Attrition in drug development due to central nervous system (CNS)-related adverse events is costly and can pose risks to volunteer safety during clinical development, underscoring the need to refine preclinical CNS screening strategies. The primary preclinical method to assess CNS risk is the Functional Observation Battery (FOB)/Irwin; however, these tests are limited by subjective assessment and restricted temporal resolution. Automated neurobehavioral assessment, such as the Home Cage Analyzer (HCA), may provide a solution to these challenges. Moreover, home cage assessments are in alignment with the 3Rs principles of refinement and reduction of animal use. Here, we detail our efforts to validate the HCA as part of GSK's CNS safety assessment strategy. To this end, we evaluated the HCA using tool compounds-amphetamine, diazepam, and chlorpromazine-each with differing pharmacology and pharmacokinetics. Additionally, we employed a 4 × 4 Latin-square crossover study design allowing each animal to serve as its own control. Our results demonstrate that the HCA captured the expected pharmacological effects of stimulant and sedative compounds across differing light phases. Notably, at the highest amphetamine dose, we observed a distinct shift in behavior: horizontal locomotor activity decreased, vertical rearing activity markedly increased, a nuanced effect that could be missed by traditional observational methods and highlights the value of multimodal assessment. Together, these data strongly support the use of the HCA as a first-line tool in preclinical CNS safety assessment.

The Aedes aegypti mosquito is the main vector of several dangerous diseases, including dengue fever (DF), chikungunya, Japanese encephalitis, West Nile fever, and yellow fever. Pongamia pinnata and Vitex trifolia are two multipurpose plant species that can be used for mosquito control. The present research aims to analyze the larvicidal and oviposition deterrent activities of P. pinnata and V. trifolia leaf extracts against Ae. aegypti. Pongamia pinnata and V. trifolia leaves were extracted using methanol, and the extracts were screened for phytochemical compounds. The extracts were tested for larvicidal and oviposition deterrent activities against Ae. aegypti at concentrations of 300, 400, 500, 800, 1000, 1500, and 2000 ppm with triplicates. Positive control (0.02% temephos) and negative control (0.01% Tween-80 in 0.5% aqueous acetone) were included. For larvicidal activity, 25 third-instar larvae were exposed to each test solution, and mortality was recorded after 24 and 48 hours. Lethal concentration 50% and 90% (LC50 and LC90) were calculated using Probit analysis. For oviposition-deterrent activity, 25 gravid female mosquitoes were placed in test cages. Eight ovitraps were placed in each cage, one for P. pinnata and another for V. trifolia test solutions. The number of eggs was counted under a dissecting microscope at 3 and 6 days. Results showed that both P. pinnata and V. trifolia leaf extracts contained phenols, tannins, flavonoids, steroids, alkaloids, and saponins. Terpenoids were only found in V. trifolia leaf extract. Larval mortality increased with increasing extract concentration. The highest larval mortality of 88% and 92% was achieved with concentrations of 2000 ppm and 1500 ppm for P. pinnata and V. trifolia extracts, respectively. The LC50 and LC90 after 24 hours of P. pinnata leaf extract were 891.41 ppm and 1252.25 ppm respectively while for V. trifolia leaf extract were 648.67 ppm and 1627.19 ppm respectively. Oviposition deterrent activity of P. pinnata leaf extract ranged from 7.02% - 19.33% at 300 - 2000 ppm, whereas V. trifolia leaf extract was 91.16 - 95.81% at 1500 - 2000 ppm. In conclusion, both P. pinnata and V. trifolia methanol leaf extracts exhibited dose-dependent larvicidal activity. Pongamia pinnata leaf extract showed low oviposition deterrent activity, with a mean of 11.59% at 300 - 2000 ppm. Vitex trifolia leaf extract showed high oviposition deterrent activity of 91.16 - 95.81% at 1500-2000 ppm.

Ferritin is a heteropolymer or homopolymer composed of 24 polypeptides forming a cage-shaped sphere. Its main function is to maintain soluble and non-toxic states of iron ions in the body. In mammals, ferritin is primarily located in the cytoplasm and the mitochondria. Cytoplasmic ferritin consists of heavy (H) and light (L) subunits, whereas mitochondrial ferritin is a homopolymer composed exclusively of a single subunit type. A notable feature of ferritin is its ability to self-assemble into nanocages in vitro, which is reversible and controllable. This unique property has enabled its widespread application in various fields including drug delivery, disease diagnosis, and vaccine development. In this review, we provide a comprehensive overview of ferritin, focusing on the following aspects: 1) structural characteristics, biological functions, dynamics, and molecular mechanisms underlying ferritin self-assembly, 2) recent advances and applications of ferritin-based self-assembled nanocages in biomedicine and bioengineering, and 3) progress in the molecular modification of ferritin using genetic engineering techniques. Additionally, we critically examined the current limitations of ferritin in research and practical applications, and proposed potential strategies for further improvement, with the aim of providing insights into the future development and utilization of ferritin in medical and scientific contexts. This work integrates the kinetics and molecular mechanisms of ferritin self-assembly with advanced genetic engineering strategies, offering a systematic framework for the rational design of ferritin-based multifunctional platforms.

