Promotion of Lymphangiogenesis by Targeted Delivery of VEGF-C Improves Diabetic Wound Healing.

Chronic wounds represent a major therapeutic challenge. Lymphatic vessel function is impaired in chronic ulcers but the role of lymphangiogenesis in wound healing has remained unclear. We found that lymphatic vessels are largely absent from chronic human wounds as evaluated in patient biopsies.

Targeting NRF2 to promote epithelial repair.

The transcription factor NRF2 is well known as a master regulator of the cellular stress response. As such, activation of NRF2 has gained widespread attention for its potential to prevent tissue injury, but also as a possible therapeutic approach to promote repair processes. While NRF2 activation affects most or even all cell types, its effect on epithelial cells during repair processes has been particularly well studied.

Ultradeep characterisation of translational sequence determinants refutes rare-codon hypothesis and unveils quadruplet base pairing of initiator tRNA and transcript.

Translation is a key determinant of gene expression and an important biotechnological engineering target. In bacteria, 5'-untranslated region (5'-UTR) and coding sequence (CDS) are well-known mRNA parts controlling translation and thus cellular protein levels. However, the complex interaction of 5'-UTR and CDS has so far only been studied for few sequences leading to non-generalisable and partly contradictory conclusions.

Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency.

Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence of effective causal treatments. Here we employ multi-layered omics profiling combined with biochemical and clinical features of individuals with MMA to reveal a molecular diagnosis for 177 out of 210 (84%) cases, the majority (148) of whom display pathogenic variants in methylmalonyl-CoA mutase (MMUT). Stratification of these data layers by disease severity shows dysregulation of the tricarboxylic acid cycle and its replenishment (anaplerosis) by glutamine.

Anticipatory countering of motor challenges by premovement activation of orexin neurons.

Countering upcoming challenges with anticipatory movements is a fundamental function of the brain, whose neural implementations remain poorly defined. Recently, premovement neural activation was found outside canonical premotor areas, in the hypothalamic hypocretin/orexin neurons (HONs). The purpose of this hypothalamic activation is unknown.

Meiotic chromosome organization and its role in recombination and cancer.

Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA.

Complications related to the access site after transaxillary implantation of a microaxial left ventricular assist device.

Background: Impella 5.0 and 5.5 (summarized as Impella 5+) are microaxial, catheter-based left ventricular assist devices (LVAD) that are implanted via a vascular graft sutured to the axillary artery and provide blood flow of up to 5.

Drone-assisted collection of environmental DNA from tree branches for biodiversity monitoring.

The protection and restoration of the biosphere is crucial for human resilience and well-being, but the scarcity of data on the status and distribution of biodiversity puts these efforts at risk. DNA released into the environment by organisms, i.e.

Lithium treatment extends human lifespan: findings from the UK Biobank.

Lithium is a nutritional trace element that is also used pharmacologically for the management of bipolar and related psychiatric disorders. Recent studies have shown that lithium supplementation can extend health and lifespan in different animal models. Moreover, nutritional lithium uptake from drinking water was repeatedly found to be positively correlated with human longevity.

Global patterns of tree density are contingent upon local determinants in the world's natural forests.

Previous attempts to quantify tree abundance at global scale have largely neglected the role of local competition in modulating the influence of climate and soils on tree density. Here, we evaluated whether mean tree size in the world's natural forests alters the effect of global productivity on tree density. In doing so, we gathered a vast set of forest inventories including >3000 sampling plots from 23 well-conserved areas worldwide to encompass (as much as possible) the main forest biomes on Earth.

Antibody-Mediated Delivery of VEGF-C Promotes Long-Lasting Lymphatic Expansion That Reduces Recurrent Inflammation.

The lymphatic vascular system plays a fundamental role in inflammation by draining interstitial fluid, immune cells, antigens, and inflammatory mediators from peripheral tissues. Site-specific delivery of the lymphangiogenic growth factor VEGF-C alleviates acute inflammation in mouse models of psoriasis and chronic colitis by enhancing local drainage. However, it is unclear whether therapeutically induced lymphangiogenesis is transient or long-lasting and whether it might prevent relapses of inflammation.

Microbial population dynamics decouple growth response from environmental nutrient concentration.

How the growth rate of a microbial population responds to the environmental availability of chemical nutrients and other resources is a fundamental question in microbiology. Models of this response, such as the widely used Monod model, are generally characterized by a maximum growth rate and a half-saturation concentration of the resource. What values should we expect for these half-saturation concentrations, and how should they depend on the environmental concentration of the resource? We survey growth response data across a wide range of organisms and resources.

