Thus, ERF1 may act as a negative modulator of flowering-time control by repressing FT transcription in Arabidopsis.The word 'metabolism' is derived from the Greek word μεταβολή (metabolē), denoting 'change'. True to this definition, it is now appreciated that a cell or tissue cannot change its behaviour without altering its metabolism. Hence, most key cell decision-making processes are tightly coupled to metabolic change. Conversely, perturbations in metabolite abundance or flux can alter cellular (and whole-body) function profoundly, giving rise to disease. This Special Issue on Systemic and Cellular Metabolism and Disease provides an integrative perspective on the importance of metabolism for health and disease alike. Spanning several orders of scale (from metabolites, proteins, organelles, organs/tissues and whole-body physiology), these review articles cover a breadth of topics, including the importance of metabolites as signalling regulators, metabolic disease, immunity, organelle function/dysfunction, ageing and neurodegenerative disease. One of the emergent themes is that just as metabolism is the fulcrum of biology, metabolic perturbances underpin most forms of acute, chronic, infectious and non-infectious human disease; ageing and senescence could be similarly viewed. Reversan in vivo Arguably most diseases are metabolic diseases; hence, modulating metabolism may help to 'change' disease outcomes. Meckel's diverticulum (MD) is the most common congenital malformation in the gastrointestinal tract. Limited up-to-date evidence is available regarding MD in pregnancy. We aim to review the available pertinent literature to help support clinical decision making and patient management in the future. The search term 'Meckel's diverticulum' was combined with 'pregnant' or 'pregnancy'. Database searches of EMBASE, Medline and PubMed were conducted. All papers published in English from 01/01/1990 to 01/01/2021 were included. Simple statistical analysis (t-test) was performed. Twenty-seven cases were included. Average age=26.9 years. Average gestation=25.1 weeks. Occurrence first trimester=3.7%; second trimester=48.1% and third trimester=48.1%. Presenting symptoms abdominal pain 88.9%; nausea/vomiting 59.3%; fever 18.5%; abdominal distension 18.5%; haematochezia 11.1%; constipation 11.1%; haematemesis 3.7%, diarrhoea 3.7% and asymptomatic 3.7%. Mean duration of preceding symptoms=3.4 days. Diagnostic imaging on.MD and associated pathology are difficult to diagnose in the pregnant cohort. Current imaging demonstrates low diagnostic accuracy and a deviation away from recognised nuclear medicine investigations. Surgery appears the definitive management with both open and laparoscopic approaches utilised. Significant maternal morbidity and foetal mortality are associated with this condition. Prior studies of telehealth report high levels of patient satisfaction, but within carefully selected clinical scenarios. The COVID-19 pandemic led to telehealth replacing face-to-face care for many surgical consultations across a variety of situations. More evidence is needed regarding patient perceptions of telehealth in surgery, in particular, exploring barriers and facilitators associated with its sustained implementation beyond the pandemic. Survey invitations were emailed to a convenience sample of surgical patients by their surgeon following a telehealth consultation during the COVID-19 pandemic. Surgeons were recruited from a sample (n=683) who completed a survey on telehealth (distributed via email to all Australian Fellows of the Royal Australasian College of Surgeons). Mixed methods analysis was performed of the patient survey data. A total of 1166 consultations were captured 50% routine reviews, 17% initial appointments and 20% post-operative reviews. Video-link was used in 49% of consultations. The majority of patients (94%), were satisfied with the quality of their surgical telehealth consultation and 75% felt it delivered the same level of care as face-to-face encounters. Telehealth was convenient to use (96%) and led to cost savings for 60% of patients. When asked about future appointment preferences after the pandemic, 41% indicated they would prefer telehealth (24% video-link and 17% telephone) over face-to-face appointments. There was a perception by patients that telehealth consultation fees should be less than face-to-face consultation fees. Patient satisfaction with surgical telehealth consultations is high. Barriers to more widespread implementation include financial, clinical appropriateness, technical and confidentiality concerns.Patient satisfaction with surgical telehealth consultations is high. Barriers to more widespread implementation include financial, clinical appropriateness, technical and confidentiality concerns.Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8+ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma-released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector-like tumor-specific CD8+ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD-L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD-L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD-L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber) (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC2 -H2 O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2 O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95-99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.