Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families.

Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the Picornaviridae family.

Modeling interdependence between climatic factors, commodities, and financial markets.

This paper introduces a comprehensive approach to studying the impact of climate-related factors on commodity and financial markets using network analysis. We utilize a Bayesian network Vector Autoregressive model to investigate whether climate risk significantly influ-ences commodity prices and financial market returns. Our findings provide evidence of a climate effect on major commodities and global financial markets.

μ-Opioid Receptor Modulation of the Glutamatergic/GABAergic Midbrain Inputs to the Mouse Dorsal Hippocampus.

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immunostaining, in situ hybridization, and patch-clamp recordings in acute brain slices to study the release mechanism and μ-opioid modulation of the dual glutamatergic/GABAergic inputs from the ventral tegmental area and supramammillary nucleus to the granule cells of the dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels.

A Novel Antigen Design Strategy to Isolate Single-Domain Antibodies that Target Human Nav1.7 and Reduce Pain in Animal Models.

Genetic studies have identified the voltage-gated sodium channel 1.7 (Na1.7) as pain target.

Unified Language for Knowledge Dissemination: The Vascular Ageing Glossary, an Initiative by VascAgeNet.

Objectives: In general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology.

Prenatal Detection and Conservative Management of Uterine Scar Dehiscence in Patient with Previous Uterine Rupture and Multiple Surgeries-A Case Report.

Uterine rupture is a rare and life-threatening condition. It usually occurs in patients with uterine scars (most commonly for a previous myomectomy or caesarean section), but it can also affect an unharmed uterus. This complication is more frequent in the third trimester and during delivery.

The Dark Side of the pollen: BSA-seq identified genomic regions linked to male sterility in globe artichoke.

Globe artichoke (Cynara cardunculus var. scolymus; 2n = 2x = 34) is a food crop consumed for its immature flower heads. Traditionally, globe artichoke varietal types are vegetatively propagated.

Biomarker-based text messages to promote lactation success in mothers of critically Ill infants: a randomized controlled pilot study.

Objective: Infrequent breast pumping limits mother's own milk production in mothers of infants admitted to the neonatal intensive care unit. We aimed to determine the feasibility and benefit of biomarker-based personalized text messages on pumping frequency and milk sodium levels. A secondary aim examined lactation outcomes.

The community health worker experience and perception toward mental illness: A multi-settings cross-sectional study in Indonesia.

Background: The experiences and perceptions of Community Health Workers toward mental illness are vital for tailoring interventions, reducing stigma, improving access to services, and fostering community engagement in mental health initiatives.

Aims: This study investigates the experiences of community health worker and their perception of mental illness.

Methods: A multi-settings cross-sectional study was conducted among 487 Community Health Workers.

Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.

We performed a comprehensive study of the morphological, functional, and genetic features of moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength. Cerebellar pathology is characterized by early and almost complete loss of unipolar brush cells as well as slowly progressive, moderate loss of Purkinje cell (PCs).

Medical device regulation in vascular ageing assessment: a VascAgeNet survey exploring knowledge and perception.

Background: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment.

Revitalizing agriculture: next-generation genotyping and -omics technologies enabling molecular prediction of resilient traits in the Solanaceae family.

This review highlights -omics research in Solanaceae family, with a particular focus on resilient traits. Extensive research has enriched our understanding of Solanaceae genomics and genetics, with historical varietal development mainly focusing on disease resistance and cultivar improvement but shifting the emphasis towards unveiling resilience mechanisms in genebank-preserved germplasm is nowadays crucial. Collecting such information, might help researchers and breeders developing new experimental design, providing an overview of the state of the art of the most advanced approaches for the identification of the genetic elements laying behind resilience.

Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions.

Modern technologies for preclinical research, including organ-on-a-chip, organoids- and assembloid-based systems, have rapidly emerged as pivotal tools for elucidating disease mechanisms and assessing the efficacy of putative therapeutics. In this context, advanced models of Parkinson's Disease (PD) offer the potential to accelerate drug discovery by enabling effective platforms that recapitulate both physiological and pathological attributes of the environment. Although these systems often aim at replicating the PD-associated loss of dopaminergic (DA) neurons, only a few have modelled the degradation of dopaminergic pathways as a way to mimic the disruption of downstream regulation mechanisms that define the characteristic motor symptoms of the disease.

