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BACKGROUND: Arteriovenous malformations (AVMs) are characteristic of hereditary hemorrhagic telangiectasia. Loss-of-function mutations in the activin receptor-like kinase 1 (Alk1) are linked to hemorrhagic telangiectasia type 2. METHODS: Endothelial-specific deletion of Alk1, endothelial lineage tracing, transcriptomics of single-cell analysis, and electron microscopy were performed to examine the vascular phenotype and characteristics of ALK1-deficient endothelial cells (ECs) after EC-specific Alk1 deletion. Ischemia assays were used to examine the cell capacity for vascular malformation. Connectivity Map with transcriptomic analysis was applied to identify chemical compounds. Specific methods for arteriovenous malformations, such as micro-computed tomography, with other molecular and cell biological tools were also performed. RESULTS: We performed endothelial-specific deletion of Alk1 in mice and found severe arteriovenous malformations and vascular leakage. The transcriptomics of single-cell analysis revealed a new distinctive cell cluster formed after Alk1 deletion where the cells coexpressed arterial and lymphatic endothelial markers. The analysis projected that these cells potentially originated from arterial ECs after Alk1 deletion. This new population was referred to as arterial-lymphatic-like ECs according to its cellular markers, and its appearance was validated in the pulmonary small arteries after Alk1 deletion. Transplantation of these cells caused vascular malformations. Endothelial lineage tracing confirmed that these new arterial-lymphatic-like ECs were derived from ALK1 depleted ECs, potentially arterial ECs. We discovered that SOX17 (SRY-box transcription factor 17) induction was responsible for the derivation of these arterial-lymphatic-like ECs. We showed that direct binding of MDM2 (mouse double minute 2) was required for Sox17 to execute this activity. Inhibition of MDM2 reduced the arteriovenous malformations in the mouse model. CONCLUSIONS: Together, our studies revealed the mechanistic underpinnings of ALK1 signaling in regulating the endothelial phenotype and provided possibilities for new therapeutic strategies in hemorrhagic telangiectasia type 2.

Cerebral arteriovenous malformations (AVMs) are the most common vascular malformations worldwide and the leading cause of hemorrhagic strokes that may result in crippling neurological deficits. Here, using recently generated mouse models, we uncovered that cerebral endothelial cells (ECs) acquired mesenchymal markers and caused vascular malformations. Interestingly, we found that limiting endothelial histone deacetylase 2 (HDAC2) prevented cerebral ECs from undergoing mesenchymal differentiation and reduced cerebral AVMs. We found that endothelial expression of HDAC2 and enhancer of zeste homolog 1 (EZH1) was altered in cerebral AVMs. These alterations changed the abundance of H4K8ac and H3K27me in the genes regulating endothelial and mesenchymal differentiation, which caused the ECs to acquire mesenchymal characteristics and form AVMs. This investigation demonstrated that the induction of HDAC2 altered specific histone modifications, which resulted in mesenchymal characteristics in the ECs and cerebral AVMs. The results provide insight into the epigenetic impact on AVMs.

