Reductive Alkenylation of Ketimines via Hydride Transfer from Aldehydes.

The first direct -heterocyclic carbene (NHC)-catalyzed preparation of allylic amines bearing a quaternary center (α-tertiary amine) from isatin-derived ketimines in the presence of vinyl selenones and aldehydes is reported. This multicomponent reaction is expected to proceed via unprecedented in situ reduction of imines through a hydride transfer from the aldehydes.

Metabolic fingerprint of patients showing responsiveness to treatment of septic shock in intensive care unit.

Objective: An early metabolic signature associated with the responsiveness to treatment can be useful in the better management of septic shock patients. This would help clinicians in designing personalized treatment protocols for patients showing non-responsiveness to treatment.

Methods: We analyzed the serum on Day 1 (n = 60), Day 3 (n = 47), and Day 5 (n = 26) of patients with septic shock under treatment using NMR-based metabolomics.

Cardiac P MR spectroscopy: development of the past five decades and future vision-will it be of diagnostic use in clinics?

In the past five decades, the use of the magnetic resonance (MR) technique for cardiovascular diseases has engendered much attention and raised the opportunity that the technique could be useful for clinical applications. MR has two arrows in its quiver: One is magnetic resonance imaging (MRI), and the other is magnetic resonance spectroscopy (MRS). Non-invasively, highly advanced MRI provides unique and profound information about the anatomical changes of the heart.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: , pharmacokinetic, and studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer changing mRNA levels of apoptosis-related proteins.

Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach.

Variation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies.

An iron(ii)-based metalloradical system for intramolecular amination of C(sp)-H and C(sp)-H bonds: synthetic applications and mechanistic studies.

A catalytic system for intramolecular C(sp)-H and C(sp)-H amination of substituted tetrazolopyridines has been successfully developed. The amination reactions are developed using an iron-porphyrin based catalytic system. It has been demonstrated that the same iron-porphyrin based catalytic system efficiently activates both the C(sp)-H and C(sp)-H bonds of the tetrazole as well as azide-featuring substrates with a high level of regioselectivity.

How Does Literacy Affect Speech Processing? Not by Enhancing Cortical Responses to Speech, But by Promoting Connectivity of Acoustic-Phonetic and Graphomotor Cortices.

Previous research suggests that literacy, specifically learning alphabetic letter-to-phoneme mappings, modifies online speech processing and enhances brain responses, as indexed by the BOLD, to speech in auditory areas associated with phonological processing (Dehaene et al., 2010). However, alphabets are not the only orthographic systems in use in the world, and hundreds of millions of individuals speak languages that are not written using alphabets.

Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?

Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer's disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a "prion-like" manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration.

RGS11-CaMKII complex mediated redox control attenuates chemotherapy-induced cardiac fibrosis.

Dose limiting cardiotoxicity remains a major limiting factor in the clinical use of several cancer chemotherapeutics including anthracyclines and the antimetabolite 5-fluorouracil (5-FU). Prior work has demonstrated that chemotherapeutics increase expression of R7 family regulator of G protein signaling (RGS) protein-binding partner Gβ, which drives myocyte cytotoxicity. However, though several R7 family members are expressed in heart, the exact role of each protein in chemotherapy driven heart damage remains unclear.

Transition-Metal-Catalyzed Denitrogenative Annulation to Access High-Valued N-Heterocycles.

Over the past few years, the development of efficient methods to construct high-valued N-heterocyclic molecules have received massive attention owing to their extensive application in the areas of medicinal chemistry, drug discovery, natural product synthesis and so on. To access those high-valued N-heterocycles, many methods have been developed. In this context, transition-metal-catalyzed denitrogenative annulation of 1,2,3-triazoles and 1,2,3,4-tetrazoles has appeared as a powerful synthetic tool because it offers a step- and atom-economical route for the preparation of the nitrogen-rich molecules.

Sinonasal mucosal melanomas: defining profiles for better survival outcomes.

Background: Sinonasal mucosal melanoma is an aggressive malignancy with a 5-year survival rate ranging from 20% to 39%. Despite the evolving surgical and radiotherapy techniques, and introduction of immune-checkpoint inhibitor therapy, overall survival rates remain poor.

Methodology: A retrospective cohort study was conducted at the Hospital Clinic de Barcelona and the Hospital de la Santa Creu i Sant Pau between 1984 and 2020; primary outcome measures were 3 and 5-year melanoma-specific survival (MSS).