Bidirectional Regulation of GABA Reversal Potential in the Adult Brain: Physiological and Pathological Implications.

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABA channels are permeable to anions, the reversal potential of GABA is very close to that of Cl, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl, respectively.

Identification of 4-amino-2-Pyridones as new potent PCSK9 inhibitors: From phenotypic hit discovery to in vivo tolerability.

Among the strategies to overcome the underperformance of statins in cardiovascular diseases (CVDs), the development of drugs targeting the Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is considered one of the most promising. However, only anti-PCSK9 biological drugs have been approved to date, and orally available small-molecules for the treatment of hypercholesterolemic conditions are still missing on the market. In the present work, we describe the application of a phenotypic approach to the identification and optimization of 4-amino-2-pyridone derivatives as a new chemotype with anti-PCSK9 activity.

Boosting grapevine breeding for climate-smart viticulture: from genetic resources to predictive genomics.

The multifaceted nature of climate change is increasing the urgency to select resilient grapevine varieties, or generate new, fitter cultivars, to withstand a multitude of new challenging conditions. The attainment of this goal is hindered by the limiting pace of traditional breeding approaches, which require decades to result in new selections. On the other hand, marker-assisted breeding has proved useful when it comes to traits governed by one or few genes with great effects on the phenotype, but its efficacy is still restricted for complex traits controlled by many loci.

Does Sexual Function and Quality of Life Improve after Medical Therapy in Women with Endometriosis? A Single-Institution Retrospective Analysis.

Background: Endometriosis is a gynecological condition affecting up to 10% of women of reproductive age and characterized by chronic pain. Pain is the major cause of the impairment of quality of life in all aspects of these patients. Previous studies have shown that endometriosis treatment, hormonal or surgical, has proven effective not only in controlling the disease but also in improving symptoms, and we can assume also effective in improving quality of life.

The elusive Na1.7: From pain to cancer.

Voltage-gated sodium channels (Na) are protein complexes that play fundamental roles in the transmission of signals in the nervous system, at the neuromuscular junction and in the heart. They are mainly present in excitable cells where they are responsible for triggering action potentials. Dysfunctions in Na ion conduction give rise to a wide range of conditions, including neurological disorders, hypertension, arrhythmia, pain and cancer.

Hypernegative GABA Reversal Potential in Pyramidal Cells Contributes to Medial Prefrontal Cortex Deactivation in a Mouse Model of Neuropathic Pain.

Deactivation of the medial prefrontal cortex (mPFC) has been broadly reported in both neuropathic pain models and human chronic pain patients. Several cellular mechanisms may contribute to the inhibition of mPFC activity, including enhanced GABAergic inhibition. The functional effect of GABA(γ-aminobutyric acid type A)-receptor activation depends on the concentration of intracellular chloride in the postsynaptic neuron, which is mainly regulated by the activity of Na-K-2Cl cotransporter isoform 1 (NKCC1) and K-Cl cotransporter isoform 2 (KCC2), 2 potassium-chloride cotransporters that import and extrude chloride, respectively.

The prevalence of and perception toward mental illness: a cross-sectional study among Indonesian mental health nurses.

Background: The emergence of the Coronavirus disease 2019 (Covid-19) pandemic has affected nurses' mental and psychological health. This study investigates the prevalence of depression, anxiety, and stress among Indonesian mental health nurses and their perception of mental illness.

Methods: A cross-sectional study was conducted shortly before the height of the Covid-19 outbreak in Indonesia.

Diversity analyses in two ornamental and large-genome species based on a low-cost Klenow NGS-based protocol.

Persian buttercup ( L.) and poppy anemone ( L.) are ornamental, outcrossing, perennial species belonging to the family, characterized by large and highly repetitive genomes.