Anneliese Lilienthal,1 Lisette Farias,1 Anne-Marie Boström,2– 4 Ann-Helen Patomella,1,5 Eric Asaba1,3,6 1Department of Neurobiology, Care Science and Society (NVS), Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 2Department of Neurobiology, Care Science and Society (NVS), Division for Nursing, Karolinska Institutet, Stockholm, Sweden; 3Unit for Research, Education, Development and Innovation, Stockholms Sjukhem Foundation, Stockholm, Sweden; 4Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden; 5Academic Primary Health Care Centre (APC), Stockholm Region, Sweden; 6Department of Health and Rehabilitation, University of Gothenburg, Gothenburg, SwedenCorrespondence: Anneliese Lilienthal, Department of Neurobiology, Care Sciences, and Society, Division of Occupational Therapy, Karolinska Institutet, Huddinge, 141 83, Sweden, Email Anneliese.Lilienthal@ki.seBackground: The care of older persons is facing several challenges, especially as care tasks are becoming increasingly rationalized with less opportunity for relational engagement between nurse assistants and older persons. Evidence suggests this engagement is needed to promote well-being and satisfaction among the older persons with whom they work. The aim of this study was to explore how care, in the context of worker perspectives, is understood and experienced in home or residential care facilities.Participants and Methods: Focus-group interviews were conducted with experienced nursing assistants (n = 14) working in urban municipalities in Sweden. Data were analyzed using reflexive thematic analysis.Findings: The main theme: “This work is more than a checklist of tasks, it’s like simultaneous mind puzzles”, exposes the shortcomings of a “task and time” oriented care system while expecting individualized relational care practices. Three subthemes emerged: “It’s about responsibility, not remuneration”, “Knowing them is part of the job” and “We do a lot that is not our job”. Participants expressed working responsibly day-to-day to find solutions to meet the needs of older persons. Tensions experienced between task and relational care orientations align to variation in understandings of care. These subthemes highlight that their work requires being context-sensitive to adapt in the moment, much like trying to solve mind puzzles.Conclusion: Increased rationalization of care, while expecting focus on relational aspects, sets nursing assistants in a challenging position. This paradox negatively affects the health of nursing assistants by creating unsustainable work. Without recognition of the required cognitive engagement in problem solving that is part of their work, the challenges of retention, sick leave and burnout are unlikely to be addressed. To ensure coordinated continuative care for older persons, nursing assistants need time and agency to enact relational practices that facilitate doing their work’s dynamic care puzzles.Keywords: assistant nurse, homecare, residential care, work, relational care, fundamental care

Background and objective: Toxicity from local salvage therapy for radiorecurrent prostate cancer (PCa) remains a concern. This phase 2 study evaluates the outcomes of salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA). Methods: Men with biochemically relapsed, biopsy-proven PCa following definitive radiotherapy underwent whole- or partial-gland sTULSA (NCT03350529). Prostate-confined recurrence was confirmed by MRI and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT). The primary endpoints were safety (Clavien-Dindo classification) and efficacy (prostate-specific antigen [PSA], PSMA PET-CT, and MRI-targeted biopsy at 12 mo). The secondary endpoints included functional and survival outcomes. Key findings and limitations: Thirty-nine patients underwent sTULSA (64% whole gland), with a median age of 73 yr (interquartile range [IQR]: 69–77) and PSA of 3.3 ng/ml (IQR: 2–6.2). Three patients had undergone prior salvage therapy, 16 were receiving hormonal therapy at enrollment, and 12 had a history of transurethral interventions. Eighteen patients had incidental urethral strictures on baseline cystoscopy. Over a median follow-up of 40 mo (IQR: 24–55), 56% experienced adverse events. Severe genitourinary toxicity (Clavien-Dindo ≥3 or hospitalization) occurred in 28%, including three patients with puboprostatic fistulas and two patients requiring cystectomy. Leak-free continence was maintained in 53%. At 12 mo, 89% showed no cancer in the targeted area, with a median PSA reduction of 95% (p

Research has shown students' study motivation is complex and demanding. It also asserts that teachers' perceptions and attitudes are decisive, complex, and demanding because they need to make many choices about planning and handling lessons and review their fundamental beliefs about study motivation. We aimed to describe teachers' perceptions of students' study motivation. We collected the data from nine focus-group interviews with 26 Swedish teachers in five primary schools. Through reflexive thematic analysis, the following six themes of perceptions emerged: emotions, teachers, teaching, learning environment, family and friends, and health and well-being. Although many teachers assumed students have more intrinsic than extrinsic motivation, they described more extrinsic motivation factors. Changing factors of importance for study motivation are primarily background factors, things needed to feel and function in everyday life, such as good health, friends, and functioning relationships. The study's results make an important contribution to understanding teachers as a starting point for understanding their didactic choices and how these choices can affect students, as well as how teaching could be changed to correspond more closely to students' needs and conditions.

Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.

