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A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase
Abstract An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first established sex- and brain-region-specific microRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific microRNA expression changes during aging. We identified three sex-independent brain aging microRNAs (miR-146a-5p, miR-155-5p, and miR-5100). For miR-155-5p, we showed that these expression changes are driven by aging microglia and target mTOR signaling pathway components and other cellular communication pathways. In this work, we identify strong sex-brain-region-specific aging microRNAs and microglial miR-155-5p as a promising therapeutic target.
Knowledge, attitudes, and practices regarding metabolic associated fatty liver disease (MAFLD) in elderly patients
Prolonged normothermic perfusion of the kidney prior to transplantation: a historically controlled, phase 1 cohort study
Abstract Kidney transplantation is the preferred treatment for end-stage renal disease and is limited by donor organ availability. Normothermic Machine Perfusion (NMP) might facilitate safe transplantation of marginal organs. NKP1 is a single centre, phase 1, 36-patient, three-stage cohort study investigating the safety and feasibility of up to 24 hours of renal NMP prior to transplantation. 30-day graft survival (primary endpoint) was 100%. Secondary objectives were assessment of the effect of NMP on post-transplant clinical outcomes and ischaemia-reperfusion injury, identification of predictive biomarkers, and characterisation of the performance of the preservation system. Clinical outcomes were comparable to a matched control cohort with 12-month estimated glomerular filtration rate (eGFR) 46.3 vs 49.5 mL/min/1.73m 2 (p = 0.44) despite much longer total preservation times (15.7 vs 8.9 hours controls, p < 0.0001). We saw strong correlations between biomarkers measured ex-situ and post-transplant outcomes, including graft function at one year (correlation between GST-Pi delta and 12-month eGFR, R = 0.54, p = 0.001). Renal NMP is useful for optimising logistics and as an organ assessment technique, and has potential to expand the donor pool. Trial registration number: ISRCTN13292277.
Predictors of incomplete childhood vaccination in four West African countries: a population based cross-sectional study
CREATE: cell-type-specific cis-regulatory element identification via discrete embedding
In vitro, genomic characterization and pre-clinical evaluation of a new thermostable lytic Obolenskvirus phage formulated as a hydrogel against carbapenem-resistant Acinetobacter baumannii
Abstract The urgent threat of carbapenem-resistant Acinetobacter baumannii (CRAB) necessitates the development of new antimicrobial strategies. Bacteriophage (phage) therapy is one of the most promising alternative strategies that can be implemented to combat multidrug-resistant (MDR) bacterial infections. Herein, an A. baumannii phage VB_AB_Acb75 that exhibited lytic activity against 6 CRAB isolates (21.43%) with stability at up to 70 °C, pH 2–12, and high concentrations of organic solvents was isolated and characterized. The transmission electron microscope (TEM) detected a tailed phage with an icosahedral head and contractile tail (myoviral morphotype). The Oxford nanopore sequencing results showed an A. baumannii phage genome size of 45,487 bp, a G + C content of 38%, and 42 open reading frames (ORFs). The phylogenetic analysis, ORF, and TEM analysis indicated that A. baumannii phage VB_AB_Acb75 belongs to a novel species in the Obolenskvirus genus. Furthermore, the phage-loaded Carbopol 940 hydrogel was preclinically evaluated for wound healing effectiveness in the burn-wound animal model infected with the CRAB isolate. The histology findings showed a marked improvement in wound healing through a thick epidermal layer and the formation of well-organized fibrous connective tissue covered by a scab at the site of injury, as well as the ability to eliminate CRAB infection, as compared to the control group. In conclusion, based on in vitro, physicochemical properties, and preclinical findings, the phage-loaded hydrogel is expected to be a promising candidate for clinical evaluation against CRAB-associated skin infections.
