Explore the vast range of titles available.

Few phenomena have been more disruptive to West European politics and society than the accumulative experience of post-WWII immigration. Against this backdrop spring two questions: Why have the immigrant-receiving states historically permitted high levels of immigration? To what degree can the social and political fallout precipitated by immigration be politically managed? Utilizing evidence from a variety of sources, this study explores the links between immigration and the surge of popular support for anti-immigrant groups; its implications for state sovereignty; its elevation to the policy agenda of the European Union; and its domestic legacies. It argues that post-WWII migration is primarily an interest-driven phenomenon that has historically served the macroeconomic and political interests of the receiving countries. Moreover, it is the role of politics in adjudicating the claims presented by domestic economic actors, foreign policy commitments, and humanitarian norms that creates a permissive environment for significant migration to Western Europe.

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1 , PU.1 , and Klf4 . This HSC-autonomous mechanism reduces the number of wound macrophages and skews their polarization towards M1 macrophages. These findings reveal a novel inflammatory mechanism by which a metabolic disorder induces an epigenetic mechanism in HSCs, which predetermines the gene expression of terminally differentiated inflammatory cells that controls their number and function. Type 2 diabetes is associated with impaired wound healing, which can lead to limb loss. Here, the authors show that in Type 2 diabetic mouse models, Dnmt1 is upregulated in hematopoietic stem cells, leading to impaired differentiation towards macrophages, reduced macrophage infiltration in the wound and skewed M1/M2 polarization.

PurposeDeveloping stable high concentration monoclonal antibody (mAb) formulations is increasingly important to move toward subcutaneous (SC) administration for better patient experience. Challenges stemming from protein–protein interactions in these crowded solutions, such as colloidal instability, limit the feasibility of some formulations because of concerns of safety, product quality, and/or manufacturability. Herein, we report novel random heteropolymer excipients that improve the colloidal stability of a high concentration mAb formulation for SC administration.MethodsA library of polymers was synthesized and screened by a high-throughput, absorbance-based assay. The lead polymers were selected and characterized for their ability to alter the precipitation kinetics of a mAb in physiologically relevant conditions using two model systems.ResultsBiophysical testing via surface tension measurements, isothermal titration calorimetry (ITC), microscale thermophoresis (MST), and intrinsic fluorescence quenching indicated that the polymers delayed onset of mAb precipitation from a combination of surfactant behaviour and interactions with the protein to prevent protein–protein interactions leading to colloidal instability.ConclusionsThe random heteropolymers described are a new class of excipients that may enable development of SC mAb formulations previously inaccessible to patients.

The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.

Chitin, the second most abundant polysaccharide in nature after cellulose, has been the subject of increasing interest in recent years, particularly in the aquaculture sector. This review focuses on the effects of chitin in aquafeed on growth, nutrient utilization, gut microbiome modulation, and the immune system of aquatic organisms. Data from the literature showed significant variability in response to chitin by species, with some species benefiting from dietary chitin supplementation in terms of growth and immune health. However, excessive chitin inclusion led to negative effects on the protein and lipid digestibility. These results suggest that optimizing the amount of chitin-containing ingredients in aquafeed requires a deep understanding of each species’ nutritional needs and other studies needed for different aquaculture species. Furthermore, studies have highlighted the potential of chitin as an immunostimulant and promoter of gut health. In conclusion, chitin appears to be a promising additive for sustainable aquaculture, but further research is needed to define best practices for its use.

Damage of enteric neurons and partial or total loss of selective neuronal populations are reported in intestinal disorders including inflammatory bowel diseases and necrotizing enterocolitis. To develop three-dimensional scaffolds for enteric neurons we propose the decoration of ionic-complementary self-assembling peptide (SAP) hydrogels, namely EAK or EAbuK, with bioactive motives. Our results showed the ability of EAK in supporting neuronal cell attachment and neurite development. Therefore, EAK was covalently conjugated to: RGD, (GRGDSP) 4 K (fibronectin), FRHRNRKGY (h-vitronectin, named HVP), IKVAV (laminin), and type 1 Insulin-like Growth Factor (IGF-1). Chemoselective ligation was applied for the SAP conjugation with IGF-1 and the other longer sequences. Freshly isolated murine enteric neurons attached and grew on all functionalized EAK but IGF-1. Cell-cell contact was evident on hydrogels enriched with (GRGDSP) 4 K and HVP. Moreover (GRGDSP) 4 K significantly increased mRNA expression of neurotrophin-3 and nerve growth factor, two trophic factors supporting neuronal survival and differentiation, whereas IKVAV decoration specifically increased mRNA expression of acetylcholinesterase and choline acetyltransferase, genes involved in synaptic communication between cholinergic neurons. Thus, decorated hydrogels are proposed as injectable scaffolds to support in loco survival of enteric neurons, foster synaptic communication, or drive the differentiation of neuronal subtypes.

Background Dietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow’s milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow’s milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow’s milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes. Methods MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology. Results Eligibility criteria were met by 17 trials ( n  = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow’s milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow’s milk resulted in moderate reductions in non-HDL-C (mean difference, − 0.26 mmol/L [95% confidence interval, − 0.43 to − 0.10]), systolic blood pressure (− 8.00 mmHg [− 14.89 to − 1.11]), and diastolic blood pressure (− 4.74 mmHg [− 9.17 to − 0.31]); small important reductions in LDL-C (− 0.19 mmol/L [− 0.29 to − 0.09]) and c-reactive protein (CRP) (− 0.82 mg/L [− 1.26 to − 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified. Conclusions Current evidence provides a good indication that replacing cow’s milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets. Trial registration ClinicalTrials.gov identifier, NCT05637866.

Hydrocephalus is currently managed by using traditional mechanical passive shunts. Due to their nature, these shunts have fundamental shortcomings including an increase in patient shunt dependency, absence of fault detection, and over drainage due to lack of shunt proactivity. There is a scientific consensus that the way forward to address these issues is through what is termed a smart shunt. The core component of this system is the mechatronic controllable valve. A design of a valve which utilises both the passive nature of the classical valves and the controllability feature of the fully automated valves is presented in this paper. The valve consists of a fluid compartment, a linear spring, and an ultrasonic piezoelectric element. The valve is designed to operate on a 5 V supply, to drain up to 300 mL/h, and it has an operational range between 10 and 20 mmHg. The design produced is considered feasible as it takes into consideration the multiple operation conditions associated with such an implanted system.