Discovery of Spirosnuolides A-D, Type I/III Hybrid Polyketide Spiro-Macrolides for a Chemotherapeutic Lead against Lung Cancer.

Four new macrolides, spirosnuolides A-D (-, respectively), were discovered from the termite nest-derived sp. INHA29. Spirosnuolides A-D are 18-membered macrolides sharing an embedded [6,6]-spiroketal functionality inside the macrocycle and are conjugated with structurally uncommon side chains featuring cyclopentenone, 1,4-benzoquinone, hydroxyfuroic acid, or butenolide moieties.

Increased Risk of Sudden Sensorineural Hearing Loss in Patients Receiving Sedative-Hypnotics: A Propensity Score Weighting Cohort Study.

Purpose: Benzodiazepine receptor agonists (BZRAs), including benzodiazepines (BZDs) and Z drugs, are widely prescribed for anxiety and sleep. Therefore, issues of tolerance, dependence and adverse effects are of concern. Recent studies suggested a potential link between BZRAs and hearing problems.

Revisiting astrocytic calcium signaling in the brain.

Astrocytes, characterized by complex spongiform morphology, participate in various physiological processes, and abnormal changes in their calcium (Ca) signaling are implicated in central nervous system disorders. However, medications targeting the control of Ca have fallen short of the anticipated therapeutic outcomes in clinical applications. This underscores the fact that our comprehension of this intricate regulation of calcium ions remains considerably incomplete.

Evidence for spinal disinhibition as a pain-generating mechanism in fibromyalgia syndrome.

Introduction: Pain phenomenology in patients with fibromyalgia syndrome (FMS) shows considerable overlap with neuropathic pain. Altered neural processing leading to symptoms of neuropathic pain can occur at the level of the spinal cord, and 1 potential mechanism is spinal disinhibition. A biomarker of spinal disinhibition is impaired H-reflex rate-dependent depression (HRDD).

A qualitative exploration of women's expectations of birth and knowledge of birth interventions following antenatal education.

Background: Expectations of birth, and whether they are met, influence postnatal psychological wellbeing. Intrapartum interventions, for example induction of labour, are increasing due to a changing pregnant population and evolving evidence, which may contribute to a mismatch between expectations and birth experience. NICE recommends antenatal education (ANE) to prepare women for labour and birth, but there is no mandated UK National Health Service (NHS) ANE curriculum.

Polyneuropathy in Parkinson's Disease is Highly Prevalent and Not Related to Treatment.

Purpose: An increased prevalence of peripheral polyneuropathy (PN) in Parkinson's disease (PD) associated with greater functional impairment has previously been reported. A possible cause has been suggested as levodopa therapy. The aim of this real-world study was to assess the prevalence and the characteristics of PN in PD and to investigate the putative association between PN and oral levodopa.

Genome-wide association study of anterior uveitis.

Background/aims: The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study (GWAS).

Methods: In this GWAS meta-analysis, we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study (PheWAS) to investigate associations across phenotypes and traits.

Infectious intestinal diseases elevate neurodegenerative disease risk based on a nationwide population-based cohort study.

Infectious intestinal diseases (IIDs) pose a significant health and economic burden worldwide. Recent observations at the Tri-Service General Hospital, Taiwan, suggest a potential association between IIDs and neurodegenerative diseases, prompting an investigation into this relationship. This study explored interactions between IIDs and neurodegenerative diseases.

Progesterone level in assisted reproductive technology: a systematic review and meta-analysis.

Elevated progesterone (EP) or inadequate progesterone levels during ART cycle monitoring may lead to cycle cancellations or further progesterone supplementation, but practice varies. It remains controversial whether modifying clinical practice in the presence or absence of EP improves clinical outcomes. This systematic review aims to investigate if progesterone levels at different phases of fresh and frozen ART cycles influence pregnancy outcomes, in particular, that pertaining to day 3 versus day 5 embryo transfers.

Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects.

Introduction: Network pharmacology has gained significant traction as a tool for identifying the mechanisms and therapeutic effects of herbal medicines. However, despite the usefulness of these approaches, their diversity underscores the critical need for a systematic evaluation to ensure consistency and reliability.

Objectives: We aimed to evaluate the network pharmacological analyses, focusing on identifying the mechanisms and therapeutic effects of herbal medicines.

