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Abstract Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73−/− cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of Trp73 −/− (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this, Trp73 and OPA1 gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.

Abstract Since the late twentieth century, the global fashion industry has been increasingly embracing the business model known as fast fashion. Characterised by rapid production cycles, fleeting trends, low-cost garments and large-scale production, fast fashion seems to meet consumer demand for affordable and trendy clothing. However, its environmental impact as a major polluter poses significant challenges to sustainability and circularity initiatives. This article presents the results of a systematic literature review, exploring the unsustainable consequences of fast fashion, focusing on both demand and supply side, from a geographical perspective. Using a Global North–Global South framework, it explores differences in socio-economic structures, consumption and production patterns, access to resources and environmental impacts. The analysis suggests that a fair and equitable transition towards a sustainable and circular fashion industry will require the links between business, society and nature to be reconsidered, to avoid perpetuating the inequalities associated with the global linear capitalist economy. The findings highlight the importance of both markets and institutions in sustainable growth. In the Global North, the most frequently discussed topics relate to investment and research and development with respect to new technologies or system innovations often with the support of well-structured political guidance. Conversely, in the Global sustainable initiatives tend to be scattered, country-specific and intricately tied to particular socio-economic and cultural contexts.

Background Acute pulmonary embolism (PE) mortality is linked to abrupt rises in pulmonary artery (PA) pressure due to mechanical obstruction and pulmonary vasoconstriction, leading to right ventricular (RV) dilation, increased RV wall tension and oxygen demand, but compromised right coronary artery oxygen supply. Oxygen is a known pulmonary vasodilator, and in preclinical animal models of PE, supplemental oxygen reduces PA pressures and improves RV function. However, the mechanisms driving these interactions, especially in humans, remain poorly understood. The overall objective of the supplemental oxygen in pulmonary embolism (SO-PE) study is to investigate the mechanisms of supplemental oxygen in patients with acute PE.Methods and analysis This randomised, double-blind, cross-over trial at Massachusetts General Hospital will include adult patients with acute PE and evidence of RV dysfunction but without hypoxaemia (SaO2 ≥90% on room air). We will enrol 80 patients, each serving as their own control, with 40 randomised to start on supplemental oxygen, and 40 randomised to start on room air. Over 180 min, patients will alternate between supplemental oxygen delivered by non-rebreather mask (60% FiO2) and room air (21% FiO2). The primary outcome will be the difference in pulmonary artery systolic pressure with and without oxygen. Secondary outcomes include additional echocardiographic measures, metabolomic profiles, vital signs and dyspnoea scores. Echocardiographic data will be compared by a paired t-test or Wilcoxon signed-rank test. For metabolomic analyses, we will perform multivariable mixed effects logistic regression models and calculate false discovery rate (q-value ≤0.05) to account for multiple comparisons. Data will be collected in compliance with National Institutes of Health and National Heart Lung and Blood Institute (NHLBI) policies for data and safety monitoring.Ethics and dissemination The SO-PE study is funded by the NHLBI and has been approved by the Institutional Review Board of Mass General Brigham (no. 2023P000252). The study will comply with the Helsinki Declaration on medical research involving human subjects. All participants will provide prospective, written informed consent.Trial registration number NCT05891886.

ABSTRACT Purpose: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats. Methods: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein. Results: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14. Conclusion: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.

Food plant diversity in bioactive compounds makes them an exploitable resource in the search for effective natural products to prevent or treat viral infections. Therefore, in the framework aimed at studying the antiviral properties of extractive mixtures from fruits (and their waste) grown in the Campania Region (Italy), jujube drupes (Zizyphus jujuba Mill.) were our focus. The drupes were dissected into their peel, pulp and seed parts, each of which was extracted by ultrasound-assisted maceration and further fractionated, thus obtaining, beyond the sugar fraction, a polyphenolic fraction and a lipid fraction. UHPLC-HR MS/MS tools highlighted that the polyphenolic component of the seed was strongly dissimilar from that of the edible parts, being constituted by swertisin and its derivatives. Moreover, the peel mostly accounted for triglycosylated flavonols, whereas the pulp was rich in volatile aromatic glycosides. Among lipids, p-coumaroyl triterpenes mainly characterized the peel. All fractions were screened for their cytotoxicity, and non-toxic concentrations of each extract were tested against herpes simplex virus type 1 (HSV-1) by plaque assays. Molecular tests and Western blot analyses were also carried out. The jujube mixtures, in detail the peel and pulp polyphenolic fractions, and peel lipophilic fraction (the latter enriched mainly in ursane-type triterpenes), showed a marked inhibitory activity against HSV-1 acting in the early stages of viral infection and preventing attachment of the virus to the host cell. The acquired data suggest jujube active mixtures as promising candidates for the prevention and treatment of herpetic lesions.

