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Phenotypic profiling of small molecules using cell painting assay in HCT116 colorectal cancer cells

Understanding how small molecules affect cellular morphology is essential for exploring their mechanisms of action (MoA) and identifying new therapeutic candidates. In this study, the Cell Painting Assay (CPA) was used to profile 196 small molecules in HCT116 colorectal cancer cells. By applying t-distributed stochastic neighbor embedding (t-SNE) followed by density-based clustering, 18 distinct phenotypic clusters were identified based on similarities in the quantitative morphological profiles generated from Cell Painting data. Although it was initially hypothesized that clustering would reflect known MoAs, most clusters showed only partial overlap with target-based classifications. Instead, compounds from different MoA classes converged on similar cellular phenotypes, suggesting common downstream effects or shared stress responses. Notably, compounds affecting DNA replication, mitosis, or transcriptional control appeared across multiple clusters, indicating functional diversity within morphologically similar groups. Clusters enriched with mTOR/PI3K inhibitors, spindle poisons, or transcriptional CDK blockers exhibited well-defined phenotypes, supporting the robustness of the assay. In contrast, compounds inducing more subtle phenotypes formed distinct micro-clusters, highlighting the method’s sensitivity. Overall, this study demonstrates that CPA can capture convergent phenotypic signatures that extend beyond target-based classification. These findings underscore the value of phenotype-driven screening for the functional annotation of chemical compounds and may help uncover unexpected relationships among molecules with diverse biological activities.

Effects of dexmedetomidine combined with erector spinae plane block on intraoperative neuromonitoring during surgical correction for adult spinal deformity

The effect of different structural decoration geometries on vibration propagation in spider orb webs

The stabilimentum, or structural decoration, in spider orb webs is a fascinating structure. While the species that construct stabilimenta and their building techniques are well-documented, the precise functions of these structures remain unclear. This knowledge gap arises from conflicting reports in the literature and the significant behavioral flexibility spiders exhibit when incorporating stabilimenta into their webs. Notably, spiders can build stabilimenta in various geometries, which may influence the dynamical properties of orb webs—a relationship that has yet to be quantitatively explored. In this study, we combined extensive field observations with computational simulations to address this gap. The fieldwork focused on documenting the range of stabilimentum geometries in Argiope bruennichi , while the simulations examined how these variations influence the propagation of elastic waves across the web. Our results suggest that the stabilimentum, acting as an additional inertial mass, does not significantly slow down the propagation of elastic waves generated by prey impact in the transverse and normal directions relative to the radial threads. However, when prey impact induces vibrations tangential to the spiral threads of the web, the presence of the stabilimentum enhances the spider’s ability to detect prey location by allowing vibrations to reach a greater number of output points compared to webs without a stabilimentum. These findings deepen our understanding of the mechanical role of stabilimenta and provide new insights for the development of bio-inspired metamaterials, particularly those with tunable dynamic elastic properties.

Retrosynthetic Design of Dinuclear Copper Enzymes for Azide–Alkyne Cycloaddition via Clickable Noncanonical Amino Acids

Ferrite chitosan curcumin nanoparticles alleviate nandrolone decanote induced liver toxicity in male albino rats

