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The cytokine interleukin-6 (IL-6) is involved in a diverse set of physiological processes. Traditionally, IL-6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL-6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion. In this context, IL-6 enables muscle-organ crosstalk, facilitating a coordinated response to help maintain muscle energy homeostasis, while also having anti-inflammatory actions. The range of actions of IL-6 can be explained by its dichotomous signaling pathways. Classical signaling involves IL-6 binding to a cell-surface receptor (mbIL-6R; present on only a small number of cell types) and is the predominant signaling mechanism during exercise. Trans-signaling involves IL-6 binding to a soluble version of its receptor (sIL-6R), with the resulting complex having a much greater half-life and the ability to signal in all cell types. Trans-signaling drives the inflammatory actions of IL-6 and is the predominant pathway in disease. A single nucleotide polymorphism (rs2228145) on the IL-6R gene can modify the classical/trans-signaling balance through increasing the levels of sIL-6R. This SNP has clinical significance, having been linked to inflammatory conditions such as rheumatoid arthritis and type 1 diabetes, as well as to the severity of symptoms experienced with COVID-19. This review will describe how acute exercise, chronic training and the rs2228145 SNP can modify the IL-6 signaling pathway and the consequent implications for health and athletic performance.

If humanity has any hope of tackling climate change, it needs to take action in this decade, sustainability researcher Kimberly Nicholas tells Richard Webb – and that challenges every aspect of howsociety works

Former central banker Mark Carney has turned his attention to the economics of the climate crisis. Solving it means realigning the values of financial markets with the values of society, he tells Richard Webb

Where once he sought to unmask the mysteries of the multiverse, Max Tegmark now has his sights on artificial intelligence. He talks to Richard Webb about cosmology, consciousness and how to make AI work for everyone

Physicists are limbering up for their greatest trick yet – explaining how decision-making beings like you and me fit into the cosmic order, says Richard Webb

An enigmatic mirror world could finally resolve the greatest mystery of our own – why it exists, says Richard Webb

The calcified cartilage zone (CCZ) is a thin interlayer between the hyaline articular cartilage and the subchondral bone and plays an important role in maintaining the joint homeostasis by providing biological and mechanical support from unmineralized cartilage to the underlying mineralized subchondral bone. The hallmark of CCZ characteristics in osteoarthritis (OA) is less well known. The aim of our study is to evaluate the structural, molecular, and biochemical composition of CCZ in tissues affected by primary knee OA and its relationship with disease severity. We collected osteochondral tissue samples stratified according to disease severity, from 16 knee OA patients who underwent knee replacement surgery. We also used meniscectomy-induced rat samples to confirm the pathophysiologic changes of human samples. We defined the characteristics of the calcified cartilage layer using a combination of morphological, biochemical, proteomic analyses on laser micro-dissected tissue. Our results demonstrated that the Calcium/Phosphate ratio is unchanged during the OA progression, but the calcium-binding protein and cadherin binding protein, as well as carbohydrate metabolism-related proteins, undergo significant changes. These changes were further accompanied by thinning of the CCZ, loss of collagen and proteoglycan content, the occurrence of the endochondral ossification, neovasculature, loss of the elastic module, loss of the collagen direction, and increase of the tortuosity indicating an altered structural and mechanical properties of the CCZ in OA. In conclusion, our results suggest that the calcified cartilage changes can reflect the disease progression.

Holographic near-eye displays can deliver high-quality three-dimensional (3D) imagery with focus cues. However, the content resolution required to simultaneously support a wide field of view and a sufficiently large eyebox is enormous. The consequent data storage and streaming overheads pose a big challenge for practical virtual and augmented reality (VR/AR) applications. We present a deep-learning-based method for efficiently compressing complex-valued hologram images and videos. We demonstrate superior performance over the conventional image and video codecs.

