Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

Operando X-Ray Tomoscopy of Laser Beam Welding.

The phenomena occurring in a weld seam during advancement of a laser beam over a metallic component are still under dispute. The occurrence and evolution of porosity and the occasional blowout of melt need to be understood. Here, a recently developed X-ray tomoscopy setup is applied, providing one hundred 3D images per second to capture the temporal evolution of the melt pool in an AlSi9Cu3(Fe) die-casting while a laser beam advances.

Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.

Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.

Detection of odorants in odour mixtures among healthy people and patients with olfactory dysfunction.

Target odorant detection in mixtures has been shown to become more difficult as the number of background odorants increases and falls below chance level in mixtures with 16 components. Our aim was to investigate target odorant detection in mixtures among healthy people and compare it between dysosmic patients and age- and gender-matched controls. Participants underwent extensive olfactory testing and performed two target odorant detection tasks.

Molecular Order Induced Charge Transfer in a C-Topological Insulator Moiré Heterostructure.

We synthesized and spectroscopically investigated monolayer (ML) C on the topological insulator (TI) BiTe. This C/BiTe heterostructure is characterized by an excellent translational order in a novel (4 × 4) C superstructure on a (9 × 9) cell of BiTe. Angle-resolved photoemission spectroscopy (ARPES) of C/BiTe reveals that ML C accepts electrons from the TI at room temperature, but no charge transfer occurs at low temperatures.

Mechanically stable polymer networks incorporating polymeric ionic liquids for enhanced conductivity in solid-state electrolytes.

Enhancing both ionic conductivity and mechanical robustness remains a major challenge in designing solid-state electrolytes for lithium batteries. This work presents a novel approach in designing mechanically robust and highly conductive solid-state electrolytes, which involves ionic liquid-based cross-linked polymer networks incorporating polymeric ionic liquids (PILs). First, linear PILs with different side groups were synthesized for optimizing the structure.

A Low-Symmetry Copper Benzenehexathiol Coordination Polymer with In-Plane Electrical Anisotropy.

Electrically conductive coordination polymers (ECCPs), particularly those incorporating benzenehexathiol (BHT) ligands, are emerging as a distinctive class of electronic materials with tunable semiconducting and metallic properties. However, the exploration of novel ECCPs with low-symmetry structures and electrical anisotropy remains under development. Here, we report the on-water surface synthesis of a novel ECCP, namely Cu5BHT, which exhibits a low-symmetry structure and unique in-plane electrical anisotropy that differs from the well-known Cu3BHT phase.

Heterologous Expression and Optimization of Fermentation Conditions for Recombinant Ikarugamycin Production.

Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis.

Dissociative episodes and concurrent heart rate in patients with PTSD - An ecological momentary assessment.

Dissociative symptoms are a frequent complication in posttraumatic stress disorders affecting about a third of all PTSD patients. While theoretical models predict a physiological hypoarousal during posttraumatic dissociations, empirical evidence is lacking. We addressed this by studying spontaneously occurring dissociative symptoms and related heart rate changes in an ecological momentary assessment.

Prospective Multicenter Evaluation of the MDS "Suggestive of PSP" Diagnostic Criteria.

Background: The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: "suggestive of PSP" for sensitive early diagnosis based on subtle clinical signs, "possible PSP" balancing sensitivity and specificity, and "probable PSP" highly specific for PSP pathology.

Objective: The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time.

Methods: Patients with "possible PSP" or "suggestive of PSP" diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP).

Predictive Potential of ECMO Blood Flow for Hemolysis and Outcome of Patients with Severe ARDS.

Treatment with veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a frequently considered rescue therapy in patients with severe acute respiratory distress syndrome (ARDS). Hemolysis is a common complication in patients treated with ECMO. Currently, it is unclear whether increased ECMO blood flow (Q̇) contributes to mortality and might be associated with increased hemolysis.

Transfemoral Compared to Transapical Transcatheter Aortic Valve Implantation in Chronic Dialysis-Dependent Patients.

Patients with end-stage kidney disease (ESRD) represent a high-risk population in terms of both development of and death by cardiovascular diseases. Outcome data of ESRD patients with severe aortic valve stenosis (AS) treated by transcatheter aortic valve implantation (AVI) are scarce. We aim to compare the outcome of ESRD patients undergoing transfemoral (TF) or transapical (TA) AVI.

