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461 papers

Epoxy Clerodane Diterpene Attenuates the Differentiated Adipocyte Hypertrophy and Enhances Mitochondrial Metabolism.

AlSedairy SA et al. · Jul 1, 2026

Adipocyte hypertrophy is an obesity-related metabolic dysfunction, which is frequently associated with decreased mitochondrial activity during adipocyte development. The current study aimed to assess the potential of epoxy clerodane diterpene (ECD) (IUPAC: 5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone) extracted from Cassia tora on adipocyte differentiation, lipid accumulation, mitochondrial function, and inflammation. Human bone marrow mesenchymal stem cells (hMSCs) were stimulated into adipocytes using the standard differentiation medium. The methodological design included the evaluation of ECD cytotoxicity, lipid accumulation, mitochondrial membrane potential, qRT-PCR, and ELISA. ECD didn't significantly reduce the cellular viability; however, it decreased lipid accumulation by 65%, 87%, and 87.5% at doses of 2, 4, and 8 μM, respectively. Also, at 4 µM of ECD, it decreased adipocyte hypertrophy, increased mitochondrial membrane potential, raised the expression of thermogenesis-related genes (UCP-1, PPARγC1α, SREBP1c), decreased the expression of adipogenic proteins (C/EBPα, PPARγ), increased adiponectin levels, and reduced inflammatory markers (IL-4, TNF-α) compared to untreated controls. Thus, ECD may hold tremendous promise as a natural agent for controlling adipogenesis, and its impacts on lipid metabolism, mitochondrial function, and inflammatory responses demonstrate its potential for therapeutic use in the treatment of obesity and associated metabolic diseases.

Agricultural and Biological Sciences

Changes in Inpatient Coding for Hepatic Encephalopathy After Introduction of ICD-10 Code K76.82.

Goble SR et al. · Jul 1, 2026

An ICD-10 code specific for hepatic encephalopathy (HE), K76.82, was introduced in October of 2022. We aimed to assess changes in HE documentation following the introduction of this code. Using the National Inpatient Sample, we compared utilization of ICD-10 codes historically used to identify HE before and after K76.82. From 2016 to 2021, 20.0% of cirrhosis hospitalizations included a non-specific HE code, decreasing to 4.7% in 2023. K76.82 was used in 20.3% of hospitalizations in 2023. The introduction of K76.82 has dramatically changed the documentation of HE, and future studies assessing HE trends and outcomes need to account for these changes.

Medicine

Indicators of maternal anxiety, stress, and depression and developmental outcomes in preterm children: A systematic review.

Silva BBRD et al. · Jul 1, 2026

The study was conducted in Brazil and aimed to systematically review empirical research examining the association between maternal indicators of anxiety, stress, and depression and the developmental outcomes of preterm children. A literature search was conducted across PubMed, Web of Science, PsycINFO, EMBASE, Scopus, LILACS, and SciELO. Sixteen studies were analyzed. The systematic review revealed a significant association between maternal anxiety, depression, and stress indicators and poorer developmental outcomes for children born prematurely. This association was observed whether it was considered a single indicator of maternal mental health or a combination of two or more indicators. The systematic review affirms the impact of maternal mental health on the development of preterm children in early childhood.

Medicine

Probiotics and Their Functional Role in Mitigating Antinutrient Effects In Vivo-A Systematic Review and Meta-Analysis.

Olar-Pop L et al. · Jul 1, 2026

Antinutrients like phytic acid and oxalates reduce mineral bioavailability by forming insoluble complexes with iron, zinc, and calcium. Probiotic supplementation may counteract these effects through enzymatic activity (e.g., phytase, oxalate decarboxylase) and microbiota modulation. This PRISMA-based meta-analysis evaluated 27 in vivo studies (chickens, mice, rats) published between 2005 and 2025. Controlled trials assessing probiotic effects on mineral absorption under antinutrient-rich diets were analyzed using random effects models, expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Probiotic supplementation may enhance selected markers of mineral bioavailability across animal models (broiler, mouse, and rats), although the certainty of evidence was low and between-study heterogeneity was substantial. In broiler chickens, probiotics increased hepatic iron (SMD = 2.05; CI: 0.91-3.20) and liver ferritin levels (SMD = 2.85; CI: 0.90-4.80). In rat models of hyperoxaluria, probiotics reduced renal calcium oxalate deposition (SMD = 0.77; p = 0.0001), though the impact on urinary oxalate levels was not significant (SMD = 0.20). In mouse models, the interventions demonstrated improved gut microbiota diversity without significant alterations in total body weight (SMD = 0.02). Based on low-certainty evidence from heterogeneous animal studies, probiotic supplementation may improve selected mineral-bioavailability outcomes and may reduce calcium oxalate deposition under antinutrient-rich conditions. These findings should be interpreted cautiously. Further well-designed, species-specific studies using standardized interventions and outcome measures are needed before firm conclusions can be drawn.