We study the action of the homeomorphism group of a surface $S$ on the fine curve graph ${\mathcal C }^\dagger(S)$. While the definition of $\mathcal{C}^\dagger(S)$ parallels the classical curve graph for mapping class groups, we show that the dynamics of the action of ${\mathrm{Homeo}}(S)$ on $\mathcal{C}^\dagger(S)$ is much richer: homeomorphisms induce parabolic isometries in addition to elliptics and hyperbolics, and all positive reals are realized as asymptotic translation lengths. When the surface $S$ is a torus, we relate the dynamics of the action of a homeomorphism on $\mathcal{C}^\dagger(S)$ to the dynamics of its action on the torus via the classical theory of rotation sets. We characterize homeomorphisms acting hyperbolically, show asymptotic translation length provides a lower bound for the area of the rotation set, and, while no characterisation purely in terms of rotation sets is possible, we give sufficient conditions for elements to be elliptic or parabolic., 30 pages, 3 figures

Introduction: We carried out systematic review and network meta-analysis to investigate the role of stem cell therapy (SCT) in the management of erectile dysfunction (ED) secondary to cavernous nerve injury in rats and post-radical prostatectomy (RP) in humans. Patients and Methods: The protocol was registered with PROSPERO database. We searched studies analyzing the efficacy of SCT for ED due to bilateral cavernous nerve injury (BCNI) in rats using Healthcare Databases Advanced Search (HDAS) Export software (MEDLINE, EMBASE, Scopus) from inception to September 2020. The outcome measurements, for 29 animal studies, were intracavernosal pressure (ICP), ICP/MAP (mean arterial pressure) ratio, and histological/molecular changes. All three available human trials evaluating SCT in post-RP ED were assessed for International Index for Erectile Function (IIEF) Score and Erection Hardness Score (EHS). Results: For ICP measurement, animal studies were divided into adipose-derived stem cells (ADSCs) subgroup and bone marrow–derived stem cells (BMSCs) subgroup. Pooled analysis of these studies showed a beneficial effect of SCT in improving erectile function in rats with BCNI using network meta-analysis (95% confidence interval, CI; p Conclusion: Our results confirm that SCT does improve the erectile function in rats having cavernous nerve injury. Similarly, early human results have shown promising results. PROSPERO registration ID: CRD42020201343.

Fabiola Gianotti is leading CERN, the biggest particle physics lab on the planet, through difficult times. Scientific collaboration has never been more vital, she tells Richard Webb

The solar system's most majestic planet is also its most mysterious – and may even have enabled life on Earth. By Leah Crane and Richard Webb

Britain has been breaking up with the continent for an age. Richard Webb tells the untold story of when it first bid adieu.

The nonsensical result of a thought experiment may mean that quantum theory has a fatal flaw, says Richard Webb

Chronic systemic inflammation is a risk factor for cardiovascular (CV) disease (CVD). Whether this relationship extends to subclinical inflammation, quantified by values of circulating markers associated with inflammation in the high range of the normal interval, remains debatable. This narrative review evaluates evidence exploring this relationship. A review of pharmacological and non-pharmacological interventions, including diet and lifestyle strategies, supplements, nutraceuticals, and other natural substances aimed at reducing inflammation was also conducted, since few reviews have synthesized this literature. PubMed and EMBASE were used to search the literature and several well-studied triggers of inflammation [oxidized LDL, Lp(a), as well as C-reactive protein (CRP)/high-sensitivity CRP (hs-CRP)] were included to increase sensitivity and address the lack of existing reviews summarizing their influence in the context of inflammation. All resulting references were assessed. Overall, there is good data supporting associations between circulating hs-CRP and CV outcomes. However, the same was not seen in studies evaluating triggers of inflammation, such as oxidized LDL or Lp(a). There is also insufficient evidence showing treatments to target inflammation and lead to reductions in hs-CRP result in improvements in CV outcomes, particularly in those with normal baseline levels of hs-CRP. Regarding pharmacological interventions, statins, bempedoic acid, and apabetalone significantly reduce circulating hs-CRP, unlike PCSK-9 inhibitors. A variety of natural substances and vitamins were also evaluated and none reduced hs-CRP. Regarding non-pharmacological interventions, weight loss was strongly associated with reductions in circulating hs-CRP, whereas various dietary interventions and exercise regimens were not, unless accompanied by weight loss.