Abstract Sr 2 NiCoAl 0.3 Fe 27.7 O 46 X-Type hexa-nano-ferrites were prepared using a co-precipitation route, coated with Chitosan, and synthesized into a ferrite chitosan curcumin nanoparticle system. This combination enhances curcumin’s therapeutic properties, chitosan’s bioavailability, and ferrite’s magnetic targeting potential, offering improved cellular uptake and diagnostic applications. Nandrolone decanote (ND), one of the class II anabolic androgenic steroids (AASs), quickly spreading as a class of medications used in both clinical and illegal settings. AAS can enhance tolerance to exercise, so they are taken illegally by bodybuilders and adolescents. However, the abuse of AASs can lead to serious and irreversible organ toxicity. This study designed to investigate the therapeutics effect of nano ferrite chitosan curcumin nanoparticles (NF-CH-CurNPs) against ND induced hepatic toxicity, proliferation, inflammation, oxidative stress, and DNA damage in male rats. 48 adult male rats assigned to 6 groups [1st Gp, control; 2nd Gp, CurNPs; 3rd Gp, NF-CH-CurNPs; 4th Gp, ND; 5th Gp, ND + CurNPs; 6th Gp. ND + NF-CH-CurNPs]. Current results revealed, a significant elevation in the levels of aspartate transaminase (AST), alanine transaminase (ALT), total proteins, liver DNA damage, injury, malondialdehyde (MDA), proliferating cell nuclear antigen (PCNA), tumor necrosis factor alpha (TNFα) and a significant depletion in albumin, catalase, superoxide dismutase (SOD), reduced glutathione (GSH) after ND administration as compared to control and CurNPs groups. Treatment of ND with CurNPs or NF-CH-CurNPs significantly improved liver functions, structure, oxidative stress, DNA damage, PCNA, and TNFα expressions, with NF-CH-CurNPs showing potential for scavenging free radicals.

Start up: A French program to support patients with pulmonary arterial hypertension during the adjustment of prostanoids to the individualized optimal dose

The Start Up program was initiated in patients with pulmonary arterial hypertension (PAH) with the objective to support them in taking their therapies targeting the prostacyclin pathway and determine the individualized optimal dose. This report focuses on selexipag, an oral prostacyclin receptor agonist that has been shown to delay the progression of PAH. Starting in 2016, patients who were prescribed selexipag for the treatment of PAH were offered participation in the Start Up program supported by the French PH network. During the dose adjustment phase, a nurse called the patients 3 days after drug initiation and after each dosage modification to provide support and to systematically grade and monitor adverse events (using Common Terminology Criteria for Adverse Events – CTCAE v4.0). The patients and the healthcare professionals rated their satisfaction with the program. Among the 406 patients who completed the program, 302 (74%) reached their individualized optimal dose for selexipag over a median period of 11 weeks. The reasons the individualized dose was not reached included treatment discontinuation (n = 78, 19%) and dropout for impaired communication skills (n = 8, 2%). Once the individualized optimal dose was reached, most patients had no, or mild (Grade 1) adverse events related to prostanoid use (49% and 45%, respectively). Both patients and healthcare professionals were satisfied with the Start Up program (scores of 9.1 ± 1.4 and 9.3 ± 0.7 on a 0–10 numerical scale, respectively). The proactive support and adverse event monitoring provided by the Start Up program during the early stages of treatment with selexipag was appreciated by patients and healthcare professionals and may contribute to improved compliance.

Competing Magnetic States in the Possible Altermagnet Candidate GdAlGe

Leishmania amazonensis infection induces PD-L1 expression on dendritic cells and impairs Th1 responses in vitro and in vivo

Functional expression of a Mo-dependent formate dehydrogenase in Escherichia coli under aerobic conditions

Background Oxygen tolerant complex metal-dependent formate dehydrogenases hold potential for biotechnological applications. Principal Findings In this work, we report the functional expression of the complex, molybdenum-dependent soluble formate dehydrogenase encoded by the fdsGBACD operon from Cupriavidus necator (CnFDH) in Escherichia coli. Expression of the operon from plasmids or from a copy integrated in the chromosome enabled growth of an energy-auxotrophic selection strain on formate as sole energy source under aerobic conditions. Growth could be accelerated in turbidostat, leading to a drop of the generation time of 1 hour. While no mutation was found in the operon of evolved isolates, genome sequencing revealed non-synonymous point mutations in the gene focA coding for a bidirectional formate transporter carried in all isolates sequenced. Reverting the mutations led to a drop in the growth rate demonstrating the focA gene as principal target of continuous culture adaptation. Significance A member of the oxygen-tolerant subclass of complex FDH showed stable formate oxidation activity when expressed in the heterologous host E. coli , a model organism of biotechnology. The integration of the operon in the chromosome offers the possibility of structure/function studies and activity enhancements through in vivo mutagenesis, which can also be applied to CO 2 reduction in appropriate selection hosts.