A Survey on the Evaluation of Monosodium Glutamate (MSG) Taste in Austria.

The umami taste is well validated in Asian culture but remains less recognized and accepted in European cultures despite its presence in natural local products. This study explored the sensory and emotional perceptions of umami in 233 Austrian participants who had lived in Austria for most of their lives. Using blind tasting, participants evaluated monosodium glutamate (MSG) dissolved in water, providing open-ended verbal descriptions, pleasantness ratings, and comparisons to a sodium chloride (NaCl) solution.

Degradation Behavior of Coated Metallic Stents: Influence of In Vitro Fluid-Dynamic Biostability Testing Conditions.

Coated metallic stents are the next generation of metallic stents with improved surface properties. To evaluate the degradation behavior of stents in vitro, different in vitro degradation models can be applied: (i) static immersion test: degradation under static fluid condition, (ii) fluid dynamic test: degradation under flowing fluid, and (iii) electrochemical corrosion test: degradation under the influence of electric potential. During these experimental procedures, stents interact with the simulated blood plasma, and degradation products are formed in the form of depositions on the stent surface, likewise in vivo experiments.

A plug-and-play system for polycyclic tetramate macrolactam production and functionalization.

Background: The biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.

Phenotypic analysis of complex bioengineered 3D models.

With advances in underlying technologies such as complex multicellular systems, synthetic materials, and bioengineering techniques, we can now generate in vitro miniaturized human tissues that recapitulate the organotypic features of normal or diseased tissues. Importantly, these 3D culture models have increasingly provided experimental access to diverse and complex tissues architectures and their morphogenic assembly in vitro. This review presents an analytical toolbox for biological researchers using 3D modeling technologies through which they can find a collation of currently available methods to phenotypically assess their 3D models in their normal state as well as their response to therapeutic or pathological agents.

The associations between paternal postpartum depressive symptoms and testosterone and cortisol levels in hair over the first two years postpartum.

Background: After the birth of a child, also fathers may develop postpartum depression. Altered steroid hormone concentrations are discussed as a possible underlying mechanism, as these have been associated with depressive symptoms in previous studies outside the postpartum period. While higher paternal testosterone levels have been found to protect against paternal postpartum depressive symptoms (PPDS), an association between higher cortisol levels and PPDS has been seen in postpartum mothers, with no comparable studies available on fathers.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Correction: Chen et al. Aerogels Based on Reduced Graphene Oxide/Cellulose Composites: Preparation and Vapour Sensing Abilities. 2020, , 1729.

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Structural Investigation of Chloride Ion-Containing Acrylate-Based Imidazolium Poly(Ionic Liquid) Homopolymers and Crosslinked Networks: Effect of Alkyl Spacer and N-Alkyl Substituents.

Understanding the interplay between the molecular structure of the ionic liquid (IL) subunit, the resulting nanostructure and ion transport in polymerized ionic liquids (PILs) is necessary for the realization of high-performance solid-state electrolytes required in various advanced applications. Herein, we present a detailed structural characterization of a recently synthesized series of acrylate-based PIL homopolymers and networks with imidazolium cations and chloride anions with varying alkyl spacer and terminal group lengths designed for organic solid-state batteries based on X-ray scattering. The impact of the concentrations of both the crosslinker and added tetrabutylammonium chloride (TBACl) conducting salt on the structural characteristics is also investigated.

Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

Background And Aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design And Setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures.

Intervention strategies to prevent mental health problems and improve resilience in employed parents from conception until the child is 5 years of age: a scoping review.

Aim: To understand the extent and type of evidence in relation to the effectiveness of intervention strategies targeting working pregnant women, and their partners, for the prevention of mental health problems (depression, anxiety) and improving resilience, from conception until the child is 5 years of age.

Methods: A scoping review was conducted searching Pubmed (including Medline), Embase, Web of Science Core Collection and Scopus. Inclusion criteria were based on population (employed parents), context (from -9 months to 5 years postpartum) and concept (mental health problems, resilience and prevention/ preventative interventions).

Determinants of perceived patient benefit in a longitudinal cohort study of patients with psoriasis and atopic dermatitis.

The Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account.