Abstract This study presents a novel approach to obtaining nano-antimicrobial hybrid material by integrating electrospun nanofibers based on cellulosic biopolymer (BP) associated with antimicrobial agents, specifically silver nanoparticles (AgNPs) and Clavanin A (ClavA), an antimicrobial peptide obtained from the marine tunicate Styela clava. The electrospinning technique produced the blended polyvinyl alcohol:BP nanofibers. Chemical crosslinking was performed to ensure the stability of the nanofibers. The nanofibers had an average diameter of 568 nm for PVA nanofibers and 648 nm for PVA nanofibers functionalized with silver nanoparticles. The nanohybrid material demonstrates significant inhibition zones against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumoniae) bacteria. P. aeruginosa exhibits a substantial inhibition zone of 15 mm. Thus, the nanohybrid material was effective against this challenging pathogen. Combining electrospun nanofibers, bacterial cellulose hydrogel, and antimicrobial agents establishes a solution that could combat microbial threats in wound care.

Objective: Negative psychological beliefs like fear avoidance and catastrophizing can interfere with exercise engagement in people with knee osteoarthritis (OA). Mindfulness, when integrated with exercise, could potentially address both psychological and physical impairments. Our objectives were to optimize and assess the feasibility of a novel telehealth, group-based mindful exercise intervention for people with knee OA. Methods: We conducted a decentralized randomized controlled trial where participants (n ​= ​40) with symptomatic knee OA were randomized into mindful exercise (n ​= ​21) or exercise-only (n ​= ​19) groups. Both groups received supervised group-based interventions weekly for 8-weeks via Zoom. Primary outcomes were safety, fidelity, and feasibility of the mindful exercise intervention. Participants completed patient-reported outcomes (PRO) for pain, function, and psychological measures at baseline, week-8, and week-14. Results: Participants were from 21 US states; >90% identified as having White race, 16% were from rural areas, and approximately 40% had an annual income < $50,000. At 8-weeks, mindful exercise and exercise groups had retention rates of 86% (18/21) and 100% (19/19), and attendance was 54% (11.4/21) and 68% (13/19) respectively. There were no adverse events in the mindful exercise group and four in the exercise group related to exacerbation of knee pain. Preliminary findings showed numerically larger improvements in several PROs for the mindful exercise group. Conclusion: An 8-week telehealth, group-based, mindful exercise intervention was safe for people with knee OA. Our decentralized approach was feasible in terms of recruitment and retention. Further refinement is needed to improve intervention attendance and participant diversity.

We study systems in arbitrary space-time dimensions where matter, deformed by TT‾-like irrelevant operators, is coupled to gravity in the Palatini formalism. The dynamically equivalent perspective is investigated, wherein the deformation transitions from the matter action to the gravitational one or vice versa. This alternative viewpoint leads to the emergence of Ricci-based gravity theories, thus providing a high-dimensional generalisation of the well-known equivalence between two-dimensional TT‾ deformations and coupling to Jackiw-Teitelboim gravity. This dynamical equivalence is examined within the framework of the recently introduced Lagrangian flow equation, which notably led to the discovery of a direct link between Nambu-Goto theory and TT‾ in d=2, as well as significant insights into nonlinear electrodynamics models in d=4. The investigation involves explicit examples in d=4 dimensions; it builds upon earlier research concerning the metric interpretation of TT‾-like perturbations, incorporates and extends recent findings in the cosmology-related literature associated to the concept of reframing. We focus on scenarios where the resulting modified gravity theories manifest as Born-Infeld and Starobinsky types.

Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome is a rare genetic disorder characterized by variable immunodeficiency. More than half of the affected individuals show mild to severe intellectual disability at early onset. This disorder is genetically heterogeneous and ZBTB24 is the causative gene of the subtype 2, accounting for about 30% of the ICF cases. ZBTB24 is a multifaceted transcription factor belonging to the Zinc-finger and BTB domain-containing protein family, which are key regulators of developmental processes. Aberrant DNA methylation is the main molecular hallmark of ICF syndrome. The functional link between ZBTB24 deficiency and DNA methylation errors is still elusive. Here, we generated a novel ICF2 disease model by deriving induced pluripotent stem cells (iPSCs) from peripheral CD34+-blood cells of a patient homozygous for the p.Cys408Gly mutation, the most frequent missense mutation in ICF2 patients and which is associated with a broad clinical spectrum. The mutation affects a conserved cysteine of the ZBTB24 zinc-finger domain, perturbing its function as transcriptional activator. ICF2-iPSCs recapitulate the methylation defects associated with ZBTB24 deficiency, including centromeric hypomethylation. We validated that the mutated ZBTB24 protein loses its ability to directly activate expression of CDCA7 and other target genes in the patient-derived iPSCs. Upon hematopoietic differentiation, ICF2-iPSCs showed decreased vitality and a lower percentage of CD34+/CD43+/CD45+ progenitors. Overall, the ICF2-iPSC model is highly relevant to explore the role of ZBTB24 in DNA methylation homeostasis and provides a tool to investigate the early molecular events linking ZBTB24 deficiency to the ICF2 clinical phenotype.

Single-molecule intramolecular dynamics were successfully measured for three variants of SARS-CoV-2 spike protein, alpha: B.1.1.7, delta: B.1.617, and omicron: B.1.1.529, with a time resolution of 100 μs using X-rays. The results were then compared with respect to the magnitude and directions of motions for the three variants. The largest 3-D intramolecular movement was observed for the omicron variant irrespective of ACE2 receptor binding. A more detailed analysis of the intramolecular motions revealed that the distribution state of intramolecular motion for the three variants was completely different with and without ACE2 receptor binding. The molecular dynamics for the trimeric spike protein of the omicron variant increased when ACE2 binding occurred. At that time, the diffusion constant increased from 71.0 [mrad2/ms] to 91.1 [mrad2/ms].

Abstract In this article, we analyze the role of social capital in the formation of sustainable energy communities. Specifically, we study the impact of different dimensions of social capital (i.e., structural, relational, cognitive) in determining willingness to participate in an energy community. Our survey data suggest that social contexts contribute to the development of energy communities, via (at least) two channels: (i) a family path, with individual perspectives showing a partial correlation with those of at least one relative, and (ii) a social channel, with higher social trust and greater interaction with neighbors favoring the propensity to participate in an energy community. The social coordination required for the formation of sustainable energy communities is determined by the quality of social interactions, and the spread of virtuous behavior is determined by not only economic policies (i.e., incentives), but also forward-looking policies favoring local aggregation and the creation of high-quality social capital. Thus, local actions and interactions can contribute to solving global climate change challenges.

Abstract Identifying the rank of species in a complex ecosystem is a difficult task, since the rank of each species invariably depends on the interactions stipulated with other species through the adjacency matrix of the network. A common ranking method in economic and ecological networks is to sort the nodes such that the layout of the reordered adjacency matrix looks maximally nested with all nonzero entries packed in the upper left corner, called Nestedness Maximization Problem (NMP). Here we solve this problem by defining a suitable cost-energy function for the NMP which reveals the equivalence between the NMP and the Quadratic Assignment Problem, one of the most important combinatorial optimization problems, and use statistical physics techniques to derive a set of self-consistent equations whose fixed point represents the optimal nodes’ rankings in an arbitrary bipartite mutualistic network. Concurrently, we present an efficient algorithm to solve the NMP that outperforms state-of-the-art network-based metrics and genetic algorithms. Eventually, our theoretical framework may be easily generalized to study the relationship between ranking and network structure beyond pairwise interactions, e.g. in higher-order networks.