The neutralization of strongly alkaline pH conditions and acceleration of mineral weathering in alkaline Fe ore tailings have been identified as key prerequisites for eco-engineering tailings-soil formation for sustainable mine site rehabilitation.

Background: Previous research has reported that elite Gaelic football players’ carbohydrate (CHO) intakes are sub-optimal, especially, in the lead up to competitive matches. Despite clear decrements in running performance across elite Gaelic football matches, there are no studies that have investigated nutrition interventions on match-related Gaelic football performance. The aim of this study was to determine whether a higher-CHO diet in line with sports nutrition guidelines can improve Gaelic football-related performance compared to lower CHO intakes previously observed in Gaelic footballers. Methods: Twelve Gaelic football players completed a Gaelic football simulation protocol (GFSP) on two occasions after consuming a high-CHO diet (7 g·kg−1) (HCHO) or an energy-matched lower-CHO diet (3.5 g·kg−1) (L-CHO) for 48 h. Movement demands and heart rate were measured using portable global positioning systems devices. Countermovement jump height (CMJ) and repeated-sprint ability (RSA) were measured throughout each trial. Expired respiratory gases were collected throughout the trial using a portable gas analyser. Blood samples were taken at rest, half-time, and post-simulation. Results: There was no significant difference in total distance (p = 0.811, η2 = 0.005) or high-speed running distance (HSRD) covered between both trials. However, in the second half of the HCHO trial, HSRD was significantly greater compared to the second half of the LCHO trial (p = 0.015). Sprint distance covered during GFSP was significantly greater in HCHO (8.1 ± 3.5 m·min−1) compared with LCHO (6.4 ± 3.2 m·min−1) (p = 0.011, η2 = 0.445). RSA performance (p &lt, 0.0001, η2 = 0.735) and lower body power (CMJ) (p &lt, η2 = 0.683) were significantly greater during the HCHO trial compared to LCHO. Overall CHO oxidation rates were significantly greater under HCHO conditions compared to LCHO (3.3 ± 0.5 vs. 2.7 ± 0.6 g·min−1) (p &lt, 0.001, η2 = 0.798). Blood lactate concentrations were significantly higher during HCHO trial versus LCHO (p = 0.026, η2 = 0.375). There were no significant differences in plasma glucose, non-esterified fatty acids (NEFAs), and glycerol concentration between trials. In both trials, all blood metabolites were significantly elevated at half-time and post-trial compared to pre-trial. Conclusion: These findings indicate that a higher-CHO diet can reduce declines in physical performance during simulated Gaelic football match play.

We're reliant on specialist knowledge to guide us through the coronavirus pandemic – so it is more important than ever to understand what expertise is and where it comes from, Roger Kneebone tells Richard Webb

Deformities of the external ear can affect psychosocial well-being and hearing. Current gold-standard reconstructive treatment is autologous costal cartilage grafting despite the vast morbidity profile. Tissue engineering using stem cells and 3D printing can create patient-specific reconstructed auricles with superior cosmetic outcomes and reduced morbidity. This review critically analyses recent and breakthrough research in the field of regenerative medicine for the pinna, considering gaps in current literature and suggesting further steps to identify whether this could be the new gold-standard.A literature review was conducted. PubMed (MEDLINE) and Cochrane databases were searched using key terms regenerative medicine, tissue engineering, 3D printing, biofabrication, auricular reconstruction, auricular cartilage, chondrocyte, outer ear and pinna. Studies in which tissue-engineered auricles were implanted into animal or human subjects were included. Exclusion criteria included articles not in English and not published within the last ten years. Titles, abstracts and full texts were screened. Reference searching was conducted and significant breakthrough studies included.8 studies, 6 animal and 2 human, were selected for inclusion. Strengths and weaknesses of each are discussed. Common limitations include a lack of human studies, small sample sizes and short follow-up times.Regenerative medicine holds significant potential to improve auricular reconstruction. To date there are no large multi-centred human studies in which tissue-engineered auricles have been implanted. However, recent human studies suggest promising results, raising the ever-growing possibility that tissue engineering is the future of auricular reconstruction. We aim to continue developing knowledge in this field.