulomb interactions, the band gap of m-ZrO2 is 3.60 eV, much lower than the experimental value (5.8 eV). By introducing the Coulomb interactions of 4d orbitals on Zr atom (U d) and of 2p orbitals on O atom (U p), we can reproduce the experimental value of the band gap. The calculated dielectric function of m-ZrO2 exhibits a small shoulder at the edge of the band gap in its imaginary part, while in the tetragonal ZrO2 and cubic ZrO2 it is absent, which is consistent with the experimental observations. The origin of the shoulder is attributed to the difference of electronic structures near the edge of the valence and conduction bands