Bone morphogenetic protein (BMP) signaling is intricately involved in adipose tissue development. BMP7 together with BMP4 have been implicated in brown adipocyte differentiation but their roles during adipose development have been difficult to fully specify. Matrix Gla protein (MGP) is an effective inhibitor of both BMP4 and BMP7, and is expressed in adipose endothelial and progenitor cells. Global and cell-specific Mgp gene deletion in combination with RNA analysis, immunostaining, thermogenic activity, and in vitro studies revealed that MGP directs brown adipose tissue development at two essential steps. Endothelial-derived MGP limits the triggering of white adipogenic differentiation in the perivascular region of brown adipose tissue (BAT), whereas MGP derived from adipose cells supports the transition of CD142-expressing progenitor cells to brown adipogenic maturity. Both steps were important to optimize the thermogenic function of BAT. In addition, MGP derived from the respective locations impacted the adipose vascular growth. The reduction of MGP in either endothelial or adipose cells expanded the endothelial cell population, suggesting that MGP is a factor in the overall plasticity of adipose tissue. Thus, MGP models a dual and cell-specific function in BAT, essentially creating a "cellular shuttle" that drives the brown adipogenic differentiation in coordination with vascular growth during development.

Abstract Porphyrin-based metal-organic frameworks (MOFs) are gaining traction for various applications due to their sorption, optoelectronic and catalytic properties. MOFs with Zr-based nodes constitute a particularly robust and versatile class of MOFs in which incorporation of metals into the porphyrin core allows further tuning of their physico-chemical properties. However, significant challenges regarding the phase-pure synthesis of Zr-porphyrin MOFs have slowed down progress in the field. Synthetic challenges in targeted phase formation originate from the densely populated phase space, due to energetically similar framework topologies accessible from the same building blocks, but also from the lack of detailed synthetic information. This Perspective discusses different synthetic approaches and detailed synthesis investigations to gain a deeper understanding while providing strategies towards suitable conditions to access phase-pure Zr-porphyrin MOFs. Transparent data reporting and holistic consideration of synthetic factors may allow for better control of these aspects. This is crucial for the establishment of structure–property relationships in such materials and will facilitate the realisation of their application potential.

Abstract Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets. Compatible mutants appear to follow structural and biophysical logic that permits intra-protein and paralogous expansion of the biosensor pool. We then apply our method to uncouple target engagement from divergent cellular activities of MutT homolog 1 (MTH1) inhibitors, dissect Nudix hydrolase 15 (NUDT15)-associated thiopurine metabolism with the R139C pharmacogenetic variant, and profile the dynamics of poly(ADP-ribose) polymerase 1/2 (PARP1/2) binding and DNA trapping by PARP inhibitors (PARPi). Further, PARP1-derived biosensors facilitated high-throughput screening for PARP1 binders, as well as multimodal ex vivo analysis and non-invasive tracking of PARPi binding in live animals. This approach can facilitate holistic assessment of drug-target engagement by bridging drug binding events and their biological consequences.

Arctic terrestrial invertebrate biodiversity is generally poorly known, but the archipelago of Svalbard has one of the most up-to-date inventories of its terrestrial and freshwater faunas of any Arctic region, offering a baseline for long term monitoring of invertebrate communities in space and time. Since the most recent review of the Svalbard invertebrate fauna was produced in 2014, knowledge of this fauna has developed and this inventory is here critically revised and updated. Our aims are (1) to critically review the inventory based on current taxonomic knowledge, (2) publish the complete species inventory, including cross-referencing to the relevant publications, in an open access data archive (GBIF), and (3) highlight the particular advantages that working in Svalbard may bring for scientists working on terrestrial, freshwater, and cryospheric environments. The inventory contains a total 1091 valid species names or interim names. A gap analysis in the Barcode of Life Data Systems reveals that 50% of the species currently documented from Svalbard lack COI (Cytochrome c oxidase subunit 1) barcode reference sequences in this database. Gaps in our knowledge of the Svalbard fauna and how these may be resolved are discussed.