Medicine

Neural and Navigational Features Influencing the Novelty Induced Benefits on Episodic Memory.

Vogelsang DA et al. · Jul 1, 2026

Studies in animals have robustly shown that exposure to novelty can promote memory for information presented in the temporal vicinity. In humans, however, evidence for such novelty-related memory benefits has been mixed. In this EEG study, we investigated the neurobiological mechanisms underlying effects of novelty on memory and whether individual differences in exploration patterns help explain these inconsistencies. We examined the role of theta oscillations in exploring a novel or familiar environment as well as whether spatial exploration behavior can modulate the beneficial effects of novelty on memory. Participants first explored one of two virtual environments and subsequently explored the same (familiar condition) or a new environment (novel condition). After exploring novel and familiar environments, participants performed a word learning task followed by a free recall and recognition memory test. Neurologically, exploration of the familiar rather than novel environment increased theta power, which may reflect environment-related memory processes. However, we did not observe any differences in theta power associated with successful encoding of words after exploring a novel versus familiar environment. Behaviorally, no main effect of novelty on free recall was observed. Crucially, when accounting for variance in spatial exploration patterns, words encoded after exploring a novel environment were recalled better than words encoded after exploring a familiar environment. Furthermore, an interaction effect between the condition and exploratory behavior revealed that increased exploration benefitted free recall specifically in the familiar condition. These findings emphasize the importance of considering the way in which individuals explore a virtual environment when examining novelty effects on memory.

Neuroscience

Chiral (Stereoselective) Drugs, Asymmetric Synthesis, and Racemic Resolution Methods.

Karayavuz B et al. · Jul 1, 2026

Chirality is of great importance in drug development since both biological targets in the organism and the majority of pharmacologically active compounds created today are chiral. The synthesis and resolution of chiral compounds are critical steps while developing chiral drugs, as the chirality of a molecule can significantly affect its efficacy, safety (side effects and toxicity), and metabolism. While one enantiomer has therapeutic properties, the other enantiomer might be harmful, toxic, or ineffective. In recent years, the trends towards developing single enantiomer drugs have increased in the pharmaceutical industry. Various synthetic strategies and racemic resolution techniques are employed to obtain optically pure chiral drugs. Regulatory authorities also give more priority to assessing the biological efficacy of each chiral drug's enantiomer. This review summarizes the asymmetric synthesis and racemic resolution methods for producing pure enantiomeric pharmaceutical active ingredients and their synthetic intermediates, with examples from the pharmaceutical industry. By examining current approaches and challenges in the field, we aim to provide a comprehensive understanding of the processes that ensure the production of safe and effective chiral-specific drugs.

Chemistry

The Empirical Bayes Variational Autoencoder-A Neural ODE Approach for Population Modeling in Pharmacology.

Baaz M et al. · Jul 1, 2026

Variational autoencoders (VAEs) combined with neural ordinary differential equations provide a flexible framework for exploring neural latent-variable models in population pharmacokinetics. In this work, we investigate an empirical Bayes VAE formulation that integrates encoder-decoder architectures with covariate-dependent population priors, enabling correlated latent representations and probabilistic inference. We evaluate the proposed framework using controlled simulation studies and a small clinical benchmark dataset. The simulation experiments assess the ability to recover known population structures and covariate effects, while the clinical study evaluates subject-specific prediction and model diagnostics. In simulation studies with correlated individual parameters, the empirical Bayes VAE consistently captured population-level variability, whereas a fixed-prior VAE baseline exhibited systematic biases. In our experiments, extrapolation beyond the training dosing schedules showed more stable predictive behavior when using the proposed input-response normalization, relative to models trained without normalization, within a limited range. Diagnostic analyses indicated clear relationships between inferred latent variables and true parameters, and estimated observation noise was consistent with simulated values. In the clinical case study, cross-validation experiments suggested predictive performance comparable to previously reported neural ODE-based approaches. Overall, the results illustrate the feasibility of combining empirical Bayes inference with neural ODE-based decoders for population modeling. The proposed framework should be viewed as a methodological proof-of-concept, highlighting both the potential and the current limitations of variational neural approaches in pharmacometric applications.