Placental Macrovascular Pattern from Pregnancies with Maternal Hypertensive and Fetal Growth Capacity Complications.

Unlabelled: Histomorphometric measurements of the wall thickness and internal diameter of the macrovessels of the chorionic villi of placentas from pregnancies complicated by preeclampsia or fetal growth restriction in comparison with normotensive pregnancy.

Methods: The research included placentas from singleton pregnancies complicated by preeclampsia and/or fetal growth restriction, women delivered in medical institutions in Karaganda city (Kazakhstan). Placentas were divided into three groups: PE ( = 59), isolated FGR ( = 24), and PE with FGR ( = 41).

Effect of a Mating Type Gene Editing in Using RNP/Nanoparticle Complex.

Gene editing using CRISPR/Cas9 is an innovative tool for developing new mushroom strains, offering a promising alternative to traditional breeding methods that are time-consuming and labor-intensive. However, plasmid-based gene editing presents several challenges, including the need for selecting appropriate promoters for Cas9 expression, optimizing codons for the Cas9 gene, the unintended insertion of fragmented plasmid DNA into genomic DNA (gDNA), and regulatory concerns related to genetically modified organisms (GMOs). To address these issues, we utilized a Ribonucleoprotein (RNP) complex consisting of Cas9 and gRNA for gene editing to modify the A mating-type gene of .

Effect of low-frequency acupuncture on muscle and fascia stiffness: examination with or without intervention.

Background: Low-frequency acupuncture is used to maintain skeletal muscle flexibility and improve joint range of motion; however, its definite effects are unclear. This study aimed to determine the effects of low-frequency acupuncture on muscle and fascial stiffness and ankle dorsiflexion range of motion.

Methods: The participants included 12 randomly selected healthy adults.

Centenarians-the way to healthy vascular ageing and longevity: a review from VascAgeNet.

The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population.

Mitochondrial homeostatic imbalance-mediated developmental toxicity to HS in embryonic zebrafish.

Hydrogen sulfide (HS) is a pervasive environmental and industrial pollutant that poses a substantial threat to human health. Even short-term exposure to HS can result in severe respiratory and neurological damage. However, the underlying mechanisms of its biotoxicity remain unclear.

In vivo self-assembled siRNAs within small extracellular vesicles attenuate LRRK2-induced neurodegeneration in Parkinson's disease models.

Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.

Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.

Life cycle and morphogenetic differentiation in heteromorphic cell types of a cosmopolitan marine microalga.

Gephyrocapsa huxleyi is a prevalent, bloom-forming phytoplankton species in the oceans. It exhibits a complex haplodiplontic life cycle, featuring a diploid-calcified phase, a haploid phase and a third 'decoupled' phase produced during viral infection. Decoupled cells display a haploid-like phenotype, but are diploid.

Dynamics of thermal tolerance plasticity across fish species and life stages.

Climate warming with associated heat waves presents a concerning challenge for ectotherms such as fishes. During heatwaves, the ability to rapidly acclimate can be crucial for survival. However, surprisingly little is known about how different species and life stages vary in their acclimation dynamics, including the magnitude of change in thermal tolerance through acclimation (i.

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines.

Early warning systems for identifying severe maternal outcomes: findings from the WHO global maternal sepsis study.

Background: Infections and sepsis are leading causes of morbidity and mortality in women during pregnancy and the post-pregnancy period. Using data from the 2017 WHO Global Maternal Sepsis Study, we explored the use of early warning systems (EWS) in women at risk of sepsis-related severe maternal outcomes.

Methods: On April 27, 2023, we searched the literature for EWS in clinical use or research in obstetric populations.

The SmARTR pipeline: A modular workflow for the cinematic rendering of 3D scientific imaging data.

Advancements in noninvasive surface and internal imaging techniques, along with computational methods, have revolutionized 3D visualization of organismal morphology-enhancing research, medical anatomical analysis, and facilitating the preservation and digital archiving of scientific specimens. We introduce the SmARTR pipeline (Small Animal Realistic Three-dimensional Rendering), a comprehensive workflow integrating wet lab procedures, 3D data acquisition, and processing to produce photorealistic scientific data through 3D cinematic rendering. This versatile pipeline supports multiscale visualizations-from tissue-level to whole-organism details across diverse living organisms-and is adaptable to various imaging sources.