Abstract Objectives To assess the role of ultrasensitive PSA values (usPSA) after radical prostatectomy in predicting the subsequent biochemical recurrence (BCR). Material and methods The study included 1836 patients who underwent open or robot‐assisted RP at Turku University Hospital between 2003 and 2018. Exclusion criteria involved patients with adjuvant treatments and those who did not reach a PSA nadir

It is well-known that a key to promoting students' mathematics learning is to provide opportunities for problem solving and reasoning, but also that maintaining such opportunities in student-teacher interaction is challenging for teachers. In particular, teachers need support for identifying students' specific difficulties, in order to select appropriate feedback that supports students' mathematically founded reasoning without reducing students' responsibility for solving the task. The aim of this study was to develop a diagnostic framework that is functional for identifying, characterising, and communicating about the difficulties students encounter when trying to solve a problem and needing help from the teacher to continue the construction of mathematically founded reasoning. We describe how we reached this aim by devising iterations of design experiments, including 285 examples of students' difficulties from grades 1-12, related to 110 tasks, successively increasing the empirical grounding and theoretical refinement of the framework. The resulting framework includes diagnostic questions, definitions, and indicators for each diagnosis and structures the diagnostic process in two simpler steps with guidelines for difficult cases. The framework therefore has the potential to support teachers both in eliciting evidence about students' reasoning during problem solving and in interpreting this evidence.

Glucocorticoid-induced bone loss is a severe and toxic effect of long-term therapy with glucocorticoids, which are currently prescribed for millions of people worldwide. Previous studies have uncovered that glucocorticoids reciprocally converted osteoblast lineage cells into endothelial-like cells to cause bone loss and showed that the modulations of Foxc2 and Osterix were the causative factors that drove this harmful transition of osteoblast lineage cells. Here, we find that the inhibition of aurora kinase A halts this transition and prevents glucocorticoid-induced bone loss. We find that aurora A interacts with the glucocorticoid receptor and show that this interaction is required for glucocorticoids to modulate Foxc2 and Osterix. Together, we identify a new potential approach to counteracting unwanted transitions of osteoblast lineage cells in glucocorticoid treatment and may provide a novel strategy for ameliorating glucocorticoid-induced bone loss.

Background: Readmission can be be related to the work of several stakeholders involved in the care of individuals throughout the community, including, for example, primary care and social care providers. A narrative review was performed to assess definitions and frequency of readmission for older adults found in previous research. In addition, a dataset for a cohort of older adults in Stockholm, Sweden, was used to quantify how different definitions of readmission affect frequency. Materials and Methods: The review was based on pre-specified search criteria within PubMed and Embase databases. All studies based on a cohort of older adults with a primary objective to assess readmission to inpatient care, were included for the assessment of readmission criteria. The dataset was based on a cohort of older adults treated at a geriatric department in Stockholm during 2016. Estimations of readmission were performed with the most common criteria found in the narrative review. Results: The narrative review showed that definitions of readmission included predominantly time-based criteria, either alone or combined with additional criteria such as medical condition or readmitting department. Frequency of readmission based on different definitions varied substantially; a 14-day time interval implied a rate of 8.0% whilst a 30-day interval—more commonly used—rendered a rate of 12.6%. The density of readmissions per day was higher during the first weeks after discharge, and then dropped continuously. Conclusion: Transparency on definitions is imperative in studies that include rates of readmission. The levels of readmission rates are highly dependent on the study population and its context. Furthermore, the actual value of readmission monitoring is dependent on what purpose it is supposed to fulfill, and it is essential to put it into context of all relevant stakeholders including, for example, the primary care providers and different social care providers throughout the community.

Background Frail older adults constitute a significant vulnerable group with complex healthcare needs requiring collaboration between various care providers and professions. Despite this requirement, there are considerable knowledge gaps in how to achieve effective collaboration. Preventive measures such as addressing pressure ulcers, falls, malnutrition and poor oral health often receive low priority compared with treating diseases or injuries. This study aims to enhance our understanding of how care collaboration in the preventive care process (PcP) using the Senior alert (SA) register could improve patient safety and equality of care for frail older adults in Sweden.Methods This study, conducted over 4 years, employs an explanatory mixed methods design, divided into three phases. The study protocol comprises the two first phases.Phase 1 (quantitative) Data from SA (2019–2021) will be analysed to compare municipalities regarding the quality of registration in the PcP. Municipalities with high and low compliance indices will be identified and analysed together with data on demographics, socioeconomics and organisation from Statistics Sweden.Phase 2 (qualitative) Focus group interviews will be conducted in residential care units in the municipalities identified in phase 1 with interprofessional teams and older persons/next of kin. Additionally, 30 semi-structured individual interviews with residential care managers and other relevant stakeholders will explore obstacles and opportunities for effective care collaboration.Discussion We foresee that the results will contribute to the development of a model for effective PcP and care collaboration that can be used to improve patient safety and quality of care for frail older adults. This model can be tested and upscaled to achieve a more effective and equitable healthcare system.Ethics and dissemination The study has been approved by the Swedish ethical review authority. Dissemination plans involve publications, data deposition and engagement with healthcare stakeholders to ensure the practical application of the findings.