Carbon fibre production using an ecofriendly water-soluble precursor
A combined model for short-term traffic flow prediction based on variational modal decomposition and deep learning
Abstract The emergence of Deep Learning provides an opportunity for traffic flow prediction. However, uncertainty and volatility exhibited by nonlinearity and instability of traffic flow pose challenges to Deep Learning models. Therefore, a combined prediction model, VMD-GAT-MGTCN, based on variational modal decomposition (VMD), graph attention network (GAT), and multi-gated attention time convolutional network (MGTCN) is proposed to enhance short-term traffic flow prediction accuracy. In the VMD-GAT-MGTCN, VMD decomposes traffic flow data to obtain the modal components, the GAT and MGTCN are integrated to design the spatio-temporal feature model to obtain the temporal and spatial features of traffic flow. The predicted value of traffic flow modal components by spatio-temporal feature model are stacked to obtain the ultimate traffic flow prediction results. The simulation experiments with the compared models and the baseline models show that the VMD-GAT-MGTCN have superior prediction accuracy and effect. It also verifies the enhancement effect of the VMD algorithm on the prediction performance of the VMD-GAT-MGTCN and the good prediction results obtained by the VMD-GAT-MGTCN in the traffic flow mutation region.
High performance relaxor ferroelectric textured ceramics for electrocaloric refrigeration
A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
Abstract Non-transfusion-dependent iron overload is the result of excessive dietary iron absorption, most commonly caused in populations of European descent by the genetic disorder HFE-related hemochromatosis (HH). In this disorder, hyperabsorption of 3–5 mg of iron per day cannot be counterbalanced by the typical passive elimination of 1–2 mg of iron each day into the feces by the shedding of enterocytes. Therefore, the current standard of care for most HH individuals who develop iron overload is to undergo systemic iron reduction with induction-phase phlebotomy therapy followed by long-term maintenance phlebotomy therapy. Unfortunately, long-term compliance with a regular phlebotomy regimen is less than 25% in some clinical settings. BBI-001 is a non-absorbed, oral therapeutic that binds dietary iron in the gut, preventing absorption and promoting iron elimination in the feces. The safety and efficacy of BBI-001 was confirmed in a single ascending dose, double-blind, Phase 1b clinical trial NCT05238207 (14/02/2022) in patients with iron deficiency. No treatment-related adverse events occurred for single doses of up to 2000 mg of BBI-001. The study also established proof-of-mechanism since BBI-001 significantly reduced the absorption of iron isotopes from breakfast meals compared to placebo. BBI-001 was most effective in subjects who hyperabsorbed iron (> 3 mg) on placebo, suggesting an ability to normalize iron absorption in at-risk patients. This study supports the further evaluation of BBI-001 as a safe pharmaceutical alternative to lifelong therapeutic phlebotomy.
Plasmonic coffee-ring biosensing for AI-assisted point-of-care diagnostics
Abstract A major challenge in addressing global health issues is developing simple, affordable biosensors with high sensitivity and specificity. Significant progress has been made in at-home medical detection kits, especially during the COVID-19 pandemic. Here, we demonstrated a coffee-ring biosensor with ultrahigh sensitivity, utilizing the evaporation of two sessile droplets and the formation of coffee-rings with asymmetric nanoplasmonic patterns to detect disease-relevant proteins as low as 3 pg/ml, under 12 min. Experimentally, a protein-laden droplet dries on a nanofibrous membrane, pre-concentrating biomarkers at the coffee ring. A second plasmonic droplet with functionalized gold nanoshells is then deposited at an overlapping spot and dried, forming a visible asymmetric plasmonic pattern due to distinct aggregation mechanisms. To enhance detection sensitivity, a deep neural model integrating generative and convolutional networks was used to enable quantitative biomarker diagnosis from smartphone photos. We tested four different proteins, Procalcitonin (PCT) for sepsis, SARS-CoV-2 Nucleocapsid (N) protein for COVID-19, Carcinoembryonic antigen (CEA) and Prostate-specific antigen (PSA) for cancer diagnosis, showing a working concentration range over five orders of magnitude. Sensitivities surpass equivalent lateral flow immunoassays by over two orders of magnitude using human saliva samples. The detection principle, along with the device, and materials can be further advanced for early disease diagnostics.