Lithium partially rescues gene expression and enhancer activity from heterozygous knockout of AKAP11 while inducing novel differential changes

Correction: Prevention and inhibition of post-harvest browning in longkong pericarp using Prunus Persica resin coating during ambient storage

Real-time PCR assay design and validation for Prevotella bivia, Peptostreptococcus anaerobius, and Dialister micraerophilus, bacteria associated with increased HIV susceptibility

Beyond the game: How social interaction and emotional gratification drive Chinese sports podcast engagement

The rapid growth of podcasting platforms has transformed digital media consumption, offering diverse content tailored to user preferences. The present research aims to identify the needs associated with engaging with sports podcasts on the Himalaya platform while exploring cognitive, emotional, and social satisfactions. Quantitative and qualitative data collection techniques used the Uses and Gratifications Theory (UGT) in the present research, including semantic network analysis, co-word clustering, and high-frequency words, to analyze the data collected from 13,692 comments of five popular sports podcast channels. The study shows that information seeking is the primary reason listeners tune in: they want game breakdowns and insiders’ opinions. This is further reinforced by self-efficacy and media convenience, which are important factors in the platform mandate of enabling users and assimilating content into their daily lives. First, the paper adds to scholarship by employing the UGT in the context of sports podcasts in China. Secondly, it provides valuable recommendations for practical use by content creators and platform developers. Overall, the results show the versatility of podcast consumption, although restrictions concerning demographic categorization and comparison with other media forms signal to undertake future studies. Such insights are relevant to improving and encouraging user interactions and how the platform delivers podcasts.

Construct Open Lipid Nano-Membranes with Controllable Lateral Behavior

Optimizing deep learning models for on-orbit deployment through neural architecture search

Lower Firmicutes abundance in gut microbiota associated with amyloid-β positivity in older adults in Japan as assessed by positron emission tomography

Background Alzheimer’s disease, marked by amyloid-β accumulation, is a leading cause of dementia. Gut microbiota may influence its development by affecting inflammation or amyloid-β metabolism. However, this association is not well studied in older adults in Japan, whose characteristic diet may uniquely impact gut bacteria. Objective To determine the association between the gut microbiota and positron emission tomography (PET)-determined brain amyloid-β positivity in community-dwelling older adults in Japan. Methods This cross-sectional study investigated 136 participants aged 68–86 years from Tokyo. Brain amyloid-β was assessed using PET imaging, and gut microbiota were analyzed from fecal samples using 16S rRNA gene sequencing processed with the QIIME2 pipeline. Taxonomic composition was evaluated at both the phylum and genus levels; participants were classified into above- and below-median groups based on the relative abundance of each taxon. Binomial logistic regression adjusted for age, sex, and antibiotic use was conducted to examine the association between bacterial abundance and PET positivity. For genus-level analyses, p-values were further corrected for multiple comparisons. In addition, α diversity (Shannon, Simpson, Observed OTUs) and β diversity (PCoA based on unweighted UniFrac distances, PERMANOVA) were compared between PET-positive and PET-negative groups. Results Of the 136 participants, 34.6% were PET-positive for amyloid-β. Firmicutes showed a significant difference: 26.4% PET-positive in the above-median group vs. 42.6% in the below-median group (p for χ² = 0.047). The binomial logistic regression analysis showed that lower Firmicutes abundance was significantly associated with an increased odds of PET positivity (odds ratio and confidence interval: 2.15 [1.03, 4.52]). At the genus level, no taxon remained significant after correction for multiple comparisons. No significant differences were observed in α or β diversity indices between groups. Conclusion A lower abundance of Firmicutes may be associated with amyloid-β accumulation in the brain, linking the gut microbiota to Alzheimer’s disease.