Sport-related injuries have been reported to occur in around one-third of agility dogs. Higher bar height in competitions has been shown to increase odds of an injury. This study evaluated the effect of bar height on the kinetics and kinematics at take-off to a bar jump. Forces from fore- and hindlimb pairs were measured with force plates. A three-dimensional motion capture system was used to measure sagittal joint kinematics of the shoulder, elbow, carpus, hip, stifle, and tarsal joints, as well as limb coordination, trunk horizontal velocity, take-off distance, and take-off angle. Data were collected for 17 Border Collies at three different bar heights: 80%, 100%, and 120% of wither height. A linear mixed model was used for statistical analysis. At higher bar height, decelerative impulses were greater and accelerative impulses decreased along with greater vertical impulses from forelimb and hindlimb pairs (p

The motivation to study may affect students' successes and setbacks in their studies. Research has shown that multiple factors affect students' motivation to study. The purpose of this article is to describe how students conceptualize the motivation to study. We gathered empirical data through group interviews with 32 Swedish students in six study programs. Through phenomenographical analyses, we identified six categories of how students experience the motivation to study: the importance of teachers, the subject, student characteristics and attitude, study results, and support from friends and family and the environment. Within each category, we distinguished various aspects. Differences in conceptions between students and programs or types of programs exist, but they are small. Only students from study preparation programs emphasized the importance of student characteristics and attitude for increasing study motivation and getting good jobs. The study's results show both general and distinctive content in the meaning of study motivation. We make recommendations to develop incentives for all students, not just those who have favourable socio-economic study conditions, to develop motivational strategies to study.

Differentiation trajectory from ECs to EC-like myofibroblasts and myofibroblasts may pass through a mesenchymal stage. This trajectory exists in a quiescent state in healthy lungs and may be activated when pathological stimuli trigger pulmonary fibrosis. https://bit.ly/3QWfgyS

Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induced β-catenin and reduced mothers against DPP homolog 1 (SMAD1) in order to redirect osteoblast-like cells towards endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency and diabetic Ins2Akita/wt mice. Here, we report that GSK3β inhibition or endothelial-specific deletion of GSK3β reduces atherosclerotic calcification. We also find that alterations in β-catenin and SMAD1 induced by GSK3β inhibition in the aortas of Apoe-/- mice are similar to Mgp-/- mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in atherosclerotic lesions through a similar mechanism to that in Mgp-/- mice.

Glucocorticoid-induced bone loss is a toxic effect of long-term therapy with glucocorticoids resulting in a significant increase in the risk of fracture. Here, we find that glucocorticoids reciprocally convert osteoblast-lineage cells into endothelial-like cells. This is confirmed by lineage tracing showing the induction of endothelial markers in osteoblast-lineage cells following glucocorticoid treatment. Functional studies show that osteoblast-lineage cells isolated from glucocorticoid-treated mice lose their capacity for bone formation but simultaneously improve vascular repair. We find that the glucocorticoid receptor directly targets Foxc2 and Osterix, and the modulations of Foxc2 and Osterix drive the transition of osteoblast-lineage cells to endothelial-like cells. Together, the results suggest that glucocorticoids suppress osteogenic capacity and cause bone loss at least in part through previously unrecognized osteoblast-endothelial transitions.