Leaflet-splitting device to prevent coronary artery obstruction in valve-in-valve transcatheter aortic valve implantation.

Coronary artery obstruction is a life-threatening complication of transcatheter aortic valve replacement procedures, and current preventive strategies are suboptimal. The novel ShortCut device splits bioprosthetic valve leaflets that are at risk of causing coronary artery obstruction after transcatheter aortic valve implantation, allowing for normal coronary flow. In this video tutorial, we demonstrate a valve-in-valve transcatheter aortic valve implantation using a dedicated leaflet-splitting device for prevention of coronary artery obstruction in transcatheter aortic valve replacement.

Electrochemical-based approaches for the treatment of forever chemicals: Removal of perfluoroalkyl and polyfluoroalkyl substances (PFAS) from wastewater.

Electrochemical based approaches for the treatment of recalcitrant water borne pollutants are known to exhibit superior function in terms of efficiency and rate of treatment. Considering the stability of Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are designated as forever chemicals, which generating from various industrial activities. PFAS are contaminating the environment in small concentrations, yet exhibit severe environmental and health impacts.

A contemporary reassessment of the enhanced transient expression system based on the tombusviral silencing suppressor protein P19.

Transient transgenic expression accelerates pharming and facilitates protein studies in plants. One embodiment of the approach involves leaf infiltration of Agrobacterium strains whose T-DNA is engineered with the gene(s) of interest. However, gene expression during 'agro-infiltration' is intrinsically and universally impeded by the onset of post-transcriptional gene silencing (PTGS).

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

Background: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice.

Results: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro.

Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.

During development, cell state transitions are coordinated through changes in the identity of molecular regulators in a cell type- and dose-specific manner. The ability to rationally engineer such transitions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein, we report the generation of synthetic gene circuits that can detect a desired cell state using AND-like logic integration of endogenous miRNAs (classifiers) and, upon detection, produce fine-tuned levels of output proteins using an miRNA-mediated output fine-tuning technology (miSFITs).

Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold.

Proper sensing of ambient temperature is of utmost importance for the survival of euthermic animals, including humans. While considerable progress has been made in our understanding of temperature sensors and transduction mechanisms, the higher-order neural circuits processing such information are still only incompletely understood. Using intersectional genetics in combination with circuit tracing and functional neuron manipulation, we identified Kcnip2-expressing inhibitory (Kcnip2) interneurons of the mouse spinal dorsal horn as critical elements of a neural circuit that tunes sensitivity to cold.

Rapid homeostatic modulation of transsynaptic nanocolumn rings.

Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization and how synaptic nano-architecture is transsynaptically regulated to enable stable synaptic transmission remain enigmatic.

Plasticity of the adult human small intestinal stoma microbiota.

The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine.

Selection of a PD-1 blocking antibody from a novel fully human phage display library.

Programmed cell death protein 1 (PD-1) is an immunoregulatory target which is recognized by different monoclonal antibodies, approved for the therapy of multiple types of cancer. Different anti-PD-1 antibodies display different therapeutic properties and there is a pharmaceutical interest to generate and characterize novel anti-PD-1 antibodies. We screened multiple human antibody phage display libraries to target novel epitopes on the PD-1 surface and we discovered a unique and previously undescribed binding specificity (termed D12) from a new antibody library (termed AMG).

Single-Center Experience With a Self-Expandable Venous Cannula During Minimally Invasive Cardiac Surgery.

Objective: Venous drainage is often problematic in minimally invasive cardiac surgery (MICS). Here, we describe our experience with a self-expandable stent cannula designed to optimize venous drainage.

Methods: The was used in 58 consecutive patients undergoing MICS for mitral valve disease ( = 40), left atrial myxoma ( = 3), left ventricular outflow tract obstruction ( = 1), and aortic valve replacement via a right anterior minithoracotomy ( = 14) procedures.

Open Ablation of the Left Ventricle During Implantation of a Left Ventricular Assist Device.

This report describes the successful treatment of persistent ventricular tachycardia in a 66-year-old patient with ischemic cardiomyopathy during left ventricular assist device (LVAD) implantation. Recurrent episodes of ventricular tachycardia led to cardiac decompensation necessitating LVAD implantation. After opening the left ventricle, an AtriCure Isolator Synergy OLL2 radiofrequency clamp was used to perform 4 sets of transmural lesions.