S2 Data Figures

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of seven transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is upregulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here it controls oxygen consumption, cell proliferation and the formation of reactive oxygen species by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human induced pluripotent stem cells, reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signalling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism thar cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.</p

Image1_Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker.TIF

Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer.Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The “survival” and “GSVA” package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model.Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared.Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer.</p

Urethral stricture formation under urethroscopy.

<p>A Urethroscopy of rabbit in D_H group. Note no significant urethral stricture formation and F13 urethroscopy could easily pass through. B Urethroscopy of rabbit in D_L group. Note urethral stricture formation and F13 urethroscopy could hardly pass through. C Urethroscopy of rabbit in C group. Note severe urethral stricture formation, stopping F13 urethroscopy pass through.</p

Urethral diameter and lumen reduction of rabbits in different treated groups.

<p>•Normal referred to diameter of urethra 1 cm distal to the injured site of all rabbits in this study.</p><p>*<i>P</i> = 0.218 compared to D_L, <i>P</i><0.01 compared to C and Normal.</p><p>**<i>P</i><0.01 compared to C and Normal.</p><p>***<i>P</i><0.01 compared to Normal.</p>#<p><i>P</i> = 0.010 compared to D_L, <i>P</i><0.01 compared to C.</p>##<p><i>P</i><0.01 compared to C.</p><p>Urethral diameter and lumen reduction of rabbits in different treated groups.</p

Urethral cross section at stricture sites (hematoxylin and eosin staining) Original magnifications, 400×.

<p>A Urethral cross section of rabbit in D_H group. Note little fibrosis tissue around urethral epithelium. B Urethral cross section of rabbit in D_L group. Note fibrosis formation around submucosa layer. C Urethral cross section of rabbit in C group. Note wide fibrous tissues distributed from epithelium to muscular layer.</p

Representative microphotographs of urethral cross section at stricture site (stained by Sirius red).

<p>A Urethral cross section of rabbit in D_H group. Note a large urethral lumen with light submucosa collagen staining. B Urethral cross section of rabbit in D_L group. Note large urethral lumen with light submucosa collagen staining. C Urethral cross section of rabbit in C group. Note almost atresic urethra with deep collagen staining.</p

Field-Effect Transistors Based on van-der-Waals-Grown and Dry-Transferred All-Inorganic Perovskite Ultrathin Platelets

Nowadays, the research on perovskite transistors is still in its infancy, despite the fact that perovskite-based solar cells and light-emitting diodes have been widely investigated. Two major hurdles exist before obtaining reliable perovskite-based transistors: the processing difficulty for their sensitivity to polar solvents and unsatisfactory perovskite quality on the transistor platform. Here, for the first time, we report on high-performance all-inorganic perovskite FETs profiting from both van der Waals epitaxial boundary-free ultrathin single crystals and completely dry-processed transfer technique without chemical contaminant. These two crucial factors ensure the unprecedented high-quality perovskite channels. The achieved FET hole mobility and on–off ratio reach 0.32 cm² V^–1 s^–1 and 6.7 × 10³, respectively. Moreover, at the low temperature, the mobility and on–off ratio can be enhanced to be 1.04 cm² V^–1 s^–1 and 1.3 × 10⁴. This work could open the door for the FET applications based on perovskite single crystals

Preoperative risk assessments.

<p>Preoperative risk assessments.</p

Demographic and clinical characteristics of study patients.

<p>Demographic and clinical characteristics of study patients.</p

X-ray images of the right femoral neck fracture in a 72-year old male patient with chronic renal failure before and after hemiarthroplasty.

<p>(A) Preoperative imaging shows compression fractures on the femoral neck of the right hip and shortening deformity of the femoral neck. (B) Representative images taken 6 months after right femoral head arthroplasty. (C) At 24 months of follow-up, the prosthesis was in the correct position. On subsequent X-ray images, there were no further changes.</p