The lack of fully trained teachers is a national challenge in Sweden despite numerous attempts by authorities to approach the issue from a long-term perspective. The proportion of fully trained teachers needs to increase by just over 50% by 2035, and the imbalance will continue for many years to come. Many actors such as the media and politicians have participated in the debate, but not those who are significantly forced to handle, control, and lead in resolving the current situation and who have an overview of the problems at a structural level, namely, the school authorities (school authority in the school system according to the Education Act (Skollagen 2010: 800) can be a municipality, county council, state, or individual who is responsible for the activities in the school. In this text, the most responsible head of a municipality in the educational department has responded to the survey). This study covers 55 school authorities' views on national tendencies and possibilities of solving this problem using an enactment policy theory. The empirical data are based on a web survey and analyzed through thematic content analysis. The result shows deep concerns about the accelerated problem, the challenges of finding fully trained teachers, and negative attitudes toward the profession. Possible solutions are higher salaries, flexible solutions to becoming teachers, higher status, and better working environments. The school authorities' perceptions of possible solutions are to some extent consistent with ongoing political initiatives. Neither do they emphasize an overall picture of the working conditions for teachers, nor the far-reaching consequences of all political reforms. In summary, their actions are interpreted as quite re-active, nonlinear, and ad hoc solutions and less proactive perceptions and actions. This can possibly be explained by the fact that the state sets limits on economic initiatives.

Abstract Ocean waves have the potential to contribute to future renewable electricity production. A wave energy converter (WEC) is a technology developed to absorb the energy of the wave and convert it to another form of energy. The Uppsala University WEC (UU WEC) is a point absorber with a direct drive permanent magnet synchronous linear generator power take off. Among other parameters affecting the value of absorbed power for UU WEC are the buoy size, mass of the system consisting of the buoy and translator, and available wave energy at the site of interest. This study reviews the earlier static model that considered only static forces as the buoyancy and gravity forces and neglected all dynamic forces. The static model was proposed to simplify the early‐stage design decision. Although the static model was applied to two UU WECs of different dimensions, the present study shows that the static model is not held for certain buoy and translator dimensions. As an alternative, the dynamic model which accounts for the impact of hydrodynamic forces and various translator masses is proposed. The dynamic model is based on Cummins' equation and the linear potential flow theory, and the damping force is approximated as a viscous damper with the constant damping coefficient optimizing the absorbed mechanical power under a particular sea condition. The dynamic model is applied to four fixed buoy geometries of two shapes (cylinder and cylinder with a moonpool), each of two different dimensions, but the method can be extended to other buoy shapes and dimensions. In addition, the impact of translator mass was assessed for two sites located on the west coast of Sweden and near Gran Canaria, Spain. A translator of 10–11 t promotes 16.8% higher annual average power absorption for a cylindrical buoy compared to a translator of 6 t for the same buoy. However, heavier translators up to 15 t provide only 1.1% increase in average annual absorbed power.

Abstract Understanding the origin of superconductivity in correlated two-dimensional materials is a key step in leveraging material engineering techniques for next-generation nanoscale devices. While it is widely accepted that phonons fluctuations only mediate conventional (s-wave) superconductivity, the common phenomenology of superconductivity in Bernal bilayer and rhombohedral trilayer graphene, as well as in a large family of graphene-based moiré systems, suggests a common superconducting mechanism across these platforms. In particular, in all these platforms some superconducting regions violate the Pauli limit, indicating unconventional superconductivity, naively ruling out conventional phonon-mediated pairing as the underlying mechanism. Here we combine first principles simulations with effective low-energy theories to investigate the superconducting mechanism and pairing symmetry in rhombohedral stacked graphene multilayers. We find that phonon-mediated superconductivity explains the main experimental findings, namely the displacement field and doping level dependence of the critical temperature, and the presence of two superconducting regions with different pairing symmetries that depend on the parent normal state. In particular, we find that intra-valley phonon scattering favors a triplet f-wave pairing when combined with electronic correlations stabilizing a spin- and valley-polarized normal state. We also propose a so far unexplored superconducting region at higher hole doping densities n h ≈ 4 × 1012 cm−2, and demonstrate how this highly hole-doped regime can be reached in heterostructures consisting of monolayer α-RuCl3 and rhombohedral trilayer graphene. Our findings promote phonon-mediated pairing as a strong contender to explain superconductivity across a wide range of graphene platforms, and demonstrate that phonons can, in fact, stabilize unconventional superconducting orders.

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.