Mathematics

Two Weeks of Mirror Exposure Enhances Sensorimotor Cortex Activation but not Facial Mimicry in 4-Month-old Infants.

Richmond C et al. · Jul 1, 2026

This study aimed to test the causal role of sensorimotor experience in the development of facial mimicry. We systematically manipulated 4-month-old infants' experience with their own facial actions, and measured the effect on their sensorimotor cortex activation and facial mimicry when they observed others' facial actions. Infants in the mirror condition received two weeks of daily sensorimotor experience with their own facial actions via a toy mirror, while infants in the control condition played with the same toy without the mirror for the same amount of time. Before and after this experience, we measured infants' facial mimicry using electromyography (EMG) and their sensorimotor cortex activation using electroencephalography (EEG) while they observed videos of other infants' facial actions. As predicted, infants in the mirror condition showed a greater increase in sensorimotor cortex activation during the observation of other infants' facial actions than infants in the control condition. However, this greater neural activation did not translate into a greater increase in facial mimicry in the mirror group. These findings suggest that although the neural processing of others' facial actions was enhanced as a result of the sensorimotor training, longer training periods may be necessary for this to lead to greater facial mimicry. SUMMARY: We investigated the role of sensorimotor experience in infant facial mimicry by assigning infants to either a mirror or control condition Infants in the mirror condition received two weeks of daily mirror exposure Mirror training enhanced sensorimotor cortex activity during the observation of facial actions No corresponding increase in facial mimicry was observed.

Psychology

Perceived Challenges and Solutions to Adopting Healthy Diets Among Women and Children: A Photovoice Study in Urban Ethiopia.

Worku M et al. · Jul 1, 2026

Ethiopia has one of the highest rates of undernutrition among children under five (U5) and women of reproductive age (WRA) globally, alongside rising overweight/obesity, particularly in urban areas. Poor diet is a shared driver of multiple forms of malnutrition. We used a participatory photography (Photovoice) approach to explore the lived experiences of WRA and their children U5 in adopting healthy diets across lower- and higher- socio-economic status (SES) groups in Addis Ababa. Women took photographs illustrating challenges to healthy diets, and five focus groups (n = 31 women) were conducted to discuss challenges and solutions, with separate sessions held for different SES groups. A hybrid thematic analysis, combining deductive and inductive approaches, identified themes/subthemes, with comparisons across SES groups. Financial and physical barriers to accessing healthy foods, time constraints and perceived poor food safety were major contributors to poor diets. In lower SES groups, women also reported limited knowledge about healthy diets, inadequate family support and poor home food environments. In higher SES groups, unhealthy food preferences coupled with easy access to and aggressive promotion of unhealthy foods were key challenges. Proposed government-level solutions included job creation, nutrition education, affordable healthy food, investment in household infrastructure, expanded childcare and restrictions on unhealthy food availability and promotion. Societal-level solutions included gender equality, strengthened community-based loan schemes and support for urban agriculture. These findings highlight that women recognise their needs and who should support them, and emphasise the importance of including women's voices in decision-making processes. Findings also underscore the need for integrated interventions targeting individual, food environment and socio-economic drivers to improve diets among women and children in urban Ethiopia.

Nursing

Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.

Hammoum T et al. · Jul 1, 2026

Peptide-based nanoparticles (PBN) have emerged as a promising alternative to lipid nanoparticles (LNP) for nucleic acid delivery and efficient cellular uptake. In this study, we evaluated the formulation of WRAP5 (W- and R-rich amphipathic peptide 5)-based PBN using a microfluidic device and assessed the impact of key process parameters, flow rate ratio (FRR), total flow rate (TFR), and mixing channel design, on nanoparticle characteristics. Across 72 formulations encapsulating small interfering RNA (siRNA) or plasmid DNA (pDNA), dynamic light scattering revealed consistent mean sizes ranging from 50 to 70 nm, with a low polydispersity index (PdI < 0.22), independent of FRR, TFR, or mixer type. Stability studies demonstrated that siRNA-loaded PBN exhibited moderate size increases during storage at 4°C, whereas pDNA-loaded PBN remained highly stable for up to 70 days. Biological assays confirmed robust activity: WRAP5:siRNA PBN achieved approximately 50% CDK4 silencing in GIST-T1 cells, and WRAP5:pDNA PBN mediated efficient mCHERRY expression in HeLa cells, regardless of formulation method or storage duration. These findings highlight the robustness and scalability of WRAP5-based PBN, contrasting with LNP systems that require stringent control of FRR and TFR, and partially underscore their potential for nucleic acid delivery applications.

Biochemistry, Genetics and Molecular Biology