An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis

Developing a new treatment for superficial fungal infection using antifungal Collagen-HSAF dressing

Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine-derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen-based HSAF (Col-HSAF) has a transparent appearance and good physical properties, and the in vitro sustained-release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col-HSAF against superficial fungal infection was explored, and Col-HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with Aspergillus fumigatus keratitis and cutaneous candidiasis. In conclusion, Col-HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections

Phenylthiourea Specifically Reduces Zebrafish Eye Size

Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos

Laser-Assisted Robotic Roller Forming of Ultrahigh-Strength Steel QP1180 with High Precision

Laser-assisted forming provides a perfect solution that overcomes the formability of low-ductility materials. In this study, laser-assisted robotic roller forming (LRRF) was applied to bend ultrahigh-strength steel sheet (a quenching and partitioning steel with a strength grade of 1180 MPa), and the effects of laser power density on the bending forces, springback, and bending radius of the final parts were investigated. The results show that LRRF is capable of reducing bending forces by 43%, and a compact profile with high precision (i.e., a springback angle smaller than 1° and a radius-to-thickness ratio of ~1.2) was finally achieved at a laser power density of 10 J/mm2. A higher forming temperature, at which a significant decrease in strength is observed, is responsible for the decrease of forming forces with a laser power density of higher than 7.5 J/mm2; another reason could be the heating-to-austenitization temperature and subsequent forming at a temperature above martensitic-transformation temperature. Forming takes place at a higher temperature with lower stresses, and unloading occurs at a relatively lower temperature with the recovery of Young’s modulus; both facilitate the reduction of springback angles. In addition, the sharp bending radius is considered to be attributed to localized deformation and large plastic strains at the heating area

Laser-Assisted Robotic Roller Forming of Ultrahigh-Strength Steel QP1180 with High Precision

Funding Information: This research was funded by Science and Technology Commission of Shanghai Municipality, grant number 21170711200 and General Motors collaborative research project, grant number GAC3599. Funding Information: Yi Liu would like to acknowledge the support from China Scholarship Council (Grant number: 202206260121). Publisher Copyright: © 2023 by the authors.Laser-assisted forming provides a perfect solution that overcomes the formability of low-ductility materials. In this study, laser-assisted robotic roller forming (LRRF) was applied to bend ultrahigh-strength steel sheet (a quenching and partitioning steel with a strength grade of 1180 MPa), and the effects of laser power density on the bending forces, springback, and bending radius of the final parts were investigated. The results show that LRRF is capable of reducing bending forces by 43%, and a compact profile with high precision (i.e., a springback angle smaller than 1° and a radius-to-thickness ratio of ~1.2) was finally achieved at a laser power density of 10 J/mm2. A higher forming temperature, at which a significant decrease in strength is observed, is responsible for the decrease of forming forces with a laser power density of higher than 7.5 J/mm2; another reason could be the heating-to-austenitization temperature and subsequent forming at a temperature above martensitic-transformation temperature. Forming takes place at a higher temperature with lower stresses, and unloading occurs at a relatively lower temperature with the recovery of Young’s modulus; both facilitate the reduction of springback angles. In addition, the sharp bending radius is considered to be attributed to localized deformation and large plastic strains at the heating area.Peer reviewe

Fracture Strain of Al–Si-Coated Press-Hardened Steels under Plane-Strain Bending

Press-hardened steel (PHS) is widely applied to fabricate vehicle body structures for attaining mass reduction and fuel economy without sacrificing occupant safety. The VDA bendability test is often used to characterize the fracture resistance of PHS under plane-strain bending conditions. As lightweighting continues to be a design imperative in the automotive industry, it is desirable to develop and adopt more press-hardened components with higher fracture resistance. In this work, four Al–Si-coated 22MnB5 steels with various initial thicknesses and coating weights were studied. A newly developed methodology was used to calculate the fracture limit strain under plane-strain bending. The results indicate that although the four investigated 22MnB5 steels exhibit similar tensile properties under uniaxial tension, their bending performance per the VDA 238-100 standard differs significantly. The PHS with a low coating weight possesses a higher bending angle and, hence, a larger fracture limit strain. Meanwhile, the peak bending force can be 10% higher than the PHS with a standard coating weight at the same sheet thickness. Therefore, it is expected that PHS with higher fracture strain will have the potential for lightweighting due to its enhanced resistance to fracture and higher energy absorption capability

FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7.

Amplification of chromosome 20q is frequently found in various types of human cancers, including breast cancer. The list of candidate oncogenes in 20q has expanded over the past decade. Here, we investigate whether FAM83D (family with sequence similarity 83, member D) on chromosome 20q plays any role in breast cancer development. The expression level of FAM83D is significantly elevated in breast cancer cell lines and primary human breast cancers. High expression levels of FAM83D are significantly associated with poor clinical outcome and distant metastasis in breast cancer patients. We show that ectopic expression of FAM83D in human mammary epithelial cells promotes cell proliferation, migration and invasion along with epithelial-mesenchymal transition (EMT). Ablation of FAM83D in breast cancer cells induces apoptosis and consequently inhibits cell proliferation and colony formation. Mechanistic studies reveal that overexpression of FAM83D downregulates FBXW7 expression levels through a physical interaction, which results in elevated protein levels of oncogenic substrates downstream to FBXW7, such as mTOR, whose inhibition by rapamycin can suppress FAM83D-induced cell migration and invasion. The results demonstrate that FAM83D has prognostic value for breast cancer patients and is a novel oncogene in breast cancer development that at least in part acts through mTOR hyper-activation by inhibiting FBXW7

FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7.

Amplification of chromosome 20q is frequently found in various types of human cancers, including breast cancer. The list of candidate oncogenes in 20q has expanded over the past decade. Here, we investigate whether FAM83D (family with sequence similarity 83, member D) on chromosome 20q plays any role in breast cancer development. The expression level of FAM83D is significantly elevated in breast cancer cell lines and primary human breast cancers. High expression levels of FAM83D are significantly associated with poor clinical outcome and distant metastasis in breast cancer patients. We show that ectopic expression of FAM83D in human mammary epithelial cells promotes cell proliferation, migration and invasion along with epithelial-mesenchymal transition (EMT). Ablation of FAM83D in breast cancer cells induces apoptosis and consequently inhibits cell proliferation and colony formation. Mechanistic studies reveal that overexpression of FAM83D downregulates FBXW7 expression levels through a physical interaction, which results in elevated protein levels of oncogenic substrates downstream to FBXW7, such as mTOR, whose inhibition by rapamycin can suppress FAM83D-induced cell migration and invasion. The results demonstrate that FAM83D has prognostic value for breast cancer patients and is a novel oncogene in breast cancer development that at least in part acts through mTOR hyper-activation by inhibiting FBXW7