Self-assembled dipeptide based fluorescent nanoparticles as a platform for developing cellular imaging probes and targeted drug delivery chaperones.

Self-assembled peptide-based nanostructures, comprised of naturally occurring amino acids, display excellent biocompatibility, biodegradability, flexible responsiveness, and synthetic feasibility and can be customized for various biomedical applications. However, the lack of inherent optical properties of peptide-based nanoparticles is a limitation on their use as imaging probes or drug delivery vehicles. To overcome this impediment, we generated Boc protected tyrosine-tryptophan dipeptide-based nanoparticles (DPNPs) with structure rigidification by Zn(ii), which shifted the peptide's intrinsic fluorescent properties from the ultraviolet to the visible range.

Fabrication of self-assembled nanostructures for intracellular drug delivery from diphenylalanine analogues with rigid or flexible chemical linkers.

Self-assembly of molecular building blocks is a simple and useful approach to generate supramolecular structures with varied morphologies and functions. By studying the chemical properties of the building blocks and tuning the parameters of their self-assembly process, the resultant supramolecular assemblies can be optimized for the required downstream applications. To this end, in the present study we have designed and synthesized three different molecular building blocks composed of two diphenylalanine (FF) units connected to each other through three different linkers: ethylenediamine, succinic acid, or terephthalaldehyde.

Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships.

Background: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors.

Asymmetric synthesis of (+)-teratosphaerone B, its non-natural analogue and (+)-xylarenone using an ene- and naphthol reductase cascade.

Herein, a one-pot bienzymatic cascade containing an ene and a naphthol reductase is developed. It is applied for the synthesis of (+)-(3,4)-teratosphaerone B, its non-natural regioisomer in both - and -forms and (+)-xylarenone by the reduction of chemically synthesized naphthoquinone precursors in high yields (76-92%) and excellent ee (>99%). This work implies similar biosynthetic steps in the formation of the synthesized natural products.

Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence.

Theory of Mind and social functioning among neuropsychiatric disorders: A transdiagnostic study.

Social dysfunction is commonly present in neuropsychiatric disorders of schizophrenia (SZ) and Alzheimer's disease (AD). Theory of Mind (ToM) deficits have been linked to social dysfunction in disease-specific studies. Nevertheless, it remains unclear how ToM is related to social functioning across these disorders, and which factors contribute to this relationship.

Structure-Correlated Magnetic Resonance Transverse Relaxivity Enhancement in Superparamagnetic Ensembles with Complex Anisotropy Landscape.

The aim of the work is to explore structure-relaxivity relationship by observing transverse relaxivity enhancement in magnetic resonance imaging (MRI) of differently organized superparamagnetic complex ensembles of zinc ferrite isotropic/anisotropic nanosystems. We observe that superparamagnetic systems show a correlation of MRI-transverse relaxivity, /, with spatial arrangement of nanoparticles, as well as magnetic easy axes and thermal-energy-dependent anisotropy energy landscape. The presence of highly random/partially aligned easy axes with enhanced anisotropy constant leads to modulation in transverse relaxation.

The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace.

Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

Background: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients.

Methods And Results: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients.

Df(h22q11)/+ mouse model exhibits reduced binding levels of GABA receptors and structural and functional dysregulation in the inhibitory and excitatory networks of hippocampus.

The 22q11.2 hemizygous deletion confers high risk for multiple neurodevelopmental disorders. Inhibitory signaling, largely regulated through GABA receptors, is suggested to serve a multitude of brain functions that are disrupted in the 22q11.

Genetic control of neuronal activity enhances axonal growth only on permissive substrates.

Background: Neural tissue has limited regenerative ability. To cope with that, in recent years a diverse set of novel tools has been used to tailor neurostimulation therapies and promote functional regeneration after axonal injuries.

Method: In this report, we explore cell-specific methods to modulate neuronal activity, including opto- and chemogenetics to assess the effect of specific neuronal stimulation in the promotion of axonal regeneration after injury.

Development of a simple and versatile in vitro method for production, stimulation, and analysis of bioengineered muscle.

In recent years, 3D in vitro modeling of human skeletal muscle has emerged as a subject of increasing interest, due to its applicability in basic studies or screening platforms. These models strive to recapitulate key features of muscle architecture and function, such as cell alignment, maturation, and contractility in response to different stimuli. To this end, it is required to culture cells in biomimetic hydrogels suspended between two anchors.