DDOX expands the repertoire of tetracyclines for Parkinson’s disease by preventing the cellular uptake and intracellular impact of α-synuclein preformed fibrils

Exploring dairy heifers’ consistency in social motivation in the absence or presence of conspecifics

Cattle are motivated to maintain social contact, but individual preference for social proximity (i.e., ‘sociability’) varies among individuals. Although personality traits, like sociability, are generally considered to be consistent across context and time, different social environments may elicit different behavioral responses in individuals. We tested individual differences in social motivation with and without the presence of conspecifics, and compared responses within and among different social contexts. Specifically, Holstein heifers (n = 36) were exposed to standardized social isolation tests (novel arena, novel object, runway test; each tested twice, 14 days apart) and a novel social-feed trade-off paradigm. In addition, heifers were subjected to a distribution test in which groups of three animals could freely move between two feed troughs. At one trough, heifers were offered 150 g of grain every two minutes (high side) and every four minutes at the other trough (low side). We expected animals to disperse proportionally to resource availability, corresponding with the Ideal Free Distribution theory (IFD), and that deviations from IFD would reveal individual differences in motivation to be with peers. We found no consistency in sociability measures derived from behaviors in the absence (vocalization, runway latency) and presence (feeding time, social-feed trade-off score) of conspecifics. Moreover, behaviors showed low repeatability within the same social contexts. We conclude that individual differences in sociability are likely context-dependent. We suggest that sociability might not be a single ‘trait’, but rather a ‘behavioral consequence’ resulting from the combined effects of internal characteristics (e.g., other personality traits such as fearfulness) and external factors (e.g., testing environment) at the time of evaluation.

Aircrew rostering workload patterns and associated fatigue and sleepiness scores in short and medium haul flights in Brazil

Abstract Relationships between workload and fatigue or sleepiness are investigated through the analysis of rosters and responses to questionnaires from Brazilian aircrews, taken from Fadigômetro database. The approach includes temporal markers—coinciding with Samn–Perelli (SP) and Karolinska Sleepiness Scale (KSS) responses—where SAFTE-FAST software outcomes are calculated. The latter results follow the increase of fatigue and sleepiness perceptions during the dawn (0h00 to 05h59), but underestimate self-rated scores during the evening (18h00 to 23h59). Importantly, the KSS scores and the inverse of SAFTE-FAST effectiveness fit the relative risk of pilot errors, representing interesting proxies for risk assessment. Linear relationships obtained between workload metrics, computed within 168-h prior to the responses, and self-rated SP and KSS scores provide a consistent method to estimate accumulated fatigue and sleepiness. Considering 7149 rosters of 2023, the duty time ( DT ), the number of flight sectors ( $$N_{CREW}$$ ) and the sum of flight sectors with sit periods longer than one hour ( $$N_{CREW}+N_{SIT}$$ ) are associated with 70.1%/60.6% of the highest predicted scores of SP/KSS. Applying the mitigations $$DT\le 44 h$$ , $$N_{CREW}\le 15$$ and $$N_{CREW}+N_{SIT} \le 19$$ for every 168-h interval yields a significant decrease in higher values of SP/KSS with minimal impact on roster coverage.

Comparison of PSA Values from capillary dried blood spot analysis and venous serum samples

Prostate-specific antigen (PSA) testing is a key tool in the early detection and monitoring of prostate cancer. While venous blood is the standard matrix for PSA measurement, capillary blood sampling represents a minimally invasive alternative that may facilitate broader access to testing. This prospective study investigated the agreement between capillary and venous measurements of total and free PSA in 224 male patients at ALTA Klinik Bielefeld, Germany. Blood samples were collected between April and June 2021 and analyzed using electrochemiluminescence immunoassays. The results showed strong correlations between capillary and venous samples for both total PSA (r = 0.99, p < 0.01) and free PSA (r = 0.98, p < 0.01). Mean differences were 0.35 ng/mL for total PSA and 0.27 ng/mL for free PSA. Bland-Altman analysis demonstrated good agreement between both methods, with most values falling within the 95% confidence limits. These findings suggest that capillary blood sampling may be a suitable alternative to venous blood for PSA testing, particularly within the clinically relevant range up to 10 ng/mL. Furthermore, the feasibility of determining both total and free PSA in capillary samples allows calculation of the fPSA/tPSA ratio, which may improve diagnostic specificity in early prostate cancer detection.