Fume hoods protect chemists and the environment from hazardous vapours and airborne substances produced during experiments. They are standard in chemistry laboratories worldwide. However, fume hoods were designed for manual chemistry, and there are still relatively few robotic systems designed to operate within these inherently confined spaces. It is challenging to design robotic systems that can perform the same variety of operations within fume hoods that can be performed by a dexterous human chemist. Here, we present an automated platform comprising a robotic arm that can perform liquid handling, solid handling, capping/decapping, heating and stirring, filtration, and sample imaging within a standard laboratory fume hood (50 cm × 120 cm × 170 cm). The broad applicability of this system was demonstrated in two materials research problems (a dye-based porosity screening workflow and the synthesis of a porous organic cage) and in a phthalimide synthesis. The success of the synthesis workflows was validated offline by NMR, X-ray diffraction, mass spectrometry and FTIR.

PURPOSE: Anti-directional segmental motion has been documented in the cervical spine but never quantified in the thoracolumbar region. We aimed to determine its prevalence and determinants in adolescents and test its independence from coronal deviation. METHODS: Idiag M360 data from 166 adolescents (103 males, 63 females; 14.4 ± 0.9 years) were retrospectively analysed. Segmental angles (Th1/2–L5/S1) in upright, flexion and extension were recorded. Anti-directional motion was defined as segmental movement opposite to the intended trunk direction. Bonferroni-corrected correlations, kyphosis tertile analysis, regression and segment-level frontal-plane comparisons were performed (STROBE). RESULTS: All 166 participants exhibited anti-directional motion (mean 10.4 ± 2.9 segments). During flexion, 4.0 ± 1.9 segments were affected, almost exclusively thoracic. Thoracic flexion ROM was the dominant determinant (r = − 0.701; regression β = − 1.31, R[2] = 0.52, adjusted R[2] = 0.51). A sharp prevalence decline across the lower thoracic spine mapped the rib cage constraint gradient: Th8/9 (39%) → Th11/12 (1.2%), corresponding to the transition from false to floating ribs. Higher kyphosis was associated with more flexion paradox (H = 14.28, p < 0.001), with a threshold near 50°. No association with coronal deviation was found at any thoracic segment (all p > 0.14). CONCLUSIONS: Anti-directional segmental motion is a universal feature of adolescent thoracolumbar kinematics. Its distribution maps the rib cage constraint gradient, and its magnitude is governed primarily by thoracic mobility and secondarily by sagittal curvature through an end-range positioning mechanism. These normative data provide a reference framework for future case–control studies investigating segmental motion sharing in adolescent spinal pathology.

Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations.

BACKGROUND: Alcohol consumption among older adults aged ≥ 80 years remains insufficiently characterised, despite increased susceptibility to alcohol-related harm. This study aimed to assess the prevalence of alcohol use and alcohol use disorder (AUD) and to examine associations with in-hospital complications in patients aged ≥ 80 years admitted to Internal Medicine. METHODS: This multicentre prospective observational study was conducted from June 2022 to July 2023 across 19 hospitals. Consecutive patients aged ≥ 80 years admitted to Internal Medicine were included. Alcohol use was assessed through structured interviews and validated screening instruments, including the Alcohol Use Disorders Identification Test (AUDIT) and the CAGE questionnaire. Data on comorbidities, medication use, functional status, laboratory parameters, and in‐hospital complications were collected. Multivariable logistic regression was performed to identify independent predictors of in-hospital complications. RESULTS: A total of 916 patients (median age 86 years; 54% female) were analysed. Active alcohol use at admission was reported by 28%, and 8% met AUDIT criteria for AUD. Alcohol use was documented in medical records in 36% of cases. Overall, 47% developed ≥ 1 complication. Alcohol withdrawal syndrome (9%) and insomnia (36%) were significantly more frequent among active drinkers. Independent predictors of in-hospital complications included AUDIT score ≥ 8 [Odds Ratio (OR) 3.8; 95% Confidence Interval (CI) 1.8–8.3], in‐hospital benzodiazepine use (OR 2.3; 95% CI 1.7–3.2), neuroleptic use (OR 4.1; 95% CI 2.9–5.7), and discharge diagnoses of infection or neurological disease. CONCLUSIONS: Alcohol consumption is common yet under-recognised in patients aged ≥ 80 years and is associated with increased odds of in‐hospital complications. Routine screening with the AUDIT in this population may improve risk stratification and facilitate early identification of patients at elevated risk of in-hospital complications.