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Cells that lack p53 signaling frequently occur in ulcerative colitis (UC) and are considered early drivers in UC-associated colorectal cancer (CRC). Epithelial injury during colitis is associated with transient stem cell reprogramming from the adult, homeostatic to a "fetal-like" regenerative state. Here, we use murine and organoid-based models to study the role of Trp53 during epithelial reprogramming. We find that p53 signaling is silent and dispensable during homeostasis but strongly up-regulated in the epithelium upon DSS-induced colitis. While in WT cells this causes termination of the regenerative state, crypts that lack Trp53 remain locked in the highly proliferative, regenerative state long-term. The regenerative state in WT cells requires high Wnt signaling to maintain elevated levels of glycolysis. Instead, Trp53 deficiency enables Wnt-independent glycolysis due to overexpression of rate-limiting enzyme PKM2. Our study reveals the context-dependent relevance of p53 signaling specifically in the injury-induced regenerative state, explaining the high abundance of clones lacking p53 signaling in UC and UC-associated CRC.

Background: Breast implants (BI) are widely used in plastic surgery, though they are not lifetime devices. Average life before rupture is reported to be around 10-15 years. No consensus exists regarding which factors are involved., Objectives: Following FDA recommendations, this study aims at identifying potential risk factors by evaluating their effect on BI rupture cases., Methods: In this observational study, 763 BI patients were operated between 2003 and 2019, with a mean implant indwelling of 12.2 years. Patients that returned for follow-up were administered a questionnaire regarding postoperative lifestyle and habits. Implant rupture rate was 15.1%, while BI lifespan was 10.1 years. We obtained complete data from 191 breast implant patients (288 implants). Twenty-three potential risk factors were evaluated and divided in four categories: patient-related, surgery-related, postoperative complications/symptoms, and postoperative care/lifestyle habits. Odds Ratio (OR) for each factor was calculated. Linear regression analysis was calculated for those with a significant OR., Results: We report 120 patients (195 implants) with intact and 71 (93 implants) with ruptured devices. BIs were macrotextured in 95.1% of cases (86.8% Allergan BIOCELL). OR was significant for underwire bra use (OR: 2.708), car seat belts (OR: 3.066), mammographic imaging (OR: 2.196), weightlifting (OR: 0.407) and carry-on heavy purses and backpacks (OR: 0.347)., Conclusion: Wearing underwire bras, seat belts and undergoing mammography increases the risk of rupture. Weightlifting and carry heavy bags do not increase that risk. Implant rupture is directly linked with time of indwelling. Postoperative recommendations in BI patients should consider findings from our study, though larger multicenter studies should be encouraged., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. The Author(s).)

Heterogeneous palladium catalysts modified by N-heterocyclic carbenes (NHCs) are shown to be highly effective toward the direct synthesis of hydrogen peroxide (H 2 O 2 ), in the absence of the promoters which are typically required to enhance both activity and selectivity. Catalytic evaluation in a batch regime demonstrated that through careful selection of the N-substituent of the NHC it is possible to greatly enhance catalytic performance when compared to the unmodified analogue and reach concentrations of H 2 O 2 rivaling that obtained by state-of-the-art catalysts. The enhanced performance of the modified catalyst, which is retained upon reuse, is attributed to the ability of the NHC to electronically modify Pd speciation.

LncRNAs have been recently implicated in the epigenetic control of muscle differentiation and their functional characterization has traditionally relied upon in vitro models of myogenic differentiation. However, the use of experimental paradigms to specifically target lncRNAs expression in muscle stem cells (MuSCs), also known as satellite cells, represents an important requisite to interrogate their function in more physiological contexts. Since isolation and culture of single myofibers preserves satellite cells within their physiological niche underneath the surrounding basal lamina, this procedure represents the optimal approach to follow satellite cell dynamics ex-vivo , such as activation from quiescence, expansion of committed progenitors, differentiation, and self-renewal. Here, we detail an optimized protocol to isolate viable single myofibers from the extensor digitorum longus (EDL) skeletal muscle of adult mice and to manipulate the expression of lncRNAs by antisense LNA GapmeRs-mediated knock-down (KD). Furthermore, we describe a method of EdU incorporation that, coupled to lncRNA KD and subsequent immunofluorescence analysis of proliferating, differentiating, and satellite cell-specific markers, permits the inference of lncRNAs function on muscle stem cells dynamics. Graphic abstract: Graphical representation of the single myofiber isolation method. Experimental workflow showing the main steps of the protocol procedure: EDL muscle harvesting from the mouse hindlimb; EDL digestion into single myofibers; transfection with antisense oligos and culture for 96h; immunofluorescence protocol and image outcome., Competing Interests: Competing interestsThe authors declare that no competing interests exist., (Copyright © The Authors; exclusive licensee Bio-protocol LLC.)

Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cell (MuSC) activity. This ability requires the proper balance between MuSC expansion and differentiation, which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated long noncoding RNA (lncRNA), Lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, Lnc-Rewind acts as an epigenetic regulator of MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct Lnc-Rewind target. We show that Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs., Competing Interests: AC, MM, GB, TS, BB, GP, AC, CM, MB No competing interests declared, (© 2021, Cipriano et al.)

Objective: To provide an overview of the currently available risk prediction models (RPMs) for cardiovascular diseases (CVDs), diabetes and hypertension, and to compare their effectiveness in proper recognition of patients at risk of developing these diseases., Design: Umbrella systematic review., Data Sources: PubMed, Scopus, Cochrane Library., Eligibility Criteria: Systematic reviews or meta-analysis examining and comparing performances of RPMs for CVDs, hypertension or diabetes in healthy adult (18-65 years old) population, published in English language., Data Extraction and Synthesis: Data were extracted according to the following parameters: number of studies included, intervention (RPMs applied/assessed), comparison, performance, validation and outcomes. A narrative synthesis was performed. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Study Selection: 3612 studies were identified. After title/abstract screening and removal of duplicate articles, 37 studies met the eligibility criteria. After reading the full text, 13 were deemed relevant for inclusion. Three further papers from the reference lists of these articles were then added., Study Appraisal: The methodological quality of the included studies was assessed using the AMSTAR tool., Risk of Bias in Individual Studies: Risk of Bias evaluation was carried out using the ROBIS tool., Results: Sixteen studies met the inclusion criteria: six focused on diabetes, two on hypertension and eight on CVDs. Globally, prediction models for diabetes and hypertension showed no significant difference in effectiveness. Conversely, some promising differences among prediction tools were highlighted for CVDs. The Ankle-Brachial Index, in association with the Framingham tool, and QRISK scores provided some evidence of a certain superiority compared with Framingham alone., Limitations: Due to the significant heterogeneity of the studies, it was not possible to perform a meta-analysis. The electronic search was limited to studies in English and to three major international databases (MEDLINE/PubMed, Scopus and Cochrane Library), with additional works derived from the reference list of other studies; grey literature with unpublished documents was not included in the search. Furthermore, no assessment of potential adverse effects of RPMs was carried out., Conclusions: Consistent evidence is available only for CVD prediction: the Framingham score, alone or in combination with the Ankle-Brachial Index, and the QRISK score can be confirmed as the gold standard. Further efforts should not be concentrated on creating new scores, but rather on performing external validation of the existing ones, in particular on high-risk groups. Benefits could be further improved by supplementing existing models with information on lifestyle, personal habits, family and employment history, social network relationships, income and education., Prospero Registration Number: CRD42018088012., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The solvent-free selective hydrogenation of nitrobenzene was carried out using a supported AuPd nanoparticles catalyst, prepared by the modified impregnation method (M Im ), as efficient catalyst >99% yield of aniline (AN) was obtained after 15 h at 90 °C, 3 bar H₂ that can be used without any further purification or separation, therefore reducing cost and energy input. Supported AuPd nanoparticles catalyst, prepared by M Im , was found to be active and stable even after four recycle experiments, whereas the same catalyst prepared by S Im was deactivated during the recycle experiments. The most effective catalyst was tested for the chemoselective hydrogenation of 4-chloronitrobenzene (CNB) to 4-chloroaniline (CAN). The activation energy of CNB to CAN was found to be 25 kJ mol -1 , while that of CNB to AN was found to be 31 kJ mol -1 . Based on this, the yield of CAN was maximized (92%) by the lowering the reaction temperature to 25 °C.